tbuckley/cabot-search huggingface dataset:
Exercise capasity and respiratory muscle strength responces to the cycle ergometer and calisthenic exercise training in chronic obstructive pulmonary diseases
Authors: Neslihan Durutürk, Hülya Arikan, Zuhal Kunduracilar, Gaye Ulubay, Öznur Akkoca Yildiz, Melda Saglam Ozturk, Ebru Çalik
Journal: European Respiratory Journal (2013)

Introduction: Exercise training is now considered an essential component of pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD). Aims: The purpose of this study was to compare cycle ergometer with calisthenic exercise on the effects of cardiorespiratory endurance and respiratory muscle strength of COPD. Metarials and Methods: Clinically stable 29 patients (GOLD level;II,III) attended in this study. Randomized 15 patients (mean age:61,26±5,02, FEV 1 :58,46±14,44%pred) received cycle ergometer training,14 patients (mean age:61,28±5,10, FEV 1 :57,28±10,54%pred) received calisthenic exercise for 6 weeks, 3 sessions per week. Lung volumes, maximal inspiratory and expiratory pressures (MIP, MEP), incremental cycle ergometer test and 6 minutes walk test were performed. Results: FVC levels significantly increased in cycle ergometer and FEV 1 , MVV levels increased in calisthenic exercise groups (p 0.05). VO 2 , VCO 2 , VE, O 2  pulse, exercise time, work load improved in both groups (p 2  decreased only in the cycle ergometer group. 6MWT walking distance (m) and distance (%pred) increased in both groups (p
GDF10 is a signal for axonal sprouting and functional recovery after stroke
Authors: Songlin Li, Esther H Nie, Yuqin Yin, Larry I Benowitz, Spencer Tung, Harry V Vinters, F Rena Bahjat, Mary P Stenzel-Poore, Riki Kawaguchi, Giovanni Coppola, S Thomas Carmichael
Journal: Nature Neuroscience (2015)
Phase III trial of ixabepilone plus capecitabine compared to capecitabine alone in patients with metastatic breast cancer (MBC) previously treated or resistant to an anthracycline and resistant to taxanes
Authors: L. T. Vahdat, E. Thomas, R. Li, J. Jassem, H. Gomez, H. Chung, R. Peck, P. Mukhopadhyay, J. Klimovsky, H. Roché
Journal: Journal of Clinical Oncology (2007)

1006 Background: Patients with MBC who have progressed after anthracyclines and taxanes have limited treatment options. Ixabepilone, a novel epothilone B analog, is active in resistant breast cancer. Methods: In this large multinational phase III trial, patients with MBC who were anthracycline pretreated and met predefined resistance criteria to taxanes were randomized to ixabepilone (40mg/m 2 IV over 3h Q3w) + capecitabine (1,000mg/m 2 PO BID Q14d) or capecitabine (1,250mg/m 2 PO BID Q14d). The primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR), safety, and overall survival (available after 2007). Response and progression were assessed by an independent review committee (IRC) and the investigators (INV). Results: 752 patients were randomized. Median age was 53; 84% had visceral disease, 48% and 43% had 1 and =2 prior metastatic regimens. Median of 5 and 4 cycles of ixabepilone + capecitabine and capecitabine were administered. Ixabepilone + capecitabine was superior to capecitabine. Significant benefit was consistently maintained across predefined subgroups, including HER2-/ER- /PR- and HER2+. *Primary analysis of PFS; hazard ratio= 0.75. Grade (G) 3/4 adverse events included neuropathy (ixabepilone + capecitabine 23% vs capecitabine 0%), hand-foot syndrome (18% vs 17%), and fatigue (9% vs 3%). Neuropathy was cumulative and reversible (median time to resolution of G3/4 to baseline/G1 was 6 weeks). G3 and 4 neutropenia were reported in 32% and 36% vs 9% and 2%, respectively; febrile neutropenia was 5% with ixabepilone + capecitabine. Toxic death rate was 3% vs 1%. Patients with liver dysfunction were at greater risk. Conclusions: Ixabepilone + capecitabine has superior efficacy to capecitabine across endpoints and has a manageable safety profile in this heavily pretreated population. It offers a new potential option for patients with MBC. [Table: see text] No significant financial relationships to disclose.
Characterization of patients with non-small cell lung cancer (NSCLC) relative to its EGFR mutational status
Authors: Ana Castro, Ana Antunes, Ana Barroso, Sara Conde, Sofia Neves, Bárbara Parente
Journal: European Respiratory Journal (2011)

