Sunday, August 05, 2012

Sessile serrated adenomas: high-risk lesions?

Authors

Salaria SN, et al. Show all

Journal

Hum Pathol. 2012 Jul 9. [Epub ahead of print]

Affiliation

The Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.

Abstract

Sessile serrated adenomas (SSAs) were unrecognized in pathology and gastroenterology practice until about 2005; we have diagnosed them since 2001, allowing up to 10 years of follow-up. We evaluated follow-up of patients with sessile serrated adenoma diagnosed between 2002 and 2004 in our teaching institution and compared it to follow-up of randomly selected tubular adenomas. Materials from patients diagnosed with sessile serrated adenoma from January 2002 to December 2004 were reviewed. A control group of patients with sporadic tubular adenomas was selected. Ninety-nine sessile serrated adenomas from 93 patients were diagnosed between January 2002 and December 2004. Forty three patients (46.2%) had follow-up colonoscopy. One or more lesions were found in 42 (97.6%) of 43 patients. Mucinous adenocarcinoma was diagnosed in 1 (2.3%) of 43 patients, and 1 (2.3%) of 43 patients had high-grade dysplasia in an sessile serrated adenoma. Sessile serrated adenomas were found in 22 (51.2%) of 43 patients, 16 (37.2%) of 43 patients had tubular adenomas, and hyperplastic polyps were diagnosed in 18 (41.9%) of 43. Ninety-two patients with tubular adenomas between January 2002 and December 2004 formed the control group. Sixty-six patients (71.7%) received follow-up colonoscopy. Most (53/66, 80.3%) patients had tubular adenomas on follow-up, 12 (18.2%) of 66 patients had hyperplastic polyps, and 2 (3.0%) of 66 patients had a sessile serrated adenoma. The follow-up of sessile serrated adenomas from the study period (2002 to 2004) was more rigorous than proposed for sporadic tubular adenomas (patients with sporadic tubular adenomas were also followed up more aggressively than suggested by guidelines). Those with follow-up were managed as per advanced adenomas; their clinical outcomes supported this. These results suggest that guidelines for following up patients with sessile serrated adenomas as per advanced adenomas are warranted.

http://www.ncbi.nlm.nih.gov/m/pubmed/22784922/?i=1&from=high%20grade%20sessile%20polyps

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Saturday, August 04, 2012

Withaferin A Synergizes the Therapeutic Effect of Doxorubicin through ROS-Mediated Autophagy in Ovarian Cancer.

http://www.ncbi.nlm.nih.gov/m/pubmed/22860102/?i=1&from=ovarian%20cancer

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Friday, August 03, 2012

PPT lynch syndrome

> e/GIM/education/ContinuingEducation/Documents/6-14-2011_AhnenD.pdf

Endocyte Secures DOXIL(R) Supply to Support Ongoing Phase 3 PROCEED Trial in Ovarian Cancer |(+doxil)

http://www.virtual-strategy.com/2012/08/02/endocyte-secures-doxilr-supply-support-ongoing-phase-3-proceed-trial-ovarian-cancer

HealthLinx to commercialise assets in the U.S. after deal with Mane Cancer Diagnostics - Proactiveinvestors (AU) OvPlex

http://www.proactiveinvestors.com.au/companies/news/32037/healthlinx-to-commercialise-assets-in-the-us-after-deal-with-mane-cancer-diagnostics-32037.html

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Vermillion ovarian cancer test shows positive results OVA1

Genetic testing by cancer site: ovary

Genetic testing by cancer site: ovary.

Abstract

ABSTRACT: Approximately 1 in every 4 to 5 women with a diagnosis of ovarian cancer has a hereditary gene mutation that is responsible for the development of her cancer. Identifying women at increased risk of developing ovarian cancer due to a hereditary cancer syndrome can allow for early detection or prevention of not only ovarian cancer, but also other cancers, depending on the causative gene. This review focuses on 3 of the most common hereditary ovarian cancer syndromes, hereditary breast and ovarian cancer syndrome (the BRCA1 and BRCA2 genes), Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer syndrome), and Peutz-Jeghers syndrome, including key features, genetics, and management of these syndromes. In addition, newly discovered genes (eg, RAD51C and RAD51D) linked to ovarian cancer are discussed.

PMID

22846732 [PubMed - in process]

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Related Citations

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http://www.ncbi.nlm.nih.gov/m/pubmed/22846732/?i=9&from=lynch%20syndrome

Thursday, August 02, 2012

John Plater, lawyer who fought for tainted blood victims dead at 46 (patient safety WHO) media

(patient safety communities - WHO)
......
McCarthy remembers Plater being inseparable from fellow lawyer and hemophiliac James Kreppner who also contracted HIV and hepatitis C from tainted blood.

