tbuckley/cabot-search huggingface dataset:
Incidence of Chemotherapy-Induced Nausea and Vomiting with Moderately Emetogenic Chemotherapy: Advice Study
Authors: Y. Escobar, G. Cajaraville, J. Virizuela, R. Alvarez Alvarez, A.J. Muñoz Martín, O. Olariaga, B. Muros, M.J. Lecumberri Biurrun, J. Feliu, P. Martinez Del Prado, J.J. Cruz Hernandez, M.J. Martínez Bautista, R. Lopez, A. Blasco, P. Gascon, V. Calvo, P. Luna Fra, J. Montalar, P. Del Barrio, M.V. Tornamira
Journal: Annals of Oncology (2014)
Age-adjusted D-dimers can safely exclude pulmonary embolism: Implications for a UK district general hospital
Authors: Craig Batista, Jonathan Ratoff
Journal: European Respiratory Journal (2013)

Introduction 

Negative D-dimers are used to reliably exclude pulmonary embolism (PE) in patients with an unlikely clinical probability. However, D-dimer values increase with age reducing the test’s specificity. Age-adjustment of the reference range’s upper limit (age x 0.01 mg/L) for patients older than 50 years has been suggested to overcome this problem. To understand how this might affect a typical district general hospital, we carried out a retrospective analysis between August and October 2012.

Method 

The medical records of all patients admitted for the radiological investigation of PE with an unlikely clinical probability (two-tier Wells score) and a positive D-dimer (> 0.5 mg/L) were analysed. Patients older than 50 years had an alternative reference range calculated retrospectively (age x 0.01 mg/L).

Results 

86 patients underwent computed tomography pulmonary angiography or ventilation perfusion imaging (78 and 8 respectively). The mean age was 70.9 years. Only 14 patients had PE (16%). A greater proportion of older patients had negative imaging: 92% (≥ 70 years) compared to 67% (< 70 years). We identified 28 patients with negative imaging, in whom PE could have been excluded with age-adjusted D-dimers alone; a potential 39% reduction in the need for radiology to exclude PE. All patients diagnosed with PE would still have undergone radiological investigation despite age-adjustment.

Discussion 

Our study demonstrates that the application of age-adjusted D-dimers is safe, improves the test’s sensitivity and significantly reduces the requirement for radiological investigation in an elderly population.
All-trans retinoic acid arrests cell cycle in leukemic bone marrow stromal cells by increasing intercellular communication through connexin 43-mediated gap junction
Authors: Yao Liu, Qin Wen, Xue-lian Chen, Shi-jie Yang, Lei Gao, Li Gao, Cheng Zhang, Jia-li Li, Xi-xi Xiang, Kai Wan, Xing-hua Chen, Xi Zhang, Jiang-fan Zhong
Journal: Journal of Hematology & Oncology (2015)

Gap junctional intercellular communication (GJIC) is typically decreased in malignant tumors. Gap junction is not presented between hematopoietic cells but occurred in bone marrow stromal cells (BMSCs). Connexin 43 (Cx43) is the major gap junction (GJ) protein; our previous study revealed that Cx43 expression and GJIC were decreased in acute leukemic BMSCs. All-trans retinoic acid (ATRA) increases GJIC in a variety of cancer cells and has been used to treat acute promyelocytic leukemia, but the effects of ATRA on leukemic BMSCs is unknown. In this study, we evaluated the potential effects of ATRA on cell cycle, proliferation, and apoptosis of leukemic BMSCs. Effects of ATRA on Cx43 expression and GJIC were also examined.Human BMSCs obtained from 25 patients with primary acute leukemia, and 10 normal healthy donors were cultured. Effects of ATRA on cell cycle, cell proliferation, and apoptosis were examined with or without co-treatment with amphotericin-B. Cx43 expression was examined at both the mRNA and protein expression levels. GJIC was examined by using a dye transfer assay and measuring the rate of fluorescence recovery after photobleaching (FRAP).ATRA arrested the cell cycle progression, inhibited cell growth, and increased apoptosis in leukemic BMSCs. Both Cx43 expression and GJIC function were increased by ATRA treatment. Most of the observed effects mediated by ATRA were abolished by amphotericin-B pretreatment.ATRA arrests cell cycle progression in leukemic BMSCs, likely due to upregulating Cx43 expression and enhancing GJIC function.
Treatment of ocular melanoma metastatic to the liver by hepatic arterial chemotherapy.
Authors: S Leyvraz, V Spataro, J Bauer, S Pampallona, R Salmon, T Dorval, R Meuli, M Gillet, F Lejeune, L Zografos
Journal: Journal of Clinical Oncology (1997)

