Harnessing Personalized Medicine for Cancer Management, Prospects of Prevention and Cure: Opinions of Cancer Scientific Leaders
Curator: Aviva Lev-Ari, PhD, RN
This is our own representation of Experts on our Team expressing Scientific Opinions and Comments on their Peers’ Scientific work
presented from our Research Category on
Interviews with Scientific Leaders
here are our members of the Team on Cancer Biology
Scientific Leaders @ http://pharmaceuticalintelligence.com
Dr. Ritu Saxena – On Personalized Medicine gearing up to tackle cancer
According to the American Cancer Society, the probability that an individual will develop or die from cancer over the course of a lifetime (lifetime risk) in the United States is less than a 1 in 2 for men; and a little more than 1 in 3 for women. Thanks to passionate and committed researchers like Dr. Tsimberidou, personalized medicine-based cancer treatments might take us a few steps closer to curing the disease. Dr. Tsimberidou concludes, “We have to develop innovative treatment protocols and to offer the best treatment possible for each of our patients”.
In:
Personalized medicine gearing up to tackle cancer
http://pharmaceuticalintelligence.com/2013/01/07/personalized-medicine-gearing-up-to-tackle-cancer/
Dr. Tilda Barlyia – On James Watson’s Examination of The “Cancer establishments”
In reply to cancer biologist Robert Weinberg of MIT
I would like to add something regarding this comment and I quote “the main reason drugs that target genetic glitches are not cures is that cancer cells have a work-around. If one biochemical pathway to growth and proliferation is blocked by a drug such as AstraZeneca‘s Iressa or Genentech’s Tarceva for non-small-cell lung cancer, said cancer biologist Robert Weinberg of MIT, the cancer cells activate a different, equally effective pathway”
“I think this is why some researching are aiming to find a drug that targets a common denominator of multiple pathways rather that “just” a specific pathway as many cancer cells activate a different equal pathway.”
In:
The “Cancer establishments” examined by James Watson, co-discoverer of DNA w/Crick, 4/1953
January 9, 2013
Dr. Stephen Williams – On James Watson’s Examination of The “Cancer establishments”
I remember back in the 90s when big pharmas were talking about developing farnesyltransferase inhibitors (the enzyme that puts the modification on ras) as well as myc inhibitors as a sliver bullet for cancer therapy but I have not heard much else.
And as far as personlized medicine, yes personalized medicine does have a role to play and can be very effective but remember we are only talking about maybe 10% of cases for a tumor type.
Kudos to both Watson and Weinstein for stating we really need to delve into tumor biology to determine functional pathways (like metabolism) which are a common feature of the malignant state
In:
The “Cancer establishments” examined by James Watson, co-discoverer of DNA w/Crick, 4/1953
January 9, 2013
Pierluigi Scalia MD, PhD — On Molecular Pathology and Personalized Medicine
Commissioned Comment by Dr. Aviva Lev-Ari
The nanotechnology field certainly provides plenty of opportunity in the field of personalized cancer treatments (Rx). One comment I wanted to make due to the high relevance and implication is in the definition of Personalized Medicine” at large. I believe you are correct to define it as a “movement” within modern medicine as it has been so far. However, I believe we have all the multidisciplinary knowledge we need to move that concept to a real science and a specific operating system in the way we do think and apply medical knowledge.
Even though your definition is definitely correct, I would provide an operating version which I believe can help many to understand WHAT are the minimum requirements to classify a Cancer treatment as part of a “personalized” cancer treatment. My take on that (which i have expressed elsewhere) is that:
“Personalized Cancer Medicine is that field of medicine using a next-generation diagnostic procedure (or a minimum cancer gene-drivers screening panel) in order to define a key number of cancer abnormalities in each patient clinical specimen for which a targeted therapy or smart integrated approach provides a definite survival advantage versus current conventional medicine”.
This operational definition anticipates the concept of applied pharmacogenomics that is currently more of a research area rather than a clinically mature field.
On the other hand, it leads us to that limiting factor towards the adoption of personalized treatments which is the evolution in molecular pathology with full adoption of genomics as the routine way to screen for a patient Oncotype as part of the routine diagnostic process.
