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Citizen science programs that record wildlife observations on and along roads can help reduce the underreporting of wildlife-vehicle collisions and identify and prioritize road sections where mitigation measures may be required. It is important to evaluate potential biases in opportunistic citizen science data. We investigated whether the opportunistic observations of live animals by volunteers along a 46-km section of Highway 3 in the Crowsnest Pass area (“Road Watch in the Pass” data collection program) in Alberta, Canada, had a similar spatial pattern as systematically collected data by the researchers along the same road section. A permutation modeling process that compared the number of observations between the two datasets for each 1-km segment, a randomization method that tested for and compared hotspot observation locations, and a bivariate Ripley's L 1.2-function analysis along a continuum of spatial scales all showed spatial agreement between the two datasets. There was spatial agreement at a scale between 1 and 4 km, and three clear hotspots of wildlife observation activity were identified for both processes. This suggests that the data collected by the volunteers are reliable and robust enough to be used to help identify road sections that may require mitigation measures. In addition, volunteers proved to be able to collect a sufficient number of observations relatively quickly. Within one year, 24 volunteers collected 640 wildlife observations, and we found that using only 150 or more of these observations always resulted in spatial similarity with the systematic observations collected by the researchers. We conclude with recommendations for other citizen science data collection programs and for further research. [Copyright &y& Elsevier]

Abstract: This study was conduced to assess the effects of a one time embryonic exposure to p,p′-DDE (dichlorodiphenyldichloroethylene; DDE) on the reproductive development and function in Japanese quail (Coturnix japonica). Embryos were exposed at day one of incubation to either 20 or 40 μg DDE or a sesame oil vehicle control (injection volume=20 μl). Onset of puberty, gonadal histopathology, sperm motility, cloacal gland size, and male copulatory behavior were assessed in adults. DDE accelerated onset of puberty in females and reduced male reproductive behaviors. Gonadal morphology and sperm motility appeared to be unaffected. Results from this study provide evidence that the neuroendocrine system may be more sensitive and less resilient to embryonic exposure to contaminants than traditional measures of reproductive success following contaminant exposure in adults. This study further supports the inclusion of behavioral assessments in toxicity tests. [Copyright &y& Elsevier]

Objective: The aim of this study was to establish a reference 24-hour urine human chorionic gonadotropin (hCG) regression curve in patients with complete hydatidiform mole (CHM) as diagnostic tool in the prediction of persistent trophoblastic disease (PTD). Methods: From 2004 to 2011, 312 cases suitable for this study were registered at the Hydatidiform Mole Registry of the Royal Women's Hospital Melbourne, Australia. hCG levels of 61 patients diagnosed as having PTD according to FIGO 2000 criteria were compared with the 95th-percentile (p95) of the normal regression curve derived from hCG levels of 251 cases of uneventful CHM. Results: In the test group of 61 patients PTD was diagnosed by FIGO 2000 criteria after a mean (±SD, min.–max.) of 7.6 (±3.4, 3.0–16.7) weeks after evacuation of the mole while in the same group hCG values for the first time exceeded the upper limit of the 95th percentile significantly earlier after 4.5 (±1.9, 2.0–9.9) weeks (P<0.001). However, hCG levels of 14% of the cases of uneventful CHM at least once exceeded the upper limit of p95, showing that one single value above p95 is not accurate enough for the diagnosis of PTD. Conclusions: The normal 24-hour urine hCG regression curve may be used as a tool in the follow-up of an individual case of CHM after evacuation. At least one hCG level exceeding the upper limit of p95 within 11weeks after evacuation could be added to the current FIGO criteria, in order to diagnose PTD early, but the lack of it may also prevent unnecessary treatment. [ABSTRACT FROM AUTHOR]