PURPOSE Ocular melanoma is characterized by a high rate of liver metastases and is associated with a median survival time less than 5 months. There is no standard treatment available. Treatment strategies have, without success, relied on the experience with metastatic cutaneous melanoma. The only effective treatment is chemoembolization using cisplatin and polyvinyl sponge, which has never become accepted on a large scale. The objective of the study was to establish prospectively the efficacy and toxicity of hepatic intraarterial fotemustine, a third-generation nitrosourea, in patients with liver metastases from ocular melanoma. PATIENTS AND METHODS Thirty-one patients were subjected to laparotomy to place a totally implantable catheter into the hepatic artery and received fotemustine 100 mg/m2 as a 4-hour infusion, first once a week for four times and then, after a 5-week rest period, every 3 weeks until progression or toxicity. Cox regression models were used to assess the prognostic role of patient survival characteristics. RESULTS Objective responses were observed in 12 of 30 assessable patients (40%; 95% confidence interval, 22% to 59%). The median duration of response was 11 months and the median overall survival time, 14 months. Lactate dehydrogenase (LDH) appeared to be the strongest prognostic factor for survival. Toxicity was minimal and treatment could be administered on an outpatient basis. CONCLUSION The results of hepatic arterial chemotherapy with fotemustine produced a high response rate and survival similar to chemoembolization therapy. It involves no major toxicity and preserves the quality of life. To assess further its effectiveness, a randomized study to compare hepatic intraarterial versus intravenous chemotherapy is being planned.
Targeting survival and cell trafficking in multiple myeloma and <scp>W</scp>aldenstrom macroglobulinemia using pan‐class <scp>I PI</scp>3<scp>K</scp> inhibitor, buparlisib
Authors: Ilyas Sahin, Feda Azab, Yuji Mishima, Michele Moschetta, Brian Tsang, Siobhan V. Glavey, Salomon Manier, Yu Zhang, Antonio Sacco, Aldo M. Roccaro, Abdel Kareem Azab, Irene M. Ghobrial
Journal: American Journal of Hematology (2014)

The phosphatidylinositol-3 kinase (PI3K) pathway is activated in multiple myeloma (MM) and Waldenstrom Macroglobulenima (WM), and plays a crucial role in tumor progression and drug resistance. In this study, we characterized the role of pan-class I PI3K inhibition on cell trafficking and survival of MM and WM cells. We tested the effect of pan-class I PI3K inhibition by siRNA silencing or pharmacologic inhibition with buparlisib on MM cell survival, apoptosis and cell cycle in vitro and tumor growth and mobilization of MM cells in vivo. We then evaluated buparlisib-dependent mechanisms of induced MM cell mobilization. Moreover, the effect of buparlisib on cell survival, apoptosis, and adhesion of WM cells to bone marrow stromal cells (BMSCs) has been evaluated. We showed that buparlisib induced toxicity in MM cells, supported by induction of apoptosis and cell cycle arrest. Buparlisib was also found to reduce tumor progression in vivo. Importantly, buparlisib enhanced MM cell mobilization in vivo which was driven by decreased adhesion of MM cells to BMSCs and increased chemotaxis via up-regulation of CXCR4 expression. Similar to its effects on MM cells, buparlisib also induced cell survival and apoptosis, and decreased adhesion in WM cells. These data highlight the critical contribution of class I PI3K signaling to the regulation of survival and cell dissemination in B-cell malignancies.
Methylation associated pathway activity deregulation in lung adenocarcinoma
Authors: Lilit Nersisyan, Henry Wurth, Aram Gevorgyan, Hans Binder, Arsen Arakelyan
Journal: European Respiratory Journal (2014)

