tbuckley/cabot-search huggingface dataset:
Clinical Importance of Myeloid-Antigen Expression in Acute Lymphoblastic Leukemia of Childhood
Authors: Susan R. Wiersma, Jorge Ortega, Eugene Sobel, Kenneth I. Weinberg
Journal: New England Journal of Medicine (1991)

Leukemic cells in 15 to 25 percent of patients with acute lymphoblastic leukemia (ALL) express myeloid antigens as well as lymphoid antigens (the latter reflecting B-cell or T-cell lineage). The relations of myeloid-antigen expression to other features of ALL and to prognosis have been controversial.We analyzed clinical and laboratory features present at diagnosis in 236 consecutive cases of ALL in children. Immunophenotyping, including single- and dual-fluorescence analyses, was used to classify leukemic cells as B or T lymphoblasts and also to identify myeloid-antigen expression--the simultaneous expression of lymphoid-associated antigens and at least one of three myeloid-associated antigens (CD33, CD13, and CD14) on cells classified as L1 or L2 according to the French-American-British system.Forty-five of 185 patients with B-lineage ALL had myeloid-antigen expression, as did 8 of 41 patients with T-lineage ALL. In 10 patients, the lineage could not be determined. Myeloid-antigen expression was associated with L2 morphology (P less than 0.05), but it did not correlate with other prognostic features recognized previously. Multivariate analysis showed that myeloid-antigen expression was an important predictor of relapse in childhood ALL and the most significant prognostic factor statistically (P less than 0.0001). A white-cell count greater than or equal to 50 x 10(9) per liter at diagnosis was also an important and highly significant prognostic feature (P less than 0.001). After 40 months, the estimated disease-free survival for patients with ALL was 84 percent for those without myeloid-antigen expression and with a low white-cell count, 57 percent for those without myeloid-antigen expression and with a high white-cell count, 47 percent for those with myeloid-antigen expression and a low white-cell count, and 26 percent for those with myeloid-antigen expression and a high white-cell count (P less than 0.00001).Myeloid-antigen expression is an important independent predictor of a poor response to chemotherapy in childhood ALL.
Abstract 1164: Parallel preparation of targeted resequencing libraries from 480 genomic regions using multiplex PCR on the Access Array system
Authors: Fiona Kaper, Jun Wang, Megan J. Anderson, Peilin Chen, Min Lin, Martin Pieprzyk, Robert C. Jones, Andrew P. May
Journal: Cancer Research (2010)

Abstract Next generation sequencing platforms have dramatically reduced sequencing costs. However, it currently remains too expensive to routinely resequence entire human genomes in order to discover genetic variants or somatic mutations underlying tumorigenesis. Therefore, a need exists for multiplexed, targeted amplification methods that allow for the analysis of multiple genomic regions in large cohorts. Available targeted enrichment technologies are either aimed at the capture of regions of interest from a single sample, exhibit uneven representation or require significant amounts of input material. The novel microfluidic platform, the Access Array system, combines 48 samples with 48 primer sets resulting in 2,304 simultaneously occurring PCR amplifications requiring as little as 50ng DNA per sample. PCR products generated on the Access Array system can be used for sequencing on all next-generation sequencing platforms, including 454 GS FLX and Illumina GAII. To increase coverage and throughput, PCR reactions can be multiplexed within Access Array chips generating up to 480 amplicons per sample. As proof-of-principal experiments, we have carried out multiplexed amplifications of a set of commonly mutated cancer gene exons across 48 genomic DNA samples. In initial experiments, 580 primer pairs were validated in individual PCR reactions in 96-well plates. Each primer pair was designed to include 5’ sequences that allow for the incorporation of 454 and Illumina adapters necessary for subsequent emPCR and cluster generation, respectively. 480 primer pairs that produced a single band of the correct size, as determined on a Caliper LabChip system, were selected for multiplex PCR experiments. Primer pairs yielding amplicons with a similar size were combined in groups of 10 sets, resulting in 48 primer pools of 10 primer pairs each. Multiplex PCR was carried out on Access Array chips, followed by harvesting of the 48 amplicon pools. Each pool was diluted and then subjected to a second round of PCR in standard 96-well plates with barcoded universal primers corresponding to the 454 and Illumina sequences. The resulting products are 48 uniquely barcoded amplicon pools, each comprising 480 amplicons derived from one sample, that are ready for sequencing. We will present sequencing data generated on both 454 and Illumina systems. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1164.
HER2 concordance between central laboratory immunohistochemistry and quantitative reverse transcription polymerase chain reaction in Intergroup Trial E2197
Authors: F. L. Baehner, R. Gray, B. H. Childs, T. Maddala, S. Rowley, S. Shak, N. E. Davidson, G. W. Sledge, L. J. Goldstein, J. A. Sparano, S. S. Badve
Journal: Journal of Clinical Oncology (2008)

