J Med Genet. 2010 July; 47(7): 464–470.
Published online 2010 June 30. doi: 10.1136/jmg.2010.076992
PMCID: PMC2991077
Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2mutation carriers
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Sunday, September 16, 2012
Meaningful Responses To ‘We-Know-the-Answer’ Syndrome
Blogger's Note: requires registration / free (Markman/ovarian cancer illustrated)
Meaningful Responses To 'We-Know-the-Answer' Syndrome
Critical thinking—like the phrase "evidence-based"—has become a rather overused mantra in clinical medicine. As an unfortunate result, this concept has lost much of its meaning and its impact on how we evaluate study results and ultimately consider their use in the non-trial setting.
If the link below does not open, please copy and past this link into your browser:
http://www.clinicaloncology.com/ViewArticle.aspx?d=Clinical+Trials&d_id=165&i=January+2012&i_id=808&a_id=20047
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Terry Fox runs being held across the country to raise money for cancer research
Terry Fox runs being held across the country to raise money for cancer research
Irene Preklet and Kris McCusker | Sun Sep 16, 8:22 AM
He's a Canadian hero known all around the world, and on Sunday thousands of people are lacing up to walk or run in his name. Terry Fox runs are being held across the country and the GTA, with the goal of continuing Terry's dream of raising money for cancer research. "What you ever you do you gotta do the best you can possibly do, and I'm going to give it everything I possibly can," Fox said. And that he did, as Fox ran his Marathon of Hope, inspiring people across a nation. Martha McLew, Ontario Director of the Terry Fox Foundation, says there are 17 runs in the GTA alone. "I think that when people come out to the Terry Fox run, they realize they are doing it for such a personal reason, they are doing it for a loved one, and to really thank Terry at the same time," McLew said. There is no per-registration needed and no mandatory fee. To find a run near you, click here.
http://www.680news.mobi/article.aspx?content_id=401999Human epididymis protein 4 (HE4) and Ovarian cancer prognosis.
Abstract
OBJECTIVE: A cohort study was conducted to evaluate whether preoperative plasma HE4 levels could predict the occurrence of death (primary endpoint) and progression (secondary endpoint) in women with ovarian cancer (OC).
METHODS: Between 1998 and 2006, we recruited 136 women newly diagnosed with OC of any FIGO stage at the University Hospital, CHUQ-L'Hôtel-Dieu de Québec, Canada. HE4 was measured using the Abbott's ARCHITECT HE4 assay. Dates of death were obtained by record linkage with the Québec mortality files. Progression was evaluated using the CA-125 or the RECIST criteria, as recommended by the Gynecology Cancer Intergroup. Adjusted hazard ratios (HR) of death and progression, as well as their 95% confidence intervals (CI), were estimated using the Cox proportional hazard regression model.
RESULTS: Preoperative levels of HE4 were strongly associated with all OC standard prognostic factors. HE4 levels increased significantly with age (p=0.02), FIGO stage (p<0.0001), grade (p=0.005), preoperative CA-125 levels (p<0.0001), and residual tumor (p<0.0001). HE4 levels above the median value (394 pmol/L) were significantly associated with mortality (HR=2.17; 95% CI: 1.42-3.32) and progression (HR=1.81; 95% CI: 1.21-2.72). After adjustment for the FIGO stage, which was the only factor significantly associated with prognosis in multivariate analyses, the association of HE4 with death remained statistically significant (HR=1.67; 95% CI: 1.08-2.59). However, the association with progression was no longer significant (HR=1.32; 95% CI: 0.87-1.99).
CONCLUSION: These results show that preoperative the plasma level of HE4 is a marker of OC aggressiveness and a predictor of death.
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Saturday, September 15, 2012
Objective evaluation of the alleviating effects of Goshajinkigan on peripheral neuropathy induced by paclitaxel/carboplatin therapy: A multicenter collaborative study.
Objective evaluation of the alleviating effects of Goshajinkigan on peripheral neuropathy induced by paclitaxel/carboplatin therapy: A multicenter collaborative study.:
Exp Ther Med. 2012 Jan;3(1):60-65
Abstract
Paclitaxel/carboplatin chemotherapy for cancer (TC therapy) exhibits neurotoxicity and causes peripheral neuropathy at a high frequency, which is difficult to cope with. In this study, we investigated the efficacy of Goshajinkigan, a traditional Japanese herbal medicine, for TC therapy-induced peripheral neuropathy. The subjects included in our study were patients with ovarian or endometrial cancer who underwent TC therapy and developed peripheral neuropathy. The patients were randomly divided into Group A, comprising of 14 patients (vitamin B12 treatment), and Group B, comprising of 15 patients (vitamin B12 + Goshajinkigan treatment). The observation period was 6 weeks following treatment initiation, and the evaluation items were as follows: i) the current perception threshold (CPT value) of the peripheral nerve, ii) visual analogue scale for numbness, iii) National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grade of neurotoxicity, and iv) a questionnaire on the subjective symptoms of peripheral neuropathy (functional assessment of cancer therapy-taxane). These were compared between the groups and no significant differences were noted in any item. However, CTCAE grade 3 neurotoxicity developed in 2 patients (14.3%) after 6 weeks of administration in Group A, whereas no neurotoxicity was observed in Group B. When the change in the frequency of abnormal CPT ratio at 6 weeks of administration from that before treatment was compared between the groups, the frequency of abnormal value was significantly lower in Group B than in Group A (p<0.05). This suggests that Goshajinkigan inhibits the progression of peripheral neuropathy.
