tbuckley/cabot-search huggingface dataset:
Abstract P5-01-06: Differences in FGF1 and FGFR2 expression in BRCA1-associated, BRCA2-associated, and sporadic breast carcinomas
Authors: S Vos, E van der Wall, PJ van Diest, P van der Groep
Journal: Cancer Research (2012)

Abstract Introduction. In contrast to BRCA1-associated breast cancer, a distinctive phenotype for BRCA2-associated carcinomas has not been identified yet as there is no clear distinction between BRCA2- and non-BRCA mutation related or sporadic carcinomas. Recently, studies suggest overexpression of fibroblast growth factor 1 (FGF1) and fibroblast growth factor receptor 2 (FGFR2) in BRCA2 related cancers. The aim of the study was therefore to investigate whether there is differential expression of FGF1 and/or FGFR2 between BRCA2 related and sporadic and BRCA1 related cancers. This would reveal the usefulness of FGF1 and FGFR2 immunohistochemistry in daily pathology practise. Method. Invasive breast carcinomas of 33 BRCA1 and 22 BRCA2 germline mutation carriers and a tissue microarray containing 104 sporadic invasive breast carcinomas were immunohistochemically stained for FGF1, FGFR2, estrogen receptor (ER), progesterone receptor (PR), HER2, epidermal growth factor receptor 1 (EGFR), cytokeratin (CK) 5/6 and CK14. Results. FGFR2 expression was seen in 68.2% and 79.0% of BRCA2-associated and sporadic carcinomas respectively, in contrast to 22.6% of BRCA1-associated tumors (p = 0.000). FGF1 expression was seen in 72.7% of BRCA2-associated carcinomas and in 45.2% and 41.8% in BRCA1-associated and sporadic carcinomas, respectively (p = 0.032). Conclusion. FGFR2 expression differs significantly between BRCA1- and BRCA2 associated breast carcinomas but not between BRCA2 and sporadic cancers. FGF1 expression differs significantly between BRCA2-associated and sporadic carcinomas and could be used as a BRCA2-specific biomarker. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-01-06.
Clinical and Biological Implications of BRAF V600E Mutation in Multiple Myeloma
Authors: Even Holth Rustad, Hong Yan Dai, Haakon Hov, Eivind Coward, Vidar Beisvag, Ola Myklebost, Eivind Hovig, Sigve Nakken, Daniel Vodák, Leonardo A Meza-Zepeda, Arne K Sandvik, Karin Fahl Wader, Kristine Misund, Anders Sundan, Harald Aarset, Anders Waage
Journal: Blood (2014)
Vincristine Neuropathy
Authors: Francis A. Forte
Journal: JAMA (1974)

<h3>To the Editor.—</h3> A caveat about the use of vincristine sulfate intravenously is warranted when the patient has a fresh surgical lesion. A significant portion of the injected vincristine may find its way into the incisional site as a result of capillary oozing, and may create an indurated, inflammatory, local, necrotic reaction. The lesion is quite similar to that caused by inadvertent subcutaneous leakage resulting from faulty intravenous injection. Two recent experiences are cited. In the first, an excisional biopsy was performed because of a fibrolipoma of the chest wall in a patient with Hodgkin disease. One day later, 2 mg vincristine sulfate were administered intravenously. Within 72 hours, a typical vincristine "slough" was present at the incisional site. The lesion healed in two weeks. A second example arose in a 14-year-old boy with acute lymphoblastic leukemia. A deep abscess in the calf muscles was treated with adequate incision and
Case 6-1974
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Sheldon Kaufman, Gerald Nash
Journal: New England Journal of Medicine (1974)