The fact of using nanotechnology in order to target and treat abnormal cancer cells and tissues adds a powerful weapon towards eradicating the disease in the foreseeable future. However, focusing on weapons when we still have not found a reliable way to build that personalized “shooting target” (Cancer Fingerprinting) still constitutes, in my opinion, the single most relevant barrier to the adoption of Personalized treatments.
In:
Nanotechnology, personalized medicine and DNA sequencing
January 9, 2013
Larry Bernstein, MD – On Modern Techniques of Molecular Pathology
A look at clinical laboratory science and its expected progress over the next decade
In Response to Dr. Scalia’s Comment on Molecular Pathology
In:
Nanotechnology, personalized medicine and DNA sequencing
Commissioned Post by Dr. Aviva Lev-Ari
January 9, 2013
Nanotechnology, personalized medicine and DNA sequencing
Promising forecasts have been made projecting great expectations for medical sciences in the year 2013 and beyond. These predictions follow a decade after completion of the Human Genome Project, and are accompanied by immense breakthroughs in computational and applied mathematics. In my view, they are:
- Genomic and allied “OMICs-technology”
- Innovation in mathematical classification (complexity)
- Nanotechnology
- Synthetic chemistry from physics, organic and inorganic chemistry
It is not my intention to go deeply into the exponential group of these advanced and integrative sciences; rather, I want raise awareness of an emerging new world that will open to the clinical laboratory scientist, and signal the need in the next generation of laboratory personnel to embrace knowledge domains that will be critical for their careers.
All of these breakthroughs are tied together by a search for personalized and integrative medicine. These breakthroughs will reinvent nutritional and pharmaceutical medicine as well as medical devices and restructure clinical laboratory and imaging applications to cardiology, oncology, radiology and anatomical pathology.
Metabolomics
What does metabolomics and metabolic profiling have to do with this? Metabolomics is the measurement of small molecules that interact with membrane receptors1 that are involved with regulation of genomic transcription and cellular regulation and upregulation or downregulation of metabolic processes essential to health. As well, these small molecules may provide targets for disease treatments, and as they are investigated, also provide further “analytes for diagnosis and, moreover, prediction of short-term or long-term outcomes.”2
As a result, the laboratory will become a more significant factor in measuring health and disease and in guiding health or disease maintenance. As our population has reached increased age limits, the laboratory has been a contributor in the public health sphere, and will have a greater role as a result of
- Improved tie in with provision of information to not only the healthcare workers, but also the patient.
- Achieve turnaround times for critical results through better workflow
- Greater control and access to a next generation of point-of-care technology integrated with the laboratory database, and a restructured electronic health record.
- Despite the hype about the BIG DATA revolution, this is achievable in the system here proposed because there is a published model to achieve this(2)
Familiar Methods
Either individually or grouped as a profile, metabolites are detected by either nuclear magnetic resonance spectroscopy or mass spectrometry, providing a basis for uses of metabolome findings extended to the early detection and diagnosis of cancer and as both a predictive and pharmacodynamics marker of drug effect. We can expect it to become the link between the laboratory and the clinic. The methods used in genomics are microarrays, and for proteomics they are the already familiar chromatographic principles that species migrate at different rates through a column matrix based on their volatility, or carries out a separation as the molecules differ by their adsorption to and elution from a solid matrix, dependent on the binding to the matrix and solubility in the solvent eluate, modified by ph, ionic concentration, and specific conditions needed for recovery. Powerful mathematical tools are used to analyze the data.3
Cardiovascular Disease
Although coronary thrombosis is the final event in acute coronary syndromes, there is increasing evidence that inflammation also plays a key role in development of atherosclerosis and its clinical manifestations, such as myocardial infarction, stroke and peripheral vascular disease. The inflammatory component was indicated by epidemiological studies of elevated serum levels of high sensitivity C-reactive protein. That eventually led to the demonstration of a benefit from reduction of CRP in individuals without characteristic lipidemia in a major clinical trial, which drew a relationship between diabetes, obesity and disordered inflammatory response in the causation of coronary artery disease, aortic valve and artery disease, carotid artery and peripheral vascular disease.
