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]
Sent from my iPhone
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.
Sent from my iPhone
Another lesson about over-aggressive screening - Health News Watchdog
SEP
12
Another lesson about over-aggressive screening
Posted by Gary Schwitzer in Screening
Sent from my iPhone
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
Sent from my iPhone
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.
Sent from my iPhone
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]
Sent from my iPhone
False Promises on Ovarian Cancer - NYTimes.com Editorial
False Promises on Ovarian Cancer
Published: September 11, 2012
Sent from my iPhone
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."
Sent from my iPhone
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
Sent from my iPhone
Preoperative Identification of Synchronous Ovarian and Endometrial Cancers: The Importance of Appropriate Workup
Preoperative Identification of Synchronous Ovarian and Endometrial Cancers: The Importance of Appropriate Workup
Objective: For treatment of patients with both endometrial and ovarian cancer, it is important to discriminate between 2 primary tumors and metastatic disease. Currently, criteria are based on postoperative findings. The aim of this study was to determine whether clinical parameters can discriminate between these groups preoperatively and whether a practical guideline could improve appropriate workup and treatment.Methods: A total of 45 patients with a diagnosis of both endometrium and ovarian cancer between 1998 and 2009 and were included for analysis. Clinical and pathological data were obtained, and initial CA-125 was registered; patients had a diagnosis of 2 primary tumors or tumors with metastasis. All patients were reclassified according to workup and treatment.
Results: Patients with synchronous primary tumors were significantly younger, presented more often with abnormal uterine bleeding, and had a lower initial CA-125 than both metastatic groups (P < 0.05). With age and CA-125 included in a polytomic logistic regression model, 83.3% of diagnoses could be classified correctly. In 15 of 17 patients presented with adnexal mass, workup was incomplete owing to lack on information of the endometrial status. In patients presenting with abnormal uterine bleeding, 13 of 21 patients had an incomplete workup leading to staging laparotomy secondary to initial surgical treatment in 2 patients.
Conclusions: Patients with synchronous endometrial and ovarian cancers are young, often present with abnormal uterine bleeding and have a low initial CA-125. Adequate workup with attention to both ovarian and endometrial status, especially in young patients with a wish to preserve fertility, is important to make the right decision for treatment.
Copyright (C) 2012 by IGCS and ESGO
Sent from my iPhone
ScienceDirect.com - Cancer Letters - Ovarian ascites-derived Hospicells promote angiogenesis via activation of macrophages
Ovarian ascites-derived Hospicells promote angiogenesis via activation of macrophages
Sent from my iPhone
Fwd: OncoLink eNews September 2012 survivor care survey
Survivor Care
Too often, cancer survivors learn to live with the pain and pitfalls of this disease simply because they can't find the right resources. The Lance Armstrong Foundation launched the 2012 Cancer Survivor Survey to help them build and refine programs that offer tangible support to survivors. If you currently have cancer or have been treated for cancer:
Take the survey and let your voice be heard
Sent from my iPhone
Begin forwarded message:
From: "OncoLink eNews" <OncoLink_eNews@mail.vresp.com>
Date: 11 September, 2012 1:32:09 PM EDT
To: sandipn@sympatico.ca
Subject: OncoLink eNews September 2012
Reply-To: "OncoLink eNews" <reply-1cc49a2d25-678cc187bf-b2a7@u.cts.vresp.com>
Survivor Care
Too often, cancer survivors learn to live with the pain and pitfalls of this disease simply because they can't find the right resources. The Lance Armstrong Foundation launched the 2012 Cancer Survivor Survey to help them build and refine programs that offer tangible support to survivors. If you currently have cancer or have been treated for cancer:
Sept. 11 anniversary to be marked without politicians' speeches
"Sept. 11 anniversary to be marked without politicians' speeches ".
This article is on the Web at:
http://www.680news.mobi/article.aspx?content_id=400251
Sent from my iPhone
Monday, September 10, 2012
PLoS ONE: Development of Multiplexed Bead-Based Immunoassays for the Detection of Early Stage Ovarian Cancer Using a Combination of Serum Biomarkers
PLoS ONE: Development of Multiplexed Bead-Based Immunoassays for the Detection of Early Stage Ovarian Cancer Using a Combination of Serum Biomarkers
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.........
Subscribe to:
Posts
(
Atom
)
