bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of diffusion weighted magnetic resonance imaging for the characterisation of mediastinal lymphadenopathy.
Authors: Garg Mandeep K , Ramamoorthy Eniyavel , Singh Paramjeet , Aggarwal Ashutosh Nath , Gupta Nalini 
Published: September 2018

e23113 Background: To assess the diagnostic performance and additional value of diffusion-weighted (DW) magnetic resonance imaging (MRI) in the characterization of mediastinal lymphadenopathy. Methods: This prospective study was approved by the institutional review board, and written informed consent was obtained from all patients. A total of 43 patients [23 males and 20 females with mean age of 49 years] with mediastinal lymphadenopathy underwent DW and T2 weighted MRI and pathological examination in the period of January 2015 to June 2016. Diffusion restriction pattern, apparent diffusion coefficient (ADC) mean value, size and T2 heterogeneous signal intensity of the nodes were evaluated. Receiver operating characteristic curve analysis was used to determine ADC mean threshold values. The best predicting combinations of these four parameters were selected by means of stepwise logistic regression analysis. Results: ADC mean value of malignant lymphadenopathy (0.873±0.109×10−3 mm2/s) was significantly different from that of benign lymphadenopathy (1.663±0.311×10−3 mm2/s) (P < 0.001). When an ADC mean value of 1.0955×10−3 mm2/s was used as a threshold value for differentiating malignant from benign nodes, the best results were obtained with a sensitivity of 94%, a specificity of 96% and area under the curve of 0.996. The three other predictor variables didn’t add anything statistically significant to the regression equation with ADC mean. Conclusions: ADC mean value of malignant mediastinal lymphadenopathy was significantly different from the benign lymphadenopathy. The ADC mean value was the strongest independent predictor of malignancy.
Genome-wide microRNA expression profiling in malignant pleural effusion to identify a ten-microRNA signature.
Authors: Zhang Meiling , Zhu Miaojun , Hu Qin , Li Chun , Zhu Zhenhua , Hou Yingyong , Xu Jing , Wang Hailong , Zhu Tong , Tang Tom , Tan Ruoying , Zhang Xin 
Published: September 2018

e23123 Background: Pleural carcinosis caused by tumors of the chest (e.g., lung and breast cancer) or elsewhere in the body (e.g., ovarian carcinoma) that metastasize to the visceral and/or parietal pleura. Recurrent malignant pleural effusion due to pleural carcinosis is one of the most common findings in oncology. The aim of the study was to identify a miRNA signature associated with clinicians’ prescription of patients with MPE. Methods: We used qRT-PCR assay to evaluate a wide range miRNAs (1920 miRNAs) signature measured from pleural effusion between patients with cancer and healthy controls. From the data of our previous studies we selected a panel of 96 miRNAs related to malignant pleural effusion. Data were compared by three classification methods software for statistics and modeling. We used a first set of 77 pleural effusion samples as training group, including 27 patients affected by Lung Adenocarcinomas (LAC), 9 with other lung cancer, 17 with other tumors and 24 inflammatory patients as negative controls. Moreover, we used more 64 pleural effusion samples for double-blind predictive study. Data analysis was performed using a machine learning approach of a Support Vector Machine classifier with a Student's t-test feature selection procedure. Results: We identified a panel of ten miRNAs with optimum classification performance. The combination of these 10-miRNAs alone could discriminate MPE cases from negative controls with an AUC of 0.969 (accuracy = 93.5%; specificity = 91.7%). The selected panel of another 10-miRNAs could separate lung cancer cases from negative controls with an AUC of 0.973 (accuracy = 94.8%; specificity = 95.8%), and a small panel of 4-miRNAs could good discriminate LAC cases from negative controls with an AUC of 0.946 (accuracy 88.9%; specificity = 100%). The accuracy rate of the double-blind predictive sensitivity value was 90.9% and specificity value was 95.8% for MPE patients with lung cancer of miRNA signature. Conclusions: Our miRNAs profile may serve as a new biomarker for MPE diagnosis. Otherwise, we identified a 10-miRNAs signature for MPE patients with lung cancer and a 4-miRNAs for MPE patients with lung adenocarcinoma.
Genomic profiling of early-stage lung cancer for patterns of recurrence.
Authors: DiPerna Costanzo A , Fine Leah 
Published: September 2018