Cancer
Because cancer cells are known to possess a highly unique metabolic phenotype, development of specific biomarkers in oncology is possible and might be used in identifying fingerprints, profiles or signatures to detect the presence of cancer, determine prognosis and/or assess the pharmacodynamic effects of therapy.4
HDM2, a negative regulator of the tumor suppressor p53, is over-expressed in many cancers that retain wild-type p53. Consequently, the effectiveness of chemotherapies that induce p53 might be limited, and inhibitors of the HDM2–p53 interaction are being sought as tumor-selective drugs.5
Coagulation
Blood coagulation plays a key role among numerous mediating systems activated in inflammation. Receptors of the PAR family serve as sensors of serine proteinases of the blood clotting system in the target cells involved in inflammation. Activation of PAR_1 by thrombin and of PAR_2 by factor Xa leads to a rapid expression and exposure on the membrane of endothelial cells of both adhesive proteins that mediate an acute inflammatory reaction and of the tissue factor that initiates the blood coagulation cascade.
The details of evolving methods are avoided in order to build the argument that a very rapid expansion of discovery has been evolving depicting disease, disease mechanisms, disease associations, metabolic biomarkers, study of effects of diet and diet modification, and opportunities for targeted drug development.
Dr. Bernstein is CEO of Triplex Medical Science, and CSO of Leaders in Pharmaceutical Intelligence http://pharmaceuticalintelligence.com. He has been involved in writing, reviewing, and a collaborative project on reducing the noise that exists in complex data, and developing a primary evidence-based classification since retiring from a career in pathology spanning 4 decades.
References
1. Bernstein LH. Metabolomics, metabonomics and functional nutrition: The next step in nutritional metabolism and biotherapeutics. Journal of Pharmacy and Nutrition Sciences, 2012, 2, (xxx).
2. David G, Bernstein LH, and Coifman RR. Generating evidence-based interpretation of hematology screens via anomaly characterization. The Open Clinical Chemistry Journal 2011;4: 10-16.
3. Grainger DJ. Megavariate statistics meets high data-density analytical methods: The future of medical diagnostics? IRTL Reviews 2003;1:1-6.
5. Fischer PM, Lane DP. Small molecule inhibitors of thep53 suppressor HDM2: Have protein-protein interactions come of age as drug targets? Trends in Pharm Sci 2004;25(7):343-346.
Other Articles on this Open Access Online Scientific Journal:
Bernstein LH. Assessing Cardiovascular Disease with Biomarkers. http://pharmaceuticalintelligence.com
Bernstein LH. Predicting Tumor Response, Progression, and Time to Recurrence. http://pharmaceticalintelligence.com
Bernstein LH. Special Considerations in Blood Lipoproteins, Viscosity, Assessment and Treatment. http://pharmaceuticalintelligence.com
Comment in Response to Dr. Scalia’s Comment In:
Nanotechnology, personalized medicine and DNA sequencing
January 9, 2013
Dr. Tilda Barlyia – On Quality control (QC) of DNA sequencing
In response to Larry Bernstein, MD comment on
Nanotechnology, personalized medicine and DNA sequencing
Quality control (QC) of DNA sequencing is of major challenge especially when sequencing long DNA strands. This is also probably one of the reasons why these nanopore DNA sequencers devices haven’t made it to the market yet. Some of the challenges that these sequencing technique have encountered are: (a) high velocity in which the DNA segment passes through the pores and which needs to be slowed down, (b) the need for high spatial resolutions and orientation of the nucleotide in the gap, (c) complex algorithms as well as error-prone DNA conversion steps (from dsDNA to ssDNA). I believe that there’s a long way before we see these devices on the shelf but it’s definitely inspiring to see how scientists vision these techniques and creatively finds ways to solve the problem.
In:
Nanotechnology, personalized medicine and DNA sequencing
January 9, 2013
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PUT IT IN CONTEXT OF CANCER CELL MOVEMENT
The contraction of skeletal muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from the sarcoplasmic reticuluma specialized network of internal membranes, similar to the endoplasmic reticulum, that stores high concentrations of Ca2+ ions. The release of Ca2+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-5 M. The increased Ca2+ concentration signals muscle contraction via the action of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Figure 11.25). Tropomyosin is a fibrous protein that binds lengthwise along the groove of actin filaments. In striated muscle, each tropomyosin molecule is bound to troponin, which is a complex of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Ca2+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, so the muscle does not contract. At high concentrations, Ca2+ binding to troponin C shifts the position of the complex, relieving this inhibition and allowing contraction to proceed.
