tbuckley/cabot-search huggingface dataset:
A phase I/II study of lenalidomide (Len) in combination with rituximab (R) in relapsed/refractory mantle cell lymphoma (MCL) with early evidence of efficacy
Authors: M. Wang, L. Fayad, F. Hagemeister, S. Neelapu, N. Bell, C. Byrne, R. Knight, J. Zeldis, L. Kwak, J. Romaguera
Journal: Journal of Clinical Oncology (2007)

8030 Background: MCL remains a therapeutic challenge. R targets CD20 antigen on MCL cells while Len may target the microenvironment of MCL cells and enhance the ADCC activity of R. To test this hypothesis, we initiated a single-center; open label, phase I/II study. We now report the completed phase I. Methods: Eligible patients (pts) had 1–4 lines of prior therapy including prior thalidomide or R, regardless of resistance. Each cycle of treatment consisted of Len given orally daily on days 1–21 of a 28-day cycle and R 375 mg/m 2 by IV infusion weekly for 4 weeks. A standard 3+3 dose escalation was used to determine MTD with Len doses at 10 mg, 15 mg, 20 mg, and 25 mg. DLT was defined as grade (G) 3 or 4 non-hematologic or G4 hematologic toxicity during the first cycle. Results: The phase I portion completed enrollment with 15 pts (4 at 10 mg, 3 at 15 mg, 6 at 20 mg and 2 at 25 mg). Thirteen pts were evaluable. Median age was 73 (62–84); median prior lines of therapy were 3 (1–4); median cycles received to date were 2 (1–7). Two DLT's occurred at 25 mg. One pt had G3 hypercalcemia. The other had G4 neutropenic fever and died of sepsis (G5) during the first cycle. Three additional pts were therefore enrolled at 20 mg. Common non-hematologic toxic events included pruritis (21 G1–2), hypercalcemia (9 G1–2, 1 G3), fatigue (9 G1–2), constipation (8 G1), diarrhea (6 G1–2), fever (6 G1–2), myalgias (4 G1–2, 1 G3) and elevated LDH (4 G1–2, 1 G3). Hematologic events included neutropenia (20 G1–2, 4 G3), thrombocytopenia (6 G1–2, 2 G3) and anemia (6 G1). There were no responses at 10 mg or 15 mg. At 20 mg after 2 cycles, 5 out of 6 pts achieved responses including 1 CR, 1 PR, 3 minor responses (MRs) and only 1 pt progressed. The 1 pt with PR went on to achieve a CR after 6 cycles. The 3 pts with MRs had tumor reductions by 43%, 40% and 38% respectively. These 3 patients with MRs continue to receive Len and might later achieve PR or CR. Conclusions: The MTD for Len with R in relapsed/refractory MCL was 20 mg, orally daily on days 1–21 of a 28-day cycle. Responses observed at 20 mg are promising with a favorable toxicity profile and are being evaluated further in an ongoing phase II study. [Table: see text]
Breast Cancer Risk Associated With Reproductive Factors and Breast Parenchymal Patterns
Authors: F de Waard, J J Rombach, H J Collette, B Slotboom
Journal: JNCI Journal of the National Cancer Institute (1984)

In a population-based study of 23,511 women 50–67 years of age at the time of first screening, a striking relationship was found between parity and age at first childbirth, on the one hand, and two radiologic aspects of breast parenchymal pattern (dysplasia and prominent duct pattern), on the other. These relationships appeared to be causal.
MO19390 (SAiL): Incidence of hemorrhage with first-line bevacizumab (Bv)-based therapy in advanced non-small cell lung cancer (NSCLC)
Authors: N. Thatcher, D. Stroyakovskiy, C. Zhou, A. Bearz, D. Isla, F. Griesinger, N. Pavlakis
Journal: Journal of Clinical Oncology (2009)

