Genetics, Inheritance and Strategies for Prevention in Populations at High Risk of Colorectal Cancer (CRC).

Genetics, Inheritance and Strategies for Prevention in Populations at High Risk of Colorectal Cancer (CRC).

Genetics, Inheritance and Strategies for Prevention in Populations at High Risk of Colorectal Cancer (CRC).

Recent Results Cancer Res. 2012;191:157-83

Authors: Burn J, Mathers J, Bishop DT

Abstract

Hereditary forms of colorectal cancer account for less than 5 % of colorectal cancer but attract disproportionate attention because they offer an opportunity for effective surgical prophylaxis, influence the health of the wider family and give insight into the critical pathways of carcinogenesis. Familial Adenomatous Polyposis (FAP) due to loss of the APC gene and Lynch syndrome or Hereditary Non-Polyposis Colon Cancer (HNPCC) due to breakdown in MisMatch Repair are the principal syndromes of broader interest and both have been the subject of chemoprevention trials. There has been a longstanding interest in non-steroidal anti inflammatories in FAP where trials have shown regression of polyps with the "pro drug"sulindac and the selective COX2 inhibitors though impact on long-term cancer risk is not confirmed. The CAPP1 trial focused on two interventions in a factorial design, aspirin and resistant starch or fermentable fibre. Resistant starch is not absorbed in the small intestine and undergoes colonic fermentation to short-chain fatty acids including butyrate which have anti-cancer effects. Polyposis registry clinicians across Europe recruited adolescents with FAP to receive aspirin (600 mg as 2 tablets/d) and/or 30 g as 2 sachets/d in a 1:1 blend of potato starch and high amylose maize starch [Hylon VII]) with placebo control for at least a year or until surgery before age 21. Fifty-nine percent (133/227) of recruits had a baseline and at least one other endoscopy. After a median of 17 months , the primary endpoint of a risk of an increased polyp number in the rectum and sigmoid colon was not significantly reduced in either treatment group with relative risks of 0.77 (aspirin; 95 % CI, 0.54-1.10;) and 1.05 (RS; 95 % CI, 0.73-1.49. The diameter of the largest polyp detected tended to be smaller in the aspirin arm. The planned subgroup analyses of patients who elected to continue on study for more than one year found a significant reduction in the size of the largest polyp in the aspirin versus non-aspirin group (p = 0.02), Mean crypt length decreased significantly over time on study in the two combined RS groups, compared with the two combined non-RS groups (p < 0.0001 for interaction), in a model of the interaction between intervention and time. In CAPP2, 1009 Lynch syndrome gene carriers were recruited from 43 international centres. 937 commenced intervention: 600mg enteric coated aspirin and/or 30grams of the resistant starch Novelose in a 2 by 2 factorial placebo controlled design. After a mean of 29 months, intervention, there was no evidence that either agent influenced ...

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http://m.prnewswire.com/news-releases/oncolytics-biotech-inc-completes-patient-enrollment-in-uk-phase-i-clinical-trial-investigating-reolysin-in-combination-with-cyclophosphamide-in-patients-with-advanced-malignances-166384116.html

Oncolytics Biotech® Inc. Completes Patient Enrollment in U.K. Phase I Clinical Trial Investigating REOLYSIN® in Combination with Cyclophosphamide in Patients with Advanced Malignances

CALGARY, Aug. 16, 2012 /PRNewswire/ - Oncolytics Biotech Inc. ("Oncolytics") (TSX:ONC) (NASDAQ:ONCY) today announced that it has completed patient enrollment in its U.K. Phase I clinical trial using intravenously-administered REOLYSIN in combination with cyclophosphamide in patients with advanced malignancies (REO 012).

"We are pleased to complete enrollment of this technical study examining cyclophosphamide's potential to modulate the immune system's response to REOLYSIN," said Dr. Matt Coffey, COO of Oncolytics. "Studies of this type help to advance our understanding of the interaction between the immune system and our product."

The primary objective of the open label, dose-escalating, non-randomized, 36-patient study is to determine the Minimum Effective Immunomodulatory Dose (MED) of cyclophosphamide necessary to obtain successful immune modulation. Secondary objectives of the trial include assessing the safety profile of the combination and gathering any evidence of antitumor activity.

Eligible patients include those who have been diagnosed with advanced or metastatic solid tumors, including pancreatic, lung and ovarian cancers that are refractory to standard therapy, or for which no standard curative therapy exists.

