Feasibility, patient compliance and acceptability of ovarian cancer surveillance using two serum biomarkers and Risk of Ovarian Cancer Algorithm compared to standard ultrasound and CA 125 among women with BRCA mutations.

OBJECTIVE: We assessed the feasibility, patient acceptability of and compliance of a new surveillance strategy for ovarian cancer surveillance in women with BRCA mutations, based on assessments of serum CA125 and HE4 every 4 months (Risk of Ovarian Cancer Algorithm (ROCA) arm), compared to Standard of Care (SOC) surveillance with CA125 blood tests and pelvic ultrasounds every 6 months. METHODS: Women were recruited 6/13/16-9/11/17 from an integrated health care system in California for this non-randomized prospective cohort study. Women were invited to participate in a novel serum biomarker surveillance strategy using ROCA or they could opt to be in the standard of care control arm with ultrasound and CA 125 every 6 months. Outcomes assessed included compliance, self-reported distress using the Impact of Event Scale (IES) and cancer anxiety using the Cancer Worry Scale. RESULTS: There were 159 women in the ROCA arm and 43 in the SOC arm. Overall, compliance was higher in the ROCA arm (83.2%) than in SOC (51.9%), p < 0.0001. Based on the IES, ROCA arm women reported less feelings about intrusion and avoidance at 12 months compared to baseline; the difference approached significance for intrusion (7.6% vs 4.1% severe, p = 0.057) and was statistically significant for avoidance (20.8% vs 9.9% severe, p = 0.034). CONCLUSIONS: This pilot demonstrated that compliance was high with blood tests performed every four months for ovarian cancer surveillance. Moreover, ROCA women had lower stress scores over time than SOC women. Given the lack of clinical utility and poor compliance shown with traditional ultrasound and CA125 tests, further investigation is warranted of longitudinal biomarker surveillance for early detection of ovarian cancer.

Pre-treatment prognostic nutritional index is superior to platelet count in predicting disease-specific survival in patients with epithelial ovarian cancer.

OBJECTIVE: Both pre-treatment prognostic nutritional index and platelet count were reported to be independent prognostic factors in epithelial ovarian cancer patients. However, their relationship has not been investigated. The aim of this study was to investigate the association between the pre-treatment prognostic nutritional index and platelet count, and to compare their utility as prognostic indicators for patients with epithelial ovarian cancer. METHODS: Clinical data from epithelial ovarian cancer patients treated between April 2007 and March 2016 were collected and retrospectively reviewed. The association between the pre-treatment prognostic nutritional index and platelet count was evaluated using Spearman's rank correlation coefficient. After determining the cut-off values for the pre-treatment platelet count and prognostic nutritional index for predicting disease-specific survival by time-dependent receiver operating characteristic (ROC) curve analysis, we compared the clinical utility of platelet counts and the prognostic nutritional index. RESULTS: A total of 308 patients were included in the analysis. Median age was 57 (range 16-81) years. The International Federation of Gynecology and Obstetrics (FIGO) clinical stage at initial diagnosis was stage I in 137 patients (44.5%), stage II in 27 patients (8.8%), stage III in 96 patients (31.2%), and stage IV in 48 patients (15.6%). Most patients (37.7%) had serous adenocarcinoma. Of the 295 patients who underwent primary or interval debulking surgery, optimal debulking was performed in 240 patients (77.9%). Decresed pre-treatment prognostic nutritional index was correlated with increased pre-treatment platelet count (p<0.0001), and when compared, the prognostic nutritional index had a significantly greater area under the ROC curve value than the platelet count for predicting disease-specific survival (0.8348 vs 0.6413, p=0.0007). An elevated platelet count was significantly associated with a shorter disease-specific survival in epithelial ovarian cancer patients (p<0.0001). However, when the prognostic nutritional index was adjusted, an elevated platelet count did not provide any prognostic information (lower prognostic nutritional index, p=0.45; higher prognostic nutritional index, p=0.77). CONCLUSIONS: The pre-treatment prognostic nutritional index was superior to the platelet count for predicting disease-specific survival for epithelial ovarian cancer patients. Although pre-treatment thrombocytosis was reported to be an independent poor prognostic factor in epithelial ovarian cancer patients, it generally reflects a lower prognostic nutritional index, and did not provide any prognostic information when the prognostic nutritional index was adjusted.

