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Ovarian cancer - Top 30 Publications

Hidden estrogen production from ovarian remnants leading to progression of disease in metastatic breast cancer.

In premenopausal women with hormone dependent breast cancers, ovarian suppression is an important part of treatment, and is often achieved with a bilateral salpingo-oophorectomy (BSO). However, this procedure can lead to ovarian remnant syndrome (ORS), a rare condition where the adnexal tissue is not completely removed and can produce estrogen. We describe a case of ORS in a patient with estrogen receptor positive (ER+) breast cancer who had progression of disease after undergoing a BSO, despite optimal therapy. ORS therefore poses a significant treatment challenge in premenopausal ER+ breast cancer patients thought to be rendered menopausal with a BSO.

Impact on disease-free survival of the duration of ovarian function suppression, as postoperative adjuvant therapy, in premenopausal women with hormone receptor-positive breast cancer: a retrospective single-institution study.

Although tamoxifen (TAM) plus ovarian function suppression (OFS) is considered as a standard adjuvant treatment for premenopausal women with hormone receptor-positive breast cancer, the optimal duration of OFS has not yet been established. This retrospective study was designed to assess the duration of OFS and the impact of the duration of OFS on the DFS in these patients.

The use of PIPAC (pressurized intraperitoneal aerosol chemotherapy) in gynecological oncology: a statement by the German "Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR)", the Swiss and Austrian AGO, and the North-Eastern German Society of Gynaecologic Oncology.

Ovarian, tubal, and peritoneal carcinomas primarily affect the peritoneal cavity, and they are typically diagnosed at an advanced tumor stage (Foley, Rauh-Hain, del Carmen in Oncology (Williston Park) 27:288-294, 2013). In the course of primary surgery, postoperative tumor residuals are, apart from the tumor stage, the strongest independent factors of prognosis (du Bois, Reuss, Pujade-Lauraine, Harter, Ray-Coquard, Pfisterer in Cancer 115:1234-1244, 2009). Due to improved surgical techniques, including the use of multi-visceral procedures, macroscopic tumor clearance can be achieved in oncological centers, in most cases (Harter, Muallem, Buhrmann et al in Gynecol Oncol 121:615-619, 2011). However, to date, it has not been shown that peritoneal carcinomatosis is, per se, an independent factor of prognosis or that it excludes the achievement of tumor clearance. Several studies have shown that a preceding drug therapy in peritoneal carcinomatosis could positively influence the overall prognosis (Trimbos, Trimbos, Vergote et al in J Natl Cancer Inst 95:105-112, 2003). In relapses of ovarian carcinoma, studies have shown that peritoneal carcinomatosis is a negative predictor of complete tumor resection; however, when it is possible to resect the tumor completely, peritoneal carcinomatosis does not play a role in the prognosis (Harter, Hahmann, Lueck et al in Ann Surg Oncol 16:1324-1330, 2009).

Identification and analysis of CHEK2 germline mutations in Chinese BRCA1/2-negative breast cancer patients.

Cell-cycle-checkpoint kinase 2 (CHEK2) is an important moderate-penetrance breast cancer predisposition gene; however, recurrent CHEK2 mutations found in Caucasian women are very rare in Chinese population. We investigated the mutation spectrum and clinical relevance of CHEK2 germline mutations in Chinese breast cancer patients.

No Evidence for the Pathogenicity of the BRCA2 c.6937 + 594T>G Deep Intronic Variant: A Case-Control Analysis.

The role of deep intronic variants in hereditary cancer susceptibility has been largely understudied. Previously, the BRCA2 c.6937 + 594T>G variant has been shown to preferentially promote the inclusion of a 95 nucleotide cryptic exon and to introduce a premature termination codon. Our objective was to further assess the pathogenicity of the BRCA2 c.6937 + 594T>G deep intronic variant.

Palladium(II)-Stabilized Pyridine-2-Diazotates: Synthesis, Structural Characterization, and Cytotoxicity Studies.

Well-defined diazotates are scarce. Here we report the synthesis of unprecedented homoleptic palladium(II) diazotate complexes. The palladium(II)-mediated nitrosylation of 2-aminopyridines with NaNO2 results in the formation of metal-stabilized diazotates, which were found to be cytotoxic to human ovarian cancer cells.

