Friday, April 19, 2013
Partial duplication of MSH2 spanning exons 7 through 14 in Lynch syndrome
Abstract
BACKGROUND:
Lynch syndrome, also referred to as hereditary nonpolyposis colorectal cancer, is the most common form of hereditary colorectal cancer, and is associated with a high incidence of multiple primary neoplasms in various organs.METHODS:
A 79-year-old woman (patient 1) diagnosed with ascending colon cancer had a history of previous carcinomas of the uterus, stomach, uroepithelial tract, and colon. One year later, she developed a brain tumor (glioblastoma). A 54-year-old female (patient 2) was diagnosed with endometrial cancer and sigmoid colon cancer. Both patients underwent genetic evaluations independently.RESULTS:
No mutations were found in an exon-by-exon analysis of genomic DNA by polymerase chain reaction (PCR) and reverse transcription (RT)-PCR. However, multiplex ligation-dependent probe amplification (MLPA) identified genomic duplication spanning from exon 7 to exon 14 of the MSH2 gene in both patients.Another NICE knockback for Avastin/ovarian cancer
Article
April 19, 2013
Avastin
will continue not to be funded by the NHS for ovarian cancer as the
drug pricing watchdog for England has again rejected its approval.
In its latest round of draft guidance NICE has said Roche’s Avastin (bevacizumab) is not recommended as an NHS treatment for a type of recurrent, advanced ovarian cancer.
This latest decision, which has been produced following a public consultation on earlier initial recommendations against the drug, again concluded that Avastin - when used with the chemotherapy drugs, Lilly’s Gemzar (gemcitabine) and carboplatin - does not represent good value for money for the NHS.
In its latest round of draft guidance NICE has said Roche’s Avastin (bevacizumab) is not recommended as an NHS treatment for a type of recurrent, advanced ovarian cancer.
This latest decision, which has been produced following a public consultation on earlier initial recommendations against the drug, again concluded that Avastin - when used with the chemotherapy drugs, Lilly’s Gemzar (gemcitabine) and carboplatin - does not represent good value for money for the NHS.
Article > UK pharma scientist jailed over trial fraud
Article
April 19, 2013
A UK-based pharma scientist has been sentenced to three months in prison for altering pre-clinical trial data designed to support applications to perform human trials.....
Cochrane signs up to AllTrials initiative to campaign for registration and reporting of all clinical trials
The Cochrane Collaboration
London, UK – April 19, 2013 – The Cochrane Collaboration,
the international not-for-profit organization that produces systematic
reviews of healthcare evidence and the largest database of randomized
controlled trials, published online in The Cochrane Library, has today formalized its commitment to the AllTrials: All Trials Registered | All Results Reported initiative to campaign for the registration and reporting of all clinical trials.
The
AllTrials campaign aims to draw attention to the crisis of unreported
trial data. Hundreds of thousands of clinical trials have been conducted
from which no or limited data have been made available; data critical
to enabling doctors and regulators to make informed decisions about
which treatments to use and fund. This is a serious problem for
evidence-based healthcare researchers including The Cochrane
Collaboration, because all the evidence about a treatment is needed to
understand its risks and benefits. Without a complete picture of trial
results available, information is lost; bad treatment decisions may be
made; financial investment into ineffective treatments are approved by
governments and regulators; opportunities for better and more effective
treatment are missed; and trials are repeated unnecessarily, duplicating
effort and wasting resources.
AllTrials was launched in January 2013.........
Health Canada to propose interim solution to close cancer drugs oversight gap - Life - Times Colonist
media
".... Both the Ontario and federal governments have acknowledged that they don't know how many companies like Marchese are mixing cancer drugs for hospitals with no oversight.
Too much saline was added to the bags containing cyclophosphamide and gemcitabine, in effect watering down the prescribed drug concentrations by up to 20 per cent. Some patients were taking the drugs for as long as a year."
Commentary: ACMG recommendations on incidental findings: a commentary
open access
"....There is little to commend in the set of recommendations except the fact that it will generate much discussion about the return of findings, both pertinent and incidental, in WGS. The strategy that has been recommended is an acceptable and possible option that certain patients may wish to consider; but not to give patients the choice of other options, or to deny them the test if they decline to receive information about secondary variants is a coercive strategy that should have no place in the modern practice of medicine."
Abagovomab As Maintenance Therapy in Patients With Epithelial Ovarian Cancer: A Phase III Trial of the AGO OVAR, COGI, GINECO, and GEICO—The MIMOSA Study
Abstract
Purpose To determine whether abagovomab maintenance therapy prolongs recurrence-free (RFS) and overall survival (OS) in patients
with ovarian cancer in first clinical remission.
Patients and Methods
Patients with International Federation of Gynecology and Obstetrics
stage III to IV ovarian cancer in complete clinical remission
after primary surgery and platinum- and
taxane-based chemotherapy were randomly assigned at a ratio of 2:1 in a
phase III,
double-blind, placebo-controlled, multicenter
study. Abagovomab 2 mg or placebo was administered as 1-mL suspension
once every
2 weeks for 6 weeks (induction phase) and then
once every 4 weeks (maintenance phase) until recurrence or up to 21
months
after random assignment of the last patient. The
primary end point was RFS; secondary end points were OS and immunologic
response.
