tbuckley/cabot-search huggingface dataset:
Gene expression profile of human colorectal cancer using oligonucleotide microarray
Authors: A. Munoz Llarena, A. Garcia, B. Suarez, M. Jangi, P. Garrido, J. Mañe, A. Sancho, A. Martinez, G. Lopez- Vivanco, S. Carrera
Journal: Journal of Clinical Oncology (2009)

e22182 Background: Current microarray technologies allow the analysis of thousands of genes simultaneously. We analyze the gene expression profile of different samples from human colorectal carcinoma in relation with the clinical stage at diagnosis. Methods: Thirty-one patients were included: 13 with stage II (transmural invasion of the colonic wall without lymph node invasion), 10 with stage III (regional lymph node invasion) and 8 with stage IV at diagnosis (metastatic). RNA was extracted from fresh tumour samples, and the quantity and quality were assessed by spectrophotometric method and capilar electrophoresis. Tumoral samples were hibrizided with a pool containing non-tumoral colonic mucosa from 33 patients with colorectal cancer. Normalized crude data were used for the initial selection of the genes, using several univariate metrics (Matusita, Kullback-Leibler, Bhattachryya). A high confidence Bayesian network was used to compare the best ranked genes with the stage of the tumour at diagnosis. Results: We identified a group of 20 genes with potential prognostic value. Of them, nine genes (HAS1, LO9861, NHLRC2, ATP6V0E2, GTFH2H2, FLJ34077 , CASP12 and RP5–1077B9.4) were able to discriminate cases with stage II-III and those with stage IV, and 11 genes (MEA1, SPRY4, TLR8, SAMSN1, DGCR14, MRCL3, SMAD2, SFRS12, LAPTM4A, CD18 and FAM111A) could discriminate between patients with stage II or III, in 95% of the cases. Data were validated with 18 new patients with colorectal cancer using a quantitative method (RT- PCR). Conclusions: Only few genes are able to discriminate the clinical stage of the tumour at diagnosis with a fresh sample of the primary. Patients with an unfavourable signature might benefit of a more extensive initial work-up. No significant financial relationships to disclose.
TGF-β1-induced transcription factor networks in Langerhans cell development and maintenance
Authors: X. Zhang, J. Gu, F.-S. Yu, L. Zhou, Q.-S. Mi
Journal: Allergy (2016)

Langerhans cells (LC) represent a specialized subset of evolutionarily conserved dendritic cells (DC) that populate stratified epithelial tissues, which are essential for the induction of skin and mucosal immunity and tolerance, including allergy. Transforming growth factor-β1 (TGF-β1) has been confirmed to be a predominant factor involved in LC development. Despite great advances in the understanding of LC ontogeny and diverse replenishment patterns, the underlying molecular mechanisms remain elusive. This review focuses on the recent discoveries in TGF-β1-mediated LC development and maintenance, with special attention to the involved transcription factors and related regulators.
Purification of Simian Virus 40 and JC T-Antigens From Transformed Cells 2
Authors: M. Cikes, E. Beth, N. Guignard, D. L. Walker, B. L. Padgett, G. Giraldo
Journal: JNCI Journal of the National Cancer Institute (1977)

Simian virus 40 (SV40) T-antigen was purified from an SV40-transformed hamster cell line (H-50) by three successive separation procedures. A crude lysate from transformed cells was chromatographed on a Biogel column under dissociating nondenaturing conditions. A peak of the immunoreactive material was found between the elution volumes of bovine serum albumin and IgG. This material was further purified by ion exchange chromatography on DEAE-cellulose and phosphocellulose columns. After the last purification step, the pooled immunoreactive material derived from SV40-transformed cells had a specific activity increased 166-fold over that of the crude cell lysate. The total recovery was 15.9%. About 15% of the 1251-labeled immunoreactive material from the last purification step could be precipitated with hamster anti-SV40 T-serum. The procedure for purification of SV40 T-antigen described here had distinct advantages over those previously described, but the known lability of the SV40 T-antigen was still an obstacle in the preparation of antigen with greater specific activity. A similar procedure was applied for the purification of JC T-antigen from a JC virus-transformed hamster cell line (HJC-15). JC T-antigen was, however, even more labile than SV40 T-antigen. The elution profiles of the two antigens on the Biogel and DEAE-cellulose columns were similar
Genetic alterations and their clinical implications in older patients with acute myeloid leukemia
Authors: C-H Tsai, H-A Hou, J-L Tang, C-Y Liu, C-C Lin, W-C Chou, M-H Tseng, Y-C Chiang, Y-Y Kuo, M-C Liu, C-W Liu, L-I Lin, W Tsay, M Yao, C-C Li, S-Y Huang, B-S Ko, S-C Hsu, C-Y Chen, C-T Lin, S-J Wu, H-F Tien
Journal: Leukemia (2016)
Brief Communication: Band T Cells in a Cat With Thymic Lymphosarcoma2
Authors: Lindsay Mackey, William Jarrett, Oswald Jarrett, Lesley Wilson
Journal: JNCI Journal of the National Cancer Institute (1975)