e19000 Background: MO19390 (SAiL) is an international, multicenter, open-label study evaluating the safety of first-line Bv in combination with a range of chemotherapy regimens in over 2,000 patients (pts). We report interim safety data with a focus on the incidence of serious bleeding events, including pulmonary hemorrhage. Methods: Primary endpoint was safety; secondary endpoints included time to disease progression and overall survival. Eligibility criteria included: non-squamous NSCLC with no prior chemotherapy, no uncontrolled hypertension (systolic &gt;150 mmHg and/or diastolic &gt;100 mmHg) or active cardiovascular disease at baseline, ECOG PS 0–2, no history of grade [g])&gt;2 hemoptysis, and no evidence of tumor abutting or invading major blood vessels. Pts received Bv (7.5 or 15mg/kg) with chemotherapy for up to six cycles, then non-progressors proceeded to receive Bv until disease progression. Results: Interim analyses were available for a safety population of 2,008 pts (data cut-off July 2008). Baseline characteristics for pts were (%): male 60.1; Caucasian/Asian/other 80.1/15.6/4.3; stage IIIB/IV 19.5/80.5 (no data for 3 pts); adenocarcinoma/large cell/other 85.8/7.1/7.1; central tumor location yes/no (Y/N) 27.3/72.7; cavitated tumor Y/N 2.6/97.4; smoking history Y/N 70/30; ECOG PS 0/1/2 38.1/56.1/5.8. The median age was 59 years. Serious bleeding events (g≥3) of any cause were reported in 43 pts (2.1%). Bv-related bleeding events (g≥3) were reported in 16 pts (0.8%), including hemoptysis in 5 pts (0.2%) and gastrointestinal hemorrhage in 3 pts (0.1%). Conclusions: In Bv-treated pts, significant bleeding and hemoptysis are rare events. Our results confirm the well established and manageable safety profile of Bv-based therapy in eligible non-squamous NSCLC pts. Updated results will be presented. [Table: see text]
Regulating Risk and the Boundaries of State Conduct: A Relational Perspective on Home Birth in Australia
Authors: Jindalae K. Skerman, Ainsley J. Newson
Journal: The American Journal of Bioethics (2016)

The concept of motivated reasoning and conflicting moral domains behind the state's conduct toward pregnant women, as described by Minkoff and Marshall (2016), can also be observed in the apparent ...
Allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia in first complete remission.
Authors: J P Vernant, G Marit, D Maraninchi, D Guyotat, M Kuentz, C Cordonnier, J Reiffers
Journal: Journal of Clinical Oncology (1988)

Twenty-seven patients ranging in age from 15 to 36 years participated in a pilot study, and underwent allogeneic bone marrow transplantation (BMT) for acute lymphoblastic leukemia (ALL) in first complete remission (CR) in four French centers. All patients were grafted from human leukocyte antigen/mixed leukocyte culture (HLA/MLC) identical sibling after conditioning regimen consisting of cyclophosphamide and total body irradiation (TBI). Sixteen patients are alive in persistent first remission, with a median follow-up of 56 months (range, 41 to 82 months). The 6-year Kaplan-Meier probability of disease-free survival (DFS) is 59%. Only three patients relapsed (5, 7, and 7 months after transplantation). These interesting results have led us to propose, in accord with a French multicentric protocol, allogeneic BMT for adults under 40 years of age during the first CR of ALL.
Microsatellite instability and loss of PTEN expression in early versus late-stage endometrial cancer: Results from studies of the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG)
Authors: H. Mackay, S. Gallinger, M. Tsao, C. M. McLachlin, K. Kieser, E. Eisenhauer, D. Tu, A. Oza
Journal: Journal of Clinical Oncology (2009)

5534 Background: Microsatellite instability (MSI+) and inactivation of the tumor suppressor gene PTEN are implicated in the development of endometrial cancer (EC). The aim of this study was to compare the prognostic value of MSI and PTEN in 2 patient (pt) populations, early stage vs. advanced/recurrent disease. Methods: Archival paraffin embedded tumor from pts with EC enrolled in closed NCIC-CTG studies: stage I/II (EN5) and advanced/recurrent disease(IND 126, 148 and 160) were examined for MSI (BAT 25/26) and for PTEN expression (immunohistochemistry). PTEN and MSI status were correlated with clinicopathologic features and outcome from NCIC-CTG trial databases. Results: 188 pt samples (97 stage I/II;91 advanced/recurrent disease) were examined. Results are available for PTEN in 129 pts and MSI in 166 pts. Overall, 55% were PTEN negative (-) and 19.3% MSI+. 33 (56.9%) pts were PTEN - in EN5 vs. 38 pts (53.5%) IND studies (p = 0.73). Overall, no association was seen between PTEN or MSI status and age, performance status (PS), tumor grade or histology. In univariate analysis, there was a trend towards improved survival (S) in pts with PTEN - EC (HR = 0.61; 95% CI, 0.36 -1.04, p = 0.07), weaker in multivariate analysis (HR = 0.56; 95% CI, 0.26–1.18 p = 0.12). In EN5, PTEN status was not associated with S in uni-or multivariate analyses. In the IND studies there was a trend towards improved S in univariate analysis (HR = 0.57; 95% CI, 0.32–1.06 p = 0.07). More pts were MSI+ in EN5, 23 (27.4%) vs. IND studies, 9 (11%) p = 0.01. In EN5, microsatellite stable (MSS) tumors were associated with a better prognosis in both univariate (HR = 0.18; 95% CI, 0.06–0.51, p &lt; 0.0001) and multivariate analysis (HR = 0.16; 95% CI, 0.05 to 0.5, p &lt; 0.0001). There was no difference in S between pts with MSS vs. MSI+ tumors overall, or in the IND studies. in uni- or multivariate analyses. There was no correlation between MSI and PTEN status overall or in either group of pts. Conclusions: MSI+ tumors are more common, and are associated with a worse prognosis, in early stage EC. There is a trend towards improved S for pts with PTEN- advanced EC. There is no association between PTEN and MSI status. No significant financial relationships to disclose.
Cathelicidin has a protective role against pulmonary emphysema
Authors: Mohamad Sadek Alalwani
Journal: European Respiratory Journal (2014)

