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Saturday, February 04, 2012

open access: The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation (references major epithelial OC cell types including clear cell)



Background
The neural transcription factor SOX11 has been described as a prognostic marker in epithelial ovarian cancers (EOC), however its role in individual histological subtypes and tumour grade requires further clarification. Furthermore, methylation-dependent silencing of SOX11 has been reported for B cell lymphomas and indicates that epigenetic drugs may be used to re-express this tumour suppressor, but information on SOX11 promoter methylation in EOC is still lacking.

Results
SOX11 expression was associated with an improved survival of patients with high grade EOC, although not independent of stage.
 
"SOX11 is a diagnostic and prognostic antigen in B cell lymphomas [12-17] and has recently been demonstrated by us to have tumour suppressor functions [18]. This transcription factor is also a prognostic antigen in EOC, where its presence is associated with improved recurrence-free survival (RFS) [19]. In the present study, we confirm the relationship between SOX11 and survival in EOC, although a larger set of endometrioid cancer needs to be investigated to show independent prognostic relevance."
 
Conclusions:

In the present study, SOX11 was demonstrated to be of prognostic value for high grade EOC, which could have a clear clinical value. The possibility to re-express SOX11 indicates a potential use of epigenetic drugs to affect cell growth through common cell regulatory pathways, controlled by SOX11, and other tumour suppressors that are silenced in EOC. 
 
Furthermore, functional investigations in vitro confirmed a growth regulatory role for SOX11 in EOC.
 
Competing interests
A patent has been filed on the use of SOX11 as a diagnostic and prognostic antigen in EOC.

open access: Intraoperative radiotherapy electron boost in advanced and recurrent epithelial ovarian carcinoma: a retrospective study - 45 pts



Blogger's Note: interesting study worth reading


Background
The aim of this study was to evaluate the clinical outcome and toxicity of intraoperative electron beam radiation therapy (IOERT) in advanced and recurrent EOC.

Conclusions
IOERT may be feasible and effective as a boosting technique for advanced and recurrent ovarian cancer. IOERT plus IP chemotherapy may achieve high locoregional disease control and survival benefit with a low risk of toxicity. Peripheral nerves in the IOERT field are dose-limiting structures requiring nerve protection policies or a dose compromise to ensure against severe neurological damage.

Patients
This study was a non-randomized trial and included retrospective analysis of 45 women with EOC who were treated with IOERT at the 1st Affiliated Hospital of the Medical College of Xi'an Jiaotong University between January 2000 and January 2010.........The mean follow-up time was 78 months (range: 11-123 months).........

Table 1
Patient Characteristics

TotalPDILR
Cases452520
Histology type


serous adenocarcinoma362116
papillary adenocarcinoma944
CA-125 level


≥ 35 U/ml382018
< 35 U/ml431
unknown321

Conclusions
IOERT may be feasible and effective as a boosting technique to treat advanced and recurrent ovarian cancers. IOERT plus IP chemotherapy may achieve high locoregional disease control and survival benefit with a low risk of toxicity. However, careful attention should be paid to peripheral nerves as specific IOERT dose-limiting structures.

abstract: Evaluation of microRNA expression profiles and their associations with risk alleles in lymphoblastoid cell lines of familial ovarian cancer



Lymphoblast - Wikipedia, the free encyclopedia

en.wikipedia.org/wiki/Lymphoblast
Lymphoblasts are immature cells which typically differentiate to form mature ... Although commonly lymphoblast refers to a precursor cell in the maturation of ...

open access: Cancer screening in the United States, 2012 - CA: A Cancer Journal for Clinicians





open access: Cancer risks associated with external radiation from diagnostic imaging procedures - Linet - 2012 - CA: A Cancer Journal for Clinicians



Blogger's Note: extensive (long) analysis; important to assess individual circumstances and as the research article indicates - risk vs benefit

 