PMID: 22969845 [PubMed - as supplied by publisher]
Evaluation of microsatellite instability in women with epithelial ovarian cancer.
Evaluation of microsatellite instability in women with epithelial ovarian cancer.:
Oncol Lett. 2012 Sep;4(3):556-560
Abstract
The function of microsatellite instability (MSI) and the optimal panel of markers for epithelial ovarian cancer (EOC) are not well established. This study aimed to use the National Cancer Institute (NCI) markers BAT25, BAT26, D2S123, D5S346 and D17S250 to evaluate MSI in patients with ovarian serous cystadenocarcinoma, compared with ovarian serous cystadenoma and normal ovaries. A total of 37 patients were divided into three groups, as follows: cystadenocarcinoma (n=13), cystadenoma (n=10) and normal ovaries (n=14). DNA was extracted with TRIzol and quantified by spectrophotometry. MSI was evaluated by polymerase chain reaction (PCR), and classified as high (MSI-H), low (MSI-L) or stable (MSS). FIGO staging was I/II in 23.1% and III/IV in 76.9% of the cystadenocarcinoma group. Polymorphisms were found using at least one marker in 32 women, and were observed with D2S123 (83.7%), D17S250 (81.1%), D5S346 (72.9%), BAT25 (21.6%) and BAT26 (16.2%) markers. In the cystadenocarcinoma group, BAT25, BAT26, D2S123, D5S346 and D17S250 markers were positive in 30.8, 76.9, 53.8, 69.2 and 69.2% of patients, respectively. The same markers were positive in 30, 50, 40, 60 and 30% of the cystadenoma group, and 50, 71.4, 71.4, 64.3 and 63.3% in the normal ovary group, respectively. MSI-H was present in 84.6, 60 and 78.6% of the cystadenocarcinoma, cystadenoma and normal patients, respectively. MSI-L was detected in 0, 30 and 7.1%, and MSS was identified in 15.4, 10 and 14.3% of the cystadenocarcinoma, cystadenoma and normal patients, respectively. The frequency of MSI in both benign epithelial ovarian neoplasms and in normal ovaries was high, as well as in EOC, with no statistically significant difference between the groups. This suggests that MSI may arise as a consequence of the ovulatory process, and not solely as a feature of malignant ovarian tumors.
PMID: 22970055 [PubMed - as supplied by publisher]
open access: Development of multiplexed bead-based immunoassays for the detection of early stage ovarian cancer using a combination of serum biomarkers.
Development of multiplexed bead-based immunoassays for the detection of early stage ovarian cancer using a combination of serum biomarkers.:
PLoS One. 2012;7(9):e44960
Abstract
CA125 as a biomarker of ovarian cancer is ineffective for the general population. The aim of this study was to evaluate multiplexed bead-based immunoassay of multiple ovarian cancer-associated biomarkers such as transthyretin and apolipoprotein A1, together with CA125, to improve the identification and evaluation of prognosis of ovarian cancer. We measured the serum levels of CA125, transthyretin, and apolipoprotein A1 from the serum of 61 healthy individuals, 84 patients with benign ovarian disease, and 118 patients with ovarian cancer using a multiplex liquid assay system, Luminex 100. The results were then analyzed according to healthy and/or benign versus ovarian cancer subjects. When CA125 was combined with the other biomarkers, the overall sensitivity and specificity were significantly improved in the ROC curve, which showed 95% and 97% sensitivity and specificity, respectively. At 95% specificity for all stages the sensitivity increased to 95.5% compared to 67% for CA125 alone. For stage I+II, the sensitivity increased from 30% for CA125 alone to 93.9%. For stage III+IV, the corresponding values were 96.5% and 91.6%, respectively. Also, the three biomarkers were sufficient for maximum separation between noncancer (healthy plus benign group) and stage I+II or all stages (I-IV) of disease. The new combination of transthyretin, and apolipoprotein A1 with CA125 improved both the sensitivity and the specificity of ovarian cancer diagnosis compared with those of individual biomarkers. These findings suggest the benefit of the combination of these markers for the diagnosis of ovarian cancer.
PMID: 22970327 [PubMed - in process]
Mucinous tumours of the ovary.
Mucinous tumours of the ovary.:
J Clin Pathol. 2012 Jul;65(7):580-4
Abstract
Mucinous epithelial ovarian cancers (mEOC) are a relatively rare subset of ovarian cancers. Despite a relatively favourable outcome in early disease, the more frequent advanced presentation is associated with poorer response to platinum/taxane chemotherapies, and poorer survival, compared to serous ovarian cancers. We consider some of the fundamental clinico-pathological and molecular features, and existing clinical trial data regarding mEOC. Underlying molecular differences, between mEOC and serous cancers may contribute to the observed clinical differences, including an increased prevalence of K-RAS mutations in mEOC, more in keeping with gastrointestinal tumours. This observation contributes to the rationale for a trial ("mEOC") investigating the use of "ovarian" versus "gastrointestinal" style chemotherapy. Looking to potential future approaches, we speculate upon the potential impact of emerging technologies on the future investigation and management of mEOC.
PMID: 22011449 [PubMed - indexed for MEDLINE]
Essays: Steven Lewis - Behavioural Economics Explains Why Ontario Doctors Are So Livid :: Longwoods.com
Behavioural Economics Explains Why Ontario Doctors Are So Livid :: Longwoods.com
Behavioural Economics Explains Why Ontario Doctors Are So Livid
Psychological outcomes of familial ovarian cancer screening: No evidence of long-term harm
Psychological outcomes of familial ovarian cancer screening: No evidence of long-term harm
View full text
Highlights
►
Abnormal results of familial ovarian cancer screening may raise women's
concerns in the short-term but not in the longer-term.