Heavy black tea consumption and elevated CA 19-9 and CA 125 levels. A case report on a patient with ovarian endometriotic cysts.

In this case report, we present a case of false positive CA 19-9 and CA 125 levels in a patient with suspected endometriotic cysts. The patient is a 34-year-old nulliparous woman with heavy black tea consumption and elevated CA 19-9 and CA 125 levels. After discontinuation of black tea intake and careful exploration of other possible factors, CA 19-9 and CA 125 levels dropped markedly. As a conclusion, heavy black tea consumption can lead to false positive results of elevated CA 19-9 and CA 125 levels.

Circulating vitamin D concentration and risk of seven cancers: Mendelian randomisation study.

Objective To determine if circulating concentrations of vitamin D are causally associated with risk of cancer.Design Mendelian randomisation study.Setting Large genetic epidemiology networks (the Genetic Associations and Mechanisms in Oncology (GAME-ON), the Genetic and Epidemiology of Colorectal Cancer Consortium (GECCO), and the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortiums, and the MR-Base platform).Participants 70 563 cases of cancer (22 898 prostate cancer, 15 748 breast cancer, 12 537 lung cancer, 11 488 colorectal cancer, 4369 ovarian cancer, 1896 pancreatic cancer, and 1627 neuroblastoma) and 84 418 controls.Exposures Four single nucleotide polymorphisms (rs2282679, rs10741657, rs12785878 and rs6013897) associated with vitamin D were used to define a multi-polymorphism score for circulating 25-hydroxyvitamin D (25(OH)D) concentrations.Main outcomes measures The primary outcomes were the risk of incident colorectal, breast, prostate, ovarian, lung, and pancreatic cancer and neuroblastoma, which was evaluated with an inverse variance weighted average of the associations with specific polymorphisms and a likelihood based approach. Secondary outcomes based on cancer subtypes by sex, anatomic location, stage, and histology were also examined.Results There was little evidence that the multi-polymorphism score of 25(OH)D was associated with risk of any of the seven cancers or their subtypes. Specifically, the odds ratios per 25 nmol/L increase in genetically determined 25(OH)D concentrations were 0.92 (95% confidence interval 0.76 to 1.10) for colorectal cancer, 1.05 (0.89 to 1.24) for breast cancer, 0.89 (0.77 to 1.02) for prostate cancer, and 1.03 (0.87 to 1.23) for lung cancer. The results were consistent with the two different analytical approaches, and the study was powered to detect relative effect sizes of moderate magnitude (for example, 1.20-1.50 per 25 nmol/L decrease in 25(OH)D for most primary cancer outcomes. The Mendelian randomisation assumptions did not seem to be violated.Conclusions There is little evidence for a linear causal association between circulating vitamin D concentration and risk of various types of cancer, though the existence of causal clinically relevant effects of low magnitude cannot be ruled out. These results, in combination with previous literature, provide evidence that population-wide screening for vitamin D deficiency and subsequent widespread vitamin D supplementation should not currently be recommended as a strategy for primary cancer prevention.

Lead, selenium and nickel concentrations in epithelial ovarian cancer, borderline ovarian tumor and healthy ovarian tissues.

OBJECTIVE: Wide variation exists in ovarian cancer incidence rates suggesting the importance of environmental factors. Due to increasing environmental pollution, trace elements and heavy metals have drawn attention in studies defining the etiology of cancer, but scant data is available for ovarian cancer. Our aim was to compare the tissue concentrations of lead, selenium and nickel in epithelial ovarian cancer, borderline tumor and healthy ovarian tissues. METHODS: The levels of lead, selenium and nickel were estimated using atomic absorption spectrophotometry in formalin-fixed paraffin-embedded tissue samples. Tests were carried out in 20 malignant epithelial ovarian cancer, 15 epithelial borderline tumor and 20 non-neoplastic healthy ovaries. Two samples were collected for borderline tumors, one from papillary projection and one from the smooth surface of cyst wall. RESULTS: Pb and Ni concentrations were found to be higher both in malignant and borderline tissues than those in healthy ovaries. Concentrations of Pb and Ni in malignant tissues, borderline papillary projections and capsular tissue samples were not different. Comparison of Se concentrations of malignant, borderline and healthy ovarian tissues did not reveal statistical difference. Studied metal levels were not found to be different in either papillary projection or in cyst wall of the borderline tumors. CONCLUSIONS: This study revealed the accumulation of lead and nickel in ovarian tissue is associated with borderline and malignant proliferation of the surface epithelium. Accumulation of these metals in epithelial ovarian cancer and borderline ovarian tumor has not been demonstrated before.