Introduction:  EGFR (Epidermal Growth Factor Receptor) mutations occur in 10-15% of non-Asian patients with NSCLC. In 2010, our Lung Cancer Centre started performing this sequencing systematically in all patients with NSCLC, regardless of histology, smoking or sex.   Objective:  Characterize the group of patients that undertook EGFR sequencing in the year 2010 and assess their frequency.   Methods:  Descriptive statistical analysis of patients with NSCLC who did EGFR sequencing in 2010.   Results:  The sequencing was performed on 126 patients, 75% males and 25% females. Average age 65 years. 69% non or ex-smokers and 31% smokers. Histology: 59%adenocarcinoma, 23%squamous cell carcinoma (SCC). Mutations were detected in 13 patients (10.3%), one mutation in exon18, 6 in exon19, 2 in exon20, 4 in exon21 and no resistance mutations were described.The mutation rate was higher in females (53%), non-smokers (46%) and adenocarcinoma (62%). Female patients with EGFR mutation: 86%nonsmokers, 85%adenocarcinoma, 15%epidermoid histology. Male with EGFR mutation: 83%ex-smokers, 67%SCC, 33%adenocarcinoma. Non-smoker mutated patients were all female, 83%adenocarcinoma, 17%SCC.   Conclusion:  Our group had a mutation rate of 10.3%, predominantly female, non-smokers, adenocarcinoma histology, accordingly with literature. This work also intends to highlight the importance of sequencing EGFR gene mutation in all patients with NSCLC, whereas mutation is also frequent in males, squamous histology and smokers. These patients are given the possibility of a 1st line treatment in the with TK inhibitors, with a greater increase in survival, improved quality of life and a better chance for other courses of chemotherapy.
Is incidence of small cell lung cancer (SCLC) on the raise?
Authors: C. Clarke, N. Mullai, C. Tong, J. Samuel, G. Myers
Journal: Journal of Clinical Oncology (2004)

7283 Background: Incidence of SCLC usually varies from 17–29% from biopsy/cytology specimens. In the SEER data, SCLC comprises of 18% of all primary lung cancer. Recently it was observed that the incidence is increasing especially in women. This study was done to evaluate SCLC incidence in an urban hospital serving predominantly African-American population. Method: A retrospective analysis of records of 100 patients diagnosed and treated for lung cancer at Provident Hospital since year 2000 was analyzed for the incidence of SCLC. Result: Male-female ratio was 1.6:1. Sixty-three percent were seen in the age group of 51–70 yr. Eighty-three percent had non-small cell lung cancer (NSCLC) and seventeen percent had small cell lung cancer. Among NSCLC adenocarcinoma was the common cancer (39%), followed by squamous cell (29%). Seventy percent of patients with SCLC were men and fifty-three percent of patients had extensive disease. Fourteen of the seventeen patients with SCLC were diagnosed and treated in year 2002–2003. Conclusion: Like the SEER data this study also shows the increasing incidence of SCLC. However the increase is seen predominantly among men in African-American population. SCLC is almost always associated with smoking and with a poor prognosis. This study stresses the importance of continued education against smoking to prevent the increasing incidence of this dismal disease. Further follow up is needed to see if this increasing trend in SCLC in African-American population is continuing. No significant financial relationships to disclose.
The Effect of Fractionated X-Ray Dosage Upon the Mouse Testis. I. Maximum Weight Loss Following 80 to 240 r Given in 2 to 5 Fractions During 1 to 4 Days
Authors: Henry I. Kohn, Robert F. Kallman
Journal: JNCI Journal of the National Cancer Institute (1955)

