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Archive for the ‘CANCER BIOLOGY & Innovations in Cancer Therapy’ Category


Drug regiment consisting of anti-inflammatories (COX-2) and anti-stress medications (β-Adrenergic Blockade) given before and after surgery could reduce cancer recurrence (biomarkers of metastatic processes)

Reporter: Aviva Lev-Ari, PhD, RN

 

“We found that the drugs were very efficient in reducing biomarkers of metastatic processes,” Prof. Ben-Eliyahu said. “For example, we found that the drug treatment reverses EMT — the process that tumor cells go through to slip out of the primary tumor and enter another organ. It is a crucially important step in the metastatic process. We also looked at indices related to the immune system and were able to improve immune competence and reduce inflammation with the drugs.”

The research team has conducted a similar study, which has not yet been published, on colorectal cancer patients and has found similar results.

The researchers are currently considering a larger-scale clinical trial to establish the clinical long-term beneficial effects of this treatment. “Positive outcomes should validate this treatment and lead to its becoming available for most cancer patients,” Prof. Ben-Eliyahu concluded.

 

Abstract

Purpose: Translational studies suggest that excess perioperative release of catecholamines and prostaglandins may facilitate metastasis and reduce disease-free survival. This trial tested the combined perioperative blockade of these pathways in breast cancer patients.

Experimental Design: In a randomized placebo-controlled biomarker trial, 38 early-stage breast cancer patients received 11 days of perioperative treatment with a β-adrenergic antagonist (propranolol) and a COX-2 inhibitor (etodolac), beginning 5 days before surgery. Excised tumors and sequential blood samples were assessed for prometastatic biomarkers.

Results: Drugs were well tolerated with adverse event rates comparable with placebo. Transcriptome profiling of the primary tumor tested a priori hypotheses and indicated that drug treatment significantly

(i) decreased epithelial-to-mesenchymal transition,

(ii) reduced activity of prometastatic/proinflammatory transcription factors (GATA-1, GATA-2, early-growth-response-3/EGR3, signal transducer and activator of transcription-3/STAT-3), and

(iii) decreased tumor-infiltrating monocytes while increasing tumor-infiltrating B cells.

Drug treatment also significantly

  • abrogated presurgical increases in serum IL6 and
  • C-reactive protein levels,
  • abrogated perioperative declines in stimulated IL12 and IFNγ production,
  • abrogated postoperative mobilization of CD16 “classical” monocytes, and
  • enhanced expression of CD11a on circulating natural killer cells.

Conclusions: Perioperative inhibition of COX-2 and β-adrenergic signaling provides a safe and effective strategy for inhibiting multiple cellular and molecular pathways related to metastasis and disease recurrence in early-stage breast cancer. Clin Cancer Res; 1–11. ©2017 AACR.

 

SOURCES

“Anti-Inflammatory and Anti-Stress Drugs Taken Before Surgery May Reduce Metastatic Recurrence.” NeuroscienceNews. NeuroscienceNews, 7 August 2017.

Original Research: Abstract for

“Perioperative COX-2 and β-Adrenergic Blockade Improves Metastatic Biomarkers in Breast Cancer Patients in a Phase-II Randomized Trial”

by Lee Shaashua, Maytal Shabat-Simon, Rita Haldar, Pini Matzner, Oded Zmora, Moshe Shabtai, Eran Sharon, Tanir Allweis, Iris Barshack, Lucile Hayman, Jesusa Arevalo, Jeffrey Ma, Maya Horowitz, Steven Cole and Shamgar Ben-Eliyahu in Clinical Cancer Research. Published online August 2017 doi:10.1158/1078-0432.CCR-17-0152

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Agios Pharmaceuticals target the metabolism of cancer cells for making drugs that essentially try to repair cancer cells

Reporter: Aviva Lev-Ari, PhD, RN

A small biotech behind a groundbreaking approach to tackling cancer just got its first drug approved

http://www.businessinsider.com/fda-approves-agios-pharmaceuticals-drug-targeting-cancer-cell-metabolism-2017-8

See

Cancer Metabolism

http://www.agios.com/research/cancer-metabolism/

Metabolic Immuno-Oncology

http://www.agios.com/research/metabolic-immuno-oncology/

 

 

The VOICE of Larry H. Bernstein, MD, FCAP

Cancer cells didn’t need as much oxygen to metabolize sugar as normal cells. 