Cathelicidin is a family of cationic antimicrobial peptide acts as immunomodulator of the innate immune system and CRAMP is the homologous molecule in mice. Cathelicidin stimulates airway proliferation and inhibits inflammatory cytokine release. Because emphysema and cathelicidin are related to inflammation and destruction, we postulated that cathelicidin might be involved in reducing severity of emphysema. The quantification of emphysema severity is performed by measuring the mean linear intercept (Lm) in lungs taken from both elastase-induced emphysema in CRAMP-deficient and WT control mice. BALF and cytospin were performed for the inflammatory cell fractions and inflammatory cytokine (ELISA). For the healing role of endogenous cathelicidin, selective injury was induced to Clara cells with naphthalene. Mice were sacrificed and lung sections were used for immunohistochemistry using monoclonal antibodies (antiCC10 protein). The healing was evaluated by counting clara cells in one millimeter of basement membrane (index). Our results showed that the presence of cathelicidin minimized significantly severity of emphysema in mice. The Lm for WT mice was (85,51µm± 3,15µm, n=8) and for CRAMP-KO was (111,7 µm± 6,850µm, n=8) markedly increased compared with the PBS groups. The number of inflammatory cells and the concentration of TNF-a and IL-1B in response to elastase were significantly higher in BALF of CRAMP-KO than WT mice. The healing of CRAMP-ko lung was significantly lower than wild type mice after 15 days of naphthalene administration. Based on our results, it can be concluded that the endogenous cathelicidin in mice reduces severity of emphysema and this may relate to anti-inflammatory and healer role of cathelicidin.
Standard-dose doxorubicin versus sequential dose-dense doxorubicin and ifosfamide in patients with untreated advanced soft tissue sarcoma (ASTS): A GEIS Study
Authors: J. Maurel, A. Lopez-Pousa, R. de las Peñas, J. Fra, J. Cruz, J. Martin, A. Casado, J. Martinez-Trufero, A. Poveda, X. Garcia del Muro
Journal: Journal of Clinical Oncology (2008)

10570 Background: To assess response rate (RR) and progression fee survival (PFS) with standard-dose doxorubicin (SDA) compared with sequential dose-dense doxorubicin and ifosfamide (DDAI) in first-line treatment of ASTS. Methods: Pts with untreated ASTS and measurable disease, performance status (PS) less than 2, age ≤ 65 years and adequate bone marrow, liver and renal function were entered on study. Stratifications were for PS (0 vs. 1), location of metastases (lung vs. other) and potentially resectable disease (yes vs. no) based on investigator criteria. They were randomized to either doxorubicin (D) 75 mg/m2 given q21d for 6 cycles (SDA) or D at 30 mg/m2 per day for 3 consecutive days (90 mg/m2) q14d for 3 cycles followed by ifosfamide at 12.5 g/m2 delivered by continuous infusion over 5 days q21d for 3 cycles (DDAI) with filgrastim or pegfilgrastim support. To detect a difference corresponding to an increase in 1-year PFS rate from 15% (SDA) to 35% (DDAI) (hazard ratio: 2.3), a total of 192 patients had to be accrued (alpha=0.05, beta=0.20). There was a clause for premature closure if less than 25% RR differences (40%, 95%CI 28–52 vs. 15%, 95%CI 4–27) were observed between DDAI and SDA arms in the first 114 evaluable pts. Two-tailed Chi-Square tests (alpha=0.05, beta=0.20). Results: Between December 2003 and September 2007, 132 pts were entered onto the study; the interim pre-planned analysis for futility allowed the premature closure. RR was 26% (SDA) vs. 25% (DDAI) (p=0.69). PFS was 7 months (m) (SDA, K-M 95%CI 3.7–10.2) vs. 6.5 m (DDAI, K-M 95% CI 4.2–8.7). Overall survival (OS) was 14.3 m (SDA, K-M 95%CI 9.8–18.7) vs. 16.1 m (DDAI, K-M 95%CI 13–19.2). Pts receiving DDAI had a higher rate of discontinuation due to toxicity than those receiving SDA (p=0.03). Conclusions: Single-agent doxorubicin remains standard treatment in ASTS. No significant financial relationships to disclose.
Economic and medical consequences of myelodysplastic syndromes from a medical perspective
Authors: S. Goldberg, N. Mody-Patel, N. Warnock
Journal: Journal of Clinical Oncology (2007)