Results
Characteristics of the 888 patients included: mean age, 56.3 years;
Eastern Cooperative Oncology Group performance status,
≤ 1 in > 99% of patients; serous papillary
subtype, 81.5%; stage III, 85.9%; and cancer antigen 125 ≤ 35U/mL after
third cycle,
80.9%. Mean exposure to study treatment (±
standard deviation) was 449.7 ± 333.08 days. Hazard ratio (HR) of RFS
for the treatment
group using tumor size categorization (≤ 1 cm,
> 1 cm) was 1.099 (95% CI, 0.919 to 1.315; P = .301). HR of OS using tumor size categorization (≤ 1 cm, > 1 cm) was 1.150 (95% CI, 0.872 to 1.518; P
= .322). The most frequently reported type of adverse event was an
injection site reaction in 445 patients (50.2%), followed
by injection site erythema and fatigue in 227
(25.6%) and 212 patients (23.9%), respectively. By the final visit,
median anti–anti-idiotypic
antibody level was 493,000.0 ng/mL, indicating a
robust response.
Conclusion Abagovomab administered as repeated monthly injections is safe and induces a measurable immune response. Administration as
maintenance therapy for patients with ovarian cancer in first remission does not prolong RFS or OS.
JCO - the Art of Oncology series: Doctor, Where Art Thou?
open access
"....M.M. and L.B. taught me to be available to my patients, even after I am no longer administering medications and even after other physicians are primarily directing their care. Even though I still believe that end-of-life care is complex and probably best primarily managed by palliative care and hospice providers, I have decided to make staying in touch with my dying patients a personal goal. For my patients and their families and for me as a developing oncologist, I need to learn how to keep a connection to the end with those whom I have promised to take care of."
2013 Ovarian Cancer National Alliance Conference - RegOnline
RegOnline
Hyatt Regency Washington on Capitol Hill
400 New Jersey Avenue NW
Washington, DC 20001
United States
400 New Jersey Avenue NW
Washington, DC 20001
United States
For registration questions and assistance:
Rose Draper
AMC Network
Phone: (707) 829-9484
Email: ocnareg@amcnetwork.com
Mammogram rate did not decline after controversial USPSTF recommendations
press release
Boston – More than three years after the United States Preventive Services Task Force (USPSTF) recommended against routine mammogram screening for women between the ages of 40 and 49, a study from Brigham and Women's Hospital (BWH) finds that mammogram rates in the United States have not declined in that age group, or any other. The study results are published in the April 19, 2013 online edition of the journal Cancer.
"If the USPSTF recommendations had been widely adopted, we would have expected to see a significant decline in mammography rates among women in their forties," said the study's lead author, Lydia Pace, MD, MPH, a global women's health fellow in the Division of Women's Health at BWH. "However, this study demonstrates that younger women are continuing to get mammograms."
Self administered screening for hereditary cancers in conjunction with mammography and ultrasound - Online First - Springer
Abstract
We evaluated the
feasibility of an automated tablet computer application providing a
family and personal history based cancer risk assessment for hereditary
breast, ovarian, endometrial and colorectal cancers. 1,002 women
presenting for screening mammography and 1,000 presenting for ultrasound
were offered screening. The application calculated the risk of BRCA
mutations using BRCAPRO, Myriad and Tyrer–Cuzick risk assessment models.
Lifetime risk of breast and ovarian cancer was assessed with the
BRCAPRO, Claus and Tyrer–Cuzick models. Colorectal and endometrial
cancer risk was calculated via the MMRpro model. Patients were
identified as high-risk based on thresholds 10 % or greater risk for
carrying genetic mutations or 20 % or greater lifetime risk of breast or
ovarian cancer. The percent of women found to be high-risk by a single
risk assessment tool ranged from 0.5 to 5.3 %. Combining assessment
tools found 9.3 % of women to be high-risk. The risk assessments
performed similarly for the mammography and ultrasound cohorts with
yields (combining assessment tools) of 9.2 and 9.4 % respectively. The
average ages of all the high-risk women were 45.8 and 39.6 years for the
mammography and ultrasound cohorts respectively. Difficulties
encountered included a need for software upgrade, wireless network
unreliability and hardware theft. Automated family history screening can
identify women probably at high-risk for hereditary cancers
efficiently. The number of women identified is increased by employing
multiple risk assessment models simultaneously. Surveying women in
conjunction with ultrasound identified women at increased risk as
effectively and at a younger age than with screening mammography.