Recommendations for Clinicians

  • 1
    Become knowledgeable about the radiation doses for the imaging studies.
  • 2
    Consider ultrasound and MRI when these are appropriate alternatives since these procedures do not subject the patient to ionizing radiation.172, 236
  • 3
    Do not order a higher radiation dose study if a lower dose study (or an imaging study that does not use ionizing radiation) can provide the clinical information needed.
  • 4
    All requests for imaging studies should be justified (eg, when all benefits and risks are considered, the study should be expected to do more good than harm).
  • 5
    Available aids for justification, such as the ACR's Appropriateness Criteria and the ACC's Appropriate Use Criteria for Cardiac Computed Tomography, should be utilized to provide guidance for choosing the most appropriate imaging examination.
  • 6
    Unnecessary imaging studies (duplicate studies and those that are not medically necessary) should not be performed.
  • 7
    In general, neither screening nor elective x-ray examinations should be performed on pregnant women.
  • 8
    Refer patients who require imaging studies to a facility that strives to optimize radiation dose, so that imaging is performed with the least amount of radiation necessary to provide adequate image quality.

How the CA-125 became a $50,000 blood test (blog) including public/professional responses



How the CA-125 became a $50,000 blood test

The New Old Age - Caring and Coping (looking after your pet/s) - 'pet trust' document



Australia: media - Charities push for overhaul of cancer funding 03/02/2012



ASHLEY HALL: "Cancer charities are calling for a massive overhaul of the $300 million fundraising and research sector.

They're becoming concerned about what they say is duplication and waste within the cancer research field.

The head of the Cancer Council of Australia says the attention paid to breast, cervix and ovarian cancer comes at the expense of other high mortality cancers including lung and pancreatic cancer....."

Art and Science: Color Explosion A fluorescence microscopy image (ovarian cancer cells/dna) competition straddles the boundary of science and art.



Research assistant at MD Anderson Cancer Center, Geoffrey Grandjean, obtained this image showing human ovarian cancer cells stained for DNA (red) and microtubules (green), during an siRNA screening. The particular gene knockdown in this screen disrupted cell division, causing the giant cell in the middle to grow very large.

The IN Cell Analyzer Image Competition winners 2011

Winning image for Asia PacificLeslie Caron
GENEA, Australia
Winning image for the AmericasGeoffrey Grandjean
MD Anderson Cancer Center, USA
Winning image for EuropeMarie Neguembor
ALEMBIC - San Raffaele Scientific Institute, Italy
Vascular smooth muscle cells differentiated from human embryonic stem cells stained for DNA (blue) and the smooth muscle markers Smoothelin (red) and Caldesmon
(green).
Enlarge
Human ovarian cancer cells stained for DNA (red) and microtubules (green).


Enlarge
Myoblast stained for DNA (blue), Myosin heavy chain (green) and methylated Histone H4 (red).

Enlarge

press release: Avoid a Pet Emergency in Overtime: Super Sunday's Parties Can Be Dangerous, Feb. 3, 2012



abstract: Importance of Histologic Subtype in the Staging of Appendiceal Tumors.




Blogger's Note: common feature is mucinous cell type; understudied is familial appendiceal carcinoid

BACKGROUND:

Malignant neoplasms of the appendix have different behavior based on their histologic subtypes in anecdotal series. Current staging systems do not capture the diversity of histologic subtypes in predicting outcomes.

METHODS:

We queried all patients with appendiceal malignancies captured in the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2007. Tumors were classified as colonic type adenocarcinoma, mucinous adenocarcinoma, signet ring cell type, goblet cell carcinoid, and malignant carcinoid. We compared incidence, overall survival, and disease-specific survival for these tumors on the basis of patient, tumor, and therapy characteristics. Estimates from Cox proportional hazard modeling were used to predict hazard ratios for differing histologic subtypes with similar tumor, node, metastasis system (TNM) stages.

