Our FIRST e-Book on Amazon (Biomed e-Books) [Kindle Edition]

The purpose of surgery is typically to remove the entire tumor, along with some of the healthy tissue around it, called the margin. If the tumor cannot be removed entirely, “debulking” surgery may be performed. Debulking surgery is a procedure in which the goal is to remove as much of the tumor as possible. Side effects of surgery include weakness, fatigue, and pain for the first few days following the procedure.

Chemotherapy

Chemotherapy is the use of drugs to kill tumor cells, usually by stopping the cells’ ability to grow and divide. Systemic chemotherapy is delivered through the bloodstream to reach tumor cells throughout the body. A chemotherapy regimen (schedule) usually consists of a specific number of cycles given over a set period of time. A patient may receive one drug at a time or combinations of different drugs at the same time. The side effects of chemotherapy depend on the individual and the dose used, but they can include fatigue, risk of infection, nausea and vomiting, loss of appetite, and diarrhea. These side effects usually go away once treatment is finished.

Radiation therapy

Radiation therapy is the use of high-energy x-rays or other particles to kill tumor cells. The most common type of radiation treatment is called external-beam radiation therapy, which is radiation given from a machine outside the body. When radiation treatment is given using implants, it is called internal radiation therapy or brachytherapy. A radiation therapy regimen usually consists of a specific number of treatments given over a set period of time. Side effects from radiation therapy may include fatigue, mild skin reactions, upset stomach, and loose bowel movements. Most side effects go away soon after treatment is finished.

Hormone therapy

The goal of hormone therapy is often to lower the levels of hormones in the body. Hormone therapy may be given to help stop the tumor from growing or to relieve symptoms caused by the tumor. In addition, for thyroid cancer, hormone therapy will be given if the thyroid gland has been removed, to replace the hormone that is needed by the body to function properly.

Immunotherapy

Immunotherapy (also called biologic therapy) is designed to boost the body’s natural defenses to fight the tumor. It uses materials made either by the body or in a laboratory to bolster, target, or restore immune system function. Examples of immunotherapy include cancer vaccines, monoclonal antibodies, and interferons. Alpha interferon is a form of biologic therapy given as an injection under the skin. This is sometimes used to help relieve symptoms caused by the tumor, but it can have severe side effects including fatigue, depression, and flu-like symptoms.

Targeted therapy

Targeted therapy is a treatment that targets the tumor’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. This type of treatment blocks the growth and spread of tumor cells while limiting damage to normal cells, usually leading to fewer side effects than other cancer medications.

Recent studies show that not all tumors have the same targets. To find the most effective treatment, the doctor may run tests to identify the genes, proteins, and other factors in the tumor. As a result, doctors can better match each patient with the most effective treatment whenever possible.

Depending on the type of endocrine tumor, targeted therapy may be a possible treatment option. For instance, targeted therapies, such as sunitinib (Sutent) and everolimus (Afinitor), have been approved for treating advanced islet cell tumors. Early results of clinical trials (research studies) with targeted therapy drugs for other types of endocrine tumors are promising, but more research is needed to prove they are effective.

Recurrent endocrine tumor

Once the treatment is complete and there is a remission (absence of symptoms; also called “no evidence of disease” or NED). Many survivors feel worried or anxious that the tumor will come back. If the tumor does return after the original treatment, it is called a recurrent tumor. It may come back in the same place (called a local recurrence), nearby (regional recurrence), or in another place (distant recurrence). When this occurs, a cycle of testing will begin again to learn as much as possible about the recurrence. Often the treatment plan will include the therapies described above (such as surgery, chemotherapy, and radiation therapy) but may be used in a different combination or given at a different pace. People with a recurrent tumor often experience emotions such as disbelief or fear. Patients are encouraged to talk with their health care team about these feelings and ask about support services to help them cope.

Metastatic endocrine tumor

If a cancerous tumor has spread to another location in the body, it is called metastatic cancer. A treatment plan that includes a combination of surgery, chemotherapy, radiation therapy, hormone therapy, immunotherapy, or targeted therapy may be recommended if required.

In addition to treatment to slow, stop, or eliminate the cancer (also called disease-directed treatment), an important part of cancer care is relieving a person’s symptoms and side effects. It includes supporting the patient with his or her physical, emotional, and social needs, an approach called palliative or supportive care. People often receive disease-directed therapy and treatment to ease symptoms at the same time.

Source References:

http://www.cancer.net/cancer-types/endocrine-tumor/treatment

http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Endocrine/Endocrinetumours.aspx

http://cancer.osu.edu/patientsandvisitors/cancerinfo/cancertypes/endocrine/Pages/index.aspx

http://cancer.northwestern.edu/cancertypes/cancer_type.cfm?category=8

http://www.cancervic.org.au/about-cancer/cancer_types/endocrine_cancer

http://www.oncolink.org/types/types1.cfm?c=4

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer Prevention: Research & Programs, Chemical Biology and its relations to Metabolic Disease, Genomic Testing: Methodology for Diagnosis, Imaging-based Cancer Patient Management, Metabolomics, Molecular Genetics & Pharmaceutical, Nutrigenomics, Personalized and Precision Medicine & Genomic Research, Pharmacogenomics, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics | Tagged Cancer - General, Chemotherapy, endocrine tumor, hormone, Immunotherapy, metastasis, oncology, Radiation, Radiation therapy, surgery, Therapy | 4 Comments »

DNA: One man’s trash is another man’s treasure, but there is no JUNK after all

June 24, 2013 by Demet Sag, Ph.D., CRA, GCP

John Rinn – Genomic Garbage Man (Photo credit: ChimpLearnGood)

DNA: One man’s trash is another man’s treasure, but there is no JUNK after all

Author: Demet Sag, PhD

One man’s trash is another man’s treasure, but there is no JUNK after all:

The JUNK has a meaning

Long non-coding RNAs recognized after transcriptome sequencing and studied more closely recently thanks to genomic tiling arrays, cDNA sequencing and RNA-Seq, which they have provided initial insights into the extent and depth of transcribed sequence across human and other genomes. How many are there in the genome? What are their mechanisms? How can we use them in molecular diagnostics and targeted therapies? How do they effect the function in a disease? Is it possible to modulate gene expression at the level of stem cell to redirect the cell differentiation? These are the main questions that we are looking for.

In early 90s actually first lincRNA was described, Xist. The main function was dosage compensation. Then in 2000s FANTOM consortium project changed the perspective on these long transcripts. Then they are called natural antisense transcripts (NATs), because very large number of these transcripts is overlapping with, and is transcribed in the antisense direction, to protein-coding genes. As a result of this study 11000 lincRNA discovered from full length cDNAs in mice. Later, yet another shift occur since these transcribed units are solely located in the introns or within “junk” DNA of protein-coding genes. Another independent study quantified that about 40% of protein-coding genes express NATs. Proven that there is nothing junk about DNA. Then, it was found that there are 8000 lincRNAs and among these 4000 are determined since they provide cell identity with multi-exogenic, polyadenylated, capped, ether in the cytoplasm or in the nucleus. However, even more recent studies show that there are about 20,000 lincRNAs. Furthermore, lincRNAs are classified under three distinct class: 1. Long-non-coding RNAs away from protein-coding genes, 2 NATs transcribed from the opposite strand of protein-coding genes, 3. Intronic lincRNAs expressed from within the introns of protein coding genes.

English: The human genome, categorized by func...

The human genome, categorized by function of each gene product, given both as number of genes and as percentage of all genes. (Photo credit: Wikipedia)

Their function is under study. However, keep in mind that they are redundant, so deleting or creating null mutations may or may not answer specific development questions. On the other hand, epigenetics, gene imprinting, and pathologies can be the best resource to identify their specific roles in biological functions and interactions. Distinct gene regulation either as a cis or trans element, gene imprinting, modulating alternative splicing, nuclear organization, determining a chromatin structure are under study. This will allow us to relate genome structure and function in health and disease better. Identification of their function during biological responses require a long way to be completed due to complexity since lincRNAs also regulate microRNAs. Regardless of many obstacles there is a progress. Disregulation of these lincRNA mainly observed in several cancer types, prostate, breast, hepatocellular carcinoma, colorectal, glioma and melanoma, possibly more. Most of the studies are done in vitro. However, there are many great model organism work as well, such as mice, zebra fish, and worm.

It was also not surprising that their regulation possibly under control of hormones based on circadian clock of our body. So better to sleep eight hour a day is not a cliché.

Next topic will include understanding of lincRNA mechanisms and epigenetics followed by lincRNAs during disease and cellular genesis.

Mechanism, Genome and Genetics:

”Long non-coding RNAs: insights into functions”. Mercer TR, Dinger ME, Mattick JS Nat. Rev. Genet. 2009;10:155–159. http://www.ncbi.nlm.nih.gov/pubmed/19188922

“Long Noncoding RNAs: Past, Present, and Future” Genetics 1 March 2013: 651-669. http://www.genetics.org/content/193/3/651.abstract

“RNA-protein analysis using a conditional CRISPR nuclease” Proc. Natl. Acad. Sci. USA 2 April 2013: 5416-5421. http://www.pnas.org/content/110/14/5416.abstract

“Noncoding RNA and Polycomb recruitment” RNA 1 April 2013: 429-442. http://rnajournal.cshlp.org/content/19/4/429.abstract

“Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs” Nucleic Acids Res 1 August 2012: 6391-6400. http://nar.oxfordjournals.org/content/40/14/6391.abstract

“Long noncoding RNAs regulate adipogenesis” Proc. Natl. Acad. Sci. USA 26 February 2013: 3387-3392. http://www.pnas.org/content/110/9/3387.abstract

“Circadian changes in long noncoding RNAs in the pineal gland” Proc. Natl. Acad. Sci. USA 14 August 2012: 13319-13324. http://www.pnas.org/content/109/33/13319.abstract

Animal and Development:

“Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis” Genome Res 1 March 2012: 577-591. http://genome.cshlp.org/content/22/3/577.abstract

“Genes for embryo development are packaged in blocks of multivalent chromatin in zebrafish sperm” Genome Res 1 April 2011: 578-589. http://genome.cshlp.org/content/21/4/578.abstract

“Long noncoding RNAs in C. elegans” Genome Res 1 December 2012: 2529-2540. http://genome.cshlp.org/content/22/12/2529.abstract

“A spatial and temporal map of C. elegans gene expression” Genome Res 1 February 2011: 325-341. http://genome.cshlp.org/content/21/2/325.abstract

“SFMBT1 functions with LSD1 to regulate expression of canonical histone genes and chromatin-related factors” Genes Dev. 1 April 2013: 749-766. http://genesdev.cshlp.org/content/27/7/749.abstract

Survivals Comparison of Coronary Artery Bypass Graft (CABG) and Percutaneous Coronary Intervention (PCI) / Coronary Angioplasty

June 23, 2013 by larryhbern

Survivals Comparison of Coronary Artery Bypass Graft (CABG) and Percutaneous Coronary Intervention (PCI) / Coronary Angioplasty

Larry H. Bernstein, MD, Writer
And
Aviva Lev-Ari, PhD, RN, Curator

This is a summary of several studies, mostly reviewing one decade of work at Texas Heart Institute, Houston, TX.

Seminal treatments of the evolving methods, leading to a recent review of options for

Survival comparison of CABD vs PCI
Mitral valve repair or mitral valve replacement for the treatment of ischemic mitral regurgitation. This might further consolidate a series of articles in these chapters.

SOURCES

1. Bypass, Angioplasty Similar in Survival 10 Years After Heart Procedures, Survival Rates Differ Little. K Doheny. WebMD Health News Oct. 15, 2007

http://www.webmd.com/heart-disease/news/20071015/bypass-angioplasty-similar-survival

2. Will Drug-Eluting Stents Replace Coronary Artery Bypass Surgery?

RM Reul, Tex Heart Inst J. 2005; 32(3): 323–330

3. Will Stent Revascularization Replace Coronary Artery Bypass Grafting? JM Wilson Tex Heart Inst J. 2012; 39(6): 856–859

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528239/

4. Coronary Artery Bypass Surgery versus Coronary Stenting. Risk-Adjusted Survival Rates in 5,619 Patients. RP Villlareal,V-V Lee, MA Elayda, JM Wilson. Tex Heart Inst J. 2002; 29(1): 3–9.

http://www.ncbi.nlm.nih.gov/pubmed/11995845

5. Should all ischemic mitral regurgitation be repaired? When should we replace? DJ LaPar, IL Kron. Curr Opin Cardiol. 2011 March; 26(2): 113–117

6. Hybrid Cath Lab Combines Nonsurgical, Surgical Treatments

http://www.dicardiology.com/article/hybrid-cath-lab-combines-nonsurgical-surgical-treatments

Bypass, Angioplasty Similar in Survival 10 Years After Heart Procedures

The survival rates 10 years after coronary artery bypass surgery and angioplasty are similar, according to a new analysis of nearly 10,000 heart patients. Five years after the procedures, 90.7% of the bypass patients and 89.7% of the angioplasty patients were still alive, says Mark A. Hlatky, MD, senior author of the analysis and a professor of health research and policy and professor of medicine at Stanford University School of Medicine in Palo Alto.

