bluuebunny/crossref_metadata_2025_split huggingface dataset:
COL1A1 copy number alterations detected in array-based comparative genomic hybridization (aCGH) inmyeloproliferative neoplasms: Implications for molecular pathogenesis and targeted therapy.
Authors: Savona Michael R. , Chandra Pranil , Ma Zeqiang , Liang Shile , Cooper R. Seth , Raefsky Eric , Gian Victor G. , Hockett Richard , Berdeja Jesus G. , Lennon P. Alan 
Published: March 2020

e22139 Background: Myeloproliferative neoplasms (MPNs) are a heterogeneous group of tumors marked by clonal proliferation of myeloid cells with variable marrow changes and clinical findings. Though progress has been made since the discovery of the JAK2V617F mutation, few data exist on the genetic distinction amongst these disorders, or pathogenesis of fibrosis seen in MPNs. Methods: Array-based comparative genomic hybridization (aCGH) was performed on genomic DNA extracted from marrow aspirate using an Agilent 180K oligonucleotide array platform in order to discover recurrent genetic aberrations, cooperating mutations, and gain insight into the hierarchy of molecular pathogenesis of fibrosis. BM aspirate from 17 pts were analyzed. Copy number alterations (CNAs) were compared to a reference set and mapped to functional genes. Genes with CNA were subjected to gene ontology, pathway and clustering analysis. Results: aCGH yielded copy number gains or losses in 17 out of 17 cases, 11 of which had normal karyotype and/or FISH. Numerous CNAs were identified within genes found in a variety of cellular pathways. In particular, alterations in COL1A1, NFKb and PDGFRb were implicated in this MPN cohort in 12, 8, and 6, pts, respectively. Interestingly, only patients with COL1A1 CNA had aberrancy within NFKb and PDGFRb. The remaining 5 pts had abnormal aCGH, but normal signals at these 3 genes. Conclusions: aCGH is a valuable tool which may be used to distinguish MPNs, particularly when standard testing does not. The presence of the COL1A1 aberration in 12/17 cases edifies evolving study of the role of TGFB superfamily in development of fibrosis and provides potential targets to exploit in the treatment of MPNs. Though aberrations within COL1A1 have not been previously reported in MPNs, a gene fusion involving COL1A1 and PDGFRb is found in 90% of dermatofibrosarcoma protuberans. The cooperation between these genes is currently under study in a larger cohort of pts with MPNs. [Table: see text]
NSCLC driver mutations in the Quebec population: Epidemiologic and clinical evaluation.
Authors: Saliba Wissam , Tehfe Mustapha Ali , Albadine Roula , Tran-Thanh Danh , Soulieres Denis , Gorska Isabelle , Weng Xiaoduan , Fan Boli , Florescu Marie , Audet Marie-Lise , Gougeon Francois , Blais Normand 
Published: March 2020

e22159 Background: Recent advances in lung cancer treatment embrace the recognition of molecular pathways implicated in its pathogenicity, paving the path to personalized therapies. We conducted a retrospective analysis to characterize the molecular features of the population treated for non-squamous non-small cell lung cancer (NS-NSCLC) in the province of Quebec. Methods: 622 patients with NS-NSCLC and adequate tumor blocks, treated at the CHUM between 2006 and 2008, were included. All samples were tested for ALK translocations (by IHC and FISH), EGFR classical exon 19 and 21 mutations by PCR (fragment analysis and qPCR) and for KRAS codon 12 and 13 mutations by mismatch PCR-RFLP. Molecular features were matched to demographic characteristics and clinical outcomes. Results: So far, complete results are available for 153 patients. Considering the amount of tumor tissue available, this population is largely represented by patients with local or loco-regional disease (n= 140, 91.5%). A minority of patients (10.3%) was never or light smokers (< 10 pack-yrs). Only 2 patients (1.3%) were of Asian descent. The following table depicts the outcomes of this cohort of patients segregated according to mutation status and extent of disease. Conclusions: ALK rearrangements were not identified in this unselected NS-NSCLC population characterized by localized disease and strong smoking history. ALK translocation prevalence in different populations is likely to be largely influenced by its tumor stage distribution, tobacco exposure and the use of selection criteria for molecular testing. An expanded cohort of patients will be presented at the meeting. [Table: see text]
Design, validation, and application of a PTEN quantitative reference standard for oncology assay development.
Authors: Frampton Jonathan Mark , Spivey Vicky , Goodall John , Schmitt Karin , Morrill Paul 
Published: March 2020