Abstract: Objectives.: To evaluate the impact of PET/CT on the restaging and management of recurrent ovarian cancer. Methods. : From January 2002 to July 2003, all women undergoing either surveillance or investigation of possible recurrent ovarian cancer at the Centre for Molecular Imaging, The Peter MacCallum Cancer Centre, were invited to take part in a prospective evaluation of the clinical impact of PET/CT. Results.: Fifty-six women having 66 scans were available for analysis. All patients had at least 12months follow-up after the PET/CT unless they died before that time. Apart from one equivocal scan, all scans performed in women with a CA125 higher than 35IU/ml had a positive PET/CT. PET/CT altered the known disease distribution in 40 scans (64%). Overall, PET/CT showed less disease in six scans (9%) and more disease in 34 scans (52%). Regardless of the value of CA125, PET/CT identified a sub group of women with apparently localized disease or no definite evidence of disease. This group showed improved survival compared with women shown to have systemic disease. PET/CT resulted in a major change of management plan in 34 patients (58%). Conclusion. : PET/CT modifies the assessment of the distribution of recurrent ovarian cancer and alters patient management in a substantial proportion of patients. PET/CT appears to offer prognostic information. [Copyright &y& Elsevier]

: ObjectiveThe known overexpression of matrix metalloproteinases (MMPs) by various tumors prompted a study to determine whether endometrial cancer could be detected by measuring MMPs in uterine cavity washings.: MethodsThe study populations comprised 95 women being treated for endometrial cancer and 98 women with other gynecological conditions. A simple method was developed for performing uterine lavage and preparing cell-free uterine supernatants for MMP analysis. Gelatin zymography revealed elevated levels of latent and active forms of MMP-2 and MMP-9 in patients with endometrial cancer. For each patient individual bands of gelatinase activity were scored from 0 to 5 and summed to provide a total MMP score for analysis.: ResultsThe mean MMP score in uterine washings of patients with endometrial cancer was 10.0 (range 1 to 22) compared with 0.8 (range 0 to 15) in the group without this cancer (P < 0.001). Receiver operating characteristic analysis showed that an MMP cutoff score of 3 gave a sensitivity of 98% and specificity of 91% for detecting endometrial cancer. With this MMP cutoff, a positive result was 11 times as likely in endometrial cancer compared to other conditions. The mean MMP score in the group with nodal metastases (14.1) was significantly higher than that without nodal involvement (9.4, P = 0.005). MMP-9 but not MMP-2 was significantly associated with nodal metastasis (P = 0.01). There was no significant association between MMP score and histological grade of tumor, vascular invasion, or depth of myometrial invasion.: ConclusionGelatinase measurement in uterine washings was reliable for confirming the presence of endometrial cancer in the population studied. [Copyright &y& Elsevier]

Previously, we described the inhibition of proinflammatory mediators such as nitric oxide, tumor necrosis factor-α (TNF-α), and prostaglandin E2 by taurine chloramine (Tau-Cl) in activated rodent macrophages. We also demonstrated that Tau-Cl suppressed superoxide anion, IL-6, and IL-8 production in activated human polymorphonuclear leukocytes separated from peripheral blood. In these studies, we report the effect of Tau-Cl on lymphocyte proliferation and the production of cytokines by activated human peripheral blood mononuclear leukocytes. Adherent and nonadherent leukocytes were activated using lipopolysaccharide (LPS) and phytohemagglutinin (PHA), respectively, in the presence or absence of Tau-Cl. Tau-Cl significantly suppressed lymphocyte proliferation as measured by tritiated (3H) thymidine. Production of IL-6, IL-8, and IL-2 in PHA-activated nonadherent leukocytes was inhibited by Tau-Cl. The production of IL-1β, IL-6, and IL-8 was also decreased in LPS-activated adherent monocytes by Tau-Cl. These data demonstrate that the ability of Tau-Cl to modulate the immune response is not species specific and extends to human leukocytes. [Copyright &y& Elsevier]