Presentation of CaseA 73-year-old man was admitted to the hospital because of dyspnea.He was well until six years before admission, when he entered the hospital for a prostatectomy. Examination disclosed splenomegaly in addition to prostatic enlargement; no other abnormality was found. Routine laboratory studies were negative except that the differential count revealed 20 per cent atypical lymphocytes. After discharge the patient was seen periodically in the clinic. Three years before entry cervical lymphadenopathy was observed; splenomegaly persisted. A biopsy of an enlarged lymph node disclosed lymphadenitis.Five months before admission he came to the clinic because of fever . . .
Critical Role for CD103+/CD141+ Dendritic Cells Bearing CCR7 for Tumor Antigen Trafficking and Priming of T Cell Immunity in Melanoma
Authors: Edward W. Roberts, Miranda L. Broz, Mikhail Binnewies, Mark B. Headley, Amanda E. Nelson, Denise M. Wolf, Tsuneyasu Kaisho, Dusan Bogunovic, Nina Bhardwaj, Matthew F. Krummel
Journal: Cancer Cell (2016)
Boosting Central Nervous System Axon Regeneration by Circumventing Limitations of Natural Cytokine Signaling
Authors: Marco Leibinger, Anastasia Andreadaki, Philipp Gobrecht, Evgeny Levin, Heike Diekmann, Dietmar Fischer
Journal: Molecular Therapy (2016)

Retinal ganglion cells (RGCs) do not normally regenerate injured axons, but die upon axotomy. Although IL-6-like cytokines are reportedly neuroprotective and promote optic nerve regeneration, their overall regenerative effects remain rather moderate. Here, we hypothesized that direct activation of the gp130 receptor by the designer cytokine hyper-IL-6 (hIL-6) might induce stronger RGC regeneration than natural cytokines. Indeed, hIL-6 stimulated neurite growth of adult cultured RGCs with significantly higher efficacy than CNTF or IL-6. This neurite growth promoting effect could be attributed to stronger activation of the JAK/STAT3 and PI3K/AKT/mTOR signaling pathways and was also observed in peripheral dorsal root ganglion neurons. Moreover, hIL-6 abrogated axon growth inhibition by central nervous system (CNS) myelin. Remarkably, continuous hIL-6 expression upon RGC-specific AAV transduction after optic nerve crush exerted stronger axon regeneration than other known regeneration promoting treatments such as lens injury and PTEN knockout, with some axons growing through the optic chiasm 6 weeks after optic nerve injury. Combination of hIL-6 with RGC-specific PTEN knockout further enhanced optic nerve regeneration. Therefore, direct activation of gp130 signaling might be a novel, clinically applicable approach for robust CNS repair.
Phase III study of radiation therapy (RT) with or without procarbazine, CCNU, and vincristine (PCV) in low-grade glioma: RTOG 9802 with Alliance, ECOG, and SWOG.
Authors: Jan C. Buckner, Stephanie L. Pugh, Edward G. Shaw, Mark R. Gilbert, Geoffrey Barger, Stephen Coons, Peter Ricci, Dennis Bullard, Paul D. Brown, Keith Stelzer, David Brachman, John H. Suh, Christopher J. Schultz, Jean-Paul Bahary, Barbara Jean Fisher, Harold Kim, Albert D Murtha, Walter J. Curran, Minesh P. Mehta
Journal: Journal of Clinical Oncology (2014)