17534 Background: The myelodysplastic syndromes (MDS) are a heterogeneous group of bone marrow failure diseases affecting the elderly. The economic impact on Medicare of MDS is largely unknown. A retrospective analysis of total healthcare resource use and cost of MDS patients (pts) was conducted. Methods: The Medicare Standard Analytic File 5% (SAF5%) claims database was used to identify pts with a new primary MDS diagnosis code in first quarter (Jan-Mar) 2003 then followed through Dec 2005. Pts with myeloid leukemia or anemias of known causes in the previous year were excluded. Newly diagnosed MDS pts were descriptively characterized based on potential cause of MDS, MDS-related complications, and MDS therapies. Total healthcare costs and resource utilization for MDS pts were analyzed. Results: Of the 1,713,502 pts in SAF5%, 705 (4 per 10,000) developed MDS in first quarter 2003, including those with a previous history of unexplained anemia 159, (23%), chemotherapy or radiotherapy exposure 43, (6%), and de novo 503 (71%). Mean age was 76 (range 29- 98); 49% male, 90% Caucasian. 2003 median Medicare payment for MDS pts was $17,556, compared to $1,459 for the total SAF5% Medicare population (mean: $28,023.67 vs. $6,739.48; p&lt; 0.001). Median Medicare payments for therapy induced were $34,271, prior anemia $17,191, and de novo MDS $16,493. 278 (39%) died; including 63% of the therapy-induced, 40% of the prior anemia and 37% of the de novo. 79% were hospitalized and 59% had at least one emergency room visit. Of 46% receiving blood transfusions 6% were coded with transfusional hemachromatosis. 314 (45%) received growth factor treatments and 108 (15%) chemotherapy. Of those at risk for MDS-related complications, 55%, 23%, and 2% experienced new onset cardiac complications, diabetes, and hepatic diseases, post MDS diagnosis. Additionally, 51% had pulmonary problems and 45% infections in the 3 year study. Conclusions: The majority of newly diagnosed MDS pts develop disease-related complications, resulting in significantly higher healthcare resource utilization and costs compared to non-MDS patients. No significant financial relationships to disclose.
Calreticulin Expression in Human Non–Small Cell Lung Cancers Correlates with Increased Accumulation of Antitumor Immune Cells and Favorable Prognosis
Authors: Jitka Fucikova, Etienne Becht, Kristina Iribarren, Jeremy Goc, Romain Remark, Diane Damotte, Marco Alifano, Priyanka Devi, Jerome Biton, Claire Germain, Audrey Lupo, Wolf Herve Fridman, Marie-Caroline Dieu-Nosjean, Guido Kroemer, Catherine Sautès-Fridman, Isabelle Cremer
Journal: Cancer Research (2016)