► Women receiving abnormal test results are more likely to withdraw from screening, primarily for salpingo-oophorectomy.
► Decision support is needed for women who are considering options for managing their risk of familial ovarian cancer.
► Women receiving abnormal test results are more likely to withdraw from screening, primarily for salpingo-oophorectomy.
► Decision support is needed for women who are considering options for managing their risk of familial ovarian cancer.
Abstract
Objectives
Ovarian
cancer screening for women at increased genetic risk in the UK involves
4-monthly CA125 tests and annual ultrasound, with further tests
prompted by an abnormal result. The study evaluated the longer-term
psychological and behavioural effects of frequent ovarian screening.
Methods
Women
completed T1 questionnaires before their first routine 4-monthly CA125
test, and T2 follow-up questionnaires one week after their result. Women
with abnormal results completed a further questionnaire one week after
return to routine screening (T3 primary end-point). T4 questionnaires
were sent at nine months. Measures included cancer distress, general
anxiety/depression, reassurance, and withdrawal from screening.
Results
A
total 1999 (62%) of 3224 women completed T1 questionnaires. T2
questionnaires were completed by 1384/1609 participants (86%): 1217
(89%) with normal results and 167/242 (69%) with abnormal results. T3
questionnaires were completed by 141/163 (87%) women, with 912/1173
(78%) completing T4 questionnaires. Analysis of covariance indicated
that, compared to women with normal results, women with abnormal results
reported moderate cancer distress (F = 27.47, p ≤ .001, η2 = 0.02)
one week after their abnormal result and were significantly more likely
to withdraw from screening (OR = 4.38, p ≤ .001). These effects were
not apparent at T3 or T4. The effect of screening result on general
anxiety/depression or overall reassurance was not significant.
Conclusions
Women
participating in frequent ovarian screening who are recalled for an
abnormal result may experience transient cancer-specific distress, which
may prompt reconsideration of risk management options. Health
professionals and policy makers may be reassured that frequent familial
ovarian screening does not cause sustained psychological harm.
Highlights
►
Abnormal results of familial ovarian cancer screening may raise women's
concerns in the short-term but not in the longer-term.
► Women receiving abnormal test results are more likely to withdraw from screening, primarily for salpingo-oophorectomy.
► Decision support is needed for women who are considering options for managing their risk of familial ovarian cancer.
► Women receiving abnormal test results are more likely to withdraw from screening, primarily for salpingo-oophorectomy.
► Decision support is needed for women who are considering options for managing their risk of familial ovarian cancer.
Green tea and green tea catechin extracts: An overview of the clinical evidence
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Green tea and green tea catechin extracts: An overview of the clinical evidence
Publication year: 2012Source:Maturitas
Rachel Johnson, Susan Bryant, Alyson L. Huntley
Background Tea leaves contain varying amounts of polyphenols of which the majority are catechins. There has been a sizable amount of research on the potential effect of green tea catechins for cancer risk, cardiovascular disease risk and weight loss; all conditions that are relevant to mid-life health. The aim was to produce an overview of the evidence for green tea for these three important health conditions. Methods The databases Medline (& Medline in process) and Embase, were searched for systematic reviews and meta-analyses using customised search strategies performed up until April 2012. Assessment of Multiple Systematic Reviews criteria were used to assess the quality of the included reviews. Relevant data were extracted into predefined tables. The results are described and discussed narratively. Results We included eight systematic reviews and meta-analyses covering the topics of cancer risk (n =2), cardiovascular risk (n =4) and weight loss (n =2). Conclusions The evidence for green tea and cancer risk is inadequate and inconclusive. However there is some positive evidence for risk reduction of breast, prostate, ovarian and endometrial cancers with green tea. RCTs of green tea and cardiovascular risk factors suggest that green tea may reduce low-density lipoproteins and total cholesterol, although studies are of short duration. There is no robust evidence to support a reduction in coronary artery disease risk in green tea drinkers. There are a considerable number of RCTs to suggest that green tea does reduce body weight in the short term, but this not likely to be of clinical relevance.
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Outcomes of cancer patients after unplanned admission to general intensive care units, Acta Oncologica, Informa Healthcare
Outcomes of cancer patients after unplanned admission to general intensive care units, Acta Oncologica, Informa Healthcare
Abstract
Background.
Acute admission to an intensive care unit (ICU) of cancer patients is
considered with increasing frequency due to a better life expectancy and
more aggressive therapies. The aim of this study was to determine the
characteristics and outcomes of cancer patients with unplanned
admissions to general ICUs, and to compare these with outcomes of
critically ill patients without cancer.
Material and methods. All
unplanned ICU admissions in the Netherlands collected in the National
Intensive Care Evaluation registry between January 2007 and January 2011
were analyzed.
Results and conclusion. Of the 140,154 patients
with unplanned ICU admission 10.9% had a malignancy. Medical cancer
patients were more severely ill on ICU admission in comparison with
medical non-cancer patients, as reflected by higher needs for mechanical
ventilation (50.8% vs. 46.4%, p < 0.001) and vasopressors within 24
hours after admission (41.5% vs. 33.0%, p < 0.001), higher Acute
Physiology and Chronic Health Evaluation (APACHE) IV scores (88.1 vs.