Difficulty in diagnosis and different prognoses between colorectal cancer with ovarian metastasis and advanced ovarian cancer: An empirical study of different surgical adoptions.

OBJECTIVE: To determine the clinical manifestations and optimal management of female patients with advanced colorectal cancer (CRC) metastasis in ovaries mimicking advanced ovarian malignancy. MATERIALS AND METHODS: A retrospective medical records review of female patients with primary CRC metastasis to ovaries, which were initially diagnosed as ovarian malignancy, and treated between 2001 and 2013. Clinical presentations, pathologic findings, and treatment outcomes were analyzed. RESULTS: In total, 19 cases were collected in the study through a hospital tumor registry. The mean age of the patients at the time of diagnosis was 45 years (range, 28-63 years). The most common symptoms were abdominal pain or increased abdominal girth (63%). None of them had rectal bleeding. The ratio of cancer antigen-125 to carcinoembryonic antigen was available in 13 out 19 patients (less than 25 in 76.9%). Barium enema or colonoscopic exam was only performed in 10 outpatients. None of them had a positive finding. All 19 patients went for surgery, all of them had ovarian metastasis but only eight of them had bilateral involvement, and 14 of them had carcinomatosis. All patients went for either optimal cytoreduction surgery or suboptimal cytoreduction surgery. The patients who received optimal cytoreduction surgery had a significant better progression-free and overall survival than those who did not. CONCLUSION: Clinical manifestations of primary CRC with ovarian metastasis may be confused with advanced ovarian cancer. Negative barium enema or colonoscopic exam cannot rule out the possibility of CRC. For patients with a cancer antigen-125 to carcinoembryonic antigen ratio less than 25, 76% are good reference of CRC metastasis to ovaries. Optimal cytoreduction surgery like that used for treating advanced ovarian cancer had a better prognosis than suboptimal cytoreduction colorectal cancer treatment.

[Purple-bluish tongue is associated with platelet counts, and the recurrence of epithelial ovarian cancer].

OBJECTIVE: To evaluate the relationship between purple-bluish tongue and platelet counts, and further to examine their associations with the recurrence of epithelial ovarian cancer. METHODS: A total of 82 epithelial ovarian cancer patients were enrolled in this study. Cluster analysis was used for grouping patients' P(RGB) (Red-R; Green-G; Blue-B; Average percentage of RGB, P(RGB)) values. Receiver operating characteristic (ROC) curve was performed for detecting the diagnostic standard of purple-bluish tongue. Χ2 test was used to assess the relationship between purple-bluish tongue and platelet counts, and the recurrence of epithelial ovarian cancer. The perioperative (preoperative) platelet level was examined with tongue image and disease recurrence. RESULTS: Tongue images were classified into two groups basing on P(RGB) values of images by cluster analysis. The numbers of cases in cluster "1" (normal color tongue) was 16 and cluster "2" (purple-bluish tongue) was 66. Two groups of P(RGB) values, classified by cluster analysis, were significantly correlated with vision-based tongue color recognition (Kappa = 0.852, P < 0.001). ROC curve showed that the ratio of P(B) to P(R) had the highest diagnostic value. The sensitivity and the specificity of the ratio of P(B) to P(R) were 95.3% and 88.9% respectively and the optimal cut-off point was 0.71. Purple-bluish tongue was significantly correlated with increased platelet counts (P < 0.001). Both the increased platelet counts (P = 0.01) and purple-bluish tongue were associated with recurrence of epithelial ovarian cancer (P < 0.001). CONCLUSION: The ratio of P(B) to P(R) greater than 0.71 could serve as an indicator for purple-bluish tongue diagnosing used in symptom pattern identification in Traditional Chinese Medicine. Purple-bluish tongue, associated with increased platelet counts, was also closely correlated with the recurrence of epithelial ovarian cancer.

Prospective association between alcohol intake and hormone-dependent cancer risk: modulation by dietary fiber intake.