e23126 Background: Currently there is no evidence to support molecular profiling for early stage resected lung cancer patients. However, up to 50% of patients experience recurrence following resection. This is a first-of-a-kind study utilizing comprehensive genomic profiling technology to characterize genomic patterns for risk of recurrence in early stage lung cancer patients within the community hospital setting who have undergone lung surgery. Methods: A total of 60 Stage I-II lung cancer patients, all having undergone pulmonary resection, were evaluated with molecular profiling of their primary lung cancer tissue using Foundation Medicine’s FoundationOneÒ test. Patient age in years ranged from 39-86, and all patients were confirmed Stage I or II based on final pathologic analysis. Samples were taken from three community hospitals that are part of the Addario Lung Cancer Foundation Centers of Excellence program. Patients whose tumors were resected between the years of 2009-2017 were included in this combined retrospective and prospective study. Results: More than 300 genes were evaluated using FoundationOneÒ and patients were segmented to establish similarities and differences. Analysis of segments include gender, recurrence, smoking status among others. Gene patterns across segments are beginning to reveal possible predictive profiles. Final analysis will be completed shortly. Conclusions: Genomic profiling could help predict lung cancer recurrence for early stage lung cancer patients. Similarities amongst patients with recurrences imply that early genomic profiling of lung cancer patients could help predict those patients who would benefit from adjuvant therapies including conventional chemotherapy. Genomic profiling for early stage lung cancer should be studied further and in greater detail to help predict those patients who would benefit from potentially early adjuvant therapies.
Distribution of ETV6-NTRK3 translocations across neoplasms identified from the Mitelman Database.
Authors: Malpartida Juan Carlos , Vick Eric , Richardson Noah Hunter , Patel Kruti , Stein Matthew K , Martin Michael Gary 
Published: September 2018

e23141 Background: Discovered as a novel aberration in congenital fibrosarcoma (CF), the ETV6-NTRK3 translocation (EN) confers oncogenic potential and is inhibited by crizotinib. The present study aims to survey the scope of neoplasms that harbor EN across tumor types. Methods: Utilizing the National Cancer Institute’s Mitelman Database (MD) of Chromosome Aberrations and Gene Fusions patients (pts) were identified with EN and categorized based on tumor type, subtype and incidence. Cancer pts who received tumor profiling with Caris were also surveyed for EN. Results: 47 pts with EN across 12 cancer types were extracted from the MD and had median age of 0.17 years (7 unreported); 38% male; 51% acquired malignancies, 49% congenital; 62% cases were pediatric, 23% adult and 15% unknown. 0/204 pts with Caris tumor profiling were found to have an EN. Cancers with the highest number of EN were: 15 (31.9% EN data set) congenital mesoblastic nephromas (CMN), 10 (21.3%) CF, 7 (14.9%) breast carcinoma (BC; 6 secretory ductal carcinoma (SD) and 1 invasive adenocarcinoma (IA)) and 3 (6.4%) colorectal carcinoma (CRC). EN were found in 8 other malignancies (Table 1). Cancer types with the highest incidence of EN+ cases in the MD were gastrointestinal stromal tumor (GIST; 100%), CMN (75%) and CF (23.3%). Conclusions: These results further our understanding of the distribution of ETV6-NTRK3 translocations in multiple tumor types across the age spectrum and suggest that pts with CMN, CF, BC and CRC requiring high order therapy should be considered for NTRK3-based treatment. [Table: see text]
Comparison of response to chemotherapy in non-Hodgkin lymphoma patients depending on their myeloid derived suppressor cell status: Insight on new immune target.
Authors: Mukherjee Kalyan Kusum , Ghosh Sarbari , Halder Subhom , Sarkar Madhurima , Dasgupta Shayani , Chakraborty Mohona , Bose Anamika , Baral Rathindranath 
Published: September 2018

