Libby's H*O*P*E* › Comments

The multivariate odds ratio (OR) for consumption of cruciferous vegetables at least once a week as compared with no/occasional consumption was significantly reduced for cancer of the oral cavity/pharynx (OR = 0.83), esophagus (OR = 0.72), colorectum (OR = 0.83), breast (OR = 0.83), and kidney (OR = 0.68). The OR was below unity, but not significant, for stomach (OR = 0.90), liver (OR = 0.72), pancreatic (OR = 0.90), laryngeal (OR = 0.84), endometrial (OR = 0.93), ovarian (OR = 0.91), and prostate (OR = 0.87) cancer. - Libby's H*O*P*E*

In models that were simultaneously adjusted for total (dietary plus supplements) calcium, total vitamin D and lactose, we observed a decreased overall risk of ovarian cancer with high intake of total calcium; the inverse association was strongest for serous borderline and mucinous tumors. High intake of total vitamin D was not associated overall with ovarian cancer risk, but was inversely associated with risk of serous borderline and endometrioid tumors. We found no evidence that lactose intake influenced ovarian cancer risk or that risk varied by tumor aggressiveness in the analyses of intake of dairy foods and nutrients. The overall inverse association with high intake of calcium and the inverse associations of calcium and vitamin D with specific histological subtypes warrant further investigation. - Libby's H*O*P*E*

BRCA mutation status has a major influence on survival in ovarian cancer patients and should be an additional stratification factor in clinical trials. Treatment outcomes in BRCA1/2 carriers challenge conventional definitions of platin resistance, and mutation status may be able to contribute to decision making and systemic therapy selection in the relapse setting. Our data, together with the advent of poly(ADP-ribose) polymerase inhibitor trials, supports the recommendation that germ-line BRCA1/2 testing should be offered to all women diagnosed with nonmucinous, ovarian carcinoma, regardless of family history. - Libby's H*O*P*E*

Using the OV2944-HM-1 model of ovarian cancer which spontaneously metastasizes to the lungs following subcutaneous implantation, researchers evaluated the efficacy of intratracheal and oral administration of SM-276001 in an adjuvant setting following surgical resection of the primary tumor. They show that both oral and intratracheal TLR7 therapy can reduce the frequency of pulmonary metastasis, and metastasis to the axillary lymph nodes. These results demonstrate that SM-276001 is a potent selective TLR7 agonist that can induce antitumor immune responses when dosed either intratracheally or orally. - Libby's H*O*P*E*

Researchers show that when used in combination, metformin + PEITC are effective in both slowing cancer cell growth and killing ovarian cancer cells in vitro. Furthermore, the combination of these drugs remains effective in cisplatin resistant cell lines. Novel combinations such as metformin and PEITC show promise in expanding ovarian cancer therapies and overcoming the high incidence of cisplatin resistant cancers. - Libby's H*O*P*E*

Radical surgery was associated with improved survival. In the subgroup of patients with stage IIIC disease with peritoneal carcinomatosis, independent prognostic factors were advanced age, radical surgery, and grossly visible residual disease. Patients with no gross residual disease had the longest overall survival (86 months) compared with residual disease 0.1-1 cm (46 months) and residual disease >1.0 cm (37 months). No gross residual disease is associated with improved overall survival, and radical surgery was effective for achieving no gross residual disease. - Libby's H*O*P*E*

Lifetime risk of developing endometrial cancer in Lynch syndrome (LS) carriers is very high and females are also at an increased risk of developing ovarian cancer. The aim of the study was to determine the impact of gynecological screening in MSH2 mutation carriers. Gynecological screening did not result in earlier gynecologic cancer detection and despite screening two young women died from ovarian cancer suggesting that prophylactic hysterectomy with bilateral salpingo-oophorectomy be considered in female mutation carriers who have completed childbearing. - Libby's H*O*P*E*

In a small Italian study of heavily pretreated, platinum-resistant advanced ovarian cancer patients, low-dose bevacizumab + chemo ((carboplatin (n = 8), oral cyclofosfamide (n = 5) or weekly paclitaxel (n = 2)) was well tolerated and active. Median progression free survival was 21 months and median overall survival was 24 months. Grade 3 adverse events related to bevacizumab were hypertension (n = 2), proteinuria (n = 1) and epistaxis (n = 5). - Libby's H*O*P*E*

This review focuses on such proteomic strategies in regards to ovarian cancer signaling pathways, as well as ovarian cancer development and its escape from the immune response. - Libby's H*O*P*E*