The mixed antiglobulin reaction and the formation of nonimmune rosettes with guinea-pig red blood cells (RBC) distinguished feline B and T cells, respectively. In a cat with thymic lymphosarcoma, the cells reacting in these tests formed separate, nonoverlapping populations. The malignant cells were large Iymphoblasts replacing the normal thymus and infiltrating local lymph nodes, where they localized only in the paracortical, i.e., thymus-dependent areas. Cells from the nodes could therefore be identified as malignant or normal by their size. The mixed antiglobulin reaction showed that the malignant cells did not carry the surface Ig characteristic of B cells, whereas these malignant cells formed nonimmune rosettes with guinea-pig RBC. Among lymph node cells, most surviving normal small lymphocytes, from outside the thymus-dependent areas, reacted as B cells. The morphologic evidence therefore corroborated the test results, which indicated that the formation of rosettes with guinea-pig RBC seems a reliable means for the demonstration of T cells in the cat.
Can obscure the true risk of certain adverse drug reactions
Authors: K R Paterson
Journal: BMJ (1995)

high.This approach has presumably been used in at least two articles in which individual rates were analysed with non-parametric rank sum tests, indicating that the assumption of normality was not met.2'Obviously, sample size calculations are possible for this kind of variable, and the sample size needed is clearly smaller than that needed in the first approach.The third method, survival analysis, can cause problems from the clinical point of view.For example, the exact time of occurrence of vertebral fractures is usually unknown.Additionally, the treatment regimens used do not generally affect patients immediately.Thus, fractures during the first months of the study may unnecessarily be regarded as being due to failures of treatment, leading to wrong conclusions and possible loss of relevant data.Recently a lot of statistical research has been conducted to allow for many events in the same patient during follow up and to take different times to the end points into account.These methods include, for example, random effects models for binary or counted data.4To our knowledge, how- ever, these techniques have not yet been included in widely used statistical programs.While waiting for the above models we prefer to choose the second alternative (individual event rate adjusted for follow up time), which fulfils the statistical assumptions, has a clear clinical interpretation, and includes information about all events.
Mouth breathing, another risk factor for asthma: the Nagahama Study
Authors: Y. Izuhara, H. Matsumoto, T. Nagasaki, Y. Kanemitsu, K. Murase, I. Ito, T. Oguma, S. Muro, K. Asai, Y. Tabara, K. Takahashi, K. Bessho, A. Sekine, S. Kosugi, R. Yamada, T. Nakayama, F. Matsuda, A. Niimi, K. Chin, M. Mishima
Journal: Allergy (2016)

Allergic rhinitis, a known risk factor for asthma onset, often accompanies mouth breathing. Mouth breathing may bypass the protective function of the nose and is anecdotally considered to increase asthma morbidity. However, there is no epidemiological evidence that mouth breathing is independently associated with asthma morbidity and sensitization to allergens. In this study, we aimed to clarify the association between mouth breathing and asthma morbidity and allergic/eosinophilic inflammation, while considering the effect of allergic rhinitis.This community-based cohort study, the Nagahama Study, contained a self-reporting questionnaire on mouth breathing and medical history, blood tests, and pulmonary function testing. We enrolled 9804 general citizens of Nagahama City in the Shiga Prefecture, Japan.Mouth breathing was reported by 17% of the population and was independently associated with asthma morbidity. The odds ratio for asthma morbidity was 1.85 (95% CI, 1.27-2.62) and 2.20 (95% CI, 1.72-2.80) in subjects with mouth breathing alone and allergic rhinitis alone, which additively increased to 4.09 (95% CI, 3.01-5.52) when mouth breathing and allergic rhinitis coexisted. Mouth breathing in nonasthmatics was a risk for house dust mite sensitization, higher blood eosinophil counts, and lower pulmonary function after adjusting for allergic rhinitis.Mouth breathing may increase asthma morbidity, potentially through increased sensitization to inhaled allergens, which highlights the risk of mouth-bypass breathing in the 'one airway, one disease' concept. The risk of mouth breathing should be well recognized in subjects with allergic rhinitis and in the general population.
Next-Generation Sequencing Of The BCR-ABL1 Kinase Domain May Be Beneficial In Decision Making Among Chronic Myeloid Leukemia Patients With Tyrosine Kinase Inhibitor Resistance
Authors: Yucel Erbilgin, Ahmet Emre Eskazan, Ozden Hatirnaz Ng, Ayse Salihoglu, Tugrul Elverdi, Sinem Firtina, Suzin Catal Tatonyan, Seniz Ongoren Aydin, Muhlis Cem Ar, Zafer Baslar, Muge Sayitoglu, A. Burhan Ferhanoglu, Yildiz Aydin, Ugur Ozbek, Teoman Soysal
Journal: Blood (2013)
The yield of multiphasic screening
Authors: B. Bates
Journal: JAMA (1972)