A high density of tumor-infiltrating mature dendritic cells (DC) and CD8(+) T cells correlates with a positive prognosis in a majority of human cancers. The recruitment of activated lymphocytes to the tumor microenvironment, primed to recognize tumor-associated antigens, can occur in response to immunogenic cell death (ICD) of tumor cells. ICD is characterized by the preapoptotic translocation of calreticulin (CRT) from the endoplasmic reticulum (ER) to the cell surface as a result of an ER stress response accompanied by the phosphorylation of eukaryotic initiation factor 2α (eIF2α). We conducted a retrospective study on two independent cohorts of patients with non-small cell lung cancer (NSCLC) to investigate the prognostic potential of CRT. We report that the level of CRT expression on tumor cells, which correlated with eIF2α phosphorylation, positively influenced the clinical outcome of NSCLC. High CRT expression on tumor cells was associated with a higher density of infiltrating mature DC and effector memory T-cell subsets, suggesting that CRT triggers the activation of adaptive immune responses in the tumor microenvironment. Accordingly, patients with elevated CRT expression and dense intratumoral infiltration by DC or CD8(+) T lymphocytes had the best prognosis. We conclude that CRT expression constitutes a new powerful prognostic biomarker that reflects enhanced local antitumor immune responses in the lung. Cancer Res; 76(7); 1746-56. ©2016 AACR.
Myocardial Structural Remodeling and Tissue Composition by Cardiac Magnetic Resonance (CMR) in Relation to Metabolic Syndrome in Type 1 Diabetes : The DCCT/EDIC Study
Authors: Evrim B Turkbey, Jye-Yu C Backlund, Patricia A Cleary, Marcelo S Nacif, Neville Gai, Rob J van der Geest, Anderson Armstrong, Gustavo J Volpe, Saman Nazarian, John M Lachin, Joao A Lima, David A Bluemke, Dcct
Journal: Circulation (2012)
Effects and dose–response relationships of resistance training on physical performance in youth athletes: a systematic review and meta-analysis
Authors: Melanie Lesinski, Olaf Prieske, Urs Granacher
Journal: British Journal of Sports Medicine (2016)

Objectives To quantify age, sex, sport and training type-specific effects of resistance training on physical performance, and to characterise dose–response relationships of resistance training parameters that could maximise gains in physical performance in youth athletes. Design Systematic review and meta-analysis of intervention studies. Data sources Studies were identified by systematic literature search in the databases PubMed and Web of Science (1985–2015). Weighted mean standardised mean differences (SMD wm ) were calculated using random-effects models. Eligibility criteria for selecting studies Only studies with an active control group were included if these investigated the effects of resistance training in youth athletes (6–18 years) and tested at least one physical performance measure. Results 43 studies met the inclusion criteria. Our analyses revealed moderate effects of resistance training on muscle strength and vertical jump performance (SMD wm 0.8–1.09), and small effects on linear sprint, agility and sport-specific performance (SMD wm 0.58–0.75). Effects were moderated by sex and resistance training type. Independently computed dose–response relationships for resistance training parameters revealed that a training period of &gt;23 weeks, 5 sets/exercise, 6–8 repetitions/set, a training intensity of 80–89% of 1 repetition maximum (RM), and 3–4 min rest between sets were most effective to improve muscle strength (SMD wm 2.09–3.40). Summary/conclusions Resistance training is an effective method to enhance muscle strength and jump performance in youth athletes, moderated by sex and resistance training type. Dose–response relationships for key training parameters indicate that youth coaches should primarily implement resistance training programmes with fewer repetitions and higher intensities to improve physical performance measures of youth athletes.
Timing of radiotherapy in the treatment of early-stage breast cancer.
Authors: B McCormick, C B Begg, L Norton, T J Yao, D Kinne
Journal: Journal of Clinical Oncology (1993)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1993.11.1.191 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8418232 Timing of radiotherapy in the treatment of early-stage breast cancer. B McCormickxB McCormickSearch for articles by this author , C B BeggxC B BeggSearch for articles by this author , L NortonxL NortonSearch for articles by this author , T J YaoxT J YaoSearch for articles by this author , D KinnexD KinneSearch for articles by this author https://doi.org/10.1200/JCO.1993.11.1.191 First Page PDF © 1993 by American Society of Clinical Oncology
alpha-Crystallin A sequences of Alligator mississippiensis and the lizard Tupinambis teguixin: molecular evolution and reptilian phylogeny.
Authors: W W de Jong, A Zweers, M Versteeg, H C Dessauer, M Goodman
Journal: Molecular Biology and Evolution (1985)

The amino acid sequences of the eye lens protein alpha-crystallin A from many mammalian and avian species, two frog species, and a dogfish have provided detailed information about the molecular evolution of this protein and allowed some useful inferences about phylogenetic relationships among these species. We now have isolated and sequenced the alpha-crystallins of the American alligator and the common tegu lizard. The reptilian alpha A chains appear to have evolved as slowly as those of other vertebrates, i.e., at two to three amino acid replacements per 100 residues in 100 Myr. The lack of charged replacements and the general types and distribution of replacements also are similar to those in other vertebrate alpha A chains. Maximum-parsimony analyses of the total data set of 67 vertebrate alpha A sequences support the monophyletic origin of alligator, tegu, and birds and favor the grouping of crocodilians and birds as surviving sister groups in the subclass Archosauria.