e23155 Background: Non Hodgkin’s Lymphoma shows different disease status after completion of standard 1st line treatment. Low grade follicular lymphoma remains stable after standard treatment for a long time and some times it autoregress . In High grade Lymphoma (Commonly diffuse B-cell lymphoma) relapsed 30-40% after 1stline treatment. Immunological target for this differentiation in tumor biology is sought for. Methods: Twenty Five CD20+NonHodgkin's Lymphoma(NHL) patients and one T cell lymphoma were treated with standard chemotherapy (6-8 cycles of RCHOP/CHOP). Within these 25 patients, 10 patients were disease free or exhibited stable disease for two years following the completion of treatment. Rest of the patients showed early relapse (within 6 months) or late relapse (within 18 to 24 months). Eight among 10 disease free patients was suffering from NHL of low grade follicular type. In order to correlate the immune cell status with lymphoma relapse, we have studied a panel of T cells, memory T cells, suppressor cells, after completion of chemotherapy and subsequently in every 6 month interval till relapse. Among several parameters studied a direct correlation between myeloid derived suppressor cells (MDSCs) profile and relapse was noted. Results: CD33+CD11b+MDSCs were remarkably high in high grade NHL patients in comparison to disease free low grade follicular lymphoma patients (p < 0.01). Moreover, all of these NHL patients possessed significantly greater proportion of MDSCs than normal healthy individuals (p < 0.001). Interestingly, single responding T cell lymphoma patient showed completely normal level of MDSCs. Studies are also being conducted to correlate with the status of memory T cells with disease relapse. Conclusions: Observed correlation between greater proportions of MDSCs with the relapse of diseases suggest MDSCs might be the potential target to enhance the relapse free survival of NHL patients, thus, demands further extensive investigation.
CLIA validation workflow of a novel tumor cell isolation platform.
Authors: Sero Valeria , Khurana Aditi , Ting Marc , Webb Judy , Verma Suman , Gerber Amanda , Bolognesi Chiara , Sims Cynthe , Gunn Shelly , Cotter Philip , Moore Mathew , Medoro Gianni , Manaresi Nicolò , Bischoff Farideh Z. 
Published: September 2018

e23161 Background: DEPArray™ technology is based on Dielectrophoresis (DEP). High quality image-based cell selection enables users to identify, isolate and recover intact specific individual rare cells of interest from complex, heterogeneous tissues such as live or fixed cell suspensions. Here we demonstrate a validation workflow for application of molecular sequencing technologies and FISH downstream of rare cell recovery. Methods: FFPE scrolls (n = 93) were dissociated and stained with markers to distinguish putative stromal and tumor populations. DNA integrity was tested using a qPCR technique to predict the amount of DNA required for a successful downstream sequencing metrics. DEPArray™ recovered stromal and tumor cells underwent NGS analysis on an Illumina platform based DEPArray™ OncoSeek Panel. Separately, recovered stromal and tumor cells were also utilized for targeted HER2 FISH. CellSearch® cartridges (19 Breast and 5 Bladder Cancers) were processed through the DEPArray to isolate WBCs (CK-/CD45+/DAPI+; n = 30), CTCs (CK+/CD45-/DAPI+; n = 33) and atypical (CK-/CD45-/DAPI+; n = 47) cells. Recovered cells underwent whole-genome amplification with Ampli1™ WGA and quality controlled by Ampli1 QC. Ampli1 LowPass kit was then used to prepare NGS libraries for absolute CNA profiling by low-pass WGS. Results: Reproducibility and reliability was reported as 100% for instrument performance. For FFPE, the OncoSeek panel simultaneously detected SNPs, indels and CNAs of 63actionable and oncology relevant genes. For FISH, 95% concordance with conventional HER2 results was observed. For CTCs, Ampli1 LowPass detected copy number gains/losses confirming tumor origin of the CK+ cells. A portion of non-conventional cells also demonstrated copy number alterations consistent with tumor origin. Conclusions: The isolation of pure single or pooled tumor cells with the DEPArray™ technology can be used as a method to improve downstream MDx analysis using different techniques, thus to inform treatment decisions and provide valuable prognostic information.
Identification of distinctive patterns in cell signaling pathways in glioblastoma multiforme subtypes using gene expression TCGA data sets.
Authors: Volyanskyy Konstantin , Zhong Minghao , Keswarpu Payal , Fallon John T , Fanucchi Michael Paul , Dimitrova Nevenka 
Published: September 2018

