Doxorubicin and paclitaxel enhance the antitumor efficacy of vaccines directed against HER 2/neu in a murine mammary carcinoma model

INTRODUCTION: The purpose of the present study was to determine whether cytotoxic chemotherapeutic agents administered prior to immunotherapy with gene vaccines could augment the efficacy of the vaccines. METHODS: Mice were injected in the mammary fat pad with an aggressive breast tumor cell line that expresses HER2/neu. The mice were treated 3 days later with a noncurative dose of either doxorubicin or paclitaxel, and the following day with a gene vaccine to HER2/neu. Two more doses of vaccine were given 14 days apart. Two types of gene vaccines were tested: a plasmid vaccine encoding a self-replicating RNA (replicon) of Sindbis virus (SINCP), in which the viral structural proteins were replaced by the gene for neu; and a viral replicon particle derived from an attenuated strain of Venezuelan equine encephalitis virus, containing a replicon RNA in which the Venezuelan equine encephalitis virus structural proteins were replaced by the gene for neu. RESULTS: Neither vaccination alone nor chemotherapy alone significantly reduced the growth of the mammary carcinoma. In contrast, chemotherapy followed by vaccination reduced tumor growth by a small, but significant amount. Antigen-specific CD8(+ )T lymphocytes were induced by the combined treatment, indicating that the control of tumor growth was most probably due to an immunological mechanism. The results demonstrated that doxorubicin and paclitaxel, commonly used chemotherapeutic agents for the treatment of breast cancer, when used at immunomodulating doses augmented the antitumor efficacy of gene vaccines directed against HER2/neu. CONCLUSIONS: The combination of chemotherapeutic agents plus vaccine immunotherapy may induce a tumor-specific immune response that could be beneficial for the adjuvant treatment of patients with minimal residual disease. The regimen warrants further evaluation in a clinical setting

Application of mRNA Technology in Cancer Therapeutics

mRNA-based therapeutics pose as promising treatment strategies for cancer immunotherapy. Improvements in materials and technology of delivery systems have helped to overcome major obstacles in generating a sufficient immune response required to fight a specific type of cancer. Several in vivo models and early clinical studies have suggested that various mRNA treatment platforms can induce cancer-specific cytolytic activity, leading to numerous clinical trials to determine the optimal method of combinations and sequencing with already established agents in cancer treatment. Nevertheless, further research is required to optimize RNA stabilization, delivery platforms, and improve clinical efficacy by interacting with the tumor microenvironment to induce a long-term antitumor response. This review provides a comprehensive summary of the available evidence on the recent advances and efforts to overcome existing challenges of mRNA-based treatment strategies, and how these efforts play key roles in offering perceptive insights into future considerations for clinical application

Ovarian carcinoma with simultaneous breast and rectum metastases

Background: Metastatic involvement of the breast and the rectum from ovarian carcinoma are very rare events. Case Report: We report a case of ovarian carcinoma with metastasis to the breast and rectum simultaneously, 6 years after initial diagnosis. Results: Morphologic and immunohistochemical findings from pathologic samples of all involved sites confirmed the ovarian origin, which spared the patient unnecessary breast and rectal surgery. To our knowledge, this is the first case of ovarian carcinoma with simultaneous metastases to the breast and rectum reported to date. Conclusion: Accurate differential diagnosis from primary breast and rectal carcinoma is very important because the prognosis and treatment differ significantly

Leptomeningeal dissemination of ovarian carcinoma through a ventriculopenitoneal shunt

Background. Dissemination of ovarian cancer occurs mainly within the peritoneal cavity and central nervous system involvement (CNS) is encountered rarely. This report describes an unusual case with iatrogenic leptomeningeal metastasis from ovarian carcinoma

Prognostic value of receptor status change following neoadjuvant chemotherapy in locally advanced breast cancer

© 2015 The Authors.IntroductionThe effect of neoadjuvant chemotherapy (NAC) on the expression of receptor status in locally advanced breast cancer (LABC) is still under investigation. Aims of this study are to evaluate changes in hormone receptor (HR) and HER-2 status post-NAC and correlation with survival. Materials and methodsLABC patients who received NAC between 2001 and 2008 at Istanbul University were analyzed retrospectively. Patients with pathologic complete response (pCR) were excluded in analysis. Immunohistochemical (IHC) analyses was performed on both initial biopsies and surgical specimens. ResultsThe median age of 128 patients was 48 years and 55% of them were premenopausal. Most of the patients had invasive ductal (81%) and histologic grade (HG) III (81%) breast cancer. Partial pathologic response (pPR) rate was 86.7%. HR status changed in 36 patients (28%). The rates of ER, PR and HER-2 receptor positivity at diagnosis and after NAC were 44-32.8%, 43-29.7%, and 24-21%, respectively. Negative-to-positive change in HR status was observed in five patients. The 5-year overall survival (OS) was 76% in patients whose HR status converted to negative, compared with 91% in patients who remained HR-positive (p<0.05). Multivariate Cox regression analysis showed that receptor status change was independently related to disease-free survival (DFS) (Hazard Ratio 6.88; p=0.002), whereas as it did not have any impact on OS (p=0.148). ConclusionNAC induced changes in HR and HER-2 expression, predominantly from positive to negative. These changes were associated with shorter DFS. Postoperative re-evaluation of receptor status may have clinical significance

Factors related to recurrence after pathological complete response to postoperative chemotherapy in patients with epithelial ovarian cancer

Aims and background. It has been appreciated for some time that the lack of detection of ovarian cancer at clinical and pathological (second-look laparotomy) evaluation is not synonymous with cure. The goal of this study was to define clinical risk factors for recurrence after complete pathological response to postoperative chemotherapy in patients with epithelial ovarian cancer

Yolk sac tumours of the ovary: Evaluation of clinicopathological features and prognostic factors

Objective: To evaluate the clinicopathological prognostic features, factors and outcomes of chemotherapy in ovarian yolk sac tumours (YST)