tbuckley/cabot-search huggingface dataset:
The role of TNF-related apoptosis inducing ligand (TRAIL) in fibrotic lung disease
Authors: Emmet McGrath, Helen Marriott, Alan Lawrie, Simon Cross, Paul Mercer, Paul Hellewell, Rachel Chambers, David Dockrell, Moira Whyte
Journal: European Respiratory Journal (2011)

We previously showed a death receptor ligand, TRAIL, accelerates neutrophil apoptosis without associated cell activation (J Immunol 170:1027-33).We studied the role of TRAIL in wild-type and TRAIL-/- mice and investigated the role of TRAIL in patients with IPF.  Mice received intratracheal bleomycin or saline control. BAL at 3,7,16 and 23 days was analysed by cytospin morphology, hemocytometer count and flow cytometry. Collagen deposition, TRAIL expression and TUNEL positive events were also analysed. Samples from IPF patients and controls were examined for TRAIL expression and concentration. Lung function and survival time were retrieved from patient charts.  BAL analysis revealed TRAIL-/- mice had increased neutrophil numbers and reduced neutrophil apoptosis. Collagen analysis revealed a significant difference at 16 days, with TRAIL-/- mice showing increased collagen deposition. At day 23, TRAIL-/- mice had decreased TUNEL positive events. Murine lung sections revealed specific TRAIL expression in BALT and alveolar macrophages. Lung sections from IPF patients revealed an absence of TRAIL expression compared to controls. IPF patients had significantly lower serum levels of TRAIL than controls which inversely correlated with TLCO and positively correlated with survival from diagnosis.  We demonstrated that the neutrophilic inflammatory response to bleomycin is increased in TRAIL-/- compared with wild-type mice and that this finding is associated with increased collagen deposition.We also demonstrated reduced pulmonary and systemic expression of TRAIL in IPF, which correlates with worse pulmonary function and clinical outcome.This data suggests TRAIL may have therapeutic potential in ameliorating IPF.
THE GIANOTTI-CROSTI SYNDROME..
Authors: MARY EILOART
Journal: British Journal of Dermatology (1966)

Journal Article THE GIANOTTI‐CROSTI SYNDROME.: Report of Forty‐Four Cases. Get access MARY EILOART, M.B., M.R.C.P. MARY EILOART, M.B., M.R.C.P. The Wimbledon Hospital, Thurston Rd., London. S.W.20 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 78, Issue 8-9, 1 August 1966, Pages 488–492, https://doi.org/10.1111/j.1365-2133.1966.tb12255.x Published: 01 August 1966
FOLFIRINOX for the treatment of advanced pancreatic cancer: U.K. West Midlands experience.
Authors: Ankit Jain, Martin Scott-Brown, Peter Denzil Correa, Sharmila Sothi, Amy Davies, Charles Candish, David Peake, Medy Tsalic, Pankaj Punia, Yuk Ting Ma
Journal: Journal of Clinical Oncology (2015)