The Effect of Fractionated X-Ray Dosage Upon the Mouse Testis. I. Maximum Weight Loss Following 80 to 240 r Given in 2 to 5 Fractions During 1 to 4 Days Henry I. Kohn, Henry I. Kohn Radiological Laboratory, Department of Radiology, University of California School of Medicine3, San Francisco, Calif. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert F. Kallman Robert F. Kallman Radiological Laboratory, Department of Radiology, University of California School of Medicine3, San Francisco, Calif. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 4, February 1955, Pages 891–899, https://doi.org/10.1093/jnci/15.4.891 Published: 01 February 1955 Article history Received: 24 September 1954 Published: 01 February 1955
Phase Ii Study of Nilotinib in Melanoma Harboring Kit Alterations Following Progression or Intolerance to Prior Kit Inhibition
Authors: R. Carvajal, D. Lawrence, J.S. Weber, T.F. Gajewski, R. Gonzalez, J. Lutzky, S. O'Day, O. Hamid, J.D. Wolchok, P. Chapman, R.J. Sullivan, J.B. Teitcher, C. Antonescu, M.C. Heinrich, B. Bastian, C.L. Corless, A. Giobbie-Hurder, J. Fletcher, F.S. Hodi
Journal: Annals of Oncology (2014)
Smoking alters α1-antitrypsin in alveolar macrophages possibly promoting misfolding
Authors: Simonetta Baraldo, Erica Bazzan, Claudia Radu, Graziella Turato, Beatrice Molena, Sara Ortolan, Riccardo Cazzuffi, Nazarena Nannini, Marco Schiavon, Fiorella Calabrese, Federico Rea, Paolo Simioni, Manuel Cosio, Marina Saetta
Journal: European Respiratory Journal (2014)

Background:  The antiprotease and anti-inflammatory roles of a1-antitrypsin (AAT) are essential in protection of lung integrity. The PiZZ allele of AAT promotes misfolding and polymerization of the molecule that is retained in the endoplasmic reticulum (ER) resulting in low AAT serum levels. Alveolar macrophages (AM) produce AAT but their level of production in relation with AAT genotype and smoking has been scantily investigated.   Aims:  To investigate AAT expression in alveolar macrophages from patients with severe COPD, with or without AATD, and smoking and nonsmoking controls.   Methods:  AAT expression and localization were studied by immunohistochemistry and immunofluorescence in 10 explanted lungs with AATD, 26 with “usual” COPD, 17 smokers without COPD and 11 nonsmokers.   Results:  The percentage of AM expressing AAT (43;3-78% vs 50;3-76% vs 42;0-100 vs 56;2-97%) was similar in all groups. AAT expression correlated with lymphocytic lung inflammation (r=0.42,p=0.01). PAS staining revealed globular inclusions in AM, suggestive of AAT molecule aggregation in the endoplasmic reticulum, in COPD lungs with or without AATD (50%) and control smokers (80%) but not in nonsmokers (p=0.01). Immunofluorescence showed low-intensity diffuse AAT staining in nonsmokers but globular staining in smokers, that was coexpressed with the ER marker calreticulin, confirming the PAS pattern.   Conclusions:  Alveolar macrophages in the lungs of non-smoking, smoking and COPD subjects express AAT. In AATD and smokers, with and without COPD, a globular form of AAT, possibly misfolded or polymerized, is seen retained in endoplasmic reticulum, suggesting that smoking alters the AAT molecule in AM promoting misfolding.
Lung deposition of inhaled colistimethate sodium in cystic fibrosis patients
Authors: Shengfang Su, Todd Riccobene, Colin Scott
Journal: European Respiratory Journal (2014)

BACKGROUND: An inhaled dry powder of colistimethate sodium (CMS) has been developed for the treatment of chronic pulmonary Pseudomonas infection in cystic fibrosis (CF) patients.

AIM: To evaluate lung deposition of CMS following inhalation via a dry powder inhaler and nebulizer in CF patients.