Methylation impairments are tightly associated with gene expression and molecular pathway deregulation in cancer development. However, other regulatory mechanisms exist, making it important to distinguish those from methylation driven changes. Here we specifically assessed molecular pathway states associated with gene methylation in lung adenocarcinoma.  Paired gene expression and methylation data (id: GSE32867 ) were obtained from Gene Expression Omnibus. Self organizing maps (Wirth, H. et al.BMC Bioinformatics 2011;12:306 ) and in-house pathway signal flow algorithms were applied to describe expression (PSF) and methylation (mPSF) states in KEGG pathways.  35 and 24 KEGG pathways had at least one branch deregulated at significance levels p 1) and 73 down-regulated (PSF 0) correlated with methylation states (see table).  In conclusion, only ∼15% of pathway deregulations were associated with changes in methylation state of genes, whereas the remainder should be attributed to other factors influencing gene expression, such as cancer-associated mutations, and alternative mechanisms of epigenetic control.
Lung structure in healthy neversmokers and smokers assessed by CT-densitometry and chest X-ray
Authors: Reza Karimi, Sven Nyrén, Åsa Wheelock, Göran Tornling, Magnus Sköld
Journal: European Respiratory Journal (2011)

Background:  Smoking causes inflammation in the lungs, which may lead to structural changes and irreversible airways obstruction, characteristic for COPD. By computered tomography (CT), areas with Hounsfield units (HU) below -950 have been considered as emphysema, while increased attenuation may indicate inflammation. We investigated changes in smokers compared to neversmokers.   Materials and methods:  40 current smokers (35±12 pack-years; mean ± SD) with normal lung function and 36 healthy neversmokers performed chest X-ray and CT. Age was 45-65 years with equal sex distribution. Lungs were defined as voxels with attenuation between -300 to -1024 HU, further divided into eight intervals. Chest X-rays were evaluated according to 4 criteria: depressed diaphragm, irregular radiolucency, abnormal retrosternal space and sternodiaphragmatic angle >90°. Two or more criteria9s was considered as emphysema.   Results:  Mean lung attenuation in male (-858HU±34; mean± SD) and female smokers (-856HU±19) was higher than in neversmokers (male -880HU±20; females- 872HU±18) (p   Discussion:  Increased lung density in smokers may indicate inflammation but this has to be correlated to other signs of local inflammation. Females may be more vulnerable than males to the effects of smoking. Despite normal lung function, a considerable number of subjects had emphysema on plan chest x-ray. Further analyses are in progress including patients with COPD.
Imbalance of pro-inflammatory and anti-inflammatory markers on circulating dendritic cells in COPD
Authors: Paul Stoll, Martin Ulrich, Kai Bratke, J. Christian Virchow, Marek Lommatzsch
Journal: European Respiratory Journal (2014)

Background: 

The specific nature of systemic inflammation in chronic obstructive pulmonary disease (COPD) is still poorly understood. Dendritic cells (DCs) control immunity, however, there is little information on specific characteristics of circulating DCs in COPD.

Methods: 

Four-colour flow cytometry was used to compare DC phenotypes in peripheral blood of 54 patients with COPD (spirometric GOLD stages 2 - 4, median FEV1: 38% predicted, median CAT score: 24) with two control groups: 21 current smokers with normal lung function and 21 never-smokers with normal lung function.