Thursday, April 18, 2013
Ginkgo May Sensitize Ovarian Cancer Cells to Cisplatin
Abstract
Ginkgolide B (GB), the primary active component of Ginkgo biloba extracts, may have antitumor properties. The objective of this study was to determine the effects and possible mechanisms of GB in ovarian cancer cells. In this study, human ovarian cancer cell lines (SKOV3 and CAOV3) were treated with different concentrations of GB alone or in combination with Cis-diaminodichloroplatinum (CDDP). An MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was performed to determine cell viability. The apoptosis rates of cells were measured by flow cytometric analysis. The expression of apoptosis-associated and proliferation-associated proteins was detected by Western blot. The cytotoxicity of GB was analyzed using a lactate dehydrogenase assay. Treatment with 100 µM GB for 3 days significantly inhibited SKOV3 and CAOV3 cell proliferation by 57.3% and 63.1% compared with control cells, respectively, as determined by MTT assay. Similarly, the apoptotic cell population was increased when treated with GB in a dose-dependent manner both in SKOV3 and CAOV3 cells. These effects were characterized by the upregulation of p21, p27, cleaved capase-3, and cleaved caspase-8 and downregulation of cyclin D1. In addition, a combined treatment of low concentrations of GB and CDDP showed an additive effect on the inhibition of SKOV3 cell proliferation. Furthermore, GB had significantly less cytotoxicity than CDDP in normal human ovarian surface epithelial cells. This study suggests that GB can be proposed as an effective antiproliferative and apoptosis-inducing agent with interesting translational application in ovarian cancers, used in addition to conventional chemotherapy.
PLOS ONE: Fluid-Flow Induced Wall Shear Stress and Epithelial Ovarian Cancer Peritoneal Spreading
open access
Introduction
Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer deaths among women, and has the highest fatality-to-case ratio of all gynecologic malignancies. The development of EOC begins at the surface epithelium and is followed by aggressive proliferation of EOC cells into the ovary. Metastases of EOC are formed early in the disease process by spreading of EOC cells mainly in the peritoneal cavity. The ovarian surface is continuously exposed to peritoneal fluid pressures and shear forces due to the bowel peristaltic motions. This mechanical micro-environment was hypothesized to be a prominent factor controlling the patterns of tumor spreading [1], [2]......A multicenter prospective external validation of the diagnostic performance of IOTA simple descriptors and rules to characterize ovarian masses
Abstract
Highlights
- •
- We externally validated IOTA clinically oriented strategy to characterize adnexal masses in three hospitals.
- •
- 1165 ultrasound scans performed over more than two years by 36 level II ultrasonography examiners.
- •
- The three-step clinical oriented strategy performs as good as the main IOTA study and better than the conventional RMI.
Objectives
To
evaluate the diagnostic performance of the IOTA (International Ovarian
Tumor Analysis group) (clinically oriented three-step strategy for
preoperative characterization of ovarian masses when ultrasonography is
performed by examiners with different background training and
experience.
Complete remission of recurrent and refractory ovarian cancers using weekly administration of bevacizumab and gemcitabine/oxaliplatin: report of two cases
Abstract
BACKGROUND:
A combination therapy with gemcitabine and oxaliplatin (GEMOX) yielded a moderate activity in platinum-resistant ovarian cancers; however, frequent severe toxicities, such as thrombocytopenia and neurotoxicity, were observed. A certain modification of schedule might therefore facilitate the clinical application of the regimen. The authors report two cases that achieved complete response to a weekly administration of bevacizumab and GEMOX.MATERIALS AND METHODS:
Two patients with platinum-resistant recurrent ovarian cancers received a weekly regimen of GEMOX with bevacizumab: 2 mg/kg of bevacizumab, 300 mg/m2 of gemcitabine, and 30 mg/m2 of oxaliplatin, three weeks on and one week off, Q4 weeks. Complete remission was observed after three to four courses of therapy. Hematologic and non-hematologic toxicities more than grade 2 were not observed during chemotherapy. The patients are now without tumor progression more than 12 months after initiation of therapy.CONCLUSION:
Weekly administration of bevacizumab and GEMOX had potential activity in recurrent and refractory ovarian carcinomas. These findings warrant necessity of further trial in such clinical settings.Identified as responsible for breast and ovarian hereditary cancer 3 mutations at BRCA1 gene | Science Codex
Science Codex
"....From this analysis, the researchers concluded that three of the seven variants of unknown biological significance are actually pathogenic and will serve clinicians to a better genetic counseling to patients and families that present these variants, allowing personalized risk assessment cancer....
New Perspectives of Curcumin in Cancer Prevention
Abstract
Numerous natural compounds have been extensively investigated for their potential for cancer prevention over the decades. Curcumin, from Curcuma longa, is a highly promising natural compound that can be potentially used for chemoprevention of multiple cancers. Curcumin modulates multiple molecular pathways involved in the lengthy carcinogenesis process to exert its chemopreventive effects through several mechanisms: promoting apoptosis, inhibiting survival signals, scavenging reactive oxidative species (ROS), and reducing the inflammatory cancer microenvironment. Curcumin fulfills the characteristics for an ideal chemopreventive agent with its low toxicity, affordability, and easy accessibility. Nonetheless, the clinical application of curcumin is currently compromised by its poor bioavailability. Here, we review the potential of curcumin in cancer prevention, its molecular targets, and mechanisms of action. Finally, we suggest specific recommendations to improve its efficacy and bioavailability for clinical applications. Cancer Prev Res; 1–14. ©2013 AACR.
Subscribe to:
Posts
(
Atom
)
