tbuckley/cabot-search huggingface dataset:
Cisplatin etoposide in heavily pretreated relapsed ovarian cancer
Authors: D. Basu
Journal: Journal of Clinical Oncology (2006)

15061 Background: Ovarian Cancer is chemo sensitive but recurrence rate is high and patients who are platinum refractory have a poor outcome. Methods: 14 patients with histologically confirmed epithelial ovarian cancer that had relapsed after 3rd line chemotherapy (with platinum combination). Chemotherapy protocol - Cisplatin IVI 50 mg/m 2 days 1,8 &amp; 15, Etoposide PO 50 mg Days 1–15; Regime Cisplatin/oral Etoposide repeat 28 days total cycles 2, then oral Etoposide if appropriate. Toxicity Profile: Haematological - neutropenia WHO grade 3 in 20% requiring dose reduction, 64% experienced at least one haematological toxicity; Neutropenic sepsis in 14% of patients but no fatalities. Non-haematological: was mild; Nausea &amp; vomiting - Grade I - II, 86%; Neurotoxicity - Grade I - II, 26%; Nephrotoxicity - Grade I - II, 18%; Fatigue - common, 70%. Results: CA 125 response in 82%; Clinical response with symptom control in 86%; Progression free survival median 6.1 months; Duration of response: 3 months to 18 months (median of 9 months); Stable disease in 7 patients, partial response in 4, complete response occurred in no patients, progression of disease in 2 patients; one patient unable to complete treatment. Conclusion: Chemotherapy for relapsed and heavily pre-treated ovarian cancer is essentially palliative. Symptomatic platinum sensitive patients have a favourable response to rechallenge. Cisplatin-etoposide has considerable activity with tolerable toxicity profile even in platinum refractory patients. Complete information about chances of response and adverse effects should be discussed with all relapsed patients. No significant financial relationships to disclose.
Major perioperative adverse events of peroral endoscopic myotomy: a systematic 5-year analysis
Authors: Xiao-Cen Zhang, Quan-Lin Li, Mei-Dong Xu, Shi-Yao Chen, Yun-Shi Zhong, Yi-Qun Zhang, Wei-Feng Chen, Li-Li Ma, Wen-Zheng Qin, Jian-Wei Hu, Ming-Yan Cai, Li-Qing Yao, Ping-Hong Zhou
Journal: Endoscopy (2016)

<b>Background and study aims: </b>Peroral endoscopic myotomy (POEM) is now a widely used treatment for esophageal achalasia, supported by several large cohort studies. Although major perioperative adverse events (mAE) are rare, in-depth investigations of related risks and preventive measures are lacking. The aim of this study was to systematically assess mAEs during POEM by analyzing their incidence, risks, prevention, and management. <b>Patients and methods: </b>This retrospective single-center analysis included all patients (n = 1680) undergoing POEM between August 2010 and July 2015 at Zhongshan Hospital. Major adverse events were defined as: vital-sign instability, intensive care unit (ICU) stay, hospital readmission, conversion to open surgery, invasive postoperative procedure, blood transfusion, or prolonged (> 5 days) hospitalization for functional impairment. <b>Results: </b>A total of 55 patients (3.3 %, 95 % confidence interval [CI] 2.5 % – 4.2 %) experienced mAEs: delayed mucosal barrier failure (n = 13, 0.8 %; 95 %CI 0.4 % – 1.3 %), delayed bleeding (n = 3, 0.2 %; 95 %CI 0.04 % – 0.5 %), hydrothorax (n = 8, 0.5 %; 95 %CI 0.2 % – 0.9 %), pneumothorax (n = 25, 1.5 %; 95 %CI 1.0 % – 2.2 %), and miscellaneous (n = 6, 0.4 %; 95 %CI 0.1 % – 0.8 %). Four patients (0.2 %) required ICU admission. No surgical conversion occurred, and 30-day mortality was zero. In stepwise multivariate regression, institution experience of < 1 year (odds ratio [OR] 3.85, 95 %CI 1.49 – 9.95), air insufflation (OR 3.41, 95 %CI 1.37 – 8.50), and mucosal edema (OR 2.01, 95 %CI 1.14 – 3.53) were identified as related risk factors. After introducing CO<sub>2</sub> insufflation, the mAE rate declined to 1.9 % (95 %CI 1.2 % – 2.7 %) and seemed to plateau after 3.5 years at ~ 1 %. <b>Conclusion: </b>In general, POEM appears to be a safe procedure. Major adverse events were rare and could usually be prevented or anticipated, and were all managed effectively.