RESULTS:

Of the 5672 patients identified, we included 5655 (99%) in our analysis. The 5-year disease-specific survival rates were 93% for malignant carcinoid, 81% for goblet cell carcinoid, 55% for colonic type adenocarcinoma, 58% for mucinous adenocarcinoma, and 27% for signet ring cell type. Predicted estimates of adjusted hazard ratios revealed an 8-fold difference between histologic subtypes for similar TNM stages.

CONCLUSIONS:

Histologic subtype is an important predictor of disease-specific survival and overall survival in patients with appendiceal neoplasms. Addition of the histologic subtype to the TNM staging is simple and may improve prognostication.

abstract: Use of Mismatch Repair Immunohistochemistry and Microsatellite Instability Testing: Exploring Canadian Practices




METHODS:

Two web-based questionnaires were administered, a general and a specialist laboratory questionnaire, to establish the availability of such tests, requisite clinical/pathology integration, current mode of test initiation, reporting and recommendation practices, and education and attitudes among pathologists. Technical aspects were reviewed on the basis of specialist laboratory practice.

RESULTS:

Of 76 respondents, 21.5% were unaware or were uncertain whether they had access to MMR immunohistochemistry. Although 78.9% of respondents had access to such testing, an integrated approach to the identification of patients with LS is lacking, being limited to just 9 centers. The majority (70%) of testing is clinician initiated, with variable implementation of reflex testing and divergent practices in recommendation to test. Standardized reporting is lacking in many centers. Education on MMR in endometrial cancer is poor compared with that in colorectal cancer (P<0.0001).

(Blogger's Note: and so it would be safe to assume, based on this abstract, that the full spectrum of Lynch Syndrome related cancers requires obviously increased attention. As a further note, this and similar abstracts should take the opportunity to detail, in the background section, the full cancer spectrum - a one-line sentence is all that is required.)

INTERPRETATION:

This multicenter questionnaire highlights heterogenous practices in dMMR testing and LS identification, both in clinical terms and with regard to technical aspects of testing. An integrated multidisciplinary approach is lacking, and there is a need to educate physicians and resolve ethical issues. A Canadian consensus statement and national guidelines on dMMR testing are urgently needed, requiring input from pathologists, clinicians, and genetic counselors.

abstract: Predicting platinum resistance in primary advanced ovarian cancer patients with an in vitro resistance index



PURPOSE:

We aimed to identify primary platinum resistance in epithelial ovarian cancer (OC) patients with FIGO stage III-IV disease by an in vitro drug-response assay and to correlate the findings with clinical response. We considered whether neoadjuvant chemotherapy or anatomic sample site and tumor heterogeneity would influence the results.

CONCLUSIONS:

This in vitro assay predicted primary platinum resistance, without misclassification of sensitive OC patients, and the results were significantly associated with PFS. We suggest that samples from primary tumor and metastatic samples have different responses to chemotherapy and that exposure to chemotherapy might induce in vitro platinum resistance.

abstract: Malignant ovarian germ-cell tumours



Malignant ovarian germ-cell tumours account for about 5% of all ovarian malignancies and typically present in the teenage years. They are almost always unilateral and are exquisitely chemosensitive. As such, the surgical approach in young women with such tumours confined to a single ovary should aim to preserve fertility.....

abstract: KRAS mutations in ovarian low-grade endometrioid adenocarcinoma: association with concurrent endometriosis (study of KRAS/BRAF mutations)



Summary

The association between ovarian endometrioid adenocarcinoma and endometriosis is well established. However, not all endometrioid adenocarcinomas are directly related to endometriosis, and it has been suggested that there may be clinicopathologic differences between endometriosis-positive and endometriosis-negative tumors. Molecular alterations in endometrioid adenocarcinoma include KRAS and BRAF mutations, but the incidence of these abnormalities in previous reports has been highly variable (0%-36% and 0%-24%, respectively).....

Keywords

  • Ovary;
  • Endometrioid;
  • Adenocarcinoma;
  • Endometriosis;
  • Molecular

The Cost of Knowledge - petition to allow open access publishing - Elsevier journals



Blogger's Note: Gynecologic Oncology is a journal published through Elsevier