450 Background: The PRODIGE 4/ACCORD 11 trial demonstrated that FOLFIRINOX significantly improved response rates and survival in patients with metastatic pancreatic cancer, compared to gemcitabine. However this regimen is associated with significant toxicity. We have thus analysed the safety, tolerability and efficacy of FOLFIRINOX given outside a clinical trial setting. Methods: A retrospective analysis was conducted on all patients treated with FOLFIRINOX for advanced pancreatic cancer between July 2012 and July 2014, within the West Midlands region in the UK. Data was collected on baseline demographics, disease stage, toxicity and response to chemotherapy. Results: A total of 60 patients were identified (28 locally advanced, 32 metastatic). The median age was 59 (range 34-74) and 12% of patients were aged 70 or over. The primary tumour was located in the head of the pancreas in 68% of patients and 38% of patients had a biliary stent. All patients had an ECOG performance status of 0 or 1 (45% and 55% respectively), and had received no prior chemotherapy for advanced pancreatic cancer. FOLFIRINOX was commenced at reduced doses in 79% of patients, and subsequent dose reductions were required in 81% of patients. The median number of FOLFIRINOX cycles administered was 6 (range 1-14) but 33% of patients currently remain on treatment. Hospital admissions were required in 58% of patients but only 22% of hospital admissions were for neutropenic sepsis. FOLFIRINOX was discontinued in 30% of patients due to toxicity. There were no treatment related deaths. Of 40 patients who were eligible for assessment of response, 38% achieved a partial response and a further 45% achieved stable disease. Four patients with LA pancreatic cancer became suitable for curative surgical resection following chemotherapy; 2 of these also received chemoradiotherapy. The median overall survival for patients with metastatic disease was 12 months and the median overall survival for patients with locally advanced disease has not been reached. Conclusions: Our data shows that FOLFIRINOX can be safely delivered in a real world setting. Even with reduced doses, the response rates and survival outcomes are comparable with the results from the PRODIGE 4/ACCORD 11 trial.
Phase II ECOG trial of irinotecan/docetaxel with or without cetuximab in metastatic pancreatic cancer: Updated survival and CA19–9 results
Authors: B. A. Burtness, M. E. Powell, J. D. Berlin, D. K. Liles, A. E. Chapman, E. P. Mitchell, A. B. Benson
Journal: Journal of Clinical Oncology (2008)

4642 Background: Gemcitabine (G) is standard for metastatic pancreatic cancer (PC), with median survivals of 6 months (m). We conducted this randomized phase II trial to determine the activity of this non-G regimen, and whether combining it with cetuximab (C ) was feasible and active. Primary endpoint was response. 50% fall in CA19–9 is examined as a response surrogate in this update because restaging was not performed in 32% of pts; we previously demonstrated 50% fall in CA19–9 to correlate with survival (p=.02). Methods: Pts required histologic confirmation of adenocarcinoma of the pancreas, distant metastases, ECOG PS 0–1, normal. bilirubin, written informed consent, and were randomly assigned to Arm A or B. CT or MR within 4 weeks (wk) was used for tumor measurement. Pts on Arm A received docetaxel 35 mg/m2 and irinotecan 35 mg/m2 weekly x 4 in a 6 wk cycle. Pts on Arm B received the same therapy, with C (400 mg/m2 wk 1, 250 mg/m2 weekly thereafter). Pts not receiving therapeutic anticoagulation received enoxaparin 40 mg per day. Pts were restaged (RECIST) after 2 cycles (12 weeks). Results: In eligible, treated pts (Arm A = 44, Arm B = 43) (EGFR = 97%): Median age Arm A: 60.2, Arm B: 60.6 years. Arm A 55% male, 34% PS 0. Arm B 86% male, 44% PS 0. Mean number of cycles Arm A = 2.8, Arm B = 3.3. Dominant grade ¾ toxicities were neutropenia, nausea, diarrhea. 32% pts were never restaged (related to baseline PS, p =.03). Responses were seen in 4.5%: Arm A (90% CI 1.5%, 18.4%) and 7%, Arm B (90% CI 2.3%, 19.3%). CA19–9 fell 50% from baseline in 30% Arm A, 39% Arm B (p=0.47). Median progression-free survival Arm A 3.9 m, Arm B 4.5 m. Median overall survival (OS), with 89% of pts known to have died, 6.5m in Arm A. With 98% of pts known to have died in Arm B, OS 5.3 m. Median OS for pooled arms was greater for pts with lesser EGFR immunoreactivity than for pts with 3+ staining on > 50% of cells (p= 0.086). Conclusions: Weekly I/D ± C is associated with grade 3/4 neutropenia/diarrhea. The study did not meet the goal of 4 responding pts in either arm; however, the rate of restaging was markedly lower than projected. The surrogate response endpoint of 50% fall in CA19–9 is exploratory: 11 pts in Arm A and 14 in Arm B experienced a 50% decline in CA19–9. Non-G containing therapy is active in metastatic PC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen, Bristol-Myers Squibb, ImClone Systems, Pfizer, sanofi-aventis Bristol-Myers Squibb, ImClone Systems, Pfizer
Contribution of inflammation and impaired angiogenesis to the pathobiology of chronic thromboembolic pulmonary hypertension
Authors: Rozenn Quarck, Marijke Wynants, Erik Verbeken, Bart Meyns, Marion Delcroix
Journal: European Respiratory Journal (2015)

