tbuckley/cabot-search huggingface dataset:
Uptake of NIV treatment in MND is dependent upon caregiver variables
Authors: Rosanna Cousins, HIkari Ando, Carolyn Young, Biswajit Chakrabarti, Robert Angus
Journal: European Respiratory Journal (2012)

There is robust evidence that NIV relieves respiratory symptoms and improves quality of life in MND. Nevertheless, about a third of those who would benefit from NIV decline the treatment. It is important to understand why the most effective treatment available for MND patients [1] is refused. To investigate this phenomenon, we undertook a cross-sectional quantitative analysis of 27 patient and caregiver dyads offered ventilatory support based on physiological markers, including forced vital capacity and nocturnal pulse oximetry. The analyses indicated that there were no differences between the patients who went on to accept NIV treatment (n=17) and those who declined (n=10) in terms of age, sex, MND symptomatology (ALS-FRS-R, ALSAQ-40, MND Dyspnoea Rating Scale, daytime sleepiness) and psychological measures (hopelessness, anxiety and depression). The similarity of the scores in the two groups is such that we are confident that we do not simply have a power issue. In view of assertions that uptake of NIV treatment increases caregiver burden, which suggests caregiver input in NIV treatment, we also analysed caregiving variables. There were no differences in general physical or mental health but caregivers who supported NIV treatment were significantly more emotionally stable and less anxious, and in terms of coping style more resilient, more committed and more in control. A regression analysis forcing MND symptoms to enter before caregiving variables still indicated that resilience: commitment alone explained 24% of the variance. We will discuss these findings, and implications for clinicians.  1 Heiman-Patterson TD, Millar RG. NIPPV: A treatment for ALS whose time has come. Neurol 2006; 67: 736-7.
The CD11b promoter directs high-level expression of reporter genes in macrophages in transgenic mice [published erratum appears in Blood 1995 Apr 1;85(7):1983]
Authors: S Dziennis, RA Van Etten, HL Pahl, DL Morris, TL Rothstein, CM Blosch, RM Perlmutter, DG Tenen
Journal: Blood (1995)
Irinotecan is an active agent in untreated patients with metastatic colorectal cancer.
Authors: J A Conti, N E Kemeny, L B Saltz, Y Huang, W P Tong, T C Chou, M Sun, S Pulliam, C Gonzalez
Journal: Journal of Clinical Oncology (1996)

To determine the response rate, survival, and toxicity of the new anticancer agent, irinotecan (CPT-11), in the treatment of metastatic colorectal cancer.Forty-one chemotherapy-naive patients with measurable metastatic colorectal cancer were treated with a 90-minute infusion of irinotecan 125 mg/m2 administered weekly for 4 weeks every 6 weeks. Pretreatment tumor biopsies to assess topoisomerase-I (Topo-I) activity were obtained from 11 patients. The pharmacokinetics for irinotecan and its active metabolite, SN-38, were determined in 18 patients.Thirteen of 41 patients (32%) had a partial response (PR; 95% confidence interval, 18% to 46%). The median response duration was 8.1 months (range, 4.0 to 16.0) and the median survival time was 12.1 months (range, 2.1 to 21.7) for all 41 patients. Grade 3 or 4 toxicities were diarrhea (29% of patients) and neutropenia (22% of patients). Grade 3 or 4 diarrhea was substantially more prevalent in the initial 18 patients on study, with an incidence rate of 56%; a significant reduction in the incidence of severe diarrhea to 9% was noted with strict adherence to an antidiarrheal regimen of loperamide and diphenyldramine. No correlations were seen between pharmacokinetics of irinotecan/SN-38 and the clinical parameters of response, survival, or incidence of diarrhea.Irinotecan has activity in the treatment of patients with metastatic colorectal cancer. Strict adherence to an antidiarrheal regimen of diphenhydramine/loperamide significantly reduced the incidence of diarrhea; the agent was thereafter well tolerated in the majority of patients.
Paraquat-induced epithelial-mesenchymal transition: Role of Rac1b/Akt/Twist
Authors: Shen Yongchun, Zhang Xiaohong, Yang Ting, Wang Tao, Wen Fuqiang
Journal: European Respiratory Journal (2011)

Objective: To examine whether paraquat (PQ), a well-known reactive oxygen species (ROS) producer, could induce epithelial-mesenchymal transition (EMT) which involving in ROS-mediated pulmonary fibrosis and possible mechanisms.

