AbstractBackgroundInnate and acquired chemoresistance to anticancer therapies are a well-known phenomenon in Esophageal Squamous Cell Carcinomas (ESCC). There are presently no viable approaches for real-time monitoring of resistance in ESCC. We used a novel method for chemo-interrogation (CI) by harvesting sufficient number of Circulating-Tumor Associated Cells (C-TACs) which are defined as apoptosis-resistant cells of tumorigenic origin and are positive for Epithelial Cell Adhesion Molecule (EpCAM)...
Thu Nov 07, 2019 02:00
AbstractBackgroundCirculating tumor cells may reflect the genetic events happening in tumor site what is especially advantageous in case of inability to make biopsy and for monitoring of disease progression and / or treatment effectiveness. Decreasing of distinct mRNA expression levels may indicate positive changes in disease course (for example, decreasing aggressiveness, and risk of metastases).Methods30 plasma samples of melanoma patients of 3-4 grades and 30 plasma samples of melanoma patients...
Thu Nov 07, 2019 02:00
AbstractBackgroundComprehensive genomic profiling (CGP) of tumours using next generation sequencing (NGS) is increasingly used to guide management. Broad panel sequencing may increase treatment options by identifying more potential targets but generates large quantities of data. Therefore, determining actionable alterations is a challenge. To address this the MTB for the Tumour chARacterisation to Guide Experimental Targeted therapy (TARGET) trial at the Manchester Cancer Research Centre has evaluated...
Thu Nov 07, 2019 02:00
AbstractBackgroundMultiple genomic and transciptomic biomarkers have been associated with response to immune checkpoint inhibitor (CPI) therapy. Emerging evidence suggests that each solid tumour type has a unique mix of factors determining CPI response, reflecting the subtle differences in antigen repertoire and immune microenvironment across histologies. Compiling large-scale sequencing datasets of patients treated with CPI therapy, from a range of solid tumour types, allows detailed comparison...
Thu Nov 07, 2019 02:00
AbstractBackgroundBRCA1/2 mutations are associated with several cancers. Our previous study indicate that microenvironmental stress conditions, induce BRCA1 protein deficiency not related to gene mutations, but resulting from attenuated translation. We propose that highly mortal pancreatic tumors might also belong to the BRCAness ones, even if not carrying BRCA1/2 mutations. In this study we developed and validated flow cytometry panel to estimate BRCA2 protein level, together with tumor and stem...
Thu Nov 07, 2019 02:00
AbstractBackgroundMagnetic nanoparticles (MNPs) enable the monitoring of therapeutic agent delivery by non-invasive and real-time magnetic resonance imaging (MRI), because this technique can rapidly acquire multi-informational high resolution images. And Modifying the surface of various inorganic nanoparticles has recently become important to the development of novel biomedical technologies including therapeutics, diagnosis and clinical imaging, it is important for the treatment of the cancer in...
Thu Nov 07, 2019 02:00
AbstractBackgroundAmong cancer therapies relying on the defects in DNA repair mechanisms, the platinum agents (e.g. cisplatin or carboplatin) are most widely used. Despite being effective in majority of patients, the tumor often relapses, and these originally sensitive cancers acquire resistance towards platinum-based drugs. The mechanism of resistance development is not well understood and there is no clinical approach to prevent or diagnose it. Therefore, there is an urgent need for better understanding...
Thu Nov 07, 2019 02:00
AbstractBackgroundWest Africa is a hotbed of hepatocellular carcinoma (HCC) partly due to aflatoxin B (AFB) contamination. In Russia, there is now a pool of patients who have liver cirrhosis due to hepatitis C virus (HCV), who were treated with direct antiviral agents and HCV negative, but due to cirrhosis are in the risk group for HCC development. MiRNAs are candidate molecules for HCC prediction panel. The question is if it is possible to use the same miRNAs for HCC development risk despite background...
Thu Nov 07, 2019 02:00
AbstractBackgroundThe recent identification of molecular alterations in some lung adenocarcinomas has led to the emergence of effective targeted therapies thus drastically improving their prognosis.The aim of our study was to investigate the association between driver oncogene alterations and metastatic patterns on imaging assessment, in a large cohort of metastatic lung adenocarcinoma patients.MethodsFrom January 2010 to May 2017, 656 patients with stage IV lung adenocarcinoma with molecular analysis...
Thu Nov 07, 2019 02:00
AbstractBackgroundPancreatic ductal adenocarcinoma (PDAC) has a poor prognosis with a 5-year survival rate of 6%, emphasizing the need for new therapeutic targets and prognostic biomarkers. The damage-specific DNA-binding protein 2 (DDB2) is involved in damaged-DNA repair through the Nucleotide Excision Repair system and has been recently demonstrated as playing a role in mammary, ovarian and colorectal carcinogenesis by stimulating tumour growth, inhibiting migration and invasion and sensitizing...