METHODS: In this randomized, open-label, three-way crossover study, 10 subjects received 3 treatments separated by 72 hours: 1 MU (80 mg) CMS (Colomycin® Injection) using a nebulizer, 200 µg salbutamol followed by 125 mg CMS using a dry powder inhaler, and 125 mg CMS using a dry powder inhaler. Lung (central, intermediate and peripheral regions) and oropharyngeal deposition was measured using radioactive scintigraphic imaging. The amount of drug retained in the nebulizer, mouthpiece, dry powder inhaler, and capsule, as well as drug recovered from exhaled air, were determined.

RESULTS: Following administration of CMS using a nebulizer, the majority of the dose (49.9%) was retained in the nebulizer; when delivered using a dry powder inhaler with or without salbutamol, the majority of the dose (70%–71%) was deposited in the oropharynx. A higher fraction (35%) of CMS dose was recovered from the exhaled air using a nebulizer. Approximately 5.9% and 11.6% of the dose was deposited in the whole lung using a nebulizer and dry powder inhaler without salbutamol, respectively. Lung penetration index (the ratio of peripheral lung zone deposition to central lung zone deposition) was approximately 1.8 and 1.2 for nebulizer and dry powder inhaler without salbutamol, respectively.

CONCLUSION: This study demonstrated a higher lung deposition of CMS in CF patients when CMS was delivered by dry powder inhaler vs delivery via a nebulizer.
Abstract P034: Association between Obesity Indices and Insulin Resistance among Healthy Korean Adolescents
Authors: Hyeon Chang Kim, Dong Phil Choi, Sun Min Oh, Ju-Mi Lee, Hye Min Cho, Won Joon Lee, Jaelim Cho, Ah-reum Lee
Journal: Circulation (2012)

OBJECTIVE: To investigate whether five indices of obesity are associated with insulin resistance in a cohort of healthy Korean adolescents. METHODS: This is a cross-sectional analysis for 821 healthy adolescents who were aged 14-17 years and free of diabetes. Percentile values of weight-for-height, body mass index (BMI)-for-age, waist circumference (WC)-for-age, and skin fold thickness (SFT)-for-age were calculated comparing to the 2007 Korean National Growth Charts. Waist-to-hip ratio (WHR) percentile value was based on the distribution of study population, because the growth chart did not include WHR values. Insulin resistance was estimated by homeostatic model assessment (HOMA-IR) based on fasting glucose and insulin levels. Logistic regression models were used to estimate odds ratio for insulin resistance according to five different obesity indices. Generalized linear models were used to assess the associations between obesity indices and continuous HOMA-IR levels. RESULTS: Mean ± standard deviation of BMI was 22.2 ± 3.3 kg/m 2 for male and 21.2 ± 2.6 kg/m 2 for female adolescents. Sex and age-adjusted odds ratio (95% CI) for insulin resistance, defined as HOMA-IR&gt;2.50, of 50-74th, 75-94th, and ≥95th percentiles of weight-for-height was 1.53 (0.88–2.63), 4.35 (2.63–7.20) and 14.95 (7.50–29.80), respectively, when compared to &lt;50th percentiles. Corresponding odds ratios (95% CI) were 1.28 (0.74-2.22), 3.70 (2.25-6.08) and 14.78 (7.41-29.47) for BMI-for-age percentiles, 1.98 (1.15-3.43), 5.53 (3.24-9.44) and 16.34 (7.70-34.70) for WC-for-age percentiles, 1.90 (1.13-3.18), 4.46 (2.61-7.60) and 15.98 (7.55-33.81) for SFT-for-age percentiles, 1.57 (0.94-2.65), 3.57 (2.19-5.81) and 12.43 (6.08-25.38) for WHR percentiles. Similar findings were observed when insulin resistance was defined as HOMA-IR&gt;3.16. Continuous measure of HOMA-IR was significantly associated with all five obesity indices both in males and females. The associations between obesity indices and insulin resistance were stronger in males than in females. Continuous measure of HOMA-IR was significantly associated with all five obesity indices both in males and females. CONCLUSION: Our findings suggest that obesity indices are strongly and progressively associated with insulin resistance even in apparently healthy adolescents.
Cross Protection &lt;italic&gt;In Vivo&lt;/italic&gt; Against Avian Sarcoma Virus Subgroups A, B, and C Induced by Rous-Associated Viruses&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Paul Meyers, M. Michael Sigel, Howard T. Holden
Journal: JNCI Journal of the National Cancer Institute (1972)