Not correct. Cancer cells metabolize glucose by aerobic glycolysis (4 ATP) with an impaired mitochondrial oxygen utilization (36 ATP). 

There is a reverse Warburg effect in which the underlying stromal cell carries out crosstalk with the epithelial cell. 

There is also a 3rd dimension. Cells undergo a series of adaptive changes tied to proteostasis. This involves the sulfur amino acid cysteine and disulfide bonds, which is involved with protein oligomerization in the ER, and also signaling in the mitochondria with mDNA and the nucleus. 

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New Treatment in Development for Glioblastoma: Hopes for Sen. John McCain

Reporter: Aviva Lev-Ari, PhD, RN

We wish all patients diagnosed with Glioblastoma to be able to benefit from the advancements in Sciences reported, below

SOURCE

Glioblastoma Is A Grim Diagnosis, But There Are Some Signs Of Hope

Karen Weintraub, July 20, 2017 Updated July 21, 2017 5:33 PM

 

Advancements in Crossing The Blood-Brain Barrier

Paula Hammond, of MIT’s Koch Institute of Integrative Cancer Research: “We believe we have a handle on a good stealth mechanism. Now, we’re looking at enhanced uptake,” she said. “We have to begin to think a little bit about how to get nature on our side on this one.”

At the Brigham, researchers are trying another approach to getting across the blood-brain-barrier: prying open holes in its armor with beams of ultrasound. Although normally used to take cool pictures during pregnancy, multiple beams of ultrasound aimed at the same area can make blood vessels of the brain “leakier,” according to research at the Brigham.

 

Advancement in Stem Cells against Tumors

There’s also a possibility that stem cells may be useful for tracking down and killing tumor cells. Khalid Shah, director for the Center for Stem Cell Therapeutics and Imaging at Brigham and Women’s Hospital, has been experimenting with delivering engineered stem cells directly to tumor sites after surgery.

William Curry at Mass. General, is that the longer a patient with glioblastoma can hang on, the better their chances of getting one of these new treatments.

“The longer you stay alive and the longer you maintain good neurological function, the more eligible you one may be to see the benefits and the fruits of a lot of the research that is really accelerating right now,” he said.

SOURCE

Glioblastoma Is A Grim Diagnosis, But There Are Some Signs Of Hope

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FDA: CAR-T therapy outweigh its risks tisagenlecleucel, manufactured by Novartis of Basel – 52 out of 63 participants — 82.5% — experienced overall remissions – young patients with Leukaemia [ALL]

 

Reporter: Aviva Lev-Ari, PhD, RN

 

Basel, July 12, 2017 – Novartis announced today that the US Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) unanimously (10-0) recommended approval of CTL019 (tisagenlecleucel), an investigational chimeric antigen receptor T cell (CAR-T) therapy, for the treatment of relapsed or refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL).

“The panel’s unanimous recommendation in favor of CTL019 moves us closer to potentially delivering the first-ever commercially approved CAR-T cell therapy to patients in need,” said Bruno Strigini, CEO, Novartis Oncology. “We’re very proud to be expanding new frontiers in cancer treatment by advancing immunocellular therapy for children and young adults with r/r B-cell ALL and other critically ill patients who have limited options. We look forward to working with the FDA as they complete their review.”

Acute lymphoblastic leukemia comprises approximately 25% of cancer diagnoses among children under 15 years old and is the most common childhood cancer in the US[1]. Effective treatment options for patients with r/r ALL are limited. In pediatric and young adult patients with B-cell ALL that have relapsed multiple times or become refractory to treatment, the five-year disease-free survival is less than 10-30%[2],[3],[4].

CTL019 was first developed by the University of Pennsylvania (Penn) and uses the 4-1BB costimulatory domain in its chimeric antigen receptor to enhance cellular responses as well as persistence of CTL019 after it is infused into the patient, which may be associated with long-lasting remissions in patients. In 2012, Novartis and Penn entered into a global collaboration to further research, develop and commercialize CAR-T cell therapies, including CTL019, for the investigational treatment of cancers. Children’s Hospital of Philadelphia (CHOP) was the first institution to investigate CTL019 in the treatment of pediatric patients and led the single site trial.

