tbuckley/cabot-search huggingface dataset:
Correlation of tumor O6 methylguanine-DNA methyltransferase levels with survival of malignant astrocytoma patients treated with bis-chloroethylnitrosourea: a Southwest Oncology Group study.
Authors: K A Jaeckle, H J Eyre, J J Townsend, S Schulman, H M Knudson, M Belanich, D B Yarosh, S I Bearman, D J Giroux, S C Schold
Journal: Journal of Clinical Oncology (1998)

Prior studies show that increased levels of the DNA repair protein O6 methylguanine-DNA methyltransferase (MGMT), also referred to as O6-alkylguanine-DNA alkyltransferase (AGT) correlate with the resistance of glioma cell lines to nitrosoureas. The observed nitrosourea sensitivity of MGMT-deficient lines (methyl excision repair negative [MER-]) and those repair-proficient lines pretreated with MGMT-specific inhibitors (eg, O6 benzylguanine) has raised the possibility that tumor MGMT levels may be an important predictor of survival in patients with gliomas.We correlated the MGMT level in malignant astrocytoma tissues, obtained from patients treated with radiotherapy and bis-chloroethylnitrosourea (BCNU) on a prior prospective trial (Southwest Oncology Group [SWOG] 8737), with overall and failure-free survival.Of 64 assessable patients with malignant astrocytoma (63% glioblastoma, 37% anaplastic astrocytoma), 64% had high (> 60,000 molecules/nucleus) MGMT levels. The overall median survival for patients with high versus low MGMT levels was 8 and 29 months, respectively (P=.0002), and median failure-free survival 3 and 6 months, respectively (P=.008). Subset analysis by histology (high v low MGMT levels) for anaplastic astrocytoma was 14 versus 62 months (n=24) and for glioblastoma was 7 versus 12 months (n=40). The overall hazards ratio (risk for death) for high versus low MGMT levels was 3.41; in young patients, the hazards ratio was higher (age 18 to 40 years, 4.19; age 41 to 60 years, 3.08) but became equal by MGMT level at age older than 60 years (1.11). Multivariate analysis showed that MGMT was independent of other known prognostic factors (age, performance status, histology).The MGMT level in tumor tissue specimens may be a predictive marker of survival in patients with malignant astrocytoma that is independent of other previously described prognostic variables.
Differential Inhibition of In Vitro Malignant Cell Assays by B16 Mouse Melanoma Variants&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: David E. Maslow, Eric Mayhew, Jean Feldman
Journal: JNCI Journal of the National Cancer Institute (1980)

Neural retina aggregation and adhesion assays, shown to be sensitive to the presence of small numbers of malignant cells, were differentially inhibited by cells or medium from B16 mouse melanoma sublines with higher metastatic characterizations, which suggests a correlation between inhibition of adhesion and aggregation and metastatic potential.
The implementation of GOLD 2011 among pulmonary specialists in the Czech Republic
Authors: Vladimir Koblizek, Ladislav Pecen, Ales Tichopad, Jaromir Zatloukal, Vitezslav Kolek, Barbora Novotna
Journal: European Respiratory Journal (2014)

Background: Physicians knowledge of global COPD guidelines varies widely across countries.  Purpose: The main objective of this survey was to assess the awareness and implementation of GOLD 2011 strategy.  Methods: Multicentre cross-sectional study of COPD treatment practice among Czech pulmonology specialists. The overall study consisted of two types of surveys; the general questionnaire and the patient-specific electronic case report form (eCRF).  Results:Data from 144 pulmonologists were obtained (Oct-Dec 2012). In total 143 (99.3%) of all respondents indicated the GOLD 2011 guidelines as leading guidelines in their practice, often along with another: Czech guidelines (83.3%) and the ERS/ATS standards (50.7%). In total 1355 consecutive patients (68,5y) were reported into the eCRF. Misclassification was apparent in 32.8% of reported cases. The most important reason for GOLD misclassification was incorrect assessment of symptoms. Evaluating the trends closely, 23.9% of all cases were underestimated and 8.9% of all cases were overestimated. The greatest error rate was observed in a group of specialists with more than 120 patients per month. Considering that the observed classification into A, B, C and D as pronounced by specialists, 19.5% of patients have been over-prescribed ICS while 12.2% had ICS under-prescribed. Female specialists failed in correct prescription more frequently than male specialists (33.6% vs. 27.3%), predominantly by over-prescribing ICS.  Conclusion: Although there seems to be high awarness of GOLD 2011, the implementation shows rather insufficient. There is an obvious tendency towards underclassification of patients and simultaneous overtreatment of COPD patients.
Refinement of clinicopathologic staging for localized soft tissue sarcoma of the extremity: a study of 423 adults.
Authors: J J Gaynor, C C Tan, E S Casper, C F Collin, C Friedrich, M Shiu, S I Hajdu, M F Brennan
Journal: Journal of Clinical Oncology (1992)

