Epigenetics does not mean that thinking makes it so : Respectful Insolence

Epigenetics does not mean that thinking makes it so : Respectful Insolence

".....The not-so-subtle implication is that the reason one gets sick is because of one's habits. Of course, there are a lot of lifestyle diseases, but the implications goes beyond the sensible, science-based observation that obesity and lack of exercise increase the risk of certain diseases, into the realm of stating that if you just eat the right foods and do the right exercises you'll never get sick.

Utter nonsense, of course.

There's also a dark side to this sort of thinking, and that's the flip side of the argument. If you can nearly completely control the state of your health by what you eat and do, the not-so-subtle implication is that if you get sick it must be your fault. After all, if we have complete control over our health through our lifestyle, then it follows that if you're sick, you must be doing something wrong....."

"The latest way that quacks are trying to push the idea that you have near total control over your health is by abusing new findings in epigenetics. Epigenetics is the study of heritable changes in gene expression or phenotype that are not caused by changes in the underlying gene sequence........ It's a fascinating area of research, because it suggests that gene expression can be altered longer than transiently by environmental influences. Of course, given that organisms and biology are affected by environmental influences, this is almost a trivial observation; the power of epigenetics is that it can explain how such changes in gene expression can come about.....

Ginkgo May Sensitize Ovarian Cancer Cells to Cisplatin: Antiproliferative and Apoptosis-Inducing Effects of Ginkgolide B on Ovarian Cancer Cells

Ginkgo May Sensitize Ovarian Cancer Cells to Cisplatin: Antiproliferative and Apoptosis-Inducing Effects of Ginkgolide B on Ovarian Cancer Cells:

Ginkgolide B (GB), the primary active component of Ginkgo biloba extracts, may have antitumor properties. The objective of this study was to determine the effects and possible mechanisms of GB in ovarian cancer cells. In this study, human ovarian cancer cell lines (SKOV3 and CAOV3) were treated with different concentrations of GB alone or in combination with Cis-diaminodichloroplatinum (CDDP). .......Furthermore, GB had significantly less cytotoxicity than CDDP in normal human ovarian surface epithelial cells. This study suggests that GB can be proposed as an effective antiproliferative and apoptosis-inducing agent with interesting translational application in ovarian cancers, used in addition to conventional chemotherapy.

The transcription factor FOXL2: At the crossroads of ovarian physiology and pathology

The transcription factor FOXL2: At the crossroads of ovarian physiology and pathology: Publication year: 2012

Source:Molecular and Cellular Endocrinology

FOXL2 is a gene encoding a forkhead transcription factor. Its mutations or misregulation have been shown to cause the blepharophimosis–ptosis–epicanthus inversus (BPES) syndrome and more recently have been associated with the development of Ovarian Granulosa Cell Tumors (OGCT). BPES is a genetic disorder involving mild craniofacial abnormalities often associated with premature ovarian failure. OGCTs are endocrine malignancies, accounting for 2–5% of ovarian cancers, the treatment of which is still challenging.

In this review we summarize recent data concerning FOXL2 transcriptional targets and molecular partners, its post-translational modifications, its mutations and its involvement in newly discovered pathophysiological processes. In the ovary, FOXL2 is involved in the regulation of cholesterol and steroid metabolism, apoptosis, reactive oxygen species detoxification and cell proliferation. Interestingly, one of the main roles of FOXL2 is also to preserve the identity of ovarian granulosa cells even at the adult stage and to prevent their transdifferentiation into Sertoli-like cells. All these recent advances indicate that FOXL2 is central to ovarian development and maintenance. The elucidation of the impact of FOXL2 germinal and somatic mutations will allow a better understanding of the pathogenesis of BPES and of OGCTs.

Foundation for Women’s Cancer Announces 2011-2012 Research Grant Awardees - Press Release - Digital Journal

Foundation for Women’s Cancer Announces 2011-2012 Research Grant Awardees - Press Release - Digital Journal

Florence and Marshall Schwid Ovarian Cancer Research Grant: Petar Jelinic, PhD, Sloan Kettering Institute for Cancer Research

Caring Together, NY Ovarian Cancer Research Grant: Jun-Min Lee, MD, National Cancer Institute

Amgen Ovarian Cancer Research Grant: Andras Ladanyi, MD, PhD, University of Chicago Hospitals

Ovarian Cancer National Alliance Ovarian Cancer Research Grant: Justin Bottsford-Miller, MD, University of Texas MD Anderson Cancer Center

St. Louis Ovarian Cancer Awareness Research Grant: Erin King, MD, University of Texas MD Anderson Cancer Center

Carol’s Cause Endometrial Cancer Research Grant: Michael Goodheart, MD, University of Iowa

Claudia Cohen Research Foundation Prize for Outstanding Gynecologic Cancer Researcher: George Coukos, MD, PhD, University of Pennsylvania

Foundation for Women’s Cancer Excellence in Ovarian Cancer Research Award: Ernst Lengyel, MD, PhD, University of Chicago