Thu Nov 07, 2019 02:00
AbstractBackgroundAberrant expression of mucins can promote the epithelial-mesenchymal transition (EMT), which leads to enhanced tumorigenesis. Carcinogenesis-related pathways involving c-MET and β-catenin involve mucins. Among the mucins, MUC5AC and MUC6 are characteristic for stomach mucins. This study characterized expressions of MET, MUC5AC, MUC5B, and MUC6 EMT signaling in human gastric cancer (GC) cell lines, and further characterized the differential susceptibility of these cell lines to tepotinib.MethodsWe...
Thu Nov 07, 2019 02:00
AbstractBackgroundIn metastatic CRC, the absence of RAS/BRAF mutation is indicative of a good response to anti-EGFR therapy. However, these patients have a distinct genomic profiles and tumors heterogeneity. This is probably the greatest difficulty regarding the detection of mutations in tumor tissue. LB can overcome this, detecting cDNA as well as early changes in mutational status before the clinical progression. Dynamic molecular analysis may allow new therapeutic sequences.MethodsNon-randomized...
Thu Nov 07, 2019 02:00
AbstractBackgroundThe ATP-binding cassette (ABC) transporters are superfamily proteins of cellular translocation machinery. Many ABC transporters release drugs to give multidrug resistance. However, ABC transporters existing in intracellular compartments give drug resistance by regulating biological processes, rather than direct release of drugs. The current study aimed to investigate the molecular mechanism that causes the drug resistance of the mitochondrial ABC transporters in cancer cells.MethodsRNA-sequencing...
Thu Nov 07, 2019 02:00
AbstractBackgroundTargeted therapy has revolutionised the systemic treatment of melanoma. Patients with stage III/IV melanoma with a mutation in BRAF are treated with BRAF inhibitors, with BRAF mutation status being assessed by tissue analysis. Cell-free DNA (cfDNA) released from tumours provides a method for detecting BRAF mutations. This project analysed BRAF status in cfDNA through digital droplet PCR (ddPCR). We aimed to assess the relationship between cfDNA BRAF status and disease relapse and...
Thu Nov 07, 2019 02:00
AbstractBackgroundFor most adolescent and young adult (AYA) cancers, age-specific molecular features are poorly understood. SPECTA, an academic translational research infrastructure for biomaterial collection and molecular analysis, will explicitly recruit AYA patients and will therefore collect empirical data to bridge the molecular gap between pediatric and adult oncology.Trial DesignThe initial pilot study, activated in February 2019 across Europe, will recruit 100 patients aged 12-29 years with...
Thu Nov 07, 2019 02:00
AbstractBackgroundBrain tumours are among “hard-to treat” world malignancy with the median survival time of 15 months for the most aggressive form - Glioblastoma multiforme (GBM). It is extremely complex and heterogeneous brain cancer, characterized by rapid progression, infiltration and therapeutic resistance. Currently, many trials for target therapy are focused on understanding the molecular heterogeneity of GBM and designing molecules that inhibit most common genetic alterations.MethodsIn the...
Thu Nov 07, 2019 02:00
AbstractBackgroundNowadays anthracycline and taxane-based chemotherapy remains the standard of care for TNBC, with pathological complete response (pCR) rates ranging ∼ 10–30%. pCR in TNBC is associated with better outcomes, while residual disease after neoadjuvant chemotherapy (NACT) have a higher relapse risk and poor prognosis. We have evaluated the utility of DNA methylation markers for TNBC pCR prediction.MethodsEpigenetic assessment of DNA extracted from 29 biopsy samples obtained from TNBC...
Thu Nov 07, 2019 02:00
AbstractBackgroundThe most recent histopathological guideliness recommend evaluation of tumor buds, as an independent prognostic factor of colorectal carcinoma (CRC). In the present paper, we examined the immunoprofile of tumor buds, using three markers of epithelial mesenchymal transition (EMT): E-cadherin, β-catenin and vimentin, which were evaluated in both tumor core and buds.MethodsIn 157 CRCs specimens, consecutive cases with curative resection, without preoperative therapy, three molecular...
Thu Nov 07, 2019 02:00
AbstractBackgroundThe detection of driver aberrations such as EGFR and ALK, in tumour tissue or plasma has become important for treating lung cancer patients. The aim of this study is to explore the feasibility of detecting therapy-guiding aberrations in RNA, isolated from platelet and plasma samples.MethodsWe applied a hybridization capture-based NGS approach on 10 platelet-derived RNA samples with 13 known variants. For validation, we applied RNA-based ddPCR focussing on T790M, L858R and E19del...