Deficient angiogenesis and systemic inflammation could be involved in the pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to characterise the histopathology of pulmonary vascular lesions from 52 CTEPH patients who underwent a pulmonary endarterectomy (PEA) and investigate a potential link between clinical, biological and morphometric parameters. Collagen, elastin, fibrin, lipid, endothelial, smooth muscle and inflammatory cell content was investigated using immunohistochemistry. Qualitative changes were evaluated using severity scores. Circulating levels of inflammatory mediators were measured using ELISA. Neointima, thrombotic, recanalised and atherosclerotic lesions were found. Accumulation of macrophages, T-lymphocytes and neutrophils was found mainly in atherosclerotic and thrombotic lesions. Angiogenesis was observed in all kinds of lesions; low-scored angiogenesis predicted adverse outcome, including persistent pulmonary hypertension post-PEA, start of medical therapy and poor survival. C-reactive protein (CRP), interleukin-10, monocyte chemotactic protein-1, macrophage inflammatory protein-1α and matrix metalloproteinase (MMP)-9 were significantly elevated in CTEPH patients. Plasma CRP and MMP-9 levels correlated with neutrophil and macrophage accumulation, respectively. Enhanced systemic inflammation parallels local inflammatory cell infiltration in major pulmonary arteries at advanced stages of CTEPH. Impaired neovascularisation is associated with poor survival, start of medical treatment and persistent pulmonary hypertension post-PEA. These findings suggest that inflammation and impaired angiogenesis could contribute to the progression of the disease.
Sentinel Lymph Node Biopsy Is Accurate After Neoadjuvant Chemotherapy for Breast Cancer
Authors: Tara M. Breslin, Lisa Cohen, Aysegul Sahin, Jason B. Fleming, Henry M. Kuerer, Lisa A. Newman, Ebrahim S. Delpassand, Rosalyn House, Frederick C. Ames, Barry W. Feig, Merrick I. Ross, S. Eva Singletary, Aman U. Buzdar, Gabriel N. Hortobagyi, Kelly K. Hunt
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Sentinel lymph node (SLN) biopsy has proved to be an accurate method for detecting nodal micrometastases in previously untreated patients with early-stage breast cancer. We investigated the accuracy of this technique for patients with more advanced breast cancer after neoadjuvant chemotherapy. PATIENTS AND METHODS: Patients with stage II or III breast cancer who had undergone doxorubicin-based neoadjuvant chemotherapy before breast surgery were eligible. Intraoperative lymphatic mapping was performed with peritumoral injections of blue dye alone or in combination with technetium-labeled sulfur colloid. All patients were offered axillary lymph node dissection. Negative sentinel and axillary nodes were subjected to additional processing with serial step sectioning and immunohistochemical staining with an anticytokeratin antibody to detect micrometastases. RESULTS: Fifty-one patients underwent SLN biopsy after neoadjuvant chemotherapy from 1994 to 1999. The SLN identification rate improved from 64.7% to 94.1%. Twenty-two (51.2%) of the 43 successfully mapped patients had positive SLNs, and in 10 of those 22 patients (45.5%), the SLN was the only positive node. Three patients had false-negative SLN biopsy; that is, the sentinel node was negative, but at least one nonsentinel node contained metastases. Additional processing revealed occult micrometastases in four patients (three in sentinel nodes and one in a nonsentinel node). CONCLUSION: SLN biopsy is accurate after neoadjuvant chemotherapy. The SLN identification improved with experience. False-negative findings occurred at a low rate throughout the series. This technique is a potential way to guide the axillary treatment of patients who are clinically node negative after neoadjuvant chemotherapy.
Macro and microscopic evaluation of paclitaxel delivery in the airway with a novel endobronchial injectable drug delivery catheter
Authors: Hisashi Tsukada, Plamena Entcheva-Dimitrov, Kirk Seward, Samaan Rafeq, Armin Ernst
Journal: European Respiratory Journal (2013)