2000 Background: Early results of R9802 (Shaw et al: J Clin Oncol. 2012; 30(25):3065-70) demonstrated that PCV given with RT at the time of initial diagnosis prolongs progression-free survival (PFS), but not overall survival (OS), compared with RT alone. Herein, we report long term follow up results. Methods: Eligibility criteria included age <40 years with subtotal resection or biopsy, age >40 with any extent of resection, and supratentorial grade II astrocytoma (A), oligo-astrocytoma (OA), or oligodendroglioma (O). Patients were stratified by age, histology, Karnofsky Performance Status, and presence versus absence of contrast enhancement on the preoperative imaging study and randomized to RT alone (54 Gy in 30 fractions) or RT followed by 6 cycles of PCV chemotherapy. Wilcoxon test was used to compare survival distributions. Cox proportional hazard models were used to identify prognostic variables. Results: 251 eligible patients were accrued from 1998 to 2002. Median follow up is 11.9 years; 55% of patients have died. Patients in the RT + PCV arm have significantly longer median survival time (MST) compared to the RT alone arm (13.3 vs. 7.8 years, p=0.03; HR=0.59) and longer median PFS (10.4 vs. 4.0 years, p=0.002; HR=0.50). 5 and 10 year OS for RT + PCV vs RT alone are 73% vs 64%, and 62% vs 41%, respectively. Cox model identified RT + PCV treatment arm as a favorable prognostic variable for OS (p=0.003; HR 0.60) and PFS (p<0.001; HR=0.49). A or A-dominant OA histology (vs O or O-dominant OA) was prognostic for worse OS (p<0.001; HR=2.16) and PFS (p<0.001; HR 1.85). Male OS but not PFS was worse than females (p=0.02; HR 1.51). Analyses of 1p/19q co-deletions and IDH mutations have not yet been completed. Conclusions: For grade 2 glioma patients with less than gross total tumor resection or >40 years of age, PCV + RT prolongs both OS and PFS compared with RT alone. Patients with A or A-dominant OA have worse outcomes, as do males. Multivariable models that incorporate 1p/19q co-deletion and IDH mutational analyses may more fully elucidate the magnitude of treatment benefit for patients with tumors identified by specific histologic type and molecular markers. Clinical trial information: NCT00003375.
AXL-Mediated Productive Infection of Human Endothelial Cells by Zika Virus
Authors: Shufeng Liu, Leon J. DeLalio, Brant E. Isakson, Tony T. Wang
Journal: Circulation Research (2016)

The mosquito-borne Zika virus (ZIKV) is now recognized as a blood-borne pathogen, raising an important question about how the virus gets into human bloodstream. The imminent threat of the ZIKV epidemic to the global blood supply also demands novel therapeutics to stop virus transmission though transfusion.We intend to characterize ZIKV tropism for human endothelial cells (ECs) and provide potential targets for intervention.We conducted immunostaining, plaque assay, and quantitative reverse transcription-polymerase chain reaction of ZIKV RNA to evaluate the possible infection of ECs by ZIKV. Both the African and the South American ZIKV strains readily infect human umbilical vein endothelial cells and human ECs derived from aortic and coronary artery, as well as the saphenous vein. Infected ECs released infectious progeny virus. Compared with the African strains, South American ZIKV isolates replicate faster in ECs and are partially cytopathic, suggesting enhanced virulence of these isolates. Flow cytometric analyses showed that the susceptibility of ECs positively correlated with the cell surface levels of tyrosine-protein kinase receptor UFO (AXL) receptor tyrosine kinase. Gain- and loss-of-function studies further revealed that AXL is required for ZIKV entry at a postbinding step. Finally, small-molecule inhibitors of the AXL kinase significantly reduced ZIKA infection of ECs.We identified EC as a key cell type for ZIKV infection. These data support the view of hematogenous dissemination of ZIKV and implicate AXL as a new target for antiviral therapy.
P234 Prevalence of Non-pulmonary complications following Lung transplantation in adult patients with Cystic Fibrosis (CF): Abstract P234 Table 1
Authors: S Kumar, C Etherington, P Whitaker, D Peckham
Journal: Thorax (2015)

