Management of Breast Cancer Survivors by Gynecologists.

Breast cancer patients commonly present to their OBGYN during the process of diagnosis and treatment of breast cancer both for specific gynecologic needs and for primary care follow up. These patients require counseling on contraception, hormone use, and fertility at diagnosis. During treatment and survivorship, patients will face a variety of side effects from treatments leading to vasomotor symptoms, vulvovaginal discomfort, sexual dysfunction, osteoporosis, and vaginal bleeding.

Cancer genetics and breast cancer.

The risk of developing breast cancer is multifactorial and, at times, modifiable. However, the risk imposed by family history and hereditary pathogenic variants in a person's genetic code is, at present, an important fixed variable. Therefore, it is imperative to identify patients at risk for hereditary breast cancer and to understand the current evidence-based approach to the management of that risk.

When Should Prophylactic Oophorectomy Be Recommended at the Time of Elective Hysterectomy?

Gynecologists are frequently confronted with the decision of when to recommend oophorectomy at the time of an elective hysterectomy. When deciding if oophorectomy should be recommended, first a careful history and risk assessment must be performed to determine if a patient is a candidate for a risk-reducing oophorectomy. If the patient does not have a hereditary ovarian cancer risk, then it is recommended the surgeon carefully consider the implications of ovarian removal on the health of their patient.

Integrated regulation of autophagy and apoptosis by EEF2K controls cellular fate and modulates the efficacy of curcumin and velcade against tumor cells.

Endoplasmic reticulum (ER) stress induces both autophagy and apoptosis yet the molecular mechanisms and pathways underlying the regulation of these two cellular processes in cells undergoing ER stress remain less clear. We report here that eukaryotic elongation factor-2 kinase (EEF2K) is a critical controller of the ER stress-induced autophagy and apoptosis in tumor cells. DDIT4, a stress-induced protein, was required for transducing the signal for activation of EEF2K under ER stress.

Differential gene expression in tamoxifen-resistant breast cancer cells revealed by a new analytical model of RNA-Seq data.

Resistance to tamoxifen (Tam), a widely used antagonist of the estrogen receptor (ER), is a common obstacle to successful breast cancer treatment. While adjuvant therapy with Tam has been shown to significantly decrease the rate of disease recurrence and mortality, recurrent disease occurs in one third of patients treated with Tam within 5 years of therapy. A better understanding of gene expression alterations associated with Tam resistance will facilitate circumventing this problem.

Phosphorylation of elongation factor-2 kinase differentially regulates the enzyme's stability under stress conditions.

Eukaryotic elongation factor-2 kinase (eEF-2K) is a Ca(2+)/calmodulin-dependent enzyme that negatively regulates protein synthesis. eEF-2K has been shown to be up-regulated in cancer, and to play an important role in cell survival through inhibition of protein synthesis. Post-translational modification of protein synthesis machinery is important for its regulation and could be critical for survival of cancer cells encountering stress.

Dysfunction of nucleus accumbens-1 activates cellular senescence and inhibits tumor cell proliferation and oncogenesis.

Nucleus accumbens-1 (NAC1), a nuclear factor belonging to the BTB/POZ gene family, has emerging roles in cancer. We report here that NAC1 acts as a negative regulator of cellular senescence in transformed and nontransformed cells, and dysfunction of NAC1 induces senescence and inhibits its oncogenic potential. We show that NAC1 deficiency markedly activates senescence and inhibits proliferation in tumor cells treated with sublethal doses of γ-irradiation.

Rational incorporation of selenium into temozolomide elicits superior antitumor activity associated with both apoptotic and autophagic cell death.

Background: The DNA alkylating agent temozolomide (TMZ) is widely used in the treatment of human malignancies such as glioma and melanoma. On the basis of previous structure-activity studies, we recently synthesized a new TMZ selenium analog by rationally introducing an N-ethylselenocyanate extension to the amide functionality in TMZ structure.

Principal Findings: This TMZ-Se analog showed a superior cytotoxicity to TMZ in human glioma and melanoma cells and a more potent tumor-inhibiting activity than TMZ in mouse glioma and melanoma xenograft model.

MK-2206, a novel allosteric inhibitor of Akt, synergizes with gefitinib against malignant glioma via modulating both autophagy and apoptosis.

Gefitinib, a small molecule inhibitor of the epidermal growth factor receptor tyrosine kinase, has been shown to induce autophagy as well as apoptosis in tumor cells. Yet, how to use autophagy and apoptosis to improve therapeutic efficacy of this drug against cancer remains to be explored. We reported here that MK-2206, a potent allosteric Akt inhibitor currently in phase I trials in patients with solid tumors, could reinforce the cytocidal effect of gefitinib against glioma.

Inhibition of eEF-2 kinase sensitizes human glioma cells to TRAIL and down-regulates Bcl-xL expression.

Elongation factor-2 kinase (eEF-2 kinase, also known as calmodulin-dependent protein kinase III), is a unique calcium/calmodulin-dependent enzyme that inhibits protein synthesis by phosphorylating and inactivating elongation factor-2 (eEF-2). We previously reported that expression/activity of eEF-2 kinase was up-regulated in several types of malignancies including Gliomas, and was associated with response of tumor cells to certain therapeutic stress. In the current study, we sought to determine whether eEF-2 kinase expression affected sensitivity of glioma cells to treatment with tumor the necrosis factor-related apoptosis-inducing ligand (TRAIL), a targeted therapy able to induce apoptosis in cancer cells but causes no toxicity in most normal cells.