Introduction: Direct injection of an anti-cancer agent into airway malignancy to maintain airway is one of the palliative interventional options. We have previously reported a new endobronchial injection catheter through a flexible bronchoscope (Seward, K. P. et al. CHEST 2010;138:420A ,421A). Normal tissue reaction against anti-cancer agent must be evaluated in vivo prior to the human application.  Aim: The purpose of the study was to assess the bronchoscopic and histopathological findings of porcine airway 1 week after injecting varying concentrations of paclitaxel (PTX).  Methods: Diluted PTX was infused through the Blowfish™ Transbronchial Micro-Infusion catheter in 1 ml volume for each treatment. The animals underwent bronchoscopic evaluation prior to sacrifice on day 7. Histological findings were evaluated by according to the semi-quantitative bronchial damage scoring system.  Results: PTX concentration of 0.05 mg/ml was injected into 13 sites (n=1), 0.5 mg/ml was injected into 13 sites (n=1), 2.5 mg/ml was injected into 5 sites (n=1), respectively. In the animal receiving 2.5 mg/ml, there was immediate injection reaction with whitening of the bronchial wall surrounded by hyperemic area which was subsequently covered by white yellowish necrotic tissue on day 7. Mild inflammation and minimal epithelium loss were observed in 0.05 mg/ml and 0.5 mg/ml injection group, moderate inflammation and significant epithelial loss were observed in 2.5 mg/ml animal.  Conclusion: A 2.5 mg/ml PTX injection developed mucosal ulceration, while 0.05 and 0.5 mg/ml injections were well tolerated. Local tissue and systemic plasma drug concentration will be analyzed.
Anti‐HLA alloantibodies in surgical patients refractory to platelet transfusion
Authors: Jeremy Ryan A. Peña, Susan L. Saidman, Timothy C. Girouard, Erin Meister, Walter H. Dzik, Robert S. Makar
Journal: American Journal of Hematology (2014)

Alloimmune platelet refractoriness (alloPR) among actively bleeding surgical patients with thrombocytopenia represents a life-threatening problem. Here we present three cases in which surgical bleeding was complicated by life-threatening thrombocytopenia and alloPR. We demonstrate that the human leukocyte antigens (HLA) antibodies associated with alloPR are broadly reactive and in high concentration, are not removed by hemodilution, and are not absorbed by transfusion of multiple doses of platelet concentrates. HLA alloPR may be under-recognized among surgical patients. Research is needed to develop pre-operative screening methods that will identify patients in need of specialized platelet support using HLA compatible donor products.
Nivolumab plus ipilimumab in the treatment of advanced melanoma
Authors: Katy K. Tsai, Adil I. Daud
Journal: Journal of Hematology & Oncology (2015)

Advanced melanoma has historically been a difficult disease to treat due to few effective systemic treatment options. However, over the past few years, scientific advancements in immune checkpoint inhibition have resulted in several novel approaches that have changed front-line management of advanced melanoma. Despite these exciting developments, there remains room for improvement in treatment outcomes. Combination immunotherapy, in particular combined cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) blockade, represents an important first step in this direction.
Mouse Mammary Tumor Virus Infectivify as a Function of Age at Inoculafion, Breeding, and Total Lapsed Time&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Dan H. Moore, Jesse Charney, B. D. Pullinger
Journal: JNCI Journal of the National Cancer Institute (1970)