IFN-γ Hinders Recovery from Mucosal Inflammation during Antibiotic Therapy for Salmonella Gut Infection
Authors: Tamas Dolowschiak, Anna Angelika Mueller, Lynn Joanna Pisan, Rounak Feigelman, Boas Felmy, Mikael Erik Sellin, Sukumar Namineni, Bidong Dinh Nguyen, Sandra Yvonne Wotzka, Mathias Heikenwalder, Christian von Mering, Christoph Mueller, Wolf-Dietrich Hardt
Journal: Cell Host & Microbe (2016)
The Spectra of Chromosomal Aberrations In Acute Leukemia and Implications for the Development of Optimal Profiles of Leukemic Fusion Genes In Multiplex RT-PCR System.
Authors: Hye Ran Kim, Hyun-Jung Choi, Hee-Jo Baek, Hyeoung Joon Kim, Hoon Kook, Jong-Hee Shin, Soon-Pal Suh, Dong-Wook Ryang, Myung-Geun Shin
Journal: Blood (2010)
Quantitative Assay of Immunoglobulin Free Light Chains (FLC): Evaluation of Monoclonal Versus Polyclonal Antibody and Immunoturbidimetric Versus Immunonephelometric Detection Technology
Authors: Dragana Segulja, Danica Matisic, Dunja Rogic, Andrea Tesija Kuna, Ines Vukasovic, Nada Vrkic, Josip Batinic, Damir Nemet
Journal: Blood (2014)
PTU-101 Rituximab and hepatitis b: are we doing it right?: Abstract PTU-101 Table 1
Authors: JK Dyson, L Jopson, S Ng, M Lowery, S McPherson
Journal: Gut (2015)

<h3>Introduction</h3> Rituximab is a potent immunosuppressant used to treat haematological malignancies, rheumatological diseases and autoimmune disorders. Patients with current or past infection with the hepatitis B virus (HBV) are at high risk of reactivation following treatment with rituximab and other immunosuppressants.<sup>1</sup>HBV reactivation can cause liver failure and is associated with a 5–12% mortality. Guidelines advise screening for HBV surface antigen (HBsAg) and core antibody (anti-HBcAb) prior to initiating immunosuppression, and recommend antiviral prophylaxis for all found to be positive.<sup>2</sup> <h3>Method</h3> A baseline audit was conducted on all patients receiving rituximab in our Trust between Sept-Dec 2012 to determine the proportion of patients tested for HBsAg and anti-HBcAb. Data was also collected on prophylactic antiviral prescriptions. Following the baseline audit, a hospital guideline was developed and targeted education was conducted for rituximab prescribers. Two follow-up audits were conducted in Feb–April 2014 and Sept–Dec 2014. <h3>Results</h3> A summary of the baseline results and follow-up audits is shown in Table 1. The baseline audit showed very low rates of HBV testing; only 23% tested for HBsAg and 19% for anti-HBcAb. None were HBsAg positive, but 2 were anti-HBcAb positive and neither received antiviral prophylaxis. One of these patients experienced HBV reactivation and despite tenofovir treatment developed liver failure requiring a 3-week hospital admission. The rituximab prescriptions were mainly from our rheumatology (56%) and haematology (32%) departments. This audit highlighted the need for education of clinicians prescribing rituximab. A Trust protocol was introduced and targeted education sessions were delivered to the specialties using rituximab. A significant stepwise increase in HBV testing was seen in