Thu Nov 07, 2019 02:00
AbstractBackgroundWe present here a case of a 67-year-old male. He presented in May 2018 with severe abdominal pain and weight loss of 25%. Alpha-feto protein (AFP) and Carbohydrate antigen 19-9 (CA19-9) were within normal limits, and CA125 was 5 times upper normal limit (ULN). Computed tomography showed liver masses and enlarged retroperitoneal lymph nodes. Biopsy from a liver mass showed Combined Hepatocellular Carcinoma (HCC)-Cholangiocarcinoma (CC) (CHC). This a rare tumor, with an incidence...
Thu Nov 07, 2019 02:00
AbstractBackgroundGenomic profiling of metastatic breast cancer (MBC) using next-generation sequencing (NGS) has identified driver mutations however, the routine sequencing to guide treatment decisions in this setting is still unclear.MethodsRetrospective study of patients with MBC presented to 4 cancer centers in Egypt, from January 1, 2013 to December 31, 2017. Patients were randomized into; group (A) patients who received chemotherapy based on genomic testing and group (B) as control group who...
Thu Nov 07, 2019 02:00
AbstractBackgroundPatients with high numbers of neoepitopes responds better to immunotherapy, but the correlation to response is imperfect, indicating that multiple layers of modulation and/or suppression plays a role in triggering an ongoing immune response. The STING/cGAS pathway senses cytosolic DNA and interact with P53 to trigger the innate immune system. Cytosolic DNA may be generated through chromosomal instability (CIN), a hallmark of cancer associated with poor prognosis. Here we investigate...
Thu Nov 07, 2019 02:00
AbstractBackgroundChemotherapy-induced anemia (CIA) contributes to poor patient outcomes and increased mortality. Prompt and effective treatment of CIA is essential to prevent fewer chemotherapy dose delays and reductions. Optimal therapy of CIA involves intravenous iron, red blood cell (RBC) transfusions, and erythrocyte stimulating agents (ESAs). Despite the baseline coagulopathies present in patients with malignancy, administration of both RBC transfusions and ESAs is independently associated...
Thu Nov 07, 2019 02:00
AbstractBackgroundThough mTOR inhibition is considered an attractive strategy for cancer management, anti-mTOR monotherapies have not shown meaningful benefits. We hypothesized that an Encyclopedic Tumor Analysis (ETA) can identify vulnerabilities in the tumor in addition to mTOR activation. We further hypothesized that tandem synergistic targeting of these vulnerabilities using combination of mTOR inhibitors and other systemic anticancer agents in a label- and organ-agnostic manner can improve outcomes...
Thu Nov 07, 2019 02:00
AbstractBackgroundMain challenges in thyroid cancer management are low sensitivity of preoperative differential diagnostics and absence of sufficient prognostic markers for choosing of therapeutic strategy, including decision regarding radioiodine therapy. The study aims evaluation of clinical utility of analyses of comprehensive set of driver and secondary mutations with targeted high-throughput sequencing.MethodsPoint mutations in 52 genes, CNVs at 1q, 9q, 17q, 22q, and fusions of 66 genes were...
Thu Nov 07, 2019 02:00
AbstractBackgroundPhaeochromocytomas and paragangliomas (PPGLs) are rare but strongly heritable neuroendocrine tumours. Most patients undergo genetic testing and approximately 40% will have a germline causal mutation. In 10% of patients, genetic analysis identifies uncharacterised mutations, or “variants of unknown significance” (VUSs). Tests to distinguish between benign and pathogenic mutations would aid clinicians’ and patients’ decision-making. One test could exploit the biology of a subset of...
Thu Nov 07, 2019 02:00
AbstractBackgroundThe All Wales Medical Genomics Service (AWMGS) receives around 90 FFPE solid tumour samples per week for genetic analysis. Streamlining of testing is required in order to ensure the laboratory has the capacity and capability to meet the growing needs of the precision medicine era. With this in mind, AWMGS aimed to validate and incorporate a single NGS panel into service for the detection of, in the first instance, single nucleotide variations in a range of tumour types using a minimum...
Thu Nov 07, 2019 02:00
AbstractBackgroundGlioma is the most common primary brain malignancy with a largely unknown pathogenesis, although complex genetic abnormalities are thought to contribute to disease development. Several independent studies have investigated the expression of Epidermal Growth Factor Receptor (EGFR), Cyclooxygenase 2 (COX-2), p53 and Cyclin D1 in gliomas. However, conflicting evidence exists for expression and prognostic significance of these markers in glioma. Furthermore, no work relating to these...
Thu Nov 07, 2019 02:00
AbstractBackgroundLeukotrienes receptor signaling is involved in tumor development and progression. Expression of leukotriene B4 receptors 1 and 2 (LTB4R and LTB4R2) promotes cell proliferation, survival, migration and metastasis. Aberrant LTB4R gene expression blocks anti-proliferative responses of TGF-β1 in breast cancer (BC) cell lines. LTB4R2 ectopic expression is associated with increased invasiveness of BC cells. Earlier, we reported LTB4R and LTB4R2 genes abnormal demethylation that is potent...
