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Objective: To describe the design of, and participant-level outcomes related to, a religiously tailored, peer-led group education program aimed at enhancing Muslim women's mammography intention. Method: Using a community-engaged approach and mixed methods, we identified and addressed barrier beliefs impeding mammography screening among Muslim American women. Our religiously tailored, mosque-based, peer-led intervention involved facilitated discussions and expert-led didactics conveying health-related religious teachings, and information about the benefits and process of mammography. Barrier beliefs were addressed through reframing, reprioritizing, or reforming such beliefs. Participant surveys were collected preintervention, postintervention, 6 months postintervention, and 1 year postintervention. These measured changes in mammography intention, likelihood, confidence, and resonance with barrier and facilitator beliefs. Results: A total of 58 Muslim women (mean age = 50 years) that had not had a mammogram in the past 2 years participated in the two-session program. Self-reported likelihood of obtaining a mammogram increased significantly (p = 0.01) and coincided with a positive trend in confidence (p = 0.08). Individuals with higher agreement with barrier beliefs preintervention had lower odds for positive change in likelihood (odds ratio = 0.80, p = 0.03), while those who were married had higher odds for positive change in likelihood (odds ratio = 37.69, p = 0.02). At 1-year follow-up, 22 participants had obtained a mammogram. Conclusion: Our pilot mosque-based intervention demonstrated efficacy in improving Muslim women's self-reported likelihood of obtaining mammograms, and increased their mammography utilization, with nearly 40% obtaining a mammogram within 12 months of the intervention. Impact: Our conceptual model for religiously tailoring messages, along with its implementation curriculum, proved effective in enhancing the likelihood and receipt of mammograms among Muslim American women. Accordingly, our work advances both the theory and practice of faith-based interventions and provides a model for addressing Muslim women's cancer screening disparities.

BackgroundMany loci have been found to be associated with risk of epithelial ovarian cancer (EOC). However, although there is considerable variation in progression-free survival (PFS), no loci have been found to be associated with outcome at genome-wide levels of significance.MethodsWe carried out a genome-wide association study (GWAS) of PFS in 2,352 women with EOC who had undergone cytoreductive surgery and standard carboplatin/paclitaxel chemotherapy.ResultsWe found seven SNPs at 12q24.33 associated with PFS (P < 5 × 10-8), the top SNP being rs10794418 (HR = 1.24; 95% CI, 1.15-1.34; P = 1.47 × 10-8). High expression of a nearby gene, ULK1, is associated with shorter PFS in EOC, and with poor prognosis in other cancers. SNP rs10794418 is also associated with expression of ULK1 in ovarian tumors, with the allele associated with shorter PFS being associated with higher expression, and chromatin interactions were detected between the ULK1 promoter and associated SNPs in serous and endometrioid EOC cell lines. ULK1 knockout ovarian cancer cell lines showed significantly increased sensitivity to carboplatin in vitro.ConclusionsThe locus at 12q24.33 represents one of the first genome-wide significant loci for survival for any cancer. ULK1 is a plausible candidate for the target of this association.ImpactThis finding provides insight into genetic markers associated with EOC outcome and potential treatment options.See related commentary by Peres and Monteiro, p. 1604.

BackgroundCoffee consumption has been shown to be associated with various health outcomes in observational studies. However, evidence for its association with epithelial ovarian cancer (EOC) is inconsistent and it is unclear whether these associations are causal.MethodsWe used single nucleotide polymorphisms associated with (i) coffee and (ii) caffeine consumption to perform Mendelian randomization (MR) on EOC risk. We conducted a two-sample MR using genetic data on 44 062 individuals of European ancestry from the Ovarian Cancer Association Consortium (OCAC), and combined instrumental variable estimates using a Wald-type ratio estimator.ResultsFor all EOC cases, the causal odds ratio (COR) for genetically predicted consumption of one additional cup of coffee per day was 0.92 [95% confidence interval (CI): 0.79, 1.06]. The COR was 0.90 (95% CI: 0.73, 1.10) for high-grade serous EOC. The COR for genetically predicted consumption of an additional 80 mg caffeine was 1.01 (95% CI: 0.92, 1.11) for all EOC cases and 0.90 (95% CI: 0.73, 1.10) for high-grade serous cases.ConclusionsWe found no evidence indicative of a strong association between EOC risk and genetically predicted coffee or caffeine levels. However, our estimates were not statistically inconsistent with earlier observational studies and we were unable to rule out small protective associations.

