Thursday, June 03, 2010
Comprehensive Analysis of Missense Variations in the BRCT Domain of BRCA 1 by Structural and Functional Assays
Comprehensive Analysis of Missense Variations in the BRCT Domain of BRCA1 by Structural and Functional Assays.
Lee MS, Green R, Marsillac SM, Coquelle N, Williams RS, Yeung T, Foo D, Hau DD, Hui B, Monteiro AN, Glover JN.
Authors' Affiliations: Department of Biochemistry, School of Systems Molecular Medicine, University of Alberta, Edmonton, Alberta, Canada; National Institute of Environmental Health Sciences, Durham, North Carolina; Risk Assessment, Detection, and Intervention Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida; and Molecular Biology Program, Institute of Biophysics Carlos Chagas Fo., Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Abstract
Genetic screening of the breast and ovarian cancer susceptibility gene BRCA1 has uncovered a large number of variants of uncertain clinical significance. Here, we use biochemical and cell-based transcriptional assays to assess the structural and functional defects associated with a large set of 117 distinct BRCA1 missense variants within the essential BRCT domain of the BRCA1 protein that have been documented in individuals with a family history of breast or ovarian cancer....... Through a correlation of the assay results with available family history and clinical data, we define limits to predict the disease risk associated with each variant. Forty-two of the variants show little effect on function and are likely to represent variants with little or no clinical significance; 50 display a clear functional effect and are likely to represent pathogenic variants; and the remaining 25 variants display intermediate activities. The excellent agreement between the structure/function effects of these mutations and available clinical data supports the notion that functional and structure information can be useful in the development of models to assess cancer risk.
2nd media article: HE4: Abbott gets FDA approval for ovarian cancer test - Chicago Breaking Business
"Abbott partnered with Fujirebio Diagnostics Inc. to develop the test. It also is approved for use in Europe, and other countries in the Asia Pacific and Latin American regions."
support group meetings - feel free to share - OCATS June 7th
OCATS Ovarian Cancer Awareness & Treatment in Saskatchewan ------------------------------------------------------------------------------------- GYNECOLOGIC CANCER SURVIVORS & SUPPORT PEOPLE WELCOME MONDAY, June 7th 4:00 p.m. to 6:00 p.m. Knox Met United Church 2340 Victoria Avenue (Pls Use Vic Ave Entrance, Ring Buzzer for Room 105) Light Supper, $4 Donation This month our peer support gathering will have our regular check in, and then a facilitated discussion about the challenges and coping strategies for socializing and traveling after diagnosis, while having treatment, during recovery. We don’t have the answers exactly but we’ll share some of the experiences we’ve had for air travel, car travel, hotels, family holidays, special events and share how people have coped and what things they found were useful and helpful or things to avoid. Please come share in the discussion, meet other cancer survivors. It’s good to get out once in awhile and share with others, learn from others. It’s even okay to be grumpy about it! If that’s where you’re at. Please call Darlene at 775-1848 or email and let us know if you plan to attend. This helps Joan prepare those lovely meals she making for us! Thank you, Darlene Gray OCATS Ovarian Cancer Awareness & Treatment in Saskatchewan A SUPPORT & ACTION GROUP FOR ANYONE AFFECTED BY GYNECOLOGIC CANCERS RPO Box 35067, Regina, SK S4X 4C6 Ph 306-775-1848, Fx 306-775-1853 Find us on Facebook too! http://www.ocats.ca
Study Testing Methylphenidate for Cancer-Related Fatigue Indicate That It Is Certainly Not a Panacea but May Be Effective for Some Groups of Patients
VIDEO ALERT: Additional audio and video resources, including excerpts from an interview with Dr. Deb Barton is available on the http://newsblog.mayoclinic.org/2010/06/02/mayo-clinic-study-shows-drug-may-be-effective-in-treating-cancer-related-fatigue-in-some-patients/ Mayo Clinic News Blog.
The BRCA1 c.5434C→G (p.Pro1812Ala) variant induces a deleterious exon 23 skipping by affecting exonic splicing regulatory elements -- Gaildrat et al. 47 (6): 398 -- Journal of Medical Genetics
Blogger's Note: in plain english - many patients who have undergone genetic testing show test results of 'unknown variants' or variants of unknown clinical significance but negative for known mutations ie; BRCA 1/2; MSH2/6; MLH1; PMS2.
Some of these unclassified variants may or may not be related to cancer. With recent research, databases are now showing UV (unclassified variants) as true mutations.
This article is one of many which shows the work being done to explain and find the significance of these variants. Many patients undergoing genetic testing will test negative for the commonly known mutations, but this is not the'end of the story', so to speak.
Conclusion These data, together with segregation data, argue for the classification of BRCA1 c.5434C→G as a pathogenic splicing mutation. These results also suggest that UVs (unclassified variants)in highly conserved nucleotide sequences of short exons may be good candidates for detecting functionally relevant splicing regulatory elements.
New blood thinners can cause dangerous drug interactions, study finds
""A high proportion of adults in the United States consume at least one of the drugs known to have some level of interaction with one of the new oral anticoagulants," the Loyola researchers write."
Stem cell researchers uncover previously unknown patterns in DNA methylation
"The findings could have implications in fighting cancer because DNA methylation patterns go awry in cancer, often causing tumor suppressor genes to switch off. The more scientists know about the cellular mechanisms that lay down the correct DNA methylation patterns, the more that process can be manipulated. In the future, this type of research may lead to techniques that result in the ability to control the patterns that go awry and lead to cancer, thus preventing a malignancy"
Wednesday, June 02, 2010
Chronix Biomedical to Launch Cancer Detection and Monitoring Service at ASCO to Advance Clinical Research Using Its Apoptotic DNA Blood Test | Business Wire
Note: in research "Chronix Biomedical to Launch Cancer Detection and Monitoring Service at ASCO to Advance Clinical Research Using Its Apoptotic DNA Blood Test —ASCO Data Show Chronix’s Apoptotic DNA Blood Test Detects Early-Stage Cancer with Excellent Sensitivity and Specificity— —“For Investigational Use Only” Clinical Trial Service Is Designed to Provide Early Data on Patient Response and Disease Progression"
Functional Proteomic Analysis of Advanced Serous Ovarian Cancer Using Reverse Phase Protein Array: TGF-β Pathway Signaling Indicates Response to Primary chemotherapy
Abstract Purpose: Using reverse phase protein array, we measured protein expression associated with response to primary chemotherapy in patients with advanced-stage, high-grade serous ovarian cancer. Conclusion: TGF-β pathway signaling likely plays an important role as a marker or mediator of chemoresistance in advanced serous ovarian cancer. On this basis, future studies to develop and validate a useful predictor of treatment failure are warranted.
A genomic and transcriptomic approach for a differential diagnosis between primary and secondary ovarian carcinomas in patients with a previous histor
CONCLUSIONS: In patients with ovarian carcinoma and a previous history of breast cancer, SNP array analysis can be used to distinguish primary and secondary ovarian tumors.
Diagnosis of Ovarian Carcinoma Cell Type is Highly Reproducible: A Transcanadian Study
Abstract:
Reproducible diagnosis of ovarian carcinoma cell types is critical for cell type-specific treatment. The purpose of this study was to test the reproducibility of cell type diagnosis across Canada. Analysis of the interobserver reproducibility of histologic tumor type was performed among 6 pathologists after brief training in the use of modified World Health Organization criteria to classify ovarian carcinomas into 1 of 6 categories: high-grade serous, endometrioid, clear cell, mucinous, low-grade serous, and other. These 6 pathologists independently reviewed a test set of 40 ovarian carcinomas. A validation set of 88 consecutive ovarian carcinomas drawn from 5 centers was subject to local review by 1 of the 6 study pathologists, and central review by a single observer. Interobserver agreement was assessed through calculation of concordance and kappa values for pair-wise comparison. For the test set, the paired concordance between pathologists in cell type diagnosis ranged from 85.0% to 97.5% (average 92.3%), and the kappa values were 0.80 to 0.97 (average 0.89). Inclusion of immunostaining results did not significantly improve reproducibility (P=0.69). For the validation set, the concordance between original diagnosis and local review was 84% and between local review and central review was 94%. The kappa values were 0.73 and 0.89, respectively. With a brief training exercise and the use of defined criteria for ovarian carcinoma subtyping, there is excellent interobserver reproducibility in diagnosis of cell type. This has implications for clinical trials of subtype-specific ovarian carcinoma treatments.