Inflammatory potential of diet and risk of pancreatic cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

Inflammation plays a central role in pancreatic cancer etiology and can be modulated by diet. We aimed to examine the association between the inflammatory potential of diet, assessed with the Dietary Inflammatory Index (DII®), and pancreatic cancer risk in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial prospective cohort. Our study included 101,449 participants aged 52 to 78 years at baseline who completed both baseline questionnaire and a diet history questionnaire. Energy-adjusted DII (E-DII) scores were computed based on food and supplement intake. Cox proportional hazards models and time dependent Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with participants in the lowest E-DII quintile (most anti-inflammatory scores) as referent. After a median 8.5 years of follow-up, 328 pancreatic cancer cases were identified. E-DII scores were not associated with pancreatic cancer risk in the multivariable model (HRQ5vsQ1 =0.94; 95% CI=0.66-1.35; P-trend=0.43). Time significantly modified the association (P-interaction=0.01). During follow up <4 years, there was suggestive evidence of an inverse association between E-DII and pancreatic cancer (HRQ5vsQ1 =0.60; 95% CI=0.35-1.02; P-trend=0.20) while there was a significant positive trend in the follow up ≥4 years (HRQ5vsQ1 =1.31; 95% CI=0.83-2.08; P-trend=0.03). Similar results were observed for E-DII from food only. Our study does not support an association between inflammatory potential of diet and pancreatic cancer risk; however, heterogeneous results were obtained with different follow-up times. These divergent associations may result from the influences of undetected disease in the short-term. This article is protected by copyright. All rights reserved.

A case of paraneoplastic elastosis perforans serpiginosa associated with ovarian malignancy.

Elastosis perforans serpiginosa (EPS) is a rare skin disorder in which there is transepithelial elimination of elastin fibers. It belongs to a group of perforating disorders of which there are four classic types. The EPS type is extremely rare. There have been no previous reports of elastosis perforans serpiginosa occurring as a paraneoplastic phenomenon. We report a case of paraneoplastic elastosis perforans serpiginosa in the setting of stage 4 ovarian cancer.

Procancerogenic activity of senescent cells: a case of the peritoneal mesothelium.

Human peritoneal mesothelial cells belong to a narrow group of somatic cells in which both the triggers and the mechanisms of senescence have already been well defined. Importantly, senescent mesothelial cells have been found in the peritoneal cavity in vivo. From a clinical point of view, peritoneal mesothelial cells have been recognized as playing a critical role in the intraperitoneal development of tumor metastases. The pro-cancerogenic behavior of mesothelial cells is even more pronounced when the cells exhaust their proliferative capacity and become senescent. In this review, we summarize the current state of art regarding the contribution of peritoneal mesothelial cells in the progression of ovarian, colorectal, and pancreatic carcinomas, with particular attention paid to the cancer-promoting activity of their senescent counterparts. Moreover, we delineate the mechanisms, mediators, and signaling pathways that are engaged by the senescent mesothelial cells to support such vital elements of cancer progression as adhesion, proliferation, migration, invasion, epithelial-mesenchymal transition, and angiogenesis. Finally, we discuss the experimental evidence regarding both natural and synthetic compounds that may either prevent or restrict cancer development by delaying senescence of mesothelial cells.

Molybdenum cluster loaded PLGA nanoparticles: an innovative theranostic approach for the treatment of ovarian cancer.

We evaluate poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles embedding inorganic molybdenum octahedral cluster for photodynamic therapy of cancer (PDT). Tetrabutyl ammonium salt of Mo6Br14 cluster unit, (TBA)2Mo6Br14, presents promising photosensitization activity in the destruction of targeted cancer cells. Stable cluster loaded nanoparticles (CNPs) were prepared by solvent displacement method showing spherical shapes, zeta potential values around -30 mV, polydispersity index lower than 0.2 and sizes around 100 nm. FT-IR and DSC analysis revealed the lack of strong chemical interaction between the cluster and the polymer within the nanoparticles. In vitro release study showed that (TBA)2Mo6Br14 was totally dissolved in 20 min, while CNPs were able to control the release of encapsulated cluster. In vitro cellular viability studies conducted on A2780 ovarian cancer cell line treated up to 72 hours with cluster or CNPs did not show any sign of toxicity in concentrations up to 20 µg/ml. This concentration was selected for photo-activation test on A2780 cells and CNPs were able to generate oxygen singlet resulting in a decrease of the cellular viability up to 50%, respectively compared to non-activated conditions. This work presents (TBA)2Mo6Br14 as a novel photosensitizer for PDT and suggests PLGA nanoparticles as an efficient delivery system intended for tumor targeting.