To determine the yield of multiphasic screening, follow-up data were gathered for consecutive abnormalities within 15 test categories. A total of 2,375 inquiries were made of 417 physicians to ascertain whether each reported abnormality was previously known or clinically obvious, whether it was confirmed, and whether it led to new diagnosis or management. The respondent rate was 90.9%. The primary block in the theoretical sequence from reported abnormality to new management lay in the physicians' failure to confirm the findings of the screening unit. Their reasons were identified. Given this lack of physician responsiveness, together with a low prevalence of disease, uncertain effectiveness of therapy, and problems of patient compliance, long-term benefits from multiphasic screening in terms of morbidity and mortality are not likely to be demonstrable. There may, however, be benefits of other kinds.
Use of posttreatment imaging and biomarker testing for survivors of breast cancer
Authors: Mary Kay Barton
Journal: CA A Cancer Journal for Clinicians (2016)

Key Points Many clinicians are still using low‐value routine surveillance imaging or biomarker testing in asymptomatic survivors of breast cancer. An imaging test for patients with early‐stage breast cancer after primary treatment was usually performed because of a symptom or clinical finding; however, almost all biomarker testing in this setting was performed as routine surveillance. Quality reporting must include the reasons behind posttreatment testing to avoid categorizing a test done to evaluate a sign or symptom as inappropriate surveillance.
In Childhood ALL, Both Blasts with a CD20−/Low and a CD20High Immunophenotype Have the Ability to Transfer the Leukemia Onto Immune-Deficient NOD/Scid Y−/− Mice.
Authors: Kerrie Wilson, Klaus Rehe, Simon Bomken, Marian Case, Leonard Shultz, Julie Irving, Josef Vormoor
Journal: Blood (2008)
Activation by 5-Bromo-2′-Deoxyuridine of Particles Resembling Guinea-Pig Leukemia Virus From Guinea-Pig Nonproducer Cells 2
Authors: J. S. Rhim, F. G. Duh, H. Y. Cho, K. D. Wuu, M. Lee Vernon
Journal: JNCI Journal of the National Cancer Institute (1973)

Particles resembling guinea-pig leukemia virus were activated from guineapig nonproducer cells after 5-bromo-2′-deoxyuridine treatment. These particles, approximately 100 mµ in the mature form, had a density of 1.16-1.17 gjml. They contained RNA-dependent DNA polymerase activity.
Efficacy and safety of AZD6244 (ARRY-142886) as second/third-line treatment of patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: V. Tzekova, C. Cebotaru, T. E. Ciuleanu, D. Damjanov, H. Ganchev, V. Kanarev, P. J. Stella, N. Sanders, G. Pover, J. D. Hainsworth
Journal: Journal of Clinical Oncology (2008)