Method: Human alveolar epithelial (A549) cells were cultured and exposed to sub-lethal doses of PQ, specific signaling pathway inhibitors and siRNAs for ROS signaling pathway. Intracellular ROS was measured with DCF-DA. Protein and RNA was evaluated by Western blot and real-time PCR, respectively.

Results: Intracellular ROS increased after various concentration paraquat stimulus for 5 minutes (p<0.05), while only PQ at the concentration of 20μM (PQ20) induced EMT manifested as increased fibronectin, decreased E-cadherin and a fibroblast-like cell appearance. mRNA of Twist, a key transcriptional factor for EMT, increased after PQ20 stimulus for 30minutes (P<0.05), accompanied with a rapid Twist nuclear translocation in A549 cells, while transfected with Twist cDNA antisense vector abolished PQ-induced EMT. Mitochondrial complex I inhibitor rotenone significantly inhibited PQ20-induced ROS. Small GTPase Rac1b involving in mitochondrial ROS mediated EMT was induced 5 minutes after PQ20 treatment, and siRNA targeted Rac1b blocked ROS generation and Akt phosphorylation induced by PQ20 (p<0.05). In addition, wortmannin, a PI3K inhibitor, could also block Akt phosphorylation and significantly reduce Twist nuclear translocation in A549 cells 2 hours after PQ20 treatment.

Conclusion: This study demonstrated that PQ could induce A549 cells EMT through Twist upregulation, which relied on Rac1b-dependent ROS generation/Akt signaling pathway and provided a better understanding of pulmonary fibrosis.
Contact x-ray brachytherapy 50 kV (CXB) for organ preservation in T2 T3a-b rectal cancer: Lyon-Nice experience in 120 patients.
Authors: Jerome Doyen, Eric Francois, Anne-Claire Frin, Karen Benezery, Fuxiang Zhou, Pascale Romestaing, Olivier Chapet, Nicolas N. Barbet, Jean-Pierre Gerard
Journal: Journal of Clinical Oncology (2015)

676 Background: Organ preservation (avoiding TME surgery) for T2 T3 a-b rectal cancer is a field of active clinical research. Contact X Ray CXB combined with external beam radiotherapy (EBRT) ± concurrent chemotherapy (CRT) is an attractive method to achieve clinical complete response (cCR) and consequently rectal preservation. We report an overview of 120 patients treated with CXB+EBRT over a 25 year period in Lyon since 1986 and then in Nice until 2012. Methods: Between 1986 and 2012, 120 patients presenting rectal adenocarcinoma T2 T3a-b (distal rectum: 87; middle rectum: 33) were treated with CXB +EBRT with conservative intent. In Lyon (1986-2001), 80 patients median age: 73y; T2:52; T3:28) risk were treated using CXB (80-110 Gy/3-4 fr/4-6 weeks) followed by EBRT (39 Gy/13 fr/18 days) and 192 Iridium implant boost (20 Gy). When cCR was achieved, close surveillance was proposed. In Nice (2002-2012), 40 patients (median age 81y; T2:22; T3:18) received CXB same regimen as in Lyon (using new Papillon 50 machine since 2009) + EBRT (45-50 Gy/5weeks) with concurrent chemotherapy (5-FU or Capecitabine). When cCR was achieved close surveillance was proposed or local excision (13 pts). Results: Median follow-up time 58 months in both groups. Local relapse occurred mainly in the 2 first years. Isolated lymph node recurrence &lt;5%. Bowel function good or excellent when rectum preserved. Main clinical outcomes in table (some improved results in Nice possibly due to better treatment approach and patient selection). Conclusions: CXB with EBRT and concurrent capecitabine achieve safely high rate of cCR with organ preservation. The OPERA randomized trial will reproduce Lyon R 96 trial (Gerard JP, JCO 2004;22:2404) and test the superiority of CXB boost for organ preservation. [Table: see text]
Intensive therapy with peripheral stem cell transplantation in 16 patients with mantle cell lymphoma
Authors: N. Ketterer, G. Salles, D. Espinouse, C. Dumontet, E.M. Neidhardt-Berard, I. Moullet, F. Bouafia, F. Berger, P. Felman, B. Coiffier
Journal: Annals of Oncology (1997)
Systemic mastocytosis in adults: 2015 update on diagnosis, risk stratification, and management
Authors: Animesh Pardanani
Journal: American Journal of Hematology (2015)