SOURCE

https://www.novartis.com/news/media-releases/novartis-car-t-cell-therapy-ctl019-unanimously-10-0-recommended-approval-fda

RISKS:

During the 2015 tisagenlecleucel trial, 47% of participants experienced an

  • extreme inflammatory reaction known as cytokine release syndrome, severe cases of which are called cytokine storms. The syndrome — characterized by symptoms such as high fevers and organ failure — can be life-threatening. But
  • Novartis says trial clinicians were able to manage the reaction successfully in all cases.
  • Neurological problems such as seizures and hallucinations were also relatively common but temporary,
  • the Novartis team reported. This is in stark contrast to some other CAR-T trials that have,
  • over the past year, reported the deaths of several participants from severe brain swelling.
  • Novartis’s therapy is not identical to the CAR-T cells used in those trials, which were administered in adults, but the deaths cast a pall over the entire field.

To generate a batch of tisagenlecleucel, white blood cells are purified from a sample of a patient’s blood and shipped to a central processing centre. There, staff use a virus to insert into the T cells genes that encode a cellular receptor — called a chimaeric antigen receptor — that will recognize leukaemia cells.

SOURCE

Engineered cell therapy for cancer gets thumbs up from FDA advisers

Treatment shows promise in young people with leukaemia, but safety risks abound.

Heidi Ledford, 12 July 2017

http://www.nature.com/news/engineered-cell-therapy-for-cancer-gets-thumbs-up-from-fda-advisers-1.22304?WT.ec_id=NEWSDAILY-20170713

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Reporter and Curator: Irina Robu, PhD

Monitoring cancer patients and evaluating their response to treatment can sometimes involve invasive procedures, including surgery.

The liquid biopsies have become something of a Holy Grail in cancer treatment among physicians, researchers and companies gambling big on the technology. Liquid biopsies, unlike traditional biopsies involving invasive surgery — rely on an ordinary blood draw. Developments in sequencing the human genome, permitting researchers to detect genetic mutations of cancers, have made the tests conceivable. Some 38 companies in the US alone are working on liquid biopsies by trying to analyze blood for fragments of DNA shed by dying tumor cells.

Premature research on the liquid biopsy has concentrated profoundly on patients with later-stage cancers who have suffered treatments, including chemotherapy, radiation, surgery, immunotherapy or drugs that target molecules involved in the growth, progression and spread of cancer. For cancer patients undergoing treatment, liquid biopsies could spare them some of the painful, expensive and risky tissue tumor biopsies and reduce reliance on CT scans. The tests can rapidly evaluate the efficacy of surgery or other treatment, while old-style biopsies and CT scans can still remain inconclusive as a result of scar tissue near the tumor site.

As recently as a few years ago, the liquid biopsies were hardly used except in research. At the moment, thousands of the tests are being used in clinical practices in the United States and abroad, including at the M.D. Anderson Cancer Center in Houston; the University of California, San Diego; the University of California, San Francisco; the Duke Cancer Institute and several other cancer centers.

With patients for whom physicians cannot get a tissue biopsy, the liquid biopsy could prove a safe and effective alternative that could help determine whether treatment is helping eradicate the cancer. A startup, Miroculus developed a cheap, open source device that can test blood for several types of cancer at once. The platform, called Miriam finds cancer by extracting RNA from blood and spreading it across plates that look at specific type of mRNA. The technology is then hooked up at a smartphone which sends the information to an online database and compares the microRNA found in the patient’s blood to known patterns indicating different type of cancers in the early stage and can reduce unnecessary cancer screenings.

Nevertheless, experts warn that more studies are essential to regulate the accuracy of the test, exactly which cancers it can detect, at what stages and whether it improves care or survival rates.

SOURCE

https://www.fastcompany.com/3037117/a-new-device-can-detect-multiple-types-of-cancer-with-a-single-blood-test

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356857/

Other related articles published in this Open Access Online Scientific Publishing Journal include the following:

Liquid Biopsy Chip detects an array of metastatic cancer cell markers in blood – R&D @Worcester Polytechnic Institute, Micro and Nanotechnology Lab

Reporters: Tilda Barliya, PhD and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/12/28/liquid-biopsy-chip-detects-an-array-of-metastatic-cancer-cell-markers-in-blood-rd-worcester-polytechnic-institute-micro-and-nanotechnology-lab/

Liquid Biopsy Assay May Predict Drug Resistance

Curator: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2015/11/06/liquid-biopsy-assay-may-predict-drug-resistance/