follow-up audits (Table 1). By Sept-Dec 2014, 79% of patients were tested for HBsAg. <h3>Conclusion</h3> In our Trust, introduction of a protocol and targeted education of clinicians has led to a dramatic increase in HBV screening prior to receiving rituximab (19% to 79%). However, reinforcement of the guidelines is needed to further increase testing rates and appropriate hepatology referrals. Importantly, prophylactic antiviral treatment was indicated for 5% of patients tested. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> EASL Guidelines: Management of chronic HBV infection. J Hepatol. 2012;57:167–185 NICE Hepatitis B guidelines, 2013
Abstract 572: A novel anti-PDL1 x anti-VEGFR2 bispecific antibody for enhanced antitumor immunity
Authors: Dan Lu, Zhanna Polonskaya, Haifan Zhang, Xenia Luna, Stella Martomo, Zhikai Zhang, Zhaojing Zhong, Yan Wu, Jeegar Patel, James Tonra, Larry Witte, Sam Waksal, Zhenping Zhu
Journal: Cancer Research (2016)

Abstract The importance of VEGF/VEGFR2 signaling in cancer growth and metastasis has been clearly highlighted by the therapeutic benefits of bevacizumab (Avastin), a humanized antibody to VEGF, and Cyramza, a fully human antibody to VEGFR2, in multiple cancer treatment modalities. Recently, immune checkpoint antagonistic antibodies to PD1 and PDL1 have shown some success in a variety of clinical settings across multiple cancer types. The overall clinical efficacy of these individual antibody therapies has been, however, rather limited and, only evident in a fraction of patients. To this end, combinations of antibodies against both VEGF/VEGFR2 and PD1/PDL1 may represent promising approaches to further enhance the antitumor efficacy of individual antibody therapies. In this study, we engineered a bispecific anti-PDL1 x anti-VEGFR2 antibody using two fully human antibodies derived from antibody phage display libraries. In this bispecific format, a high affinity single chain antibody to PDL1 was genetically fused to the C-terminus of the heavy chain of a conventional IgG antibody against VEGFR2. The bispecific antibody was efficiently expressed in mammalian cells and could be purified to homogeneity via single step affinity chromatography. The bispecific antibody retained the binding activity of its parental antibodies to PDL1 and VEGFR2, and strongly blocked both VEGF/VEGFR2 and PDL1/PD1 interaction. Further, the bispecific antibody inhibited VEGF-stimulated VEGFR2 phosphorylation and proliferation of endothelial cells, and promoted proliferation of human T cells and secretion of cytokine such as IL2 and INFγ. The bispecific antibody is currently being evaluated in vivo in relevant animal models. Citation Format: Dan Lu, Zhanna Polonskaya, Haifan Zhang, Xenia Luna, Stella Martomo, Zhikai Zhang, Zhaojing Zhong, Yan Wu, Jeegar Patel, James Tonra, Larry Witte, Sam Waksal, Zhenping Zhu. A novel anti-PDL1 x anti-VEGFR2 bispecific antibody for enhanced antitumor immunity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 572.
Predisposing germline mutations in young patients with oral cavity tumors identified by next generation sequencing.