The prognostic value of factors used in clinicopathologic staging of localized soft tissue sarcoma (STS) of the extremity were analyzed comprehensively.Four hundred twenty-three patients with STS that was confined to the extremity were admitted to Memorial Sloan-Kettering Cancer Center from 1968 to 1978. Cox models for the hazards rates of tumor mortality, development of a distant metastasis, strictly local recurrence, and postmetastasis survival were developed. Tests of changes in the prognostic value of the important variables over time were performed, as well as an analysis of the effect of a local recurrence on the hazard rate of distant metastasis.Three unfavorable characteristics contained independent prognostic value for the rates of distant metastasis and tumor mortality: high grade (P less than .00001), deep location (P less than .0002), and size greater than or equal to 5 cm (P less than .007). Their Cox model coefficients did not differ significantly (P greater than or equal to .65); thus, a staging scheme based on the risk of ever developing a distant metastasis would assign equal prognostic weights to grade, depth, and size. The tumor grade effect during the initial 18 months was much larger in magnitude than those for depth and size, and its effect disappeared beyond that time (P = .0003). Thus, a staging scheme based on the risk of early metastatic spread would assign a distinctly larger prognostic weight to grade and lesser but equal weights to depth and size. There was no local recurrence effect on the rate of distant metastasis in the high-risk group (high grade, deep, and greater than or equal to 5 cm; P = .75), but there was a significant association among the remaining groups combined (P = .0039). The magnitude of this association actually increased according to the number of favorable characteristics presented (P = .0024).The refinement of clinicopathologic staging may depend on the choice of outcome variable: ultimate prognosis versus early metastatic spread. Additionally, the observed local recurrence effect may be explained by a tendency for some patients to acquire one or more unfavorable risk factors at the time of local recurrence.
Gefitinib in second line treatment of metastatic or locally advanced synovial sarcoma expressing HER1: A phase II trial of EORTC Soft Tissue and Bone Sarcoma Group
Authors: J. Blay, A. Le Cesne, J. Whelan, A. Van Oosterom, I. Ray-Coquard, L. Judson, P. Hogendorn, S. Marreaud, C. Hermans, M. Van Glabbeke
Journal: Journal of Clinical Oncology (2006)

9517 Background: Synovial sarcomas (SyS) have been reported to overexpress HER1 in gene expression profile experiments and immunohistochemistry. Gefitinib, a specific inhibitor of HER1, was therefore tested in advanced or metastatic SyS failing doxorubicin (Doxo) ± ifosfamide (Ifo). Methods: Patients (pts) with advanced or metastatic SyS expressing HER1 using IHC were included. The principal inclusion criterias were: disease not curable with surgery and/or radiation, presence of a measurable progressive lesion(s), pretreatment with 1–3 line of chemotherapy in metastatic phase, ECOG PS 0 to 2, age ≥18 years. Gefitinib was given at 500mg/day until progression or intolerance. Primary endpoint was the rate of progression free survival at 3 months. A two step Simon design was used with a p0 of 25% and a p1 of 45%, with α and β of 0.1. 44 patients were scheduled to be recruited. Results: Between 10/02 and 10/05, 48 pts were included in 12 EORTC STBSG centers, 27 (56%) males and 21 (44%) females. Median age was 42 years (range 19–66). Metastatic sites were lung in 92% and soft tissue or lymph nodes in 42%, of the patients. Respectively 42, 40 and 18% of the patients had received 1, 2 and &gt;2 lines of CT. As of December 2005, 37 pts are evaluable for toxicity and 39 for the primary endpoint. Median treatment duration was 11 weeks (range 2–25). Toxicity (G1–4) reported included fatigue (43%), diarrhea (54%), cough (35%), dyspnea (43%), cutaneous (73%). G3–4 toxicities were dyspnea (9), fatigue (4), cutaneous (2), cough (1), neurological (2), thombosis (2), hypoxia (1), infection (1). There was no drug related death. No dose reduction has been reported so far, but treatment had to be temporarily interrupted in 23% of the patients. As of December 2005, there were no objective response reported. Seven (18%) pts achieved stable disease as best response. At 3 months, 5 of the 39 (13%) evaluable patients achieved PFS; 6 and 12 months PFS were 10% and 3% respectively. Conclusions: 13% of SyS expressing HER1 achieved prolonged progression free survival at least 12 weeks) with gefitinib. Gene expression profiling and protein expression were not accurate predictors of gefitinib activity in this model. No significant financial relationships to disclose.
shRNA targeting α-synuclein prevents neurodegeneration in a Parkinson’s disease model
Authors: Alevtina D. Zharikov, Jason R. Cannon, Victor Tapias, Qing Bai, Max P. Horowitz, Vipul Shah, Amina El Ayadi, Teresa G. Hastings, J. Timothy Greenamyre, Edward A. Burton
Journal: Journal of Clinical Investigation (2015)