Objective To determine endometrial cancer (EC) risk according to family cancer history, including assessment by degree of relatedness, type of and age at cancer diagnosis of relatives. Methods Self-reported family cancer history was available for 1353 EC patients and 628 controls. Logistic regression was used to quantify the association between EC and cancer diagnosis in ≥ 1 first or second degree relative, and to assess whether level of risk differed by degree of relationship and/or relative's age at diagnosis. Risk was also evaluated for family history of up to three cancers from known familial syndromes (Lynch, Cowden, hereditary breast and ovarian cancer) overall, by histological subtype and, for a subset of 678 patients, by EC tumor mismatch repair (MMR) gene expression. Results Report of EC in ≥ 1 first- or second-degree relative was associated with significantly increased risk of EC ( P = 3.8 × 10 − 7 ), independent of lifestyle risk factors. There was a trend in increasing EC risk with closer relatedness and younger age at EC diagnosis in relatives ( P Trend = 4.43 × 10 − 6 ), and with increasing numbers of Lynch cancers in relatives ( P Trend ≤ 0.0001). EC risk associated with family history did not differ by proband tumor MMR status, or histological subtype. Reported EC in first- or second-degree relatives remained associated with EC risk after conservative correction for potential misreported family history (OR 2.0; 95% CI, 1.24–3.37, P = 0.004). Conclusion The strongest predictor of EC risk was closer relatedness and younger EC diagnosis age in ≥ 1 relative. Associations remained significant irrespective of proband MMR status, and after excluding MMR pathogenic variant carriers, indicating that Lynch syndrome genes do not fully explain familial EC risk. [ABSTRACT FROM AUTHOR]

Objective This study evaluated single nucleotide polymorphisms (SNPs) associated with progression free (PFS) and overall survival (OS) in patients with advanced stage serous EOC. Methods Patients enrolled in GOG-172 and 182 who provided specimens for translational research and consent were included. Germline DNA was evaluated with the Illumina's HumanOMNI1-Quad beadchips and scanned using Illumina's iScan optical imaging system. SNPs with allele frequency > 0.05 and genotyping rate > 0.98 were included. Analysis of SNPs for PFS and OS was done using Cox regression. Statistical significance was determined using Bonferroni corrected p -values with genomic control adjustment. Results The initial GWAS analysis included 1,124,677 markers in 396 patients. To obtain the final data set, quality control checks were performed and limited to serous tumors and self-identified Caucasian race. In total 636,555 SNPs and 289 patients passed all the filters. The pre-specified statistical level of significance was 7.855e − 08 . No SNPs met this criteria for PFS or OS, however, two SNPs were close to significance (rs10899426 p -2.144e − 08 ) (rs6256 p -9.774e − 07 ) for PFS and 2 different SNPs were identified (rs295315 p -7.536e − 07 ; rs17693104 p -7.734e − 07 ) which were close to significance for OS. Conclusions Using the pre-specified level of significance of 1 × 10 − 08 , we did not identify any SNPs of statistical significance for OS or PFS, however several were close. The SNP's identified in this GWAS study will require validation and these preliminary findings may lead to identification of novel pathways and biomarkers. [ABSTRACT FROM AUTHOR]

Objective Cancer-related lymphedema is a debilitating condition that adversely influences function, health and quality of life. The purpose of this study was to assess the prevalence, incidence, and risk factors of lower-limb lymphedema pre- through to 24 months post-surgery for gynecological cancer. Methods A clinic-based sample of women (n = 408) with gynecological cancer participated in a prospective, longitudinal study (2008–2011) using self-reported measures (swelling in one or both legs) and objectively measured lymphedema (bioimpedance spectroscopy) at baseline (pre-surgery), six weeks–three months, 6–12 months, and 15–24 months post-surgery. Results At pre-surgery, 15% of women self-reported lymphedema and 27% had measurable evidence of lymphedema. By 24 months post-surgery, incidence of new self-reported or measured lymphedema was 45% and 37%, respectively. Three-quarters of these new cases presented by 12-months post-treatment. While lymphedema was transient for some women, 60% had persistent lymphedema. More extensive lymph node dissection, receipt of chemotherapy and radiation therapy, increasing body mass index, insufficient levels of physical activity, diagnosis of vulvar/vaginal cancer and presence of pre-treatment lymphedema were identified as potential risk factors (p < 0.05). Conclusion Findings support the need for integration of pre-surgical assessment, and prospective, post-treatment surveillance of lymphedema into gynecological cancer care. Future research exploring the role of maintaining healthy body weight, regular physical activity and education about early detection of lymphedema to improve gynecological cancer survivorship is warranted. [ABSTRACT FROM AUTHOR]