67.5, p < 0.001) and a longer ICU stay (5.1 vs. 4.6 days, p
< 0.001). In contrast, surgical cancer patients only displayed a
modestly higher APACHE IV score on admission when compared with
non-cancer surgical patients, whereas the other afore mentioned
parameters were lower in the surgical cancer patients group. In-hospital
mortality was almost twice as high in medical cancer patients (40.6%)
as in medical patients without cancer (23.7%). In-hospital mortality of
surgical cancer patients (17.4%) was slightly higher than in patients
without cancer (14.6%). These data indicate that unplanned ICU admission
is associated with a high mortality in patients with cancer when
admitted for medical reasons.
Hereditary Gynecological Malignancies: Advances in Screening
Hereditary Gynecological Malignancies: Advances in Screening and Treatment
DOI: 10.1111/his.12028
© 2012 Blackwell Publishing Ltd
Additional Information(Show All)
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Cell-cell and cell-matrix dynamics in intraperitoneal cancer metastasis.
Cell-cell and cell-matrix dynamics in intraperitoneal cancer metastasis.
Abstract
The peritoneal metastatic route of cancer dissemination is shared by cancers of the ovary and gastrointestinal tract. Once initiated, peritoneal metastasis typically proceeds rapidly in a feed-forward manner. Several factors contribute to this efficient progression. In peritoneal metastasis, cancer cells exfoliate into the peritoneal fluid and spread locally, transported by peritoneal fluid. Inflammatory cytokines released by tumor and immune cells compromise the protective, anti-adhesive mesothelial cell layer that lines the peritoneal cavity, exposing the underlying extracellular matrix to which cancer cells readily attach. The peritoneum is further rendered receptive to metastatic implantation and growth by myofibroblastic cell behaviors also stimulated by inflammatory cytokines. Individual cancer cells suspended in peritoneal fluid can aggregate to form multicellular spheroids. This cellular arrangement imparts resistance to anoikis, apoptosis, and chemotherapeutics. Emerging evidence indicates that compact spheroid formation is preferentially accomplished by cancer cells with high invasive capacity and contractile behaviors. This review focuses on the pathological alterations to the peritoneum and the properties of cancer cells that in combination drive peritoneal metastasis.
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Influence of a family history of breast and/or ovarian cancer on breast cancer outcomes.
Influence of a family history of breast and/or ovarian cancer on breast cancer outcomes.
Influence of a family history of breast and/or ovarian cancer on breast cancer outcomes.
Exp Ther Med. 2011 9;2(5):917-923
Authors: Cao AY, He M, DI GH, Wu J, Lu JS, Liu GY, Shen ZZ, Shao ZM
Abstract
Various published studies have been inconclusive in attempting to relate a family history of breast and/or ovarian cancer (BOC) to the survival of breast cancer patients. The aim of the study was to investigate the association of a family history of BOC with tumor characteristics, treatment response and the difference between the prognosis of familial breast cancer (FBC) patients and sporadic breast cancer (SBC) patients. Data on 348 operable FBC patients and 345 SBC patients were retrospectively analyzed. The overall survival (OS) and recurrence/metastasis-free survival (RFS) were compared for both groups. FBC cases were diagnosed at a relatively younger age (51.1±10.4 vs. 53.7±11.0 years, P=0.054) and presented a lower T stage (P=0.000) than the SBC cases. Patients with a family history of BOC had a significantly greater risk of recurrence/metastasis (P= 0.04) and a non-significantly increased risk of death (P=0.06) compared to the SBC patients. In a multivariate analysis, family history of BOC was an independent predictive factor for both recurrence/metastasis rate (P=0.01, HR=0.012, 95% CI 0.02-0.57) and mortality (P=0.044, HR=0.43, 95% CI 0.19-0.98) in the hormone receptor-positive population. Our results found that women diagnosed with FBC had an early onset of disease in the population studied, and the poor outcome of patients with a family history of BOC associated with survival was restricted to the hormone receptor-positive population.
PMID: 22977598 [PubMed - as supplied by publisher]
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Friday, September 14, 2012
Gregory Pawelski on Expert Opinion: A US Perspective On Beating Cancer (ovarian....)
Gregory Pawelski on Expert Opinion: A US Perspective On Beating Cancer:
I first came across in 2003, the disparities in cancer care between the US and the UK in a clinical trial by Dr. Ian Cree, studying how well chemosensitivity assays predict response to chemotherapy in patients with persistent, refractory, or recurrent ovarian epithelial, peritoneal, or fallopian tube cancer. The results were highly suggestive of an effect due to the assay, and the most successful drug regimens used were nearly all developed using the assay. However, UK results in cancer are always lower than in the US for a variety of reasons. Part of this is probably lead time bias, but data on surgical debulking may be part of the explanation. Patients in the US get a whole lot more surgery along the way than in Europe. Even in the underpowered Cree, et al study, the use of his ATP assay changed treatment decisions in something like 90% of the cases, but the study was too small to show that the changed treatment decisions were to the benefit of the patient, in terms of long survival. The study allowed the physician's choice arm to include Dr. Cree's own drug combination as the trial accrued (BMC Cancer. 2003: 3:19). This experience taught me to look at those disparities closer, particularly when it comes to the British National Institute for Clinical Excellence (NICE). Based on clinical trials, results showing no difference between single-agent platinums versus platinum/taxol (GOG Trial #132, ICON3, ICON4), NICE determined that platinum/taxol should no longer be considered as standard therapy, and that a range of therapies are equally acceptable (Lancet 2002;360:500-501, 505-515). In the US, where the administration of platinum/taxol had been much more profitable to the treating oncologist than single-agent platinum, there had been the dogged insistance that platinum/taxol remained standard, despite clear lack of support for this position, based on the entirety of the clinical trials literature. Platinum-taxol is not superior to single-agent carboplatin and single-agent cisplatin. I wrote a paper "Who Needs Taxol?" One of the researchers listed in the foot notes of the paper (Carcinomatous Meningitis: Taxane-Induced) which found what is called "dissemination after taxane-based chemotherapy," had told me that the study he finally published in the journal Oncology, was rejected by all other American & European cancer journals (Journal of Clinical Oncology, Cancer, Annals of Oncology, European Journal of Cancer, International Journal of Cancer) where it had been submitted. The journal were reluctant to publish such a scientific report, simply because taxanes (both taxol and taxotere) were at the time very intensively advertised in these journals. Why would the UK look to the US with a tinge of envy about what we do when it comes to providing cancer care? Yes, the problem is we can't afford to keep doing this, while NICE is trying to do something about it.
