tbuckley/cabot-search huggingface dataset:
Glycolytic phenotype of non-small cell lung cancer: Implication of anaerobic glycolysis on malignant potential
Authors: I. Yoshino, T. Kameyama, Y. Shikada, T. Kometani, D. Kawano, A. Osoegawa, T. Yohena, M. Yamaguchi, Y. Maehara
Journal: Journal of Clinical Oncology (2005)

9634 Background: One of the most common phenotypes of malignancy is their ability to metabolize glucose at high rates. Recently, a mitochondria bound type II hexokinase (HK2) is focused on in the high glycolytic phenotype. On the other hand, the expression of the β-H+-ATP-synthase (β-F1-ATPase), which is required for aerobic energy-provision, is reported to down-reulated in colon and kidney cancer. To invstigate the status and significance of glucose catabolism in non-small cell cancer (NSCLC), expression of glycolytic enzymes were examined. Methods: HK2, glycolytic glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and β-H+-ATP-synthase (β-F1-ATPase) mRNA were quantified by a real-time reverse transcription polymerase chain reaction in both tumor and non-tumor-bearing lung tissues of 40 patients with NSCLC. To analyze the role of HK2 in vitro, a NSCLC cell line (PC9) was transfected with small interfering RNA, and examined for its growth. Results: All three mRNAs of enzymes were higher expressed in tumor tissues than in normal tissues. The high expression level of anaerobic enzymes such as HK2 and GAPDH showed positive relationship with poor prognosis, whereas that of β-F1-ATPase showed no relationship with prognosis.Moreover, the high expression of these two glycolytic molecules also had positive relationship with smoking and pathological staging. Introduction of HK2 siRNA into PC9 leads to significanct growth inhibition in MTS assay. Conclusion: Glycolytic enzymes involved in energy provision in anaerobic condition are related to tumor progression, and HK2 can be a crucial target for arresting or slowing the growth of NSCLC. No significant financial relationships to disclose.
Abstract 1783: Puupehenol natural product inhibits STAT3 signaling and induces antitumor cell effects in vitro against human glioblastoma cells
Authors: Tyvette S. Hilliard, Christopher Chock, Philip Williams, James Turkson
Journal: Cancer Research (2014)

Abstract Glioblastoma multiforme (GBM) is a malignant brain tumor that lacks effective therapeutics and has a high mortality rate. Constitutively-activated signal transducer and activator of transcription 3 (STAT3) protein is prevalent and implicated in GBM phenotype and represents a valid anti-GBM target. To discover novel STAT3 inhibitors suitable for GBM therapy, natural product extracts were investigated. Whole extracts from marine organisms were first screened for effects against cell viability using the human glioma model line, U251MG that harbors aberrantly-active STAT3 and normal fibroblasts that do not. The screening campaign identified the puupehenol, CC-1-2 from the whole extracts of leiodermatium sp as a bioactive compound that suppressed U251MG cell viability, with an IC50 4.1±0.1 µM, compared to an IC50 value of 7.3±0.3 µM against normal NIH3T3 mouse fibroblasts. Western blot analysis showed pSTAT3 levels in U251MG cells substantially decreased in a time-dependent manner in response to CC-1-2. Decreased pSTAT3 in treated cells occurred in parallel with partial suppression of both phospho- Janus kinase (Jak) 2 and pSrc levels and no induction of protein tyrosine phosphatase, PTP1B. Phosphorylated extracellular signal-regulated kinase (Erk) 1/2 levels also decreased in time-dependent manner, while pAkt remained unchanged in U251MG cells under the same treatment conditions. Furthermore, treatment of U251MG cells with CC-1-2 led to dramatic morphological changes that occurred in a dose- and time-dependent manner, compared to minimal changes observed for similarly-treated MCF-7 breast cancer cells that do not harbor aberrantly-active STAT3. Colony survival assay of U251MG cells revealed single treatment with 1-10 µM CC-1-2 decreased colony sizes and numbers in a dose-dependent manner, compared to moderate effects on MCF-7. In vitro wound-healing assay further showed reduced U251MG cell migration into the denuded area in response to CC-1-2 treatment. CC-1-2 further induced apoptosis in U251MG cells in a dose-dependent manner and suppressed the expression of c-Myc, Cyclin D1, and Bcl-2 levels, which are known STAT3-regulated genes. Studies together identify CC-1-2 as a natural product inhibitor of STAT3 that preferentially induces antitumor cell effects against human glioblastoma cells. Citation Format: Tyvette S. Hilliard, Christopher Chock, Philip Williams, James Turkson. Puupehenol natural product inhibits STAT3 signaling and induces antitumor cell effects in vitro against human glioblastoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1783. doi:10.1158/1538-7445.AM2014-1783
...has been amended
Authors: R C A Graham
Journal: BMJ (1994)