Kreppner also died of complications from HIV and hepatitis C in 2009 at the age of 47......"

http://metronews.ca/news/canada/321004/john-plater-man-who-fought-for-tainted-blood-victims-dead-at-46/

Risk of venous thromboembolism in patients with cancer

"Risk of Venous Thromboembolism in Patients with Cancer: A Systematic Review and Meta-Analysis"

Tuesday, July 31, 2012

Ovarian cancer in elderly patients: a difference in treatment based on age?

http://www.ncbi.nlm.nih.gov/m/pubmed/22843035/?i=11&from=ovarian%20cancer

Constitutive promoter methylation of BRCA1 and RAD51C in patients with familial ovarian cancer and early-.....

Journal Genet. 2012 Jul 27

Abstract

Genetic defects in breast cancer susceptibility genes, most importantly BRCA1 and BRCA2 account for approximately 40% of hereditary breast and ovarian cancers. Little is known about the contribution of constitutive (soma-wide) epimutations to the remaining cases. We developed bisulfite pyrosequencing assays to screen > 600 affected BRCA1/BRCA2 mutation-negative patients from the German Consortium for Hereditary Breast and Ovarian Cancer for constitutive hypermethylation of ATM, BRCA1, BRCA2, RAD51C, PTEN, and TP53 in blood cells. In a second step, patients with ≥ 6% promoter methylation were analyzed by bisulfite plasmid sequencing to demonstrate the presence of hypermethylated alleles (epimutations), indicative of epigenetic gene silencing. Altogether we identified 9 (1.4%) patients with constitutive BRCA1 and three (0.5%) with RAD51C hypermethylation. Epimutations were found in both sporadic cases, in particular in 2 (5.5%) of 37 patients with early-onset breast cancer, and familial cases, in particular 4 (10%) of 39 patients with ovarian cancer. Hypermethylation was always confined to one of the two parental alleles in a subset (1240%) of the analyzed cells. Because epimutations occurred in cell types from different embryonal layers, they most likely originated in single cells during early somatic development. We propose that analogous to germline genetic mutations constitutive epimutations may serve as the first hit of tumor development. Because the role of constitutive epimutations in cancer development is likely to be largely underestimated, future strategies for effective testing of susceptibility to breast and ovarian cancer should include an epimutation screen.

http://www.ncbi.nlm.nih.gov/m/pubmed/22843497/?i=10&from=ovarian%20cancer

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Open access - Multi-center evaluation of post-operative morbidity and mortality after optimal cytoreductive surgery for advanced ovarian cancer.

http://www.ncbi.nlm.nih.gov/m/pubmed/22844394/?i=4&from=ovarian%20cancer

Pre-targeting and direct immunotargetin - Open access

http://www.ncbi.nlm.nih.gov/m/pubmed/22844475/?i=3&from=ovarian%20cancer

Monday, July 30, 2012

Vermillion ovarian cancer test shows positive result

I thought you might be interested in this:

http://reut.rs/Q58BNC

I found this using the Thomson Reuters News Pro for iPhone app.

To install News Pro on your iPhone or iPad, visit:

http://reuters.com/mobile

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Study investigates molecular markers in drug-resistant ovarian cancer

A new study by TCD researchers investigates drug-resistant ovarian cancer cells. The findings which have been recently published in the international publication, PLoS One will increase understanding of molecular markers in drug-resistant ovarian cancer with a view to improving clinical treatment.

Worldwide there are more than 204,000 new cases of ovarian cancer each year, accounting for around 4% of all cancers diagnosed in women. For many cancers, including ovarian, chemotherapy remains the only treatment option. While chemotherapy has its success stories, the majority of ovarian cancer patients will go on to develop chemotherapy-resistant disease. Determining which chemotherapy drug to give a patient is a complicated process. Most decisions are made based on the type of cancer the patient has and how advanced it is. Currently, there is a shift towards individually tailoring chemotherapy to each patient. A personalised approach has improved treatment outcomes in breast cancer by targeting therapy according to its subtype.

In the case of ovarian cancer, research fellow and lead author Dr Britta Stordal says:
"If we can subdivide ovarian cancer patients into different resistance categories we can start personalising the treatment of this disease. The cost of patients receiving chemotherapy that they do not respond to is high, both personally for the patients and financially for the healthcare system. By understanding how chemotherapy resistance develops in ovarian cancer we can determine the best drug to prescribe to each patient. The individual tailoring of chemotherapy for relapsed patients can only improve cancer treatment in terms of increased response rates. "

The research studies drug-resistant ovarian cancer cells called IGROVCDDP. The cells were originally developed in a laboratory in the Netherlands. IGROV-1 cells, were firstly derived from an ovarian cancer patient. IGROV-1 cells were put through cycles of chemotherapy in the laboratory to simulate what a cancer patient receives in the clinic. The daughter cells produced are the IGROVCDDP cells, which were grown in tissue culture and examined as to how they became drug resistant.