e22164 Background: The phosphatase PTEN is a tumor suppressor whose deletion is associated with tumor progression and results in loss of PTEN protein expression. This results with the activation of both phosphoinositide 3-kinase/AKT and mitogen-activated protein kinase pathways. The PI3K/PTEN pathway is a potential target for molecular therapy and controls multiple cellular functions (cell metabolism, proliferation, apoptosis, migration, and survival). Both PI3K and PTEN are frequently mutated in human cancer. Diagnostic testing for PTEN deletion can be performed using sequencing based methods across the coding region, intron-exon borders and promoter or alternatively using an antibody IHC based assay. Currently, however, reliable and reproducible methods for measuring PTEN expression on formalin-fixed tissue are not standardized. Methods: An isogenic X-Man (gene-X, Mutant And Normal) PTEN heterozygous deletion cell line was developed using our gene editing technology (GENESIS) using a HCT116 human colon carcinoma cell background. A 10kb fragment of PTEN, containing both exon6 and exon7, was deleted to generate a PTEN (Δex6Δex7/+) cell line. The engineering event was confirmed using sequencing, gene expression analysis and digital PCR. Metaphase spreads of the mutant and corresponding matched wild type cell line were generated for CISH and SISH analysis. In addition to this FFPE blocks containing either an allelic frequency of 25% PTEN (Δex6Δex7/+) or 100% PTEN (+/+) were developed for CISH, SISH and IHC analysis. Results: Cell validation results indicated that the PTEN (Δex6Δex7/+) was successfully engineered in a HCT116 background and digital PCR data confirmed the allelic frequency of the PTEN (Δex6Δex7/+) mixed FFPE block at 25%. Preliminary data indicates that the metaphase spreads and FFPE reference slides provide consistent results for CISH, SISH and IHC and are continuing to be used for assay development. Conclusions: Here we show data for the requirement of a Quantitative Reference Standard that can be used to standardize PTEN assay development as well as facilitate the development of potentially new diagnostic assays using SISH and CISH.
The role of macrophages in docetaxel (DTX) resistance in castrate-resistant prostate cancer (CRPC).
Authors: Horvath Lisa , Chatfield Mark D. , Lee-Ng Michelle , Lin Hui-Ming , Castillo Lesley , Breit Samuel N. , Brown David A. , Molloy Mark P. , Marx Gavin M. , Pavlakis Nick , Boyer Michael J. , Stockler Martin R. , Wykes Richard , Henshall Susan M. , Mahon Kate Lynette 
Published: March 2020

e22175 Background: DTX improves symptoms and survival in advanced CRPC, however ~ 50% of patients have chemoresistant disease. Given the toxicity of cytotoxic treatment in this population, there is an urgent need for early chemoresistance markers, a greater understanding of chemoresistance mechanisms and the development of new therapies. This study examined whether early changes in cytokine levels predict chemoresistance and explored the role of macrophages in cytokine generation and chemoresistance in vitro. Methods: 28 cytokines were measured pre/post cycle 1 of chemotherapy from 59 men with metastatic CRPC. Cytokine levels were correlated with PSA response and OS. DTX sensitive PC3 and DTX resistant PC3Rx cells were cultured alone and in coculture with U937 monocytes +/- DTX treatment. Conditioned media (CM) was analysed by a 36 cytokine array panel and by ELISA for MIC1. CM from U937 cells exposed to DTX was used to treat PC3 cells combined with escalating DTX doses. Results: Change in the levels of 10 cytokines over 1 cycle of chemotherapy (MIC-1 p=0.003; IL1ra p=0.004; IL1b p=0.01; IL4 p<0.001; IL5 p=0.041; IL6 p=0.003; IL7 p=0.009; IL8 p=0.017; IL12 p=0.004; IFNg p=0.001) was associated with clinical benefit (PR + SD vs PD). The combination of changes in MIC1, IL4 and IL6 best predicted PSA response (ROC AUC 0.88, 95% CI 0.79-0.97). PC3Rx/U937 coculture expressed more cytokines, chiefly markers of alternative macrophage differentiation, compared to PC3/U937 co-culture (IL10 17-fold; IL27 15-fold). DTX treatment enhanced cytokine production by PC3Rx/U937 coculture while reducing cytokine levels in PC3/U937 CM. The IC70 for DTX in PC3 cells incubated with CM from DTX exposed U937 cells was 10 fold greater than with U937 CM without DTX exposure. Conclusions: Early changes in circulating cytokine levels, especially those involved in macrophage activity, were associated with chemoresistance in men with CRPC. In vitro studies revealed a cytokine-mediated interaction between the macrophages and the DTX resistant cells when treated with DTX that was not apparent in the DTX sensitive cell model. When considered together, these data suggest a significant role for host macrophages in the development of DTX resistance in CRPC.
Progressive multifocal leucoencephalopathy (PML): A novel complication of brentuximab vedotin from the Southern Network on Adverse Reactions (SONAR) project.
Authors: Bennett Charles L. , Carson Kenneth Robert , Newsome Scott D. , Kim Ellen J. , Norris LeAnn B. , Jalan Pankaj , Raisch Dennis W. , Major Gene 
Published: March 2020