<h3>Background</h3> Lung transplantation is currently the most effective means of improving quality of life and survival in patients with end stage CF. Improvements in surgical technique, lung preservation, immune suppression and infection management have improved short and long term mortality and morbidity. The number of significant medical complications encounter following lung transplantation can have significant impact on long term management of CF. <h3>Aim</h3> To identify the frequency of medical complications that occur in a large cohort of post-transplant CF patients. <h3>Method</h3> Retrospective review of electronic records to assess complications in all patients with CF who underwent Lung transplantation between September 1992 and June 2015. <h3>Results</h3> 54 patients underwent lung transplantation (heart/lung -3, lung/liver -1) at different transplant centres, (female-35, male-19 current median age 36 years (range,22–66), current 10, 15 and 20 year survival rates are 43%, 22% and 7% respectively (median 87 months). Complications are shown in Table 1. 9 (17%) post-transplant patients died (median survival 77 months). Of these, 3 (33%) died secondary to malignancy. <h3>Conclusion</h3> In addition to organ rejection and infective causes common systemic complications included hypertensive disease (50%), gastro-oesophageal reflux disease (30%), chronic kidney disease (26%), and osteoporosis (19%). It is notable that one third of patient mortality was due to malignancy. As patient survival improves we may need to consider increased screening of these high risk patients. Frequent monitoring and excellent collaboration between transplant and CF centres may lead to earlier detection and treatment of these complications.
Distinct DNA Methylation and Expression Profiles Underlie CMML Responsiveness to Decitabine and Uncover Novel Mechanism of Resistance
Authors: Kristen Meldi, Tingting Qin, Francesca Buchi, Jean-Baptiste Micol, Jason Sotzen, Erico Masala, Bernadino Allione, Daniela Gioia, Antonella Poloni, Monia Lunghi, Omar Abdel-Wahab, Valeria Santini, Maria E Figueroa
Journal: Blood (2014)
TMEM2 Is a SOX4-Regulated Gene That Mediates Metastatic Migration and Invasion in Breast Cancer
Authors: Hyeseung Lee, Hani Goodarzi, Sohail F. Tavazoie, Claudio R. Alarcón
Journal: Cancer Research (2016)

The developmental transcription factor SOX4 contributes to the metastatic spread of multiple solid cancer types, but its direct target genes that mediate cancer progression are not well defined. Using a systematic molecular and genomic approach, we identified the TMEM2 transmembrane protein gene as a direct transcriptional target of SOX4. TMEM2 was transcriptionally activated by SOX4 in breast cancer cells where, like SOX4, TMEM2 was found to mediate proinvasive and promigratory effects. Similarly, TMEM2 was sufficient to promote metastatic colonization of breast cancer cells and its expression in primary breast tumors associated with a higher likelihood of metastatic relapse. Given earlier evidence that genetic inactivation of SOX4 or TMEM2 yield similar defects in cardiac development, our findings lead us to propose that TMEM2 may not only mediate the pathologic effects of SOX4 on cancer progression but also potentially its contributions to embryonic development. Cancer Res; 76(17); 4994-5005. ©2016 AACR.
Case 48-1969
Authors: W. Davies Sohier, Benjamin Castleman
Journal: New England Journal of Medicine (1969)

Presentation of CaseA sixty-five-year-old man was admitted to the hospital because of abdominal pain and petechiae.Ten weeks previously a mild cough productive of blood-tinged sputum developed. Three weeks later petechiae began to appear on the abdomen and legs. Shortly thereafter there was the onset of a steady, mild mid-epigastric pain. He lost 20 pounds in weight. Two weeks before admission the cough recurred, accompanied by fever. Tetracycline and prednisone, 60 mg per day, were begun. During the week before entry more petechiae became evident, and a subconjunctival hemorrhage and hematuria occurred.He had had no serious illness. As . . .
A phase I/II study of belinostat (PXD101) in patients with unresectable hepatocellular carcinoma
Authors: W. Yeo, R. Lim, B. B. MA, P. Hui, L. Chan, F. K. Mo, S. C. Yu, S. S. Ho, J. Koh, A. T. Chan, B. Goh
Journal: Journal of Clinical Oncology (2007)