Hlatky and colleagues stress that their analysis only applies to a select group of heart patients: those for whom either procedure would be considered a reasonable choice. For patients who are eligible for either heart intervention, “either is feasible,” Hlatky tells WebMD. The report is released early online and will be published in the Nov. 20 issue of the Annals of Internal Medicine.

CABG vs. Angioplasty

The researchers evaluated the results of 23 clinical trials in which 5,019 patients (average age 61 years; 73% men) were randomly assigned to get angioplasty with or without stents (PCI), and 4,944 were assigned to get coronary artery bypass graft surgery (CABG) In angioplasty, interventional cardiologists push a balloon-like device into the coronary arteries and inflate the balloon to widen the vessel. An expandable wire mesh tube called a stent may be inserted to keep the vessel open. Some stents are coated with drugs meant to help prevent the artery from clogging up. In 2005, about 645,000 angioplasty procedures were done in the U.S. In bypass surgery, cardiac surgeons harvest a segment of a healthy blood vessel from another part of the body and use it to bypass the clogged artery or arteries, rerouting the blood to improve blood flow to the heart. About 261,000 bypass procedures were done in the U.S. in 2005.

Findings

Besides similar survival rates overall, the researchers found no significant survival differences between the two procedures for patients with diabetes, although earlier research had seemed to favor bypass surgery. Similar numbers of patients suffered heart attacks within five years of the procedures. While 11.9 of those who got angioplasty had a heart attack within five years, 10.9% of those who got bypass did. Repeat procedures were more common in angioplasty patients. While 46.1% of angioplasty patients who didn’t get a stent needed repeat procedures, 40.1% of those who got a stent did. But just 9.8% of surgery patients needed another procedure. The study didn’t include information on drug-coated stents.

Second Opinions

The new analysis is “very complete,” says Kim A. Eagle, MD, director of the Cardiovascular Center and Albion Walter Hewlett Professor of Internal Medicine at the University of Michigan, Ann Arbor. The study shows, he says, that if either procedure is considered appropriate for an individual patient, the decision can rest on patient attitudes and preferences. Patients preferences might be based on lower need to repeat in favor of surgery, or on avoidance of surgery in favor of angioplasty. But it is important to note, acoording to Curtis Hunter at Santa-Monica-UCLA, that the studies cover the least sick with heart disease, so the two procedures are shown to be equal in a very small subset of the patients.

Coronary Artery Bypass Surgery versus Coronary Stenting – Risk-Adjusted Survival Rates in 5,619 Patients THIJ. 2002

We used the Texas Heart Institute Cardiovascular Research Database to retrospectively identify patients who had undergone their 1st revascularization procedure with coronary artery bypass surgery (CABG; n=2,826) or coronary stenting (n=2,793) between January 1995 and December 1999. Patients were classified into 8 anatomic groups according to the number of diseased vessels and presence or absence of proximal left anterior descending coronary artery disease. Mortality rates were adjusted with proportional hazards methods to correct for baseline differences in severity of disease and comorbidity.

We found that in-hospital mortality was significantly greater in patients undergoing CABG than in those undergoing stenting (3.6% vs 0.75%; adjusted OR 8.4; P <0.0001). At a mean 2.5-year follow-up, risk-adjusted survival was equivalent (CABG 91%, stenting 95%; adjusted OR 1.26; P = 0.06). When subgroups matched for severity of disease were compared, no differences in risk-adjusted survival were seen. A survival advantage of stenting was noted in 3 categories of patients: those >65 years of age (OR 1.33, P = 0.049), those with non-insulin-requiring diabetes (OR 2.06, P = 0.002), and those with any noncoronary vascular disease (OR 1.59, P = 0.009).

In this nonrandomized observational study, CABG had a higher periprocedural mortality rate than did percutaneous stenting. At 2.5 years, however, the survival advantage of stenting was no longer evident. These data suggest that there is no intermediate-term survival advantage of CABG over stenting in patients who have multivessel disease with lesions that can be treated percutaneously. (Tex Heart Inst J 2002;29:3–9)

Fig. 1 Adjusted and unadjusted survival rates in all patients treated with CABG or PCI-stenting
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC101260/table/t3-2/?report=previmg

TABLE III. Multivariate Correlates of Intermediate-Term (2.5-Year) Mortality
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC101260/table/t3-2/?report=previmg

Fig. 2 Adjusted odds ratios comparing the results of CABG and PCI-stenting in the 8 anatomic subgroups.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC101260/bin/2FF2.jpg

TABLE IV. Intermediate-Term (2.5-Year) Survival According to Treatment in Each of the 8 Anatomic Groups
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC101260/bin/2TT4.jpg

Fig. 3 Adjusted odds ratios comparing the results of CABG and PCI-stenting in the various prespecified subsets.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC101260/bin/2FF3.gif

Will Drug-Eluting Stents Replace Coronary Artery Bypass Surgery?

Abstract

Introduction

The growth of the PCI industry and the consequent decline in the number of patients referred for CABG has produced much speculation about the future role of each type of intervention. Because the new drug-eluting stents allow PCI to be performed with lower rates of early restenosis than do bare-metal stents or percutaneous transluminal coronary angioplasty (PTCA) alone, 2–8 some have predicted that surgical revascularization will soon be obsolete.

CABG vs Pharmaco-Therapy

Randomized clinical trials performed during the 1970s and early 1980s clearly established the advantages of CABG over medical therapy in patients with triple-vessel CAD, left main coronary artery stenosis, double-vessel CAD with proximal left anterior descending (LAD) coronary artery stenosis, or left ventricular dysfunction. Problems arose subsequently because of the limitations built into the trial so that the results were biased in favor of medical therapy. These were:

stringent exclusion criteria that eliminated a large percentage of potential participants
left main CAD and an ejection fraction of less than 0.40, eliminated patients for whom CABG would have been beneficial
the high rate of crossover from the medical to the surgical groups

The numerous technical and technological advances made since these trials were completed limit the degree to which their results resemble those of the CAD treatments used today. The maximal medical therapy used during the trials did not routinely include lipid-lowering agents, β-blockers, angiotensin-converting enzyme (ACE) inhibitors, clopidogrel, or some of the other drugs currently used for CAD. Nor did the CABG groups benefit from advances that were subsequently made in preoperative imaging, perfusion and myocardial protection, anesthesia, and perioperative and intensive care practices. CABG did not then include the use of left internal mammary artery (LIMA) grafts, much less other arterial conduits. Finally, PCIs, including balloon angioplasty and stenting, were not included in these trials.

CABG vs PTCA

Randomized trials comparing PTCA with CABG revealed dramatically higher re-intervention rates in the PTCA groups and better angina relief in the CABG groups, although there were no significant differences in death or myocardial infarction rates. The Duke database study. 9 showed better survival rates with PTCA than with CABG in patients with single-vessel CAD, whereas CABG produced better survival than did PTCA in patients with severe, triple-vessel CAD.

These results are not necessarily representative of the results obtainable today with PTCA and CABG, for several reasons.

1. stents were not used in the PTCA patients in these trials

2. operative mortality rates for the CABG groups were higher than the rates currently found in the Society of Thoracic Surgeons (STS) database

3. the inclusion/exclusion criteria of these studies eliminated a high percentage of those patients who might have benefited more from CABG than from PTCA

CABG vs Stents

The introduction of coronary artery stenting resulted in better outcomes than those produced by balloon angioplasty or by other adjuncts, including rotational atherectomy, brachytherapy, and laser angioplasty. Since then, stent designs and delivery techniques have advanced considerably. The use of coronary stents has greatly decreased the necessity of emergent CABG for technical failure of PCI and for dissection or rupture of coronary arteries during PCI. Another major advance in the application of PCI is the use of the antiplatelet agent clopidogrel in addition to aspirin after PCI, as well as the use of glycoprotein (GP) IIb/IIIa receptor inhibitors during the procedure. These adjuncts have significantly reduced the incidence of acute and subacute thrombosis after PTCA with stenting.

Randomized trials comparing PTCA plus stenting with PTCA alone have shown that stenting significantly reduces rates of restenosis and re-intervention, as well as the frequency of emergent CABG. On the other hand, randomized trials of stenting versus surgery have produced less conclusive results regarding the mid-term survival and freedom from adverse events. For example, the Stent or Surgery (SOS) trial reported a greater need for repeat revascularization in the stent group (21%) than in the CABG group (6%) and a survival advantage in the CABG group (hazard ratio, 2.91; 95% CI, 1.29–6.53; P = 0.01) during the 3-year follow-up period. Additionally, angina and the use of anti-angina medications were less common in the CABG group at 1-year follow-up.

The ARTS and ERACI trials also reported an increased need for revascularization in the stent groups but did not show a survival advantage in the CABG groups. This was due in part to a higher operative mortality rate in the CABG group than reported in the STS database. Like the PCI versus CABG trials mentioned previously, these randomized trials involved a select group of patients with relatively low expected mortality rates and relatively high expected technical success with PCI.

Observational data in retrospective analyses of large patient databases comparing CABG with PCI plus stenting does indicate that, because of the greater invasiveness of surgical revascularization, CABG produces greater operative mortality than does PCI. However, in patients with multivessel CAD, the risk-adjusted survival rates at 2.5 years of follow-up are no better for PCI than for CABG, and 3 recent risk-adjusted observational studies showed that the CABG patients had a significant survival advantage at 3- to 8-year follow-up. The CABG patients had significantly more preoperative risk factors than did the PCI patients in each study, so that unadjusted, the CABG groups in each study included significantly more patients with triple-vessel disease and fewer patients with double-vessel disease than did the PCI groups. Again, we have a moving target with recent advances in both surgery and PCI technology.

Disadvantages of Stenting

The Achilles’ heel of PCI is restenosis and the need for repeat revascularization. Stents have decreased the rate of acute and subacute periprocedural thrombosis. The newer, drug-eluting stents (DESs) have improved in-stent restenosis rates, especially in the carefully selected patient populations studied in the early DES trials. In the RAVEL trial, the early reports of zero in-stent restenosis compared favorably with the 27% in-stent restenosis rates in the bare-metal stent control group at 6-month follow-up. However, the RAVEL trial excluded patients with lesions longer than 18 mm, ostial targets, calcified or thrombosed targets, or target arteries less than 2.5 mm in diameter.

The media frenzy that followed the release of these findings created a public demand for these new “miracle” stents that apparently did not re-occlude. Stories of CAD patients refusing conventional PCI and CABG —instead, adding their names to the list of patients waiting for U.S. Food and Drug Administration (FDA) approval of DESs—appeared to change the practice patterns of cardiologists and cardiac surgeons overnight. And then there were the calls for class-action lawsuits and recall of various DES models. After the FDA approved the Cordis Cypher™ DES (Cordis Corporation, a Johnson & Johnson company; Miami Lakes, Fla), a few reports of subacute thrombosis and hypersensitivity reactions prompted the FDA to release a public health notification on 29 October 2003.

The SIRIUS trial had slightly less strict exclusion criteria than did the RAVEL trial, admitting patients with target lesions 2.5 to 3.5 mm in diameter and 15 to 30 mm long, as well as patients with diabetes mellitus (who constituted 26% of the total group). The SIRIUS trial also differed from the RAVEL trial in that the reported end-point was in-segment restenosis, rather than in-stent restenosis. The results showed a significant advantage of DESs over bare-metal stents for preventing in-segment restenosis (9.2% vs 32.3%) and target failures (10.5% vs 19.5%), but major adverse cardiac events were more frequent in the DES group than in the bare-metal stent group (3.7% vs 1.0%). Interestingly, the 6-month restenosis rates of the bare-metal stents in the RAVEL and SIRIUS control groups were much higher than the 19% 12-month restenosis rate associated with bare-metal stents in an earlier study comparing bare-metal stents with PTCA. In fact, the restenosis rates in the RAVEL and SIRIUS control groups more closely resembled the 40% restenosis rate reported for the PTCA control group in the earlier study.