Disease overview : Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in one or more extracutaneous organs. Diagnosis : The major criterion is presence of multifocal clusters of morphologically abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC expression of CD25 and/or CD2, and presence of KIT D816V. Risk stratification : The 2008 World Health Organization classification of SM has been shown to be prognostically relevant. Classification of SM patients into indolent SM (ISM), aggressive SM (ASM), SM associated with a clonal non‐MC lineage disease (SM‐AHNMD), and mast cell leukemia (MCL) subgroups is a useful first step in establishing prognosis. Management : SM treatment is generally palliative. ISM patients have a normal life expectancy and receive symptom‐directed therapy; infrequently, cytoreductive therapy may be indicated for refractory symptoms. ASM patients have disease‐related organ dysfunction; interferon‐α (+/−corticosteroids) can control dermatological, hematological, gastrointestinal, skeletal, and mediator‐release symptoms, but is hampered by poor tolerability. Similarly, cladribine has broad therapeutic activity, with particular utility when rapid MC debulking is indicated; the main toxicity is myelosuppression. Imatinib has a therapeutic role in the presence of an imatinib‐sensitive KIT mutation or in KIT D816‐unmutated patients. Treatment of SM‐AHNMD is governed primarily by the non‐MC neoplasm; hydroxyurea has modest utility in this setting; there is a role for allogeneic stem cell transplantation in select cases. Investigational Drugs : Recent data confirms midostaurin's significant anti‐MC activity in patients with advanced SM. Am. J. Hematol. 90:251–262, 2015. © 2015 Wiley Periodicals, Inc.
Tumor-Promoting Desmoplasia Is Disrupted by Depleting FAP-Expressing Stromal Cells
Authors: Albert Lo, Liang-Chuan S. Wang, John Scholler, James Monslow, Diana Avery, Kheng Newick, Shaun O'Brien, Rebecca A. Evans, David J. Bajor, Cynthia Clendenin, Amy C. Durham, Elizabeth L. Buza, Robert H. Vonderheide, Carl H. June, Steven M. Albelda, Ellen Puré
Journal: Cancer Research (2015)