Thu Nov 07, 2019 02:00
AbstractBackgroundBetween 2013 and 2017, the RAIDs consortium conducted a European biobanking study, [BioRAIDs (NCT02428842)] aiming at prospectively annotating cervical cancer (CC) patients and identifying molecular patterns associated with outcome. Dominant oncogenic alterations were reported in PIK3CA (40%), while dominant suppressor gene alterations were seen in KMT2D (15%) and KMT2C (16%). A “metagene” combining these alterations was associated with outcome (https://doi.org/10.1016/j.ebiom.2019.03.069).MethodsWES...
Thu Nov 07, 2019 02:00
AbstractBackgroundTreatment of glioblastoma multiforme remains little effective due to the rapidly developing recurrence of the tumour, due to its high tumorigenic potential, resistance to chemoradiation therapy and increased dissemination of glioma stem cells (GSC). Molecular mechanisms of these cell interaction with extracellular matrix (ECM) are practically not studied. At present, it is also not clear the signalling of the ECM-receptor interaction (ECM-RI) differs for GSC and differentiated glioma...
Thu Nov 07, 2019 02:00
AbstractBackgroundPrecision oncology, guided by high-resolution molecular diagnostics, refers to the ability to identify patients that are likely to respond to specific anticancer therapies. Although recent studies demonstrated the utility of comprehensive molecular profiling based on whole-exome/genome sequencing and transcriptome sequencing to guide therapeutic decisions in individual patients, many questions remain unanswered.MethodsWe report the clinical results of MASTER, a multicenter, cross-entity...
Thu Nov 07, 2019 02:00
AbstractBackgroundBreast cancer remains one of the top threats to women's health. The current lack of tumor markers with desirable sensitivity and specificity is a major obstacle to future management of breast cancer. Many studies have been directed to revealing the diagnostic and prognostic potentials of circulating miRNAs in breast cancer.MethodsWe measured the levels of miRNA-135 and miRNA-9 in sera from 126 participants representing two different groups, 40 healthy individuals and 86 breast cancer...
Thu Nov 07, 2019 02:00
AbstractBackgroundAPOBEC3B has been shown to be expressed in glioma and to contribute to temozolomide resistance. However, little is known about the role of APOBEC3B as well as other APOBEC3 genes expression as prognostic markers in glioma.MethodsOncolnc and The cancer genome atlas databases were used to obtain the data of mRNA expression of seven APOBEC3 (A,B,C,D,F,G.H) genes as well as the age, sex, race and tumor grade regarding lower grade glioma (LGG) patients.mRNA expression was classified...
Thu Nov 07, 2019 02:00
AbstractBackgroundBone metastases from solid tumours remain a serious burden on patient morbidity leading to decreased quality of life, increased narcotic use, and higher healthcare cost. We examined the current use of anti-osteolytics including RANK-L inhibitors and Bisphosphonates with the frequency of Skeletal Related Events (SRE) in coordination with current ESMO treatment guidelines.MethodsPatients with bone metastases from solid tumours in the University of Pennsylvania Hospital system (UPHS)...
Thu Nov 07, 2019 02:00
AbstractBackgroundColorectal cancer (CRC) represents a relevant public health problem. The identification of new markers involved in the mechanisms of invasiveness represents a priority in order to better understand cancer development and generate new therapeutic targets. Recently, our group demonstrated overexpression of ZNF518B gene, which encodes an unknown zinc finger transcription factor, in CRC. A transcriptome-wide gene expression profile revealed its implication in different biological processes...
Thu Nov 07, 2019 02:00
AbstractBackgroundRefractory cancers pose formidable management challenges. We hypothesized that such malignancies have unexplored vulnerabilities that can be identified using Encyclopedic Tumor Analysis (ETA) and effectively targeted using conventional agents in a label- and organ-agnostic manner to yield treatment benefit. The pan-cancer RESILIENT trial addressed patients with advanced refractory malignancies who were treated with ETA guided treatments regimens without any restrictive eligibility...
Thu Nov 07, 2019 02:00
AbstractBackgroundExtensive use of NGS profiling in precision oncology is uncovering a staggering amount of novel alterations in the sequenced genes. Strikingly, the number of variants of uncertain significance (VUS) increases linearly with the addition of sequenced samples. While some of the VUS are inconsequential mutations many other VUS lead to activation of the proteins and are therefore involved in oncogenicity and may cause drugs resistance. These new activating mutations can also serve as...
Thu Nov 07, 2019 02:00
AbstractBackgroundResistance on the 1st or 2nd generation TKIs in patients with EGFR mutated NSCLC to the therapy occurs on average after 8-12 months. The most common (49-60%) resistance mechanism is the appearance of the T790M. Its determination is possible by different methods of examination: ctDNA (false-negative probability 23%) and tumor tissue (sensitivity of 88%). The appointment of osimertinib in the second line allows to increase ORR, but also PFS relative to standard chemotherapy.MethodsIn...