e22181 Background: BV is FDA approved for angio-immunoblastic large cell lymphoma and refractory Hodgkin’s lymphoma (HL). BV-linked PML cases reviewed. Methods: Case 1—Age:47/HIV negative male relapsed stage IIIB mixed cellularity undergoing treatment with BV. Prior therapies: 8 cycles of ABVD, ESHAP, BEAM, autologous stem cell transplant, involved field radiotherapy to the neck and mediastinum in 2008 and GVD ending in 2009. A 2011 relapse treated with BV q 3 weeks. Patient complained of impaired coordination and left greater than right dysdiadokinesis after 2 BV doses. Third BV cycle administered. Patient formed dysarthria, left-sided hemianopsia, hemiparesis. CSF analysis for JC virus DNA by PCR positive. Patient died shortly after. Case 2—Age:38/female revealed cutaneous anaplastic T-cell lymphoma refractory started on BV in mid-2011 led to loss of cutaneous tumors. A day after 2ndBV dose, difficulty finding words and unsteady gait. MRI revealed multifocal white matter lesions in bilateral cerebral hemispheres. Brain biopsy revealed PML. Prednisone initiated. Patient continued mixed non-fluent aphasia, quadriparesis, gait ataxia. MRI showed white matter lesions and contrast enhancement consistent with IRIS. High dose oral corticosteroids continued. Repeat MRI shows decreased lesion load, resolution of enhancement. Patient improving. Case 3—Age:72/female stage IB mycosis fungoides (MF) controlled with topical steroids and nitrogen mustard, phototherapy and interferon alpha, developed painful ulcerated plaques and tumors 4 years after diagnosis. BV administered, clinical response of skin tumors, decreased pain. Two weeks after 3rdBV dose: disoriented, poor short term memory. MRI revealed right frontal white matter. CSF sent for JC virus DNA was negative. Patient died 2 months after last BV dose. Autopsy: demyelination associated JC virus positive cells. Results: Shown. Conclusions: Unexpected PML occurrences after 2 or more BV doses, with IRIS and survival in 1 patient.
HIT antibody positivity as a predictor for early cancer diagnosis.
Authors: Alirhayim Zaid , Dyal Herman , Heidemann Danielle , Perez Cesar Ochoa , Alarhayem Abdulqader , Hassan Syed , Qureshi Sophia , Khalid Fatima , Alqalyoobi Shehabaldin , Qureshi Waqas 
Published: March 2020