Cochrane request: Take part in an innovative pilot study using your iPhone, iPad, or iPod Touch
Take part in an innovative pilot study using your iPhone, iPad, or iPod Touch:
Dear Cochrane colleagues
We are pleased to invite you to take part in an innovative research study using your iPhone, iPad, or iPod Touch. I realise many of you, myself included, don't have one of these devices...but we'd be really grateful if you could help us out by passing this invitation on to friends, relations and colleagues who do. We are particularly interested in recruiting people unfamiliar with Cochrane and EBM, including older school students.
External link for more information:
Contributor's name:
Caroline Struthers
Email address:
caroline.struthers@ndm.ox.ac.uk
DOD Announces Research Funding Opportunities
DOD Announces Research Funding Opportunities:
The following pre-announcement on a postdoctoral fellowship award may be of interest to those working on colon cancer/breast cancer or pancreatic cancer/breast cancer (BRCA2 mutations) research.
The fiscal year 2012 (FY12) Defense Appropriations Act provides $120 million to the Department of Defense Breast Cancer Research Program (BCRP) to support innovative, high-impact breast cancer research. The BCRP is administered by the U.S. Army Medical Research and Materiel Command through the Office of Congressionally Directed Medical Research Programs (CDMRP).
The FY12 BCRP program announcement and general application instructions for the following award are anticipated to be posted on grants.gov in October.
Eligibility
- Principal Investigator: doctoral graduates (PhD or MD). Clinical investigators are eligible to apply. Must have no more than two years experience in the proposed research setting and no more than four years of postdoctoral research experience as of the application deadline.
- Mentor or formal co-mentor must have breast cancer research experience, including current funding and publications.
- Supports the training of exceptionally talented recent doctoral or medical graduates who have demonstrated that they are the "best and brightest" of their peers.
- Individualized training program and mentorship should prepare the principal investigator for an independent career at the forefront of breast cancer research.
- Proposed research should address a critical problem in breast cancer.
- Maximum funding of $300,000 for direct costs ($100,000 per year, plus indirect costs).
- Period of performance not to exceed three years.
Position Opening: Executive Director | Society for Participatory Medicine
Position Opening: Executive Director | Society for Participatory Medicine
The Society for Participatory Medicine (SPM) seeks a part-time executive director. SPM is a nonprofit organization that promotes Participatory Medicine through its journal, online community, meetings, and other channels. Participatory Medicine is a cooperative model of healthcare that encourages and expects active involvement by all connected parties (patients, caregivers, healthcare professionals, etc.) as integral to the full continuum of care. The Executive Director will report to the Board of Directors and participate in bi-weekly executive committee meetings and other organizational meetings.
Major areas of responsibility include:...............
Non-steroidal anti-inflammatory drug use and ovarian cancer risk: findings from the NIH-AARP Diet and Health Study and systematic review.
Non-steroidal anti-inflammatory drug use and ovarian cancer risk: findings from the NIH-AARP Diet and Health Study and systematic review.:
| Related Articles |
Cancer Causes Control. 2012 Sep 13;
Abstract
BACKGROUND: Chronic inflammation has been proposed as a risk factor for ovarian cancer. Some data suggest that anti-inflammatory medications may be protective against ovarian cancer; however, results have been inconsistent. METHODS: We evaluated the risk of epithelial ovarian cancer with regular use of NSAIDs prospectively in the NIH-AARP Diet and Health Study, using Cox proportional hazard models. We also examined the risk of common subtypes of epithelial ovarian cancer (serous, mucinous, endometrioid, clear cell, and other epithelial) with regular use of NSAIDs. In addition, we performed meta-analyses summarizing the risk of ovarian cancer with "regular use" of NSAIDs in previously published studies. RESULTS: We did not observe a significant association between regular use of NSAIDs with ovarian cancer risk in the AARP cohort (aspirin: RR 1.06, 95 % CI 0.87-1.29; non-aspirin NSAIDs: RR 0.93, 95 % CI 0.74-1.15); however, summary estimates from prospective cohort studies demonstrated that use of non-aspirin NSAIDs may reduce the risk of ovarian cancer (RR 0.88, 95 % CI 0.77-1.01). Although not significant, we found that mucinous tumors were inversely associated with non-aspirin NSAID use (RR 0.69, 95 % CI 0.23-2.10) in the AARP cohort, which was supported by the meta-analysis (RR 0.69, CI 0.50-0.94.) CONCLUSION: Although results from the NIH-AARP cohort study were not statistically significant, our meta-analysis suggests that non-aspirin NSAIDs may be protective against ovarian cancer. Additional analyses, focusing on dose, duration, and frequency of NSAID use and accounting for ovarian cancer heterogeneity are necessary to further elucidate the association between NSAID use and ovarian cancer risk.