Results: 

Concentrations of plasmacytoid and myeloid DCs and the ratio of myeloid to plasmacytoid DCs did not significantly differ between the groups. Markers of systemic inflammation (concentrations of leukocytes, c-reactive protein and fibrinogen in peripheral blood) and some DC surface molecules (such as CD86, BDCA-1 or BDCA-3) were increased compared with never-smoking controls, but did not significantly differ between current smokers with normal lung function and patients with COPD. In contrast, patients with COPD were specifically characterised by a decreased expression of the anti-inflammatory marker PD-L1 on plasmacytoid DCs and an increased expression of the pro-inflammatory marker OX40 ligand on myeloid DCs, as compared with both control groups.

Conclusion: 

COPD is characterised by an imbalance in the expression of pro-inflammatory and anti-inflammatory surface molecules on circulating dendritic cells.
Deletion of aquaporin-4 in APP/PS1 mice exacerbates brain Aβ accumulation and memory deficits
Authors: Zhiqiang Xu, Na Xiao, Yali Chen, Huang Huang, Charles Marshall, Junying Gao, Zhiyou Cai, Ting Wu, Gang Hu, Ming Xiao
Journal: Molecular Neurodegeneration (2015)

Preventing or reducing amyloid-beta (Aβ) accumulation in the brain is an important therapeutic strategy for Alzheimer's disease (AD). Recent studies showed that the water channel aquaporin-4 (AQP4) mediates soluble Aβ clearance from the brain parenchyma along the paravascular pathway. However the direct evidence for roles of AQP4 in the pathophysiology of AD remains absent. Here, we reported that the deletion of AQP4 exacerbated cognitive deficits of 12-moth old APP/PS1 mice, with increases in Aβ accumulation, cerebral amyloid angiopathy and loss of synaptic protein and brain-derived neurotrophic factor in the hippocampus and cortex. Furthermore, AQP4 deficiency increased atrophy of astrocytes with significant decreases in interleukin-1 beta and nonsignficant decreases in interleukin-6 and tumor necrosis factor-alpha in hippocampal and cerebral samples. These results suggest that AQP4 attenuates Aβ pathogenesis despite its potentially inflammatory side-effects, thus serving as a promising target for treating AD.
Psoriasis, cardiovascular disease and flow‐mediated dilatation: reply from authors
Authors: C.L. Martyn‐Simmons, C.H. Smith, J.N.W.N. Barker
Journal: British Journal of Dermatology (2011)

Journal Article Psoriasis, cardiovascular disease and flow‐mediated dilatation: reply from authors Get access C.L. Martyn‐Simmons, C.L. Martyn‐Simmons St John’s Institute of Dermatology, Division of Genetics and Molecular Medicine, King’s College London & Guy’s and St Thomas’ NHS Foundation Trust, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar C.H. Smith, C.H. Smith St John’s Institute of Dermatology, Division of Genetics and Molecular Medicine, King’s College London & Guy’s and St Thomas’ NHS Foundation Trust, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.N.W.N. Barker J.N.W.N. Barker St John’s Institute of Dermatology, Division of Genetics and Molecular Medicine, King’s College London & Guy’s and St Thomas’ NHS Foundation Trust, London, U.K. Jonathan Barker. E‐mail: jonathan.barker@kcl.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 165, Issue 4, 1 October 2011, Pages 924–925, https://doi.org/10.1111/j.1365-2133.2011.10500.x Published: 01 October 2011
Correlation of nutritional status using subjective global assessment (SGA) on pulmonary function parameters in patients with COPD at the Philippine Heart Center
Authors: Cristito Alea, Ma. Paz Mateo
Journal: European Respiratory Journal (2013)