ObjectiveThis study evaluated single nucleotide polymorphisms (SNPs) associated with progression free (PFS) and overall survival (OS) in patients with advanced stage serous EOC.MethodsPatients 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.ResultsThe 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.ConclusionsUsing 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.

We previously identified associations with ovarian cancer outcome at five genetic loci. To identify putatively causal genetic variants and target genes, we prioritized two ovarian outcome loci (1q22 and 19p12) for further study. Bioinformatic and functional genetic analyses indicated that MEF2D and ZNF100 are targets of candidate outcome variants at 1q22 and 19p12, respectively. At 19p12, the chromatin interaction of a putative regulatory element with the ZNF100 promoter region correlated with candidate outcome variants. At 1q22, putative regulatory elements enhanced MEF2D promoter activity and haplotypes containing candidate outcome variants modulated these effects. In a public dataset, MEF2D and ZNF100 expression were both associated with ovarian cancer progression-free or overall survival time. In an extended set of 6,162 epithelial ovarian cancer patients, we found that functional candidates at the 1q22 and 19p12 loci, as well as other regional variants, were nominally associated with patient outcome; however, no associations reached our threshold for statistical significance (p

Glutamine, glutamate, asparagine, and aspartate are involved in an enzyme-network that controls nitrogen metabolism. Branched-chain-amino-acid aminotransferase-1 (BCAT1) promotes proliferation of gliomas with wild-type IDH1 and is closely connected to the network. We hypothesized that metabolism of asparagine, glutamine, and branched-chain-amino-acids is associated with progression of malignant gliomas. Gene expression for asparagine synthetase (ASNS), glutaminase (GLS), and BCAT1 were analyzed in 164 gliomas from 156 patients [33-anaplastic gliomas (AG) and 131-glioblastomas (GBM), 64 of which were recurrent GBMs]. ASNS and GLS were twofold higher in GBMs versus AGs. BCAT1 was also higher in GBMs. ASNS expression was twofold higher in recurrent versus new GBMs. Five patients had serial samples: 4-showed higher ASNS and 3-higher GLS at recurrence. We analyzed grade and treatment in 4 groups: (1) low ASNS, GLS, and BCAT1 (n = 96); (2) low ASNS and GLS, but high BCAT1 (n = 26); (3) high ASNS or GLS, but low BCAT1 (n = 25); and (4) high ASNS or GLS and high BCAT1 (n = 17). Ninety-one  % of patients (29/32) with grade-III lesions were in group 1. In contrast, 95 % of patients (62/65) in groups 2-4 had GBMs. Treatment was similar in 4 groups (radiotherapy-80 %; temozolomide-30 %; other chemotherapy-50 %). High expression of ASNS, GLS, and BCAT1 were each associated with poor survival in the entire group. The combination of lower ASNS, GLS, and BCAT1 levels correlated with better survival for newly diagnosed GBMs (66 patients; P = 0.0039). Only tumors with lower enzymes showed improved outcome with temozolomide. IDH1(WT) gliomas had higher expression of these genes. Manipulation of amino acid metabolism in malignant gliomas may be further studied for therapeutics development.

Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded.

This study explored the role of God and spirituality in cancer patients to gain deeper insight into how patients use their spirituality to cope during illness, including how they see the medical team meeting their spiritual needs. From our work, some naturally emerging themes included Finding God in Cancer and Healing, Spiritual Support Desired from Medical Community, Doctor as "Gift from God"?, and Communication and the Power of Talk. Cancer patients not only acknowledged a spiritual need, but a desire for it to be addressed by their medical team as part of their treatment. [ABSTRACT FROM AUTHOR]