The practical advantages of DESs over bare-metal stents are evident; nonetheless, we still do not have sufficient mid-term or long-term clinical data to argue that PTCA with DESs is preferable to CABG in “real-world” patients who require revascularization. Although DESs will likely provide better outcomes than bare-metal stents for many patients for whom stenting is indicated, a general extrapolation of existing data to justify the use of DESs in patients for whom CABG is currently indicated is unknown, perhaps undeterminable because the lesion and patient characteristics that lead to the failure of PCI are multifactorial, and the size of the population with lesions having unfavorable characteristics , such as,

longer
total occlusion
branch
small-diameter
calcified
multiple
left main
ostial, and
diffuse lesions

are being treated with PCI more often, as well as diabetics, multiple lesions, and patients with multiple comorbidities.

Advantages of CABG

Over the last 4 decades, surgical coronary artery revascularization techniques and technology have advanced significantly. As a result, despite an increasingly older and sicker patient population, CABG outcomes continue to improve. Observed operative mortality rates have decreased because advances in preoperative evaluation, including more precise coronary artery and myocardial imaging and diagnostic techniques, have allowed more appropriate patient selection and surgical planning. In addition, preoperative, intraoperative, and postoperative monitoring and therapeutic interventions have made CABG safer, even for critically ill and high-risk patients. Improvements in cardiopulmonary perfusion and careful myocardial protection, as well as the use of off-pump and on-pump beating- heart techniques in selected patients, have also decreased perioperative morbidity and mortality rates.

LIMA-to-LAD Long-Term Patency

The long-term benefits of CABG with regard to survival and quality of life are dependent on prolonged graft patency. The LIMA-to-LAD bypass, which is now performed in more than 90% of CABG procedures, shows excellent patency in 10- to 20-year angiographic follow-up studies, setting the gold standard with which other revascularization strategies should be compared. Tatoulis et al. reported that LIMA-to-LAD grafts had a 97.1% patency rate in patients who underwent angiography for cardiac symptoms. Those authors also found high patency rates at 5-year (98%), 10-year (95%), and 15-year (88%) follow-up. However, there are not yet long-term data on bare-metal stents or DESs, and by the time 10- or 20-year data are available, DESs probably will have been replaced by a newer, more advanced technology.

Because of the reported success of the LIMA-to-LAD bypass, other types of arterial conduits are also being used much more frequently. Conduit selection has become an area of great interest to cardiac surgeons, and conduit studies are expanding our understanding of the mechanisms of graft failure and ways to improve bypass graft patency. For example, studies have shown that patients who undergo CABG with both LIMA and right internal mammary artery (RIMA) conduits have better results than those who undergo CABG with one IMA and one or more saphenous vein grafts.

Techniques to Improve Conduit Patency

To maximize the odds of long-term graft patency, surgeons carefully harvest the graft as a pedicled or skeletonized conduit using “no touch” techniques. Using careful anastomotic technique to avoid excessive turbulence at the anastomosis site will prolong graft patency, and the quality of the conduit is crucial. Long-term graft patency depends not only on the conduit chosen but also on the target artery and the degree of stenosis proximal to the anastomosis. Maintaining flow patterns in the native artery, including residual flow (that is, competitive flow) and outflow, is important to avoid stasis in the graft, turbulence at the anastomosis, and vasospasm, especially in arterial conduits. Studies have shown an inverse relationship between the degree of proximal stenosis and graft patency. Targeting the LAD produces the highest patency rates. The characteristics of the target artery also determine graft patency, including –

1. the diameter of the target artery,

2. the presence or absence of diffuse disease within the artery,

3. whether or not the artery requires endarterectomy

Surgeons can avoid atheroembolic events by handling the aorta carefully or not at all. They can also improve safety by

1. using aggressive myocardial protection techniques;

2. avoiding the induction of inflammatory mediators; and

3. carefully controlling

blood pressure,
body temperature, and
electrolyte and glucose levels.

Although there have been major innovations that have enabled surgeons to perform cardiac surgery (including CABG) less invasively, minimally invasive surgical procedures are useful only if they are at least as efficacious as conventional surgery. New technology is being developed to enhance the evolving field of minimally invasive coronary bypass surgery.

Hybrid Coronary Revascularization

As PCI technology improves and techniques of LIMA-to-LAD grafting become less invasive, hybrid coronary revascularization is becoming a distinct possibility. For example, a minimally invasive, off-pump, direct LIMA-to-LAD anastomosis can be combined with DES placement in a focal mid-right-coronary-artery lesion in a patient with complex proximal LAD lesions. Hybrid coronary revascularization procedures are currently being performed, with promising early results. A few centers now have hybrid operating rooms with cardiac surgical and coronary angiographic capabilities that make it possible to perform simultaneous hybrid coronary revascularizations.

Although coronary artery bypass grafting (CABG) remains the treatment of choice for certain types of coronary artery disease (CAD), percutaneous coronary intervention (PCI)—particularly coronary angioplasty with stenting—has become the most popular nonmedical treatment approach to CAD. Some have speculated that, with the advent of drug-eluting stents (DESs), PCI will replace CABG entirely. However, the complete disappearance of CABG is both unlikely and unwarranted, for several reasons. Published randomized trials of CABG, PCI, and medical approaches to CAD compared only highly selected subgroups of patients because of strict exclusion criteria that often favored the PCI cohorts. Therefore, their results do not constitute sufficient evidence for the superiority of PCI over CABG in all CAD patients requiring revascularization. As PCI indications broaden to include more complex lesions and more high-risk patients, outcomes will not remain as favorable. In addition, although PCI is less invasive than surgery, CABG offers more complete revascularization and better freedom from repeat revascularization. Furthermore, no long-term patency data on DESs yet exist, whereas excellent 10- and 20-year patency rates have been reported for the left internal mammary artery-to-left anterior descending artery graft used in most CABG procedures. While PCI has been changing, CABG has not been stagnant; recently, advances in many aspects of the CABG procedure have improved short- and long-term outcomes in CABG patients. Both CABG and PCI technologies will continue to advance, not necessarily exclusive of one another, but no data yet exist to suggest that DESs will render CABG obsolete any time soon.

Will Stent Revascularization Replace Coronary Artery Bypass Grafting?

When we discuss revascularization outcomes, we are talking about 3 major endpoints: death, myocardial infarction, and symptom control. With respect to death, we know that revascularization benefits patients who have severe multivessel disease and left ventricular dysfunction or other physiologic indicators of high risk. 2-vessel disease with proximal left anterior descending coronary artery (LAD) stenosis has been accepted as an indication for revascularization, even though the supporting data come from a small subgroup in a single trial. There has been no success in proving that endovascular treatment has a positive impact on stable CAD, but it is relevant because we leave the native arteries relatively intact. Attempts to improve graft performance beyond the relatively spectacular performance of the pedicled internal mammary artery (IMA) graft to the LAD have been disappointing.

Fig. 1 Graph of graft patency shows deterioration rates over 10 years and the comparative superiority of using the internal mammary artery (IMA) instead of the saphenous vein (SVG).http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528239/bin/25FF1.gif

Percutaneous Transluminal Coronary Angioplasty

When angioplasty was introduced, the hope was for a method of revascularization that would rival coronary artery bypass grafting. However, the results were mixed. Angioplasty worked well in patients with no major risk factors, such as diabetes mellitus, but failed miserably in diabetic patients. In fact, the Bypass Angioplasty Revascularization Investigation (BARI) taught us this: if revascularization is needed, regardless of physiologic markers of high risk, the use of percutaneous coronary intervention (PCI) is potentially harmful in comparison with an IMA bypass for the LAD.

Stents and Short-Term Outcomes

The use of stents drastically reduced the probability of emergent surgery after attempted; however, the probability of new lesion formation or restenosis after intervention did not decrease.

Fig. 2 Diagrams show the calculated success (after percutaneous revascularization) of A) percutaneous transluminal coronary angioplasty (PTCA), and B) bare-metal and C) drug-eluting stenting in patients with 3-vessel coronary artery disease (CAD).
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528239/bin/25FF2.gif

At the same time, surgeons got better. Myocardial preservation techniques improved, and the use of the pedicled IMA graft changed the game. As a result, successful revascularization, meaning long-term success, became the domain of the surgeon. We at the Texas Heart Institute/St. Luke’s Episcopal Hospital (THI/SLEH) examined our long-term outcomes after stenting or surgery, and we initially reported that stenting was just as beneficial as surgery. This was in accord with the results of several trials: whenever placing a stent was feasible, stent therapy and surgery had the same outcome.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528239/bin/25TT1.jpg

success after PTCA vs bare-metal and drug-eluting stents

Stents and Long-Term Outcomes

Later, when we looked at longer-term follow-up data and the effects of multiple procedures, this picture began to change. Stented patients underwent more procedures. When the risk of one surgical procedure was compared with that of multiple endovascular procedures, the outcomes became more similar, especially in patients with bifurcation lesions or lesions with severe calcification. Drug-eluting stents, with their promise of no restenosis, substantially increased interventional cardiologists’ reach, but not their grasp. In patients with multivessel disease and high-risk lesions, DES placement was almost as risky as surgery and did not yield the same long-term benefit.

Nevertheless, we found locally that the introduction of the DES, with its lower risk of restenosis, was treated as a blessing to proceed with stenting (Table I). This did not follow the data, but cardiologists continued anyway, given the promise of less restenosis. Early risk was discounted, glycoprotein IIb/IIIa inhibitor use declined overnight, and the rate of endovascular procedural complications rose to meet that of surgery without the promise of an IMA graft in our future.

Table I. Independent Predictors of 30-Day Major Adverse Cardiac Events and 3-Year Survival after Drug-Eluting Stent Placement
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528239/bin/25TT1.jpg

Comparing Stenting and Surgery

For decades, methods have been sought to quantify lesion complexity in order to compare the early and late risks associated with stenting versus surgery. Although no perfect system has been devised, the SYNTAX was an important step forward. The SYNTAX score is a simple, computer-based tool for evaluating the risk of complications or failure after PCI. And there are other tools for estimating the same complications after surgery. These estimates enable cardiologists to give patients objective advice regarding the revascularization method that has the best short- and long-term probability of success.

In the patient with non-life-threatening disease (that is, not left main or severe multivessel CAD with left ventricular dysfunction or severely impaired function), stent revascularization has become a reasonable, although not ideal, alternative to surgical revascularization. However, this is true only if stenting is confined to patients whose anatomy and physiology are suited to it—considerations that are well quantified in the SYNTAX score. Whenever questions arise as to the most appropriate therapy, the SYNTAX score should be weighed against clinical characteristics that affect surgical risk. This will guide discussions between the cardiologist, cardiovascular surgeon, patient, and treating physician.

I think that our THI risk is more useful than the other available scores. It uses simple clinical data and can be easily calibrated to the geographic location of its use. Other scores require data that might not be available at the time of clinical decision-making or at all—making such predictions hazardous, at best.

Conclusion

With regard to the chosen mode of revascularization, it is perhaps safe to say that the decision goes beyond the individual physician and must become collective. When a patient has multivessel disease, a reasoned approach must be taken, using these predictive tools and considering the patient’s wishes. Treatment decisions should include all interested parties: the patient, cardiologist, cardiovascular surgeon, and anesthesiologist. The time of ad hoc angioplasty for the patient with multivessel CAD has passed.

Should all ischemic mitral regurgitation be repaired? When should we replace? Curr Opin Cardiol. 2011

Abstract

Purpose of review

Ischemic mitral regurgitation (IMR) is a major source of morbidity and mortality. Although mitral valve repair has become recently popularized for the treatment of IMR, select patients may derive benefits from replacement. The purpose of this review is to describe current surgical options for IMR and to discuss when mitral valve replacement (MVR) may be favored over mitral valve repair.

Recent findings

Current surgical options for the treatment of IMR include surgical revascularization alone, mitral valve repair, or MVR. Although surgical revascularization alone may benefit patients with mild–moderate IMR, most surgeons advocate the performance of revascularization in combination with either mitral valve repair or replacement. In the current era, mitral valve repair has proven to offer improved short-term and long-term survival, decreased valve-related morbidity, and improved left ventricular function compared with MVR. However, MVR should be considered for high-risk patients and those with specific underlying mechanisms of IMR.

Summary

In the absence of level one evidence, mitral valve repair offers an effective and durable surgical approach to the treatment of mitral insufficiency and remains the operation of choice for IMR. MVR, however, is preferred for select patients. Future randomized, prospective clinical trials are needed to directly compare these surgical techniques.