PMID: 22972000 [PubMed - as supplied by publisher]
Frequency of mismatch repair deficiency in ovarian cancer: a systematic review This article is a US Government work and, as such, is in the public domain of the United States of America.
Frequency of mismatch repair deficiency in ovarian cancer: a systematic review This article is a US Government work and, as such, is in the public domain of the United States of America
Int J Cancer. 2011 Oct 15;129(8):1914-22
Abstract
Loss of mismatch repair (MMR) capacity may represent an important tumor initiating mechanism in ovarian cancer. We conducted a systematic review to analyze the frequency of microsatellite instability (MSI), immunohistochemical (IHC) staining for MMR proteins, and hypermethylation of the MLH1 promoter region in ovarian cancers. Studies examining MSI, loss of MMR gene expression by IHC staining and MLH1 promoter hypermethylation in ovarian cancer were identified by a systematic literature search of the PubMed electronic database through August 31, 2009. Pertinent data was extracted from eligible studies and estimates for pooled proportions were computed using random effects models. The pooled proportion of MSI detection was 0.10 (95% CI, 0.06-0.14) among 1,234 cases in 22 studies. Dinonucleotide markers had a higher frequency of instability than mononucleotide markers. The pooled proportion of MLH1 or MSH2 staining loss was 0.06 (95% CI, 0.01-0.17) among 474 cases in three studies, with a higher frequency of loss in MLH1. The pooled proportion of MLH1 methylation was 0.10 (95% CI, 0.06-0.15) among 672 cases in seven studies. Data reporting MSI and loss of MMR staining in the same cases was limited. Although MMR deficiency was found in all histologic subtypes, endometrioid cancers had the highest proportion.
Approximately 10% of unselected ovarian cancers are related to MMR deficiency. While MMR deficiency is associated with improved survival in other MMR-deficiency related cancer sites, epidemiological and clinical factors related to the MMR-deficient phenotype have not been adequately studied in ovarian cancer to date.
PMID: 21140452 [PubMed - indexed for MEDLINE]
Paclitaxel inhibits ovarian tumor growth by inducing epithelial cancer cells to benign fibroblast-like cells - Corrected Proof
Paclitaxel inhibits ovarian tumor growth by inducing epithelial cancer cells to benign fibroblast-like cells - Corrected Proof:
Highlights:
► Paclitaxel can induce the EMT of epithelial cancer.
► Fibroblast-like cells induced by paclitaxel are benign in nature.
► Epithelial cancer cells and benign fibroblasts may be interchangeable.
Abstract: Paclitaxel is commonly used to treat multiple human malignancies, but its mechanism of action is still poorly defined. Human ovarian cancer SKOV3 cells (parental SKOV3) were treated with paclitaxel (1μM) for 2days, and the morphologic changes in the cells were monitored for more than 4months. Parental SKOV3 underwent a markedly morphologic transition from the epithelial to fibroblast-like phenotype following treatment with paclitaxel; the resulting cells were designated as SKOV3-P. The SKOV3-P cells’ proliferative ability was assessed via a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. The molecular characteristics of these cells were assessed via immunocytochemical staining and Western blot analysis. Their invasiveness and tumor formation ability was evaluated via wound-scratch and colony formation assays. The tumorigenicity of SKOV3-P cells was assessed in vivo after subcutaneous injection of tumor cells between injections of parental and paclitaxel-treated cells in nude mice. SKOV3-P cells have decreased the proliferation and invasion ability, decreased colony-forming ability when cultured in Matrigel and lost their tumor formation as compared with parental SKOV3 cells when injected in nude mice. SKOV3-P cells have decreased expression of E-cadherin, cytokeratin, Snail, PI3K, and P-Akt-Ser473, and increased expression of fibronectin, vimentin, Slug, P27, and PTEN. These results demonstrated that paclitaxel can inhibit tumor growth by inducing ovarian cancer epithelial cells toward a benign fibroblast-like phenotype through dysregulation of previously known pathways involved in the regulation of epithelial to mesenchymal transition (EMT), which may represent a novel mechanism for paclitaxel-induced tumor suppression.