BACKGROUND: Alcohol intake is associated with increased circulating concentrations of sex hormones, which in turn may increase hormone-dependent cancer risk. This association may be modulated by dietary fiber intake, which has been shown to decrease steroid hormone bioavailability (decreased blood concentration and increased sex hormone-binding globulin concentration). However, this potential modulation has not been investigated in any prospective cohort. OBJECTIVES: Our objectives were to study the relation between alcohol intake and the risk of hormone-dependent cancers (breast, prostate, ovarian, endometrial, and testicular) and to investigate whether dietary fiber intake modulated these associations. DESIGN: This prospective observational analysis included 3771 women and 2771 men who participated in the Supplémentation en Vitamines et Minéraux Antioxydants study (1994-2007) and completed at least 6 valid 24-h dietary records during the first 2 y of follow-up. After a median follow-up of 12.1 y, 297 incident hormone-dependent cancer cases, including 158 breast and 123 prostate cancers, were diagnosed. Associations were tested via multivariate Cox proportional hazards models. RESULTS: Overall, alcohol intake was directly associated with the risk of hormone-dependent cancers (tertile 3 vs. tertile 1: HR: 1.36; 95% CI: 1.00, 1.84; P-trend = 0.02) and breast cancer (HR: 1.70; 95% CI: 1.11, 2.61; P-trend = 0.04) but not prostate cancer (P-trend = 0.3). In stratified analyses (by sex-specific median of dietary fiber intake), alcohol intake was directly associated with hormone-dependent cancer (tertile 3 vs. tertile 1: HR: 1.76; 95% CI: 1.10, 2.82; P-trend = 0.002), breast cancer (HR: 2.53; 95% CI: 1.30, 4.95; P-trend = 0.02), and prostate cancer (HR: 1.37; 95% CI: 0.65, 2.89; P-trend = 0.02) risk among individuals with low dietary fiber intake but not among their counterparts with higher dietary fiber intake (P-trend = 0.9, 0.8, and 0.6, respectively). The P-interaction between alcohol and dietary fiber intake was statistically significant for prostate cancer (P = 0.01) but not for overall hormone-dependent (P = 0.2) or breast (P = 0.9) cancer. CONCLUSION: In line with mechanistic hypotheses and experimental data, this prospective study suggested that dietary fiber intake might modulate the association between alcohol intake and risk of hormone-dependent cancer. This trial was registered at clinicaltrials.gov as NCT00272428.

A complementary care study combining flaxseed oil, caffeine, fasting, and exercise in women diagnosed with advanced ovarian cancer: findings from a case study.

This article presents the experiences of 1 participant with advanced ovarian cancer enrolled in a proof of concept complementary therapy study evaluating the effects of a combined intervention of flaxseed oil, fasting, caffeine, and exercise. Improvements were observed in physical and psychological symptoms. The participant adopted positive lifestyle modifications.

25(OH)D3 in patients with ovarian cancer and its correlation with survival.

OBJECTIVES: The aim of this study was to examine vitamin 25(OH)D3 concentration in ovarian cancer patients in relation to a pathological subtype of the tumor, FIGO stage, grading, menopause status and overall 5-year survival. DESIGN AND METHODS: 72 epithelial ovarian cancer patients aged 37-79, who undergone optimal cytoreductive surgery were enrolled to the study group. Serum 25(OH)D3 concentration was measured using an electrochemiluminescence immunoassay before surgery. Serum concentration of 25(OH)D3 was also measured in a group of 65 healthy non-obese women aged 35-65 years. RESULTS: In patients with ovarian cancer serum concentration of 25(OH)D3 was lower than in the reference group (12.5±7.75 ng/mL vs 22.4±6.5 ng/mL). No significant correlation was found between serum 25(OH)D3 concentration and histological subtype, grading, FIGO stage and menopausal status. The study group was divided into two subgroups and the survival curves were analyzed. Overall 5-year survival rate was significantly higher in the subgroup of patients with 25(OH)D3 concentration over 10 ng/mL compared to women with concentration below 10 ng/mL. CONCLUSIONS: Low 25(OH) D3 concentration associated with lower overall survival rate might suggest for the important role of severe deficiency in more aggressive course of ovarian cancer. Testing for 25(OH)D in the standard procedure could help to find ovarian cancer patients with worse prognosis, who would benefit of special attention and supplementation.