Introduction

Ischemic mitral regurgitation (IMR) describes insufficiency of the mitral valve in the setting of myocardial ischemia, resulting from coronary artery disease. Although IMR may present in the acute setting, usually as a papillary rupture (Carpentier type II), it is usually a consequence of chronic myocardial ischemia that typically presents weeks following a complete infarction. IMR describes mitral insufficiency in the absence of degenerative (structural) mitral valve disease. The underlying pathophysiologic mechanisms of IMR are often complex, resulting from several different structural changes involving left ventricular geometry, the mitral annulus, and the valvular/subvalvular apparatus. Although changes to any one component may result in detectable mitral valve insufficiency, moderate-to-severe IMR requiring surgical correction often involves the complex interplay of several co-existent anatomic changes. These underlying mechanisms result in clinically significant valve incompetence due to the combined effects of decreased ventricular function and restricted motion of the valve itself due to tethering.

IMR is a major source of patient morbidity and mortality. Although the frequency of IMR differs based upon imaging modality, estimates have suggested that nearly 20–30% of patients experience mitral insufficiency following myocardial infarction. Furthermore, its intimate association with heart failure and poor outcomes for suboptimal medical management further complicates the management of clinically significant IMR. Recent evidence suggests that moderate or severe mitral regurgitation may be associated with a three-fold increase in the adjusted risk of heart failure and a 1.6-fold increase in risk-adjusted mortality at 5-year follow-up. In addition, unfavorable patient profiles and co-existing comorbid disease, including renal failure, chronic obstructive pulmonary disease, diabetes, and impaired left ventricular function, further complicate the clinical picture for those with IMR. Consequently, surgical correction of this condition is often required.

The purpose of this review is to analyze published results for the surgical correction of IMR and to provide current opinion regarding the selection of mitral valve procedure in the setting of myocardial ischemia. Herein, we review current surgical options for IMR and discuss when MVR may be favored over mitral valve repair.

Surgical options for ischemic mitral regurgitation: surgical revascularization alone

Surgical revascularization alone with CABG may be beneficial for some patients. Although CABG alone may be performed in cases of mild-to-moderate IMR, for the treatment of severe IMR, evidence supports performance of CABG with a mitral valve. In fact, a lack of evidence exists to support the performance of CABG alone for severe IMR. In one retrospective review of propensity-matched cohorts, Diodato et al. suggested that addition of a mitral valve procedure to patients undergoing CABG for moderately severe to severe IMR did not increase mortality or improve survival over the performance of CABG alone. This study, however, was limited by small sample sizes (51 CABG + mitral valve repair vs. 51 CABG alone) and 3-year follow-up. To the contrary, substantial evidence exists to support the performance of surgical revascularization alone in cases of mild-to-moderate IMR.

A study by Aklog et al. investigated the role of CABG alone in the correction of moderate IMR. In their series of 136 patients with moderate IMR, they demonstrated that performance of revascularization alone conferred improvement of mitral regurgitation in 51% of patients with complete resolution in an additional 9%. Despite these results, 40% of patients remained with 3–4+ mitral regurgitation, leading the authors to conclude that CABG alone may not be the optimal therapy for most patients and suggest that concomitant mitral annuloplasty may improve results. Other series similarly suggest that complete resolution of functional IMR is uncommon following revascularization alone. Despite the presence of residual mitral regurgitation following revascularization, the impact of performance of CABG without a valve procedure on long-term survival remains ill defined. Currently, on-going prospective evaluation may help to define the potential role of revascularization alone for patients with moderate IMR. Until the completion of these trials, however, evidence supports the performance of surgical revascularization combined with a mitral valve procedure for moderate-to-severe mitral regurgitation.

Surgical revascularization with a mitral valve procedure

The majority of patients with moderate-to-severe IMR require surgical revascularization with a concomitant mitral valve procedure (MVR or mitral valve repair). Historically, these procedures have been associated with high morbidity and mortality as well as poor long-term. However, improved surgical techniques and postoperative management have improved contemporary outcomes. Those favoring mitral valve repair promote its beneficial effects on survival, preserved ventricular function, and the avoidance of long-term anticoagulation, whereas those favoring MVR argue that it ensures long-term freedom from recurrent mitral insufficiency.

Mitral valve replacement vs. mitral valve repair

The use of MVR for IMR eliminates the possibility of recurrent IMR. In addition, previous literature suggests improvements in surgical technique for MVR 29–32. For patients with IMR, MVR with preservation of the subvalvular apparatus using a chordal sparing technique has been shown to be beneficial 33. David and Ho 33 demonstrated a significant survival benefit for patients undergoing MVR with preservation of chordae tendineae (89%) compared with complete excision of the mitral valves (59%) in a cohort of 51 patients with IMR. In addition, Cohn et al. suggested disproportionate survival benefits favoring MVR in a cohort of 150 patients with both functional and structural IMR, concluding that survival following performance of mitral valve procedures for IMR was more dependent on underlying pathophysiology rather than surgical technique. More recently, series have suggested equivalent results for the MVR and mitral valve repair. Mantovani et al. report that prosthetic MVR and mitral valve repair offer very similar results for chronic IMR, demonstrating similar operative mortality and 5-year actuarial survival for both techniques. In a similar report, Magne et al.•• compared short-term and long-term outcomes for 370 patients undergoing mitral valve repair (n = 186) and MVR (n = 184) for IMR. Although operative mortality was lower for mitral valve repair compared with MVR (9.7 vs. 17.4%, P = 0.03), 6-year survival was similar for both operations (73 ± 4 vs. 67 ± 4%, P = 0.17). Type of procedure was also not an independent predictor of mortality following risk adjustment. As a result, the authors suggest that mitral valve repair is not superior to MVR for patients with IMR.

In contrast, other series favor the performance of mitral valve repair for functional IMR. Although several repair techniques exist, restrictive annuloplasty remains the most commonly performed operation 37• and has been shown to be beneficial in both functional and chronic IMR 38•. The purported benefits of improved survival, decreased valve-related morbidity, and improved left ventricular function have been previously established, and several series have reported lower hospital mortality with mitral valve repair compared with MVR.

The Cleveland Clinic published a landmark review of 482 patients undergoing mitral valve procedures for IMR to study the influence of mitral valve procedure type on survival 1. In this series, propensity-matched cohorts were compared: mitral valve repair (n = 397) vs. MVR (n = 85). Concomitant CABG was performed in 95% of operations, and annuloplasty for repair occurred in 98% of cases. After matching, patients were risk stratified into five quintiles. Group 1 represented the highest-risk patients with higher degrees of heart failure and emergent operations, and group 5 represented the lowest-risk patients. Subsequent survival analysis revealed that overall 5-year survival was poor for patients with IMR (58% mitral valve repair vs. 36% MVR, P = 0.08). Moreover, within matched quintiles, the highest-risk patients (quintile 1) had the worst survival, but survival was similar (P = 0.4) despite mitral valve procedure type. In contrast, survival favored mitral valve repair over replacement for quintiles III–V (P = 0.003).

In the absence of published randomized trials, two recently published meta-analyses provide more robust comparisons of the influence of surgical mitral valve repair or replacement. Shuhaiber and Anderson compared outcomes of 29 studies, including over 10 000 patients. Study groups were stratified based upon mitral valve etiology into ischemic, degenerative/myxomatous, rheumatic, and mixed groups. Summary analyses indicated worse overall survival for MVR (early mortality odds ratio = 2.24 and total survival hazard ratio = 1.58) compared with repair. Mitral valve repair was also associated with lower rates of thromboembolism. Moreover, a nonsignificant trend toward lower 30-day mortality favored mitral valve repair for those with IMR. The most recent meta-analysis to date compared short-term and long-term survival of mitral valve repair vs. replacement specifically for IMR ••. In this analysis, nine studies were included based upon stringent exclusion criteria to ensure direct comparisons of survival for mitral valve procedures exclusively performed for IMR. Interestingly, in this series, although patients undergoing MVR were older, those undergoing repair often had higher rates of hypertension and diabetes with lower ejection fractions. Further, the proportion of patients with severe ventricular dysfunction was similar between procedure groups. These findings conflict with a common assumption that an inherent selection bias exists within published studies for the performance of mitral valve repair in healthier patients. Nevertheless, MVR was associated with worse short-term mortality (odds ratio = 2.667) and long-term mortality (hazard ratio = 1.35) compared with mitral valve repair, and the authors advocate that choice in mitral procedure should be based upon individual patient profile.

When not to repair ischemic mitral regurgitation?

Within the context of published literature and current dogma among practicing surgeons, the fundamental question of when not to repair an ischemic mitral valve remains. For several years, accumulated evidence supports the performance of mitral valve repair over replacement for the surgical treatment of functional IMR. The aforementioned benefits of repair include improved long-term survival, durability and efficacy, improved ventricular function, and avoidance of chronic anticoagulation therapy. Nevertheless, MVR still plays a select role in the treatment of IMR.

With respect to the performance of MVR, the use of bioprosthetic valves and the avoidance of mechanical valve replacement are preferred. This choice is largely driven by the avoidance of complications due to long-term anticoagulation use as well as by the belief that it is unlikely that the majority of patients requiring MVR are likely to encounter bioprosthetic deterioration in their lifetime. In addition, MVR with techniques to preserve the subvalvular apparatus should be performed when possible.

Summary

Undoubtedly, the debate regarding when to perform repair or replacement for IMR remains unsettled. In the recent era, mitral valve repair has proven efficacious and remains the preferred surgical strategy for most cases of IMR. MVR should be considered for severe tethering, complex or uncertain mechanisms of mitral insufficiency, regurgitation due to papillary muscle rupture, and perhaps for the sickest and highest-risk patients.

The present review was supported by Award Number 2T32HL007849-11A1 (D.J.L.) from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors.

Hybrid Cath Lab Combines Nonsurgical, Surgical Treatments 2008

A new cardiac treatment facility that couples the benefits of interventional cardiology with cardiothoracic surgery for critically ill newborns, children and adults has opened at Rush University Medical Center, Chicago. Toshiba’s new biplane hybrid cardiac suite, which is one of only three facilities of its kind in the U.S., is equipped with the latest in continuous, real-time imaging technology and radio frequency identification (RFID) technology which allows “all-in-one-room” care. The suite allows collaboration between the surgeon and interventional cardiologist on complex heart problems. For example, fixing a very large hole in the heart can be done by inserting a catheter through a small incision in the chest rather than relying on major surgery to open the chest to reach the heart. “Now, interventional cardiologists and cardiothoracic surgeons working together in this suite will reduce the amount of time required to correct complex heart problems and reduce the emotional and physical stress placed on a patient and their family – which translates into less pain, less scarring and a faster recovery time,” Ziyad Hijazi, M.D., director of the new Rush Center for Congenital and Structural Heart Disease. The hybrid suite is equipped with the latest technology for minimally invasive interventional cardiology that involves the use of a catheter and an image-guidance system to thread tiny instruments through blood vessels to repair the heart. Through these special catheters, physicians at Rush can implant stents, artificial heart valves and insert patches for holes in the heart. In many complex cardiac cases, patients who would otherwise have no other option but to undergo open-heart bypass surgery can now have minimally invasive procedures that would otherwise not be available to them. “We can now communicate with colleagues and obtain their expertise in real time for very complex situations,” said Dr. Hijazi. “If physicians decide another procedure is needed, even surgery, the suite can be converted into an operating room and the surgical team can be assembled in the new suite ”Patients at Rush will stay in one place in the new hybrid cardiac suite where all the imaging technology and implantable devices that might be needed are stored and located. The additional ability it gives us to provide surgical treatments allows us to provide the most comprehensive care in the most sensitive manner for patients with often extremely fragile conditions.” The new hybrid cardiac catheterization suite has the most advanced imaging technologies and can still get a precise, optimal image of any region of the heart regardless of the size or complexity of congenital heart disease. The imaging system also features eight-inch cardiac flat panel detectors designed to deliver distortion-free images. The suite also includes intravascular ultrasound machines, which takes real-time images to allow physicians to see the progress of the procedure taking place inside the patient’s body. A high-tech, automated clinical resource management system located in the suite stores and tracks the medication, surgical tools, medical devices, and implantable devices and supplies using the latest RFID enabled technology.

Hybrid Cath Lab/ORs Are the Way of the Future

Recent developments in cardiac surgery and interventional cardiology with new percutaneous alternatives for aneurysm repair, valve replacements, shunt closure devices and aortic arch reconstruction have led to the creation of integrated, hybrid cath lab/operating rooms (OR) that allow both surgical and intravascular procedures. These rooms offer both surgical equipment and high-end angiographic equipment. Creating such rooms requires special planning and design from both surgical and interventional cardiologists working closely together. Cath labs have high-quality fluoroscopy equipment, but generally are smaller rooms and lack the sterile requirements and equipment needed for surgical procedures. ORs tend to use lower quality mobile C-arms, which are not ideal for interventional procedures. The hybrids aim to provide the best of both worlds. The trend toward hybrid labs has been reinforced by digital angiography manufacturers partnering with surgical equipment companies to create easy-to-integrate hybrid room solutions with coordinated installation. Philips partners with both Skytron and Steris. Toshiba partners with MAQUET. GE Healthcare, Siemens and Toshiba also offer hybrid installations. Philips said while some hospitals want to combine interventional procedures with minimally invasive surgeries, they also want a properly equipped room in case emergency surgery is needed.