Objectives Few studies have assessed the risk and impact of lymphedema among women treated for endometrial cancer. We aimed to quantify cumulative incidence of, and risk factors for developing lymphedema following treatment for endometrial cancer and estimate absolute risk for individuals. Further, we report unmet needs for help with lymphedema-specific issues. Methods Women treated for endometrial cancer (n = 1243) were followed-up 3-5 years after diagnosis; a subset of 643 completed a follow-up survey that asked about lymphedema and lymphedema-related support needs. We identified a diagnosis of secondary lymphedema from medical records or self-report. Multivariable logistic regression was used to evaluate risk factors and estimates. Results Overall, 13% of women developed lymphedema. Risk varied markedly with the number of lymph nodes removed and, to a lesser extent, receipt of adjuvant radiation or chemotherapy treatment, and use of nonsteroidal anti-inflammatory drugs (pre-diagnosis). The absolute risk of developing lymphedema was > 50% for women with 15 + nodes removed and 2-3 additional risk factors, 30-41% for those with 15 + nodes removed plus 0-1 risk factors or 6-14 nodes removed plus 3 risk factors, but ≤ 8% for women with no nodes removed or 1-5 nodes but no additional risk factors. Over half (55%) of those who developed lymphedema reported unmet need(s), particularly with lymphedema-related costs and pain. Conclusion Lymphedema is common; experienced by one in eight women following endometrial cancer. Women who have undergone lymphadenectomy have very high risks of lymphedema and should be informed how to self-monitor for symptoms. Affected women need greater levels of support. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To quantitatively assess and compare the quality of life (QoL) of women with a self-reported diagnosis of lower limb lymphedema (LLL), to women with lower limb swelling (LLS), and to women without LLL or LLS following treatment for endometrial cancer. Methods: 1399 participants in the Australian National Endometrial Cancer Study were sent a follow-up questionnaire 3–5years after diagnosis. Women were asked if they had experienced swelling in the lower limbs and, if so, whether they had received a diagnosis of lymphedema by a health professional. The 639 women who responded were categorized as: Women with LLL (n=68), women with LLS (n=177) and women without LLL or LLS (n=394). Multivariable-adjusted generalized linear models were used to compare women's physical and mental QoL by LLL status. Results: On average, women were 65years of age and 4years after diagnosis. Women with LLL had clinically lower physical QoL (M =41.8, SE =1.4) than women without LLL or LLS (M =45.1, SE =0.8, p =.07), however, their mental QoL was within the normative range (M =49.6; SE =1.1 p =1.0). Women with LLS had significantly lower physical (M =41.0, SE =1.0, p =.003) and mental QoL (M =46.8; SE =0.8, p <.0001) than women without LLL or LLS (Mental QoL: M =50.6, SE =0.8). Conclusion: Although LLL was associated with reductions in physical QoL, LLS was related to reductions in both physical and mental QoL 3–5years after cancer treatment. Early referral to evidence-based lymphedema programs may prevent long-term impairments to women's QoL. [Copyright &y& Elsevier]