Authors: Florentia Fostira, George Koutsodontis, Christos Perisanidis, Nick Papadogeorgakis, Chryssa Economou, Drakoulis Yannoukakos, Clarence Sasaki, Amanda Psyrri
Journal: Journal of Clinical Oncology (2016)

6058 Background: Oral cavity squamous cell cancers (SCCOC) and in particular oral squamous cell tongue cancers (SCCOT) occur with a rising incidence in younger patients often lacking the typical risk factors of tobacco use, alcohol use and human papilloma virus infection. While SCCOT tumors in young and older patients appear genetically similar, the cause for the increasing incidence in young patients remains unknown. We therefore sought to identify germline mutations that can predispose to SCCOT in young patients, unselected for family history. Methods: We prospectively collected 27 young HPV negative patients with SCCOC. Informed consent was provided from all the individuals that underwent genetic testing. Patients were treated with surgery followed by radiation or chemoradiation based on prognostic features. DNA extracted from peripheral blood lymphocytes was analyzed by a customized 94-gene panel through massive parallel sequencing. The minimum base coverage was 50x, while the variant calling was performed with GATK. Tumor samples from all the patients with definitely pathogenic mutations were subsequently tested for loss of heterozygosity (LOH) of the wild-type allele. Results: The median age of diagnosis was 33.2 (range 15-52 years). Germline loss-of-function mutations in three genes were identified in 18.5% (5/27) of the individuals tested, while 10 patients carried variants of unknown clinical significance (VUS) in six additional cancer genes. CDKN2Awas the most frequently mutated gene seen in 11.1% of the individuals and recurrence was not observed in any of these patients. Moreover, LOH in these tumors, represented by either reduction or loss of the wild type allele was confirmed. None of these patients had family history of cancer suggestive of an underlying genetic defect. Conclusions: This is the first study that correlates germline mutations in three cancer predisposing genes with SCCOC in young patients, suggesting that early age of diagnosis alone indicates a risk factor. These data may have significant clinical implications for individuals and their families, while potentially aberrant pathways amenable to targeted therapeutic strategies can be highlighted.
The combination of [<sup>18</sup>F]fluorodeoxy-glucose and 16α-[<sup>18</sup>F]fluoro-17β-estradiol positron emission tomography for identifying leiomyosarcoma in uterine smooth muscle tumors.
Authors: Y. Yoshida, T. Kurokawa, Y. Sawamura, A. Shinagawa, F. Kotsuji
Journal: Journal of Clinical Oncology (2010)

5056 Background: Preoperative histologic examination of uterine myometrial lesions is not possible, and thus imaging plays an important role in the choice of treatment for uterine smooth muscle tumor (USMT). The aim of this study was to assess whether the positron emission tomography (PET) parameters of the [18F]fluorodeoxy-glucose (FDG) /16α-[18F]fluoro-17β-estradiol (FES) ratio predicts leiomyosarcoma, the most common malignant USMT. Methods: Over a 2-week period 28 patients suspected of having malignant USMT underwent FES-PET and FDG-PET. Regional values of tracer uptake were evaluated using the standardized uptake value (SUV). Receiver-operating-characteristic (ROC) analysis was performed to determine the optimal cut-off SUV value to differentiate malignant and benign USMTs. Sensitivity and specificity, and Cohen's kappa with 95% CI were computed to quantify the agreement between the SUV ratio of FDG/FES and the histopathological findings. Results: Of the 28 patients, 6 had a final diagnosis of malignant USMT, while 22 had benign USMT. The optimal cut-off SUV value for FDG/FES was 1.5 by ROC analysis. The overall accuracy of an FDG/FES ratio greater than 1.5 was 100% (95% CI 88%-100%), sensitivity was 100% (52%-100%), specificity was 100% (82%-100%), and the kappa value was 1.0, indicating very good correlation between malignant USMT and a high SUV ratio of FDG/FES. Conclusions: These findings support the potential clinical use of direct assessment of malignant USMT in patients with “suspected malignant” USMT. No significant financial relationships to disclose.