One blood sample can be tested for a comprehensive array of cancer cell biomarkers: R&D at WPI

Curator: Marzan Khan, B.Sc

https://pharmaceuticalintelligence.com/2017/01/05/one-blood-sample-can-be-tested-for-a-comprehensive-array-of-cancer-cell-biomarkers-rd-wpi

 

 

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SEE OUR NEW CANCER BOOK ON AMAZON.com

Editor-in-Chief: Aviva Lev-Ari, PhD, RN

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Pharmacotyping Pancreatic Cancer Patients in the Future: Two Approaches – ORGANOIDS by David Tuveson and Hans Clevers and/or MICRODOSING Devices by Robert Langer

Curator: Aviva Lev-Ari, PhD, RN

 

This curation provides the resources for edification on Pharmacotyping Pancreatic Cancer Patients in the Future

 

  • Professor Hans Clevers at Clevers Group, Hubrecht University

https://www.hubrecht.eu/onderzoekers/clevers-group/

  • Prof. Robert Langer, MIT

http://web.mit.edu/langerlab/langer.html

Langer’s articles on Drug Delivery

https://scholar.google.com/scholar?q=Langer+on+Drug+Delivery&hl=en&as_sdt=0&as_vis=1&oi=scholart&sa=X&ved=0ahUKEwixsd2w88TTAhVG4iYKHRaIAvEQgQMIJDAA

organoids, which I know you’re pretty involved in with Hans Clevers. What are your plans for organoids of pancreatic cancer?

Organoids are a really terrific model of a patient’s tumour that you generate from tissue that is either removed at the time of surgery or when they get a small needle biopsy. Culturing the tissue and observing an outgrowth of it is usually successful and when you have the cells, you can perform molecular diagnostics of any type. With a patient-derived organoid, you can sequence the exome and the RNA, and you can perform drug testing, which I call ‘pharmacotyping’, where you’re evaluating compounds that by themselves or in combination show potency against the cells. A major goal of our lab is to work towards being able to use organoids to choose therapies that will work for an individual patient – personalized medicine.

Organoids could be made moot by implantable microdevices for drug delivery into tumors, developed by Bob Langer. These devices are the size of a pencil lead and contain reservoirs that release microdoses of different drugs; the device can be injected into the tumor to deliver drugs, and can then be carefully dissected out and analyzed to gain insight into the sensitivity of cancer cells to different anticancer agents. Bob and I are kind of engaged in a friendly contest to see whether organoids or microdosing devices are going to come out on top. I suspect that both approaches will be important for pharmacotyping cancer patients in the future.

From the science side, we use organoids to discover things about pancreatic cancer. They’re great models, probably the best that I know of to rapidly discover new things about cancer because you can grow normal tissue as well as malignant tissue. So, from the same patient you can do a comparison easily to find out what’s different in the tumor. Organoids are crazy interesting, and when I see other people in the pancreatic cancer field I tell them, you should stop what you’re doing and work on these because it’s the faster way of studying this disease.

SOURCE

Other related articles on Pancreatic Cancer and Drug Delivery published in this Open Access Online Scientific Journal include the following:

 

Pancreatic Cancer: Articles of Note @PharmaceuticalIntelligence.com

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/05/26/pancreatic-cancer-articles-of-note-pharmaceuticalintelligence-com/

Keyword Search: “Pancreatic Cancer” – 275 Article Titles

https://pharmaceuticalintelligence.wordpress.com/wp-admin/edit.php?s=Pancreatic+Cancer&post_status=all&post_type=post&action=-1&m=0&cat=0&paged=1&action2=-1

Keyword Search: Drug Delivery: 542 Articles Titles

https://pharmaceuticalintelligence.wordpress.com/wp-admin/edit.php?s=Drug+Delivery&post_status=all&post_type=post&action=-1&m=0&cat=0&paged=1&action2=-1

Keyword Search: Personalized Medicine: 597 Article Titles

https://pharmaceuticalintelligence.wordpress.com/wp-admin/edit.php?s=Personalized+Medicine&post_status=all&post_type=post&action=-1&m=0&cat=0&paged=1&action2=-1

  • Cancer Biology & Genomics for Disease Diagnosis, on Amazon since 8/11/2015

http://www.amazon.com/dp/B013RVYR2K

 

 

VOLUME TWO WILL BE AVAILABLE ON AMAZON.COM ON MAY 1, 2017

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