There is evidence that prophylactic penicillin is effective in children with sickle cell disease, and it seems sensible to give similar prophylaxis to hyposplenic patients with other diseases.Identifying such patients is now relatively easy with the method of counting pitted red cells under differen- tial interference contrast microscopy.The risks of fulminant sepsis in patients who may be hypo- splenic must be borne in mind, and such patients should be treated promptly with antibiotics when they become febrile.At present there is insufficient evidence to justify giving pneumococcal vaccine to all patients who may be hyposplenic.Nevertheless, it seems prudent to vaccinate certain high risk groups such as children with sickle cell disease and patients with severe extensive chronic inflammatory bowel disease.
Outcomes after thrombus aspiration for ST elevation myocardial infarction: 1-year follow-up of the prospective randomised TOTAL trial
Authors: Sanjit S Jolly, John A Cairns, Salim Yusuf, Michael J Rokoss, Peggy Gao, Brandi Meeks, Sasko Kedev, Goran Stankovic, Raul Moreno, Anthony Gershlick, Saqib Chowdhary, Shahar Lavi, Kari Niemela, Ivo Bernat, Warren J Cantor, Asim N Cheema, Philippe Gabriel Steg, Robert C Welsh, Tej Sheth, Olivier F Bertrand, Alvaro Avezum, Ravinay Bhindi, Madhu K Natarajan, David Horak, Raymond C M Leung, Saleem Kassam, Sunil V Rao, Magdi El-Omar, Shamir R Mehta, James L Velianou, Samir Pancholy, Vladimír Džavík
Journal: The Lancet (2015)
A novel platform for cancer therapy using extracellular vesicles
Authors: Naoomi Tominaga, Yusuke Yoshioka, Takahiro Ochiya
Journal: Advanced Drug Delivery Reviews (2015)

Extracellular vesicles (EVs) are nanometer-sized membranous vesicles and are involved in cell-to-cell communication. EVs contain several types of functional molecules, such as proteins, mRNAs, and microRNAs (miRNAs). Over the past several years, EVs have emerged as potential tools for a drug delivery system (DDS) that can target organs or cells. EVs have a function of organ tropism and are naturally occurring from cells. Therefore, EVs have expected as naturally DDSs, which have the organ tropism and a low side effect. Actually, some reports showed that EVs delivered drugs to specific organ. However, despite observed the organ tropism, the mechanisms of organ tropism of EVs are still unclear. Moreover, preservation and efficient collection of EVs are desired to be investigated. Here, we provide an overview of the methods for using EVs as DDSs.
Breathing patterns in patients with chronic respiratory disease before and after a six week Pulmonary Rehabilitation programme
Authors: Rokhsaneh Tehrany, Anne Bruton, Anna Barney
Journal: European Respiratory Journal (2014)

Background: Pulmonary Rehabilitation (PR) has been reported to increase exercise tolerance and health related quality of life in patients with chronic respiratory disease (CRD). Currently it is not known if breathing patterns alter following this intervention.   Aim:  To examine whether quiet breathing and speech breathing patterns alter in patients with CRD following a six week PR programme.   Method: Twenty patients (mean age 69.7±8.81) with CRD (COPD (n=14) and Bronchiectasis (n=6)) were recruited from a UK NHS hospital. Breathing patterns were recorded non-invasively using Respiratory Inductive Plethysmography (RIP) on the first day, at three weeks and then on the last day of PR during four tasks each lasting two minutes (quiet breathing, reading, spontaneous speech and counting). Six breathing parameters were extracted; Inspiration and expiration time (T I  and T E ), breathing cycle duration (Ttot), respiratory rate (RR) and inspiration and expiration volume (I V  and E V ).   Results:  No statistically significant differences (p>0.05) were found for any of the breathing parameters measured pre and post PR. Self reported breathlessness measured at rest also did not change significantly between the baseline and six week session following PR.   Conclusion: These preliminary findings suggest that breathing patterns produced during quiet breathing and speech remain stable following a six week PR programme in patients with CRD. Further research is needed to determine whether breathing patterns remain stable following interventions that aim to modify breathing pattern (breathing retraining), because breathing pattern analysis has potential to be used for monitoring purposes.
Polar solvents: a novel class of antineoplastic agents.
Authors: E N Spremulli, D L Dexter
Journal: Journal of Clinical Oncology (1984)

