tbuckley/cabot-search huggingface dataset:
Multimodal therapy for limited small-cell lung cancer: a randomized study of induction combination chemotherapy with or without thoracic radiation in complete responders; and with wide-field versus reduced-field radiation in partial responders: a Southwest Oncology Group Study.
Authors: M S Kies, J G Mira, J J Crowley, T T Chen, R Pazdur, P N Grozea, S E Rivkin, C A Coltman, J H Ward, R B Livingston
Journal: Journal of Clinical Oncology (1987)

In 1979 we initiated a phase III study in the Southwest Oncology Group (SWOG) which was designed to determine the value of chest radiation in limited-stage small-cell lung cancer patients achieving complete response after induction chemotherapy, and to test the use of wide-field v more limited-volume radiation in patients with partial responses (PRs) and patients with stable disease (SD). The induction chemotherapy (VMV-VAC) consisted of vincristine, 2 mg intravenously (IV) every week for six doses; methotrexate, 60 mg/m2 IV days 1 and 43; VP-16, 50 mg/m2/d IV days 1 to 5 and 43 to 47; doxorubicin, 60 mg/m2 IV days 22 and 64; and cyclophosphamide, 1,000 mg/m2 IV days 22 and 64. Four hundred ninety-four patients were registered, of whom 473 were eligible. Of 466 response-evaluable patients, 153 (33%) achieved complete disease remission (CR) with chemotherapy. A total of 387 patients entered the consolidation phase of treatment after chemotherapy and response determination. CR patients were prospectively randomized to receive chest radiation, consisting of 4,800 rad administered in a split-course scheme, or to continue chemotherapy without interruption. The treatment volume was based on tumor extent before the induction chemotherapy. Maintenance chemotherapy consisted of cyclophosphamide and VP-16 administered for four cycles before a period of reinduction chemotherapy consisting of VMV-VAC as described above. Patients receiving chest radiation therapy were given the same maintenance and reinduction chemotherapy programs following completion of the chest radiation. One hundred ninety-one eligible patients achieving PR or SD status after induction chemotherapy were randomized to a preinduction treatment volume or to a postinduction reduced tumor volume, with treatment portals designed according to tumor extent before or after induction chemotherapy, respectively. After completion of the entire treatment plan, there were 218 (47%) CRs and 121 (26%) PRs. These figures represent the greatest response achieved at any point in the treatment program. The median survival for all eligible patients was 57 weeks (74 weeks for CRs). Overall survival for CR patients was not different for patients who did or did not receive chest radiation. However, patterns of tumor relapse were affected by the chest radiation, as 38 of 42 relapsing patients who did not receive radiation had intrathoracic recurrences in comparison to only 20 of 36 radiated patients.(ABSTRACT TRUNCATED AT 400 WORDS)
Magnetic resonance with diffusion weighted imaging: A new method to detect active lung inflammation in patients with primary antibody deficiencies
Authors: Federica Pulvirenti, Cinzia Milito, Goffredo Serra, Francesco Fraioli, Isabella Quinti
Journal: European Respiratory Journal (2014)

