tbuckley/cabot-search huggingface dataset:
An experimental model of elastase and cigarette smoke- induced emphysema in mice
Authors: Rubia Rodrigues, Alyne Riane, Juliana Lourenço, Clarice Olivo, Petra Arantes, Francine Almeida, Mílton A. Martins, Fernanda D.T.Q.S. Lopes
Journal: European Respiratory Journal (2014)

Aims:  Although, the cigarette smoke (CS) induced models appear to best represent human emphysema ,an important limitation of these models is that no matter how long animals are exposed, the resulting emphysema is mild. Considering that the mostly accepted hypothesis to explain the emphysema development is the protease-antiprotease imbalance, the porcine pancreatic elastase (PPE) instillation is extensively used to induce severe emphysema in rodents depending on dose in short time.  Methods:  C57BL / 6 mice were divided into four groups: Control, Elastase, Smoke and Smoke/Elastase. The Smoke/Elastase animals group received an intranasal instillation of PPE (0.33 IU) and exposed to cigarette smoke for two months. The control group received the same treatment with NaCl 0.9 %. Animals were exposed to CS for 30min, 2 times / day, 5 days a week .  After 2 months,we performed the respiratory mechanics assessment, inflammatory profile analysis in BALF and morphometry measurements to quantify the mean linear intercept (Lm); positive cells for MMP-12 and MAC-2  Results:  We observed functional changes with decreased tissue elastance (Htis) in Smoke/Elastase group compared to other experimental groups, with an increased number of total cells in BAL (with a predominance of macrophages), increased LM and positive cells for MAC -2 and MMP-12 in the airways and lung parenchyma, respectively. Conclusions:  Our results suggest that 2 months was sufficient to induce emphysema in mice exposed to CS that received previously a low-dose of PPE instillation. The alveolar enlargement evaluated by LM measurements showed similar values to the PPE-induced models studies.  Supported by FAPESP, LIMHC-FMUSP, CNPq, Brazil.
Induction of Lymphoma and Associated Xenotropic Type C Virus in C57L Mice by Whole-Body Irradiation2
Authors: Paul Arnstein, John L. Riggs, Lyndon S. Oshiro, Robert J. Huebner, Edwin H. Lennette
Journal: JNCI Journal of the National Cancer Institute (1976)

Adult C57L mice received sublethal whole-body X-irradiation. Between 3 and 11 months later, 5 of the 7 exposed mice developed histopathologically confirmed malignant lymphomas (lymphocytic type) that primarily involved the thymus. The lymphomas were readily transplantable to other C57L mice of any age, which developed fetal lymphomatous involvement; the tumor cells could also be propagated in tissue culture. A xenotropic murine type C virus (MuX) was isolated from the cultured lymphoma cells after cocultivation with a permissive dog line. MuX activity was demonstrated by electron microscopy, complement fixation, indirect fluorescent antibody, infectivity, and genome rescue.
Phase I and Pharmacologic Study of Docetaxel and Irinotecan in Advanced Non–Small-Cell Lung Cancer
Authors: Noriyuki Masuda, Shunichi Negoro, Shinzoh Kudoh, Takahiko Sugiura, Kazuhiko Nakagawa, Hideo Saka, Minoru Takada, Hisanobu Niitani, Masahiro Fukuoka
Journal: Journal of Clinical Oncology (2000)

PURPOSE: We conducted a phase I trial of docetaxel, a new antimicrotubule agent, combined with irinotecan (CPT-11), a topoisomerase I inhibitor. The aim was to determine the maximum-tolerated dose (MTD) of docetaxel combined with CPT-11, as well as the dose-limiting toxicities (DLTs) of this combination in advanced non–small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Thirty-two patients with stage IIIB or IV NSCLC were treated at 4-week intervals with docetaxel (60 minutes, day 2) plus CPT-11 (90 minutes, days 1, 8, and 15). The starting doses of docetaxel/CPT-11 were 30/40 mg/m 2 , and doses were escalated in 10-mg/m 2 increments until the MTD was reached. RESULTS: The MTD of docetaxel/CPT-11 was 50/60 mg/m 2 (level 5A), or 60/50 mg/m 2 (level 5B). Neutropenia and diarrhea were the DLTs. CPT-11 did not affect the pharmacokinetics of docetaxel. There were 11 (37%) partial responses among 30 patients. The median survival time was 48 weeks, and the 1-year survival rate was 44.9%. CONCLUSION: The combination of docetaxel and CPT-11 seems to be active against NSCLC, with acceptable toxicity. The recommended dose for phase II studies is 50 mg/m 2 of CPT-11 (days 1, 8, and 15) and 50 mg/m 2 of docetaxel (day 2) administered every 28 days.
Effect of the Level of Dietary Protein on Vascular Repair in Wounds
Authors: Harold W. Chalkey, Glenn H. Algire, Harold P. Morris
Journal: JNCI Journal of the National Cancer Institute (1946)