Thu Nov 07, 2019 02:00
AbstractBackgroundRadiotherapy of pelvic or abdominal cancer may cause radiation enteritis or colitis. We have reported previously that atorvastatin which is a cholesterol-lowering drug and attenuate radiation-induced intestine damage including apoptosis, inflammatory, fibrogenesis and oxidative stress through activation of autophagy. Several studies have been demonstrated that statin drugs have effects of inhibiting of tumor cell proliferation. We sought to explore whether atorvastatin can play...
Thu Nov 07, 2019 02:00
AbstractBackgroundAdvancement in molecular biology research has allowed the measurement of multiomics data points from a single tumor biopsy sample in a reasonable time frame for making significant clinical decisions. There have been tremendous advances from the bioinformatics and systems biology perspective to analyse integrated multi‐scale analysis of the data will prove invaluable for a combined systems‐level understanding of the important biological network processes contributing to the initiation,...
Thu Nov 07, 2019 02:00
AbstractBackgroundcfDNA analysis could represent an alternative to invasive biopsy in patients with NSCLC to better understand disease profile. We report a real-world experience of genomic assessment of an Italian patients’ cohort.MethodsWe evaluated 58 non-oncogene-addicted aNSCLC patients treated at our Institution from January 2018 to May 2019. All patients were characterized using cfDNA NGS Guardant360® platform (Guardant Health, Redwood City, CA). Association between a positive result (defined...
Thu Nov 07, 2019 02:00
AbstractBackgroundThe most common subtypes of bone sarcomas are osteosarcoma and Ewing sarcoma. They are rare and heterogeneous form of cancers of mainly mesenchymal origin. Neo-adjuvant chemotherapy followed by wide surgical resection followed by adjuvant chemotherapy and radiotherapy are the main treatment options for these tumors. But despite all measures, mortality rates have not come down in last few decades. Immunotherapies with various vaccines and cytokines had limited success in clinical...
Thu Nov 07, 2019 02:00
AbstractBackgroundGenomic alterations of receptor tyrosine kinases (RTK) or ligands are biomarkers for some targeted therapies in a fraction of cancers, with heterogeneous responses across tumor types. A general model to predict the efficacy of a targeted treatment in a given tumor type bearing a RTK genomic alteration is lacking. Through database and literature review, we investigated whether the role of a RTK in the normal lineage could predict the response to RTK inhibitors in cancers arising...
Thu Nov 07, 2019 02:00
10PCirculating miR-652-3p as a biomarker of drug resistance in metastatic colorectal cancer patients
AbstractBackgroundMicroRNAs (miRs) are small non-coding RNAs involved in cell homeostasis, carcinogenesis and control multiple oncogenic pathways. Numerous miRs deregulation is associated with clinical outcome. Chemo-refractory metastatic CRC (mCRC) patients are often treated with regorafenib. Given the limited clinical benefits of regorafenib in unselected patient populations, there is an unmet need for better patient selection and identification of mechanisms of resistance. Here we aimed to identify...
Thu Nov 07, 2019 02:00
AbstractBackgroundTumor cell invasion is an integral component of breast cancer progression. In cell motility, including tumor cells, involves the actin cytoskeleton, which is a complex system with many regulatory points. The new tumor supressor protein LIMCH1, which has an actin binding domain, is a promising molecular target to suppress invasion. The presented work is aimed at revealing features of LIMCH1 expression in cells that demonstrate various forms of invasion in breast cancer.MethodsThe...
Thu Nov 07, 2019 02:00
AbstractBackgroundRecently, the Janus kinase 3 (JAK3) tyrosine kinase, is a well-known tumor-related gene in the JAK/STAT pathway. While the genetic variability of JAK3 mutations non-small cell lung cancer (NSCLC) patients is unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring JAK3 mutations.MethodsA total of 938 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of JAK3 mutations and other genes were detected...
Thu Nov 07, 2019 02:00
AbstractBackgroundMore than 70% of patients diagnosed with colorectal cancer with liver metastasis have unresectable disease, so the available treatment is systemic chemotherapy that has limited efficacy and causes harmful side-effects. Thus novel and more effective drugs are needed to improve patients’ survival and quality of life. Recent studies have identified several genomic alterations in CRLM that can theoretically be targeted by novel cancer-specific drugs. Among those is the gain-of-function...
Thu Nov 07, 2019 02:00
AbstractBackgroundBreast cancer is one of the most common cancers worldwide and - despite significant advances in prevention and treatment - contributes significantly to the overall mortality from cancer. This emphasizes the need for better treatments and improved patient stratification.Histologic as well as genetic testing is able to substantially improve treatment selection and benefit as well as patient management. Within the CATCH (Comprehensive assessment of clinical features and biomarkers...