Elucidating the gene regulatory networks modulating cancer stem cells and non-stem cancer cells in high grade serous ovarian cancer.

The origin and pathogenesis of epithelial ovarian cancer have perplexed investigators for decades. The most prevalent type of it is the high-grade serous ovarian carcinoma (HGSOv) which is a highly aggressive disease with high relapse rates and insurgence of chemo-resistance at later stages of treatment. These are driven by a rare population of stem cell like cancer cells called cancer stem cells (CSCs). We have taken up a systems approach to find out the common gene interaction paths between non-stem cancer cells and CSCs in HGSOv. Detailed investigation reveals a set of 17 Transcription Factors (named as pivot-TFs) which can govern changes in the mode of gene regulation along these paths. Overall, this work highlights a divergent road map of functional information relayed by these common key players in the two cell states, which might aid towards designing novel therapeutic measures to target the CSCs for ovarian cancer therapy.

Natural Killer Cell-Based Immunotherapy in Gynecologic Malignancy: A Review.

Harnessing the immune system has proven an effective therapy in treating malignancies. Since the discovery of natural killer (NK) cells, strategies aimed to manipulate and augment their effector function against cancer have been the subject of intense research. Recent progress in the immunobiology of NK cells has led to the development of promising therapeutic approaches. In this review, we will focus on the recent advances in NK cell immunobiology and the clinical application of NK cell immunotherapy in ovarian, cervical, and uterine cancer.

A Systematic Assessment of Google Search Queries and Readability of Online Gynecologic Oncology Patient Education Materials.

The Internet is a major source of health information for gynecologic cancer patients. In this study, we systematically explore common Google search terms related to gynecologic cancer and calculate readability of top resulting websites. We used Google AdWords Keyword Planner to generate a list of commonly searched keywords related to gynecologic oncology, which were sorted into five groups (cervical cancer, ovarian cancer, uterine cancer, vulvar cancer, vaginal cancer) using five patient education websites from . Each keyword was Google searched to create a list of top websites. The Python programming language (version 3.5.1) was used to describe frequencies of keywords, top-level domains (TLDs), domains, and readability of top websites using four validated formulae. Of the estimated 1,846,950 monthly searches resulting in 62,227 websites, the most common was . The most common TLD was *.com. Most websites were above the eighth-grade reading level recommended by the American Medical Association (AMA) and the National Institute of Health (NIH). The SMOG Index was the most reliable formula. The mean grade level readability for all sites using SMOG was 9.4 ± 2.3, with 23.9% of sites falling at or below the eighth-grade reading level. The first ten results for each Google keyword were easiest to read with results beyond the first page of Google being consistently more difficult. Keywords related to gynecologic malignancies are Google-searched frequently. Most websites are difficult to read without a high school education. This knowledge may help gynecologic oncology providers adequately meet the needs of their patients.

Dermatoglyphic patterns on fingers and gynecological cancers.

Fingerprints have so far been used for determining the basis of certain malignant diseases, with positive outcomes. Considering the high rates of cancer-related mortality in Iran, this study was conducted for the purpose of examining the dermatoglyphic pattern of fingers in patients with gynecological cancers as compared to healthy people.

Serum miR-1181 and miR-4314 associated with ovarian cancer: MiRNA microarray data analysis for a pilot study.

This study aims to identify serum microRNAs (miRNAs) related to ovarian cancer.

Adherence to practice guidelines is associated with reduced referral times for patients with ovarian cancer.

Patients with ovarian cancer tend to receive the highest quality of care at high-volume cancer centers with gynecologic oncologists. However, the care that they receive prior to gynecologic oncology consult has not been examined. We investigated the quantity and quality of care given to patients with ovarian cancer before being seen by a gynecologic oncologist.