Figure 11.25
Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated muscle, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more ) Contractile Assemblies of Actin and Myosin in Nonmuscle Cells
Contractile assemblies of actin and myosin, resembling small-scale versions of muscle fibers, are present also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin II, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to one another (Figure 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin II, probably by competing with filamin for binding sites on actin.
Figure 11.26
Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin II produce contraction by sliding actin filaments in opposite directions. Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to attachment of the actin cytoskeleton to regions of cell-substrate and cell-cell contacts (see Figures 11.13 and 11.14). The contraction of stress fibers produces tension across the cell, allowing the cell to pull on a substrate (e.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is particularly important during embryonic development, when sheets of epithelial cells fold into structures such as tubes.
The most dramatic example of actin-myosin contraction in nonmuscle cells, however, is provided by cytokinesisthe division of a cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile ring consisting of actin filaments and myosin II assembles just underneath the plasma membrane. Its contraction pulls the plasma membrane progressively inward, constricting the center of the cell and pinching it in two. Interestingly, the thickness of the contractile ring remains constant as it contracts, implying that actin filaments disassemble as contraction proceeds. The ring then disperses completely following cell division.
Figure 11.27
Cytokinesis. Following completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin II divides the cell in two.
http://www.ncbi.nlm.nih.gov/books/NBK9961/
This is good. I don’t recall seeing it in the original comment. I am very aware of the actin myosin troponin connection in heart and in skeletal muscle, and I did know about the nonmuscle work. I won’t deal with it now, and I have been working with Aviral now online for 2 hours.
I have had a considerable background from way back in atomic orbital theory, physical chemistry, organic chemistry, and the equilibrium necessary for cations and anions. Despite the calcium role in contraction, I would not discount hypomagnesemia in having a disease role because of the intracellular-extracellular connection. The description you pasted reminds me also of a lecture given a few years ago by the Nobel Laureate that year on the mechanism of cell division.
PUT IT IN CONTEXT OF CANCER CELL MOVEMENT
The contraction of skeletal muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from the sarcoplasmic reticuluma specialized network of internal membranes, similar to the endoplasmic reticulum, that stores high concentrations of Ca2+ ions. The release of Ca2+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-5 M. The increased Ca2+ concentration signals muscle contraction via the action of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Figure 11.25). Tropomyosin is a fibrous protein that binds lengthwise along the groove of actin filaments. In striated muscle, each tropomyosin molecule is bound to troponin, which is a complex of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Ca2+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, so the muscle does not contract. At high concentrations, Ca2+ binding to troponin C shifts the position of the complex, relieving this inhibition and allowing contraction to proceed.
Figure 11.25
Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated muscle, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more ) Contractile Assemblies of Actin and Myosin in Nonmuscle Cells
Contractile assemblies of actin and myosin, resembling small-scale versions of muscle fibers, are present also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin II, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to one another (Figure 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin II, probably by competing with filamin for binding sites on actin.
Figure 11.26
Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin II produce contraction by sliding actin filaments in opposite directions. Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to attachment of the actin cytoskeleton to regions of cell-substrate and cell-cell contacts (see Figures 11.13 and 11.14). The contraction of stress fibers produces tension across the cell, allowing the cell to pull on a substrate (e.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is particularly important during embryonic development, when sheets of epithelial cells fold into structures such as tubes.
The most dramatic example of actin-myosin contraction in nonmuscle cells, however, is provided by cytokinesisthe division of a cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile ring consisting of actin filaments and myosin II assembles just underneath the plasma membrane. Its contraction pulls the plasma membrane progressively inward, constricting the center of the cell and pinching it in two. Interestingly, the thickness of the contractile ring remains constant as it contracts, implying that actin filaments disassemble as contraction proceeds. The ring then disperses completely following cell division.