Sevelamer crystals in the bronchus: a case report
Authors: Shroque Zaher, Ahsan Ali, Paul Babu
Journal: Thorax (2016)

An 80-year-old woman was admitted with a history of cough and gradually worsening shortness of breath of 3 months duration. Respiratory system examination revealed tracheal shift to the left, together with impaired percussion, diminished breath sounds and crackles at the left base. Her medical history included chronic renal failure for which she received haemodialysis three times a week. Her current medications included Sevelamer tablets 800 mg three times a day. The patient was on this particular medication for a period of 10 months prior to admission. There was no history of any …
Abstract 2985: Molecular mechanisms of dianhydrogalactitol (VAL-083) in cancer treatment
Authors: Beibei Zhai, Anne Steino, Jeffrey Bacha, Dennis Brown, Mads Daugaard
Journal: Cancer Research (2016)

Abstract Dianhydrogalactitol (VAL-083) is a unique bi-functional alkylating agent causing methylation of N7-guanine and inter-strand DNA crosslinks. VAL-083 is a small water-soluble molecule that readily crosses the blood-brain-barrier. In China, VAL-083 is approved as a chemotherapeutic drug for the treatment of chronic myelogenous leukemia (CML) and lung cancer. In the United States, VAL-083 has been evaluated in more than 40 National Cancer Institute (NCI)-sponsored phase I and phase II clinical trials. Preclinical studies and clinical trial data suggested antineoplastic effects of VAL-083 in a variety of malignancies, including lung cancer, brain tumors, leukemia, cervical cancer, and ovarian cancer. Here we report new insight into VAL-083 mechanism of action by showing that VAL-083 leads to irreversible cell cycle arrest and cell death caused by replication-dependent DNA damage. In lung (H2122, H1792, H23 and A549) and prostate (PC3 and LNCaP) cancer cell lines, VAL-083 treatment caused irreversible cell cycle arrest in late S and G2 phase as measured by propidium iodide (PI) and immunofluorescent (IF) staining in synchronized cultures. Importantly, VAL-083 was cytotoxic to all cell lines tested (IC50 range 3.06 - 25.7 μM). Western blot and IF analyses of DNA repair markers were employed to investigate the DNA damage response induced by VAL-083 in cancer cells. VAL-083 treatment led to phosphorylation of the proximal DNA double-strand break (DSB) sensor Ataxia Telangiectasia Mutated kinase (ATM), the single-strand DNA-binding Replication Protein A (RPA32), and the histone variant H2A.X (γH2A.X). Importantly, the DNA damage was specific to cells in S phase indicating that VAL-083-induced DNA cross-links translates into more severe DNA lesions during replication. Furthermore, S/G2 phase cell cycle arrest and increased phosphorylation of γH2A.X in cancer cells persisted after pulse-treatment with VAL-083, indicating irreversible DNA lesions. Taken together, VAL-083 displayed broad anti-neoplastic activity in lung and prostate cancer cells through the induction of replication-dependent DNA damage. Elucidation of the molecular mechanisms underlying VAL-083 cytotoxicity in cancer cells will offer help in identifying and predicting efficacy of combination treatments. Citation Format: Beibei Zhai, Anne Steino, Jeffrey Bacha, Dennis Brown, Mads Daugaard. Molecular mechanisms of dianhydrogalactitol (VAL-083) in cancer treatment. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2985.
Germline variation in <i>NFE2L2</i>/<i>CUL3</i>/<i>KEAP1</i> and risk of head and neck squamous cell carcinoma (HNSCC).
Authors: Siddharth Sheth, Joel L. Weissfeld, Marjorie Romkes, Robert L. Ferris, Jennifer R. Grandis, Julie E. Bauman, Brenda Diergaarde
Journal: Journal of Clinical Oncology (2015)

1540 Background: Nuclear factor (erythroid-derived 2)-like 2 (NFE2L2) is a key transcription factor regulating oxidative stress. Activated NFE2L2 translocates to the nucleus and binds anti-oxidant response elements in the promoter regions of cytoprotective genes. It is negatively regulated by its protein complex partners, CUL3 and KEAP1. Recent HNSCC genome profiling studies identified NFE2L2, CUL3 and KEAP1 as recurrent somatically altered genes, suggesting an important role in HNSCC carcinogenesis. We hypothesized that germline variation in NFE2L2, CUL3 and KEAP1affects risk of HNSCC. Methods: The study population consisted of 751 cases (459 oral cavity, 292 oropharynx; 69% smoker) and 862 controls (50% smoker) from the University of Pittsburgh HNSCC case-control study. Subjects were genotyped for 22 single nucleotide polymorphisms (SNPs) located in or near NFE2L2 (10), CUL3 (8) and KEAP1(4) using Sequenom’s iPLEX assay. Odds ratios (OR) for HNSCC risk and corresponding 95% confidence intervals (CI) were calculated using logistic regression models. Additive and dominant genetic models were evaluated; common allele homozygotes were used as the reference group. All analyses were adjusted for age (continuous), sex (male, female), smoking status (never, ever) and alcohol use (never, ever). Results: Two SNPs in NFE2L2 (rs13001694, rs6726395) and two SNPS in CUL3 (rs1466723, rs3738952) were significantly associated with HNSCC risk in our study population (P< 0.05). The minor alleles of these SNPs were associated with increased risk of developing HNSCC (rs13001694, OR: 1.16, 95%CI: 1.00-1.35; rs6726395, OR: 1.17, 95%CI: 1.02-1.35; rs1466723, OR: 1.27, 95%CI: 1.03-1.56; and rs378952, OR: 1.54, 95%CI: 1.20-1.98). Conclusions: Our results suggest that germline variation in the NFE2L2/CUL3/KEAP1pathway affects risk of developing HNSCC. Improved understanding of the role of genetic variation in HNSCC carcinogenesis may aid the development of more effective, personalized prevention and diagnostic strategies.