8029 Background: The Raf/MEK/ERK signaling pathway is necessary for oncogenic function, and in NSCLC pts constitutive activation of this pathway has been correlated with BRAF/KRAS gene mutations. MEK1/2 inhibition block the Raf/MEK/ERK pathway since these kinases lie downstream of Ras, and ERK1/2 are the only known substrates of MEK1/2. Here we evaluate the efficacy and safety of oral AZD6244 - a potent, selective, ATP uncompetitive inhibitor of MEK1/2 - vs pemetrexed (PEM), which is currently approved and widely used for second/third-line treatment, in pts with advanced NSCLC. Methods: Pts who have previously received one or two chemotherapy regimens (prior surgery and/or localized radiation allowed) were randomized 1:1 to oral AZD6244 (100 mg BID) or iv infusion of PEM (500 mg/m2 over 10 min q3w). Pts in the PEM arm also received corticosteroid premedication and vitamin supplementation. The primary objective of this Phase II exploratory study was to evaluate the efficacy of AZD6244 vs PEM as second- or third-line treatment of advanced NSCLC by assessment of disease progression. Results: Of 84 pts aged 21–80 years, 40 were randomized to AZD6244 and 44 to PEM. The majority (79%) were second-line. Baseline characteristics of the two groups were comparable. There were 28 (70%) and 26 (59%) pts with a progression event in the AZD6244 and PEM groups, respectively (HR 1.35; 80% CI 0.93, 1.94; p=0.30). A secondary analysis of PFS (AZD6244: median 67 days; PEM median 90 days; HR 1.08, 80% CI 0.75, 1.54; p=0.79) supported the primary endpoint. Two objective responses were seen in each arm. Most pts in both arms experienced adverse events (AEs): 73% with AZD6244, 80% with PEM. Dermatitis acneiform (43%), diarrhea (33%), nausea (20%) and vomiting (20%) were the most common with AZD6244. Fatigue (37%), anemia (29%), nausea (24%) and anorexia (22%) were the most common with PEM. Of 11 pts with serious AEs (4 AZD6244) only neutropenia occurred in 2 pts (PEM). Conclusion: Although there was evidence of anti-tumor activity with AZD6244, there was no significant difference observed between AZD6244 and PEM for the primary disease progression endpoint. AZD6244 was well tolerated in this patient population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca
Natural Product Vibsanin A Induces Differentiation of Myeloid Leukemia Cells through PKC Activation
Authors: Zu-Yin Yu, He Xiao, Li-Mei Wang, Xing Shen, Yu Jing, Lin Wang, Wen-Feng Sun, Yan-Feng Zhang, Yu Cui, Ya-Jun Shan, Wen-Bing Zhou, Shuang Xing, Guo-Lin Xiong, Xiao-Lan Liu, Bo Dong, Jian-Nan Feng, Li-Sheng Wang, Qing-Liang Luo, Qin-Shi Zhao, Yu-Wen Cong
Journal: Cancer Research (2016)

Abstract All-trans retinoic acid (ATRA)-based cell differentiation therapy has been successful in treating acute promyelocytic leukemia, a unique subtype of acute myeloid leukemia (AML). However, other subtypes of AML display resistance to ATRA-based treatment. In this study, we screened natural, plant-derived vibsane-type diterpenoids for their ability to induce differentiation of myeloid leukemia cells, discovering that vibsanin A potently induced differentiation of AML cell lines and primary blasts. The differentiation-inducing activity of vibsanin A was mediated through direct interaction with and activation of protein kinase C (PKC). Consistent with these findings, pharmacological blockade of PKC activity suppressed vibsanin A–induced differentiation. Mechanistically, vibsanin A–mediated activation of PKC led to induction of the ERK pathway and decreased c-Myc expression. In mouse xenograft models of AML, vibsanin A administration prolonged host survival and inhibited PKC-mediated inflammatory responses correlated with promotion of skin tumors in mice. Collectively, our results offer a preclinical proof of concept for vibsanin A as a myeloid differentiation-inducing compound, with potential application as an antileukemic agent. Cancer Res; 76(9); 2698–709. ©2016 AACR.
A Chimeric Switch-Receptor Targeting PD1 Augments the Efficacy of Second-Generation CAR T Cells in Advanced Solid Tumors
Authors: Xiaojun Liu, Raghuveer Ranganathan, Shuguang Jiang, Chongyun Fang, Jing Sun, Soyeon Kim, Kheng Newick, Albert Lo, Carl H. June, Yangbing Zhao, Edmund K. Moon
Journal: Cancer Research (2016)