e23162 Background: Cancer is characterized by a variety of heterogeneous genomic and transcriptomic patterns involving highly complex signaling biological pathways. The problem of identification of the factors driving tumor progression becomes even more challenging due to intricate interaction mechanisms between these pathways. Using novel approaches in machine learning, we demonstrate the ability to quantitatively describe characteristic signaling patterns in cancer based on transcriptomic data Methods: We used RNASeq data from 20531 genes in 174 samples of GBM from The Cancer Genome Atlas including 5 major histological subtypes – Classical, G-CIMP, Mesenchymal, Neural, and Proneural, anddeveloped predictive computational framework for molecular subtype differentiation from normal tissue relying on variance based gene selection and random forest algorithm. Results: We obtained a few key findings – (1) genes from cell signaling pathways alone differentiate each subtype from normal tissue with 100% accuracy; (2) predictive genes are specific to each subtype; (3) inferred pathway interactions are also specific to each subtype; (4) typically most of the predictive genes involved in signaling are down-regulated in tumor compared to normal tissue (MAPT, PRKCG, PDE2A, RYR2, ATP1B1, GRN1, GNAO1), however, in each subtype we observed a smaller subset of predictive genes which are highly up-regulated in tumor (ID3, FN1, JAG1, F2R, COL4A1, EDAR, CDK2, CDK4, MFNG, BIRC5, CCNB2). We detected and quantitatively evaluated characteristic signaling pathway involvement across the GBM subtypes for MAPK, RAP1, RAS, Notch, PI3K-Akt, mTOR, FoxO, Jak-STAT, Wnt, cAMP, and Calcium Signaling, providing a unique approximation for each subtype signaling profile. Conclusions: In this study, we identified gene expression profiles and associated signaling pathways for distinguishing GBM Multiforme subtypes from normal tissue. We observed and described a dense complex picture of interacting signaling pathways. The detected interactions may provide clinical insights and could be used to identify potential therapeutic targets, however, more research is needed to confirm this.
Precision medicine for recalcitrant cancers with the patient-derived orthotopic xenograft (PDOX) mouse models for identification of effective therapy.
Authors: Murakami Takashi , Kawaguchi Kei , Kiyuna Tasuku , Igarashi Kentaro , Miyake Kentaro , Hiroshima Yukihiko , Nelson Scott D. , Dry Sarah M , Li Yunfeng , Singh Arun S. , Eilber Frederick C. , Hoffman Robert M. 
Published: September 2018