Thu Nov 07, 2019 02:00
AbstractBackgroundDespite a primary benefit, almost all patients (pts) develop acquired resistance to EGFR TKIs. Some mechanisms were related to the selective pressure of the different generations (G) EGFR TKIs, but the complete alteration profile at resistance remains to be elucidated.MethodsMetastatic NSCLC pts who performed a tissue and plasma biopsy at EGFR TKI progression, and optionally before, were identified from the prospective MATCH-R trial (NCT02517892). Targeted next-generation sequencing...
Thu Nov 07, 2019 02:00
AbstractBackgroundAround 30% of non-small cell lung cancer (NSCLC) patients harbor sensitizing mutations in the epidermal growth factor receptor (EGFR) gene. Most common EGFR mutations are exon 19 deletions and EGFR-L858R, that comprise 85% of EGFR-mutated cases, and whose drug sensitivity profile is already known. However, rare EGFR mutations represent 10-15% of EGFR-mutated NSCLCs with diverse sensitivity to different EGFR inhibitors.MethodsScientific literature and database search were conducted...
Thu Nov 07, 2019 02:00
AbstractBackgroundIntrahepatic cholangiocarcinoma (iCCA) is a liver neoplasm with few treatment options and a dismal prognosis. To date, the only curative option remains the surgery. New insights concerning its molecular pathogenesis and genetic heterogeneity are recently coming to light and are promising to widen the treatment landscape.MethodsWe evaluated data of the first 39 patients with iCCA included in the “Next Generation Sequencing in Intrahepatic Cholangiocarcinoma” study (EtherBil study,...
Thu Nov 07, 2019 02:00
AbstractBackgroundCancer-related fatigue (CRF), cachexia, or poor performance status, which occurs among patients with advanced malignancy, has always frustrated clinicians and patients and been primarily managed via conservative treatments. The botanically derived drug extracted from Astragalus membranaceus(PG2) has been approved by Taiwan FDA as a standard of choice for CRF management. We show real-world practice about combination treatment of PG2, dose-modified chemotherapy, and anti-PD1 checkpoint...
Thu Nov 07, 2019 02:00
AbstractBackgroundMost of glioblastomas (GBMs) frequently recur at sites of radiotherapy, but it is unclear if changes in the tumor microenvironment by radiotherapy affect GBM recurrence.MethodsGBM cells were injected into the nude mice brain. At 3 weeks post injection, the whole brains of mice were irradiated 5 times at 2 Gy per day. Rat anti-Ly6G antibodies were used for Ly6G+ inflammatory cell depletion to figure out the roles of Ly6G+ cells in irradiated tumor tissue. To detect cell senescence,...
Thu Nov 07, 2019 02:00
AbstractBackgroundMantle cell lymphoma (MLC) is nowadays an aggressive and incurable Non-Hodgkin’s lymphoma, characterized by multiple relapses.The persistent activation of B-cell receptor pathway is critical for pathogenesis. Ibrutinib is a potent covalent inhibitor of Bruton’s tyrosine kinase (BTK) that inhibits B-cell antigen receptor signaling downstream of BTK and changed for better how MCL is treated in relapsed/refractory setting. However, resistance is common and response limited.MethodsRetrospective...
Thu Nov 07, 2019 02:00
AbstractBackgroundMolecular biomarkers aim to stratify cancer patients into disease subtypes predictive of outcome, improving diagnostic precision beyond clinical descriptors such as tumour stage. Transcriptomic intra-tumour heterogeneity (RNA-ITH) has been shown to confound existing expression-based biomarkers across multiple cancer types.MethodsHere, we analyse multi-region whole-exome and RNA sequencing data for 156 tumour regions from 48 TRACERx patients to explore and control for RNA-ITH in...
Thu Nov 07, 2019 02:00
AbstractBackgroundThe utility of next generation sequencing (NGS) is rapidly evolving within our medical practice with various applications. The 100K Genomes Project was established to sequence 100 000 genomes from NHS patients with cancer or rare diseases, and to date actionable findings have been found for approximately 50% of cancer cases. Data from the 100K Genomes Project were reviewed at Guy’s Hospital Molecular Tumour Board (MTB).MethodsWhole genome sequencing (WGS) was performed for the 100K...
Thu Nov 07, 2019 02:00
AbstractBackgroundEpigenetic inactivation of MGMT by methylation of its promoter is a prognostic factor and is predictive of Temozolomid (TMZ) response in glioblastoma (GBM). MGMT is located on chromosome 10q26 and the loss of chromosome 10q is observed in 70% of GBM. In this study, we assessed the hypothesis that the dual inactivation of MGMT, by hypermethylation of MGMT promoter and by loss of chromosome 10q, may confer greater sensitivity to TMZ.MethodsA total of 149 patients diagnosed with GBM,...