Recurrent respiratory infections and granulomas are hallmark of primary antibodies deficiencies (PAD). Because of the long life course of PAD, respiratory infections and chronic lung disease, PAD patients undergo to frequent radiological examinations. Since an increased radio sensitivity, the Magnetic Resonance Imaging (MRI), a radiation free technique, represents a possible option to manage PAD comorbidities. Moreover, MRI with diffusion weighted imaging (DWI)might be using to study lung abnormalities. No previous DWI-MRI studies in PAD have been reported.Single center longitudinal study on18 PAD patients who underwent chest-MRI with BLADE sequences and pulmonary function tests at baseline and after 18 months. DWI sequences were added at follow-up. All assessments were evaluated with Bhalla modified score. Parenchymal and bronchial scores correlated negatively with FEV1. At follow up a mild improvement was documented for bronchial wall thickening, mucus plugging and bronchial generations involvement; bronchiectasis were stable. Consolidations and nodules were recorded in 40% of patients. Nodule dimension was stable in the majority of patients, while number decreased. Fifty per cent of consolidations and 30% of nodules presented DWI abnormalities. Patients with DWI restricted consolidations had lower FEV1 andhigher CD21low B cells frequencies. Correlation with clinical and immunological parameters underlines that DWI may be a promising tool to detect lung inflammation in PAD patients. Further studies are needed to explore this specific field and find the pathological substrates of diffusion alterations in PAD patients.
5-Aza-2′-deoxycytidine induces growth inhibition and upregulation of epidermal growth factor receptor on human epithelial cancer cells
Authors: M. Caraglia, A. Pinto, P. Correale, V. Zagonel, G. Genua, A. Leardi, S. Pepe, A.R. Bianco, P. Tagliaferri
Journal: Annals of Oncology (1994)
Abstract 696: Cardiosphere-derived Cells Engraft Long-term in Infarcted Mice and Preserve Left Ventricular Function
Authors: Rachel R Smith, Michelle K Leppo, Isotta Chimenti, John Terrovitis, Andreas S Barth, Eddy Kizana, Elisa Messina, Alessandro Giacomello, M. R Abraham, Eduardo Marbán
Journal: Circulation (2007)

Cardiosphere-derived cells (CDCs) were grown from rat hearts and percutaneous endomyocardial adult human biopsy specimens. Rat CDCs plated as single cells formed clones with a doubling time of 42.2 ± 0.7 hours (n = 9). Clones from rat CDCs divided steadily for 27 days before proliferation spontaneously slowed and morphological changes occurred in most cells. After 56 days, rat clonal populations contained a small fraction of c-Kit + cells as determined by flow cytometry, and large subsets of cells expressing cardiac troponin I, α-smooth muscle actin, and von Willebrand factor as determined by immunofluorescence, indicative of their multipotentiality in vitro . To assess therapeutic potential, acute myocardial infarcts (MIs) were created in immunodeficient mice and actively proliferating polyclonal human CDCs were injected into the border zone. Echocardiographic left ventricular function, histological examination, and immunofluorescence served as endpoints. CDC-injected animals showed no significant deterioration in ejection fraction (EF) from 2 days (EF = 45.2 ± 4.8%) to 6 weeks post-MI (EF = 40.2 ± 4.5%, n = 7, p = NS), in contrast to fibroblast-injected control animals (EF = 42.8 ± 4.3% at 2 days vs 27.3 ± 4.0% at 6 weeks, p &lt; 0.01). At the 6 week endpoint, the CDC group had thicker infarct walls as measured histologically compared to the fibroblast group (0.26 ± 0.03mm vs 0.12 ± 0.01mm, n = 5, p &lt; 0.01). CDC engraftment was determined by immunofluorescence using a human-specific antibody. CDCs stably engrafted for up to 6 weeks and could be found distributed primarily throughout the infarct (57 ± 3% of engrafted CDCs, n = 5 animals), as well as the border zone (30 ± 5%) and viable tissue (13 ± 3%). After 6 weeks, CDCs within the infarct had formed small myocytes with little cytoplasmic cardiac troponin I, while CDCs within the viable myocardium had formed large myocytes with well-defined sarcomeric organization. We conclude that CDCs are clonogenic and spontaneously multipotent in vitro and capable of preserving heart function in a mouse infarct model. Functional preservation is presumably due in part to maintenance of infarct wall thickness, likely secondary to stable CDC engraftment within the infarct, as well as the formation of morphologically mature myocytes throughout the non-infarcted tissue.
Healthcare associated pneumonia does not accurately identify potentially resistant pathogens: A systematic evaluation
Authors: Catriona Rother, Waleed Salih, James D. Chalmers
Journal: European Respiratory Journal (2013)