Malignant cells drive the generation of a desmoplastic and immunosuppressive tumor microenvironment. Cancer-associated stromal cells (CASC) are a heterogeneous population that provides both negative and positive signals for tumor cell growth and metastasis. Fibroblast activation protein (FAP) is a marker of a major subset of CASCs in virtually all carcinomas. Clinically, FAP expression serves as an independent negative prognostic factor for multiple types of human malignancies. Prior studies established that depletion of FAP(+) cells inhibits tumor growth by augmenting antitumor immunity. However, the potential for immune-independent effects on tumor growth have not been defined. Herein, we demonstrate that FAP(+) CASCs are required for maintenance of the provisional tumor stroma because depletion of these cells, by adoptive transfer of FAP-targeted chimeric antigen receptor (CAR) T cells, reduced extracellular matrix proteins and glycosaminoglycans. Adoptive transfer of FAP-CAR T cells also decreased tumor vascular density and restrained growth of desmoplastic human lung cancer xenografts and syngeneic murine pancreatic cancers in an immune-independent fashion. Adoptive transfer of FAP-CAR T cells also restrained autochthonous pancreatic cancer growth. These data distinguish the function of FAP(+) CASCs from other CASC subsets and provide support for further development of FAP(+) stromal cell-targeted therapies for the treatment of solid tumors.
Phase III study of irinotecan/5FU/LV (FOLFIRI) or oxaliplatin/5FU/LV (FOLFOX) ± cetuximab for patients (pts) with untreated metastatic adenocarcinoma of the colon or rectum (MCRC): CALGB 80203 preliminary results
Authors: A. Venook, D. Niedzwiecki, D. Hollis, S. Sutherland, R. Goldberg, S. Alberts, A. Benson, J. Wade, R. Schilsky, R. Mayer
Journal: Journal of Clinical Oncology (2006)

3509 Background: FOLFIRI or FOLFOX are 1st-line treatments (Rx) for MCRC. Cetuximab is an IgG1 Mab that targets the epidermal growth factor receptor (EGFR) and is approved as monotherapy or in combination with irinotecan in irinotecan-refractory, EGFR + pts with MCRC. CALGB 80203 randomized untreated MCRC pts to FOLFOX or FOLFIRI ± cetuximab (independent of EGFR status.) Methods: Pts with performance status 0–1 with tumor blocks available for EGFR analysis received either irinotecan 180 mg/m 2 over 1.5 hours (h) or oxaliplatin 85 mg/m 2 over 2h combined with LV 400 mg/m 2 over 2h and 5FU 400 mg/m 2 bolus, then 46–48h CI 5FU 2400 mg/m 2 q o w. Cetuximab dose: 400 mg/m 2 loading dose, then 250 mg/m 2 qw. Rx continued until progression or toxicity; subsequent Rx was not mandated although information was collected on such rx. Accrual goal was 2200 pts with intended 1° endpt of overall survival (OS). 80203 closed administratively in 1/05 (due to slow accrual) with 238 pts accrued. 2° endpts of response rate (RR), progression free survival (PFS), duration of R and toxicity are now able to be analyzed. Results: Accrual: FOLFIRI (A) - 61; FOLFIRI + cetuximab (B) - 59: FOLFOX (C) - 60; FOLFOX + cetuximab (D) - 58; approx median follow-up (f/u) is 12 months. RR (CR + PR, not all yet confirmed): A - 34%; B - 42%; C - 32%; D - 55%. RR was similar in the FOLFIRI or FOLFOX arms (A+B v. C+D; 38% v. 43%, p=0.44; chi-square) while C225 containing arms (B+D) v. non-C225 arms (A+C) had a superior RR (49% v. 33%; p=0.014, chi-square) It is too early to tell if there are differences in PFS, duration of response or OS. No significant differences in gr III diarrhea or any gr IV toxicities were seen. Conclusions: These results suggest that FOLFIRI and FOLFOX are similar in efficacy for pts with untreated MCRC and that adding cetuximab to either in1st-line Rx appears to increase response rates. PFS and duration of response do not appear different at this analysis. Further f/u and an analysis of prospective companion correlative studies may help to further clarify these results. [Table: see text]
Asynchronous breathing movements during slow controlled deep inspiration in chronic stroke patients
Authors: Illia Lima, Gardênia Ferreira, Tânia Campos, Rodrigo Melo, Maria Clara Góes, Rêncio Florêncio, Guilherme Fregonezi
Journal: European Respiratory Journal (2012)