Figure 11.27
Cytokinesis. Following completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin II divides the cell in two.
http://www.ncbi.nlm.nih.gov/books/NBK9961/
This is good. I don’t recall seeing it in the original comment. I am very aware of the actin myosin troponin connection in heart and in skeletal muscle, and I did know about the nonmuscle work. I won’t deal with it now, and I have been working with Aviral now online for 2 hours.
I have had a considerable background from way back in atomic orbital theory, physical chemistry, organic chemistry, and the equilibrium necessary for cations and anions. Despite the calcium role in contraction, I would not discount hypomagnesemia in having a disease role because of the intracellular-extracellular connection. The description you pasted reminds me also of a lecture given a few years ago by the Nobel Laureate that year on the mechanism of cell division.
PUT IT IN CONTEXT OF CANCER CELL MOVEMENT
The contraction of skeletal muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from the sarcoplasmic reticuluma specialized network of internal membranes, similar to the endoplasmic reticulum, that stores high concentrations of Ca2+ ions. The release of Ca2+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-5 M. The increased Ca2+ concentration signals muscle contraction via the action of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Figure 11.25). Tropomyosin is a fibrous protein that binds lengthwise along the groove of actin filaments. In striated muscle, each tropomyosin molecule is bound to troponin, which is a complex of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Ca2+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, so the muscle does not contract. At high concentrations, Ca2+ binding to troponin C shifts the position of the complex, relieving this inhibition and allowing contraction to proceed.
Figure 11.25
Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated muscle, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more ) Contractile Assemblies of Actin and Myosin in Nonmuscle Cells
Contractile assemblies of actin and myosin, resembling small-scale versions of muscle fibers, are present also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin II, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to one another (Figure 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin II, probably by competing with filamin for binding sites on actin.
Figure 11.26
Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin II produce contraction by sliding actin filaments in opposite directions. Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to attachment of the actin cytoskeleton to regions of cell-substrate and cell-cell contacts (see Figures 11.13 and 11.14). The contraction of stress fibers produces tension across the cell, allowing the cell to pull on a substrate (e.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is particularly important during embryonic development, when sheets of epithelial cells fold into structures such as tubes.
The most dramatic example of actin-myosin contraction in nonmuscle cells, however, is provided by cytokinesisthe division of a cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile ring consisting of actin filaments and myosin II assembles just underneath the plasma membrane. Its contraction pulls the plasma membrane progressively inward, constricting the center of the cell and pinching it in two. Interestingly, the thickness of the contractile ring remains constant as it contracts, implying that actin filaments disassemble as contraction proceeds. The ring then disperses completely following cell division.
Figure 11.27
Cytokinesis. Following completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin II divides the cell in two.
http://www.ncbi.nlm.nih.gov/books/NBK9961/
This is good. I don’t recall seeing it in the original comment. I am very aware of the actin myosin troponin connection in heart and in skeletal muscle, and I did know about the nonmuscle work. I won’t deal with it now, and I have been working with Aviral now online for 2 hours.
I have had a considerable background from way back in atomic orbital theory, physical chemistry, organic chemistry, and the equilibrium necessary for cations and anions. Despite the calcium role in contraction, I would not discount hypomagnesemia in having a disease role because of the intracellular-extracellular connection. The description you pasted reminds me also of a lecture given a few years ago by the Nobel Laureate that year on the mechanism of cell division.
PUT IT IN CONTEXT OF CANCER CELL MOVEMENT
The contraction of skeletal muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from the sarcoplasmic reticuluma specialized network of internal membranes, similar to the endoplasmic reticulum, that stores high concentrations of Ca2+ ions. The release of Ca2+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-5 M. The increased Ca2+ concentration signals muscle contraction via the action of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Figure 11.25). Tropomyosin is a fibrous protein that binds lengthwise along the groove of actin filaments. In striated muscle, each tropomyosin molecule is bound to troponin, which is a complex of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Ca2+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, so the muscle does not contract. At high concentrations, Ca2+ binding to troponin C shifts the position of the complex, relieving this inhibition and allowing contraction to proceed.
Figure 11.25
Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated muscle, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more ) Contractile Assemblies of Actin and Myosin in Nonmuscle Cells
Contractile assemblies of actin and myosin, resembling small-scale versions of muscle fibers, are present also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin II, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to one another (Figure 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin II, probably by competing with filamin for binding sites on actin.