e23164 Background: Our laboratory has developed the patient-derived orthotopic xenograft (PDOX) mouse model of all major cancer types. Methods: Sarcomas from patients were transplanted into the right bicep femoris muscle of nude mice or at a site corresponding to their metastasis. Melanomas were transplanted in nude mice at the orthotopic site corresponding to their metastasis in the patient. An HER-2-expressing cervical cancer was transplanted to the uterine cervix of nude mice. Results: A Ewing’s sarcoma with a FUS-ERG fusion and a CDKN2A-deletion was resistant to doxorubicin as was the patient and sensitive to palbociclib and linsitinib. A spindle-cell sarcoma PDOX was resistant to doxorubicin, but sensitive to pazopanib. A pleomorphic rhabdomyosarcoma PDOX was found resistant to cyclophosphamide, but sensitive to the combination of temozolomide and irinotecan. A melanoma with a BRAF-V600E mutation PDOX was resistant to vemurafenib even thought it targets the BRAF-V600E mutation and was sensitive to trametinib, but resistant to cobimetinib, although both are MEK inhibitors. The primary tumor in a cervical cancer PDOX was resistant to endostatin, but the metastasis in this model was sensitive. Conclusions: The PDOX models have distinguished differential sensitivity of primary and metastatic tumors to the same drug. PDOX models can also distinguish effective drugs when they are sensitive to first-line therapy. Most importantly, the PDOX models can find potential effective therapeutics for recalcitrant disease. Drug evaluation with the PDOX models demonstrate that mutational analysis of the patient tumor may not be sufficient to direct therapy by itself and together with PDOX testing, can result potentially in precision treatment.
Analyses on expression of trimethylation of histone H3 at lysine 27 and DNA methylation at CCGG sites in smoking and nonsmoking non-small cell lung cancer patients and their clinical significance.
Authors: Chen Xiaohui , Deng Yujie , Zhu Kunshou , Nagayasu Takeshi , Hu Dan , Xu Chunwei , Lin Gen , Huang Cheng , Chen Gang , Zheng Xiongwei , Cai Yibin , Lu Jian-ping , Weng Guibin 
Published: September 2018

e23179 Background: Smoking usually leads to epigenetic alterations like DNA methylation and histone modifications. We analyzed the effect that smoking had on DNA methylation level at CCGG sites and expression of trimethylation of histone H3 lysine 27 (H3K27me3), enhancer of zeste homolog 2 (EZH2) and their interactions in non-small cell lung cancer (NSCLC) patients. Methods: 42 NSCLC patients, 22 adenocarcinomas and 20 squamous cell carcinomas were enrolled. Expression of H3K27me3, EZH2 and PCNA were immunohistochemically detected. Apoptotic index in NSCLC with different smoking status was evaluated via TUNEL method. DNA methylation at CCGG sites was evaluated by HELMET method. Their correlation with clinicopathological data were calculated in relation to different smoking status. Results: Compared to the nonsmokers, smoker NSCLC patients were found more often of lower level of DNA methylation at CCGG sites, lower H3K27me3 expression and higher EZH2 expression, and lower apoptotic cell index ( P< 0.05). DNA methylation level at CCGG sites negatively correlated to the Binkman Index( P= 0.017). Further, trend of H3K27me3 and EZH2 expression was in the same direction in most smokers, while in nonsmokers, their expression trend was mostly in the opposite direction ( P= 0.015). Trend of PCNA and EZH2 expression was in the opposite direction in most smokers, while in nonsmokers, their expression trend was mostly in the same direction ( P= 0.048). In addition, trend of CCGG methylation ratio and immunohistochemical expression of H3K27me3 was in the same direction in most smokers, while in nonsmokers, the trend was mostly in the opposite direction ( P= 0.049). Conclusions: NSCLC patients of different smoking status exhibit completely different epigenetic characteristics, and DNA methylation at CCGG sites would probably determine the expression trend of H3K27me3, EZH2 and PCNA.
Sex hormones as regulators of levels of growth factors in tissues of multiple primary tumors of female reproductive organs.
Authors: Kit Oleg Ivanovich , Frantsiyants Elena Mikhaylovna , Moiseenko Tatiana , Vereskunova Marina I. , Adamyan Meri Viktorovich , Saforian Natalya S. , Gurnak Viktor Viktorovich , Ilchenko Maria G. 
Published: September 2018