Introduction  Healthcare Associated Pneumonia (HCAP) has been suggested as a new category of pneumonia separate from hospital and community-acquired pneumonia (CAP). This concept is controversial. We systematically evaluated the ability of the HCAP concept to predict resistant pathogens in patients with pneumonia.  Methods  Systematic review and meta-analysis of studies comparing microbiology and outcomes in patients with HCAP and CAP. Studies were pooled using a random effects model. The accuracy of HCAP for identifying MRSA, Pseudomonas aeruginosa and enterobacteriaceae were estimated using the area under the receiver operator characteristic curve (AUC).  Results  20 studies were included with a total of 20,181 patients. Only 7 studies were prospective and 6 were rated as high quality. All studies reported increased mortality in HCAP odds ratio 2.4 (95%CI 2.2-2.7, p  Conclusion  HCAP is poorly predictive of resistant pathogens. Research into HCAP is affected by low study and publication bias. Our results do not support a change in management practices based on the HCAP concept.
VortigERN: Variation of radiotherapy target volume definition, dose to organs at risk (OAR), and clinical target volumes using anatomic (CT) versus combined anatomic and molecular imaging (PET-CT): Intensity-modulated radiotherapy delivered using a tomotherapy hi art machine.
Authors: S. Chatterjee, J. Frew, J. B. Wilsdon, H. M. Mccallum, J. H. Mott, P. Stevenson, W. Dobrowsky, R. J. Maxwell, C. G. Kelly
Journal: Journal of Clinical Oncology (2010)

TPS267 Background: Intensity-modulated radiotherapy (IMRT) has become the standard of care for radical radiotherapy treatment of head and neck squamous cell carcinomas (SCC). Whle benefits of IMRT include improving long-term xerostomia, accurate target localization is necessary to prevent geographical miss while sparing organs at risk (OAR). Although standard radiotherapy treatment planning (RTP) is performed using contrast enhanced CT scans (CE-CT), molecular imaging using 18FDG PET-CT scans are increasingly being explored to improve tumor localization. Recurrence following IMRT usually occurs within the high-dose area with early data raising the possibility of increased cure rates with dose escalation. Vortigern addresses the issue of optimal imaging for RTP volume definition and explores dose escalation in oropharyngeal SCC. Methods: Patients with oropharyngeal SCC suitable for radical radiotherapy are consented to take part in the study, 14 out of the planned 30 have been recruited. A PET-CT scan is acquired in the treatment position. The PET scan is initially thresholded to 40% of maximum tumor intensity. The fused PET-CT images are then adjusted on a case-by-case basis to ensure optimal tumor visualization. Gross Tumor Volumes (GTV), Clinical Target Volumes (CTV), Planning Target Volumes (PTV), and OAR are outlined using the CT data blinded, to PET-CT; and then on the PET-CT dataset for comparison. Median dose prescribed to PTV1 and PTV2 is 65Gy and 54Gy in 30 fractions respectively. The feasibility of dose escalation will be tested in 10 cases. A dose-escalated volume (PTV3) is created around the PET-CT GTV with a 5 mm isotropic margin. Based on a tumor α/β of 10 and late effects α/β of 3, doses of 67.2Gy, 63Gy and 56Gy in 28 fractions will be prescribed to the PTV3, 2 and1 respectively. This is based on delivering a 9% increase in dose to the primary tumor.The dose escalation is based on a previous U.K. dose-escalation study in hypopharyngeal SCC. UK NCRI portfolio: MREC No: 08/H0907/127, UKCRN ID 7341. No significant financial relationships to disclose.
Elevated ribonuclease activity in the thymus and white blood cells of genetically cancer prone mice.
Authors: W P Drake, D R Pokorney, S Chipman, C C Levy, M R Mardiney
Journal: The Journal of Experimental Medicine (1975)