22009 Background: Laboratory assessment of HER2 is of marked clinical importance. Accurate quantification remains problematic within and between laboratories. Here we report central laboratory HER2 results comparing IHC and quantitative RT-PCR using Oncotype DX in patients enrolled in a large adjuvant breast cancer trial. Methods: 755 patients with 0 to 3 positive lymph nodes from Intergroup study E2197 were studied. Central IHC for HER2 was performed using duplicate 1.0 mm microarrays (HercepTest; Dako). Percent positive cells and staining intensity (0–3+) was assessed, where IHC positive cases exhibited 3+ staining in >30% cells, IHC equivocal cases exhibited 3+ staining in <30% cells or 2+ staining, and IHC negative cases exhibited 0 or 1+ staining. Quantitative RT-PCR for HER2 used Oncotype DX and pre-defined cutoffs: positive ≥11.5 units, equivocal >10.7-<11.5 units, and negative ≤10.7 units (each unit represents a 2-fold change in expression). Concordance analysis excluded the equivocal range from both assays according to ASCO/CAP Guidelines (Wolff et al, 2006). Results: HER2 expression by IHC and by RT-PCR is shown in the Table below. 175 cases were equivocal by IHC (165 of these were HER2 negative by RT-PCR). 26 cases were equivocal by RT-PCR (3 of these were HER2 negative by IHC). The overall concordance for HER2 status by central IHC and central RT-PCR was 95% (95% CI, 92%, 96%). Conclusions: There is a high degree of overall concordance between central IHC and central RT-PCR positive and negative HER2 cases. Assessment of HER2 status by RT-PCR using Oncotype DX is an alternative to IHC. FISH is in progress and results will be reported. IHC - RT-PCR HER2 Concordance HER2 Central IHC Positive Central IHC Equivocal Central IHC Negative Total RT-PCR RT-PCR Positive 94 0 4 98 RT-PCR Equivocal 13 10 3 26 RT-PCR Negative 27 165 439 631 Total IHC 134 175 443 755 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genomic Health
Xenoestrogens and Breast Cancer
Authors: Stephen H. Safe
Journal: New England Journal of Medicine (1997)

Chemophobia, the unreasonable fear of chemicals, is a common public reaction to scientific or media reports suggesting that exposure to various environmental contaminants may pose a threat to health. The specter of cancer, birth defects, and irreversible effects on infants and children invariably scares people and leads to demands for action. During the past five to six years, there has been widespread scientific debate and media coverage concerning a new potential threat to human health — environmental exposure to chemicals with endocrinologic activity. Attention has focused primarily on the weakly estrogenic organochlorine pollutants, including commercially produced chemicals such as polychlorinated . . .
Abstract 475: Resection of primary tumor improves survival in mouse metastatic breast cancer model
Authors: Omar M. Rashid, Masayuki Nagahashi, Subramaniam Ramachandran, Sheldon Milstien, Sarah Spiegel, Kazuaki Takabe
Journal: Cancer Research (2010)