Abstract: Objective: HE4 has emerged as a promising biomarker in gynaecological oncology. The purpose of this study was to evaluate serum HE4 as a biomarker for high-risk phenotypes in a population-based endometrial cancer cohort. Methods: Peri-operative serum HE4 and CA125 were measured in 373 patients identified from the prospective Australian National Endometrial Cancer Study (ANECS). HE4 and CA125 were quantified on the ARCHITECT instrument in a clinically accredited laboratory. Receiver operator curves (ROC), Spearman rank correlation coefficient, and chi-squared and Mann–Whitney tests were used for statistical analysis. Survival analysis was performed using Kaplan–Meier and Cox multivariate regression analyses. Results: Median CA125 and HE4 levels were higher in stage III and IV tumours (p<0.001) and in tumours with outer-half myometrial invasion (p<0.001). ROC analysis demonstrated that HE4 (area under the curve (AUC)=0.76) was a better predictor of outer-half myometrial invasion than CA125 (AUC=0.65), particularly in patients with low-grade endometrioid tumours (AUC 0.77 vs 0.64 for CA125). Cox multivariate analysis demonstrated that elevated HE4 was an independent predictor of recurrence-free survival (HR=2.40, 95% CI 1.19–4.83, p=0.014) after adjusting for stage and grade of disease, particularly in the endometrioid subtype (HR=2.86, 95% CI 1.25–6.51, p=0.012). Conclusion: These findings demonstrate the utility of serum HE4 as a prognostic biomarker in endometrial cancer in a large, population-based study. In particular they highlight the utility of HE4 for pre-operative risk stratification to identify high-risk patients within low-grade endometrioid endometrial cancer patients who might benefit from lymphadenectomy. [Copyright &y& Elsevier]

Abstract: Ovarian cancer is a prevalent gynecological malignancy with potent immune-suppression capabilities; regulatory T cells (Tregs) are significant contributors to this immune-suppression. As ovarian cancer patients present with high levels of TNF and Tregs expressing TNFR2 are associated with maximal suppressive capacity, we investigated TNFR2+ Tregs within these patients. Indeed, TNFR2+ Tregs from tumor-associated ascites were the most potent suppressor T cell fraction. They were abundantly present within the ascites and more suppressive than peripheral blood TNFR2+ Tregs in patients. The increased suppressive capacity can be explained by a distinct cell surface expression profile, which includes high levels of CD39, CD73, TGF-β and GARP. Additionally, CD73 expression level on TNFR2+ Tregs was inversely correlated with IFN-γ production by effector T cells. This Treg fraction can be selectively recruited into the ascites from the peripheral blood of patients. Targeting TNFR2+ Tregs may offer new approaches to enhance the poor survival rates of ovarian cancer. [Copyright &y& Elsevier]

Abstract: Objective: Previous studies on prognostic factors in ovarian tumors of low malignant potential (LMP) were too small for robust conclusions. We examined the prognostic impact of preoperative serum CA125≥50U/ml levels in patients diagnosed with ovarian LMP tumors in a large multinational cohort. Methods: This retrospective study included 940 patients with ovarian LMP tumors diagnosed between 1985 and 2008 at six gynecologic cancer centers. Patients either had radical treatment (bilateral salpingo-oophorectomy with or without hysterectomy) or conservative, fertility-sparing treatment. Multivariate Cox proportional hazard models were used to determine independent prognostic factors for disease-free (DFS) and overall survival (OS). Based on receiver operating characteristic curve (ROC), a preoperative serum CA125 level≥50U/ml was considered “elevated”. Results: CA125 was more often elevated in serous than in mucinous tumors and in advanced FIGO stages (2 to 4) compared to stage1. DFS at 5years was 89% and 95% in patients with elevated and normal CA125 levels (p<0.05). Similarly, the 5-year OS was 90% among patients with elevated CA125 compared to 95% among patients with normal levels (p<0.05). For both DFS and OS elevated CA125 levels and advanced stages of the disease were independent prognostic factors. Analysis of subgroups revealed that CA125 was only prognostic in serous LMP tumors. Conclusions: In the context of serous ovarian LMP tumors, elevated preoperative serum CA125 represents a biomarker independently associated with impaired disease-free and overall survival. CA125 is available in most centers and could inform surgeons about the risk of treatment failure. [Copyright &y& Elsevier]