Ribonuclease activity in cell-free thymus homogenates was elevated for five strains of mice genetically predisposed toward leukemia or reticulum cell neoplasms (AKR, C58, PL, RF, and SJL). Such increased activity was directed against polyuridylic acid and was observed in 8-wk old mice, well before the onset of neoplastic transformation. Similarly, white blood cell ribonuclease activity was elevated in mice of the strains AKR, C2H/He, PL and RF. Statistical analysis indicated that such elevated activity in these strains related to their high incidence of spontaneous neoplastic disease. Elevated ribonuclease activity thus represents a new biochemical marker relating to the genetic propensity of some strains of mice to die prematurely of spontaneous neoplasia.
Brief Report: Autoantibodies to DNA Mismatch Repair Enzymes in Polymyositis/Dermatomyositis and Other Autoimmune Diseases: A Possible Marker of Favorable Prognosis
Authors: Yoshinao Muro, Ran Nakashima, Yuji Hosono, Kazumitsu Sugiura, Tsuneyo Mimori, Masashi Akiyama
Journal: Arthritis & Rheumatology (2014)

Objective. Myositis-specific autoantibodies(MSAs) are useful tools for identifying clinical subsets of patients with idiopathic inflammatory myopathies(IIMs). There have been few reports on antibodies to some DNA mismatch repair enzymes (MMREs) inpatients with IIMs. This study was undertaken to determine the frequencies and clinical associations of antibodies to 7 types of MMREs (MLH1, MLH3, MSH2,MSH3, MSH6, PMS1, and PMS2) in patients with IIMs and other systemic autoimmune diseases.Methods. Clinical data and serum samples were collected from 239 Japanese patients with IIMs (147 with adult dermatomyositis, 13 with juvenile dermatomyositis,57 with polymyositis, and 22 with myositis overlap syndrome). One hundred patients with other diseases, including 40 with systemic lupus erythematosus(SLE), were assessed as disease controls. The presence of anti-MMRE antibodies in serum was examined by immunoprecipitation, enzyme-linked immunosorbenassay, and immunoprecipitation/Western blotting.Results. Anti-MMRE antibodies were found in 1 patients with IIMs and 3 patients with SLE. They were restricted to MLH1, PMS1, MSH2, and PMS2, with simultaneous positivity for more than one of these antibodies occurring in some patients. Nine IIM patients with anti-MMREs also had other MSAs and their associated clinical features. All patients with anti-MMREs were still living at the time of the present analysis.Conclusion. Anti-MMRE antibodies, which often co exist with other MSAs, may be serologic markers forgood prognosis in IIMs.
γ-Glutamyl Transpeptidase in Transplantable, Chemically Induced Rat Hepatomas and “Spontaneous” Mouse Hepatomas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Silvio Fiala, Anna E. Fiala, Benjamin Dixon
Journal: JNCI Journal of the National Cancer Institute (1972)

In our previous work, we found high levels of a polarographically active thiol compound in several transplantable hepatomas of chemical origin. High levels of this compound were found also in extracts from primary hepatomas induced by 3′-methyl-4-dimethylaminoazo-benzene. In the present work this compound was identified as L-cysteine. Cysteine was formed from glutathione by a high level of the enzyme γ-glutamyl transpeptidase (glutathionase). The level of glutathionase in fetal and normal neonatal rat liver was as high as in rat hepatomas, but in adult rat liver the activity of this enzyme was only 1/50–1/100 that in hepatomas. In mice, as in rats, the neonatal liver contained a high, the adult liver a low, level of glutathionase, but among 4 mouse hepatomas of “spontaneous” origin, 3 showed no change. The high activity of glutathionase appears to be a distinctive feature of at least some chemically induced rat hepatomas.
Changes in bronchial responsiveness, circulating leucocytes and ex vivo cytokine production by blood monocytes after PAF inhalation in allergic asthmatics
Authors: R Louis, D Degroote, T Bury, JL Corhay, JM Kayembe, P Franchimont, MF Radermecker
Journal: European Respiratory Journal (1995)