Abstract Introduction: Removal of the primary tumor is not currently standard treatment for metastatic breast cancer. It is thought that doing so would induce metastatic proliferation and death. However, multiple retrospective studies over the last decade suggest a possible survival benefit from primary tumor resection. The purpose of this study, therefore, is to evaluate the role of primary tumor resection in metastatic breast cancer using a mouse model. However, because there is no consensus on which model best mimics human breast cancer metastasis, the first objective is to compare the different mouse models. Then, using the best mouse model, the primary tumor in metastatic cancer is removed to evaluate the effect on metastatic progression and survival. Methods: The models evaluated include tail vein (TV), subcutaneous (SQ), percutaneous mammary (PM) and open mammary (OM) implantation of 4T1-luc2 cells,a luciferase transfected murine estrogen receptor negative breast cancer cell line. Tumor burden was quantified in vivo by measuring the photons emitted after injection of luciferin. After mice were diagnosed with metastatic breast cancer, they were prospectively randomized to two groups; primary tumor resection versus observation. Student's t-test and Kaplan-Meier survival statistical analysis were used. Results: TV produces a 50% tail tumor rate and SQ produces intradermal and intramuscular implamantation. When compared to other methods, OM provides the most reproducible method of implanting cells into the mammary fat pad. In addition, OM produces more cancer proliferation and invasion 4 days after implantation than the other methods. When compared to SQ, OM produces larger tumors (p&amp;lt;0.02) and greater mortality (40% versus 0% at 28 days). In addition, OM breast cancer cells in mice metastasize to the axillary lymph nodes prior to metastasizing to distant organs, similar to human breast cancer. Although OM takes slightly more time to perform than other methods, it is easy to learn even for the inexperienced. Resection of the primary tumor in metastatic breast cancer does not induce metastatic proliferation. In fact, primary tumor resection instead provides a significant survival benefit in mice, 100% mortality in the observation group at 46 days versus 80% mortality in the surgery group at 75 days (p&amp;lt;0.02). Conclusions: OM is the mouse model which best mimics human breast cancer metastasis. Reducing tumor burden by primary tumor resection provides a significant survival benefit in mice with metastatic breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 475.
Abstract 3223: Severe dietary restriction enhances cancer treatment: Protecting normal cells and sensitizing malignant cells to chemotherapy by fasting
Authors: Changhan Lee, Fernando Safdie, Lizzia Raffaghello, Min Wei, Valter Longo
Journal: Cancer Research (2010)

Abstract Chemotherapy is a standard treatment modality for many cancers. However, its full clinical potential is greatly limited by toxic side-effects manifested as myelosuppression, gastrointestinal damage, fatigue, and in some case even death. Therefore, strategies or interventions that can selectively protect normal cells but not cancer cells will increase the therapeutic index of chemo drugs. We have previously reported that fasting can selectively protect tumor-bearing mice but not the cancer cells from chemo toxicity by down-regulating growth factors including IGF-I and its downstream pathways involving AKT/TOR and Ras. Here, using dietary and genetic interventions in yeast, mammalian cell culture, and mice, we show evidence that fasting not only provides selective protection to normal cells but may also sensitize certain cancer cells to chemotherapy or the severe dietary restriction itself. Using mouse models of cancer, fasting for 48-hours was sufficient to drastically suppress tumor progression. In a mouse model of breast cancer, fasting alone caused more than a 50% decrease in tumor growth. Furthermore, when combined with chemotherapy, fasting sensitized cancer cells to chemo drugs and was able to further reduce tumor growth up to 90% compared to controls. In parallel, in vitro studies using these breast cancer cells revealed similar results where glucose restriction was sufficient to reduce proliferation and also sensitize the cells to 2 different types of the standard drugs for breast cancer treatment, doxorubicin and cyclophosphamide. Comparable results were obtained using mouse models of glioma, neuroblastoma and melanoma. Furthermore, in a metastatic model of melanoma, fasting/chemotherapy not only extended survival time, but also resulted in fewer organs affected by metastasis. Since chemotherapy is generally administered as a combination of drugs, we tested the effect of fasting on a cocktail of drugs in neuroblastoma-bearing mice and demonstrated significantly enhanced survival accompanied by reducing both drug toxicity and metastasis. In addition, we provide evidence that this protection is due to reduced DNA damage to normal cells. In fact, in our yeast studies, the deletion of the AKT/S6K homolog Sch9 or RAS provides enhanced protection against multiple types of chemotherapy-induced DNA mutations. Considering the global increase in elderly population and that aging is the major risk factor for cancer, differential protection of normal cells concurrently with selective sensitization of malignant cells to chemotherapy may prove to be beneficial in cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3223.
Can proximal biliary disorders be accurately assessed with curvilinear EUS?
Authors: H Imazu, Y Uchiyama, H Kakutani, K Goda, S Omar, M Kawamura, H Tajiri
Journal: Endoscopy (2006)