Abstract/full free access: Legislation for trial registration and data transparency
"Public confidence in clinical trials has been eroded by data suppression, misrepresentation and manipulation. Although various attempts have been made to achieve universal trial registration- e.g., Declaration of Helsinki, WHO clinical Trial Registry Platform (WHO ICTRP), the International Committee of Medical Journal Editors requirement- they have not succeeded, probably because they lack the enough power of enforcement. Legislation appears to be the most efficient and effective means to ensure that all researchers register their trials and disseminate their data accurately and in a timely manner. We propose that a global network be established. This could be accomplished in two steps. The first step is to legislate about trial registration and data transparency, such as USA's FDAAA Act 2007; and the second step to establish a global network to ensure uniform, international consistency in policy and enforcement of trial registration and data transparency."
focus on: Cancer Neuropathic Pain: Overview of Current Status and Future Objectives -- The Oncologist
ARTICLES
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Cancer Neuropathic Pain: Overview of Current Status and Future Objectives
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Frederick H. Hausheer, Kathleen M. Foley
The Oncologist 2010; 15(Supplement 2): 1-2; doi:10.1634/theoncologist.2009-S506[Full Text] [PDF]
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Mark J. Lema, Kathleen M. Foley, Frederick H. Hausheer
The Oncologist 2010; 15(Supplement 2): 3-8; doi:10.1634/theoncologist.2009-S505[Abstract] [Full Text] [PDF] SUMMARY: This article briefly surveys the types and causes of neuropathic pain and then discusses what is known about the epidemiology of cancer-related neuropathic pain.
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Gary J. Bennett
The Oncologist 2010; 15(Supplement 2): 9-12; doi:10.1634/theoncologist.2009-S503[Abstract] [Full Text] [PDF] SUMMARY: The article reviews some of the work that has been done to study the peripheral causes of neuropathic pain as it relates to cancer.
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Charles S. Cleeland, John T. Farrar, Frederick H. Hausheer
The Oncologist 2010; 15(Supplement 2): 13-18; doi:10.1634/theoncologist.2009-S501[Abstract] [Full Text] [PDF] SUMMARY: This article briefly outlines the currently accepted measures of neuropathy and neuropathic pain, discusses their commonalities and limitations, and offers thoughts on improvements to current assessment strategies.
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Barrie R. Cassileth, Francis J. Keefe
The Oncologist 2010; 15(Supplement 2): 19-23; doi:10.1634/theoncologist.2009-S504[Abstract] [Full Text] [PDF] SUMMARY: This article briefly describes research illustrating the promise of important integrative oncology therapies for the treatment of cancer-related neuropathic pain, including massage therapy, acupuncture, and psychological/behavioral interventions.
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Miroslav Backonja, Clifford J. Woolf
The Oncologist 2010; 15(Supplement 2): 24-29; doi:10.1634/theoncologist.2009-S502[Abstract] [Full Text] [PDF] SUMMARY: This article briefly reviews emerging treatments for neuropathic pain and discusses specific opportunities to alter the drug discovery paradigm, stressing the need for an approach that emphasizes the unbiased evaluation of the particular neurobiological mechanisms contributing to neuropathic pain in individual patients.
Tuesday, June 01, 2010
Welcome to Cancereducation.com
"The landscape of oncolgy continues to evolve as the results from studies are evaluated. All of us at http://www.cancereducation.com are pleased to provide coverage of these critical issues in oncology through our attendance at the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, IL, from June 4–8.
With over 30,000 oncology professionals gathering to discuss the latest innovations in research, quality of life issues, practice, and technology in the oncology community, our staff will attend several of the education and scientific sessions at ASCO.
Their daily updates will be posted on our blog* which can be accessed by clicking on the link at the top of the http://www.cancereducation.com home page."
Marshall Edwards Announces Final Results From Halted Phase 3 Clinical Trial of Phenoxodiol - MarketWatch
Note: these results have been awaited since late last year as per past blogged postings (pending compilation of data)
press release
June 1, 2010, 8:31 a.m. EDT · Recommend · Post:
Marshall Edwards Announces Final Results From Halted Phase 3 Clinical Trial of Phenoxodiol
SYDNEY, AUSTRALIA and SAN DIEGO, CA, Jun 01, 2010 (MARKETWIRE via COMTEX) -- Marshall Edwards, Inc., an oncology company focused on the clinical development of novel anti-cancer therapeutics, announced today that a final analysis of its Phase 3 OVATURE trial of orally administered phenoxodiol in women with recurrent ovarian cancer determined that the trial did not show a statistically significant improvement in its primary (progression-free survival) or secondary (overall survival) endpoints. As previously announced, the trial was closed for recruitment before completion of enrolment with only 142 out of a planned 340 patients enrolled.
This multi-center, randomized, double-blind trial assessed the safety and efficacy of daily phenoxodiol in combination with weekly carboplatin versus weekly carboplatin with placebo in patients with platinum-resistant or platinum-refractory, late-stage epithelial ovarian, fallopian or primary peritoneal cancer following at least second line platinum therapy.
"Owing to the fact that this trial was significantly underpowered due to the small number of patients enrolled, we were disappointed, but not entirely surprised by the final outcome," said Dr. Daniel P. Gold, newly appointed Chief Executive Officer of Marshall Edwards. "However, we remain confident that our investigational isoflavone platform, including triphendiol, a potentially more potent, second-generation analogue of phenoxodiol, may be of benefit to women with ovarian cancer, particularly when administered intravenously.
"Previously reported results of a Phase 2 trial," continued Dr. Gold, "which tested the activity of intravenous phenoxodiol plus weekly cisplatin in a similar platinum-resistant or refractory patient population, demonstrated a 30% response rate (6 out of 20) compared to less than 1% (1 out of 142) in the OVATURE study in which phenoxodiol was administered orally. In addition, we remain excited with the progress of another product candidate in our pipeline, NV-128, a novel isoflavone analogue with a mode of action distinct from both phenoxodiol and triphendiol.
"Lastly, I want to take this opportunity to personally thank the patients and their families for their participation in this trial. I would also like to thank the clinical investigators and trial coordinators for their dedication and support."
Safety Outcomes
As previously noted, phenoxodiol had a good safety profile and was well tolerated. The number of patients experiencing at least one adverse event was similar in each treatment group, as was the number of patients experiencing adverse events of Grade 3 or higher.
About OVATURE and the Phenoxodiol Clinical Program
The OVATURE ("OVArian TUmor REsponse") trial was a multi-center international Phase 3 clinical trial of orally administered investigational drug phenoxodiol in combination with carboplatin in women with advanced ovarian cancer resistant or refractory to platinum-based drugs to determine its safety and effectiveness when used in combination with carboplatin.
The trial recruited ovarian cancer patients whose cancer initially responded to chemotherapy, but had since become resistant or refractory to traditional platinum treatments. The study was closed to enrolment in April 2009 at which time 142 patients had been randomized to the study. Changes in standards of care over the period of the trial and the stringency of inclusion/exclusion criteria of the OVATURE protocol had slowed patient recruitment rates and consequently the Company deemed it prudent not to continue the trial to completion. The Independent Data Monitoring Committee (IDMC) supported the Company's decision to close the study to accrual, and, in a review of the available safety data, the IDMC confirmed that there were no safety concerns with phenoxodiol in these subjects.