Researchers confirm that RAD51C is a susceptibility gene for ovarian and breast cancer, noting that this gene should be screened for mutations in families with multiple breast cancer/ovarian cancer cases. - Libby's H*O*P*E*

Researchers synthesized a doxorubicin-curcumin composite nanoparticle formulation called "NanoDoxCurc" (NDC) for overcoming DOX resistance. Compared to DOX alone, NDC inhibited the MDR phenotype and caused striking growth inhibition both in vitro and in vivo in several models of DOX-resistant cancers (multiple myeloma, acute leukemia, prostate and ovarian cancers, respectively). Notably, NDC-treated mice also demonstrated complete absence of cardiac toxicity, as assessed by echocardiography, or any bone marrow suppression, even at cumulative dosages where free DOX and pegylated liposomal DOX (Doxil®) resulted in demonstrable attenuation of cardiac function and hematological toxicities. This improvement in safety profile was achieved through a reduction of DOX-induced intracellular oxidative stress, as indicated by total glutathione levels and glutathione peroxidase activity in cardiac tissue. A composite DOX-curcumin nanoparticle that overcomes both MDR-based DOX chemoresistance and DOX-induced cardiotoxicity holds promise for providing lasting and safe anticancer therapy. - Libby's H*O*P*E*

In this phase I trial, the combination of the PKC and AKT pathway inhibitor enzastaurin with bevacizumab (Avastin) did not appear to alter the pharmacokinetics or toxicity profiles of either drug. Antitumor activity was particularly promising in ovarian cancer and when enzastaurin was given twice daily. In ovarian cancer patients, the response rate was 32.3%, with 4 complete responses, 6 partial responses, and 14 pts with stable disease. The median time to disease progression or death in ovarian cancer was 8.3 months, longer than the researchers would have anticipated with bevacizumab monotherapy. - Libby's H*O*P*E*

Only few ovarian cancer patients were HER2 overexpressed measured by IHC or FISH and thus could be eligible for antibody-based therapy with trastuzumab (Herceptin). Interestingly, the researchers found an increased number of HER2 positive patients by real-time PCR analysis on microdissected cancer cells, suggesting a number of HER2 positive patients not detected by current methods. - Libby's H*O*P*E*

Carboplatin + pegylated liposomal doxorubicin (Doxil) led to delayed progression and similar overall survival compared with carboplatin + paclitaxel (Taxol) in platinum-sensitive, recurrent ovarian cancer patients. - Libby's H*O*P*E*

Twenty patients were enrolled between 06/07 and 12/09. The median age was 61 years (42-82) with a median of 2 prior regimens (0-6), and 71% had platinum-sensitive disease. The response rate was 40% (3 complete responses, (15%); 5 partial responses, (25%)),10 (50%) had stable disease, and 2 were not evaluable. The progression-free survival (PFS) 6-month actuarial estimate was 86%. The median PFS and overall survival were 7.8 and 16.2 months, respectively. - Libby's H*O*P*E*

Inflammation plays a role in the pathogenesis of endometriosis. Endometriosis-associated ovarian carcinogenesis might be promoted through oxidative stress-induced increased genomic instability, aberrant methylation, and aberrant chromatin remodeling, as well as mutations of tumor suppressor genes. Aberrant expression of ARID1A, PIK3CA, and NF-kB genes has been recognized as the major target genes involved in oxidative stress-induced carcinogenesis. HNF-1beta appears to play a key role in anti-oxidative defense mechanisms. - Libby's H*O*P*E*

Green tea decreases ovarian cancer-associated protein expression in cell lines. ► Green tea-fed mice develop smaller, less vascularized ovarian cancer xenografts. ► Green tea intake could decrease ovarian cancer occurrence and recurrence in women. - Libby's H*O*P*E*

Ovarian CCC tumors tend to present at earlier stages. ► Ovarian CCC has been associated with endometriosis, ARID1A and PIK3CA mutations. ► Future studies should explore the role of targeted therapies in the management of ovarian CCC. - Libby's H*O*P*E*

Endometriosis-associated endometrioid ovarian tumors possess a different biologic signature when compared to cancers not associated with the disease. ► Clinical and molecular features of the two types of endometrial cancer reflect those of endometriosis-associated and non-associated endometrioid ovarian tumor. - Libby's H*O*P*E*