Philips said hybrids also allow hospitals with lower PCI numbers to get a bigger bang for their buck by allowing the same room to serve the needs of surgeons. Penn Presbyterian Medical Center in Philadelphia, PA, created a hybrid lab with help from Siemens, which opened in November. Wilson Szeto, M.D., cardio-thoracic surgeon, and William Matthai, M.D., interventionalist, both from Penn Presbyterian said hybrid labs are ideally suited for procedures that require both percutaneous and surgical interventions, percutaneous valve replacements, deploying percutaneous septal occluders or installing aortic stent grafts. Interventionalists can also be called in after cardiac surgery to perform a completion angiography.

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45. Madan P, Elayda MA, Lee VV, Wilson JM. Predicting major adverse cardiac events after percutaneous coronary intervention: the Texas Heart Institute risk score. Am Heart J 2008; 155(6):1068–74. [PubMed]

46. Gillinov AM, Wierup PN, Blackstone EH, et al. Is repair preferable to replacement for ischemic mitral regurgitation? J Thorac Cardiovasc Surg. 2001;122:1125–1141. [PubMed]

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52. Micovic S, Milacic P, Otasevic P, et al. Comparison of valve annuloplasty and replacement for ischemic mitral valve incompetence. Heart Surg Forum. 2008;11:E340–E345. [PubMed]

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56•. Goland S, Czer LS, Siegel RJ, et al. Coronary revascularization alone or with mitral valve repair: outcomes in patients with moderate ischemic mitral regurgitation. Tex Heart Inst J. 2009;36:416–424. This series documents current outcomes for the performance of CABG alone with/without concomitant mitral valve repair for ischemic mitral regurgitation. The authors report similar 5-year survival rates for both techniques; however, revascularization with repair resulted in significantly reduced mitral regurgitation grade, improved left ventricular function, and functional class compared with revascularization alone. This study provides an important comparison of these two techniques in the current surgical era. [PMC free article] [PubMed]

57••. Magne J, Girerd N, Senechal M, et al. Mitral repair versus replacement for ischemic mitral regurgitation: comparison of short-term and long-term survival. Circulation. 2009;120(11 Suppl):S104–S111. In this study, the authors compare postoperative outcomes for mitral valve repair and replacement for ischemic mitral regurgitation. Despite lower operative mortality following mitral valve repair, long-term survival was equivalent between surgical groups. This study adds important long-term comparisons of mitral valve procedures to accumulating data examining surgical treatments for ischemic mitral regurgitation. [PubMed]

58. Silberman S, Klutstein MW, Sabag T, et al. Repair of ischemic mitral regurgitation: comparison between flexible and rigid annuloplasty rings. Ann Thorac Surg. 2009;87:1721–1726. discussion 1726–1727. This study provides a contemporary comparison between the use of flexible and rigid annuloplasty rings for the surgical treatment of IMR. The authors report significantly improved clinical and hemodynamic results for rigid mitral annuloplasty rings compared with flexible rings. [PubMed]

59•. Tekumit H, Cenal AR, Uzun K, et al. Ring annuloplasty in chronic ischemic mitral regurgitation: encouraging early and midterm results. Tex Heart Inst J. 2009;36:287–292. This study reports early and midterm results for the use of flexible annuloplasty rings for the surgical treatment of chronic IMR. The authors demonstrate that use of flexible mitral valve annuloplasty conferred a reduction in left ventricular diameter with improved New York Heart Association functional class. This study reports current, encouraging results and provides a context for future investigations comparing flexible and rigid annuloplasty rings for chronic IMR. [PMC free article] [PubMed]

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No dishonour in depression

June 23, 2013 by larryhbern

Larry H Bernstein, MD, … received

http://No dishonour in depression/2013/06/23

Nature | Editorial

No dishonour in depression

The stigma associated with mental illness discourages investment in finding cures — even though the burden of the disorders on society is immense.

Comedian and writer Ruby Wax, a regular on British television, has clinical depression. In her book published last week, Sane New World (Hodder & Stoughton, 2013), she describes her struggles with different therapies and her fear of being ‘found out’. She is not alone. A 2010 survey in Europe revealed that 38% of people had a diagnosed mental disorder — including 7% with major depression. The proportion is likely to be similar in all populations, even in Africa, where psychiatric disease barely features on the health agenda.

The stigma attached to such disorders means that many people do not admit to their illness. The same stigma discourages investment, so that research funding is not proportional to the distress these disorders cause. Why lobby for better treatments for depression or schizophrenia when there are ‘real’ diseases out there, such as cancer?

Wax has been through the catalogue of available therapies and says that she has settled on an approach known as ‘mindfulness’, which helps to keep her depression under control. It may seem that the various therapies are inadequate, given that initial treatment of depression fails in 60% or more of cases. It is true that more treatment options are badly needed. Yet evidence-based cognitive behavioural therapies and drugs already developed by the pharmaceutical industry can work splendidly for long periods — if they are given to the right patients.

How do you recognize the right patients? Treatment decisions tend to be based on the preferences of physicians or their patients, often with a missionary zeal that gives no credence to the idea that a personalized approach would be more appropriate. Some hold that drugs have unacceptable side effects, whereas others say that cognitive therapy wastes time if the depressed brain is not first chemically lifted. It is becoming increasingly common to offer patients both treatments at once in the belief that drugs can prepare the brain to respond to cognitive therapy. That may be so, but it is also possible that the improved response rates are simply the result of catching two different populations.

The situation would improve drastically if simple tests could be developed to predict treatment outcome. Many exploratory clinical trials are now under way to search for biomarkers in genes or in the brain itself that might be predictive. This week sees the description of the first potential biomarker for discriminating between responders and non-responders to drugs or cognitive therapy in major depressive disorder (C. L. McGrath et al. JAMA Psychiatry http://dx.doi.org/10.1001/jamapsychiatry.2013.143; 2013).

“The stigma attached to mental disorders will fade when treatment becomes more effective.”

The study, led by neurologist Helen Mayberg of Emory University in Atlanta, Georgia, used positron emission tomography (PET) scans to measure metabolic activity in various brain regions of people with untreated depression (see also Nature http://doi.org/mtc; 2013). Patients were randomized into groups and treated for 12 weeks with either a commonly used antidepressant drug or cognitive behaviour therapy. The study’s results were clear-cut. Below-average activity in a brain area called the right anterior insula — which is linked with depression-relevant behaviours such as emotional self-awareness and decision-making — was associated with the patient showing a good response to cognitive behavioural therapy and a poor response to the drug. Above-average insula activity was predictive of the opposite.

This potential biomarker must still be tested in prospective clinical trials, which will assign patients to a treatment on the basis of their insula activity. It may fail. But if the biomarker comes up trumps, it could be transformative for many patients who would not have to endure two or three months of treatment trial and error.

If attitudes to mental illness do not change, even a successful biomarker of this type will have a hard time being accepted by health systems that foot the bills. Unlike a simple blood test, a PET scan is inconvenient because not all physicians have easy access to the technology and, at up to US$2,000 a shot, the procedure is not cheap. Although expensive treatments for other diseases and arguments about how to fund them are nothing new, this rational debate is harder for mental illnesses because of the irrational stigma that is attached to them.

Fifty years ago, the stigma surrounding cancer meant that physicians would sometimes lie to patients about the diagnosis from kindness. That has now faded because cancer is not always the death sentence it once was — thanks in part to the development of biomarkers that guide therapy. The stigma attached to mental disorders will also fade when treatment becomes more effective. But to break out of a vicious circle of underinvestment in a stigmatized disease area will require continued effort to get the problem recognized. This is a good week for that.

Journal name:: Nature
Volume:: 498,
Pages:: 137
Date published:: (13 June 2013)
DOI:: http://dx.doi.org/10.1038/498137a

Cognitive behavior therapy or drugs for patients with depression? A brain scan could tell (medcitynews.com)
A New Biomarker for Treatment Response in Major Depression? Not Yet. (neurocritic.blogspot.com)
Brain Insula Signals Response to Depression Treatment (brainposts.blogspot.com)
Brain Scans Predict Treatment Outcome in Depression Patients (technologyreview.com)
Overcoming the stigma of mental illness (stopstigmas.com)

PET at NIH Clinical Center. General Electric (GE) Advance positron emission tomography (PET) scanner. (Photo credit: Wikipedia)

Posted in Chemical Biology and its relations to Metabolic Disease, Chemical Genetics, Innovations in Neurophysiology & Neuropsychology | Tagged Atlanta, Cognitive behavioral therapy, Emory University, Helen Mayberg, Major depressive disorder, Mental disorder, Positron Emission Tomography, Ruby Wax | Leave a Comment »

First case in the US: Valve-in-Valve (Aortic and Mitral) Replacements with Transapical Transcatheter Implants – The Use of Transfemoral Devices

June 23, 2013 by larryhbern

First case in the US: Valve-in-Valve (Aortic and Mitral) Replacements with Transapical Transcatheter Implants – The Use of Transfemoral Devices

Writer: Larry H Bernstein, MD, FCAP

and

Curator: Aviva Lev-Ari, PhD, RN

UPDATED on 9/24/2018

TCT: Long-Term Data Reassuring for Valve-in-Valve TAVR

New valve performs well through 3 years

by Nicole Lou, Contributing Writer, MedPage Today

September 23, 2018

Transcatheter valve-in-valve replacement had lasting benefits in a high-risk patient population requiring valve reintervention, registry data showed.

Starting with 365 patients who got valve-in-valve transcatheter aortic valve replacement (TAVR), death took its toll in 12.1%, 22.2%, and 32.7% by 12, 24, and 36 months, respectively. Stroke and repeat valve replacement had plateaued to 5.1% and 0.6% over 24 months, rising to 6.2% and 1.9% at the 36-month mark.

Valve performance was sustained the whole time, as effective orifice area had a significant boost from baseline to discharge, staying stable thereafter out to 3 years; mean gradient dropped after the procedure and similarly stayed unchanged over time, according to John Webb, MD, of St. Paul’s Hospital in Vancouver, at the Transcatheter Cardiovascular Therapeutics (TCT) conference.

Among survivors, early improvements in functional status were also maintained over the 3-year period, Webb said. Most patients started off in New York Heart Association class 3 and 4 and were reclassified as class 1 and 2 after TAVR. Quality of life also was better, as shown in improved Kansas City Cardiomyopathy Questionnaire overall summary scores: 43.1 at baseline to 70.8 at 30 days (P<0.0001), and staying stable out to 3 years.

The results were not influenced by surgical valve size, failure mode, approach, or residual gradient.

These data are “certainly reassuring out 2-3 years” but the concern lies in anticipation of lower-risk and younger patients who are expected to start getting TAVR in the future, commented Stephan Windecker, MD, of the University of Bern in Switzerland, who was a panelist at the TCT late-breaker trial session.

There are some concerns regarding coronary obstruction, Webb acknowledged. “This is true in surgical valves and it would be every bit as true in transcatheter valves, if not more so.”

Primary Source

Transcatheter Cardiovascular Therapeutics

Source Reference: Webb JG “Late follow-up from the PARTNER aortic valve-in-valve registry” TCT 2018.

SOURCE

https://www.medpagetoday.com/meetingcoverage/tct/75261?xid=nl_mpt_ACC_Reporter_2018-09-23&eun=g5099207d2r

UPDATED on 4/13/2014

Replacement of the Mitral Valve: Using the Edwards’ Sapien Aortic Valve Device

http://pharmaceuticalintelligence.com/2014/04/10/replacement-of-the-mitral-valve-using-the-edwards-sapien-aortic-valve-device/

June 23, 2013

The following is a report of the first case in the US of both aortic and mitral valve transcatheter replacements using transfemoral devices via the transapical approach.

It is part of a series on the cardiovascular team at the Columbia Univarsity Medical Center/New York Presbyterian Hospital and the Cardiovascular Research Foundation in the Partner trial.