About Phenoxodiol
Phenoxodiol is being developed as a chemosensitizing agent in combination with platinum drugs for late stage, chemoresistant ovarian cancer and as a monotherapy for prostate and cervical cancers. It is believed to have a unique mechanism of action, binding to cancer cells via a cell membrane oxidase, causing major downstream disturbances in expression of proteins necessary for cancer cell survival and responsible for the development of drug resistance.
Phenoxodiol appears to selectively inhibit the regulator known as S-1-P (sphingosine-1-phosphate) that is overexpressed in cancer cells. In response to phenoxodiol, S-1-P content is decreased, with a consequent decrease in expression of the pro-survival proteins XIAP and FLIP, inducing cell death via caspase expression and promoting sensitivity to other chemotherapeutics. In laboratory studies, it has been demonstrated that drug-resistant ovarian cancer cells pre-treated with phenoxodiol were killed with lower doses of chemotherapy drugs. Importantly, phenoxodiol has been shown not to adversely affect normal cells in animal and laboratory testing.
Phenoxodiol has been granted Fast Track status from the FDA to facilitate its development as a therapy for recurrent ovarian and prostate cancers. Fast Track designation is designed to facilitate the review of products that address serious or potentially life-threatening conditions for which there is an unmet medical need and provides the option to file a New Drug Application on a rolling basis. This permits the FDA to review the filing as it is received, expediting the review process. Phenoxodiol is an investigational drug and, as such, is not commercially available. Under U.S. law, a new drug cannot be marketed until it has been investigated in clinical trials and approved by FDA as being safe and effective for the intended use.
Memorandum to Shareholders From Dr. Amnon Gonenne, MabCure's Chief Executive Officer - MarketWatch
June 1, 2010, 8:00 a.m. EDT · Recommend · Post:
Memorandum to Shareholders From Dr. Amnon Gonenne, MabCure's Chief Executive Officer
HASSELT, Belgium, Jun 01, 2010 (BUSINESS WIRE) -- MabCure, Inc. /quotes/comstock/11k!mbci (MBCI 0.32, -0.01, -3.03%) :
Dear Shareholders:
I am pleased to update you on the progress of our research and development.
Over the past several months we have been working intensively on advancing our various programs with an emphasis on melanoma and ovarian cancer diagnostics. We consider these two projects near-term in their respective development stages, as I describe below.
In January 2010, we announced the commencement of our clinical trials at the Ramathibodi Hospital in Bangkok, Thailand to evaluate the potential of our panel of monoclonal antibodies (MAbs) to diagnose ovarian cancer in high risk patients. Since the study began, patients have been recruited at a solid pace and in line with our schedule. In addition, we are privileged that the Thai National Cancer Institute has decided to join our study and is currently reviewing our study protocol. The study is estimated to be completed within 5-6 months, as originally planned.
In parallel to our study in Thailand, we are planning to commence a study in collaboration with a major medical center in Belgium of several hundred blood samples which were obtained from patients over the past several years. The purpose of this "retrospective" study is to provide additional proof of the ability of our MAbs to correctly diagnose ovarian cancer, and is of considerable importance given the significant number of blood samples to be tested.
The study will be "blind" to all involved (i.e. the samples will be coded and neither the clinicians nor MabCure scientists will know the identity of the specimens until the study is complete), so as to prevent any bias in the analysis of the results. The study is expected to last several weeks and will commence once a formal agreement has been signed with the Belgian medical center. As a prelude to this study, we conducted a pilot study on a limited number of these "retrospective" specimens to calibrate the optimal technical conditions for our MAbs.
Activism among exceptional patients with cancer. [Support Care Cancer. 2010] - PubMed result
Abstract
BACKGROUND: The "exceptional patients" with cancer are survivors who had advanced cancer considered incurable by medical report and who subsequently became disease-free or experienced unexplained survival time given the nature of their disease or treatment. This experience is a puzzling phenomenon that has not been formally investigated in a cancer population. The purpose of this study was to understand exceptional patients' accounts of their experience.
MATERIALS AND METHODS: This study used a narrative approach with a cross-case thematic analysis. Recruitment took place at health care centers in the USA and Israel. Oncologists in both centers were asked to identify patients who had an exceptional disease course. Patients were then contacted and interviewed; an audio recording was made of each narrative account and then transcribed. Interviews and thematic analyses were conducted independently at each site. These thematic findings from each site were discussed with both research teams and a common underlying theme was identified, which is the focus of this report.
RESULTS: Twenty-six participants were interviewed: 14 from the USA and 12 from Israel. All the participants have had advanced disease with a range of diagnoses that included breast, colorectal, pancreatic, ovarian cancer, glioblastoma multiforme, and others. The main recurrent theme from both the US and Israeli sites was personal activism. This was manifested in taking charge and getting involved in the process of diagnosis and treatment, as well as becoming more altruistic in their relationships with others. In many cases, this was reflected in a change in a philosophy about life
CONCLUSIONS: In this study, we found that activism was a major theme that was independently observed in both Israel and the USA. This has implications for health care providers to facilitate patient engagement in the care and treatment of their disease. Further research on this phenomenon is needed.
Medical News: Hand Hygiene in Hospitals Not Up to Par - in Infectious Disease, Infection Control from MedPage Today
Each year, an estimated 2.5 million patients in the U.S. develop healthcare-associated infections that result in 90,000 deaths and cost the healthcare system an estimated $4.5 to $5.7 billion dollars
Anti-MUC1 Antibodies and Ovarian Cancer Risk: Prospective Data from the Nurses' Health Studies — Cancer Epidemiology, Biomarkers & Prevention
Note: MUC1 has been/is being studied in numerous cancers
Conclusion: Anti-MUC1 (glycoprotein) antibodies evaluated several years before diagnosis may be associated with lower risk of subsequent ovarian cancer in women <64 years old at assessment.
May 20th, 2010 SGO statement - (U.S.) statement - House Defense Appropriations Subcomittee
Note: clicking above uploads directly the pdf file version
Statement of Daniel L. Clarke-Pearson, M.D. President - Society of Gynecologic Oncologists Professor and Chair, Obstetrics and Gynecology University of North Carolina Medical School Chapel Hill, North Carolina On Behalf of The Society of Gynecologic Oncologists Before The House Defense Appropriations Subcommittee
Thursday, May 20, 2010 at 10:00 am
SGO E-Learning Center
SGO's 41st Annual Meeting on Women's Cancer Webcast Available Now!
FREE Introduction to Presidential Address, Cornelius Granai, MD
FREE Presidential Address, David Mutch, MD
FREE ACS Lectureship, Paul Goodfellow, PhD
Monday, May 31, 2010
Survivorship in Lynch Syndrome Families - Full Text View - Clinical Trial
Further study details as provided by M.D. Anderson
Cancer Center:
Primary Outcome Measures: Compare Predictors of Health-Related Quality of Life (QOL) among Colorectal Cancer (CRC) Survivors who have Lynch Syndrome (LS) with patients who have Sporadic CRC [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
Simulation in Surgery: Perfecting the Practice
abstract
The apprenticeship model that surgical training has traditionally relied on has proven to be an expensive, time-consuming, and inconsistent model for producing skilled surgeons. Combined with increased public scrutiny on patient safety, financial concerns, restricted work hours, and expanding skill requirements, it has become clear that a new pedagogic paradigm is required. This article reviews the evidence supporting the need and justification of simulation in surgical education and explores the existing and potential roles of simulation in the training and evaluation of future surgeons.