Multiple convergent lines of evidence implicate both α-synuclein (encoded by SCNA) and mitochondrial dysfunction in the pathogenesis of sporadic Parkinson's disease (PD). Occupational exposure to the mitochondrial complex I inhibitor rotenone increases PD risk; rotenone-exposed rats show systemic mitochondrial defects but develop specific neuropathology, including α-synuclein aggregation and degeneration of substantia nigra dopaminergic neurons. Here, we inhibited expression of endogenous α-synuclein in the adult rat substantia nigra by adeno-associated virus-mediated delivery of a short hairpin RNA (shRNA) targeting the endogenous rat Snca transcript. Knockdown of α-synuclein by ~35% did not affect motor function or cause degeneration of nigral dopaminergic neurons in control rats. However, in rotenone-exposed rats, progressive motor deficits were substantially attenuated contralateral to α-synuclein knockdown. Correspondingly, rotenone-induced degeneration of nigral dopaminergic neurons, their dendrites, and their striatal terminals was decreased ipsilateral to α-synuclein knockdown. These data show that α-synuclein knockdown is neuroprotective in the rotenone model of PD and indicate that endogenous α-synuclein contributes to the specific vulnerability of dopaminergic neurons to systemic mitochondrial inhibition. Our findings are consistent with a model in which genetic variants influencing α-synuclein expression modulate cellular susceptibility to environmental exposures in PD patients. shRNA targeting the SNCA transcript should be further evaluated as a possible neuroprotective therapy in PD.
Relapse rate of tuberculosis and related factors in Korea; by using the nationwide tuberculosis notification data
Authors: Hyungmin Lee, Yoon-sung Park, Jusang Kim, Eun-hee Cho, Sang-suk Shin, Bo Youl Choi
Journal: European Respiratory Journal (2012)

Background : The relapse rate of tuberculosis(TB) was one of the indicators that assess indirectly the level of TB control. In Korea propotion of relapse TB was reported in about 12%.   Aims : To estimate the relapse rate of TB and investigate the related factors with relapse of TB by using the nationwide TB notification data in Korea.   Materials and Methods : Data source was the nationwide TB notification data in 2005. For them to check that TB patients had been reported again from 2006 to 2010. Related factors were analyzed by using multivariate logistic regression.   Results : Of 45,434 TB patients in 2005, 4,371(9.6%) were reported with TB again and 564 were reported two or more. So the cumulative relapse cases were 5,072(11.2%). A relapse rate was 4.8% in 2006, 2.4% in 2007, 1.6% in 2008, 1.4% in 2009, and 1.0% in 2010.   Conclusion : The five-year relapse rate was 9.6%. It was likely to be underestimated because reporting rate was estimated to be 65-70%. A relapse was decresed over time, 65% of relapse occured within two years. Related factors with relapse were various. Especially previous treatment failure or default were related strongly.
Usefulness of a selective neutrophil elastase inhibitor and a recombinant human soluble thrombomodulin in patients with ARDS and DIC
Authors: Seigo Miyoshi, Ryoji Ito, Aki Kato, Hitoshi Katayama, Kazunori Irifune, Hironobu Hamada, Kentaro Dote, Mayuki Aibiki, Takafumi Okura, Jitsuo Higaki
Journal: European Respiratory Journal (2013)

