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Background: Ovarian cancer constitutes nearly 4% of all cancers among women and is the leading cause of death from gynecologic malignancies in the Western world. Standard first line adjuvant chemotherapy treatments include Paclitaxel (Taxol) and platinum-based agents. Taxol, epothilone B (EpoB) and discodermolide belong to a family of anti-neoplastic agents that specifically interferes with microtubules and arrests cells in the G2/M phase of the cell cycle. Despite initial success with chemotherapy treatment, many patients relapse due to chemotherapy resistance. In vitro establishment of primary ovarian cancer cells provides a powerful tool for better understanding the mechanisms of ovarian cancer resistance. We describe the generation and characterization of primary ovarian cancer cells derived from ascites fluids of patients with epithelial ovarian cancer. Methods: Chemosensitivity of these cell lines to Taxol, EpoB and discodermolide was tested, and cell cycle analysis was compared to that of immortalized ovarian cancer cell lines SKOV3 and Hey. The relationship between drug resistance and αβ-tubulin and p53 status was also investigated. Results: All newly generated primary cancer cells were highly sensitive to the drugs. αβ-tubulin mutation was not found in any primary cell lines tested. However, one cell line that harbors p53 mutation at residue 72 (Arg to Pro) exhibits altered cell cycle profile in response to all drug treatments. Immortalized ovarian cancer cells respond differently to EpoB treatment when compared to primary ovarian cancer cells, and p53 polymorphism suggests clinical significance in the anti-tumor response in patients. Conclusions: The isolation and characterization of primary ovarian cancer cells from ovarian cancer patients’ specimens contribute to further understanding the nature of drug resistance to microtubule interacting agents (MIAs) currently used in clinical settings. [ABSTRACT FROM AUTHOR]

The utility of cancer antigen 125 (CA-125) levels as an adjunct method of monitoring patients with uterine papillary serous carcinoma (UPSC) or endometrial serous carcinoma after surgery and adjuvant treatment has been reported. Our goal was to determine the significance of rising CA-125 levels within the normal range in these patients in the posttreatment surveillance setting. All patients with UPSC who underwent surgical staging and had preoperative CA-125 measurement from 1999 to 2008 were included in this analysis. Information was extracted from records to assess the changes in CA-125 values with clinical and/or radiographic detection of recurrence. Of the 56 evaluable patients, 23 (41%) recurred. Of the 23 patients that recurred, 11 had serial CA-125 levels measured in remission. Elevated CA-125 levels at diagnosis were significantly associated with disease recurrence and advanced stage (P = .01, P = .001, respectively). The rise in CA-125 by 10 U/mL in the normal range and ≥15 U/mL were associated with disease recurrence (P < .001, P < .001, respectively). In multivariate analysis, only CA-125 level ≥15 U/mL was significantly associated with worse progression-free survival. In this small cohort of patients with recurrent UPSC after remission, surveillance of CA-125 levels may have a role in disease surveillance and management. [ABSTRACT FROM PUBLISHER]

There are limited data regarding the end-of-life care for women with gynecologic malignancies. We set out to generate pilot data describing the care that women with gynecologic malignancies received in the last 6 months of life. Patient demographics, patterns of care, and utilization of palliative medicine consultation services were evaluated.One hundred patients who died of gynecologic malignancies were identified in our institutional database. Only patients who had received treatment with a gynecologic oncologist within 1 year of death were included. Medical records were reviewed for relevant information. Data were abstracted from the electronic medical record, and analyses were made using Student t test and Mann-Whitney U test with SPSS software.The mean age of patients was 60 years (range, 30-94 years). Racial/ethnic distribution was as follows: 38%, white; 34%, black; and 15%, Hispanic. Seventy-five percent of patients received chemotherapy within the last 6 months of life, and 30% received chemotherapy within the last 6 weeks of life. The median number of days hospitalized during the last 6 months of life was 24 (range, 0-183 days). During the last 6 months of life, 19% were admitted to the intensive care unit, 17% were intubated, 5% had terminal extubation, and 13% had cardiopulmonary resuscitative efforts. Sixty-four percent had a family meeting, 50% utilized hospice care, and 49% had palliative medicine consultations. There was a significant difference in hospice utilization when comparison was made between patients who had 14 days or more from consultation until death versus patients who had 14 days or less or no consultation, 21 (72%) versus 29 (41%), P = 0.004. Patients who were single were less likely to have a palliative medicine consultation, P = 0.005.End-of-life care for patients with gynecologic malignancies often includes futile, aggressive treatments and invasive procedures. It is unknown whether these measures contribute to longevity or quality of life. These pilot data suggest that factors for implementation of timely hospice referral, family support, and legacy building should include specialists trained in palliative medicine. [ABSTRACT FROM AUTHOR]

While the clinical benefit of MEK inhibitor (MEKi)-based therapy is well established in Raf mutant malignancies, its utility as a suppressor of hyperactive MAPK signaling in the absence of mutated Raf or Ras, is an area of ongoing research. MAPK activation is associated with loss of ERα expression and hormonal resistance in numerous malignancies. Herein, we demonstrate that MEKi induces a feedback response that results in ERα overexpression, phosphorylation and transcriptional activation of ER-regulated genes. Mechanistically, MEKi-mediated ERα overexpression is largely independent of erbB2 and AKT feedback activation, but is ERK-dependent. We subsequently exploit this phenomenon therapeutically by combining the ER-antagonist, fulvestrant with MEKi. This results in synergistic suppression of tumor growth, in vitro and potentiation of single agent activity in vivo in nude mice bearing xenografts. Thus, we demonstrate that exploiting adaptive feedback after MEKi can be used to sensitize ERα-positive tumors to hormonal therapy, and propose that this strategy may have broader clinical utility in ERα-positive ovarian carcinoma. [ABSTRACT FROM AUTHOR]

Cancer is a leading cause of death of men and women worldwide. Tumor cell motility contributes to metastatic invasion that causes the vast majority of cancer deaths. Extracellular receptors modified by α2,3-sialic acids that promote this motility can serve as ideal chemotherapeutic targets. For example, the extracellular domain of the mucin receptor podoplanin (PDPN) is highly O-glycosylated with α2,3-sialic acid linked to galactose. PDPN is activated by endogenous ligands to induce tumor cell motility and metastasis. Dietary lectins that target proteins containing α2,3-sialic acid inhibit tumor cell growth. However, anti-cancer lectins that have been examined thus far target receptors that have not been identified. We report here that a lectin from the seeds of Maackia amurensis (MASL) with affinity for O-linked carbohydrate chains containing sialic acid targets PDPN to inhibit transformed cell growth and motility at nanomolar concentrations. Interestingly, the biological activity of this lectin survives gastrointestinal proteolysis and enters the cardiovascular system to inhibit melanoma cell growth, migration, and tumorigenesis. These studies demonstrate how lectins may be used to help develop dietary agents that target specific receptors to combat malignant cell growth. [ABSTRACT FROM AUTHOR]