LISTSERV Choice Awards: vote for your favourite listserv (ACOR/Ovarian Cancer results to date)
Should Cause of Death From the Death Certificate Be Used to Examine Cancer-Specific Survival? A Study of Patients With Distant Stage Disease; Cancer Investigation
ABSTRACT
Death certificates are used to classify cause of death for studies of cancer survival and mortality. Using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program, we evaluated cause of death (site-specific, cancer cause-specific, or other cause of death) for 229,181 patients with distant stage disease during 1994–2003 who died by 2005. Agreement between coded cause of death and initial diagnosis was 85% in patients with only one primary and 64% in patients with more than one primary. Our findings support the usefulness of site and cancer cause-specific causes of death reported on the death certificate for distant stage patients with a single cancer.
abstract/free full pdf access:P redictive and Prognostic Protein Biomarkers in Epithelial Ovarian Cancer: Recommendation for Future Studies Cancers
"Abstract: Epithelial ovarian cancer is the most lethal gynecological malignancy. Due to its lack of symptoms, this disease is diagnosed at an advanced stage when the cancer has already spread to secondary sites. While initial rates of response to first treatment is >80%, the overall survival rate of patients is extremely low, mainly due to development of drug resistance. To date, there are no reliable clinical factors that can properly stratify patients for suitable chemotherapy strategies. Clinical parameters such as disease stage, tumor grade and residual disease, although helpful in the management of patients after their initial surgery to establish the first line of treatment, are not efficient enough. Accordingly, reliable markers that are independent and complementary to clinical parameters are needed for a better management of these patients. For several years, efforts to identify prognostic factors have focused on molecular markers, with a large number having been investigated. This review aims to present a summary of the recent advances in the identification of molecular biomarkers in ovarian cancer patient tissues, as well as an overview of the need and importance of molecular markers for personalized medicine in ovarian cancer."
..........
"High grade serous tumors show particular differences in terms of their development, genetic alterations and prognosis. This has led to the classification of ovarian cancer into two types: type 1 tumors, which are low grade and slowly developing (endometrioid, mucinous and low grade serous tumors), and type 2 tumors, which rapidly progress (high grade serous). In addition, the association of biomarker expression with survival varies substantially between subtypes, and can easily be overlooked in whole cohort analyses. Although these data suggest substantial differences between subtypes, until recently ovarian carcinomas were typically approached as a monolithic entity by researchers and clinicians. This practice impeded progress in understanding the biology or improving the management of the less common ovarian carcinoma subtypes. To avoid this effect, each subtype within a cohort should be analyzed individually. Therefore, molecular classifiers of ovarian cancer are of high clinical relevance in the management of these cancer patients...." cont'd
Fertility Success: Researchers Determine How Chemo Affects Female Fertility
"Chemotherapy induces menopause in some hormone-dependent cancers. It has a beneficial effect because it's withdrawing the stimulants for the cancer cells. Menopause is contributing to the cure," said Astsaturov. "It's still debated whether we should preserve menstrual function at all costs."
Emerging drugs for ovarian cancer
"Strategies currently being exploited in clinical trials include attempts to deliver more killing selectively to tumours (e.g., intraperitoneal administration of cisplatin or radiolabelled monoclonal antibodies), agents designed to target drug resistance mechanisms (e.g., TLK-286 activated by glutathione transferase), agents targeting proteins/receptors shown to be selectively expressed in the disease (e.g., monoclonal antibodies recognising CA-125 or HER1; small molecules targeting HER1 such as gefitinib) and disrupting established tumour vasculature (e.g., 5,6-dimethyl xanthenone 4-acetic acid). At the pre-clinical level, agents being developed to target the phosphatidylinositol 3 kinase/AKT/mTOR pathway, and K-Ras inhibitors, may offer efficacy in the future."
Saturday, May 29, 2010
Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts
BACKGROUND:
Genetic screening of breast cancer patients and their families have identified a number of variants of unknown clinical significance in the breast cancer susceptibility genes, BRCA1 and BRCA2.
CONCLUSIONS:
These results illustrate the need for improved methods for predicting functional ESEs and the potential consequences of sequence variants contained therein.
Patient navigation in breast cancer: a systematic review
Note: the abstract does not provide a definition of 'patient navigator'
IMPLICATIONS FOR PRACTICE: Data describing the role of patient navigation in breast cancer will assist in better defining future direction for the breast navigation role. Ongoing research will better inform issues related to role definition, integration into clinical breast cancer care, impact on quality of life, cost-effectiveness, and sustainability.
Thursday, May 27, 2010
abstract/full free access; pilot study assessing social support among cancer patients enrolled
Conclusions: Younger subjects reported worse symptoms, a smaller social support network, and fewer close friends and relatives than older subjects. Having someone to discuss decisions and seeing friends or relatives often was associated with longer survival.
Peri- and post-menopausal incidental adnexal masses and the risk of sporadic ovarian malignancy: new insights and clinical management.
Abstract
Adnexal masses are common among peri- and post-menopausal women. Although ovarian cancer is a significant cause of mortality in menopausal women, large population-based studies demonstrate that the majority of adnexal masses are benign. Despite this, the appearance of an adnexal mass is a concern for the patient and an insight exercise for physicians. In most cases, an adnexal enlargement is an incidental finding, generally corresponding to a benign cyst and easily diagnosed by conventional ultrasound. Exceptionally an ovarian tumour may be malignant and should be treated as early as possible. When conventional ultrasound renders complex morphology other diagnostic tools must be used such as: colour Doppler and functional tumour vessel properties, serum CA 125 levels, nuclear magnetic resonance imaging and in some cases laparoscopy. Several new tumour markers are being studied for clinical application, although there are presently no clear recommendations. Adnexal masses with benign morphological and functional properties must be periodically monitored as an alternative to surgery since malignant transformation is exceptional.
Abstract / full free text: Expression signatures of TP53 mutations in serous ovarian cancers
Conclusions This represents the first attempt to define a genomic signature of TP53 mutation in ovarian cancer. Patterns of gene expression characteristic of TP53 mutation could be discerned and included several genes that are known p53 targets or have been described in the context of expression signatures of TP53 mutation in breast cancer.
DiaTech Oncology MiCK Chemotherapy Induced Apoptosis Assay Shows Increased Response and Survival in... -- NASHVILLE, Tenn., May 26 /PRNewswire/ --
Findings Published at the ASCO Conference Provide a New Treatment Strategy for Patients and Support Favorable Reimbursement Coverage Policies
NASHVILLE, Tenn., May 26 /PRNewswire/ -- DiaTech Oncology announced today that the American Society of Cancer Oncology (ASCO) has published the results of a comprehensive study to determine the effectiveness of the Microculture Kinetic (MiCK) assay for apoptosis in predicting increased response and survival rates for ovarian cancer patients. In the MiCK assay, the tumor cells of an individual patient are exposed to multiple doses of several chemotherapeutic drugs either as single drugs or in combinations. A sophisticated algorithm is used to monitor and compute the amounts of apoptosis caused by each of the drugs to establish a drug sensitivity profile of the patient's tumor cells. Knowledge of a patient's drug sensitivity profile allows the treating oncologists to prescribe chemotherapy that would be the most effective against the tumor cells of that patient.
The results showed overall survival significantly better in 92% of patients who received the best chemotherapy as predicted by the MiCK assay compared to only 76% of patients who received treatment not recommended by the assay. There was also a significantly higher overall response rate (82% vs. 54%) for patients who received a treatment the assay showed would be preferred. Ovarian cancer patients in stage 3 or 4 and treated with a highly active assay score had significantly increased survival rates (94% vs. 77% alive at 24 months). The clinical benefit rate was 85% for patients with chemotherapy that was highly active in the assay, compared to only 57% for those patients receiving less active chemotherapy.....