Systematic lymphadenectomy may have a therapeutic value and be significantly associated with improved survival in stage IIIC ovarian cancer patients with grossly no visible residual disease. - Libby's H*O*P*E*

BRCA mutation status has a major influence on survival in ovarian cancer patients and should be an additional stratification factor in clinical trials. Treatment outcomes in BRCA1/2 carriers challenge conventional definitions of platin resistance, and mutation status may be able to contribute to decision making and systemic therapy selection in the relapse setting. Our data, together with the advent of poly(ADP-ribose) polymerase inhibitor trials, supports the recommendation that germ-line BRCA1/2 testing should be offered to all women diagnosed with nonmucinous, ovarian carcinoma, regardless of family history. - Libby's H*O*P*E*

Fertility drug use does not significantly contribute to ovarian cancer risk among the majority of women; however, women who despite infertility evaluation and fertility drug use remain nulligravid, may have an elevated risk for ovarian cancer. - Libby's H*O*P*E*

When the US Preventive Services Task Force (USPSTF) updated its ovarian cancer screening recommendation in April 2012. After reviewing 3 more recent randomized controlled trials, the task force upheld its position that the evidence doesn't support routinely screening asymptomatic women with average-risk profiles. Gynecologic oncologists applauded the updated recommendation. - Libby's H*O*P*E*

Women with ovarian cancer may have somewhat better survival odds when they feel emotionally supported by family and friends, a new study suggests. Researchers found that of 168 ovarian cancer patients, there were 95 deemed to have "high social attachment" - meaning they had relationships that made them feel emotionally secure and closely connected to at least one other person. And after almost five years, 59 percent of those women were still alive, versus 38 percent of patients with lesser emotional bonds. - Libby's H*O*P*E*

Could ovulation be the link to ovarian cancer? Joanna Burdette of the University of Illinois at Chicago College of Pharmacy thinks it might be, and she's working to find out. Burdette, assistant professor of medicinal chemistry and pharmacognosy at UIC, is conducting new research to discover if ovulation increases a signaling pathway that transforms cells of the ovary surface or the lining of the Fallopian tubes into ovarian cancer. Burdette has received a four-year $720,000 grant from the American Cancer Society of Illinois for her research, which focuses on epithelial cells, or surface and lining cells, in this case, of the female reproductive system. - Libby's H*O*P*E*

Fujirebio Diagnostics, the industry leader in oncology biomarker assays, announced today that it has received 510(k) clearance from the U.S. Food and Drug Administration (FDA) to market the company's HE4 Test in an algorithm called ROMA(TM) (HE4 EIA + ARCHITECT CA 125 II(TM))* to aid in assessing whether a premenopausal or postmenopausal woman who presents with an ovarian adnexal mass is at high or low likelihood of finding malignancy on surgery. - Libby's H*O*P*E*

17-year old Taylor Steele, founder of the Strong As Steele Cancer Foundation, lost her life to ovarian cancer. Taylor's life represents a "master class" to the living - how to live life to the fullest despite difficult or tragic circumstances. - Libby's H*O*P*E*

Mass General finds that mTOR inhibitor rapamycin may be effective against select forms of endometrioid ovarian cancer (i.e., those with dysregulated Wnt/β-catenin and Pten/PI3K signaling). - Libby's H*O*P*E*

Womens Oncology Research & Dialogue (WORD) is a Libby's H*O*P*E* partner. We highly recommend that you watch these inspirational ovarian cancer survivor stories on the WORD weblog. - Libby's H*O*P*E*

A novel agent that works by blocking MET and vascular endothelial growth factor receptor 2 (VEGFR2) exhibited activity in patients with a broad spectrum of solid tumors in a randomized, phase II discontinuation trial (Abstract CRA3010). "MET is upregulated, amplified, or downregulated in a wide range of malignancies," Michael S. Gordon, MD, of Pinnacle Oncology Hematology, said during yesterday’s Oral Abstract Session: Developmental Therapeutics — Experimental Therapeutics. "It tends to drive tumor cell invasion as well as metastogenesis. Both MET and VEGF collaborate in the driving of angiogenesis, as well as tumor–bone interactions." The study enrolled patients with a wide range of cancers: hepatocellular, prostate, ovarian, breast, pancreatic, gastric, melanoma, non-small cell lung cancer, and small cell lung cancer. These malignancies were selected for study because of known associations with MET dysregulation, Dr. Gordon said. The randomized discontinuation trial format was... - Libby's H*O*P*E*