Aim : To assess the asynchronous index of respiratory movements during the slow controlled deep inspiration in chronic stroke patient9s and healthy subjects.   Methods : Ten chronic stroke patients (experimental group - EG) (53.1 ± 9.2 years) and ten age-matched healthy subjects (control group, CG) (53.6 ± 9.4 years) were studied by Optoelectronic Plethysmography in 3 moments, quite breathing (QB) slow controlled deep inspiration (DeepI,3 series/10 repetitions) and recovery quite breathing (rQB). We measured the phase angle (PhAng), inspiratory phase relation (PhRIB), expiratory phase relation (PhREB) and time of the phase shift between the chest wall compartments.   Results : Both groups were similar during the QB and rQB. During DeepI series we observed a distinct behavior between EG and CG, in series 1 to 3 respectively. Time of the phase shift between the rig cage and abdominal compartments during the DeepI series were 0.23 ± 0.2s  vs.  0.15 ± 0.11s, 0.22 ± 0.2  vs . 0.11 ± 0.1s, 0.21 ± 0.2s  vs.  0.12 ± 0.1, p= 0.037.   Conclusion:  Slow controlled deep inspiration induces more asynchronous breathing movements in chronic stroke patients than healthy subjects.
Impaired migration of bone marrow mesenchymal stem cells in COPD
Authors: Konstantinos Karagiannis, Katerina Antoniou, Despoina Moraitaki, Anna Psaraki, Gianna Soufla, Christina Kalpadaki, Nikolaos Siafakas, Nikolaos Tzanakis
Journal: European Respiratory Journal (2013)

Chronic inflammatory response and defective tissue repair are major mechanisms of the pathogenesis of the COPD, indicating a potential therapeutic role for Mesenchymal Stem Cells (MSCs). Although MSC’s role in COPD pathophysiology is unknown, their anti-inflammatory and tissue repair characteristics may mediate certain disease’s features. Recent studies showed that SDF-1/CXCR4 axis plays a crucial role in MSCs migration and disturbances in that pathway may lead to a defective MSCs mobilization.

The aim of the current study is to probe disturbances in Bone Marrow MSCs (BMMSCs) migration through the SDF-1/CXCR4 pathway in COPD patients.

BMMSCs were studied in 15 COPD patients and 7 age and smoking matched, healthy control subjects. MSCs were obtained from iliac crest marrow aspirate and were cultured to passage 2. They were identified by their immunophenotypic characteristics and their potential to differentiate towards adipocytes/ osteocytes/ chondrocytes. Subsequently, mRNA expression of SDF-1 (transcripts 1 and 2) was measured in BMMSCs using real time PCR.

There was no significant difference in age, gender and smoking status between COPD patients and healthy smoking subjects. BMMSCs of COPD patients and healthy controls displayed normal immunophenotypic characteristics and differentiation potential. SDF-1tr1 and SDF-1tr2 were both decreased in BMMSCs of COPD patients compared to healthy controls in a statistically significant way (p=0.05, p=0.01 respectively).

Our results suggest that BMMSCs migration through SDF-1/CXCR4 axis is defective in COPD patients. A possible correlation between this disturbance and the abnormal tissue repair or the increased inflammatory response in COPD is a challenge for future research.
Discharge to Primary Care for Survivorship Follow-Up: How Are Patients With Early-Stage Breast Cancer Faring?
Authors: Cindy Railton, Sasha Lupichuk, Jennifer McCormick, Lihong Zhong, Jenny Jaeeun Ko, Barbara Walley, Anil A. Joy, Janine Giese-Davis
Journal: Journal of the National Comprehensive Cancer Network (2015)