A randomized parallel-group dietary study for stages II-IV ovarian cancer survivors.

OBJECTIVE: Few studies have examined the dietary habits of ovarian cancer survivors. Therefore, we conducted a study to assess the feasibility and impact of two dietary interventions for ovarian cancer survivors. METHODS: In this randomized, parallel-group study, 51 women (mean age, 53 years) diagnosed with stages II-IV ovarian cancer were recruited and randomly assigned to a low fat, high fiber (LFHF) diet or a modified National Cancer Institute diet supplemented with a soy-based beverage and encapsulated fruit and vegetable juice concentrates (FVJCs). Changes in clinical measures, serum carotenoid and tocopherol levels, dietary intake, anthropometry, and health-related quality of life (HRQOL) were assessed with paired t-tests. RESULTS: The recruitment rate was 25%, and the retention rate was 75% at 6 months. At baseline, 28% and 45% of women met guidelines for intake of fiber and of fruits and vegetables, respectively. After 6 months, total serum carotenoid levels and α- and ß-carotene concentrations were significantly increased in both groups (P<0.01); however, ß-carotene concentrations were increased more in the FVJC group. Serum ß-cryptoxanthin levels, fiber intake (+5.2g/day), and daily servings of juice (+0.9 servings/day) and vegetables (+1.3 servings/day) were all significantly increased in the LFHF group (all P<0.05). Serum levels of albumin, lutein and zeaxanthin, retinol, and retinyl palmitate were significantly increased in the FVJC group (all P<0.05). No changes in cancer antigen-125, anthropometry, or HRQOL were observed. CONCLUSION: Overall, this study supports the feasibility of designing dietary interventions for stages II-IV ovarian cancer survivors and provides preliminary evidence that a low fat high fiber diet and a diet supplemented with encapsulated FVJC may increase phytonutrients in ovarian cancer survivors.

Apolipoprotein A-I (apoA-I) and apoA-I mimetic peptides inhibit tumor development in a mouse model of ovarian cancer.

We examined whether reduced levels of Apolipoprotein A-I (apoA-I) in ovarian cancer patients are causal in ovarian cancer in a mouse model. Mice expressing a human apoA-I transgene had (i) increased survival (P < 0.0001) and (ii) decreased tumor development (P < 0.01), when compared with littermates, following injection of mouse ovarian epithelial papillary serous adenocarcinoma cells (ID-8 cells). ApoA-I mimetic peptides reduced viability and proliferation of ID8 cells and cis-platinum-resistant human ovarian cancer cells, and decreased ID-8 cell-mediated tumor burden in C57BL/6J mice when administered subcutaneously or orally. Serum levels of lysophosphatidic acid, a well-characterized modulator of tumor cell proliferation, were significantly reduced (>50% compared with control mice, P < 0.05) in mice that received apoA-I mimetic peptides (administered either subcutaneously or orally), suggesting that binding and removal of lysophosphatidic acid is a potential mechanism for the inhibition of tumor development by apoA-I mimetic peptides, which may serve as a previously unexplored class of anticancer agents.

Stanniocalcin 1 and ovarian tumorigenesis.

BACKGROUND: Stanniocalcin 1 (STC1) is a secreted glycoprotein hormone. High expression of STC1 has been associated with several cancers including ovarian cancer, but its role in the development of ovarian cancer is not clear. METHODS: We used five human ovarian epithelial cancer cell lines (OVCA420, OVCA432, OVCA433, SKOV3, and HEY), immortalized human ovarian surface epithelial cells (T29 and T80), ovarian cancer tissues from 342 patients, serum from 73 ovarian cancer patients and from58 control subjects, and 116 mice, with six or eight per group. Protein expression was assessed. Cells overexpressing STC1 protein were generated by ectopic expression of human STC1 cDNA. STC1 expression was silenced by using small interfering RNA against STC1. Cell proliferation, migration, colony formation, and apoptosis were assessed. Xenograft tumor growth in mice was studied. Neutralizing anti-STC1 antibody was used to inhibit STC1 function. All statistical tests were two-sided. RESULTS: STC1 protein expression was higher in all human ovarian cancer cell lines examined than in immortalized human ovarian epithelial cell lines, higher in ovarian cancer tissue than in normal ovarian tissue (P < .001), and higher in serum from ovarian cancer patients than from control subjects (P = .021). Ovarian cancer cells with STC1 overexpression, compared with corresponding control cells, had increased cell proliferation, migration, and colony formation in cell culture and increased growth of xenograft tumors in mice. These activities in normal or malignant ovarian cells with STC1 overexpression, compared with control cells, were also accompanied by increased expression of cell cycle regulatory proteins and antiapoptotic proteins but decreased cleavage of several caspases. Within 24 hours of treatment, apoptosis in cultures of HEY ovarian cancer cells treated with neutralizing anti-STC1 monoclonal antibody was higher (17.3% apoptotic cells) than that in cultures treated with mouse IgG control cells (4.4%) (12.9% difference, 95% confidence interval = 11.6% to 14.2%). CONCLUSIONS: STC1 protein may be involved in ovarian tumorigenesis.