15081 Background: Hepatocellular carcinoma (HCC) is a common cause of cancer morbidity and mortality. It is a highly aggressive tumor with 90% presenting with unresectable disease, resulting in a median survival of 3–6 months. Inhibitors of histone deacetylase (HDAC) have been demonstrated in HCC cell lines and xenografts to induce apoptosis and tumor regression, and have anti-proliferative, anti-metastatic and anti-invasive effects. Belinostat (N-hydroxy-3-[phenylsulphamoylphenyl] acryl amide) is a novel, low molecular weight, HDAC inhibitor. The Cancer Therapeutic Research Group (CTRG) is conducting a phase I/II study of belinostat as the first line therapy for pts with unresectable HCC. The phase I study aims to determine dose limiting toxicity (DLT) and maximum tolerated dose (MTD). Methods: Patient eligibilities include histologically or cytologically confirmed unresectable HCC, ECOG = 2, adequate hematologic, renal and hepatic functions. The dose of belinostat was started at 600 mg/m 2 /day i.v. on day 1–5 every 3 weeks; with increment of 300 mg/m 2 /day up to 1200 mg/m 2 /day. Dose limiting toxicities (DLT) are defined as grade 4 hematological toxicity or grade 3 or 4 nonhematological toxicity during cycle 1 (according to NCI CTC v3), or treatment delay &gt;2 weeks. The MTD is defined as the dose below which ≥ 2 of 3 or ≥ 2 of 6 patients experiencing DLT. After determination of the MTD, 3 additional patients will be treated at this dose to further define toxicity. Results: From June-December 2006, 12 pts were entered; 3 were treated at level I (600 mg/m 2 /day), 3 at level 2 (900 mg/m 2 /day), and 6 at level 3 (1200 mg/m 2 /day). There were no DLTs on level 1, 2 or 3. Therefore, the MTD of belinostat was not reached. Overall toxicities were WBC gr. 0/1/2/3/4: 12/0/0/0/0, ANC gr. 0/1/2/3/4: 12/0/0/0/0; Hb gr. 0/1/2/3/4: 4/7/0/1/0; platelet gr. 0/1/2/3/4: 8/4/0/0/0; lethargy gr. 0/1/2/3: 12/0/0/0/0, phlebitis gr. 0/1/2/3: 10/0/2/0; Cough gr. 0/1/2/3: 9/0/3/0; Nausea gr. 0/1/2/3: 7/3/2/0 and vomiting gr. 0/1/2/3: 9/3/0/0. Conclusions: At the maximum dose of 1200 mg/m 2 /day (level 3), MTD has not been reached. Belinostat is very well tolerated. Phase II study will be started at dose level 1200 mg/m 2 /day. Sponsor: The Division of Cancer Treatment and Diagnosis, National Cancer Institute, USA. No significant financial relationships to disclose.
<i>CSN1</i> Somatic Mutations in Penile Squamous Cell Carcinoma
Authors: Andrew Feber, Daniel C. Worth, Ankur Chakravarthy, Patricia de Winter, Kunal Shah, Manit Arya, Muhammad Saqib, Raj Nigam, Peter R. Malone, Wei Shen Tan, Simon Rodney, Alex Freeman, Charles Jameson, Gareth A. Wilson, Tom Powles, Stephan Beck, Tim Fenton, Tyson V. Sharp, Asif Muneer, John D. Kelly
Journal: Cancer Research (2016)

Abstract Other than an association with HPV infection, little is known about the genetic alterations determining the development of penile cancer. Although penile cancer is rare in the developed world, it presents a significant burden in developing countries. Here, we report the findings of whole-exome sequencing (WES) to determine the somatic mutational landscape of penile cancer. WES was performed on penile cancer and matched germline DNA from 27 patients undergoing surgical resection. Targeted resequencing of candidate genes was performed in an independent 70 patient cohort. Mutation data were also integrated with DNA methylation and copy-number information from the same patients. We identified an HPV-associated APOBEC mutation signature and an NpCpG signature in HPV-negative disease. We also identified recurrent mutations in the novel penile cancer tumor suppressor genes CSN1(GPS1) and FAT1. Expression of CSN1 mutants in cells resulted in colocalization with AGO2 in cytoplasmic P-bodies, ultimately leading to the loss of miRNA-mediated gene silencing, which may contribute to disease etiology. Our findings represent the first comprehensive analysis of somatic alterations in penile cancer, highlighting the complex landscape of alterations in this malignancy. Cancer Res; 76(16); 4720–7. ©2016 AACR.
Infections à Escherichia coli 0157 associées au lait non pasteurisé
Authors: F Allerberger, M Wagner, P Schweiger, H P. Rammer, A Resch, M P Dierich, A W Friedrich, H Karch
Journal: Eurosurveillance (2001)