It has been known for many decades that certain murine and human cancers can spontaneously mature to benign tissue. These observations have stimulated investigators to attempt to induce a state of more normal or benign differentiation in cancer cells using biologic substances or chemicals. Polar solvents including dimethylsulfoxide, dimethylformamide, and monomethylformamide have proven to be good inducers of maturational events in murine and human cancer cells. Moreover, several laboratories have demonstrated that polar solvents inhibit the growth of human tumor xenografts in nude mice. These findings have resulted in the entry of monomethylformamide into phase I clinical trials in America and Europe. Preclinical work further suggests that polar solvents may be useful agents in combination with conventional treatment modalities. The use of drugs such as monomethylformamide that can convert neoplastic cells to benign cells rather than kill the tumor cells represents an important conceptual departure from standard cytotoxic chemotherapy. The use of maturational-agent therapy should be considered as an important new development in the design of cancer treatment protocols.
Immunology of the Lower Respiratory Tract
Authors: H. B. Kaltreider, S. E. Salmon
Journal: Journal of Clinical Investigation (1973)

While the alveolar macrophage has been studied extensively, little attention has been directed toward the immune functions of the bronchoalveolar lymphocyte. These cells, obtained by bronchopulmonary lavage of the normal canine lung, are derived from the air side of the alveolar-capillary membrane of the lower respiratory tract. The distribution of lymphocyte types within the bronchoalveolar cell population was determined and compared with that of leukocytes from blood and spleen.
Incentives could help delivery of essential health services by frontline workers, study finds
Authors: C. Travasso
Journal: BMJ (2015)

Offering incentives and supporting frontline workers in record keeping could help to improve the delivery of essential health interventions, a study carried out in Bihar, India, has found.

Each year about 3.1 million children under 5 worldwide die due to undernutrition. These deaths could be reduced by about 15% if there was 90% coverage of essential health and nutrition interventions, including immunisation information and services, general nutrition information, food supplements, and pregnancy care information. In India these interventions are primarily delivered through home visits or at special health centres by the Integrated Child Development Services and the National Rural Health Mission.

The study used data from 6000 randomly selected, eligible households across …
Abstract 22: Genetic re-programming of the acute myeloid leukemia cell line HL-60: Regulation of cell proliferation, differentiation, and programmed cell death
Authors: Michael Roberts, Cassandra Holbert, Mansoor Ghoto, Juliana Schneider, Abigail Marriott, Jeffrey Forrester
Journal: Cancer Research (2015)

Abstract The human acute myeloid leukemia cell line, HL-60, in response to phorbol esters, undergoes genetic re-programming leading to cell cycle arrest, macrophage differentiation, and apoptosis. The induced program overrides the oncogenic mutations driving the leukemia program, illustrating that changes in gene expression can reverse the cancer phenotype. Whole genome exon DNA microarray analyses identifies 1260 genes whose RNA expression levels change significantly during the reprogramming. We define a subset of 186 genes functionally assigned to the biological processes of regulation of cell proliferation, differentiation, and/or programmed cell death showing specific temporal expression patterns, and suggest that a subset of these genes, which are down-regulated during the reversal of the leukemia phenotype while showing overexpression in AML patient samples, may represent new therapeutic targets in AML. Among the genes showing immediate early up-regulation (2-fold or greater by one hour post-PMA treatment), promoter analysis reveals highly significant overrepresentation of binding sites for the transcription factors STAT5A, HIF1A and NF-kB. Delayed early up-regulated genes (2-fold or greater by three hours post-PMA treatment), have promoters highly enriched in binding sites for EGR1, SP1:SP3, ZFP206 and E2F4. A phorbol ester response “signature” related to reversal of the leukemic phenotype and initiation of apoptosis has been defined and examined in two additional AML cell lines (THP-1 and Kasumi-1). Among the significantly up-regulated genes are MCL1, CDKN1A, NR4A1, and BCL6. Down-regulated genes include MYC, KIT, LGALS12, and ZBTB16. HL-60 cell lines with CRISPR-mediated knockouts of several of these genes are currently being evaluated for their effects on the leukemic phenotype and phorbol ester-induced apoptosis. Citation Format: Michael Roberts, Cassandra Holbert, Mansoor Ghoto, Juliana Schneider, Abigail Marriott, Jeffrey Forrester. Genetic re-programming of the acute myeloid leukemia cell line HL-60: Regulation of cell proliferation, differentiation, and programmed cell death. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 22. doi:10.1158/1538-7445.AM2015-22
Systematic review of ill-health outbreaks associated with exposure to water-based metalworking fluids
Authors: Clare Burton, Brian Crook, Helena Scaife, Gareth Evans, Chris Barber
Journal: European Respiratory Journal (2011)