Concomitant Transcatheter Aortic and Mitral Valve-in-Valve Replacements Using Transfemoral Devices Via the Transapical Approach

Paradis J-M, Kodali SK, Hahn RT, George I, Daneault B, et al.
ColumbiaUniversityMedicalCenter/NewYork-Presbyterian Hospital, New York, NY fJACC:CARDIOVASCULARINTERVENTIONS 2013;6(1):94-96
http://dx.doi.org/10.1016/j.jcin.2012.07.018

Case Presentation

This is an 85 year old man with congestive heart failure (CHF) NYHA class III/IV and hemolytic anemia. He had a previous history of S. viridans bacterial endocarditis that caused severe aortic and mitral regurgitations. Both aortic and mitral valves were replaced in 2002. A recenttTransesophageal echocardiogram (TEE) showed the left ventricular ejection fraction (LVEF) was 55%. This was related to severe mitral regurgitation caused by a flail leaflet, and its internal diameters measured 21-23.8 mm. There was, in addition, severe stenosis of the Carpentir-Edwards valve in the aortic position with an aortic valve area (AVA) of only 0.9 cm, which was 24 mm internal diameter measured by 3-D TEE.

Action Taken

The patient was felt to require reoperative aortic and mitral valve replacements, but he was deemed inoperable by 2 cardiothoracic surgeons. Therefore they decided to proceed with transapical transcatheter double valve-in-valve implantation using 2 commercially available RetroFlex 3 transfemoral devices (Edwards Lifesciences, Irvine, CA). A 26-mm Edwards SAPIEN transcatheter heart valve (THV) was placed within the Carpentier-Edwards valve in the aortic position without pre-dilatation under rapid ventricular pacing. An Edwards SAPIEN 26-mm THV was then deployed within the Hancock modiﬁed bioprosthesis in the mitral position with a 2-step inflation technique. TEE after deplonment of both valves showed excellent function. The new aortic prosthetic valve had an AVA of 2.08 cm, peak and mean gradients of 12 and 6 mm Hg, respectively, and no aortic insufficiency. The mitral valve area was 1.65 cm, and there was only trace mitral regurgitation.

Figure 1.TEE Showing the Mitral Bioprosthetic Valve

Transesophageal echocardiogram (TEE) demonstrating (A) color Doppler through the mitral bioprosthetic valve. Severe intraprosthetic mitral regurgitation caused by a ﬂail leaﬂet generates an eccentric regurgitant jet (see Online Video1).The effective regurgitant oriﬁce was calculated to be 0.42cm. (B) Measurements of the internal dimensions of the mitral bioprosthesis using 3-dimensional reconstruction imaging.

Figure 2.TEE Showing the Aortic Bioprosthetic Valve.

Transesophageal echocardiogram (TEE) showing (A) planimetry of the oriﬁce and (B) measurement of the internal diameter of the aortic bioprosthesis.

Figure 3.The 4 Prosthetic Heart Valves.

Final ﬂuoroscopic images showing the 4 prosthetic heart valves (Hancock modiﬁed,Carpentier-Edwards, and 2 Edwards SAPIEN transcatheter heart valves) in different angulations

Postdilatation to Reduce Paravalvular Regurgitation During Transcatheter Aortic Valve Replacement (pharmaceuticalintelligence.com)
Deployment Of New Device For TAVI In Aortic Insufficiency (medicalnewstoday.com)
Direct Flow Transcatheter Aortic Heart Valve Gets FDA Feasibility Trial OK (VIDEO) (medgadget.com)
New Data on Edwards PERIMOUNT Valves Demonstrate Long-Term Durability in Patients Aged 60 and … (biomedreports.com)
Know More About Severe Aortic Stenosis (tavrvalvereplacement.wordpress.com)
Mitral Valve Prolapse – Part 6, Alarm, Confusion, Controversy, Frustration and Getting to Where We Need to be (myheartnet.wordpress.com)
Positive Animal Data Presented at EuroPCR Sets Stage for Advancing Neovasc’s Tiara(TM) Transcatheter Mitral Valve into Human Trials (prnewswire.com)

“The SILENCE of the Lambs” Introducing The Power of Uncoded RNA

June 23, 2013 by Demet Sag, Ph.D., CRA, GCP

“The SILENCE of the Lambs” Introducing The Power of Uncoded RNA

Curator: Demet Sag, PhD

Screen Shot 2021-07-19 at 7.06.12 PM

Word Cloud By Danielle Smolyar

An illustration of the central dogma of molecular biology annotated with the processes ncRNAs are involved in. (Photo credit: Wikipedia)

X-ray structure of the tRNA Phe from yeast. Data was obtained by PDB 1ehz and rendered with PyMOL. violet: acceptor stem wine red: D-loop blue: anticodon loop orange: variable loop green: TPsiC-loop yellow: CCA-3′ of the acceptor stem grey: anticodon (Photo credit: Wikipedia)

Our genome must be packed tightly to fit into the nucleus. Genome is the blue print of a living organism whether made up off a single or multiple cell. Recently, the genome seen as a functional network of physical contacts within (cis) and between (trans) chromosomes. It became necessary to map these physical DNA contacts at high-resolution with technologies such as the “chromosome conformation capture” (3C) and other 3C-related methods including 3C-Carbon Copy (5C) and Hi-C. Yet, we all know that in vivo conformation, gene to gene interactions from a long distance, histones and 3D have an impact on gene regulation and expression. The game is not just a sequence but functional genomics with a correct translation of sequence for development so that proper molecular diagnostics can be applied not only for prevention but also for monitoring the efficacy of the intervention. Thus, we can provide a targeted therapy for personalized medicine.

On the other hand, we still know very little about genome organization at the molecular level, although spatial genome organization can critically affect gene expression. It is important to recognize who is there to be present and who is there to create the functional impact for regulation in a specific tissue and time. In addition, mediation of these chromatin contacts based on a specific tissue is quite essential. For example, during long-range control mechanism specific enhancers and distal promoters needed to be invited to a close physical proximity to each other by transcription factors that has been found at other loci. Furthermore, chromatin-binding proteins such as the CCCTC-binding factor (CTCF) and cohesin seem to have critical roles in genome organization and gene expression. Let’s not forget about epigenetics, since there are so many methods to regulate chromatin interactions like cytosine methylation, maternal gene, gradient level, post-translational modifications and non-coding RNAs.

The non-coding RNAs (ncRNAs) are silent but they have the 99% power because ncRNAs are a broad class of transcripts consisting of structural (rRNAs, tRNAs, snRNAs, snoRNAs, etc.), regulatory (miRNAs, piRNAs, etc.), and of sense/antisense transcripts. Among these an interesting class is the latter group. This class includes transcriptional “features” (eRNAs, tiRNAs), and a very large number of long non-coding RNAs (lncRNAs), length from 200 nt to 100 kb. The magnificent future of lncRNAs comes from their production, as they can be transcribed nearby known protein-coding genes or from their introns. As a result, because of their intergenical production they are also called as “lincRNAs (long intergenical non-coding RNAs). They are abundant and specific as microRNAs. Hence, their inclusion into the biomarker list and assuming their roles during targeted therapy don’t require us to be a wizard but a functional genomicist knowing evolution, development and molecular genetics and plus signaling.

lincRNA can both activate and repress the gene either cis or trans acting to effect gene regulation will be discussed next.

As a result, one gene expression regulation needs from twenty to several hundred genes. As they say raising a child needs a village.

References:

“Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs”.

Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang HY. Cell. 2007 Jun 29; 129(7):1311-23.

“Long noncoding RNA as modular scaffold of histone modification complexes”

Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E, Chang HYScience. 2010 Aug 6; 329(5992):689-93.

“Capturing Chromosome Conformation”.

Dekker J, Rippe K, Dekker M, Kleckner N.Science.2002;295:1306–1311.

“Chromosome Conformation Capture Carbon Copy (5C): a massively parallel solution for mapping interactions between genomic elements”.

Dostie J, Richmond TA, Arnaout RA, Selzer RR, Lee WL, Honan TA, Rubio ED, Krumm A, Lamb J, Nusbaum C, Green RD, Dekker J.Genome Res. 2006;16:1299–1309.

“Chromosome conformation capture carbon copy technology”.

Dostie J, Zhan Y, Dekker J. Curr. Protoc. Mol. Biol. 2007 Chapter 21, Unit 21 14.

“Comprehensive mapping of long-range interactions reveals folding principles of the human genome”.

Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A, Amit I, Lajoie BR, Sabo PJ, Dorschner MO, Sandstrom R, Bernstein B, Bender MA, Groudine M, Gnirke A, Stamatoyannopoulos J, Mirny LA, Lander ES, Dekker J. Science. 2009;326:289–293.

“Chromatin conformation signatures: ideal human disease biomarkers?”

Crutchley JL, Wang XQ, Ferraiuolo MA, Dostie J.Biomark. Med. 2010;4:611–629.

“Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. Identification of eight new ANRIL splice variants”.

Folkersen L, Kyriakou T, Goel A, Peden J, Mälarstig A, Paulsson-Berne G, Hamsten A, Hugh Watkins, Franco-Cereceda A, Gabrielsen A, Eriksson P, PROCARDIS consortia

PLoS One. 2009 Nov 2; 4(11):e7677.

” A myelopoiesis-associated regulatory intergenic noncoding RNA transcript within the human HOXA cluster”.

Zhang X, Lian Z, Padden C, Gerstein MB, Rozowsky J, Snyder M, Gingeras TR, Kapranov P, Weissman SM, Newburger PE. Blood. 2009 Mar 12; 113(11):2526-34.

“Genomic imprinting”.

Monk M. Genes Dev. 1988 Aug; 2(8):921-5.

“Hox genes specify vertebral types in the presomitic mesoderm“

Marta Carapuço,¹ Ana Nóvoa,¹ Nicoletta Bobola,² and Moisés Mallo^{1,3 .}Genes Dev. 2005 September 15; 19(18): 2116–2121.

“Hox genes in vertebrate development”.

Krumlauf R. Cell. 1994 Jul 29; 78(2):191-201.

“Noncoding RNA synthesis and loss of Polycomb group repression accompanies the colinear activation of the human HOXA cluster”.

Sessa L, Breiling A, Lavorgna G, Silvestri L, Casari G, Orlando V. RNA. 2007 Feb; 13(2):223-39.

“Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs”.

Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang HY. Cell. 2007 Jun 29; 129(7):1311-23.

“Long noncoding RNAs with enhancer-like function in human cells”.

Ørom UA, Derrien T, Beringer M, Gumireddy K, Gardini A, Bussotti G, Lai F, Zytnicki M, Notredame C, Huang Q, Guigo R, Shiekhattar R

“Histone modifications at human enhancers reflect global cell-type-specific gene expression”.

Heintzman ND, Hon GC, Hawkins RD, Kheradpour P, Stark A, Harp LF, Ye Z, Lee LK, Stuart RK, Ching CW, Ching KA, Antosiewicz-Bourget JE, Liu H, Zhang X, Green RD, Lobanenkov VV, Stewart R, Thomson JA, Crawford GE, Kellis M, Ren B. Nature. 2009 May 7; 459(7243):108-12.

“Tiny RNAs associated with transcription start sites in animals”.

Taft RJ, Glazov EA, Cloonan N, Simons C, Stephen S, Faulkner GJ, Lassmann T, Forrest AR, Grimmond SM, Schroder K, Irvine K, Arakawa T, Nakamura M, Kubosaki A, Hayashida K, Kawazu C, Murata M, Nishiyori H, Fukuda S, Kawai J, Daub CO, Hume DA, Suzuki H, Orlando V, Carninci P, Hayashizaki Y, Mattick JS. Nat Genet. 2009 May; 41(5):572-8.

“Chromatin modifications and their function”.

Kouzarides T. Cell. 2007 Feb 23; 128(4):693-705.

“The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation”.

Tripathi V, Ellis JD, Shen Z, Song DY, Pan Q, Watt AT, Freier SM, Bennett CF, Sharma A, Bubulya PA, Blencowe BJ, Prasanth SG, Prasanth KV. Mol Cell. 2010 Sep 24; 39(6):925-38.

Selected Further Reading

“Small and long non-coding RNAs in cardiac homeostasis and regeneration”

Ounzain, S.; Crippa, S.; Pedrazzini, T. BBA – Molecular Cell Research vol. 1833 issue 4 April, 2013. p. 923-933

“Regulatory mechanisms of long noncoding RNAs in vertebrate central nervous system development and function.”

Knauss, J.L.; Sun, T. “Neuroscience vol. 235 April 3, 2013. p. 200-214

“Comparative genomics reveals ‘novel’ Fur regulated sRNAs and coding genes in diverse proteobacteria.”