Objective: Studies suggest that American Muslim women underutilize mammography. While religion has a strong influence upon Muslim health behaviors, scant research has examined how religion-related beliefs inform Muslim women's intention for mammography. Our study identifies and examines such beliefs.Methods: Muslim women aged 40 years and older sampled from mosques participated in focus groups and individual interviews. Drawing upon the theory of planned behavior, interviews elicited salient behavioral, normative, and control beliefs regarding mammography and the influence of Islam upon screening intention.Results: Fifty women participated in 6 focus groups and 19 in semistructured interviews, with near-equal numbers of African American, South Asian, and Arab Muslims. Forty-two percent of participants had not had a mammogram within the past 2 years. Across differences in race/ethnicity and mammography status, women voiced four religion-related salient beliefs that inform mammography intention: (1) the perceived duty to care for one's health, (2) religious practices as methods of disease prevention, (3) fatalistic notions about health, and (4) comfort with gender concordant health care.Conclusions: Religious beliefs influence decisions to pursue mammography across the ethnic/racial diversity of Muslim women. Notions about duty to God and the stewardship of one's body appear to enhance mammography intention. Theocentric notions of cure and illness and varied views regarding personal agency also inform decisional frames that impact mammography intention. Given the salience of religion among our participants, religiously tailored messages in interventions have the potential to enhance cancer screening. [ABSTRACT FROM AUTHOR]

Objective To identify predictors of anxiety and depression symptom trajectories, as distinct from general distress, in the 96 weeks following diagnosis of breast or gynaecologic cancer. Methods Participants completed the Hospital Anxiety and Depression Scale anxiety subscale (HADS-A) and Centre for Epidemiological Studies Depression Scale (CES-D) at diagnosis and at 8-weekly intervals for 96 weeks. Linear mixed models were used to determine the effects of age, relationship status, tumour stream, cancer stage, living situation, residential area, educational status, current and previous anxiety/depression treatment and neuroticism on symptom trajectories. Results Participants were 264 women with a mean (SD) age of 54 (12) years. Compared to non-treatment-receiving counterparts, women who received anxiety/depression treatment in the past had depression and anxiety symptom severity scores that were 4.58 and 1.24 higher, respectively. Women receiving such treatment at cancer diagnosis had depression and anxiety scores that were 4.34 and 2.35 points higher, respectively, than their counterparts. Compared to women with the lowest neuroticism scores, women with the highest scores scored 8.48 and 3.82 higher on the CES-D and HADS-A, respectively. Depressive severity remained stable but anxiety severity decreased as a function of neuroticism. Conclusions In settings with limited resources, women with high neuroticism or a depression/anxiety treatment history should be the initial target of psychological screening. Identification of women with these characteristics at the earliest point of entry into the oncology service followed by heightened surveillance and/or referral to psychosocial services may be useful to prevent chronic psychological morbidity. [ABSTRACT FROM AUTHOR]

Aims Cyclophosphamide was widely used as a single agent prior to the advent of platinum-based regimens for epithelial ovarian cancer, and, in combination with platinum, prior to the adoption of platinum and paclitaxel as standard first-line therapy. As cyclophosphamide currently has no defined role in ovarian cancer we aimed to assess its activity in women with recurrent disease. Methods A retrospective review was conducted of patients from three centers in Melbourne, Australia who had received oral cyclophosphamide treatment for recurrent ovarian cancer. The primary end-point was response rate to oral cyclophosphamide (150 mg p.o. day 1-14) based on Gynecologic Cancer InterGroup ( GCIG) CA125 and/or Response Evaluation Criteria in Solid Tumors ( RECIST) criteria. Secondary end-points included overall and progression-free survival and toxicity. Results In all, 26 patients were identified and 23 patients were evaluable for response. The median number of prior chemotherapy regimens was three (range 1-6). The response rate to oral cyclophosphamide was 44% with 10 of the 23 patients achieving a partial response ( PR) based on GCIG ( CA125) criteria. The median number of cycles received was three (range 1-16). Cyclophosphamide showed activity both in patients with platinum-sensitive (seven of 13 PR) and resistant or refractory disease (three of 10 PR). There was no grade 3 or 4 toxicity but two patients ceased cyclophosphamide due to less severe non-hematological toxicity. Conclusion Single agent oral cyclophosphamide is active and well tolerated in recurrent ovarian cancer. Further investigation of oral cyclophosphamide in patients with platinum-sensitive and platinum-resistant disease is warranted. [ABSTRACT FROM AUTHOR]