Abstract: Ovarian cancer remains a leading cause of cancer death. A comparative proteomic study was performed on normal ovarian tissue (n =5) and grade 3 ovarian tumours (n =5) to search for differentially expressed proteins. In contrast to other studies, here we extracted proteins in soluble and insoluble protein fractions using commercial kits and also utilised three medium-range IPG strips that encompassed the broad pH range of 3–10 (pH 3–6, 5–8 and 7–10). Protein fractions were compared by 2D-PAGE and MALDI-TOF/TOF-MS. Nineteen differentially expressed proteins were identified: HSP60, Grp78, CK19, EF-Tu, MRLC2, prohibitin, Stress-70 protein, TPI and tubulin α6 were up-regulated in grade 3 tumours whereas annexin A2 and A5, antithrombin-III precursor, CBR1, GSTM2, GSTM3, RALDH1, serum albumin precursor, transthyretin precursor and vimentin were found to be down-regulated in grade 3 ovarian tumours. These proteins are associated with cytoskeleton rearrangement, cell metabolism, tumour suppression function, apoptosis and induction of host response. [Copyright &y& Elsevier]

Abstract: Endocrine disrupting chemicals (EDCs) from a variety of sources occur widely in the environment, but relationships between exposure to EDCs and long term effects on bird populations can be difficult to prove. Embryonic exposure to EDCs may be particularly detrimental, with potential long-term effects on reproduction and ultimately individual fitness. Because many EDCs may have subtle sublethal effects, it is necessary to establish sensitive end points as biomarkers of EDC exposure in birds. Because the effects of EDCs may be both short- and long-term, it is important to determine if embryonic exposure impacts sexual differentiation and development of the reproductive axis in hatchlings and if there are effects on reproductive function in adults. Our studies have focused on the effects of estrogen- and androgen-active EDCs on the hypothalamic gonadotropin releasing hormone–I (GnRH-I) system in an avian model of precocial species, the Japanese quail. Estrogen- or androgen-active EDCs were administered between 0 and embryonic day 4, and hypothalamic GnRH-I was measured in hatchlings and adults. Treatment with vinclozolin and PCB126 depressed the concentration of embryonic GnRH-I peptide while methoxyclor had an inconsistent stimulatory effect. Treatment with atrazine or trenbolone had no significant effects on hypothalamic GnRH-I in adults. Overall these observations support the view that the developing avian GnRH-I neural system may be vulnerable to EDCs with potential to alter lifelong reproductive function. [Copyright &y& Elsevier]

Abstract: Objective : To investigate the efficacy of different treatment modalities used in microinvasive adenocarcinoma (AC) of the uterine cervix (FIGO stage IA1 and IA2), and review the literature. Methods : Medical and histopathological records of 38 patients treated for microinvasive AC of the cervix were studied retrospectively, and compared with the literature. Results : Twenty-nine patients had stage IA1 and nine stage IA2 cancers. Treatment modalities ranged from radical hysterectomy with pelvic lymph node dissection (PLND) to conization only. Eighteen patients underwent a conization, including two patients with stage IA2 disease, of whom 11 had 18 pregnancies in total, resulting in 13 live births, two terminations and three spontaneous abortions. In two patients a hysterectomy was performed after pregnancy. No recurrences were noted during an average follow-up of 72 months. In the literature 1565 patients were reported. Of the 814 patients undergoing PLND, 12 had positive nodes. Lymphvascular space invasion (LVSI) was present in 25 patients, all without node involvement. None of the 356 described parametria were involved. Twenty-nine recurrences occurred. In total, 21 pregnancies with 16 live births occurred in those patients treated to preserve fertility. Conclusions : There is no uniformity in the treatment of microinvasive AC of the uterine cervix. For stage IA1 disease, conization seems to be safe and PLND is only recommended where LVSI is present. Although the number of reported cases is small, for stage IA2 disease, conization with PLND in case of LVSI seems advisable. More studies are desirable to define the optimal treatment for patients with microinvasive AC of the cervix, especially with regard to those patients with stage IA2 disease. [Copyright &y& Elsevier]