IGROVCDDP cells are resistant to the two chemotherapy drugs used in the first line treatment of ovarian cancer, cisplatin and paclitaxel. By studying the IGROVCDDP cells we can identify genes and proteins that have changed and may be useful as molecular markers of chemotherapy resistance in the clinic. IGROVCDDP cells have many molecular markers of chemotherapy resistance and highlight the multiple mechanisms that can exist simultaneously in drug-resistant cancer cells. IGROVCDDP cells have increased levels of the drug-efflux pump, P-glycoprotein. This causes resistance to paclitaxel by pumping the drug out of the cancer cell. The study highlights that the P-glycoprotein can co-exist with multiple mechanisms of resistance to cisplatin. Cisplatin resistance is mediated in part by detoxification by the glutathione pathway and decreased uptake of drug into the cell. This is a step towards understanding how molecular markers of drug resistance interact and overlap in in ovarian cancer patients.

"We will now go on to examine molecular markers identified in IGROVCDDP in samples of tumours from ovarian cancer patients. Hopefully we will find markers that can separate patients who respond and those who do not respond to cisplatin and paclitaxel chemotherapy. Patients we think that will respond could be given the standard cisplatin/paclitaxel chemotherapy, and those who have a poor chance of responding could be given alternative treatment," concluded Dr Stordal.

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Study investigates molecular markers in drug-resistant ovarian cancer

http://www.news-medical.net/news/20120727/Study-investigates-molecular-markers-in-drug-resistant-ovarian-cancer.aspx

Sunday, July 29, 2012

Evaluation of HE4, CA125, Risk of Ovarian Malignancy Algorithm (ROMA) and Risk of Malignancy Index (RMI) as diagnostic tools of epithelial ovarian cancer in patients with a pelvic mass.

http://www.ncbi.nlm.nih.gov/m/pubmed/22835718/?i=6&from=ovarian%20cancer

Evaluation of HE4, CA125, Risk of Ovarian Malignancy Algorithm (ROMA) and Risk of Malignancy Index (RMI) as diagnostic tools of epithelial ovarian cancer in patients with a pelvic mass.

Abstract

OBJECTIVE: Diagnostic factors are needed to improve the currently used serum CA125 and Risk of Malignancy Index (RMI) in differentiating ovarian cancer (OC) from other pelvic masses, thereby achieving precise and fast referral to a tertiary centre and correct selection for further diagnostics. The aim was to evaluate serum Human Epididymis protein 4 (HE4) and the Risk of Ovarian Malignancy Algorithm (ROMA) for these purposes.

METHODS: Serum from 1218 patients in the prospective ongoing pelvic mass study was collected prior to diagnosis. The HE4 and CA125 data were registered and evaluated separately and combined in ROMA and compared to RMI.

RESULTS: 809 benign tumors, 79 borderline ovarian tumors, 252 OC (64 early and 188 late stage), 9 non-epithelial ovarian tumors and 69 non-ovarian cancers were evaluated. Differentiating between OC and benign disease the specificity was 62.2 (CA125), 63.2 (HE4), 76.5 (ROMA) and 81.5 (RMI) at a set sensitivity of 94.4 which corresponds to RMI=200. The Areas Under the Curve (AUC) were 0.854 (CA125), 0.864 (HE4), 0,897 (ROMA) and 0.905 (RMI) for benign vs. early stage OC. For premenopausal benign vs. OC AUC were 0.925 (CA125), 0.905 (HE4), 0.909 (ROMA) and 0.945 (RMI).

CONCLUSION: HE4 and ROMA increase differentiating OC from other pelvic masses, even in early stage OC. ROMA might be valuable as a first line biomarker for selecting high risk patients for referral to a tertiary centre and further diagnostics. Further improvements of HE4 and ROMA in differentiating pelvic masses are still needed, especially regarding premenopausal women.

Although bone pain in osteoporosis and skeletal metastasis is an expected consequence of fracture, there are other underlying causes responsible. Our study demonstrated that ovarian cancer G-protein-coupled receptor 1 detected extracellular protons in MG63 cells, and regulated osteoblast functions, such as prostaglandin E2 production, in response to acidic circumstances. In this work, we measured inositol phosphate production, intracellular Ca(2+) concentration, prostaglandin E2 production, and cyclic adenosine monophosphate accumulation in MG63 cells exposed to extracellular acidification. Extracellular acidity induced a transient increase in Ca(2+) concentration and inositol phosphate production. Acidification also induced prostaglandin E2 production, resulting in cyclic adenosine monophosphate accumulation. A small interfering RNA specific for the ovarian cancer G-protein-coupled receptor 1 markedly inhibited these proton-induced actions in MG63 cells. These results indicated that the involvement of ovarian cancer G-protein-coupled receptor 1 in acidic extracellular environment may be an underlying mechanism responsible for bone pain in osteoporosis or bone metastasis without clinically proved fractures.

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