We investigated the effects of inhaled platelet-activating factor (PAF) on methacholine bronchial responsiveness, circulating leucocyte counts, and ex vivo tumour necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) production from blood monocytes in eight allergic asthmatics. Bronchial responsiveness was defined as the provocative concentration of methacholine causing a 20% decrease in forced expiratory volume in one second (PC20). Circulating leucocytes were counted by means of an automatic haemocytometer, and cytokines were measured with specific immunoassays. The different variables were measured before and 4, 24, 48, 72 and 168 h after a PAF (225 micrograms), a lyso-PAF (225 micrograms) and a saline bronchial challenge. When compared with lyso-PAF and saline, inhalation of PAF resulted in a significant decrease in PC20 over a period of one week. Two falls in bronchial responsiveness were identified, the first by 4 h and the second beginning 48 h and reaching a maximum by 168 h. The increases in spontaneous TNF alpha and IL-1 production which occurred during the week after both PAF, lyso-PAF and saline, did not differ significantly. Likewise, the changes in circulating neutrophil counts, characterized by a transient rise by 4 h after PAF and lyso-PAF but not saline, followed by a fall by 24 h and a persistent decrease until 168 h, were not significantly different after PAF, lyso-PAF and saline. On the other hand, in comparison with lyso-PAF and saline, inhaled PAF caused a significant protracted augmentation in circulating eosinophil counts, which was maximal by 48 h but did not correlate with the delayed decline in PC20.(ABSTRACT TRUNCATED AT 250 WORDS)
Low density lipoprotein receptor-related protein 1 is a novel activator of β1 Integrin-dependent fibroblast adhesion, spreading and migration
Authors: Lukasz Wujak, Ying Chen, Klaus T. Preissner, Malgorzata Wygrecka
Journal: European Respiratory Journal (2014)

Low density lipoprotein receptor-related protein 1 (LRP1) is an endocytic receptor which mediates clearance of extra cellular matrix components and regulates cell proliferation, migration and adhesion. Based on previous reports demonstrating a pivotal role of LRP1 in the development of fibrotic diseases, we hypothesized that LRP1 function may be impaired in idiopathic pulmonary fibrosis (IPF). PCR and western blot analysis revealed reduced LRP1 expression in lung fibroblasts isolated from IPF patients and bleomycin-challenged mice. Cell migration, adhesion and spreading were markedly decreased in human lung fibroblasts after LRP1 knock-down and in LRP1-deficient mouse embryonic fibroblasts (MEF). Over-expression of truncated LRP1 variant containing second ligand-binding cluster rescued adhesion of LRP-/- MEF. Further investigations showed reduced β1 Integrin endocytosis in LRP-/- MEF indicating that LRP1 promotes β1 Integrin internalization. Analysis of LRP1 and β1 Integrin subcellular distribution revealed that LRP1 and β1 Integrin colocalize in the perincuclear space. GST pull-down and CoIP experiments demonstrated that cytoplasmatic region of LRP1 binds β1 Integrin activator, Kindlin2. Interestingly, over-expression of Kindlin2 rescued cell spreading, filopodia and lamellipodia formation in LRP-/- MEF cells. Collectively, we propose that LRP1 is a novel regulator of β1 Integrin metabolism which acts via Kindlin2 to enhance β1 Integrin endocytosis, thus promoting cell adhesion, spreading and migration. Hence, suppressed LRP1 expression may modulate lung fibroblast behaviour in IPF.
Comment on Nordwall et al. Impact of HbA1c, Followed From Onset of Type 1 Diabetes, on the Development of Severe Retinopathy and Nephropathy: The VISS Study (Vascular Diabetic Complications in Southeast Sweden). Diabetes Care 2015;38:308–315
Authors: Mitsuyoshi Takahara
Journal: Diabetes Care (2015)

I read with great interest a recent article by Nordwall et al. (1) that investigated the association of long-term glycemic control with microvascular complications in patients with type 1 diabetes. They obtained data of HbA1c measured during the whole follow-up period of 20–24 years and calculated weighted mean HbA1c (wHbA1c) as a marker of long-term glycemic control.