Objective This study aims to investigate the course and prevalence of anxiety and depression symptoms over 56 weeks in women with newly diagnosed breast and gynaecologic cancer and determine the acceptability and efficiency of incorporating routine screening into practice. Methods Participants completed the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A) and Centre for Epidemiological Studies Depression Scale (CES-D) at diagnosis and again every 8 weeks for 56 weeks. Changes over time were analysed with repeated measures ANOVA adjusted for post hoc comparisons. Thresholds for caseness/referral to mental health were ≥11 and ≥16 on the HADS-A and CES-D, respectively. Results Participants were 167 women (101 breast, 66 gynaecologic). Mean ± SD age was 57.63 ± 22.66 years. Rates of anxiety (17.7%), depression (32.5%) and combined anxiety and depression (35%) symptoms were highest at diagnosis. Mean ± SD scores of anxiety (6.43 ± 3.83) and depression symptoms (12.68 ± 9.47) were highest at diagnosis with significant improvements observed by 8 and 24 weeks, respectively, and maintained thereafter. Overall rates of anxiety, depression and combined symptoms were 7.5%, 23.4% and 24.1%, respectively. Patients with breast and gynaecologic cancer did not differ. Referral was offered at least once to 94 women (56.3%), of whom 45 (47.9%) declined, 23 (24.5%) accepted and 26 (27.7%) were already receiving treatment. Patient evaluation was favourable. Conclusions Women are most vulnerable to psychological morbidity at diagnosis. Symptoms improve significantly over time. Reported rates are lower than those in the literature. Regular screening by self-report is acceptable to patients but may not be the most efficient method of improving patient outcomes. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The ovarian surface epithelium (OSE) is the precursor of common epithelial ovarian carcinomas. In the present study, we examined the molecular mechanisms and possible physiological basis for the propensity of OSE cells to undergo epithelio-mesenchymal transition (EMT) in response to environmental influences. We hypothesized that EMT may be a homeostatic mechanism that permits displaced OSE to assume a stromal phenotype within the ovarian cortex. We report that EGF in conjunction with hydrocortisone is the EMT-inducing factor of OSE as shown by changes to a fibroblast-like morphology and growth pattern. EGF increased cell motility, enhanced the activities of secreted pro-matrix metalloproteinase (MMP)-2 and -9, and enhanced expression and activation of Erk and integrin-linked kinase (ILK). Increased ILK expression correlated with the activation of PKB/Akt, the phosphorylation of GSK-3β, and the increased expression of cyclin E and cdk2 kinase. EGF withdrawal resulted in a more epithelial morphology and reversal of the EGF-induced activation of signaling pathways and pro-MMP activity. In contrast, treatment of EGF-treated cells with specific inhibitors of phosphatidylinositol 3-kinase, Mek, or ILK inhibited the inhibitor-specific pathways. The inhibitors caused suppression of EGF-induced migration and pro-MMP-2/-9 activities but did not lead to any change in EGF-induced mesenchymal morphology. ILK small interfering RNA inhibited Akt phosphorylation and reduced pro-MMP-2/-9 activities but had no effect on Erk activation or cell morphology. These results indicate that the EGF-induced morphological and functional changes in OSE cells are controlled by distinct signaling mechanisms working in concert. EMT of OSE cells displaced by ovulation likely permits their survival and integration with a fibroblast-like identity within the stroma. Failure to do so may lead to the formation of epithelium-derived inclusion cysts, which are known preferential sites of malignant transformation. [ABSTRACT FROM AUTHOR]

Aims and objectives: Social and cultural factors are identified that impact on complementary therapy use among Australia-born and immigrant women diagnosed with gynaecological cancer. Methods: A qualitative study design including in-depth interviews with women diagnosed with gynaecological cancer (N=53) and participant observation was conducted. Results: Approximately one-third of women utilized complementary and alternative medicine, with this being determined by current health concerns and health beliefs related to the efficacy of different modalities. Four types of complementary therapy users emerged: consequential, therapeutic, informed and exploratory. Conclusion: There was a relatively low uptake of complementary treatments. Choice was influenced by women's socio-demographic background, clinical and personal history, lack of personal experiences of gynaecological cancer among study participants' kin and friends, and lack of popular alternative literature on such cancer. Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 49-year-old multiparous premenopausal woman who was diagnosed with menorrhagia and ovarian cyst. In December 1997, the patient showed menopausal signs, and began a trial of continuous combined hormone replacement therapy (HRT) that was stopped due to migraine. She has experienced vaginal bleeding, demonstrating complex hyperplasia with atypia. It discusses the synthetic steroid pro-hormone called tibolone and endometrial hyperplasia.