Figure 11.26
Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin II produce contraction by sliding actin filaments in opposite directions. Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to attachment of the actin cytoskeleton to regions of cell-substrate and cell-cell contacts (see Figures 11.13 and 11.14). The contraction of stress fibers produces tension across the cell, allowing the cell to pull on a substrate (e.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is particularly important during embryonic development, when sheets of epithelial cells fold into structures such as tubes.
The most dramatic example of actin-myosin contraction in nonmuscle cells, however, is provided by cytokinesisthe division of a cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile ring consisting of actin filaments and myosin II assembles just underneath the plasma membrane. Its contraction pulls the plasma membrane progressively inward, constricting the center of the cell and pinching it in two. Interestingly, the thickness of the contractile ring remains constant as it contracts, implying that actin filaments disassemble as contraction proceeds. The ring then disperses completely following cell division.
Figure 11.27
Cytokinesis. Following completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin II divides the cell in two.
http://www.ncbi.nlm.nih.gov/books/NBK9961/
This is good. I don’t recall seeing it in the original comment. I am very aware of the actin myosin troponin connection in heart and in skeletal muscle, and I did know about the nonmuscle work. I won’t deal with it now, and I have been working with Aviral now online for 2 hours.
I have had a considerable background from way back in atomic orbital theory, physical chemistry, organic chemistry, and the equilibrium necessary for cations and anions. Despite the calcium role in contraction, I would not discount hypomagnesemia in having a disease role because of the intracellular-extracellular connection. The description you pasted reminds me also of a lecture given a few years ago by the Nobel Laureate that year on the mechanism of cell division.
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Many thanks,Annette
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Many thanks,Annette
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Open Journals vs. Subscription-based « Pharmaceutical Intelligenceâ, very compelling plus the blog post ended up being a good read.
Many thanks,Annette
I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
Open Journals vs. Subscription-based « Pharmaceutical Intelligenceâ, very compelling plus the blog post ended up being a good read.
Many thanks,Annette
I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
Open Journals vs. Subscription-based « Pharmaceutical Intelligenceâ, very compelling plus the blog post ended up being a good read.
Many thanks,Annette
I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
Open Journals vs. Subscription-based « Pharmaceutical Intelligenceâ, very compelling plus the blog post ended up being a good read.
Many thanks,Annette
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Open Journals vs. Subscription-based « Pharmaceutical Intelligenceâ, very compelling plus the blog post ended up being a good read.
Many thanks,Annette
I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
Open Journals vs. Subscription-based « Pharmaceutical Intelligenceâ, very compelling plus the blog post ended up being a good read.
Many thanks,Annette
This is very insightful. There is no doubt that there is the bias you refer to. 42 years ago, when I was postdocing in biochemistry/enzymology before completing my residency in pathology, I knew that there were very influential mambers of the faculty, who also had large programs, and attracted exceptional students. My mentor, it was said (although he was a great writer), could draft a project on toilet paper and call the NIH. It can’t be true, but it was a time in our history preceding a great explosion. It is bizarre for me to read now about eNOS and iNOS, and about CaMKII-á, â, ã, ä – isoenzymes. They were overlooked during the search for the genome, so intermediary metabolism took a back seat. But the work on protein conformation, and on the mechanism of action of enzymes and ligand and coenzyme was just out there, and became more important with the research on signaling pathways. The work on the mechanism of pyridine nucleotide isoenzymes preceded the work by Burton Sobel on the MB isoenzyme in heart. The Vietnam War cut into the funding, and it has actually declined linearly since.
A few years later, I was an Associate Professor at a new Medical School and I submitted a proposal that was reviewed by the Chairman of Pharmacology, who was a former Director of NSF. He thought it was good enough. I was a pathologist and it went to a Biochemistry Review Committee. It was approved, but not funded. The verdict was that I would not be able to carry out the studies needed, and they would have approached it differently. A thousand young investigators are out there now with similar letters. I was told that the Department Chairmen have to build up their faculty. It’s harder now than then. So I filed for and received 3 patents based on my work at the suggestion of my brother-in-law. When I took it to Boehringer-Mannheim, they were actually clueless.