However, their analysis was at risk for misevaluation of glycemic control. In their analysis, wHbA1c …
Browning of Subcutaneous White Adipose Tissue in Humans after Severe Adrenergic Stress
Authors: Labros S. Sidossis, Craig Porter, Manish K. Saraf, Elisabet Børsheim, Ravi S. Radhakrishnan, Tony Chao, Arham Ali, Maria Chondronikola, Ronald Mlcak, Celeste C. Finnerty, Hal K. Hawkins, Tracy Toliver-Kinsky, David N. Herndon
Journal: Cell Metabolism (2015)
Experimental vs control interventions in cancer therapy: Which is better?—The Children's Oncology Group Experience
Authors: A. Kumar, H. P. Soares, R. J. Wells, A. Khayat, M. Clarke, R. K. Hills, A. Bleyer, G. Reaman, B. Djulbegovic
Journal: Journal of Clinical Oncology (2004)

6016 Background: The outcomes in childhood cancers have dramatically improved since 1950. However, it is unclear to what extent this improvement has been a result of continuous progress with experimental treatments, or a consequence of variable successes and failures of the new treatments according to the equipoise hypothesis (Cur Oncol Rep 2001;3:389). Methods: To accurately describe the outcomes of innovations, tested in randomized controlled trials (RCTs), three factors are paramount: publication rate, quality of trials and the choice of control intervention. We reviewed all completed phase III RCTs conducted by the Children's Oncology Group (1972 to 2000). Published and unpublished data were used. Seventy three (104 comparisons) RCTs were identified. The success rate of experimental vs. standard treatment was evaluated both semi-quantitatively (on a scale 1–6 describing the authors' conclusions about treatment success) and quantitatively using a standard meta-analytic technique. Results: Overall, the trials were of high methodological quality. Publication rate was 97% (72/74; 4 abstracts, 68 papers). Innovative treatment was favored in 45% of trials, with a hazard ratio (HR) of 0.91 (95% CI 0.86, 0.96) for event-free survival (p=0.0001), and a HR 0.96 (95% CI 0.89, 1.05) for overall survival (p=0.3). There was no difference in results when restricting analyses to primary outcome measures or according to the type of treatment, disease or comparator. Conclusions: There is no predictable pattern of innovative successes in pediatric oncology. Even in situations where in retrospect, tremendous improvements in therapeutic outcomes occur, there is no evidence that the outcomes of RCTs, in aggregate, consistently and predictably favor experimental over control interventions, in spite of the trialists' hopes that the new interventions are better. Nevertheless, individual experimental treatments can be more or less successful. However, identifying which experimental treatment is a success is only known after a RCT is conducted. Improvement in clinical outcomes can only come from continuing empirical testing of new treatments in RCTs. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration US NIH (grant# R01 NS044417–01)
Delay of Tumor Growth in Hamsters Treated With Lynestrenol and Effect of Staphylococcus aureus Cowan A2
Authors: Joseph Wybran, Lise Thiry
Journal: JNCI Journal of the National Cancer Institute (1978)

The action of lynestrenol, a synthetic progesterone-like substance, was studied in Syrian golden hamsters inoculated with cells transformed by herpes simplex virus type I. Daily ip injections of 1 mg lynesterol/kg delayed tumor growth. Lynestrenol alone only slightly increased the survival of the animals. This effect was more marked when the animals were also given injections of Staphylococcus aureus Cowan A. Survivors showed an increased resistance to challenge with infected cells. Hamsters previously given injections of killed transformed cells and then challenged with living cells showed a facilitation of tumor growth. This facilitation was inhibited by lynestrenol alone or combined with S. aureus Cowan A.