Abstract Chimeric antigen receptor (CAR)–modified adoptive T-cell therapy has been successfully applied to the treatment of hematologic malignancies, but faces many challenges in solid tumors. One major obstacle is the immune-suppressive effects induced in both naturally occurring and genetically modified tumor-infiltrating lymphocytes (TIL) by inhibitory receptors (IR), namely PD1. We hypothesized that interfering with PD1 signaling would augment CAR T-cell activity against solid tumors. To address this possibility, we introduced a genetically engineered switch receptor construct, comprising the truncated extracellular domain of PD1 and the transmembrane and cytoplasmic signaling domains of CD28, into CAR T cells. We tested the effect of this supplement, “PD1CD28,” on human CAR T cells targeting aggressive models of human solid tumors expressing relevant tumor antigens. Treatment of mice bearing large, established solid tumors with PD1CD28 CAR T cells led to significant regression in tumor volume due to enhanced CAR TIL infiltrate, decreased susceptibility to tumor-induced hypofunction, and attenuation of IR expression compared with treatments with CAR T cells alone or PD1 antibodies. Taken together, our findings suggest that the application of PD1CD28 to boost CAR T-cell activity is efficacious against solid tumors via a variety of mechanisms, prompting clinical investigation of this potentially promising treatment modality. Cancer Res; 76(6); 1578–90. ©2016 AACR.
Modern Surgical Considerations for Gastric Cancer
Authors: Quan P. Ly, Aaron R. Sasson
Journal: Journal of the National Comprehensive Cancer Network (2008)

Surgical resection remains the mainstay of treatment for localized gastric adenocarcinoma. The type and extent of resection depends on tumor location. Although the incidence of gastric cancer has been declining, a shift has occurred to more tumors involving the proximal compared with the distal stomach. Appropriate treatment depends on a thorough staging process to exclude the presence of distant metastatic disease. Current staging modalities include high-quality CT scan, endoscopic ultrasound, PET, and laparoscopy. The value of peritoneal lavage to detect occult peritoneal disease is under investigation. The principles of surgical resection have always included negative resection margins and adequate lymph node examination. Controversial topics requiring further study include laparoscopic resections and hepatic metastasectomy. This review highlights the salient points of current surgical management of gastric adenocarcinoma.
Opposing role of tumor necrosis factor receptor 1 signaling in T cell–mediated hepatitis and bacterial infection in mice
Authors: Raluca Wroblewski, Marietta Armaka, Vangelis Kondylis, Manolis Pasparakis, Henning Walczak, Hans‐Willi Mittrücker, Christoph Schramm, Ansgar W. Lohse, George Kollias, Hanno Ehlken
Journal: Hepatology (2016)

Death receptor (DR) ligands such as tumor necrosis factor (TNF) have been identified as fundamental mediators of liver damage both in mouse models and in humans. While the essential site of function of DR signaling is conceivably the hepatocyte, a systematic analysis is missing. Using mice with conditional gene ablation, we analyzed the tissue‐specific function of DR signaling in T cell–dependent (concanavalin A) and independent (lipopolysaccharide/galactosamine) hepatitis and in models of bacterial infection ( Listeria monocytogenes , lipopolysaccharide). We report that lipopolysaccharide/galactosamine‐induced liver injury depends on hepatocyte‐intrinsic TNF receptor 1 (p55, TNFR1). In contrast, we show that T cell–induced hepatitis was independent of TNFR1 signaling in hepatocytes, T cells, or endothelial cells. Moreover, T cell–induced hepatitis was independent of hepatocyte‐intrinsic Fas‐associated protein with death domain, TNF‐related apoptosis‐inducing ligand receptor, or Fas signaling. Instead, concanavalin A–induced hepatitis was completely prevented in mice with myeloid‐derived cell (MDC)–specific deletion of TNFR1. Significantly, however, mice lacking TNFR1 in MDCs succumbed to listeria infection, although they displayed similar sensitivity toward endotoxin‐induced septic shock when compared to control mice. These results suggest that TNFR1 signaling in MDCs is a critical mediator of both the detrimental and the protective functions of TNF in T cell–induced hepatitis and bacterial infection, respectively. Conclusion : The critical site of action of DRs is completely dependent on the nature of hepatitis; the data specify MDCs as the essential cell type of TNFR1 function in T cell–mediated hepatitis and in the response to listeria, thereby identifying the opposing role of MDC TNFR1 in autoimmunity and bacterial infection. (H epatology 2016;64:508‐521)
The metabolic gene HAO2 is downregulated in hepatocellular carcinoma and predicts metastasis and poor survival
Authors: Sandra Mattu, Francesca Fornari, Luca Quagliata, Andrea Perra, Maria Maddalena Angioni, Annalisa Petrelli, Silvia Menegon, Andrea Morandi, Paola Chiarugi, Giovanna Maria Ledda-Columbano, Laura Gramantieri, Luigi Terracciano, Silvia Giordano, Amedeo Columbano
Journal: Journal of Hepatology (2015)