TIMP-1 and VEGF-165 serum concentration during first-line therapy of ovarian cancer patients.

BACKGROUND: Angiogenesis appears to play an important role in ovarian cancer. Vascular endothelial growth factor (VEGF) has recently been implicated as a therapeutic target in ovarian cancer. The tissue inhibitor of metalloproteinase 1 (TIMP-1) is involved in tissue invasion and angiogenesis. The application of serum TIMP-1 and VEGF to monitor primary therapy and predict clinical outcome of patients with ovarian cancer is unclear. METHODS: Patients with epithelial ovarian cancer who presented for primary surgery were included in this study. A total of 148 serum samples from 37 patients were analyzed. Samples were prospectively collected at 4 predefined time points: 1. before radical debulking surgery, 2. after surgery and before platinum/taxane based chemotherapy, 3. during chemotherapy, 4. after chemotherapy. Serum VEGF-165 and TIMP-1 as well as CA-125 were quantified by ELISA or ECLIA and correlation with response and long-term clinical outcome was analyzed. RESULTS: Serum levels of all markers changed substantially during first-line therapy. High CA-125 (p = 0.002), TIMP-1 (p = 0.007) and VEGF-165 (p = 0.02) after chemotherapy were associated with reduced overall survival. In addition, elevated CA-125 (p < 0.001) and VEGF-165 (p = 0.006) at this time point predicted poor progression-free survival. TIMP-1 and VEGF-165 were closely correlated at all time-points during therapy. CONCLUSIONS: TIMP-1 and VEGF serum levels changed significantly during first-line therapy of ovarian cancer patients and predicted prognosis. These findings support the role of angiogenesis in ovarian cancer progression and the use of antiangiogenic therapy.

Serum S100A6 concentration predicts peritoneal tumor burden in mice with epithelial ovarian cancer and is associated with advanced stage in patients.

BACKGROUND: Ovarian cancer is the 5th leading cause of cancer related deaths in women. Five-year survival rates for early stage disease are greater than 94%, however most women are diagnosed in advanced stage with 5 year survival less than 28%. Improved means for early detection and reliable patient monitoring are needed to increase survival. METHODOLOGY AND PRINCIPAL FINDINGS: Applying mass spectrometry-based proteomics, we sought to elucidate an unanswered biomarker research question regarding ability to determine tumor burden detectable by an ovarian cancer biomarker protein emanating directly from the tumor cells. Since aggressive serous epithelial ovarian cancers account for most mortality, a xenograft model using human SKOV-3 serous ovarian cancer cells was established to model progression to disseminated carcinomatosis. Using a method for low molecular weight protein enrichment, followed by liquid chromatography and mass spectrometry analysis, a human-specific peptide sequence of S100A6 was identified in sera from mice with advanced-stage experimental ovarian carcinoma. S100A6 expression was documented in cancer xenografts as well as from ovarian cancer patient tissues. Longitudinal study revealed that serum S100A6 concentration is directly related to tumor burden predictions from an inverse regression calibration analysis of data obtained from a detergent-supplemented antigen capture immunoassay and whole-animal bioluminescent optical imaging. The result from the animal model was confirmed in human clinical material as S100A6 was found to be significantly elevated in the sera from women with advanced stage ovarian cancer compared to those with early stage disease. CONCLUSIONS: S100A6 is expressed in ovarian and other cancer tissues, but has not been documented previously in ovarian cancer disease sera. S100A6 is found in serum in concentrations that correlate with experimental tumor burden and with clinical disease stage. The data signify that S100A6 may prove useful in detecting and/or monitoring ovarian cancer, when used in concert with other biomarkers.