Wednesday, May 26, 2010
Health Canada Approves Trabectedin for Relapsed Ovarian Cancer (Trabectedin//Yondelis)
May 26, 2010 — Health Canada has approved trabectedin (Yondelis; PharmaMar SA [Zeltia SA], marketed by Centocor Ortho Biotech Products, LP) in combination with pegylated liposomal doxorubicin (PLD) for the treatment of relapsed platinum-sensitive ovarian cancer.
The treatment is indicated for patients who have failed (blogger comment - ho hum!) first-line platinum-based chemotherapy regimen, including adjuvant therapy, and who are not expected to benefit from, are ineligible for, or are unwilling to undergo additional platinum-based chemotherapy.
Approval was based on radiologic data from a multinational phase 3 clinical study (n = 672) showing that administration of trabectedin (1.1 mg/m2) plus doxorubicin (30 mg/m2) in 3-week cycles significantly increased progression-free survival by 21% compared with PLD alone (50 mg/m2) given every 4 weeks (7.3 months vs 5.8 months; hazard ratio [HR], 0.79; P = .019).
These findings were confirmed by an independent radiologic assessment that considered clinical as well as radiologic imaging data in assessing tumor progression (HR, 0.72; P = .0008). These study results were presented at the 2008 European Society for Medical Oncology Congress, and reported by Medscape Oncology during the conference.
In July 2009, the FDA declined approval of trabectedin for ovarian cancer, citing the potential for variations in radiologic data assessment and questioning whether the 6-week increase in progression-free survival offset an increased risk for toxicity, as previously reported by Medscape Oncology.
Trabectedin previously was approved in the European Union for the treatment of platinum-sensitive ovarian cancer and soft tissue sarcoma.
abstract: How to follow-up patients with epithelial ovarian cancer.
Abstract
PURPOSE OF REVIEW: Despite optimal primary treatment most patients with advanced epithelial ovarian cancer will relapse. This review discusses the controversy regarding surveillance and the timing of treatment for recurrent disease.
RECENT FINDINGS: Routine physical examination has a limited role in the detection of recurrent ovarian cancer. PET/computed tomography (CT) has been shown to be useful in detecting small volume disease not apparent on traditional imaging in patients with suspected recurrence based on symptoms and/or rising CA125. The results of PET/CT can alter treatment plans and have particular use in guiding site-directed therapy. The benefits of early detection and systemic treatment of recurrence are now in doubt following the presentation of the MRC/EORTC CA125 surveillance trial. The impact on survival of secondary cytoreductive surgery requires more investigation.
SUMMARY: Uncertainties remain in the surveillance and timing of treatment for relapsed disease. Patients should be informed of these uncertainties and become involved in decisions regarding their follow-up.
Tuesday, May 25, 2010
Chemoresponse Assay Could Lower Treatment Costs in Ovarian Cancer - ChemoFx
"...In the study, the authors assumed, for the sake of analysis, that the "outcomes are likely no worse when chemoresponse testing is performed than when an empiric choice of regimen is made."
However, if, in currently ongoing studies, the assay helps clinicians choose more effective therapies and thus improve survival, it would be "very attractive from a health economics perspective," say the authors, because the current study has already shown it to be cost effective."
The study was funded by Precision Therapeutics.
Karen Mason: Ovarian Cancer represented on Capitol Hill, Washington DC | Ovarian Cancer National Alliance
"Current treatments are brutal and consist of long “debulking” surgeries followed by months of chemotherapies..... During my nine years of survivorship, I have befriended many women who also had late-stage ovarian cancer. One by one, I have watched most of these women die...."
A genomic and transcriptomic approach for a differential diagnosis between primary and secondary ovarian carcinomas in patients with a previous history of breast cancer.
ABSTRACT:
BACKGROUND: The distinction between primary and secondary ovarian tumors may be challenging for pathologists. The purpose of the present work was to develop genomic and transcriptomic tools to further refine the pathological diagnosis of ovarian tumor after a previous history of breast cancer.
METHODS: Sixteen paired breast-ovary tumors from patients with a former diagnosis of breast cancer were collected.. ... A hierarchical clustering of these samples was performed, combined with a dataset of well-identified primary and secondary ovarian tumors.
RESULTS: In 12 of the 16 paired tumors analyzed, the comparison of genomic profiles confirmed the pathological diagnosis of primary ovarian tumor (n = 5) or metastasis of breast cancer (n = 7). Among four cases with uncertain pathological diagnosis, genomic profiles were clearly distinct between the ovarian and breast tumors in two pairs, thus indicating primary ovarian carcinomas, and showed common patterns in the two others, indicating metastases from breast cancer.
CONCLUSIONS: In patients with ovarian carcinoma and a previous history of breast cancer, SNP array analysis can be used to distinguish primary and secondary ovarian tumors. Transcriptomic analysis may be used when primary breast tissue specimen is not available.
Genetic/Familial high-risk assessment: breast and ... [J Natl Compr Canc Netw. 2010] - PubMed result
Abstract
Overview
All cancers develop as a result of mutations in certain genes, such as those involved in the regulation of cell growth and/or DNA repair,(1,2) but not all of these mutations are inherited from a parent. For example, sporadic mutations can occur in somatic/tumor cells only, and de novo mutations can occur for the first time in a germ cell (i.e., egg or sperm) or in the fertilized egg itself during early embryogenesis. However, family studies have long documented an increased risk for several forms of cancer among first-degree (i.e., parents, siblings, and children) and second-degree relatives (i.e., grandparents, aunts or uncles, grandchildren, and nieces or nephews) of affected individuals. These individuals may have an increased susceptibility to cancer as the result of 1 or more gene mutations present in parental germline cells; cancers developing in these individuals may be classified as hereditary or familial cancers. Hereditary cancers are often characterized by mutations associated with a high probability of cancer development (i.e., a high penetrance genotype), vertical transmission through either mother or father, and an association with other types of tumors.(3,4) They often have an early age of onset and exhibit an autosomal dominant inheritance pattern (i.e., occur when the individual has a mutation in only 1 copy of a gene). Familial cancers share only some features of hereditary cancers. For example, although familial breast cancers occur in a given family more frequently than in the general population, they generally do not exhibit the inheritance patterns or onset age consistent.
Vismodegib, a small-molecule inhibitor of the hedgehog pathway for the treatment of advanced cancers
"Vismodegib is currently undergoing phase II clinical trials for the treatment of advanced BCC, metastatic colorectal cancer, ovarian cancer, MB and other solid tumors. Because of its low toxicity and specificity for the Hh (hedgehog) pathway, this drug has potential advantages compared with conventional chemotherapy, and may also be used in combination treatments. Clinical trials with other Hh inhibitors are also ongoing and their therapeutic potential will need to be compared with vismodegib."
Attitudes Toward Information About Genetic Risk for Cognitive Impairment After Cancer Chemotherapy: Breast Cancer Survivors Compared With Healthy Controls
Conclusion
Results suggest lessened enthusiasm for genetic information that maintains or increases uncertainty about a specific course of action and highlight the importance of including clinically relevant groups in treatment decision-making research that employs hypothetical scenarios. Although women generally believe it is important to receive genetic information, they might benefit from assistance (eg, decision aid) in the difficult task of integrating information about survival and risk for adverse late effects from cancer treatment.
Pegylated Liposomal Doxorubicin and Carboplatin Compared With Paclitaxel and Carboplatin for Patients With Platinum-Sensitive Ovarian Cancer in Late Relapse
Pegylated Liposomal Doxorubicin and Carboplatin Compared With Paclitaxel and Carboplatin for Patients With Platinum-Sensitive Ovarian Cancer in Late Relapse
ABSTRACT
Purpose This randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of the combination of pegylated liposomal doxorubicin (PLD) with carboplatin (CD) compared with standard carboplatin and paclitaxel (CP) in patients with platinum-sensitive relapsed/recurrent ovarian cancer (ROC).