Background:   Neutrophil elastase, alveolar thrombin generation and fibrin deposition plays a crucial role in the development of acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC). The usefulness of the combination therapy of a selective neutrophil elastase inhibitor, Sivelestat, and a recombinant human soluble thrombomodulin (rhTM) for patients with ARDS and DIC is still unknown.   Methods:   A retrospective data analysis of 97 ARDS patients with DIC was conducted to investigate the effects of Sivelestat and rhTM. We divided these patients into 4 groups (control group [patients without Sivelestat and rhTM treatment], Sivelestat group, rhTM group and combination group). The efficacy of these drugs was evaluated based on survival rate, the number of ventilator free days (VFD), and changes in PaO 2 /F I O 2  (P/F) ratio before and 7 days after diagnosis of ARDS with DIC.   Results:   The combination therapy with Sivelestat and rhTM significantly prolonged the survival of patients with ARDS and DIC compared to control group. VFD was significantly higher in combination group than in control group. P/F ratio significantly improved in Sivelestat, rhTM or combination group than in control group. Multivariate analysis by Cox proportional hazards model showed that gas exchange, organ failure, cause, associated disease (GOCA) score, serum levels of C-reactive protein and combination therapy was a predictor of mortality in patients with ARDS and DIC.   Conclusion:   Our results suggest that the combined therapy with Sivelestat and rhTM might have beneficial effect on survival and pulmonary function of patients with ARDS and DIC.
Impact of chronic obstructive pulmonary disease in the outcome of intensive care unit-acquired pneumonia
Authors: Mariano Rinaudo, Miquel Ferrer, Hugo Loureiro, Rogelio Peralta, Silvia Terraneo, Francesca De Rosa, Gianluigi Li Bassi, Antoni Torres
Journal: European Respiratory Journal (2013)

Rationale: In patients with ventilator-associated pneumonia, underlying chronic obstructive pulmonary disease (COPD) was independently associated with poor outcome in one study. We assessed the impact of underlying COPD on the outcome of intensive care unit-acquired pneumonia (ICUAP), regardless patients were previously ventilated or not.

Methods: Prospective, observational study on the characteristics, microbiology, systemic inflammatory response and outcomes of 381 consecutive patients with ICUAP clustered according to the presence or not of COPD.

Results: Eighty-two (21.5%) patients had COPD. Patients with COPD were older, had more frequently cardiac co-morbidity, history of solid cancer, and less SOFA score, and longer stay before the onset of pneumonia, compared with non-COPD patients. The rate of etiologic diagnosis was similar between groups, with a trend to higher rate of P. aeruginosa in patients with COPD. Serum levels of interleukin (IL)-6 and IL-8 at onset of pneumonia were lower in COPD patients. Mortality at 28 days was similar between both groups; however, mortality at 90 days was significantly higher in COPD patients (48, 62% vs. 118, 43%, odds-ratio 2.16, 95% confidence interval 1.29-3.61, p=0.003). After adjusting for possible confounders, the association of COPD with increased mortality at 90 days disappeared (adjusted odds-ratio 1.71, 95% confidence interval 0.88-3.31, p=0.11).

Conclusions: In patients with ICUAP, underlying COPD is associated with decreased systemic inflammatory response. COPD was not related with increased mortality at 90 days after adjusting for potential confounders.
Effect of Hyperthermia and Environmental Acidity on the Proteolytic Activity in Murine Ascites Tumor Cells2
Authors: J. Overgaard, H. Skovgaard Poulsen
Journal: JNCI Journal of the National Cancer Institute (1977)

The influence of hyperthermia and environmental pH on proteolytic activity was studied in murine ascites tumor cells in vitro. PNJ ascites tumor cells were incubated with [125I]cytochrome c at 42.5 or 37 degrees C in a modified Krebs-Ringer buffer adjusted to pH 7.2 or 6.4. Incubation at normal temperature at pH 6.4 and 7.2 or at 42.5 degrees C and pH 7.2 resulted in identical protein digestion. However, hyperthermic incubation at pH 6.4 resulted in a significant increased activity. This was also observed after only 1 hour of hyperthermic incubation followed by subsequent incubation in an acidic environment at normal temperature. The increased proteolytic activity following hyperthermic treatment under acidic conditions may support the hypothesis that increased lysosomal activity is of primary importance in the hyperthermic tumor-cell destruction in vivo.
Immune status of patients with inherited bone marrow failure syndromes
Authors: Neelam Giri, Blanche P. Alter, Keri Penrose, Roni T. Falk, Yuanji Pan, Sharon A. Savage, Marcus Williams, Troy J. Kemp, Ligia A. Pinto
Journal: American Journal of Hematology (2015)