Abstract: Background. : No consensus exists which patients with surgical stage 1 epithelial ovarian should receive postoperative chemotherapy. The purpose of this study was to evaluate the prognostic impact of preoperative CA-125 and to establish a prognostic index to identify patients in different risk categories. Methods. : Data of 600 surgically staged patients with FIGO stage 1 EOC treated in eleven gynecological cancer centers in Australia, the USA and Europe were analyzed. Eligible patients include those with invasive EOC where a preoperative CA-125 was obtained and standard surgical staging performed. Overall survival (OS) was chosen as study endpoint. Preoperative CA-125 values were compared with other prognostic factors, and univariate and multivariate Cox models were calculated. Results. : Two hundred and one patients (33.5%) had preoperative CA-125 ≤30 U/ml and CA-125 levels ≤30 U/ml were associated with lower grade, substage 1A and mucinous histologic cell type. Patients with elevated CA-125 levels were more likely to receive chemotherapy. OS probability was 95% and 85% for patients with pretreatment CA-125 ≤30 U/ml and >30 U/ml, respectively (p 0.003). Multivariate analysis confirmed preoperative serum CA-125 >30 U/ml (OR 2.7) and age at diagnosis >70 years (OR 2.6) as the only independent predictors for overall survival. Conclusion. : Pretreatment of CA-125 ≤30 U/ml dominates over histologic cell type, substage and grade to identify a subgroup of FIGO stage 1 patients with a genuinely good prognosis with extremely good survival and who could possibly be spared with adjuvant chemotherapy. [Copyright &y& Elsevier]

Objective. To determine the activity of capecitabine in women with platinum-resistant ovarian cancer.Methods. In this multi-centre phase II trial, 35 patients with platinum-resistant ovarian, primary peritoneal or fallopian tube carcinomas were treated with capecitabine 1250 mg/m2 twice daily for 14 days every 21 days. Platinum resistance was defined as progression within 4 months of completing the last platinum and all patients had previously received a taxane. Response was assessed by both RECIST criteria for patients with measurable disease and CA125 criteria. Responders were defined as patients with measurable disease who achieved a CR or PR according to RECIST criteria, patients without measurable disease who met the CA125 criteria for response and patients with stable measurable disease who met the CA125 criteria for response.Results. Patients had received a median of four prior chemotherapy regimens (range 1–9). The median number of cycles of capecitabine administered was 3 (range 1–10). The response rate using the combined RECIST and CA125 criteria was 9% (95% CI 2–25%). In patients evaluable using RECIST criteria, the response rate was 5% (95% CI 0–25%). In patients evaluable for CA125 response, the response rate was 7% (95% CI 1–22%). The median progression-free survival was 2.3 months, and the median survival was 7.1 months. Treatment was generally well tolerated with most frequent grade 3 toxicities being hand–foot syndrome (17%) and diarrhea (9%).Conclusion. Capecitabine is well tolerated but has limited activity in patients with heavily pre-treated platinum-resistant ovarian cancer. [Copyright &y& Elsevier]

Objective. Elevated levels of proteases are linked to the malignant phenotype in a wide variety of solid tumors. Therefore, the expression of plasminogen, matrix metalloproteinases (MMP-2 and MMP-9), and of the serine protease urokinase-type plasminogen activator (uPA) in serous epithelial carcinoma of the ovary were investigated.Methods. Plasminogen antigen was analyzed in tissue extracts and in the urine of patients with normal (n = 12), benign (n = 6), borderline (n = 9), and invasive serous tumors (n = 22) by Western immunoblotting using rabbit polyclonal plasminogen and murine monoclonal angiostatin antibodies. In the same tissue extracts, semiquantitative estimates of MMP-2, MMP-9, total MMP activity, and uPA activity were determined using semiquantitative gelatin zymography in the presence or absence of human plasminogen.Results. Bands corresponding to Glu-plasminogen (approximately 92 kDa) and Lys-plasminogen (approximately 86 kDa) were detected in all ovarian tissues and in corresponding urine samples. Densitometric analysis of combined Glu- or Lys-plasminogen levels showed significantly decreased levels in malignant compared to normal tissue. In Grade 3 cancers, there was no evidence of Glu-plasminogen or angiostatin. MMP activity was significantly elevated in both borderline and in Grade 3 ovarian cancer tissues. Increased tissue uPA activity on zymograms was detected only in Grade 3 ovarian cancer tissue.Conclusion. These data suggest that proteolytic activity of the plasminogen activation cascade increases in serous epithelial ovarian carcinoma. [Copyright &y& Elsevier]