Background: There is a general agreement that complete visualization of proximal bile duct including right or left hepatic duct (HD) is not possible with EUS. Percutaneous cholangiography or endoscopic retrograde cholangiography (ERC) are the standard imaging modalities for evaluation of proximal biliary disorders (PBD), although these procedures are relatively invasive and limited to obtaining cholangiogram without the visualization of mass lesions. We described 4 cases of PBD which were accurately diagnosed with curvilinear EUS (c-EUS) and influenced the further management of these patients.
CS-36 * IkappaB ZETA OVEREXPRESSION DRIVES HUMAN GLIOMA RESISTANCE TO NECROPTOSIS
Authors: M. Willems, J. Kroonen, N. Dubois, S. Berendsen, B. Nguyen, M. Bredel, M. Artesi, H. Kim, M. Rados, A. Chakravarti, V. Bours, P. Robe
Journal: Neuro-Oncology (2014)

BACKGROUND: The objective was to analyze the role of IkappaB-zeta in the cell death resistance and growth of glioblastomas. METHODS: The CNV, mRNA and protein expression of NFKBIZ/IKB-zeta were assessed in low grade and high grade glioma samples from the TCGA, the Rembrandt and proprietary cohorts of tumors, totaling 1195 samples. Data were correlated to histological grade and patient survival. IKBzeta expression was knocked down using inducible sh-RNA technology in GBM cultures, and clonogenic assays, MTT counts, caspase activation and LDH release assays, Western blotting, FACS and DNA damage assays and in situ xenograft models of malignant gliomas in nude mice were analyzed in these conditions. IKB-zeta interacting proteins were defined using immunoprecipitation, mass spectroscopy and proximity ligation assays, and protein localization was identified using selective compartmental protein extractions methods. RESULTS: NFKBIZ was amplified in 2.3% of LGG and 10% of GBM (P < 0.0001, Chi-Sqare), and its mRNA and protein expression increased with grade. NFKBIZ mRNA expression significantly associated with poor survival in a multivariate continuous Cox model (465 tumors) that also included patient age and molecular subclass (classical, mesenchymal, neural, proneural) : p = 0.030, HR: 1.12, 95%-CI: 1.01-1.24. IKB-zeta knock-down allows the translocation of STAT proteins to the mitochondria, induces a massive necroptotic cell death through a transcription-independent, TNF-related mechanism, and prevents tumor growth in xenograft models of human GBM. CONCLUSIONS: NFKBIZ is overexpressed in malignant gliomas, protects them from necroptotic cell death via a transcription-independent mechanism and constitutes a promising therapeutic target for these tumors.
Abstract 2264: Lumican as a new target to develop molecularly-targeted drugs for pancreatic cancer
Authors: Tetsushi Yamamoto, Toshiyuki Ishiwata, Yoko Matsuda, Munehiko Onda, Kazuya Yamahatsu, Kiyoko Kawahara, Yoko Kawamoto, Eiji Uchida, Zenya Naito
Journal: Cancer Research (2010)

Abstract Background: Lumican is a member of a small leucine-rich proteoglycan family and its overexpression has been reported in breast, colorectal, neuroendocrine cell, uterine cervical and pancreatic cancers. The expression of lumican in stromal tissues in breast cancer is associated with a high tumor grade, a low estrogen receptor expression level, and young age. Lumican expression in the cytoplasm in advanced colorectal cancer is correlated with a poor prognosis. Lumican expression was previously reported in pancreatic cancer, but the role of lumican in pancreatic cancer is still not well understood. In this study, we clarified the role of lumican in pancreatic cancer. Methods: Immunohistochemical analysis using anti-lumican antibody was performed in 65 pancreatic cancer patients. Lumican mRNA and protein were examined in pancreatic cancer cell lines (i.e. PANC-1, MIA PaCa-2, KLM-1) by real-time PCR and western blot. Lumican stably transfected PANC-1 cells were prepared. Then, the growth rates in vitro and in vivo were compared with mock cells. The lumican expression of PANC-1 cell was knocked down using siRNA. Then, the growth rate in vitro was compared with the control cell. Results: Immunohistochemically, lumican was localized in the cytoplasm of cancer cells in 33 of 65 patients (51%). Lumican expression in cancer cells did not correlated with clinicopathological factors. However, the survival rate of patients with lumican-positive cancer cells was significantly lower than those with lumican-negative cancer cells in the surgery-only group. Lumican mRNA and the protein were detected in all pancreatic cancer cell lines and PANC-1 cells expressed median level of lumican in the cancer cell lines examined. The growth rate of lumican-transfected PANC-1 cells was significantly higher than that of mock cells both in vitro and in vivo. Moreover, the growth rate of lumican-knocked down PANC-1 cell was significantly lower than that of the control cell. Conclusion: Lumican might regulate pancreatic cancer cell growth and become a new target to develop anti-cancer drug for pancreatic cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2264.
Maurice George Philpott
Authors: N. Philpott
Journal: BMJ (2014)