Phase I combination study of the PARP inhibitor veliparib plus carboplatin and gemcitabine in patients with advanced ovarian cancer and other solid malignancies.

Determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of veliparib combined with carboplatin and gemcitabine in patients with advanced ovarian cancer and other nonhematologic malignancies.

Exceptional response to pembrolizumab in a metastatic, chemotherapy/radiation resistant ovarian cancer patient harboring a CD274/PD-L1-genetic rearrangement.

Ovarian carcinoma no longer responsive to surgery and chemotherapy remains an incurable disease. Alternative therapeutic options remain desperately needed.

Phosphorylation of EZH2 by AMPK Suppresses PRC2 Methyltransferase Activity and Oncogenic Function.

Sustained energy starvation leads to activation of AMP-activated protein kinase (AMPK), which coordinates energy status with numerous cellular processes including metabolism, protein synthesis, and autophagy. Here, we report that AMPK phosphorylates the histone methyltransferase EZH2 at T311 to disrupt the interaction between EZH2 and SUZ12, another core component of the polycomb repressive complex 2 (PRC2), leading to attenuated PRC2-dependent methylation of histone H3 at Lys27. As such, PRC2 target genes, many of which are known tumor suppressors, were upregulated upon T311-EZH2 phosphorylation, which suppressed tumor cell growth both in cell culture and mouse xenografts. Pathologically, immunohistochemical analyses uncovered a positive correlation between AMPK activity and pT311-EZH2, and higher pT311-EZH2 correlates with better survival in both ovarian and breast cancer patients. Our finding suggests that AMPK agonists might be promising sensitizers for EZH2-targeting cancer therapies.

FANCM and RECQL genetic variants and breast cancer susceptibility: relevance to South Poland and West Ukraine.

FANCM and RECQL have recently been reported as breast cancer susceptibility genes and it has been suggested that they should be included on gene panel tests for breast cancer predisposition. However, the clinical value of testing for mutations in RECQL and FANCM remains to be determined. In this study, we have characterised the spectrum of FANCM and RECQL mutations in women affected with breast or ovarian cancer from South-West Poland and West Ukraine.

Tibolone and risk of gynecological hormone sensitive cancer.

Risk of ovarian cancer with hormone therapy is associated with use of both unopposed estrogen therapy and combined estrogen-progestin therapy, whereas for endometrial cancer addition of continuous progestin decreases the estrogen induced increased risk. Less is known about risk with use of tibolone; a synthetic steroid with estrogenic, progestagenic, and androgenic properties. We assessed these associations in a prospective cohort study, including all Danish women 50-79 years of age and followed 1995-2009. National Danish Registers captured individually updated exposure information, cancer cases including histology and confounding factors. Poisson regression analyses provided multiple adjusted incidence rate ratio's (IRR). More than 900,000 women were followed for 9.8 years on average; 4,513 were diagnosed with ovarian cancer and 6,202 with endometrial cancer. Compared to women never on postmenopausal hormone therapy, current users of tibolone had an increased IRR for ovarian cancer (1.42(95% confidence interval [CI], 1.01-2.00) and serous ovarian tumors (2.21(95%CI 1.48-3.32)). The risk increased with duration of use, particularly for serous ovarian tumors. Compared to never users, the IRR of endometrial cancer was 3.56(95%CI 2.94-4.32) among current users of tibolone and 3.80(95%CI 3.08-4.69) of Type 1 endometrial cancer. The steepest risk increase with duration of use was for Type I tumors. In conclusion, tibolone is associated with increased risk for ovarian and endometrial cancer overall; and particular the risk of serous ovarian tumors and Type 1 endometrial cancer. Because the associations are stronger with increasing durations of use - and for hormone sensitive tumors -the results seem indicative of causality. This article is protected by copyright. All rights reserved.

Strategies to Maintain Fertility in Young Breast Cancer Patients.

Breast cancer is the most frequently occurring cancer in women of reproductive age. Treatments for breast cancer may eliminate or diminish fertility, making discussions about fertility preservation essential prior to initiation of gonadotoxic therapies. Additionally, even in patients who do not require chemotherapy, the use of adjuvant endocrine therapy will often push patients out of the reproductive window before treatment is completed. The only established methods for fertility preservation are oocyte or embryo cryopreservation, but experimental methods, such as ovarian suppression with GnRH agonists and ovarian tissue cryopreservation, show great promise. Early referral to a fertility specialist for interested patients affords patients the most fertility preservation options, with only minimal delay to cancer treatment.