By use of a recently developed test for the antigen to mouse mammary tumor virus, the effect of inoculation age on infection was measured and correlated with the eventual development of mammary tumors. Over the age range of 2–10 weeks, the total lapsed time from inoculation to the appearance of antigen in the milk or the development of tumors was approximately constant, irrespective of age at inoculation. Inoculation at 12 weeks of age gave a relatively lower incidence of infection and tumor development. All age groups had a gradual increase in antigen incidence from the first to the third lactation. Force-breeding to the second or third lactation of mice inoculated at age 10 and 12 weeks did not shorten the lapsed time for obtaining equivalent antigen incidences. Inoculation during first pregnancy gave negative antigen-assay results at the third and even at the sixth lactation. Inoculating mice at ages between 4 and 10 weeks, mating them at 10–12 weeks, and testing their milk at the second lactation gave a practical assay requiring about 15 weeks. With this schedule, dose-response regression curves were obtained typical of other virus endpoint dilution assays, and 50% Reed-Muench endpoints could be calculated.
Efficacy of cytology, cell blocks and thoracoscopic pleural biopsy in malignant pleural effusion diagnosis
Authors: Edward Altman, Larisa Spiridonov, Sonkin Vadim, Livoff Alejandro, Gavrilov Alexei, Cohen I. Hector
Journal: European Respiratory Journal (2013)

Introduction:  Thoracocentesis and cytological examination with cell blocks are considered optimal for malignant pleural effusion (MPE) diagnosis. No study has separately evaluating efficacy of these two methods compared with thoracoscopic pleural biopsy.   Objectives:  To compare diagnostic efficacy of thoracocentesis with cytological examination of pleural fluid intensified by cell blocks with surgical thoracoscopic pleural biopsy and histological examination of specimen. To reduce diagnostic time.   Methods:  Retrospective review of 115 MPE patients in Western Galilee Hospital from 2001-2011. MPE diagnosis was established by thoracocentesis, cytological examination of fluid with cell blocks. Thoracoscopy, pleural biopsy and histological examination were done in cases of false negative or inconclusive cytology.   Results:  Of 115 patients 60 were male, 55 female; mean age 67.8y. Cytological examination of pleural fluid was positive in 85.7% of 28 breast carcinoma cases, 79.5% of 39 bronchogenic carcinomas, 61.9% of 21 other malignancies. Use of cell blocks increased positive results in 3-12%. Mesothelioma (27 cases) cytological results were inconclusive.  Thoracoscopy was performed in 64 patients. Histological diagnosis was done in 100 %. Mean duration of diagnostic process was 12.58 days in 85 patients., but longer in others due to repeated thoracocentesis, again with false negative results.   Conclusions:  Cytological examination of pleural fluid in MPE patients was diagnostically effective (61.9-85.7%) except for mesothelioma. Cell blocks increased positive results.  Thoracoscopy with pleural biopsy in cases of negative or inconclusive cytological results was very effective (100%).
Phase II trial of suramin, leuprolide, and flutamide in previously untreated metastatic prostate cancer.
Authors: N A Dawson, W D Figg, M R Cooper, O Sartor, R C Bergan, A M Senderowicz, S M Steinberg, A Tompkins, B Weinberger, E A Sausville, E Reed, C E Myers
Journal: Journal of Clinical Oncology (1997)