Thu Nov 07, 2019 02:00
AbstractBackgroundA number of genomic alterations detected in plasma DNA have been associated with worse outcome in mCRPC (Jayaram et al Cancer Discov). We hypothesized that patients (pts) who harbored a genomic alteration that decreased after 1C of treatment derive treatment benefit and this would distinguish them from truly resistant pts.MethodsPlasma DNA (128 C1 day (D) 1,134 C2 D1, and 41 progression [PD] from chemotherapy-naïve mCRPC pts in a phase 2 study of AA (NCT01867710), recently reported...
Thu Nov 07, 2019 02:00
AbstractBackgroundTissue precursors of uterine carcinosarcomas remain unknown, therefore targeted therapy has not been determined.MethodsThis research is based on the investigation of formalin‐fixed, paraffin‐embedded tissue blocks from 17 women undergoing primary surgical treatment between 1961–2010, that were retrieved from the pathoanatomical department of the Institute of Oncology named after N.N.Petrov. In the present study, molecular investigations were applied to determine the pathogenesis...
Thu Nov 07, 2019 02:00
AbstractBackgroundThe five-year-survival-rate for paediatric patients with Acute Myeloid Leukaemia (AML) is from 60-70%. The most common causes of death are disease relapse and chemo-resistance. Typically, drug dose response testing is performed at atmospheric oxygen (21%) in a 2-Dimensional (2-D) format; however, AML cells reside in the hypoxic (1% O2), 3-Dimensional (3-D) bone marrow structure along with other cells. Therefore, the drug response observed in typical culture conditions (2D, 21% O2)...
Thu Nov 07, 2019 02:00
AbstractBackgroundSurvival in high grade serous ovarian cancer (HGSOC) is impacted by the emergence of resistance to platinum chemotherapy. The traditional ethos of killing the greatest number of cancer cells with the maximum tolerated dose of chemotherapy may be flawed in evolutionary terms, facilitating the growth of resistant subclones and accelerating decreased treatment efficacy. Adaptive therapy is a new model of cancer treatment that exploits the competitive interactions between drug-sensitive...
Thu Nov 07, 2019 02:00
AbstractBackgroundRadiotherapy (RT), a major part of anti-cancer treatment, directly kills tumor cells, and subsequent anti-tumor immune responses are up-regulated. However, immunologic impacts of RT on PD-1/PD-L1 immune checkpoint activity has not been much investigated. This study evaluated RT-induced alterations of the PD-1/PD-L1 checkpoint molecules based on murine colon carcinoma models.MethodsCT26 colon carcinoma cell line was subcutaneously inoculated on the right hind leg of BALB/c mice....
Thu Nov 07, 2019 02:00
AbstractBackgroundPlumbagin (PLB) is a naphthoquinone compound isolated from the root of Plumbago indica. In our previous study reported that PLB was able to inhibit cell growth in estrogen receptor (ER)-positive and endocrine resistant cells in vitro. The overexpression of human epidermal growth factor receptor 2 (HER2) and nuclear receptor coactivator 3 (NCOA3) was reported in endocrine resistant cells. However, the molecular mechanism underlying of inhibitory effect of PLB remains to be elucidated....
Thu Nov 07, 2019 02:00
AbstractBackgroundCirculating microRNAs (cmiRNAs) are emerging as promising non-invasive biomarkers in cancer for their diagnostic, prognostic and predictive potential. Several platforms have been developed to determine the presence of miRNAs in biological fluids, including specific focus panels. In this pilot study, we aimed at comparing different platforms for detection of cmiRNAs against the same cohort of plasma samples alongside RT-qPCR and NGS technologies.MethodsRNA was isolated from 24 plasma...
Thu Nov 07, 2019 02:00
AbstractBackgroundPancreatic Neuroendocrine Tumours (PanNETs) are the second most common form of pancreatic cancer. We previously identified two principal subtypes of PanNET: insulinomas (islet tumors; IT) and metastasis-like primaries (MLP), corresponding to the low- and high-grade classification of human PanNETs. This study describes the mechanisms by which PanNETs progress from IT to more aggressive MLP tumors and eventually metastasize.MethodsWe profiled single cell transcriptomes, bulk mRNA...
Thu Nov 07, 2019 02:00
AbstractBackgroundColorectal cancer (CRC) keeps an upward incidence and rejuvenation trend in Kazakhstan, as well as worldwide, which is the motive for revising traditional risk factors and searching for cause-effective relationships at the genome level. Genetic nature of early-onset CRC is still unclear. The aim of this study was to determine the spectrum of cancer-related gene mutations among early-onset CRC patients.MethodsThe study included 125 CRC patients aged between 17 and 50 from Kazakhstan....