e22184 Background: Heparin induced thrombocytopenia (HIT) is known to be caused by the presence of PF 4 antibody. Tumors exert immunomodulatory effects on the host immune response, including development of antibodies. Our aim was to analyze the presence of HIT in cancer patients and determine if HIT Ab is an adverse risk factor in patients with cancer. Methods: Patients with suspected HIT were selected. A case – control study was designed with 1:1 age and gender matched controls. We used chi – square analysis to compare proportions and Cox proportional hazard model to detect various predictors. Time to survival analysis was performed using Kaplan – Meier method. Results: Of 600 patients, 300 (63±15 years, women 48.8%) had a mean 4T pre – probability score of 4 ± 1.6. There were 132 cancers in both groups. 65 of these (49.2%) were in patients with probable HIT. The numbers of carcinomas and sarcomas were not significantly different between the two groups. There were no significant differences between the two groups when comparing the number of cancer diagnoses or the particular types of cancer diagnosed. The mean time to detection of cancer was within 9 ± 23 months for patients with HIT Ab versus 31 ± 54 months in cancer patients without HIT Ab (p <0.0001). In addition, there was a greater number of patients with at least 2 primary cancers among the HIT Ab positive group (p = 0.003). No predictive relationship between the type of cancer and the presence of HIT Ab was found (p >0.05). Patients with advanced cancer (stage 3 or 4) were also more likely to be HIT Ab positive (HR 3.61; 95% CI 1.31 – 10.11, p = 0.013). Cancer patients with HIT Ab were more likely to have venous thromboembolism as compared to cancer patients without HIT Ab (7.7% vs. 4.7, p = 0.0001). Kaplan – Meier’s showed worse mortality for cancer patients with HIT Ab than patients without the HIT Ab (Breslow statistic = 0.04). Conclusions: Among our cohort with suspected HIT, cancer was a common finding. Patients with HIT antibody positivity were more likely to have a new cancer diagnosis within 1 year of a positive result. These patients were also more likely to have thromboembolic complications and worsened mortality. These findings require further study, but perhaps suggest that the presence of HIT Ab should trigger earlier surveillance for cancer.
Association between c-Met and lymphangiogenic factors in patients with colorectal cancer.
Authors: Kim Kyoungha , Kim Hanjo , Lee Min Young , Ahn Tae Sung , Yun Jina , Kim Se Hyung , Kim Hyun Jung , Lee Sang Cheol , Bae Sang-Byung , Kim Chan Kyu , Lee Namsu , PARK Seong Kyu , Lee Kyu Taek , Won Jong-Ho , Hong Dae Sik , Park Hee Sook , Park Suk-Young , Lee Moon Soo , Baek Moo Jun 
Published: March 2020

e22199 Background: Lymphangiogenesis plays an important role in cancer metastasis. Although animal models show a strong relationship between lymphangiogenesis and lymph node metastasis and survival, the clinical significance of lymphangiogenesis in colorectal cancer (CRC) remains uncertain. The goal of this study was to evaluate the association between c-Met and lymphangiogenic factors and to elucidate their prognostic significance for patients with CRC. Methods: A total of 379 tissue samples were obtained from surgically resected specimens from patients with CRC in Soonchunhyang University Cheonan Hospital between January 2002 and December 2010. The expressions of c-Met, vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, and podoplanin were examined by immunohistochemistry. The expression of each marker and clinical factors were analyzed. Results: Three hundred and one of 379 (79.4%) tissues had c-Met expression. High expression of c-Met in tumor cells was significantly associated with high expression of VEGF-C (P < .001) and VEGFR-3 (P = .001). But, there was no statistically significant association with podoplanin (P = .587) and VEGF-D (P = .096). Of the 103 evaluable patients, expression of c-Met in tumor cells was significantly associated with advanced clinical stage (P = .020), positive lymph node status (P = .038), and high expression of VEGF-C (P = .020). But, there was no statistically significant association with podoplanin (P = .518), VEGFR-3 (P = .085), VEGF-D (P = .203), and overall survival (P = .360). Conclusions: Our results provide indirect evidence for an association and possible regulatory link of c-Met with the lymphangiogenic factors. But, c-Met expression in patients with CRC are not prognostic indicator for overall survival in this retrospective study.
Cyclophosphamide-induced renal damage in nude mice prevented by traditional Chinese medicine (TCM) herbal mixture LQ.
Authors: Wu Chengyu , Zhang Lei , Hoffman Robert M. 
Published: March 2020

e22210 Background: Renal damage is a dose-limiting side effects of cyclophosphamide (CYC). In the current study, we determined if a TCM herbal mixture LQ could be protective against CYC renal toxicity. Methods: Mice were treated with CYC or CYC+LQ. The histology of each organ was observed under microscopy after H&E staining. Results: The histology of the heart, liver, spleen, lung and intestine showed normal histopathological structure in all groups. The kidney of the CYC-treated mice showed toxicity including the glomeruli, the tubules, and the interstitium. The structures of the cortex in CYC pretreated group showed a disconnection between glomeruli and tubules. The ducts in the medulla were destroyed. In contrast, the kidneys in the control mice, LQ-treated mice, and CYC+LQ-treated mice showed normal architecture of the kidney cortex and medulla. In the untreated controls and the CYC+LQ-treated mice, the cortex showed normal renal corpuscles, proximal convoluted tubules, and distal convoluted tubules. The inner medulla and outer medulla all contained a thick ascending limb of the loop of Henle, and interstitial connective tissue. LQ also protected against weight loss and cachexia induced by CYC. Conclusions: TCM is a promising for combination with CYC to reduce toxicity.
Randomized phase III trial of imatinib (IM) rechallenge versus placebo in patients (pts) with metastatic and/or unresectable gastrointestinal stromal tumor (GIST) after failure of at least both IM and sunitinib (SU): Right study.
Authors: Kang Yoon-Koo , Ryu Min-Hee , Ryoo Baek-Yeol , Kim Hyun Jin , Lee Jong Jin , Yoo Changhoon , Nam Byung-Ho , Ramaiya Nikhil , Jagannathan Jyothi Priya , Demetri George D. 
Published: March 2020