Carol’s Cause Award for Outstanding Paper by a Fellow: Nicole Fleming, MD, University of Texas MD Anderson Cancer Center

open access: Editorial: Molecular Scores to Predict Ovarian Cancer Outcomes: A Worthy Goal, but Not Ready for Prime Time

Molecular Scores to Predict Ovarian Cancer Outcomes: A Worthy Goal, but Not Ready for Prime Time

"... The premature application of inadequately validated biomarkers may adversely impact the successful implementation of individualized therapies."

open access: A DNA Repair Pathway–Focused Score for Prediction of Outcomes in Ovarian Cancer Treated With Platinum-Based Chemotherapy (serous)

A DNA Repair Pathway–Focused Score for Prediction of Outcomes in Ovarian Cancer Treated With Platinum-Based Chemotherapy

Patient Samples

We extracted clinical data for 511 patients with serous ovarian cystadenocarcinoma from The Cancer Genome Atlas (TCGA) database (44) website (http://tcga-data.nci.nih.gov) on February 17, 2011, representing the largest available dataset of epithelial ovarian cancer gene expression profiles (see Supplementary Table 2, available online, for further details on which ovarian cancer samples were included in this study). These were all the patients for whom full sets of tumor gene expression data were available for download..... 


Table 1

Clinicopathologic characteristics of ovarian cancer patients in The Cancer Genome Atlas (TCGA) dataset^*

Table 2

Genes in platinum-specific DNA repair pathways that were used to construct the score^*

(For each gene, “high” means higher than median gene expression was associated with improved overall survival in The Cancer Genome Atlas dataset, and “low” means higher than median gene expression was associated with worse overall survival  

                                  ^{~~~~~~~~~~~~~~}

CONTEXT AND CAVEATS

Prior knowledge

At present, there are no effective prognostic tools for prediction of response in ovarian cancer patients, a majority of whom are diagnosed with an advanced stage (stages III and IV) and undergo surgical debulking followed by and platinum-based chemotherapy.

Study design

Gene expression data was extracted from The Cancer Genome Atlas (TCGA) database for patients with advanced ovarian cancer, and a molecular score was developed by focusing exclusively on the genes involved in platinum-induced DNA damage repair pathways. Patients were divided into low (0–10) and high (11–20) scores, and the prognostic value of the score for overall survival, recurrence-free survival, and progression-free survival was assessed. Data were validated in two independent datasets.

Contribution

Patients with high scores showed statistically significant associations with improved overall survival compared with patients with low scores. The score was predictive of overall survival, recurrence-free survival, and progression-free survival in ovarian cancer patients who received first-line platinum-based chemotherapy.

Implication

This score has the potential to become an important prognostic tool to determine whether advanced-stage ovarian cancer patients will benefit from first-line platinum-based chemotherapy.

Limitation

The score has not been tested prospectively in a clinical trial.

Why we need a good screening test for ovarian cancer - CNN.com

Why we need a good screening test for ovarian cancer - CNN.com

Ovarian Cancer and Us blog: top 5 most read items this week

#1:  abstract: Low-Stage Ovarian Clear Cell Carcinoma: Population-Based Outcomes in British Columbia, Canada, With Evidence for a Survival Benefit As a Result of Irradiation

#2:  abstract: Cochrane Review: Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer

#3:  Stem Cell Network Blog: 35 reasons to like stem cells - images and art/voting open on FB "Cells I See"

#4:  Abstract: Adherence to Colorectal Cancer Screening: A Randomized Clinical Trial of Competing Strategies

#5:  The Medicare NewsGroup introduces new website for journalists

20 Great Challenges (of health and medicine): Votes are in! | TEDMED Blog

20 Great Challenges: Votes are in! | TEDMED Blog

20 Great Challenges: Votes are in!

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Posted on April 12, 2012 by Stacy Lu

 

Jay Walker just announced the results of voting on the 20 Great Challenges of health and medicine. The program, sponsored by the Robert Wood Johnson Foundation, looks at the most persistent and complex issues facing health and medicine today.

The Top 20 Great Challenges:

#22.  Inventing Wellness Programs

#34.  The Caregiver Crisis

#19.  The Role of the Patient

#2.    The Obesity Crisis

#1.    Achieving Medical Innovation

#8.    Managing Chronic Diseases

#18.  Medical Communication

#26.  Reducing Childhood Obesity

#3.    Making Prevention Popular

#9.    End-of-life Care

#51.  Causes of Sleep Deprivation

#15.  Impact of Poverty on Health

#12.  Faster Adoption of Best Practices

#32.  Impact of Stress

#4.    Future of Personalized Medicine

#33.  Promoting Active Lifestyles

#10.  Preparing for Dementia

#16.  Addressing Healthcare Costs

#39.  Whole-Patient Care

#23.  Eliminating Medical Errors

Throughout the year, the Great Challenges Program will generate a lively national dialog on the 20 Challenges chosen by the TEDMED community. The program will include TV-style interviews with leaders across fields, a series of webinars on each of the 20 Great Challenges, and the opportunity for TEDMED community members to add their voice.