Patients and Methods Patients with histologically proven ovarian cancer with recurrence more than 6 months after first- or second-line platinum and taxane-based therapies were randomly assigned by stratified blocks to CD (carboplatin area under the curve [AUC] 5 plus PLD 30 mg/m2) every 4 weeks or CP (carboplatin AUC 5 plus paclitaxel 175 mg/m2) every 3 weeks for at least 6 cycles. Primary end point was progression-free survival (PFS); secondary end points were toxicity, quality of life, and overall survival.
Results Overall 976 patients were recruited. With median follow-up of 22 months, PFS for the CD arm was statistically superior to the CP arm (hazard ratio, 0.821; 95% CI, 0.72 to 0.94; P = .005); median PFS was 11.3 versus 9.4 months, respectively. Although overall survival data are immature for final analysis, we report here a total of 334 deaths. Overall severe nonhematologic toxicity (36.8% v 28.4%; P < .01) leading to early discontinuation (15% v 6%; P < .001) occurred more frequently in the CP arm. More frequent grade 2 or greater alopecia (83.6% v 7%), hypersensitivity reactions (18.8% v 5.6%), and sensory neuropathy (26.9% v 4.9%) were observed in the CP arm; more hand-foot syndrome (grade 2 to 3, 12.0% v 2.2%), nausea (35.2% v 24.2%), and mucositis (grade 2-3, 13.9% v 7%) in the CD arm.
Conclusion To our knowledge, this trial is the largest in recurrent ovarian cancer and has demonstrated superiority in PFS and better therapeutic index of CD over standard CP.
Abstracts 2010 ASCO Annual Meeting
search terms: "ovarian cancer' (note some duplication/non relevance) The abstracts can be search a variety of ways: eg. gynecologic cancer, brca, etc...
New early screening for ovarian cancer 'promising': study
WASHINGTON — A new screening approach to detect early stage ovarian cancer in post-menopausal women has proven promising, researchers said of results to a study released Thursday.
"More than 70 percent of ovarian cancers are diagnosed when they have already grown to an advanced stage, so identifying a reliable screening test for early-stage disease would be like finding the Holy Grail," said the study's lead author Karen Lu, of the University of Texas' Anderson Cancer Center.
"This study is one step forward in that direction. If confirmed in larger studies, this approach could be a useful and relatively inexpensive tool for detecting ovarian cancer in its early, more curable stages," she said.
The results were presented by the American Society of Clinical Oncology (ASCO) ahead of its annual conference, to be held June 4-8 in Chicago.
The new method uses a mathematical model to assess trends in CA-125 blood test results -- a protein known to rise during the cancer's development -- and a patient's age. The model is then "followed by transvaginal ultrasound and referral to a gynecologic oncologist, if necessary," researchers said.
For up to eight years, the study followed 3,238 post-menopausal women aged 50 to 74 who had no significant family history of breast or ovarian cancer, and the accuracy of using the mathematical model followed by ultrasound was 99.7 percent, indicating few false-positives using the approach, researchers said.
A larger study involving more than 200,000 women is currently underway in Britain, with results expected by 2015.
Society of Gynecologic Oncologists Releases 'Gynecologic Oncology 2010: State of the Subspecialty' Survey Results -- CHICAGO, May 18 /PRNewswire-USNewswire/ --
Highlights from the survey include:
- A movement in the profession to younger-aged practitioners and a larger number of women entering the specialty;
- A shift away from private practice as the primary practice setting into salaried positions and an increase in group or multi-specialty practice from individual practice;
- An increase in the number of medical assistants, nurse practitioners and physician assistants employed in gynecologic oncology practices;
- A continued dedication to providing chemotherapy services to patients regardless of the changes in reimbursement rates, as well as the continuation of enrollment of patients into cooperative studies versus the more revenue neutral or positive industry-sponsored trials;
- The positive effect of caps on non-economic and total damages on the cost of medical liability/malpractice insurance; and the
- An overall willingness of gynecologic oncologists to accept/treat women with a gynecologic cancer without knowledge of insurance coverage and the preponderance of Medicare and Medicaid patients seen in a practice, versus private insurance.
How Does Older Age Influence Oncologists' Cancer Management? - The Oncologist
Reference to ovarian cancer:
10. Eisenhauer EL, Tew WP, Levine DA et al. Response and outcomes in elderly patients with stages IIIC-IV ovarian cancer receiving platinum-taxane
chemotherapy. Gynecol Oncol 2007;106:381–387.
High cumulative incidence of cancer in patients with cardio-renal-anaemia syndrome (chronic kidney disease)
Aims
The combination of chronic kidney disease (CKD), chronic heart failure (HF), and anaemia, the so-called cardio-renal-anaemia syndrome (CRA) is associated with dysregulation of erythropoietin levels and inflammation. Both have been associated with the development of cancer. This study aimed to determine the cumulative incidence of cancer in patients with CRA, as compared with anaemic CKD and control patients.
Expert Comments On Radon Recommendations
Note: this is not 'new' news
"Radon, a radioactive, invisible, odorless gas that comes from the decay of naturally occurring uranium in the earth's soil, can accumulate in enclosed areas, such as underground mines and homes. It is the second leading cause of lung cancer in the United States and the leading cause of lung cancer among people who have never smoked, according to the report."
Impact of caregivers’ unmet needs for supportive care on quality of terminal cancer care delivered and caregiver’s workforce performance
Conclusions
Caregivers’ unmet needs negatively affected both the quality of EOL care they delivered and their workplace performance. More investment in caregiver support and public policies that meet caregiver needs are needed, and hospice use should be encouraged.
Sexual issues in early and late stage cancer: a review
"Few studies have assessed sexuality in the advanced stage of disease. Nevertheless, advanced cancer patients are willing to talk about their sex lives and the impact of the disease on their sexual function."
HighWire Medline Abstract
define: gonadotropin - hormone secreted by the anterior pituitary gland and placenta; stimulates the gonads and controls reproductive activity
Harvard Reproductive Endocrine Sciences Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Isolated gonadotropin-releasing hormone (GnRH) deficiency is a treatable albeit rare form of reproductive failure that has revealed physiological mechanisms controlling human reproduction, but despite substantial progress in discovering pathogenic single-gene defects, most of the genetic basis of GnRH deficiency remains uncharted. Although unbiased genetic investigations of affected families have identified mutations in previously unsuspected genes as causes of this disease in some cases, their application has been severely limited because of the negative effect of GnRH deficiency on fertility; moreover, relatively few of the many candidate genes nominated because of biological plausibility from in vitro or animal model experiments were subsequently validated in patients. With the advent of exciting technological platforms for sequencing, homozygosity mapping, and detection of structural variation at the whole-genome level, human investigations are again assuming the leading role for gene discovery. Using human GnRH deficiency as a paradigm and presenting original data from the screening of numerous candidate genes, we discuss the emerging model of patient-focused clinical genetic research and its complementarities with basic approaches in the near future.
Saturday, May 22, 2010
NKTR-102 Phase 2 Clinical Data Accepted for Oral Presentation at 2010 ASCO... -- SAN CARLOS, Calif., May 20 /PRNewswire-FirstCall/ --
Nektar To Host Investor Breakfast at ASCO on Monday, June 7, 2010
Nektar will also webcast a presentation to investors and analysts to be held at the 2010 ASCO Meeting on Monday, June 7, 2010 at 8 AM Central Time.
Panelists at the investor event will include:
* Ignace Vergote, M.D., Ph.D., Head of the Department of Obstetrics and Gynaecology and Gynaecologic Oncology at the Catholic University of Leuven, Belgium;
* Robert Coleman, M.D., Director of Clinical Research, Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; and
* Daniel Von Hoff, M.D., F.A.C.P., Chief Scientific Officer, TGen Clinical Research Services at Scottsdale Healthcare and U.S. Oncology, and Clinical Professor of Medicine at the University of Arizona College of Medicine and 2010 recipient of the ASCO David A. Karnofsky Memorial Award Lecture.
