IGFBP-4 tumor and serum levels are increased across all stages of epithelial ovarian cancer

<p>Abstract</p> <p>Background</p> <p>We sought to identify candidate serum biomarkers for the detection and surveillance of EOC. Based on RNA-Seq transcriptome analysis of patient-derived tumors, highly expressed secreted proteins were identified using a bioinformatic approach.</p> <p>Methods</p> <p>RNA-Seq was used to quantify papillary serous ovarian cancer transcriptomes. Paired end sequencing of 22 flash frozen tumors was performed. Sequence alignments were processed with the program ELAND, expression levels with ERANGE and then bioinformatically screened for secreted protein signatures. Serum samples from women with benign and malignant pelvic masses and serial samples from women during chemotherapy regimens were measured for IGFBP-4 by ELISA. Student's t Test, ANOVA, and ROC curves were used for statistical analysis.</p> <p>Results</p> <p>Insulin-like growth factor binding protein (IGFBP-4) was consistently present in the top 7.5% of all expressed genes in all tumor samples. We then screened serum samples to determine if increased tumor expression correlated with serum expression. In an initial discovery set of 21 samples, IGFBP-4 levels were found to be elevated in patients, including those with early stage disease and normal CA125 levels. In a larger and independent validation set (82 controls, 78 cases), IGFBP-4 levels were significantly increased (p < 5 × 10^-5). IGFBP-4 levels were ~3× greater in women with malignant pelvic masses compared to women with benign masses. ROC sensitivity was 73% at 93% specificity (AUC 0.816). In women receiving chemotherapy, average IGFBP-4 levels were below the ROC-determined threshold and lower in NED patients compared to AWD patients.</p> <p>Conclusions</p> <p>This study, the first to our knowledge to use RNA-Seq for biomarker discovery, identified IGFBP-4 as overexpressed in ovarian cancer patients. Beyond this, these studies identified two additional intriguing findings. First, IGFBP-4 can be elevated in early stage disease without elevated CA125. Second, IGFBP-4 levels are significantly elevated with malignant versus benign disease. These findings provide the rationale for future validation studies.</p

Application of RNA-Seq transcriptome analysis: CD151 is an Invasion/Migration target in all stages of epithelial ovarian cancer

<p>Abstract</p> <p>Background</p> <p>RNA-Seq allows a theoretically unbiased analysis of both genome-wide transcription levels and mutation status of a tumor. Using this technique we sought to identify novel candidate therapeutic targets expressed in epithelial ovarian cancer (EOC).</p> <p>Methods</p> <p>Specifically, we sought candidate invasion/migration targets based on expression levels across all tumors, novelty of expression in EOC, and known function. RNA-Seq analysis revealed the high expression of CD151, a transmembrane protein, across all stages of EOC. Expression was confirmed at both the mRNA and protein levels using RT-PCR and immunohistochemical staining, respectively.</p> <p>Results</p> <p>In both EOC tumors and normal ovarian surface epithelial cells we demonstrated CD151 to be localized to the membrane and cell-cell junctions in patient-derived and established EOC cell lines. We next evaluated its role in EOC dissemination using two ovarian cancer-derived cell lines with differential levels of CD151 expression. Targeted antibody-mediated and siRNA inhibition or loss of CD151 in SKOV3 and OVCAR5 cell lines effectively inhibited their migration and invasion.</p> <p>Conclusion</p> <p>Taken together, these findings provide the first proof-of-principle demonstration for a next generation sequencing approach to identifying candidate therapeutic targets and reveal CD151 to play a role in EOC dissemination.</p

Factors of Affecting Sleep Quality in Cancer Patients

Aim:Sleep disorders are one of the most common problems in patients with malignancy and they severely decrease the quality of life. We sought to investigate the frequency of sleep disturbances, its quantity, quality and possible correlation with related factors such as depression and anxiety.Materials and Methods:150 patients participated and the Pittsburgh Sleep Quality Index was used to evaluate the sleep quality. It is a self-administered questionnaire and standardized measure of sleep quality. Total score of ≥5 shows that the quality of sleep is remarkably bad. Also a self-report measure of depression, the Beck Depression Inventory (BDI); and a self-report measure of anxiety, Beck Anxiety Inventory (BAI) were used.Results:Of the 150 patients, 74.0% has bad sleep quality (score >5 ). Mean PSQI total score was 7.34 (min 0-max 20). No differences were found between PSQI mean scores in terms of gender, radiotherapy (RT), chemotherapy (CHT), having chronic disease or having metastatic disease. NSAIDs and opioids were significantly correlated with PSQI (p<0.001). PSQI total scores are strongly associated with the BDI score (r=.424, p<0.001) and BAI score (r=.417, p<0.001).Conclusion:We found a high prevalence rate of bad sleep quality at 74%. Effective sleep treatment and psychological support should be provided in oncology clinics

Design, synthesis and molecular modelling studies of some pyrazole derivatives as carbonic anhydrase inhibitors

Supuran, Claudiu/0000-0003-4262-0323; Ece, Abdulilah/0000-0002-3087-5145WOS: 000520863700001PubMed: 31797703In this study, newly synthesised compounds 6, 8, 10 and other compounds (1-5, 7 and 9) and their inhibitory properties against the human isoforms hCA I and hCA II were reported for the first time. Compounds 1-10 showed effective inhibition profiles with K-I values in the range of 5.13-16.9 nM for hCA I and of 11.77-67.39 nM against hCA II, respectively. Molecular docking studies were also performed with Glide XP to get insight into the inhibitory activity and to evaluate the binding modes of the synthesised compounds to hCA I and II. More rigorous binding energy calculations using MM-GBSA protocol which agreed well with observed activities were then performed to improve the docking scores. Results of in silico calculations showed that all compounds obey drug likeness properties. The new compounds reported here might be promising lead compounds for the development of new potent inhibitors as alternatives to classical hCA inhibitors

The demographic characteristics, prognosis, and relationship with cancer subtypes of hospitalized COVID-19 patients with malignancy: A single-center experience

Undoubtedly, cancer patients have suffered the most from the COVID-19 pandemic process. However, cancer is a heterogeneous disease, and each patient has responded differently to COVID-19. We aimed to describe the clinical characteristics and outcomes of patients with cancer and COVID-19. We retrospectively reviewed 45 cancer patients hospitalized in the Cerrahpasa Medical Faculty COVID-19 department from March 23 to October 23, 2020. We analyzed the demographic characteristics, symptoms, laboratory findings, treatment, prognosis, and cancer subtypes of patients and mortality who were hospitalized for COVID-19. Between March 23 and October 23, 2020, 45 hospitalized cancer patients who had laboratory-confirmed COVID-19 infection were included, with a median age of 60 years (range: 23-92). Patients were divided into two groups a survivor and a non-survivor. Symptoms, demographic information, comorbidities, treatments for COVID-19, and laboratory findings of the two groups were evaluated separately. Two parameters were found, which showed a significant difference between non-survivors and survivors displaying a disadvantage for COPD and low platelet count (p = 0.044-0.038). The mortality rate of all patients was 66%. The presence of comorbidities such as COPD and low platelet count in cancer patients with COVID-19 infection may draw the attention of physicians