Ki67 Proliferative Index in Carcinoid Tumors Involving Ovary.

Primary ovarian carcinoid tumors are rare neoplasms that constitute less than 0.1% of all ovarian carcinomas. However, carcinoid tumors metastatic to ovaries are more common. Cell proliferative rate is an important factor in the determination of neuroendocrine tumor prognosis. Limited data are available as regards Ki67 proliferation index in predicting the physiological features of carcinoid tumors involving the ovary. Pathology files of Mayo Clinic Rochester (1995-2014) were searched, and clinical information was collected from medical records. All cases were stained with an antibody against Ki67, and digital analysis was performed with digital imaging analysis. A total of 36 cases (median age 64 years, range 33-83 years), including 9 primary (median age 68 years, range 33-73 years) and 27 metastatic carcinoid cases (median age 64 years, range 36-83 years), were investigated in the current study. Seven out of nine (77.8%) primary ovarian carcinoids are associated with mature teratoma. Twenty two metastatic carcinoids (81.5%) were from the GI tract, four (14.8%) from the pancreas, and one (3.7%) from the posterior thorax location. There was significant difference of Ki67 index between primary (median 2.3%, range, 0.6-8.4%) and metastatic carcinoid tumors (median 9.7%, range, 1.3-46.7%) (p = 0.002). The survival time is much shorter among patients with metastatic carcinoid tumor (median survival 5.8 years) comparing to primary ovarian carcinoid tumor (median 14.2 years) (p = 0.0005). A strong association between Ki67 index and patient survival time was identified (Hazard ratio for 1-percentage point increase 1.11, p = 0.001). Comparing to primary ovarian carcinoid tumor, metastatic carcinoid usually exhibits a higher Ki67 index and a worse outcome.

Feasibility and outcome of primary laparoscopic cytoreductive surgery for advanced epithelial ovarian cancer: a comparison to laparotomic surgery in retrospective cohorts.

To assess the feasibility and outcome of primary laparoscopic cytoreductive surgery on advanced epithelial ovarian cancer in comparison with conventional open surgery.

No association between TP53 Arg72Pro polymorphism and ovarian cancer risk: evidence from 10113 subjects.

The TP53 gene product is an important regulator of cell growth and a tumor suppressor. The association between TP53 Arg72Pro polymorphism and ovarian cancer risk has been widely investigated, but the results are contradictory. We therefore searched the PubMed, EMBASE and Chinese Biomedical databases for studies on the relation between TP53 Arg72Pro polymorphism and ovarian cancer risk. Our final meta-analysis included 24 published studies with 3271 cases and 6842 controls. Pooled results indicated that there was no significant association between TP53 Arg72Pro polymorphism and ovarian cancer risk [Pro/Pro vs. Arg/Arg: odds ratio (OR) =1.04, 95% confidence interval (CI) = 0.81-1.34; Arg/Pro vs. Arg/Arg: OR = 1.14, 95% CI = 0.96-1.36; recessive: OR = 1.05, 95% CI = 0.90-1.22; dominant: OR = 1.12, 95% CI = 0.94-1.33; and Pro vs. Arg: OR = 1.06, 95% CI=0.93-1.20]. Likewise, stratified analyses failed to reveal a genetic association. Despite some limitations, the present meta-analysis provides statistical evidence indicating a lack of association between TP53 Arg72Pro polymorphism and ovarian cancer risk.

Silencing ROR1 and ROR2 inhibits invasion and adhesion in an organotypic model of ovarian cancer metastasis.

Elevated expression of the ROR1 and ROR2 Wnt receptors has been noted in both the tumour and stromal compartments of ovarian cancer patient tissue samples. In vitro studies have suggested these receptors play a role in ovarian cancer metastasis. However, these previous studies have utilised simple 2D in vitro models to investigate cancer cell growth and migration, which does not allow investigation of stromal involvement in Wnt driven metastasis.

Roflumilast restores cAMP/PKA/CREB signaling axis for FtMt-mediated tumor inhibition of ovarian cancer.