The event will be accessible live and by replay and can be accessed from the homepage of the company's website at www.nektar.com beginning on June 7, 2010 at 8:00 AM Central Time.
podcast: CA-125 Change Over Time Shows Promise as Screening Tool for Early Detection of Ovarian Cancer
CA-125 Change Over Time Shows Promise as Screening Tool for Early Detection of Ovarian Cancer
Blood test currently approved to find recurrence full of new possibility; invasive, high-grade disease uncovered at curable stageMD Anderson News Release 05/20/10
Genetic/Familial High-Risk Assessment: Breast and Ovarian — J Natl Compr Canc Network NCCN
Note: full free access; includes risks of Li-Fraumeni, Cowden and Lynch Syndromes
PLoS ONE: Repertoire of microRNAs in Epithelial Ovarian Cancer as Determined by Next Generation Sequencing of Small RNA cDNA Libraries
Note: full free access / technical
Background
MicroRNAs (miRNAs) are small regulatory RNAs that are implicated in cancer pathogenesis and have recently shown promise as blood-based biomarkers for cancer detection. Epithelial ovarian cancer is a deadly disease for which improved outcomes could be achieved by successful early detection and enhanced understanding of molecular pathogenesis that leads to improved therapies. A critical step toward these goals is to establish a comprehensive view of miRNAs expressed in epithelial ovarian cancer tissues as well as in normal ovarian surface epithelial cells.
Conclusions
This report expands the body of miRNAs known to be expressed in epithelial ovarian cancer and provides a useful resource for future studies of the role of miRNAs in the pathogenesis and early detection of ovarian cancer.
Discussion
The work reported here was motivated by the hypothesis that the entire repertoire of miRNAs expressed in ovarian cancer, including potentially tissue- and cancer-specific miRNAs, had not yet been elucidated.Vitamin D receptor rs2228570 polymorphism and invasive ovarian carcinoma risk: Pooled analysis in five studies within the Ovarian Cancer Association Consortium
"This pooled analysis provides further evidence that the VDR rs2228570 polymorphism might influence ovarian cancer susceptibility."
Clinical Care Options database - inPractice
Note: no sign on required/searchable database
Jointly sponsored by USF Health and Clinical Care Options, LLC:
Use inPractice’s search to quickly access answers to your point-of-care questions. inPractice searches the following resources at the same time:
- HIV inPractice
- Oncology inPractice
- Drug Information
- Guidelines
- PubMed
- CCO CME/CE
Perioperative morbidity and outcome of secondary cytoreduction for recurrent epithelial ovarian cancer.
CONCLUSION:
Secondary cytoreduction in relapsed ovarian cancer is safe and feasible and perioperative outcome is not inferior compared to primary cytoreduction. Surgery-associated morbidity should represent a minor aspect in the selection and counselling of patients regarding treatment options for recurrent ovarian cancer.
AJR Am J Roentgenol. 2010 Role of PET/CT in Ovarian Cancer
Abstract OBJECTIVE: The purpose of this article is to review the role of FDG PET/CT in ovarian cancer, which is the leading cause of death among gynecologic cancers. CONCLUSION: FDG PET/CT can significantly modify the assessment of the extent of primary and recurrent ovarian cancer and, hence, often alters patient management substantially. FDG PET/CT has thus become a critical tool for the preoperative evaluation of women with primary ovarian cancer and for postoperative follow-up assessment for evidence of recurrence in these patients.
Pre-counseling Education for Low Literacy Women at Risk of Hereditary Breast and Ovarian Cancer (HBOC): Patient Experiences Using the Cancer Risk...
Pre-counseling Education for Low Literacy Women at Risk of Hereditary Breast and Ovarian Cancer (HBOC): Patient Experiences Using the Cancer Risk Education Intervention Tool (CREdIT)
Thursday, May 20, 2010
Giving Honest Information to Patients With Advanced Cancer Maintains Hope - Cancer Network
"Background: Oncologists often do not give honest prognostic and treatment-effect information to patients with advanced disease. One of the primary reasons stated for witholding this information is to “not take away hope.” We could find no study that tested if hope was influenced by honest clinical information...cont'd"
ORC Oncology report - fill out form to receive copy of the report
Note: once the form is filled out the paper uploads a pdf file of the report automatically
ORC’s Oncology Report examines three important Oncology issues: Assessing the Impact of Revised NSCLC Staging, Genetically Linked Breast Cancer and PARP-1 Inhibitors and Reactions to New Mammogram Recommendations. Submit the information below and download the full report.
What is Molecular Biology?
* ''Biochemistry'' is the study of the chemical substances and vital processes occurring in living organisms. Biochemists focus heavily on the role, function, and structure of biomolecules. The study of the chemistry behind biological processes and the synthesis of biologically active molecules are examples of biochemistry.
* ''Genetics'' is the study of the effect of genetic differences on organisms. Often this can be inferred by the absence of a normal component (e.g. one gene). The study of "mutants" – organisms which lack one or more functional components with respect to the so-called "wild type" or normal phenotype. Genetic interactions (epistasis) can often confound simple interpretations of such "knock-out" studies.
* ''Molecular biology'' is the study of molecular underpinnings of the process of replication, transcription and translation of the genetic material. The central dogma of molecular biology where genetic material is transcribed into RNA and then translated into protein, despite being an oversimplified picture of molecular biology, still provides a good starting point for understanding the field. This picture, however, is undergoing revision in light of emerging novel roles for RNA.
Wednesday, May 19, 2010
Validation of My Family Health Portrait for six co... [Genet Med. 2010] - PubMed result
CONCLUSIONS:
These data support the validity of My Family Health Portrait pedigrees for four common conditions-diabetes and colon, breast, and ovarian cancer.
Tuesday, May 18, 2010
Risk of Cancer Following Hospitalization for Type 2 Diabetes The Oncologist
ABSTRACT
Objectives. Cancer and type 2 diabetes (T2D) are two common diseases that may share risk factors. We aimed at determining subsequent cancer risks in patients hospitalized for T2D in Sweden.
Methods. T2D patients were obtained from the nationwide Hospital Discharge Register; cancers were recorded from the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for cancer
following last hospitalization for T2D. The comparison group was the general Swedish population.
Results. The number of hospitalized T2D patients from 1964 to 2007 was 125,126, of whom 26,641 had an affected family member. Altogether 24 cancers showed an elevated risk when follow-up was started after the
last hospitalization. The highest SIRs were for pancreatic (6.08) and liver (4.25) cancers. The incidences of these cancers were even elevated when follow-up was started 5 years after the last hospitalization for T2D, with primary liver cancer showing the highest SIR of 4.66. Also increased were the incidences of upper aerodigestive tract, esophageal, colon, rectal, pancreatic, lung, cervical, endometrial, ovarian, and kidney cancers. Prostate cancer showed a lower risk. Familial T2D patients showed no exceptional elevated cancer risks but their prostate cancer and melanoma risks were lower.
Conclusions. This study, covering approximately one half of Swedish T2D patients, showed an elevated risk for several cancers after hospitalization for T2D, probably indicating the profound metabolic disturbances of the underlying disease. The highest risks were found for
liver and pancreatic cancers. No excess cancer risks were observed in familial diabetics. The lower risk for prostate cancer remains intriguing
(ovarian cancer incidence rates 15.61/per 100,000 population; risk 1.84 (>1.0 = increased risk)
CCR Clinical Trials at NIH: Health Care Professionals: Join Our Mailing List
Health care professionals who join the National Cancer Institute Clinical Trials at NIH mailing list receive: * Quarterly e-mail notifications about clinical trials * Information about the National Cancer Institute's programs and clinical opportunities
NCI: Talking About Trials: Overcoming Bottlenecks in Clinical Communication (enrolment)
".......“Patient refusal rates may be less of a problem than low rates of trial offers,” wrote the authors."