Nutritional Status plays an important part in the management of diseases especially among patients suffering from COPD and critically ill. Subjective Global Assessment is well validated screening tool for malnutrition. It is the aim of this study to determine if there is a correlation between Nutritional Status using SGA and Pulmonary Function Parameters of Filipino COPD patients according to GOLD criteria. This is a Cross Sectional Study. Patients 40 years old and above diagnosed with COPD confirmed with Pulmonary Function Test (PFT) are included in the study. Nutritional status were assessed using anthropometric indices such as weight, height, Body Mass Index (BMI), Mid Arm Circumference (MAC) and Subjective Global Assessment. Leukocyte count and serum albumin were also tested. Nutritional status and PFT were correlated. One hundred twelve COPD patients participated in the study. Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 second (FEV1), and FEV1/FVC ratio significantly decrease as SGA score worsens (p=0.003,p=0.000,p=0.000 respectively). Among the anthropometric measurements performed, weight and mid arm circumference have positive correlation with FEV1 and FEV1/FVC ratio. BMI was noted to be positively correlated with FEV1/FVC ratio. However, no correlation was noted on both leukocyte count and albumin with PFT parameters. SGA, weight, MAC, BMI can be a gauge to monitor the severity of COPD without doing frequent PFT especially among difficult COPD patients.
Cisplatin and etoposide followed by concurrent chemo-radiation therapy for limited stage small cell lung cancer (SCLC-LS)
Authors: G. Benedetti, M. Fedele, S. Tamberi, F. Rastelli, G. Finocchiaro, A. Maestri, F. Salvi, C. Calandri, G. Frezza, L. Crino
Journal: Journal of Clinical Oncology (2005)

7339 Background: Small Cell Lung Cancer (SLCL) is a chemoresponsive tumor but overall survival remains poor even with limited disease (LS). Cisplatin and Etoposide (PE) is considered the standard regimen to be given concurrently with radiation therapy. We investigated a sequential approach of induction chemotherapy (PE) followed by concurrent thoracic irradiation (TI) and chemotherapy (PE) with the aim of debulking the initial tumor volume and thus reducing chemoradiation-related toxicity. Methods: From July 2000 to April 2004, 20 consecutive SCLC-LS patients were enrolled and treated at our Institutions. Two courses of Cisplatin 80 mg/ms d 1 and Etoposide 120 mg/ms d 1, 2 and 3 were given every 3 weeks. After tumor response assessment TI was administered starting with the third course of PE at a dose of 45 Gy in 25 fractions. Six courses of PE were given in total. Prophylactic Cranial Irradiation was provided for patients with evidence of complete response. Results: 20 patients were evaluable for response. One complete response (CR) and 13 partial responses (PR) were observed after the inital 2 courses of chemotherapy. After completion of planned treatment 17/20 patients (85%) had evidence of response with 14 CR and 3 PR. One patient had stable disease and 2 patients had progressed. Median progression-free survival and overall survival on 18 evaluable patients were 9.5 and 17.5 months respectively. One-year and 2-year survival were 67 and 28% respectively. Five patients are in continuous complete remission at 15+ to 49+ months. Toxicity was mild consisting mainly in grade II esophagitis and grade II myelosuppression. Conclusions: In SCLC-LS patients a sequential approach based on standard PE chemotherapy followed by concurrent chemoradiation therapy seems feasible and effective No significant financial relationships to disclose.
Experimental Induction of Hepatomas, Mammary Tumors, and Other Tumors With Metronidazole in Noninbred Sas:MRC(WI)BR Rats2
Authors: Maria Rustia, Philippe Shubik
Journal: JNCI Journal of the National Cancer Institute (1979)