Selenium supplementation reduced oxidative DNA damage in adnexectomized BRCA1 mutations carriers.

Some experimental evidence suggests that BRCA1 plays a role in repair of oxidative DNA damage. Selenium has anticancer properties that are linked with protection against oxidative stress. To assess whether supplementation of BRCA1 mutation carriers with selenium have a beneficial effect concerning oxidative stress/DNA damage in the present double-blinded placebo control study, we determined 8-oxodG level in cellular DNA and urinary excretion of 8-oxodG and 8-oxoGua in the mutation carriers. We found that 8-oxodG level in leukocytes DNA is significantly higher in BRCA1 mutation carriers. In the distinct subpopulation of BRCA1 mutation carriers without symptoms of cancer who underwent adnexectomy and were supplemented with selenium, the level of 8-oxodG in DNA decreased significantly in comparison with the subgroup without supplementation. Simultaneously in the same group, an increase of urinary 8-oxoGua, the product of base excision repair (hOGG1 glycosylase), was observed. Therefore, it is likely that the selenium supplementation of the patients is responsible for the increase of BER enzymes activities, which in turn may result in reduction of oxidative DNA damage. Importantly, in a double-blinded placebo control prospective study, it was shown that in the same patient groups, reduction in cancer incidents was observed. Altogether, these results suggest that BRCA1 deficiency contributes to 8-oxodG accumulation in cellular DNA, which in turn may be a factor responsible for cancer development in women with mutations, and that the risk to developed breast cancer in BRCA1 mutation carriers may be reduced in selenium-supplemented patients who underwent adnexectomy.

Serum soluble Fas levels and prediction of response to platinum-based chemotherapy in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is treated mainly by platinum-based combination chemotherapy. Chemotherapy induces apoptosis in which the Fas/Fas ligand pathway is important. Serum soluble Fas (sFas) is a biomarker of this pathway and functionally inhibits Fas-/FasL-mediated apoptosis. In this study, we have investigated the role of sFas in prediction of response to chemotherapy in EOC. Thirty-five patients were recruited and their serum sFas levels were estimated by ELISA at 4 time points-preoperative (sFas1), postoperative (sFas2), midchemotherapy (sFas3) and at the end of chemotherapy (sFas4). The response to chemotherapy was documented clinically, radiologically and by CA-125 levels, based on which, 2 groups were identified: primary chemosensitive (n = 24) and primary chemoresistant (n = 11). Based on the disease status at last follow-up, 2 groups were identified: No Evidence of Disease (n = 15) and Evidence of Disease (n = 20). The primary chemoresistant tumors showed significantly higher median sFas2 levels (p = 0.033) with the sFas2/sFas1 ratio > or =1 (p = 0.001). A multivariate Cox proportional hazards regression model identified sFas2/sFas1 ratio as a significant factor for the prediction of response to platinum-based chemotherapy (p = 0.011). Receiver operating characteristic (ROC) analysis showed that at a ratio of 1.2, sFas2/sFas1 achieved a sensitivity of 82% and specificity of 100% for prediction of chemotherapeutic response. sFas2/sFas1 and sFas3/sFas1 ratio was also higher in patients with evidence of disease (p = 0.018 and p = 0.028, respectively). Progression-free survival rates in patients with sFas2/sFas1 ratio <1 exceeded those with ratio > or =1 (p = 0.004). In conclusion, serum sFas is a useful biomarker for predicting response to platinum-based chemotherapy in EOC.

Weekly low-dose paclitaxel and carboplatin therapy in gynecological cancer patients with venous thrombosis.