Abstract 5098: In vitro designer microenvironments for modeling the endothelin axis in brain cancer
Authors: Simone C. Rizzi, Charlotte Mermier, Sophie Crettaz, Valeria Blumer-Nesca, Céline Gandar.
Journal: Cancer Research (2016)

Abstract Preclinical studies in vivo have demonstrated that the endothelin (ET) axis is implicated in drug resistance of several tumors (e.g. brain and ovarian). Indeed, antagonists, blocking the binding of endothelin-1 to endothelin receptors (ETRs) overexpressed by cancer cells, have shown to make tumors more sensitive to conventional chemotherapies. In vitro, however, mechanistic studies have been hampered by the lack of adequate models, in which cell lines sufficiently express all key elements of the ET axis (e.g. ETRs), as they do in xenografts. We argue that limitations of conventional in vitro systems are mainly due to their inability to take into account the role of the extracellular microenvironment (ME). To overcome these limitations we have exploited the design flexibility of the QGel Matrix technology to identify 3D cell microenvironments that induced cancer cells to naturally express ETRs in vitro. Briefly, brain cancer cells LN229 were grown clonogenically in differently functionalized poly(ethylene glycol) (PEG)-based gels whose biological and biophysical characteristics were combinatorially varied. AlamarBlue™ assays and intracellular calcium release measurements (ICRM) were employed to measure cell growth and functionality of ETRs in the different gel ME over time. All assays were performed in 384-well plate format with liquid handling devices. ETR expression and functionality was confirmed in control cell lines when grown as clonogenic spheroids in MEs or as monolayer on tissue culture plastic (2D). Likewise, LN229 growth was observed in all tested MEs and in 2D. However, ETR functionality of LN229 differed considerably depending on the ME. For instance, in 2D, ICRM did not show ETR functionality. In contrast, clonogenically grown cell spheroids, in gel MEs containing cell integrin binding sites, showed significantly higher ETR functionality compared to LN229 in control gel MEs. Ongoing studies are further investigating the influence of other matrix characteristics (stiffness and degradability) to optimise expression and functionality of ETRs by LN229 for drug testing applications. These data suggest that engineered MEs are powerful tools for the development of cell-based assays with enhanced physiological relevance. With their proven compatibility with standard laboratory automation systems and assay miniaturization, these in vitro disease models can be translated to industry for making more relevant decisions on compound efficacy in preclinical tests. Citation Format: Simone C. Rizzi, Charlotte Mermier, Sophie Crettaz, Valeria Blumer-Nesca, Céline Gandar. In vitro designer microenvironments for modeling the endothelin axis in brain cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5098.
HLA-DPB1 Mismatching Results in the Generation of a Full Repertoire of HLA-DPB1 Specific T Cell Responses Showing Immunogenicity of All HLA-DPB1 Alleles
Authors: Caroline E. Rutten, Simone A.P. van Luxemburg-Heijs, Edith D. van der Meijden, Marieke Griffioen, Roelof Willemze, J.H. Frederik Falkenburg
Journal: Blood (2008)