A Phase 2 Study of the IDO Inhibitor INCB024360 Versus Tamoxifen for Subjects With Biochemical-recurrent-only EOC, PPC or FTC Following Complete Remission With First-line Chemotherapy
A Phase 2 Study of the IDO Inhibitor INCB024360 Versus Tamoxifen for Subjects With Biochemical-recurrent-only EOC, PPC or FTC Following Complete Remission With First-line Chemotherapy:
Conditions: Biochemical-recurrent Only Epithelial Ovarian Cancer; Primary Peritoneal Carcinoma; Fallopian Tube Cancer
Interventions: Drug: INCB024360; Drug: tamoxifen
Sponsors: Incyte Corporation; Incyte Corporation
Recruiting - verified September 2012
A Phase 2 Study of the IDO Inhibitor INCB024360 Versus Tamoxifen for Subjects With Biochemical-recurrent-only EOC, PPC or FTC Following Complete Remission With First-line Chemotherapy
A Phase 2 Study of the IDO Inhibitor INCB024360 Versus Tamoxifen for Subjects With Biochemical-recurrent-only EOC, PPC or FTC Following Complete Remission With First-line Chemotherapy:
Conditions: Biochemical-recurrent Only Epithelial Ovarian Cancer; Primary Peritoneal Carcinoma; Fallopian Tube Cancer
Interventions: Drug: INCB024360; Drug: tamoxifen
Sponsors: Incyte Corporation;
Recruiting - verified September 2012
Cancer: Heat Bio vaccine to target bladder, ovarian cancers | MedCity News
"...Heat is in phase 2 clinical trials studying its vaccine candidate HS-110 to treat nonsmall cell lung cancer. The company plans to start additional clinical studies in bladder and ovarian cancer this year. Heat's proprietary Immune Pan-Antigen Cytotoxic Therapy, or ImPACT, reprograms live tumor cells to continually produce antigens that prompt the body's immune system to fight disease. ImPACT is used to make off-the-shelf vaccines that can be used by a general population of patients, unlike some of the personalized medicine therapies that are patient specific....
http://medcitynews.com/2012/01/vaccine-developer-heat-biologics-lands-250k-clinical-trials-for-bladder-ovarian-cancers-planned/
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Thursday, September 13, 2012
Wednesday, September 12, 2012
Immunobiology of human mucin 1 in a preclinical ovarian tumor model.
Immunobiology of human mucin 1 in a preclinical ovarian tumor model.
Immunobiology of human mucin 1 in a preclinical ovarian tumor model.
Oncogene. 2012 Sep 10;
Authors: Budiu RA, Elishaev E, Brozick J, Lee M, Edwards RP, Kalinski P, Vlad AM
Abstract
Epithelial ovarian cancer is an aggressive malignancy, with a low 5-year median survival. Continued improvement on the development of more effective therapies depends in part on the availability of adequate preclinical models for in vivo testing of treatment efficacy. Mucin 1 (MUC1) glycoprotein is a tumor-associated antigen overexpressed in ovarian cancer cells, making it a potential target for immune therapy. To create a preclinical mouse model for MUC1-positive ovarian tumors, we generated triple transgenic (Tg) mice that heterozygously express human MUC1(+/-) as a transgene, and carry the conditional K-rasG12D oncoallele (loxP-Stop-loxP-K-ras(G12D/+)) and the floxed Pten gene (Pten/(loxP/loxP)). Injection of Cre recombinase-encoding adenovirus (AdCre) in the ovarian bursa of triple (MUC1KrasPten) Tg mice triggers ovarian tumors that, in analogy to human ovarian cancer, express strongly elevated MUC1 levels. The tumors metastasize loco-regionally and are accompanied by high serum MUC1, closely mimicking the human disease. Compared with the KrasPten mice with tumors, the MUC1KrasPten mice show increased loco-regional metastasis and augmented accumulation of CD4+Foxp3+ immune-suppressive regulatory T cells. Vaccination of MUC1KrasPten mice with type 1 polarized dendritic cells (DC1) loaded with a MUC1 peptide (DC1-MUC1) can circumvent tumor-mediated immune suppression in the host, activate multiple immune effector genes and effectively prolong survival. Our studies report the first human MUC1-expressing, orthotopic ovarian tumor model, reveal novel MUC1 functions in ovarian cancer biology and demonstrate its suitability as a target for immune-based therapies.Oncogene advance online publication, 10 September 2012; doi:10.1038/onc.2012.397.
PMID: 22964632 [PubMed - as supplied by publisher]
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Combined expression of KLK4, KLK5, KLK6, and KLK7 by ovarian cancer cells leads to decreased adhesion and paclitaxel-induced chemoresistance.
Combined expression of KLK4, KLK5, KLK6, and KLK7 by ovarian cancer cells leads to decreased adhesion and paclitaxel-induced chemoresistance.
Abstract
OBJECTIVE: Chemoresistance is a critical feature of advanced ovarian cancer with only 30% of patients surviving longer than 5years. We have previously shown that four kallikrein-related (KLK) peptidases, KLK4, KLK5, KLK6 and KLK7 (KLK4-7), are implicated in peritoneal invasion and tumour growth, but underlying mechanisms were not identified. We also reported that KLK7 overexpression confers chemoresistance to paclitaxel, and cell survival via integrins. In this study, we further explored the functional consequenses of overexpression of all four KLKs (KLK4-7) simultaneously in the ovarian cancer cell line, OV-MZ-6, and its impact on integrin expression and signalling, cell adhesion and survival as contributors to chemoresistance and metastatic progression.
METHODS: Quantitative gene and protein expression analyses, confocal microscopy, cell adhesion and chemosensitivity assays were performed.
RESULTS: Expression of α5β1/αvβ3 integrins was downregulated upon combined stable KLK4-7 overexpression in OV-MZ-6 cells. Accordingly, the adhesion of these cells to vitronectin and fibronectin, the extracellular matrix binding proteins of α5β1/αvβ3 integrins and two predominant proteins of the peritoneal matrix, was decreased. KLK4-7-transfected cells were more resistant to paclitaxel (10-100nmol/L: 38-54%), but not to carboplatin, which was associated with decreased apoptotic stimuli. However, the KLK4-7-induced paclitaxel resistance was not blocked by the MEK1/2 inhibitor, U0126.
CONCLUSIONS: This study demonstrates that combined KLK4-7 expression by ovarian cancer cells promotes reduced integrin expression with consequently less cell-matrix attachment, and insensitivity to paclitaxel mediated by complex integrin and MAPK independent interactions, indicative of a malignant phenotype and disease progression suggesting a role for these KLKs in this process.