Sridhar, J.; Sabarinathan, R.; Gunasekaran, P.; Sekar, K. Gene vol. 516 issue 2 March 10, 2013. p. 335-344 DOI: 10.1016/j.gene.2012.12.057. ISSN: 0378-1119.

“miRNAs Regulate Expression and Function of Extracellular Matrix Molecules”

Rutnam, Z.J.; Wight, T.N.; Yang, B.B.Matrixixix Biology vol. 32 issue 2 March 11, 2013. p. 74-85 DOI: 10.1016/j.matbio.2012.11.003. ISSN: 0945-053X.

“Transcript profiling of microRNAs during the early development of the maize brace root via Solexa sequencing”

Liu, P.; Yan, K.; Lei, Y.x.; Xu, R.; Zhang, Y.m.; Yang, G.d.; Huang, J.g.; Wu, C.A.; Zheng, C.C.Genomics vol. 101 issue 2 February, 2013. p. 149-156 DOI: 10.1016/j.ygeno.2012.11.004. ISSN: 0888-7543.

“Regulatory mechanisms of long noncoding RNAs in vertebrate central nervous system development and function”

Knauss, J.L.; Sun, T. Neuroscience vol. 235 April 3, 2013. p. 200-214 DOI: 10.1016/j.neuroscience.2013.01.022. ISSN: 0306-4522.

“The dynamic biliary epithelia: Molecules, pathways, and disease”

O’Hara, Steven P.; Tabibian, James H.; Splinter, Patrick L.; LaRusso, Nicholas F. Journal of Hepatology vol. 58 issue 3 March, 2013. p. 575-582 DOI: 10.1016/j.jhep.2012.10.011. ISSN: 0168-8278

ABBREVIATIONS

3C = Chromosome conformation capture

rRNAs = Ribosomal RNAs

tRNAs = Transfer RNAs

snRNAs = Small nuclear RNAs

snoRNAs = Small nucleolar RNAs

miRNAs = MicroRNAs

piRNAs = Piwi-interacting RNAs

eRNAs = Enhancer RNAs

tiRNAs = Transcription initiation RNAs

spliRNAs = Splice-site RNAs

lincRNAs = Long intergenic non-coding RNAs

lncRNPs = Long non-coding ribonucleoprotein complexes

Igf2r = Insulin-like growth factor II receptor

HMTs = Histone methyl transferases

TSSs = Transcriptional start sites

TFs = Transcription factors

RNAi = RNA interference

PTMs = Post-translational modifications

Patent. (postdocstreet.wordpress.com)

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Posted in Biological Networks, Gene Regulation and Evolution, Biomarkers & Medical Diagnostics, CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer Prevention: Research & Programs, Cell Biology, Signaling & Cell Circuits, Genome Biology, Genomic Testing: Methodology for Diagnosis, Medical and Population Genetics, Molecular Genetics & Pharmaceutical, Personalized and Precision Medicine & Genomic Research, Pharmacogenomics, Population Health Management, Genetics & Pharmaceutical, Stem Cells for Regenerative Medicine, Uncategorized | Tagged Biology, Chromatin, CTCF, DNA, eRNAs, gene expression, genetics, Long non-coding RNA, MicroRNA, Non-coding RNA, piRNAs, PubMed, RNA, Small nucleolar RNA, snoRNAs, snRNAs, tiRNAs, transcription | 4 Comments »

Demythologizing sharks, cancer, and shark fins

June 22, 2013 by larryhbern

Larry H Bernstein, MD, Writer, Curator
http://pharmaceutical intelligence.com/2013/06/22/ Demythologizing sharks, cancer, and shark fins/lhbern

Screen Shot 2021-07-19 at 6.26.48 PM

Word Cloud By Danielle Smolyar

Sharks have survived some 400 million years on Earth. Could their longevity be due in part to an extraordinary resistance to cancer and other diseases? If so, humans might someday benefit from the shark’s secrets—but leading researchers caution that today’s popular shark cartilage “cancer cures” aren’t part of the solution.

The belief that sharks do not get cancer is not supported in fact, but it is the basis for decimating a significant part of the shark population for shark fins, and for medicinal use. The unfortunate result is that there is no benefit.

A basis for this thinking is that going back to the late 1800s, sharks have been fished commercially and there have been few reports of anything out of the ordinary when removing internal organs or preparing meat for the marketplace. In addition, pre-medical students may have dissected dogfish sharks in comparative anatomy, but you don’t see reports of cancerous tumors.

Carl Luer of the MOTE Marine Laboratory’s Center for Shark Research in Sarasota, Florida, has been studying sharks’ cancer resistance for some 25 years. Systematic surveys of sharks are difficult to conduct, as capturing the animals in large numbers is time-consuming, and cancer tests would likely require the deaths of large numbers of sharks. Of the thousands of fish tumors in the collections of the Smithsonian Institution, only about 15 are from elasmobranchs, and only two of these are thought to have been malignant.

Scientists have been studying cancerous tumors in sharks for 150 years.

The first chondrichthyes’ (cartilaginous fishes, including sharks) tumor was found on a skate and recorded by Dislonghamcps in 1853. The first shark tumor was recorded in 1908. Scientists have since discovered benign and cancerous tumors in 18 of the 1,168 species of sharks. Scarcity of studies on shark physiology has perhaps allowed this myth to be accepted as fact for so many years.

In April 2000, John Harshbarger and Gary Ostrander countered this shark myth with a presentation on 40 benign and cancerous tumors known to be found in sharks, and soon after a blue shark was found with cancerous tumors in both its liver and testes. Several years later a cancerous gingival tumor was removed from the mouth of a captive sand tiger shark, Carcharias Taurus. Advances in shark research continue to produce studies on types of cancer found in various species of shark. Sharks, like fish, encounter and take in large quantities of environmental pollutants, which may actually make them more susceptible to tumorous growth. Despite recorded cases of shark cancer and evidence that shark cartilage has no curative powers against cancer sharks continue to be harvested for their cartilage.

Sharks and their relatives, the skates and rays, have enjoyed tremendous success during their nearly 400 million years of existence on earth, according to Dr. Luer. He points out that one reason for this certainly is their uncanny ability to resist disease. Sharks do get sick, but their incidence of disease is much lower than among the other fishes. While statistics are not available on most diseases in fishes, reptiles, amphibians, and invertebrates, tumor incidence in these animals is carefully monitored by the Smithsonian Institution in Washington, D.C.

The Smithsonian’s enormous database, called the Registry of Tumors in Lower Animals, catalogs tissues suspected of being tumorous, including cancers, from all possible sources throughout the world. Of the thousands of tissues in the Registry, most of them are from fish but only a few are from elasmobranchs. Only 8 to 10 legitimate tumors are among all the shark and ray tissues examined, and only two of these are thought to have been malignant.

An observation by Gary Ostrander, a Professor at Johns Hopkins University, is that there may be fundamental differences in shark immune systems so that they aren’t as prone to cancer. The major thrust of the Motes research focuses on the immunity of sharks and their relatives the skates and rays. While skates aren’t as interesting to the public as their shark relatives, their similar biochemical immunology and their ability to breed in captivity make them perhaps more vital to Luer’s lab work. The result is to study the differences and similarities to the higher animals, and what might possibly be the role of the immune system in their low incidence of disease.

This low incidence of tumors among the sharks and their relatives has prompted biochemists and immunologists at Mote Marine Laboratory (MML) to explore the mechanisms that may explain the unusual disease resistance of these animals. To do this, they established the nurse shark and clearnose skate as laboratory animals. They designed experiments to see whether tumors could be induced in the sharks and skates by exposing them to potent carcinogenic (cancer-causing) chemicals, and then monitored pathways of metabolism or detoxification of the carcinogens in the test animals. While there were similarities and differences in the responses when compared with mammals, no changes in the target tissues or their genetic material ever resulted in cancerous tumor formation in the sharks or skates.

The chemical exposure studies led to investigations of the shark immune system. As with mammals, including humans, the immune system of sharks probably plays a vital role in the overall health of these animals. But there are some important differences between the immune arsenals of mammals and sharks. The immune system of mammals typically consists of two parts which utilize a variety of immune cells as well as several classes of proteins called immunoglobulins (antibodies).

Compared to the mammalian system, which is quite specialized, the shark immune system appears primitive but remarkably effective. Sharks apparently possess immune cells with the same functions as those of mammals, but the shark cells appear to be produced and stimulated differently. Furthermore, in contrast to the variety of immunoglobulins produced in the mammalian immune system, sharks have only one class of immunoglobulin (termed IgM). This Immunoglobulin normally circulates in shark blood at very high levels and appears to be ready to attack invading substances at all times.

Another difference lies in the fact that sharks, skates, and rays lack a bony skeleton, and so do not have bone marrow. In mammals, immune cells are produced and mature in the bone marrow and other sites, and, after a brief lag time, these cells are mobilized to the bloodstream to fight invading substances. In sharks, the immune cells are produced in the spleen, thymus and unique tissues associated with the gonads (epigonal organ) and esophagus (Leydig organ). Some maturation of these immune cells occurs at the sites of cell production, as with mammals. But a significant number of immune cells in these animals actually mature as they circulate in the bloodstream. Like the ever-present IgM molecule, immune cells already in the shark’s blood may be available to respond without a lag period, resulting in a more efficient immune response.

Research was being carried out during the 1980’s at the Massachusetts Institute of Technology (MIT) and at Mote Marine Laboratory designed to understand how cartilage is naturally able to resist penetration by blood capillaries. If the basis for this inhibition could be identified, it was reasoned, it might lead to the development of a new drug therapy. Such a drug could control the spread of blood vessels feeding a cancerous tumor, or the inflammation associated with arthritis.

The results of the research showed only that a very small amount of an active material, with limited ability to control blood vessel growth, can be obtained from large amounts of raw cartilage. The cartilage must be subjected to several weeks of harsh chemical procedures to extract and concentrate the active ingredients. Once this is done, the resulting material is able to inhibit blood vessel growth in laboratory tests on animal models, when the concentrated extract is directly applied near the growing blood vessels. One cannot assume that comparable material in sufficient amount and strength is released passively from cartilage when still in the animal to inhibit blood vessel growth anywhere in the body.

Tumors release chemicals stimulating the capillary growth so a nutrient-rich blood supply is created to feed the tumorous cells. This process is called angiogenesis. If scientists can control angiogenesis, they could limit tumor growth. Cartilage lacks capillaries running through it. Why should this be a surprise? Cartilage cells are called chondrocytes, and they fuction to produce a acellular interstitial matrix consisting of hyaluronan (complex carbohydrate formed from hyaluronic acid and chondroitin sulfate) which is protective of interlaced collagen. Early research into the anti-angiogenesis properties of cartilage revealed that tiny amounts of proteins could be extracted from cartilage, and, when applied in concentration to animal tumors, the formation of capillaries and the spread of tumors was inhibited.

Henry Brem and Judah Folkman from the Johns Hopkins School of Medicine first noted that cartilage prevented the growth of new blood vessels into tissues in the 1970s. The creation of a blood supply, called angiogenesis, is a characteristic of malignant tumors, as the rapidly dividing cells need lots of nutrients to continue growing. It is valuable to consider that these neovascular generating cells are not of epithelial derivation, but are endothelial and mesenchymal. To support their very high metabolism, tumors secrete a hormone called ‘angiogenin’ which causes nearby blood vessels to grow new branches that surround the tumor, bringing in nutrients and carrying away waste products

Brem and Folkman began studying cartilage to search for anti-angiogenic compounds. They reasoned that since all cartilage lacks blood vessels, it must contain some signaling molecules or enzymes that prevent capillaries from forming. They found that inserting cartilage from baby rabbits alongside tumors in experimental animals completely prevented the tumors from growing. Further research showed calf cartilage, too, had anti-angiogenic properties.

A young researcher by the name of Robert Langer repeated the initial rabbit cartilage experiments, except this time using shark cartilage. Indeed, shark cartilage, like calf and rabbit cartilage, inhibited blood vessels from growing toward tumors. Research by Dr. Robert Langer of M.I.T. and other workers revealed a promising anti-tumor agent obtainable in quantity from shark cartilage. The compound antagonistic to the effects of angiogenin, called ‘angiogenin inhibitor’, inhibits the formation of new blood vessels, neovascularization, that is essential for supporting cancer growth.

The consequence of the”shark myth” is not surprising. An inhabitant of the open ocean, the Silky Shark is ‘hit’ hard by the shark fin and shark cartilage industries – away from the prying eyes of a mostly land bound public. As a consequence of this ‘invisibility’, mortality of Silkies is difficult to estimate or regulate. North American populations of sharks have decreased by up to 80% in the past decade, as cartilage companies harvest up to 200,000 sharks every month in US waters to create their products. One American-owned shark cartilage plant in Costa Rica is estimated to destroy 2.8 million sharks per year. Sharks are slow growing species compared to other fish, and simply cannot reproduce fast enough to survive such sustained, intense fishing pressure. Unless fishing is dramatically decreased worldwide, a number of species of sharks will go extinct before we even notice.