NCI Cancer Bulletin for May 18, 2010 - SPECIAL ISSUE
Additional Clinical Trials Resources
Cancer Clinical Trials at NIH
NCI supports cancer clinical trials across the country (U.S) through its extramural research program. Meanwhile, on NIH’s main campus, the Institute’s intramural researchers in the Center for Cancer Research (CCR) conduct hundreds of trials each year at the NIH Clinical Center in Bethesda, MD, and these trials often differ from those available elsewhere.While some cancer centers also offer early-stage clinical trials, the difference is that CCR focuses almost exclusively on early-stage trials, said Dr. Bill Dahut, CCR’s clinical director.
NCI’s intramural program is able to pay the transportation costs for patients who are enrolled in Clinical Center trials. This allows CCR to see many more patients with rare cancers, or rare subtypes of common cancers, than other research sites because CCR can fly in patients from around the country to be treated in investigational studies.
One commonly cited barrier to entering clinical trials is the worry among both patients and their physicians of losing control. “An important point about treatment at NCI is that everything we do here for patients is done in close collaboration with their local physicians back home,” Dr. Dahut explained. “Our physicians provide expert clinical care to patients while they are being treated on protocol at NCI, but our physicians can see patients only while they are at the Clinical Center. Thus, continued care by local physicians is incredibly important to allow patients to access standard treatments or other trials not available here. Local physicians must remain closely involved with patients on NCI studies because side effects, from the cancer or the therapy, may occur when the patient is home and far from Bethesda.”
Patients and physicians interested in exploring cancer clinical trials at NIH can visit CCR’s clinical trials Web site. The site includes detailed descriptions of clinical trials currently recruiting patients; information for the general public about clinical trials and participating in trials at NCI; and information for health professionals about referring patients, the Center’s clinical programs and investigators, and ways to keep up to date with CCR research and opportunities.
“We’d really like to encourage physicians to join our mailing list,” said Susan McMullen, patient outreach and recruitment coordinator for CCR’s Office of the Clinical Director. “One of the barriers to recruiting patients at NIH is that our doctors don’t have a patient base outside of clinical trials to draw from, so we rely on community doctors to refer patients to us.”
Family Cancer Registries
To determine what genetic factors may be at work and how environmental influences alter those genetic risks, researchers rely on those affected by familial cancer to participate in family cancer registries.
“Our major goal in studying these families is to identify what are called high-risk susceptibility genes,” explained Dr. Peggy Tucker, director of the Human Genetics Program and chief of the Genetic Epidemiology Branch in NCI’s Division of Cancer Epidemiology and Genetics (DCEG). “We then try to understand the function of those genes, how they confer risk, and what other factors within the family modify risk.
“Ultimately, we want to be able to alter the risk of cancer in these families either by identifying susceptibility factors we can modify—for example, avoiding sun exposure in melanoma families—or designing interventions that can affect risk—such as prophylactic oophorectomy for women in families with high risk of both breast and ovarian cancer,” she said.
Family cancer registry studies can also help inform researchers about cancer susceptibility risks in the general population. For example, researchers identified dysplastic nevi as a major risk factor for melanoma by studying families at high risk of melanoma.
Researchers at NCI first began conducting family registry studies in the mid-1960s. These long-term studies follow families through successive generations, and allow researchers to examine the role of inherited high-susceptibility genes and cancer. Today, DCEG researchers are studying families with a number of inherited cancers or cancer-susceptibility syndromes, and researchers in NCI’s Division of Cancer Control and Population Sciences (DCCPS) sponsor the Breast and Colon Cancer Family Registries.
Whereas DCEG’s family registries are conducted at the NIH Clinical Center, the family registries based in DCCPS are found throughout the United States, Australia, and Canada. “Currently, we have about 78,000 men and women from nearly 26,000 families participating in these registries,” said Dr. Sheri Schully, program officer for the DCCPS family registries program. “The main objective of these registries is to identify and characterize cancer susceptibility genes, but the investigators also look at gene–gene and gene–environment interactions as well.”
Although family registry studies do not provide treatment to participating families, investigators often provide test results that can help family members learn which of them may be at higher risk because of certain susceptibility genes, such as mutations in the BRCA1 and BRCA2 genes or those associated with Lynch syndrome, said Dr. Schully.
Additionally, the studies are an opportunity for people who are often desperate for answers to ask questions.
“We like to think it’s a positive experience for them because they have a whole day at NIH to meet with physicians and nurses who know a lot about the disease,” Dr. Tucker explained. “We try to keep them updated with new findings about the diagnosis and management of the cancer that affects their family, and they know they can always come to us for referrals for care of the disorders that we’re studying.”
Learn More About Clinical Trial Enrollment....
Breast Cancer Research | Full text | Familial relative risks for breast cancer by pathological subtype: a population-based cohort study
Conclusions
"We may conclude from our results that the FRR (familial relative risk) for breast cancer is significantly increased for each pathological subtype except TN tumours, although the numbers in the latter category were too small to draw definitive conclusions.
When analyzed by tumour subtype, a surprisingly high proportion of FRR (familial relative risk) for ER-negative disease is already explained.
We estimate that 32% of breast cancer FRR for ER-negative disease is explained by BRCA1 and BRCA2 mutations alone.
Patients carrying such mutations may be advised to undergo prophylactic therapies such as oophorectomy or mastectomy.
About 10% of the FRR for ER-positive disease is explained by 12 newly discovered SNPs, and the contributions of these SNPs to FRR are likely to be somewhat higher once the true causal variants are identified.
The construction of informative risk prediction models for ER-positive disease is particularly important as the risk of ER-positive disease can be reduced by chemoprevention such as tamoxifen.
It is possible that including novel (new) genetic variants associated with breast cancer susceptibility in models may improve risk prediction for subtype specific disease."
BSB4uD (Be Smart Before You Donate - see blog posting and income comparisons non-profit employees vs professional salaries) - note updated information on Canadian family physician salaries - average
Blogger Author's Opinion: based on these averages, most family physicians are underpaid
Family Physician salaries as per CMAJ April 9th 2010: $225,521. Cdn avg CMAJ
Update: May 18th, 2010
A separate, unpublished CIHI indice which weights all payments — whether fee-for-service, salary or other form of capitation — for all services, against a national median indicates that Newfoundland and Labrador doctors essentially earn 6.78% less than a national median of $224 875 earned by doctors in 2007–08. On that scale, doctors in Alberta (7.22% above the median) were the highest paid in the country, followed by those in British Columbia (5.84% above), New Brunswick (4.6% above), Saskatchewan (4.24% above), Nova Scotia (1.68% above), Ontario (1.68% below) and Manitoba (4.88% below). Only doctors in Prince Edward Island (18.28% below) and Quebec (28.66% below) earned less than those in Newfoundland and Labrador.
http://www.cmaj.ca/cgi/content/full/182/8/E339?etoc
EpCAM As a Target in Cancer Therapy -- Journal of Clinical Oncology
Function: (ref source WIKI) EpCAM is a pan-epithelial antigen that is expressed on almost all carcinomas. Its constitutional function is being elucidated.
Note: search blog for other references to EpCAM and in particular to Lynch Syndrome"...Like for every targeted therapy, the level of EpCAM target expression will have an impact on the outcome of a trial. This was evident for the human anti-EpCAM antibody adecatumumab in patients with metastatic breast cancer. Although a high level and frequency of EpCAM expression can be assumed for patients with colorectal cancer, none of the previous trials prospectively or retrospectively analyzed patients for levels of EpCAM expression on tumor tissue. Particularly for a low-affinity antibody, such as edrecolomab, it may be of importance that tumor cells express EpCAM at a high and not just at an intermediate level..... Future studies will certainly benefit from stratifying patients for their level of EpCAM target expression."
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