Presents a case report of minimal deviation adenocarcinoma (MDA) in an aged woman with cervical adenocarcinoma. Medical history of the woman; Result of the woman's trachelectomy; Characteristics of patients with MDA.

A response by David D.L. Bowtell and his colleagues to a letter to the editor on their article "The genesis and evolution of highgrade serous ovarian cancer," published in a previous issue of the journal is presented.

Drawing on data from interviews and other ethnographic research, we examine how Australian women from different ethnic and cultural backgrounds make sense of having gynecological cancer. Alternative explanatory models often co-exist in a single narrative, but there is significant consistency in the etiology of cancer among Australian-born and immigrant women. In acknowledging the unpredictability of cancer and the prognosis of particular disease, women contextualize their own experience as a matter of luck, outside their control or influence. Most often women relate their own occurrence of cancer to their social setting and relational factors rather than personal behavior, but at the same time, they acknowledge the interaction of external forces and individual factors, particularly in the case of diet and stress. Women can control diet to some extent, although many note the irony of having developed cancer even when they have eaten well. Stress, on the other hand, is largely considered as external to and beyond women's control. Women speak of stress as a characteristic of contemporary social life, as well as their own public and domestic, physical and emotional lives; for these women stress in any of these areas can create physical vulnerability that may result in cancer. Since women associate cancer with loss of control, the idea of cancerous cells out-of-control within their bodies operates as a metonym of women's views of themselves interpersonally and socially. [ABSTRACT FROM AUTHOR]

Objective: To revise FIGO staging of carcinoma of the cervix uteri, allowing incorporation of imaging and/or pathological findings, and clinical assessment of tumor size and disease extent.Methods: Review of literature and consensus view of the FIGO Gynecologic Oncology Committee and related societies and organizations.Results: In stage I, revision of the definition of microinvasion and lesion size as follows. Stage IA: lateral extension measurement is removed; stage IB has three subgroups-stage IB1: invasive carcinomas ≥5 mm and <2 cm in greatest diameter; stage IB2: tumors 2-4 cm; stage IB3: tumors ≥4 cm. Imaging or pathology findings may be used to assess retroperitoneal lymph nodes; if metastatic, the case is assigned stage IIIC; if only pelvic lymph nodes, the case is assigned stage IIIC1; if para-aortic nodes are involved, the case is assigned stage IIIC2. Notations 'r' and 'p' will indicate the method used to derive the stage-i.e., imaging or pathology, respectively-and should be recorded. Routine investigations and other methods (e.g., examination under anesthesia, cystoscopy, proctoscopy, etc.) are not mandatory and are to be recommended based on clinical findings and standard of care.Conclusion: The revised cervical cancer staging is applicable to all resource levels. Data collection and publication will inform future revisions. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Depression is common in cancer patients but frequently undetected. Consensus regarding validity and optimal thresholds of screening measures is lacking. We investigated the validity of the Hospital Anxiety and Depression Scale (HADS-D) and Center for Epidemiological Studies Depression Scale (CES-D) relative to a referent diagnostic standard in women with breast or gynecologic cancer. Method: Participants were 100 patients who completed the CES-D and HADS-D within a larger study. The Mini International Neuropsychiatric Interview was the criterion standard. Sensitivity, specificity, predictive values and likelihood ratios for various thresholds were calculated using receiver operating characteristics. Participants were assigned to two diagnostic groups: ‘major depressive disorder’ or ‘any depressive disorder’. Results: Separate analyses were conducted whereby participants found to be receiving depression/anxiety treatment at the time of validation (n=28) were excluded. Both measures had good internal consistency and criterion validity. There were no statistical differences in global accuracy between the measures for detecting either group. For optimal sensitivity and specificity in both groups, generally recommended thresholds were lowered for the HADS-D. For the CES-D, the threshold was lowered for ‘any depressive disorder’ and raised for ‘major depressive disorder’. Negative predictive values associated with our recommended cutoffs were excellent, but positive predictive values were poor. Conclusions: The HADS-D and CES-D have acceptable properties and are equivalent for detecting depression in this population. Depending on the purpose of screening, the CES-D may be more suitable for identifying major depression. Threshold choice may have serious implications for screening program effectiveness, and the use of generally recommended thresholds should be cautious. [Copyright &y& Elsevier]