We have reported that immunization of chickens with either subtumorigenic doses of live Rous sarcoma virus [RSV(RAV-1)] or live Rous-associated virus (RAV-1) elicits strong resistance against tumor induction after challenge with RSV(RAV-1). The present report confirms these findings and indicates that leukosis virus-induced immunity is demonstrable with various antigenically homologous and heterologous combinations of viruses of the avian leukosis-sarcoma complex. Birds inoculated with live Rous-associated viruses of subgroups A, B, or C were protected against tumor viruses of any of these antigenically distinct subgroups. Almost complete protection could be obtained with the homologous combinations of immunizing and challenge virus, whereas protection was least effective, though significant, with combinations of immunizing and challenge viruses of subgroups A and C. This protective effect is not dependent on humoral antiviral neutralizing antibody, because birds resistant to challenge had antibodies only to the immunizing virus but not to the heterologous challenge virus. Thus the protection appears to be mediated by cellular immunity directed against either common viral antigens or common virus-induced antigens.
Is patient self-reporting more accurate than clinician reporting of symptoms for predicting survival in patients with cancer? Meta-analysis of 30 closed EORTC randomized controlled trials
Authors: A. Bottomley, C. Coens, M. King, D. Osoba, M. J. Taphoorn, B. Reeve, J. Ringash, J. Schmucker-Von Koch, J. Weis, C. Quinten
Journal: Journal of Clinical Oncology (2009)

9597 Background: This study investigated whether patient self-reporting of symptoms improved prediction of survival as compared to clinician reporting or whether it provided an additive value when taken together with clinician assessment of the same symptoms. Methods: Patients with advanced cancer from 30 European Organisation for Research and Treatment of Cancer (EORTC) Randomized Controlled Trials were included in this retrospective pooled analysis. Clinician [Common Toxicity Criteria (CTC)] and patient (EORTC QLQ-C30) symptom assessment were reported at entry into the study. Data were obtained for six symptoms: pain, fatigue, vomiting, nausea, diarrhea and constipation. The prognostic accuracy for survival was assessed by modeling the contrast in reporting using the Harrell's discrimination c-index (c). Results: Data were available from patient and clinician assessment for pain [number of trials (t) =8, number of patients (n) =1214], fatigue [t=5, n=1237], vomiting [t=5, n=824], nausea [t=6, n=1393], diarrhea [t=6, n=815] and constipation [t=4, n=751]. Fatigue (c=0.59 vs 0.55, p&lt;.01) and constipation (c=0.57 vs 0.52, p=0.03) as reported by patients (vs clinicians) were significantly higher in predicting survival. Patient reported pain (c=0.59 vs 0.58, p=0.17), nausea (c=0.54 vs 0.52, p=0.51), vomiting (c=0.55 vs 0.52, p=0.21) and diarrhea (c=0.51 vs 0.52, p=0.49) did not predict survival any more accurately than clinician assessment. Patient and clinician assessment combined (vs clinicians alone) improved the prognostic accuracy for fatigue (c=0.61 vs 0.55, p=0.01), pain (c=0.60 vs 0.58, p&lt;0.01), nausea (c=0.54 vs 0.52, p=0.04), vomiting (c=0.56 vs 0.52, p=0.04) and constipation (c=0.5 vs 0.52, p=0.01), but not for diarrhea (c=0.52 vs 0.52, p=0.44). Conclusions: Our results suggest that patients’ ratings of their own fatigue and constipation have more prognostic value than clinicians’ ratings of these symptoms. Further, the prognostic value of clinicians's ratings can be improved by combining them with patients’ assessments for the symptoms pain, fatigue, constipation, nausea and vomiting. No significant financial relationships to disclose.
Advantages of Cryopreserved Lymphocytes for Sequential Evaluation of Human Immune Competence. I. Mitogen Stimulation
Authors: Henry F. Sears, Steven A. Rosenberg
Journal: JNCI Journal of the National Cancer Institute (1977)