Journal Article Experimental Induction of Hepatomas, Mammary Tumors, and Other Tumors With Metronidazole in Noninbred Sas:MRC(WI)BR Rats Get access Maria Rustia, Maria Rustia 3Eppley Institute for Research in Cancer, University of Nebraska Medical Center, 42d St. and Dewey Ave., Omaha, Nebr. 68105. Search for other works by this author on: Oxford Academic PubMed Google Scholar Philippe Shubik Philippe Shubik 3Eppley Institute for Research in Cancer, University of Nebraska Medical Center, 42d St. and Dewey Ave., Omaha, Nebr. 68105. 4We thank Dr. David Clayson for his suggestions, Dr. K. Patil for statistical evaluation, Ms. Rita Koll for excellent technical assistance, Ms. Mardelle Susman for editorial help, and Mr. Andrew Washington and Mr. Walter Williams for preparation of the illustrations. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 63, Issue 3, September 1979, Pages 863–868, https://doi.org/10.1093/jnci/63.3.863 Published: 01 September 1979 Article history Received: 26 December 1978 Accepted: 30 March 1979 Published: 01 September 1979
Open letter to clinicians and pharmacists from Berkeley Phillips, UK medical director, and Seema Patel, established pharma medical director, Pfizer UK
Authors: Berkeley Phillips, Seema Patel
Journal: BMJ (2015)

There has been some discussion and media reporting about our patent for the use of Lyrica (pregabalin) in the treatment of pain over recent months.1 We recognise this has been the cause of concern for some of you, and we apologise if this has been the case. We hope this letter will help to bring further clarity and reassurance to all concerned.

We wish we had been able to explain this patent situation earlier and better. This was new territory for all of us and there was no system or policy in place to deal with it. We were finding our way, as was the NHS. Our intention was neither to cause confusion, nor to add to your workload. As a physician and pharmacist, respectively, we appreciate the work you are all doing under many, and often conflicting, pressures.

Ultimately, Pfizer’s goal is to discover and develop new drugs for …
Lifespan of γ/δ T Cells
Authors: David F. Tough, Jonathan Sprent
Journal: The Journal of Experimental Medicine (1998)

Information on the turnover and lifespan of murine γ/δ cells was obtained by administering the DNA precursor, bromodeoxyuridine (BrdU), in the drinking water and staining lymphoid cells for BrdU incorporation. For TCR-γ/δ (Vγ2) transgenic mice, nearly all γ/δ thymocytes became BrdU+ within 2 d and were released rapidly into the peripheral lymphoid tissues. These recent thymic emigrants (RTEs) underwent phenotypic maturation in the periphery for several days, but most of these cells died within 4 wk. In adult thymectomized (ATx) transgenic mice, only a small proportion of γ/δ cells survived as long-lived cells; most of these cells had a slow turnover and retained a naive phenotype. As in transgenic mice, the majority of RTEs generated in normal mice (C57BL/6) appeared to have a restricted lifespan as naive cells. However, in marked contrast to TCR transgenic mice, most of the γ/δ cells surviving in ATx normal mice had a rapid turnover and displayed an activated/memory phenotype, implying a chronic response to environmental antigens. Hence, in normal mice many γ/δ RTEs did not die but switched to memory cells.
Inhibition and Stimulation of the Growth of Krebs-2 Carcinoma by BCG Vaccine
Authors: V.I. Kaledin, Y. N. Kurunov, I. A. Serova
Journal: JNCI Journal of the National Cancer Institute (1977)

The effect of BCG vaccine on the growth of imtransplants of Krebs-2 carcinoma in mice was studied. The simultaneous injection of BCG and tumor cells either inhibited tumor growth (BCG given in admixture with tumor cells) or stimulated it (BCG injected contralateral to the tumor transplantation site). The BCG dose was directly related to the effect. Tumor growth was also stimulated by the ip injection of starch or liquid paraffin. In these experiments, the BCG effect was attributed to the redistribution of cells involved in nonspecific and specific tumor resistance. Shortly after BCG prevaccination, particularly when BCG doses were high and mice were susceptible to vaccine infection, BCG was either without effect or stimulated tumor growth; later, however, tumor growth was inhibited regardless of the BCG dose and the injection site of the BCG. The effect of BCG prevaccination was suggested to be due to: 1)the distraction of macrophages and T-lymphocytes to defend the host against the multiplying mycobacteria, and 2)the activation of the pool of these cells that become capable to participate in antitumor resistance after mycobacteria elimination.