Objectives:  Aims to identify and review all previously published reports of outbreaks of ill health due to water-based metalworking fluids (MWFs), in order to identify aetiological risk factors for disease, and highlight areas requiring further research.   Methods:  A multidisciplinary team agreed appropriate search terms for a systematic literature review. From a total of 1346 titles, 35 relevant articles, relating to 29 separate outbreaks of ill health attributed to MWF exposure were selected.   Results:  17 outbreaks related to respiratory disease, 4 to skin disease, and 8 to a combination of both. There was a peak incidence between 1996 and 2000. The majority were from the United States, from large car manufacturing plants using a central sump.The mean attack rate for allergic respiratory disease during outbreaks was 5.9% of the exposed workforce. Outbreaks were identified with all types of water-based MWFs, and mean MWF aerosol levels were below recommended exposure limits in most cases. For respiratory disease outbreaks, bacteria were isolated in 76%, fungi in 71% and opportunistic mycobacteria in 59% of workplaces. Endotoxin contamination of MWF ranged from non-detectable to 5.3×10 5  EU/ml, and measured airborne endotoxin levels ranged from 0.52 EU/m 3  to 126 EU/m 3 .   Conclusions:  Despite numerous investigations, significant knowledge gaps remain, particularly regarding the aetiology, natural history and risk factors for these outbreaks. The available evidence supports the hypothesis that microbial contamination is important in the aetiology of occupational lung disease in this group, and improvements in workplace hygiene have generally been associated with a cessation of new cases.
Phase II trial of vinblastine, ifosfamide, and gallium combination chemotherapy in metastatic urothelial carcinoma.
Authors: L H Einhorn, B J Roth, R Ansari, R Dreicer, R Gonin, P J Loehrer
Journal: Journal of Clinical Oncology (1994)