The principal investigators for the study are Dr. James Spicer of King's College, London, Dr. Johann de Bono and Dr. Kevin Harrington of the Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London, and Professor Hardev Pandha of the Royal Surrey County Hospital NHS Trust, Surrey and Mount Alvernia Hospitals.

About Oncolytics Biotech Inc.

Oncolytics is a Calgary-based biotechnology company focused on the development of oncolytic viruses as potential cancer therapeutics. Oncolytics' clinical program includes a variety of human trials including a Phase III trial in head and neck cancers using REOLYSIN, its proprietary formulation of the human reovirus. For further information about Oncolytics, please visit: www.oncolyticsbiotech.com.

This press release contains forward-looking statements, within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements, including the Company's expectations related to the U.K. Phase I clinical trial with REOLYSIN in combination with cyclophosphamide , and the Company's belief as to the potential of REOLYSIN as a cancer therapeutic, involve known and unknown risks and uncertainties, which could cause the Company's actual results to differ materially from those in the forward-looking statements. Such risks and uncertainties include, among others, the availability of funds and resources to pursue research and development projects, the efficacy of REOLYSIN as a cancer treatment, the tolerability of REOLYSIN outside a controlled test, the success and timely completion of clinical studies and trials, the Company's ability to successfully commercialize REOLYSIN, uncertainties related to the research and development of pharmaceuticals and uncertainties related to the regulatory process. Investors should consult the Company's quarterly and annual filings with the Canadian and U.S. securities commissions for additional information on risks and uncertainties relating to the forward-looking statements. Investors are cautioned against placing undue reliance on forward-looking statements. The Company does not undertake to update these forward-looking statements, except as required by applicable laws.

SOURCE Oncolytics Biotech Inc.

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Universal health coverage achieved by Mexico in less than a decade

Is the controversy on breast cancer as part of the Lynch-related tumor spectrum still open?

Increased incidence of brain metastases in BRCA1-related ovarian cancers.

http://www.ncbi.nlm.nih.gov/m/pubmed/22889437/?i=5&from=ovarian%20cancer

Consumer awareness and attitudes about insurance discrimination post enactment of the Genetic Information Nondiscrimination Act.

http://www.ncbi.nlm.nih.gov/m/pubmed/22890887/?i=3&from=ovarian%20cancer

Kramer explains results of the PLCO trial « NCI Benchmarks

http://benchmarks.cancer.gov/2012/08/kramer-explains-results-of-the-plco-trial/

Delays Plague Breast and Ovarian Cancer Research – The Jewish Daily Forward

-research

Launching a 'social networking war' against cancer

http://medicalxpress.com/news/2012-08-social-networking-war-cancer.html

Pre-test genetic counseling increases cancer knowledge for BRCA patients - podcast

http://m.medicalxpress.com/news/2012-08-pre-test-genetic-cancer-knowledge-brca.html

CCR: Pre-invasive ovarian mucinous tumors are characterized by CDKN2A and RAS pathway aberrations.

http://m.clincancerres.aacrjournals.org/content/early/2012/08/11/1078-0432.CCR-12-1103


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Health News - Mechanisms of Acquired Chemoresistance in Ovarian Cancer Identified

-Ovarian-Cancer-Identified.html?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+healthnewshc%2FOxfp+%28Health+News+from+HealthCanal.com%29&utm_content=Google+Reader

JTM | open access | Correlation of pretreatment drug induced apoptosis in ovarian cancer cells with patient survival and clinical response (MiCK assay)

JTM | Abstract | Correlation of pretreatment drug induced apoptosis in ovarian cancer cells with patient survival and clinical response

Conclusion

The MiCK assay can predict the chemotherapy associated with better outcomes in ovarian cancer patients. This study quantifies outcome benefits on which a prospective randomized trial can be developed.

BMC Palliative Care | Full text | A national study of chaplaincy services and end-of-life outcomes

BMC Palliative Care | Full text | A national study of chaplaincy services and end-of-life outcomes

open access: Constitutive promoter methylation of BRCA1 and RAD51C in patients with familial ovarian cancer and early-onset sporadic breast cancer

Constitutive promoter methylation of BRCA1 and RAD51C in patients with familial ovarian cancer and early-onset sporadic breast cancer

Olanzapine for the Relief of Nausea in Patients With Advanced Cancer and Incomplete Bowel Obstruction | DocGuide

Olanzapine for the Relief of Nausea in Patients With Advanced Cancer and Incomplete Bowel Obstruction | DocGuide

Cancer Australia Connect - July 2012 issue (includes resources, guidelines....)