The abrogation of cAMP generation by overexpression of PDE isoforms promotes the inflammatory pathology, and the PDE inhibitors have showed the potential anti-inflammation effects in clinical. However, the function of PDE inhibitors in cancer treatment remains unclear. We here investigated the role of PDE4 inhibitor Roflumilast in the treatment of ovarian cancer. We found that Roflumilast could effectively inhibit the proliferation, and induce apoptosis and cell cycle arrest in two ovarian cancer cell lines OVCAR3 and SKOV3. Meanwhile, the cAMP/PKA/CREB signals was activated by Roflumilast, which was accompanied by the up-regulation of mitochondrial ferritin (FtMt) level. Interestingly, forced expression of FtMt in ovarian cancer enhanced the apoptosis and inhibited tumor growth and the PKA inhibitor H89 and knockdown of CREB significantly repressed the expression of FtMt to restore the tumor proliferation and inhibit apoptosis. In addition, we found that Roflumilast-induced phosphorylated CREB directly promoted transcription of FtMt, indicating that Roflumilast up-regulated the expression of FtMt in ovarian cancer via cAMP/PKA/CREB signals. The anti-tumor role of Roflumilast in vivo was also demonstrated, the treatment of roflumilast effectively inhibited tumor proliferation and elevated the FtMt expression to restrict the tumor growth via the activation of cAMP/PKA/CREB signals in ovarian cancer.

Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer.

Pathogenic germline BRCA1, BRCA2 (BRCA1/2), and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma (OC), although variant frequency and relevance information is scarce in Japanese women with OC. Using targeted panel sequencing, we screened 230 unselected Japanese women with OC from our hospital-based cohort for pathogenic germline variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were identified in 41 (17.8%) women: 19 (8.3%; BRCA1), 8 (3.5%; BRCA2), 6 (2.6%; mismatch repair genes), 3 (1.3%; RAD51D), 2 (0.9%; ATM), 1 (0.4%; MRE11A), 1 (FANCC), and 1 (GABRA6). Carriers of BRCA1/2 or any other tested gene pathogenic variants were more likely to be diagnosed younger, have first or second-degree relatives with OC, and have OC classified as high-grade serous carcinoma (HGSC). After adjustment for these variables, all 3 features were independent predictive factors for pathogenic variants in any tested genes whereas only the latter two remained for variants in BRCA1/2. Our data indicate similar variant prevalence in Japanese patients with OC and other ethnic groups and suggest that HGSC and OC family history may facilitate genetic predisposition prediction in Japanese patients with OC and referring high-risk patients for genetic counseling and testing.

TPGLDA: Novel prediction of associations between lncRNAs and diseases via lncRNA-disease-gene tripartite graph.

Accumulating evidences have indicated that lncRNAs play an important role in various human complex diseases. However, known disease-related lncRNAs are still comparatively small in number, and experimental identification is time-consuming and labor-intensive. Therefore, developing a useful computational method for inferring potential associations between lncRNAs and diseases has become a hot topic, which can significantly help people to explore complex human diseases at the molecular level and effectively advance the quality of disease diagnostics, therapy, prognosis and prevention. In this paper, we propose a novel prediction of lncRNA-disease associations via lncRNA-disease-gene tripartite graph (TPGLDA), which integrates gene-disease associations with lncRNA-disease associations. Compared to previous studies, TPGLDA can be used to better delineate the heterogeneity of coding-non-coding genes-disease association and can effectively identify potential lncRNA-disease associations. After implementing the leave-one-out cross validation, TPGLDA achieves an AUC value of 93.9% which demonstrates its good predictive performance. Moreover, the top 5 predicted rankings of lung cancer, hepatocellular carcinoma and ovarian cancer are manually confirmed by different relevant databases and literatures, affording convincing evidence of the good performance as well as potential value of TPGLDA in identifying potential lncRNA-disease associations. Matlab and R codes of TPGLDA can be found at following: .

Which patients are not included in the English Cancer Waiting Times monitoring dataset, 2009-2013? Implications for use of the data in research.

Cancer waiting time targets are routinely monitored in England, but the Cancer Waiting Times monitoring dataset (CWT) does not include all eligible patients, introducing scope for bias.