Phase II trial in metastatic urothelial carcinoma using a novel combination chemotherapy regimen consisting of vinblastine, ifosfamide, and gallium nitrate (VIG).Twenty-seven patients were entered onto this phase II study. Dosages were vinblastine 0.11 mg/kg days 1 and 2, ifosfamide 1.2 gm/m2 days 1 through 5 (with mesna), and gallium 300 mg/m2 as a 24-hour infusion days 1 through 5, with calcitriol (1,25-dihydroxycholecalciferol) 0.5 microgram/d orally starting 3 days before each course (except the first) and continuing throughout gallium administration, plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) (filgrastim) 5 micrograms/kg/d days 7 through 16. Courses were repeated every 21 days for a maximum of six cycles.The major toxicity was granulocytopenia. Fifteen patients (55.6%) had grade 3 or 4 granulocytopenia, including eight patients with granulocytopenic fevers. Eleven patients had grade 3 or 4 anemia and four had grade 3 or 4 nephrotoxicity, which was reversible. Other grade 3 to 4 toxicities included hypocalcemia (three patients), thrombocytopenia (two), encephalopathy (one), and temporary blindness (one). There was one treatment-related mortality. Toxicity was more severe in patients older than 70 years and those with prior pelvic irradiation, prior cisplatin adjuvant therapy, or prior nephrectomy. We now decrease VIG by 20% in this patient population. Eighteen patients (67%) achieved an objective response, including 11 (41%) who attained a disease-free status (five with VIG alone and six with subsequent surgery). Median duration of remission was 20 weeks, with five patients still in remission at 22+ to 56+ weeks.VIG combination chemotherapy is very active in patients with metastatic urothelial carcinoma. Toxicity was significant but manageable.
TrkC Expression Predicts Good Clinical Outcome in Primitive Neuroectodermal Brain Tumors
Authors: M.A. Grotzer, A.J. Janss, K.-M. Fung, J.A. Biegel, L.N. Sutton, L.B. Rorke, H. Zhao, A. Cnaan, P.C. Phillips, V.M.-Y. Lee, J.Q. Trojanowski
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To identify biologic prognostic factors in childhood primitive neuroectodermal tumors (PNET), including medulloblastoma, that accurately define patient groups with sufficiently good prognosis to permit a reduction in treatment intensity. PATIENTS AND METHODS: We determined expression levels of the neurotrophin receptor TrkC mRNA in formalin-fixed tumor samples from 87 well characterized PNET patients using in situ hybridization. Comparison of TrkC mRNA expression levels with clinical and other laboratory variables was performed using univariate and multivariate Cox regression analysis. RESULTS: High TrkC mRNA expression was found to be associated more with higher 5-year cumulative survival rate than was low TrkC mRNA expression (89% v 46%, respectively). When compared with established clinical prognostic factors and laboratory variables of potential prognostic significance, TrkC mRNA expression, by univariate analysis, was found to be the single most powerful predictor of outcome (hazards ratio, 4.81; P &lt; .00005), exceeding all clinical prognostic factors. In multivariate analysis, the hazards ratio remained significant (P &lt; .00005). CONCLUSION: High TrkC mRNA expression in PNET is a powerful independent predictor of favorable clinical outcome. Assessment of TrkC mRNA levels may aid in treatment planning for patients with PNETs and should be incorporated prospectively into PNET clinical trials.
Survey of thrombophilia causes in patient with deep vein thrombosis admitted in Sari's Imam Khomini Hospital during 2009
Authors: Ali Sharifpour, Qasem Janbabaee, Hasan Nattaj, Davoodi, Okhovvatian, Ahmadi Nejad
Journal: European Respiratory Journal (2011)

Introduction: Thrombophilia is a condition in which there is a tendency for clot formation and has an incidence of 1 per 1000 annually. About 2/3 of attacks occurs as DVT and the remainder as PE or associated with DVT. Knowing these hereditary factors can be helpful in designating a proper diagnostic template when after it will be possible for each thrombophilic patient to be diagnosed in its proper way.

Materials and methods: This is a descriptive study. Our patients were 70 DVT patients whom were bedridden at Imam hospital, Sari, Mazandran, Iran. After admission, they underwent heparin therapy followed by warfarin therapy for 6 months. In the next stage warfarin was stopped and after 2 weeks of heparin therapy, required lab tests were requested. Needed data were collected by a questionnaire and data were processed by SPSS18 statistical software.

Findings: 22 people (31.4%) were males and 48 people (68.6%) were females. Mean age was 42.06±14.6 y. 12 of patients (17.1%) had diminished levels of factor V Leiden while 58 people (82.9%) had normal levels. In 84% of patients there were normal levels of fibrinogen and other 14% had increased levels of fibrinogen.

Result: 

View this table:

Table 1. Results





Conclusion: Our study shows that DVT is most common in females. In through of non lab factors, OCP, history of no activity and trauma is more companionship with incidence of DVT. In through of genetic factors, FVL and high level of fibrinogen and low level of S protein are common.
Therapeutic Advances in Relapsed or Refractory Multiple Myeloma
Authors: Kenneth C. Anderson
Journal: Journal of the National Comprehensive Cancer Network (2013)

The past decade has been a time of rapid progress in multiple myeloma, but the future therapeutic landscape may be even more promising, as new agents are better tolerated and novel pathways are exploited. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) now include the proteasome inhibitor carfilzomib and immunomodulatory drug pomalidomide, which are more potent than previous generations of these drugs have been. These agents are extending progression free and overall survival of patients with relapsed refractory myeloma, as is maintenance therapy with lenalidomide after initial therapy of patients with newly diagnosed disease At the NCCN 18th Annual Conference, Dr. Kenneth C. Anderson from Dana-Farber Cancer Institute reviewed the data leading to the approval of these exciting agents, discussed the efficacy of current regimens, and described the future landscape and the exciting potential of new agents to further improve and extend the lives of patients with myeloma.