Human lymphocytes were harvested from normal volunteer donors and cryopreserved. Various concentrations of dimethyl sulfoxide and human serum in the cryoprotective media were evaluated to optimize the recovery and function of viable cells. Multiple samples were then drawn from volunteers over a number of days, processed individually, and used in mitogen stimulation assays. These cells were also cryopreserved, immediately thawed, and cultured simultaneously with the fresh cells. In all instances fresh and cryopreserved lymphocytes exhibited similar levels of stimulation by mitogens. Cryopreserved cells from these sequential bleedings were then recovered and cultured simultaneously in mitogen stimulation assays. The results obtained in these assays with cryopreserved cells had less day-to-day variation than those with cells cultured individually. Coefficients of variance of individual cultures of mitogen stimulation assays were reduced from 26–59% to 5–17% by use of cryopreserved cells. The findings suggested that use of cryopreservation techniques decreases the variability of cellular immune assays and thus allows more accurate longitudinal study of the immune competence of patients.
Phase I/II and pharmacokinetic study of combination chemotherapy with S-1 and oxaliplatin in patients with previously untreated metastatic or recurrent gastric cancer
Authors: I. Park, J. Lee, M. Ryu, H. Chang, T. Kim, S. Sym, S. Lee, G. Jang, K. Bae, Y. Kang
Journal: Journal of Clinical Oncology (2008)

4557 Background: A novel oral fluoropyrimidine, S-1, and oxaliplatin (OX) have been reported to be highly active in advanced gastric cancer (AGC). The objectives of this study were to define the maximal-tolerated dose (MTD) of S-1 in combination with a fixed dose of OX, and to determine the activity and safety of this combination regimen at the recommended dose (RD) when used as the first line treatment of AGC. Methods: Treatment consisted of intravenous OX at a fixed dose of 130 mg/m2 on D1 followed by twice a day oral S-1 [35 mg/m2; level 1(n=3), 40 mg/m2; level 2(n=6), 45 mg/m2; level 3(n=3), or 50 mg/m2; level 4(n=6)] from D1-D14 of a 21-day cycle. At each level, a cohort of 3 patients (pts), which could be expanded to 6 pts, was studied. Dose-limiting toxicities (DLT) were determined during the first treatment cycle. Pharmacokinetic analysis of tegafur, 5-FU, CDHP, and oxonate was performed in 6 pts treated with RD using an optimized HPLC and UV absorption spectrophotometry. Results: In phase I part of the study(n=18), DLT occurred only one pt at level 2 who experienced unconscioussness due to hyponatremia. DLT was not observed in any other pts even though the level 4 dose cohort was expanded to 6 pts. The RD was determined to be level IV and 47 eligible pts, including 2 pts with measurable disease allocated to dose level 4 in the phase I portion, were enrolled in phase II portion. A total of 250 cycles of chemotherapy were administered. The median age was 55 years (31–70) and ECOG PS was 0/1 in 89% of pts. The objective response was observed in 26 (61%; 95% CI, 53–73%) of 43 evaluable pts. SD was achieved in 13 (30%) pts. With a median FU of 19.1 months (m) (95% CI, 18.5–19.7m), median PFS was 6.6 m (95% CI, 4.0–9.2m) with a median OS of 12.5 m (95% CI, 9.2–15.8m). G3–4 toxicities included thrombocytopenia (39%), neutropenia (28%), anemia (17%), febrile neutropenia (FN, 8%), asthenia (8%), and anorexia (8%). There was one G5 FN during the 1st cycle which appeared to be related with DPD deficiency. The pharmacokinetic profiles of S-1 components or its active metabolite did not differ whether S-1 was administered singly or combined with OX. Conclusions: OX plus S-1 regimen is highly active against AGC with favorable toxicity profiles in patients with AGC. No significant financial relationships to disclose.