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Another lesson about over-aggressive screening - Health News Watchdog
SEP
12
Another lesson about over-aggressive screening
Posted by Gary Schwitzer in Screening
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Epithelial Ovarian Cancer Clinical Trial: Study With Wee-1 Inhibitor MK-1775 and…
Study With Wee-1 Inhibitor MK-1775 and Carboplatin to Treat p53 Mutated Refractory and Resistant Ovarian Cancer
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Loss-of-heterozygosity on chromosome 19q in early-stage serous ovarian cancer is associated with recurrent disease
Loss-of-heterozygosity on chromosome 19q in early-stage serous ovarian cancer is associated with recurrent disease
Background:Ovarian cancer is a heterogeneous disease and prognosis for apparently similar cases of ovarian cancer varies. Recurrence of the disease in early stage (FIGO-stages I-II) serous ovarian cancer results in survival that is comparable to those with recurrent advanced-stage disease. The aim of this study was to investigate if there are specific genomic aberrations that may explain recurrence and clinical outcome.
Methods:
Fifty-one women with early stage serous ovarian cancer were included in the study. DNA was extracted from formalin fixed samples containing tumor cells from ovarian tumors. Tumor samples from thirty-seven patients were analysed for allele-specific copy numbers using OncoScan single nucleotide polymorphism arrays from Affymetrix and the bioinformatic tool Tumor Aberration Prediction Suite. Genomic gains, losses, and loss-of-heterozygosity that associated with recurrent disease were identified.
Results:
The most significant differences (p < 0.01) in Loss-of-heterozygosity (LOH) were identified in two relatively small regions of chromosome 19; 8.0-8,8 Mbp (19 genes) and 51.5-53.0 Mbp (37 genes). Thus, 56 genes on chromosome 19 were potential candidate genes associated with clinical outcome. LOH at 19q (51-56 Mbp) was associated with shorter disease-free survival and was an independent prognostic factor for survival in a multivariate Cox regression analysis. In particular LOH on chromosome 19q (51-56 Mbp) was significantly (p < 0.01) associated with loss of TP53 function.
Conclusions:
The results of our study indicate that presence of two aberrations in TP53 on 17p and LOH on 19q in early stage serous ovarian cancer is associated with recurrent disease. Further studies related to the findings of chromosomes 17 and 19 are needed to elucidate the molecular mechanism behind the recurring genomic aberrations and the poor clinical outcome.
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Platelets increase the proliferation of ovarian cancer cells.
Platelets increase the proliferation of ovarian cancer cells.
Platelets increase the proliferation of ovarian cancer cells.
Blood. 2012 Sep 10;
Authors: Cho MS, Bottsford-Miller J, Vasquez HG, Stone R, Zand B, Kroll MH, Sood AK, Afshar-Kharghan V
Abstract
Platelets promote metastasis and angiogenesis but their effect on tumor cell growth is uncertain. Here we report a direct proliferative effect of platelets on cancer cells both in vitro and in vivo. Incubation of platelets with ovarian cancer cells from murine (ID8 and 2C6) or human (SKOV3 and OVCAR5) origin increased cell proliferation. The proliferative effect of platelets was not dependent on direct contact with cancer cells, and preincubation of platelets with blocking antibodies against platelet adhesion molecules did not alter their effect on cancer cells. The proliferative effect of platelets was reduced by fixing platelets with paraformaldehyde, preincubating platelets with a TGFβ1-blocking antibody, or reducing expression of TGFβR1 receptor on cancer cells with siRNA. Infusing platelets into mice with orthotopic ovarian tumors significantly increased the proliferation indices in these tumors. Ovarian cancer patients with thrombocytosis had higher tumor proliferation indices compared to patients with normal platelet counts.
PMID: 22966171 [PubMed - as supplied by publisher]
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False Promises on Ovarian Cancer - NYTimes.com Editorial
False Promises on Ovarian Cancer
Published: September 11, 2012
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Tuesday, September 11, 2012
OCNA: ovarian cancer screening
"The task force's recommendation underscores how badly we need an effective screening test forovarian cancer," said Cara Tenenbaum, Vice President for Policy and External Affairs at theOvarian Cancer National Alliance. "Ovarian cancer is the deadliest gynecologic cancer because it often isn't detected until the disease is in an advanced state."
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Fenretinide in Healthy Young Women at Genetic and Familial Risk - Full Text View - ClinicalTrials.gov
Eligibility| Ages Eligible for Study: | 20 Years to 46 Years |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 20-46 years old women with a known BRCA ½ mutation or with a risk of being a mutation carrier ≥20%.
- Performance status =0
- Willingness to avoid pregnancy during treatment and 12 months after drug cessation
- No clinical and radiological evidence of breast cancer and ovarian disease
- Signed informed consent
Exclusion Criteria:
- History of breast cancer or any other malignancy with the exclusion of CIN and non-melanoma skin cancer
- Child bearing or breast feeding
- Genetic test result (BRCA)=true negative
- Blood test alterations (grade ≥2 based on the NCI Common Toxicity Criteria)
- Previous or concurrent use of SERMs, e.g. tamoxifen (for more than 12 months; if less, a two-months wash-out is required before entering the study)
- Severe psychiatric disorders or inability to comply to the protocol procedures
- Any other factor that, at the investigator's discretion, contraindicates the use of fenretinide
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