LBA10502 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June, 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
MAP plus maintenance pegylated interferon α-2b (MAP-IFN) versus MAP alone in patients (pts) with resectable high-grade osteosarcoma and good histologic response to preoperative MAP: First results of the EURAMOS-1 good response randomization.
Authors: Bielack Stefan S. , Smeland Sigbjorn , Whelan Jeremy , Marina Neyssa , Hook Jane , Jovic Gordana , Krailo Mark D. , Butterfass-Bahloul Trude , Kühne Thomas , Eriksson Mikael , Teot Lisa A. , Gelderblom Hans , Kager Leo , Sundby Hall Kirsten , Gorlick Richard Greg , Randall R. Lor , Hogendoorn Pancras C. W. , Calaminus Gabriele , Sydes Matthew Robert , Bernstein Mark L. 
Published: March 2020

LBA10504 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June, 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation: Final results of the multicenter, randomized, open-label, controlled, phase III CENTRIC study.
Authors: Stupp Roger , Hegi Monika E. , Gorlia Thierry , Erridge Sara , Grujicic Danica , Steinbach Joachim Peter , Wick Wolfgang , Tarnawski Rafal , Nam Do-Hyun , Weyerbrock Astrid , Hau Peter , Taphoorn Martin JB , Nabors Louis B. , Reardon David A. , Van Den Bent Martin J. , Perry James R. , Hong Yong Kil , Hicking Christine , Picard Martin , Weller Michael ,   on behalf of the European Organisation for Research and Treatment of Cancer (EORTC), the Canadian Brain Tumor Consortium, and the CENTRIC Study Team
Published: March 2020

LBA2009 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Sunday, June, 2, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.
Molecular predictors of outcome and response to bevacizumab (BEV) based on analysis of RTOG 0825, a phase III trial comparing chemoradiation (CRT) with and without BEV in patients with newly diagnosed glioblastoma (GBM).
Authors: Sulman Erik P. , Won Minhee , Blumenthal Deborah T. , Vogelbaum Michael A. , Colman Howard , Jenkins Robert B. , Chakravarti Arnab , Jeraj Robert , Brown Paul D. , Jaeckle Kurt A. , Schiff David , Dignam James , Atkins James Norman , Brachman David , Werner-Wasik Maria , Komaki Ritsuko , Gilbert Mark R. , Mehta Minesh P. , Aldape Kenneth D. 
Published: March 2020

LBA2010 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Sunday, June, 2, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.
SAMIT: A phase III randomized clinical trial of adjuvant paclitaxel followed by oral fluorinated pyrimidines for locally advanced gastric cancer.
Authors: Yoshida Kazuhiro , Tsuburaya Akira , Kobayashi Michiya , Yoshino Shigefumi , Takahashi Masazumi , Takiguchi Nobuhiro , Tanabe Kazuaki , Takahashi Naoto , Imamura Hiroshi , Tatsumoto Naokuni , Hara Akinori , Nishikawa Kazuhiro , Fukushima Ryoji , Kurita Akira , Kojima Hiroshi , Miyashita Yumi , Oba Koji , Buyse Marc E. , Morita Satoshi , Sakamoto Junichi 
Published: March 2020

LBA4002 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June, 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Clinical outcomes in patients with castrate-refractory prostate cancer (CRPC) metastatic to bone randomized in the factorial trapeze trial to docetaxel (D) with strontium-89 (Sr89), zoledronic acid (ZA), neither, or both (ISRCTN 12808747).
Authors: James Nicholas David , Pirrie Sarah , Barton Darren , Brown Janet Elizabeth , Billingham Lucinda , Collins Stuart I. , Daunton Adam , Birtle Alison J. , Chakraborti Prabir Ranjan , Ford Daniel , Hussain Syed A. , Jones Helen , Pope Ann , Porfiri Emilio , Russell John Martin , Stanley Andrew , Staffurth John , McLaren Duncan , Parker Chris , Wylie James 
Published: March 2020

LBA5000 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Sunday, June 2, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.