Untitled Document

doc2doc forum: Why are 25% of deaths not being properly recorded?

http://tinyurl.com/dxg6gvn

Forums  »  Open clinical  »  General clinical  »  Why are 25% of deaths not being properly recorded?

Taking Action Health Equity in Canada - Canadian Doctors for Medicare

TakingActionHealthEquity

Incidence and predictors of venous thromboembolism (VTE) among ambulatory high-risk cancer patients undergoing chemotherapy in the United States - Khorana - 2012 - Cancer - Wiley Online Library

Abstract

BACKGROUND:

Recent studies suggest that thromboprophylaxis is beneficial in preventing venous thromboembolism (VTE) in cancer outpatients, but this is not widely adopted because of incomplete understanding of the contemporary incidence of VTE and concerns about bleeding. Therefore, the authors examined the incidence and predictors of VTE in ambulatory patients with bladder, colorectal, lung, ovary, pancreas, or gastric cancers.

METHODS:

Data were extracted from a large health care claims database of commercially insured patients in the United States between 2004 and 2009. Demographic and clinical characteristics of the cancer cohort (N = 17,284) and an age/sex-matched, noncancer control cohort were evaluated. VTE incidence was recorded during a 3-month to 12-month follow-up period after the initiation of chemotherapy. Multivariate analyses were conducted to identify independent predictors of VTE and bleeding.

RESULTS:

The mean age of the study population was 64 years, and 51% of patients were women. VTE occurred in 12.6% of the cancer cohort (n = 2170) over 12 months after the initiation of chemotherapy versus 1.4% of controls (n = 237; P < .0001); incidence ranged by cancer type from 19.2% (pancreatic cancer) to 8.2% (bladder cancer). Predictors of VTE included type of cancer, comorbidities (Charlson Comorbidity Index score or obesity), and commonly used specific antineoplastic or supportive care agents (cisplatin, bevacizumab, and erythropoietin).

CONCLUSIONS:

This large, contemporary, real-world analysis confirmed high rates of VTE in select patients with solid tumors and suggested that the incidence of VTE is high in the real-world setting. Awareness of the benefits of targeted thromboprophylaxis may result in a clinically significant reduction in the burden of VTE in this population. Cancer 2012. © 2012 American Cancer Society.

http://onlinelibrary.wiley.com/doi/10.1002/cncr.27772/abstract;jsessionid=48B8081B141F0857048BECC4CDB4F41D.d04t01

All-cause mortality and cancer incidence

http://www.ncbi.nlm.nih.gov/m/pubmed/22886909/

Roche’s Avastin may receive ovarian cancer recommendation from NICE if lower than approved dose is considered - FT.com

ADzHH

Social media in healthcare- a BMC Medicine twitter chat now on Storify!

Social media in healthcare- a BMC Medicine twitter chat now on Storify!

Following the publication of 'Medicine, morality and health care social media' in BMC Medicine, author Farris Timimi (Medical Director, Mayo Clinic Center for Social Media, @FarrisTimimi) and his colleague Lee Aase (Director, Mayo Clinic Center for Social Media, @LeeAase) joined BMC Medicine Editor Sabina Alam (@BMCMedicine) in a twitter chat to discuss the ideas raised in Timimi's commentary.

It was apparent there was consensus amongst the contributors of the twitter chat – social media should be used as a tool by healthcare providers to interact with patients. Some systems are already in place, but more work is required to develop the right kind of social media platforms, and perhaps more importantly, more physicians should be encouraged to learn how to use social media to engage with the general public. Whether the medical institutions should make this a requirement remains to be determined.

A summary of the discussion with a selection of the contributions can be viewed at Storify.

Following the success of this chat we are considering having more in the future. If you feel there are any topics that should be discussed please get in touch via email, or of course tweet at us ! (@BMCMedicine)

Patients with Lynch Syndrome Mismatch Repair Gene Mutations Are at Higher Risk for Not Only Upper Tract Urothelial Cancer but Also Bladder Cancer.

Patients with Lynch Syndrome Mismatch Repair Gene Mutations Are at Higher Risk for Not Only Upper Tract Urothelial Cancer but Also Bladder Cancer.

Patients with Lynch Syndrome Mismatch Repair Gene Mutations Are at Higher Risk for Not Only Upper Tract Urothelial Cancer but Also Bladder Cancer.