To assess the efficacy and toxicity of suramin, hydrocortisone, leuprolide, and flutamide in previously untreated metastatic prostate cancer.Patients with stage D2 and poor-prognosis stage D1 prostate cancer were given suramin on a pharmacokinetically derived dosing schedule to maintain suramin concentrations between 175 and 300 micrograms/mL. Additionally, all patients received flutamide 250 mg orally three times daily, initiated on day 1 and continued until disease progression; depot leuprolide 7.5 mg intramuscularly begun on day 5 and repeated every 4 weeks indefinitely; and replacement doses of hydrocortisone.Fifty patients were entered onto the study: 48 with stage D2 and two with stage D1 disease. The median age was 59 years (range, 42 to 79) and 31 patients had a Karnofsky performance status (KPS) of 100%. Forty-five patients had bone metastases and 25 had measurable soft tissue disease. Forty-one (82%) had severe disease. The overall response rate in 49 assessable patients was three complete responses (CRs) and 30 partial responses (PRs) for an overall response rate of 67%. Eighteen patients have died. The median survival time has not been reached, with a median potential follow-up duration of 44 months. Grade 3 to 4 toxicity was seen in 38% of patients and was predominantly hematologic and reversible.The high response rate and prolonged survival in a poor-prognosis group of patients with metastatic prostate cancer warrant a phase III randomized comparison of this regimen versus hormonal therapy alone. Toxicity was moderate and reversible.
Virus-Free Friend Virus-Induced Tumor: &lt;italic&gt;In Vitro&lt;/italic&gt; and &lt;italic&gt;In Vivo&lt;/italic&gt; Characteristics&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: A H Fieldsteel, P J Dawson, J Scholler
Journal: JNCI Journal of the National Cancer Institute (1966)

An ascites tumor variant of a friend virus-induced tumor was grown in tissue culture. The cells grew rapidly in vitro and characteristically remained suspended in the medium. Morphologically, they closely resembled the tumor cells grown in vivo and, when transplanted back into mice, produced reticulum cell sarcomas indistinguishable from those of the original tumor line. After 32 passages in tissue culture, friend virus could no longer be detected in the cells, nor could it be isolated from serially transplanted tumors during 10 subsequent passages in mice. The average number of cells required to produce tumors was lower for the virus-free tumor cells than the original tumor which was rich in virus. It is concluded that the virus plays little part in determination of either transplantability or virulence of the tumor, once the original transformation has occurred.
Serum from patients with sarcoidosis promotes the proliferation of epithelial cell lines in vitro
Authors: Iris Zampira, Athena Gogali, Petros Oikonomidis, Evaggelia Ntzani, Agellos Evagelou, Fanny Tachmatzoglou, Maria Matthaiou, Panagiotis Canavaros, Stavros Constantopoulos, Yotanna Dalavanga
Journal: European Respiratory Journal (2012)

INTRODUCTION: Several epidemiological studies have linked sarcoidosis with neoplasia, but this is questioned by many investigators. The present study is an experimental approach to the subject. Our hypothesis was that if sarcoidosis can influence one of the two basic steps of malignancy: cancerous transformation of the cells or out of control cell growth, this could be regarded as an indirect sign of relation to neoplasia.  MATERIALS AND METHODS: A549 and SKMES cell lines were treated with serum from patients with sarcoidosis, COPD and healthy individuals. Their effect on cell proliferation was examined. The influence of cytokines and EGFR on cell proliferation was also investigated.  RESULTS: When serum from patients with sarcoidosis was added to the culture medium of both epithelial cell lines, there was a statistically significant increase of cell proliferation (p  CONCLUSION: Out of control cell growth is a basic step towards malignancy. The increase of epithelial cell proliferation in the presence of sarcoidosis serum, documented in the present study, could represent a link of this disease with neoplasia, under favorable circumstances.
Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL) : I. As2O3 exerts dose-dependent dual effects on APL cells
Authors: Guo-Qiang Chen, Xue-Geng Shi, Wei Tang, Shu-Min Xiong, Jun Zhu, Xun Cai, Ze-Guang Han, Jian-Hua Ni, Gui-Ying Shi, Pei-Ming Jia, Meng-Min Liu, Kai-Li He, Chao Niu, Jun Ma, Peng Zhang, Ting-Dong Zhang, Pascale Paul, Tomoki Naoe, Kunio Kitamura, Wilson Miller, Samuel Waxman, Zhen-Yi Wang, Sai-Juan Chen, Zhu Chen
Journal: Blood (1997)