Cet article decrit deux cas d’infection a Escherichia coli 0157 chez des enfants, dont l’un a developpe un syndrome hemolytique uremique (SHU). Tous deux avaient bu du lait cru de vache ou de chevre dans la semaine precedant l’apparition de la maladie. Le sous-typage moleculaire a permis d’identifier une souche d’E. coli 0157:H fermentant du sorbitol, a partir d’echantillons preleves chez une vache laitiere. Cette souche differait des souches de 0157:H produisant des toxines Shiga, mises en evidence chez le petit garcon de six ans atteint du SHU. Ce resultat souligne l’importance de prospecter d’autres causes d’infection, meme lorsque la consommation de lait cru est documentee. Dans le second cas, il a ete impossible de distinguer des souches 0157:H humaines ne fermentant pas le sorbitol, de souches animales issues de prelevements sur des chevres. L’isolement de souches identiques d’E. coli 0157:H ne fermentant pas le sorbitol, chez l’homme et chez des animaux contacts, conforte l’association entre les SHU et la consommation de lait de chevre cru, et souligne a nouveau l’importance de pasteuriser le lait.
A prospective investigation of nutritional status in 517 Irish cancer patients undergoing chemotherapy: prevalence of malnutrition, cachexia, sarcopenia and impact on quality of life.
Authors: Derek Gerard Power, Samantha Cushen, Seamus O'Reilly, Eadaoin Ni Bhuachalla, Peter Mceneaney, Louise Daly, Aoife M Ryan
Journal: Journal of Clinical Oncology (2015)

e20629 Background: Malnutrition is a significant factor in predicting cancer patients’ quality of life (QoL), tolerance to treatment, and overall survival. This study aimsto describe the prevalence of malnutrition, cancer cachexia (CC), sarcopenia and their impact on QoL for the first time in Irish cancer patients undergoing chemotherapy. Methods: A prospective study of adult cancer patients undergoing chemotherapy was conducted. Malnutrition Universal Screening Tool scores (MUST) and QoL (EORTC QLQ-C30) were measured. CC was defined as weight loss (WL) > 5% over the past 6 months or WL > 2% in combination with a Body Mass Index (BMI) < 20kg/m2 or sarcopenia. Skeletal muscle was measured by CT scan. Sarcopenia was defined using published cut offs. Results: In total,517 patients receiving chemotherapy (302 male), with a mean age of 61.8 (SD 10.5) were included. The percentage of patients with colorectal cancer was highest (30%) followed by upper gastrointestinal cancer (23%) and lung cancer (12%). 42.1% were treated with curative intent. According to BMI, 4.6% were underweight ( < 18.5kg/m2), 42.4% were normal weight (18.5-24.9 kg/m2) and 53% were overweight or obese (BMI ≥ 25 kg/m2). Sarcopenia was present in 47.3% and CC was present in 44.8 %. The highest rates of muscle wasting were seen in patients with tumours of the genitourinary system (61.7%), oesophagus (53%) and hepatobillary organs (50%). Based on MUST scores, 40% were at medium to high risk of malnutrition and the remainder, (309 patients, 59.7%) were classified as ‘low’ nutritional risk. However, 9.4% of these ‘low risk’ patients had CC and 26% were sarcopenic. CC, sarcopenia and nutritional risk were significantly associated with low global QoL scores (P < 0.05). Conclusions: A significant proportion of Irish cancer patients undergoing chemotherapy experience severe involuntary WL, sarcopenia and CC, however identification of malnourished patients presents challenges in the era of obesity. The routine availability of CT scans in oncology provides a unique opportunity to incorporate body composition into nutrition screening and assessment.