e23180 Background: Sex hormones are known to be able to influence the synthesis of growth factors in breast and uterine tumors; however, their relationship in multiple primary tumors is poorly studied. The purpose of the study was to analyze correlations between sex steroids and growth factors in tissues of solitary and synchronous breast cancer and uterine myoma. Methods: Levels of estrogens (E1, E2, E3), 2OHE1 and 16α-OHE1, Р4, VEGА and EGF were measured by ELISA in tissues of breast cancer (BC, n = 37), uterine myoma (n = 27) and in synchronous BC and uterine myoma (n = 36). Results: Strong positive correlations were observed in synchronous BC and uterine myoma: E3 with VEGF (r1= 83, r2= 79; p1,2< 0.05) and EGF (r1= 78, r2= 82; p1,2< 0.05), Е1 with VEGF ( r1= 81, r2= 77; p1,2< 0.05) and EGF (r1= 76, r2= 80; p1,2< 0.05), 16-OHE1 with VEGF and EGF (r1= 80, r2= 77; p1,2< 0.05 and r1= 79 r2= 80; p1,2< 0.05). We found strong negative correlations of Е3 and VEGF (r1= 80, r2= 77; p1,2< 0.05) and EGF (r1= 79 r2= 80; p1,2< 0.05), Р4 and VEGF (r1= - 81, r2= -79; p1,2< 0.05) and EGF (r1= - 77, r2= -80; p1,2< 0.05). Solitary breast tumors showed moderate positive correlations of E2 and E1 with VEGF (r1= 56, r2= 63; p1,2< 0.05) and EGF (r1= 61, r2= 65; p1,2< 0.05) and a moderate negative correlation between VEGF and EGF and Р4 (r1= - 61, r2= -59; p1,2< 0,05). A strong negative correlation of EGF with Е1 and 16-OHE1 (r1= -79, r2= -76; р1,2< 0.05) was registered in uterine myoma. Conclusions: Tissues of synchronous primary breast tumors and uterine myoma had similar correlations between levels of growth factors and sex hormones. Solitary breast tumors and uterine myoma showed correlations typical of the tumor type. Thus, expression of growth factors in multiple primary tumors, but not in solitary ones, is subject to a clearly determined regulatory role of sex steroids and their metabolites.
JAK2 variations and functions in lung adenocarcinoma.
Authors: Yanjun Xu , Yun Fan 
Published: September 2018

e23181 Background: Lung cancer ranks as the first most common cancer and the first leading cause of cancer-related death in China and worldwide. Due to the difficulty in early diagnosis and the onset of cancer metastasis, the 5-year survival rate of lung cancer remains extremely low. JAK2 has emerged as pivotal participant in biological processes, often dysregulated in a range of cancers, including lung cancer. Recently we found that JAK2 might play an important role in lung cancer pathogenesis as an oncogene. While our understanding of JAK2 in the onset and progression of lung cancer is still in its infancy, there is no doubt that understanding the activities of JAK2 will certainly secure strong biomarkers and improve treatment options for lung cancer patients. Methods: The expression level of JAK2 mRNA was assayed using RT-PCR. JAK2 mutations and amplification were detected using next-generation sequencing (NGS). MTT assay, Transwell migration and invasion assay were conducted to study the proliferation, migration and invasion abilities of lung adenocarcinoma cells independently. The shRNA and overexpression plasmids of JAK2 were conducted. Results: JAK2 is up-regulated in lung adenocarcinoma tissues when compared with their adjacent non-tumor tissues, and was associated with lymph node metastasis ( p< 0.05). JAK2 V617F and N30S mutations and JAK2 amplification were detected by NGS in lung adenocarcinoma patient samples. Downregulation of JAK2 inhibits the proliferation, migration and invasion abilities of lung cancer cells. Moreover, overexpression of JAK2 induced the proliferation, migration and invasion abilities of lung cancer cells. Conclusions: These findings demonstrate that JAK2, whose expression is up-regulated in lung adenocarcinoma, whose mutation and amplification were detected in lung adenocarcinoma, may participate in lung cancer progression by regulating cancer cells proliferation, migration and invasion.