Immune function abnormalities have been reported in patients with Fanconi anemia (FA), dyskeratosis congenita (DC) and, rarely, in Shwachman–Diamond syndrome (SDS), and Diamond–Blackfan anemia (DBA), but large systematic studies are lacking. We assessed immunological parameters in 118 patients with these syndromes and 202 unaffected relatives. We compared the results in patients with reference values, and with values in relatives after adjusting for age, sex, corticosteroid treatment, and severe bone marrow failure (BMF). Adult patients (≥18 years) with FA had significantly lower immunoglobulins (IgG, IgA and IgM), total lymphocytes, and CD4 T cells than reference values or adult relatives ( P &lt; 0.001); children with FA had normal values. Both children and adults with FA had lower B‐ and NK cells ( P &lt; 0.01) than relatives or reference values. Patients with DC had essentially normal immunoglobulins but lower total lymphocytes than reference values or relatives, and lower T‐, B‐, and NK‐cells; these changes were more marked in children than adults ( P &lt; 0.01). Most patients with DBA and SDS had normal immunoglobulins and lymphocytes. Lymphoproliferative responses, serum cytokine levels, including tumor necrosis factor‐α and interferon‐γ, and cytokine levels in supernatants from phytohemagglutinin‐stimulated cultures were similar across patient groups and relatives. Only patients with severe BMF, particularly those with FA and DC, had higher serum G‐CSF and Flt3‐ligand and lower RANTES levels compared with all other groups or relatives ( P &lt; 0.05). Overall, immune function abnormalities were seen mainly in adult patients with FA, which likely reflects their disease‐related progression, and in children with DC, which may be a feature of early‐onset severe disease phenotype. Am. J. Hematol. 90:702–708, 2015. © 2015 Wiley Periodicals, Inc.
Diagnostic yield of nonfunctional pancreatic neuroendocrine tumor using endoscopic ultrasound-guided fine needle aspiration biopsy
Authors: K. Matsumoto, A. Sawaki, Y. Kobayashi, N. Mizuno, K. Hara, T. Takagi, Y. Sawai, Y. Shimizu, Y. Yatabe, K. Yamao
Journal: Journal of Clinical Oncology (2009)

e15680 Background: Radiological examinations including computed tomography (CT) and endoscopic ultrasound sonography (EUS) are important for the diagnosis of pancreatic neuroendocrine tumors (PNETs). Pathological diagnosis is not needed with functional PNETs because the diagnosis is made by biochemical testing. Therefore, pathological diagnosis is essential for the non-functional PNETs (nf-PNETs). In this study, we examined the diagnostic yield of radiological examinations and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for nf-PNETs. Methods: From January 1997 to December 2007, consecutive 38 cases were pathologically diagnosed from as nf-PNETs at Aichi Cancer Center Hospital. Of these 33 patients was diagnosed with surgical specimen, 5 patients with EUS-FNA specimen. Of 33 patients, 16 patients underwent EUS-FNA preoperatively, and were examined further: their EUS-FNA specimens were submitted for additional immunohistochemical examination for CD 56, chromogranin A, synaptophysin, somatostatin receptor 2A (SSTR2A) and Ki-67 using cell block method. Staging of PNETs was performed according to WHO classification. Results: 16 patients (10 men and 6 women) who ranged in age from 23 to 81 years. The mean of tumor size was 2.2 cm and ranged from 0.7 to 4.4 cm. Diagnosis by CT and EUS was 12 (75.0%) PNETs, two pancreatic cancer, one solid papillary tumors and one malignant lymphoma. Accurate diagnosis by cytology and immunohistochemistry was 75.0% and 93.8%, respectively. The Ki-67 in specimens of malignancy tended to be higher than those of benign or uncertain behavior. If we assumed that a tumor with Ki-67 of more than 2% was malignancy, the diagnostic accuracy was 75.0%. Positive reaction to SSTR2A was up to 14 out of 16 nf-PNETs. Conclusions: The EUS-FNA is a useful tool for diagnosing nf-PNETs with immunohistochemical staining compared to cytology and radiological examinations. Ki-67 may be also effective to predict the degree of malignancy. No significant financial relationships to disclose.
Hospital Variation and Characteristics of Implantable Cardioverter-Defibrillator Use in Patients With Heart Failure
Authors: Bimal Shah, Adrian F. Hernandez, Li Liang, Sana M. Al-Khatib, Clyde W. Yancy, Gregg C. Fonarow, Eric D. Peterson
Journal: Journal of the American College of Cardiology (2009)
Translational Activation of HIF1α by YB-1 Promotes Sarcoma Metastasis
Authors: Amal M. El-Naggar, Chansey J. Veinotte, Hongwei Cheng, Thomas G.P. Grunewald, Gian Luca Negri, Syam Prakash Somasekharan, Dale P. Corkery, Franck Tirode, Joan Mathers, Debjit Khan, Alastair H. Kyle, Jennifer H. Baker, Nancy E. LePard, Steven McKinney, Shamil Hajee, Momir Bosiljcic, Gabriel Leprivier, Cristina E. Tognon, Andrew I. Minchinton, Kevin L. Bennewith, Olivier Delattre, Yuzhuo Wang, Graham Dellaire, Jason N. Berman, Poul H. Sorensen
Journal: Cancer Cell (2015)