Sources:
1. National Geographic News: NATIONALGEOGRAPHIC.COM/NEWS

2. Do Sharks Hold Secret to Human Cancer Fight?
by Brian Handwerk for National Geographic News. August 20, 2003

3. Busting Marine Myths: Sharks DO Get Cancer!
by Christie Wilcox November 9th 2009

Sharks Extinction Imminent If Current Illegal Trade Persists (guardianlv.com)
Cancer Cells More Than Just Proliferate, Overuse Blood Sugar To Evade Immune System [VIDEO] (medicaldaily.com)
Combating Metastatic Cancer Through Immune System Modulation (medicalnewstoday.com)
Study Finds Ways of Training Immune System to Fight Cancer (counselheal.com)

Sand tiger shark (Carcharias taurus) at the Newport Aquarium. (Photo credit: Wikipedia)

Angiogenesis (Photo credit: Wikipedia)

The immune response (Photo credit: Wikipedia)

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, Cell Biology, Signaling & Cell Circuits, Chemical Biology and its relations to Metabolic Disease, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Glycobiology: Biopharmaceutical Production, Pharmacodynamics and Pharmacokinetics, Molecular Genetics & Pharmaceutical, Nutritional Supplements: Atherogenesis, lipid metabolism | Tagged Antibody, Cancer - General, immune system, Johns Hopkins University, Luer, Massachusetts Institute of Technology, Mote Marine Laboratory, Smithsonian Institution | Leave a Comment »

Biomedical Measurement Science Program @ Stanford with NIST, Life Tech and Agilent

June 21, 2013 by 2012pharmaceutical

Reporter: Aviva Lev-Ari, PhD, RN

Stanford University and NIST, Launch Biomedical Measurement Science Program; Partners Include Life Tech and Agilent

June 21, 2013

By Matt Jones

NEW YORK (GenomeWeb News) – Stanford University and the National Institute of Standards and Technology have launched a new program that aims to develop methods for measuring the accuracy and comparability of life sciences and genomics technologies, particularly tools that are expanding beyond the lab and into clinical medicine.

The Advances in Biomedical Measurement Science (ABMS) program will use funding and resources from Stanford and NIST, as well as from commercial partners Life Technologies and Agilent Technologies, to develop industry consensus standards and standard reference materials for a range of genomics and imaging technologies, Marc Salit, leader of NIST’s Multiplexed Biomolecular Science Group, Biosystems and Biomaterials Divisions, told GenomeWeb Daily News today.

The ABMS partners plan to focus on technology areas that are edging their way into clinical medicine and other applications, including the use of high-throughput sequencing for HLA typing; stem cell phenotyping and genotyping; quantitative imaging for non-invasive cancer diagnosis and for drug response and screening; synthetic biology; and multiparameter protein measurement.

The partners expect that improving the accuracy and comparability of data from these tools will make it easier and faster to make decisions about how they will be used in research and in the clinic, and how they might be regulated.

The initiative is part of an effort by NIST to expand its presence in biotechnology, healthcare, and biomedicine, particularly through partnerships with universities that have competencies, medical facilities, and expertise in areas that the institute lacks.

“Stanford has a critical mass of some of these assets, and NIST thought [the ABMS program] would be an efficient way to expand its presence in the healthcare and biomedical areas,” Salit said.

“NIST was a spectacular resource for the century of physics in the 20th Century; we want to be that resource for the century of biology, this century,” he told GWDN. “We wanted to see if we could take what we had developed in chemistry — in terms of measurement assurance and the kinds of things that bring confidence to measurement results — and transfer it into genomic measurement.”

Several NIST researchers have relocated to Stanford from their offices in Gaithersburg, Md., and will work directly with established Stanford investigators and postdocs, while around half of Salit’s team will remain at the Maryland lab, he said.

Another selling point of this partnership for NIST is that it enables the agency to establish “a permanent presence” on the West Coast, near Silicon Valley, Salit said.

NIST has other well-established joint institutes at US universities, and the long-term aim is that the ABMS will be “a seed from which such a joint institute could grow,” Salit explained.

The program will operate as a virtual center at first, where investigators from NIST, Stanford, and the industry partners will “work shoulder to shoulder” to study genomics and imaging technologies that are working their way into clinical care, he added.

“Some of these [Stanford and industry] research groups have instruments and technologies that exist commercially which would benefit from a real thorough study, from a measurement science perspective” said Salit.

Tom Baer, director of the Advances in Biomedical Measurement Science Program, told GWDN that the life sciences companies involved in the program have a strong interest in working with partners to test, measure, and analyze their technologies in new ways. The two companies already involved, and any future industry partners, will pay annual fees to help support the program, he noted.

“We expect that there will be significant standards reference materials and protocols that will come out of the joint research here with Mark’s group on campus. And [Life Technologies and Agilent] are going to benefit because there will be some really first-class scientists working with their instrumentation, studying how well they perform now and coming up with ways that they could potentially be improved,” said Baer, who also is executive director of the Stanford Photonics Research Center.

Salit noted that NIST does not develop government regulations but informs their development, and added that in working with tech companies its mission is to help “grow the whole pie bigger,” and to support the US technology industry enterprise broadly.

This kind of partnership, he said, also will engage experts from the Food and Drug Administration, which will “bring real value” to these companies.

The HLA typing project, which will study the use of high-throughput sequencing and other nucleic acid-based technologies for identifying immune responses to bone marrow and stem cell transplantation, is a “perfect example” of the kind of program the partners will pursue, Baer explained. “This has great resonance with at least one of the commercial partners, who is trying to develop methods and products around HLA typing,” he added.

“We’re looking to identify areas of great medical need in the whole area of tissue transplants, both as it exists today and as it is going to grow with the stem cell and regenerative medicines initiatives that are underway,” said Baer. “This is an area of critical medical need where measurement science can play a very important role with the new quantitative technologies that are currently available.”

He said the HLA typing effort is “a prototype of how we’re developing the research programs at ABMS.” The goal is “to look not just at the concept of how you do this measurement, but what is the problem, where is measurement playing a role, and how we can improve the performance of the systems and technologies through both standards development, better understanding, and measurement science,” Baer said.

Baer also said that he expects this project will serve to educate regulatory agencies about “what is legitimate scientific data with a legitimate use of particular instrumentation, and what protocols have intellectual or scientific merit or not.”

He noted that NIST wasn’t aware of this need prior to beginning a dialogue with the Stanford researchers. “By coming here and interacting directly with groups that have patient contact, and dealing with developing solutions to significant medical problems, we are able to focus NIST on these areas and bring the resources of the medical community here at Stanford to bear with NIST, as well as with the companies that are supplying the instrumentation,” said Baer.

Matt Jones is a staff reporter for GenomeWeb Daily News. He covers public policy, legislation, and funding issues that affect researchers in the genomics field, as well as the operations of research institutes. E-mail Matt Jones or follow GWDN’s headlines at @DailyNewsGW.

Nrf2 Role in Blocking DNA Damage

June 21, 2013 by larryhbern

Larry H Bernstein, MD, Reporter & Curator
http://pharmaceuticalintelligence.com/2013/06/21/Nrf2 Role in Blocking DNA Damage/lhbern

DNA damage has been a central focus of carcinogenesis. The following is of great interest in this respect.

Nrf2 as a novel molecular target for chemoprevention.

Lee JS, Surh YJ.

Cancer Lett. 2005 Jun 28;224(2):171-84. Epub 2004 Nov 11.

Source

National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-ku, Seoul 151-742, South Korea.

Abstract

One of the rational and effective strategies for chemoprevention is the blockade of DNA damage caused by carcinogenic insult. This can be achieved either

by reducing the formation of reactive carcinogenic species
or stimulating their detoxification.

A wide spectrum of xenobiotic metabolizing enzymes catalyze both phase I (oxidation and reduction) and phase II biotransformation (conjugation) reactions involved in carcinogen activation and/or deactivation. Several antioxidant-response element (ARE)-regulated gene products such as

glutathione S-transferase,
NAD(P)H:quinone oxidoreductase 1,
UDP-glucuronosyltransferase,
gamma-glutamate cysteine ligase, and
hemeoxygenase-1

are known to mediate detoxification and/or to exert antioxidant functions thereby protecting cells from genotoxic damage.

The transcription of ARE-driven genes is regulated, at least in part,

by nuclear transcription factor erythroid 2p45 (NF-E2)-related factor 2 (Nrf2),
which is sequestered in cytoplasm by Kelch-like ECH-associated protein 1 (Keap1).

Exposure of cells to ARE inducers results in

the dissociation of Nrf2 from Keap1 and
facilitates translocation of Nrf2 to the nucleus,
where it heterodimerizes with small Maf protein, and
binds to ARE,

eventually resulting in the transcriptional regulation of target genes.

The Nrf2-Keap1-ARE signaling pathway can be modulated by several upstream kinases including

phosphatidylinositol 3-kinase,
protein kinase C, and
mitogen-activated protein kinases.

Selected Nrf2-Keap1-ARE activators, such as

oltipraz,
anethole dithiolethione,
sulforaphane,
6-methylsulphinylhexyl isothiocyanate,
curcumin,
caffeic acid phenethyl ester,
4′-bromoflavone, etc.

are potential chemopreventive agents. This mini-review will focus on a chemopreventive strategy directed towards

protection of DNA and other important cellular molecules by
inducing de novo synthesis of phase II detoxifying or antioxidant genes via the Nrf2-ARE core signaling pathway.

PMID: 15914268 [PubMed – indexed for MEDLINE]

Nrf2 Pathway Regulates Multidrug-Resistance-Associated Protein 1 in Small Cell Lung Cancer (plosone.org)
antioxidant advancements (ericalawrencenaturopathy.wordpress.com)
Proteomic Profiling Reveals That Resveratrol Inhibits HSP27 Expression and Sensitizes Breast Cancer Cells to Doxorubicin Therapy (plosone.org)
LKB1 is a master kinase in cancer (pharmastrategyblog.com)
Stopping Tumor Survival In Low-Oxygen Environments (medicalnewstoday.com)

English: Graph of Nrf2 publications (pubmed search) by year (Photo credit: Wikipedia)

Most lifespan influencing genes affect the rate of DNA damage (Photo credit: Wikipedia)

Single-strand and double-strand DNA damage (Photo credit: Wikipedia)

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy | Tagged Biology, Cancer - General, DNA, DNA repair, Keap1/Nrf2 pathway, NFE2L2, Nrf2, Nrf2 nuclear translocation, oxidative stress, PubMed, Seoul National University | Leave a Comment »

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Fig. 1 Adjusted and unadjusted survival rates in all patients treated with CABG or PCI-stenting http://www.ncbi.nlm.nih.gov/pmc/articles/PMC101260/table/t3-2/?report=previmg

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Will Drug-Eluting Stents Replace Coronary Artery Bypass Surgery?

Abstract

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CABG vs PTCA

CABG vs Stents

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Advantages of CABG

LIMA-to-LAD Long-Term Patency

Techniques to Improve Conduit Patency

Hybrid Coronary Revascularization

Will Stent Revascularization Replace Coronary Artery Bypass Grafting?

Fig. 1 Graph of graft patency shows deterioration rates over 10 years and the comparative superiority of using the internal mammary artery (IMA) instead of the saphenous vein (SVG).http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528239/bin/25FF1.gif

Percutaneous Transluminal Coronary Angioplasty

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Comparing Stenting and Surgery

Conclusion

Should all ischemic mitral regurgitation be repaired? When should we replace? Curr Opin Cardiol. 2011

Purpose of review

Recent findings

Summary

Introduction

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Figure 2.TEE Showing the Aortic Bioprosthetic Valve.

Figure 3.The 4 Prosthetic Heart Valves.

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Fig. 1 Adjusted and unadjusted survival rates in all patients treated with CABG or PCI-stenting
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC101260/table/t3-2/?report=previmg

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC101260/table/t3-2/?report=previmg

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC101260/bin/2FF2.jpg

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC101260/bin/2TT4.jpg

Fig. 3 Adjusted odds ratios comparing the results of CABG and PCI-stenting in the various prespecified subsets.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC101260/bin/2FF3.gif

Table I. Independent Predictors of 30-Day Major Adverse Cardiac Events and 3-Year Survival after Drug-Eluting Stent Placement
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528239/bin/25TT1.jpg