Eur Urol. 2012 Aug 2;

Authors: Skeldon SC, Semotiuk K, Aronson M, Holter S, Gallinger S, Pollett A, Kuk C, van Rhijn B, Bostrom P, Cohen Z, Fleshner NE, Jewett MA, Hanna S, Shariat SF, Van Der Kwast TH, Evans A, Catto J, Bapat B, Zlotta AR

Abstract

BACKGROUND: Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer, is caused by mutations in mismatch repair (MMR) genes. An increased risk for upper tract urothelial carcinoma (UTUC) has been described in this population; however, data regarding the risk for bladder cancer (BCa) are sparse. OBJECTIVE: To assess the risk of BCa in MMR mutation carriers and suggest screening and management recommendations. DESIGN, SETTING, AND PARTICIPANTS: Cancer data from 1980 to 2007 were obtained from the Familial Gastrointestinal Cancer Registry in Toronto for 321 persons with known MMR mutations: mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) (MLH1); mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) (MSH2); mutS homolog 6 (E. coli) (MSH6); and PMS2 postmeiotic segregation increased 2 (S. cerevisiae) (PMS2). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Standardized incidence ratios from the Ontario Cancer Registry, using the Surveillance Epidemiology and End Results public database, were used to compare cancer risk in patients with MMR mutations with the Canadian population. Microsatellite instability analysis and immunohistochemistry (IHC) of the MMR proteins were also performed and the results compared with matched sporadic bladder tumors. RESULTS AND LIMITATIONS: Eleven of 177 patients with MSH2 mutations (6.21%, p<0.001 compared with the Canadian population) were found to have BCa, compared with 3 of 129 patients with MLH1 mutations (2.32%, p>0.05). Of these 11 tumors, 81.8% lacked expression of MSH2 on IHC, compared with the matched sporadic cases, which all displayed normal expression of MSH2 and MLH1. The incidence of UTUC among MSH2 carriers was 3.95% (p<0.001), and all tumors were found to be deficient in MSH2 expression on IHC. Mutations in the intron 5 splice site and exon 7 of the MSH2 gene increased the risk of urothelial cancer. Limitations include possible inflated risk estimates due to ascertainment bias. CONCLUSIONS: LS patients with MSH2 mutations are at an increased risk for not only UTUC but also BCa and could be offered appropriate screening.

PMID: 22883484 [PubMed - as supplied by publisher]

[Ovarian cancer--modern approach to its origin and histogenesis].

[Ovarian cancer--modern approach to its origin and histogenesis].

[Ovarian cancer--modern approach to its origin and histogenesis].

Abstract

Ovarian cancers (OC) belong to a heterogeneous group of pathologies and are traditionally classified with regard to histological type and degree of differentiation. OC was hypothesized to originate from ovarian surface epithelium (OSE) and inclusion cysts epithelium (IC). Unfortunately this theory was never supported by any clinical or molecular evidence linking carcinogenesis with OSE and was refuted. OC subtypes demonstrate morphologic features that resemble Müllerian duct-derived epithelia of the genital tract. Investigations of the HOX gene family Müllerian epithelial differentiation markers, confirmed the HOX genes expression in many subtypes of OC but not in OSE. The first step towards connecting OC origin with other than OSE genital tract structures were epidemiological observations indicating a minor OC risk after tubal ligation in women with the BRCA mutation. The first in situ carcinoma was found in the Fallopian tube fimbriae. Further research confirmed the same mechanism in sporadic OC. Endometriosis and endometrium cells may be a highly probable place of endometrioid OC initiation. Mucinous types share common futures with gastrointestinal tract cancers and there one needs to search for their precursors. Clear cell carcinoma may arise from glandular epithelium of endocervix or from endometrioid foci. The new classification of OC was proposed in 2004, suggesting to divide all OC into two types: I and II. Type II includes serous and endometrioid G3 subtypes, carcinosarcomas and undifferentiated OC. They are responsible for 75% of OC morbidity identified usually in FIGO stages Ill or IV, have poor prognosis and relapse early The remaining hystiotypes, with better prognosis and earlier FIGO stages at time of diagnosis, were classified as type I. Serous and endometrioid poorly differentiated ovarian cancers demonstrate mutation in TP53 gene (type II) and highly differentiated ones, generally in BRAS and KRAS genes (type I). The differences in molecular pathways also confirm different patterns of carcinogenesis of both OC types. Modern approach to OC histogenesis and origin emphasizes the necessity to verify OC screening, detection and treatment methods.

PMID: 22880466 [PubMed - in process]