BACKGROUND: To evaluate the safety and toxicity of weekly low-dose paclitaxel plus carboplatin therapy in gynecological cancer patients with venous thrombosis (VT). MATERIALS AND METHODS: Ovarian or endometrial cancer patients with VT who were scheduled to receive neoadjuvant or adjuvant chemotherapy were eligible. Each 21-day cycle of treatment consisted of carboplatin (AUC 2.0) and paclitaxel (80 mg/m2) on days 1, 8 and 15. At the end of chemotherapy, each patient's VT was checked by ultrasonography. RESULTS: Twenty-five gynecological cancer patients who received warfarin therapy with a target international normalized ratio (INR) of 1.5-2.5 were enrolled in this study. Neutropenia and peripheral neuropathy (grades 3 or 4) occurred in 26% and 4% of the patients, respectively. Chemotherapy did not cause any changes of the INR in any patient. After chemotherapy, the VT showed resolution in 19 patients (76%) and no patient developed fresh thrombosis. CONCLUSION: Weekly low-dose paclitaxel plus carboplatin therapy is a reasonable treatment option for gynecological cancer patients with VT.

Chronotherapy of ovarian cancer: effect on blood variables and serum cytokines. A case report.

A 7-year-old patient with Stage III-c ovarian cancer was subjected to 8 cycles, approximately four weeks apart, of chronobiologically-optimized treatments with combination of three anti-cancer agents: Four cycles at AM, Cytoxan and PM, cis-Platinum; four cycles at AM, Adriamycin and PM, cis-Platinum. A second look laporoscopy revealed clean intestines, no definite masses in the pelvis area although there was an apparent mass in the right upper pelvis and several slightly enlarged lymph nodes in the base of mesentery. Six cycles of Taxol were administered at about Noon. Seven months remission appeared evident as judged by no changes in monthly examinations, in blood work or in CA-125 marker levels which remained below 12 U/ml. During the eight month the CA-125 marker began to rise, 36 then to 52 U/ml. A second 6 cycle series of Taxol was initiated but the CA-125 marker continued to rise, 57, 65, 72, 86, and 87 U/ml level. The patient declined in spirit, in well-being and expired 2 weeks later, 31 months after the initial diagnosis of cancer. Blood hematology, chemistry, and cytokines variables were analyzed at about weekly intervals. Significant reductions in total WBC, neutrophiles and platelet levels were evident during the second week of all cycle treatments, while increases were noted in serum levels of IL-2, IL-6 and IL-10 following Cytoxan-cis-Platinum-Adriamycin, but not Taxol. After each infusion moderate and temporary increases in RBC levels were noted. The treatments impact on hematology, chemistry, cytokine variables and on the integrity of the patient, are presented and briefly discussed.

Cancer screening and risk-reducing behaviors of women seeking genetic cancer risk assessment for breast and ovarian cancers.

PURPOSE/OBJECTIVES: To examine breast and ovarian cancer screening and risk-reducing behaviors of women seeking genetic cancer risk assessment (GCRA). DESIGN: Descriptive, cross-sectional. SETTING: An insurance-based clinic that serves high-risk patients in a southern California cancer center. SAMPLE: 134 women with breast or ovarian cancer (affected group) and 80 women with a family history of breast or ovarian cancer (unaffected group). The mean age of the sample was 48 years (range = 21-86), 79% were Caucasian, 66% were married, 60% were college educated, and 78% had children. Most affected women had early-stage disease. Unaffected women had a family history of breast (86%) or ovarian (14%) cancer. METHODS: Mailed surveys assessed pre-GCRA health behaviors and health and family histories. MAIN RESEARCH VARIABLES: Breast cancer screening (mammograms, clinical breast examination [CBE], breast self-examination), ovarian cancer screening (CA-125, pelvic ultrasound), and breast and ovarian cancer risk-reducing strategies (tamoxifen, bilateral mastectomy, oral contraceptive pills, bilateral salpingo-oophorectomy). FINDINGS: Twenty-one percent of the women who should have been having a mammogram had not had an annual examination as recommended, and 30% of affected women had not had annual CBEs. Few women took tamoxifen or oral contraceptive pills or had a bilateral salpingo-oophorectomy or bilateral mastectomy for cancer risk reduction. Twelve percent likely had unnecessary ovarian cancer screening. About 35% used other means, including herbs and homeopathy, for cancer prevention. CONCLUSIONS: Nearly a third of the affected women had not had appropriate breast cancer screening. About 12% used unsubstantiated, potentially harmful cancer "prevention" measures (e.g., herbs). IMPLICATIONS FOR NURSING: Nurses should assess clients' personal and family breast and ovarian cancer histories and promote cancer screening and risk-reducing behaviors that are appropriate for age and risk level.