Maurice George Philpott was born in London and attended Hitchin Grammar School after his family moved to Welwyn Garden City in the early 1920s. At school he developed a deep interest in science and aspired to become a doctor from an early age. He was also a keen member of the school Scout troop, which developed his enthusiasm for travel, preferably with a Spartan edge. After qualifying, his early interest in paediatrics was marked by his attaining a DCH in 1944.

Much of his service in the Royal Army Medical Corps was spent on the hospital ship Oxfordshire , repatriating sick and wounded military personnel to many parts of the …
HEAD TO HEAD COMPARISON OF INFLAMMATION AND NEOVASCULARIZATION IN HUMAN CAROTID PLAQUES
Authors: Fabian Demeure, Caroline Bouzin, Veronique Roelants, François-Xavier Hanin, Anne Bol, Bernhard Gerber, Anne-Catherine Pouleur, Agnes Pasquet, Jean-Louis J. Vanoverschelde, David Vancraeynest
Journal: Journal of the American College of Cardiology (2015)
Intense Focal F-18 FDG Uptake in Vocal Cord Associated with Injection of Calcium Hydroxylapatite Microspheres
Authors: Benjamin S. Halpern, Scott H. Britz-Cunningham, Chun K. Kim
Journal: Clinical Nuclear Medicine (2011)

Lower F-18 fluorodeoxyglucose (FDG) uptake on PET/CT is generally expected on the side of a paralyzed vocal cord (VC). The contrary pattern of increased uptake can raise concern for metastasis or a primary VC malignancy. We present a case showing paradoxical development of intense FDG uptake in the paralyzed VC, unrelated to malignancy. History revealed injection of calcium hydroxylapatite microspheres for treatment of VC paralysis. This new synthetic material can stimulate local fibroblast activity and macrophage accumulation, leading to increased FDG uptake. The case illustrates the importance of obtaining accurate history before interpreting intense FDG uptake in a paralyzed VC.
Small-Bowel Length and the Dose of Cyclosporine in Children after Liver Transplantation
Authors: Peter F. Whitington, Jean C. Emond, Susan H. Whitington, Christoph E. Broelsch, Alfred L. Baker
Journal: New England Journal of Medicine (1990)

Children, particularly infants, require large oral doses of cyclosporine to achieve immunosuppression after liver transplantation. In 53 children who had received liver transplants, we examined the relation of height, weight, residual small-bowel length, and (in 17 children) the terminal plasma clearance rate of cyclosporine to the dose of cyclosporine required to achieve blood levels of 200 ng per milliliter.
Fatal outcome following gastric endoscopic submucosal dissection in a patient with liver cirrhosis
Authors: H. Lee, E. Kim, Y. Lee, Y. Ha, K. Cho, K. Park
Journal: Endoscopy (2012)

A 73-year-old woman was admitted to hospital for management of early gastric cancer. Esophagogastroduodenoscopy (EGD) demonstrated a 2-cm elevated mucosal lesion with a central depression on the lesser curvature of the distal antrum, which after forceps biopsy was confirmed histopathologically to be a well-differentiated adenocarcinoma ([Fig. 1]). The patient's medical history was significant for liver cirrhosis related to hepatitis C virus, hypertension, and type 2 diabetes mellitus. She had been monitored for 3 years for Child–Pugh class A liver cirrhosis. Her vital signs were stable. Her laboratory test results were as follows: white blood cell count 2.2 × 109/L, hemoglobin 9.1 g/L, platelet count 62 × 109/L, creatinine 0.8 mg/dL, albumin 3.2 g/dL, aspartate aminotransferase 90 U/L, alanine aminotransferase 54 U/L, and glucose 129 mg/dL. Abdominal computed tomography (CT) confirmed the presence of liver cirrhosis with splenomegaly. An endoscopic submucosal dissection (ESD) was performed using propofol and midazolam for balanced sedation. The lesion was successfully removed in 85 minutes and no adverse event occurred. The tumor was confined within the muscularis mucosa without lymphovascular involvement and the resection margins were clear.