A Syngeneic ErbB2 Mammary Cancer Model for Preclinical Immunotherapy Trials.

In order to develop a practical model of breast cancer, with in vitro and syngeneic, immune-intact, in vivo growth capacity, we established a primary cell line derived from a mammary carcinoma in the transgenic FVB/N-Tg(MMTV-ErbB2*)NDL2-5Mul mouse, referred to as "NDL". The cell line is adapted to standard cell culture and can be transplanted into syngeneic FVB/N mice. The line maintains a stable phenotype over multiple in vitro passages and rounds of in vivo transplantation.

Pathobiology of the 129:Stat1 mouse model of human age-related ER-positive breast cancer with an immune infiltrate-excluded phenotype.

Background: Stat1 gene-targeted knockout mice (129S6/SvEvTac-Stat1 ) develop estrogen receptor-positive (ER), luminal-type mammary carcinomas at an advanced age. There is evidence for both host environment as well as tumor cell-intrinsic mechanisms to initiate tumorigenesis in this model. In this report, we summarize details of the systemic and mammary pathology at preneoplastic and tumor-bearing time points.

Validation of RNAi Silencing Efficiency Using Gene Array Data shows 18.5% Failure Rate across 429 Independent Experiments.

No independent cross-validation of success rate for studies utilizing small interfering RNA (siRNA) for gene silencing has been completed before. To assess the influence of experimental parameters like cell line, transfection technique, validation method, and type of control, we have to validate these in a large set of studies. We utilized gene chip data published for siRNA experiments to assess success rate and to compare methods used in these experiments.

Glucose Uptake and Intracellular pH in a Mouse Model of Ductal Carcinoma In situ (DCIS) Suggests Metabolic Heterogeneity.

Mechanisms for the progression of ductal carcinoma in situ (DCIS) to invasive breast carcinoma remain unclear. Previously we showed that the transition to invasiveness in the mammary intraepithelial neoplastic outgrowth (MINO) model of DCIS does not correlate with its serial acquisition of genetic mutations. We hypothesized instead that progression to invasiveness depends on a change in the microenvironment and that precancer cells might create a more tumor-permissive microenvironment secondary to changes in glucose uptake and metabolism.

A Network-Based Target Overlap Score for Characterizing Drug Combinations: High Correlation with Cancer Clinical Trial Results.

Drug combinations are highly efficient in systemic treatment of complex multigene diseases such as cancer, diabetes, arthritis and hypertension. Most currently used combinations were found in empirical ways, which limits the speed of discovery for new and more effective combinations. Therefore, there is a substantial need for efficient and fast computational methods.

MEK1 is associated with carboplatin resistance and is a prognostic biomarker in epithelial ovarian cancer.

Background: Primary systemic treatment for ovarian cancer is surgery, followed by platinum based chemotherapy. Platinum resistant cancers progress/recur in approximately 25% of cases within six months. We aimed to identify clinically useful biomarkers of platinum resistance.

Biomarkers for systemic therapy in ovarian cancer.

Epithelial ovarian cancer (EOC) is the most deadly tumor of the female reproductive system. Despite improvements in understanding the biology of EOC, therapeutic strategies still depend on surgery and combination of taxane and platinum agents. Here, we provide a summary of clinically tested biomarkers potentially useful to predict drug response.

Identifying resistance mechanisms against five tyrosine kinase inhibitors targeting the ERBB/RAS pathway in 45 cancer cell lines.

Because of the low overall response rates of 10-47% to targeted cancer therapeutics, there is an increasing need for predictive biomarkers. We aimed to identify genes predicting response to five already approved tyrosine kinase inhibitors. We tested 45 cancer cell lines for sensitivity to sunitinib, erlotinib, lapatinib, sorafenib and gefitinib at the clinically administered doses.

Parallel evolution under chemotherapy pressure in 29 breast cancer cell lines results in dissimilar mechanisms of resistance.

Background: Developing chemotherapy resistant cell lines can help to identify markers of resistance. Instead of using a panel of highly heterogeneous cell lines, we assumed that truly robust and convergent pattern of resistance can be identified in multiple parallel engineered derivatives of only a few parental cell lines.

Methods: Parallel cell populations were initiated for two breast cancer cell lines (MDA-MB-231 and MCF-7) and these were treated independently for 18 months with doxorubicin or paclitaxel.

[Gene expression based multigene prognostic and predictive tests in breast cancer].

Patient tailored therapy will serve the fundamentals of future cancer treatment. For this it will be imperative to characterize the tumor and to acquire precise predictive and prognostic information. We can achieve this by using not only monogenic (like ER, PR, HER-2, Ki-67) but also multigene assays, which can provide answers to several diagnostic questions simultaneously.