Purpose: Oncology centers in public health systems often transfer routine follow-up of patients with early-stage breast cancer (BC) to primary care physicians because of the increasing numbers of survivors and evidence supporting the safety of this practice. After transfer of care, it is unknown how BC survivors fare with treatment and surveillance goals, and whether they have unmet needs for access to specialist care. This study conducted in a sample of women in Alberta, Canada, examined adherence with follow-up guidelines, symptoms, and need for a telephone-based survivorship clinic. Methods: Through the Alberta Cancer Registry, we randomly invited women with stage I–III invasive BC (N=960) to participate. Of those, 272 responded, and 240 consented to a structured telephone interview and chart review. Results: Women adhered well to follow-up guidelines for mammogram, but less so for clinical examination and endocrine therapy (ET). However, most patients reported ongoing bothersome symptoms, which tended to be higher in those not on ET. More than one-third of patients reported ongoing needs (managing weight, side effects, exercise adherence, and psychosocial health). Younger, fatigued or depressed, nonurban women not on ET reported the most need for a telephone clinic. Conclusions: Adherence with follow-up goals (examination, mammography, ET) was better than expected. Despite this, interest in a telephone survivorship clinic was high. Perceived needs included symptom management plus support for lifestyle behavior change. Medical follow-up needs might be well-met by discharge to primary care. However, high levels of ongoing symptoms and psychosocial needs would suggest that telephone-based survivorship clinics, psychosocial and exercise interventions, or transition programs might benefit the survivorship experience of patients with BC.
Lipoprotein Lipase
Authors: Jeffrey S. Flier, Lisa H. Underhill, Robert H. Eckel
Journal: New England Journal of Medicine (1989)

LIPOPROTEIN lipase, a hydrolytic enzyme produced by many tissues, is rate-limiting for the removal of lipoprotein triglycerides from the circulation. It also has distinct roles in many normal tissues, as well as an important role in certain metabolic diseases, including obesity. More than 40 years ago, Hahn noticed that intravenous heparin totally cleared diet-induced lipemia in dogs.1 The addition of heparin to plasma in vitro did not reproduce this effect, suggesting that the causative agent was released into plasma by heparin in vivo. This factor, ultimately identified as a triglyceride lipase, was activated in the presence of high-density lipoproteins (HDLs) . . .
Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck: a Southwest Oncology Group study.
Authors: A A Forastiere, B Metch, D E Schuller, J F Ensley, L F Hutchins, P Triozzi, J A Kish, S McClure, E VonFeldt, S K Williamson
Journal: Journal of Clinical Oncology (1992)

PURPOSE The Southwest Oncology Group (SWOG) conducted a randomized comparison of cisplatin plus fluorouracil (5-FU) and carboplatin plus 5-FU versus single-agent methotrexate (MTX) in patients with recurrent and metastatic squamous-cell carcinoma (SCC) of the head and neck. The primary objective was to compare separately the response rates of each combination regimen to standard weekly MTX. PATIENTS AND METHODS Two hundred seventy-seven patients diagnosed with SCC of the head and neck were randomized to one of three treatments: (1) cisplatin 100 mg/m2 intravenously (IV) on day 1 and 5-FU 1,000 mg/m2 per day for a 96-hour continuous infusion repeated every 21 days; (2) carboplatin 300 mg/m2 IV on day 1 and 5-FU 1,000 mg/m2 per day for a 96-hour continuous infusion repeated every 28 days; and (3) MTX 40 mg/m2 IV given weekly. RESULTS All three treatment regimens were well tolerated. However, both hematologic and nonhematologic toxicities were significantly greater with cisplatin plus 5-FU compared with MTX (P = .001). Toxicity from carboplatin plus 5-FU was intermediate compared with the other regimens. The complete and partial response rates were 32% for cisplatin plus 5-FU, 21% for carboplatin plus 5-FU, and 10% for MTX. The comparison of cisplatin plus 5-FU to MTX was statistically significant (P less than .001), and the comparison of carboplatin plus 5-FU to MTX was of borderline statistical significance (P = .05). Median response durations and median survival times were similar for all three treatment groups. Logistic regression models showed that only treatment assigned was associated significantly with response (P = .001). Cox proportional hazards models indicated that only performance status was associated significantly with survival (P less than .01). CONCLUSIONS We conclude that combination chemotherapy resulted in improved response rates but was associated with an increased toxicity and no improvement in overall survival. Therefore, new treatments that may alter the course of disease in recurrent head and neck cancer patients still need to be identified.