Thu Nov 07, 2019 02:00
AbstractBackgroundNrf2 is a transcription factor associated with cancer growth and chemotherapy resistance. Nrf2 expression levels may be associated with prognosis of lung cancer, but previous results have been inconsistent.MethodsThe expression of Nrf2 in 1037 surgically resected lung adenocarcinoma (LAD) specimens was evaluated by immunohistochemistry. Nrf2 positivity was defined based on the intensity of stained nucleus of tumor cells on the tissue microarray: negative, weakly positive and strongly...
Thu Nov 07, 2019 02:00
AbstractBackgroundInhibiting PI3Kδ preferentially targets regulatory T cells and myeloid derived suppressor cells, breaking tumour-induced immune tolerance and restoring anti-tumour immunity. Bioinformatics and protein expression studies have shown that PIK3CD / PI3Kδ is highly expressed in certain solid malignancies, and therefore inhibition of PI3Kδ may modulate tumour growth and development via intrinsic as well as immune driven effects.MethodsIn vitro proliferation of primary human T cells demonstrated...
Thu Nov 07, 2019 02:00
AbstractBackgroundFor many years, researchers have tried to find more effective ways to find out if a person has cancer, and find it at an early stage, when it is most curable. One idea that is gaining popularity is called liquid biopsy.MethodsFrom 2016 to 2018 we studied 1050 patients with non-small-cell lung cancer (NSCLC). Before the treatment and then every 2 months after, whole blood was taken for qualitative assessment of ctDNA dynamics by RT-PCR. The aim of the study was to assess the relationship...
Thu Nov 07, 2019 02:00
AbstractBackgroundMetastatic colorectal cancer (mCRC) affects 20% of patients diagnosed with colorectal malignancy and is a major cause of cancer-related death worldwide. Epidermal growth factor receptor (EGFR) blockade with monoclonal antibodies, in combination with chemotherapy, has been shown to benefit patients with RAS wild type tumours. Our project explores real-time assessment of mCRC mutational profile, by use of two methods of circulating tumour DNA (ctDNA) analysis, and its potential to...
Thu Nov 07, 2019 02:00
Abstract Introduction Quantitative methylation specific PCR (qMSP) is a frequently used technique to assess MGMT gene promoter methylation in glioblastoma patients. The optimal technical cut-off value to distinguish methylated from unmethylated samples is nevertheless still undetermined. In literature, a “grey zone” of diagnostic uncertainty has been described. Methods ...
Thu Nov 07, 2019 02:00
Foreword. This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author’s clinical recommendations. Stage. A 58-year-old…
Thu Nov 07, 2019 02:00
Despite improved management, overall survival rates at hospital discharge among patients with out-of-hospital cardiac arrests do not exceed 20%, and neurologic outcomes remain poor. Even though controversies persist, targeted temperature management at 32 to 36°C remains recommended in patients with…
Thu Nov 07, 2019 02:00
Abstract CpcA is a conserved transcriptional activator for the cross-pathway control of amino acid biosynthetic genes in filamentous fungi. Previous studies of this regulator mainly revealed its function under amino acid starvation condition, where amino acid biosynthetic inhibitors were added in the culture. In this study, the biological function of CpcA in Penicillium oxalicum was investigated under different cultivation conditions. Disruption of cpcA led to decreased cell growth...
Thu Nov 07, 2019 02:00
Journal of Investigative Medicine High Impact Case Reports, Volume 7, Issue , January-December 2019. A 29-year-old female with past medical history of chronic serous otitis media presented with worsening neck stiffness and pain over a period of 2 weeks. The patient described non-specific symptoms that were localized to the right side of her neck. She presented to the hospital only when the pain was so extreme that it limited her range of motion. The differential for acute neck pain without fever,...
Thu Nov 07, 2019 09:12
Abstract Bromodomain and extra terminal inhibitors (BETi) delay tumor growth, in part, through tumor cell intrinsic alterations and initiation of anti‐tumor CD8+ T cell responses. By contrast, BETi effects on pro‐tumoral immune responses remain unclear. Here, we show that the next generation BETi, PLX51107, delayed tumor growth to differing degrees in Braf V600E melanoma syngeneic mouse models. These differential responses were associated with the influx of tumor‐associated macrophages during BETi...
Wed Nov 06, 2019 19:23
Abstract Background Balance is a complex process involving the coordinated activities of multiple sensory, motor and biomechanical components. Balance function may be disturbed in subjects suffering from hearing loss but the impairment has been attributed to the pathology underlying the hearing loss. Aim The purpose of the study was to investigate the possible interference of simulated conductive hearing loss with the ability to maintain postural balance. Methods Twenty normal hearing...
Wed Nov 06, 2019 19:20
Journal of International Medical Research, Ahead of Print.
Thu Nov 07, 2019 07:02
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