Effect of the Level of Dietary Protein on Vascular Repair in Wounds Get access Harold W. Chalkey, Harold W. Chalkey senior physiologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Glenn H. Algire, Glenn H. Algire senior assistant surgeon National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Harold P. Morris Harold P. Morris senior nutrition chemist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 6, Issue 6, June 1946, Pages 363–372, https://doi.org/10.1093/jnci/6.6.363 Published: 01 June 1946
Influence of statin treatment on cancer mortality in COPD patients: Retrospective observational cohort study
Authors: Perrine Crequit, Isabella Annesi Maesano, Christos Chouaid, Gilles Hejblum
Journal: European Respiratory Journal (2012)

Background:

The anti-inflammatory and immunomodulatory statin properties have been suggested for preventing cancer development in patients with Chronic Obstructive Pulmonary Disease (COPD). However, the effect of statin on cancer mortality in COPD patients is poorly documented. The study endpoint is to evaluate the impact of statin on cancer mortality of COPD patients.

Methods:

Based on a large pharmaceutical French database of the North area, a retrospective cohort study was conducted in order to evaluate the effect of statin on cancer mortality in COPD patients. Analysis, based on a Cox proportional hazards model with statin exposure handled as a time-dependent variable, included the 66 429 individuals 40 years old or more who had at least one pharmaceutical dispensation between 01/01/2000 and 05/11/2007. In this cohort, 9531 COPD patients were identified; 18.1% of COPD patients were considered exposed to statin.

Findings:

The overall death rate of COPD patients is 40.8%. The various causes accountable for COPD patients' death were: cardiovascular diseases for 33.7%, respiratory diseases for 33.7% and cancer for 24.8%. Statin treatment was significantly associated with a decrease of cancer mortality in COPD patients with estimates (hazard ratio [95% CI], p value) at 0.586 [0.465-0.739], p=<0.0001.

Interpretation:

It seems that statin delivery to COPD patient reduces the cancer death rate. However the result has to be checked out by prospective randomized studies.
Utility of total body FDG PET/CT imaging in the initial staging of soft-tissue sarcoma
Authors: D. Roberge, M. Hickeson, M. Charest, R. E. Turcotte
Journal: Journal of Clinical Oncology (2009)

10531 Background: Soft-tissue sarcoma spreads predominantly to the lung. It is currently unclear how often PET scan will detect metastases not already obvious by chest imaging or clinical examination. Methods: Soft-tissue sarcoma cases were identified retrospectively. Ewing's sarcoma, rhabdomyosarcoma and GIST tumors were excluded as were patients imaged for follow-up, response assessment or recurrence. Patients all had had a diagnostic chest CT scan as part of their staging. Directed studies were requested to follow-up on abnormal findings in the clinical history or physical examination. All charts and pre-treatment imaging were reviewed retrospectively. Results: From 2004 to 2008, 75 patients met the criteria for this review. These 75 patients had total body FDG-PET/CT imaging on routine initial staging of their sarcoma. The median age was 51. In 21% of cases, the primary tumor had been removed by excisional biopsy or unplanned excision prior to staging. 97% of the previously unresected primary tumors were FDG avid (SUV ≥ 2). 81% of tumors were high-grade (FNCLCC Grade 2–3). The primary tumor was stage T2b in 68% of cases. The most common primary site was the lower extremity (55%). The most common pathological diagnoses were: leiomyosarcoma (21%), liposarcoma (19%) and synovial sarcoma (17%). At the end of staging, 17% of patients were considered to have metastatic disease. PET scans were negative for distant disease in 64/75 cases. Seven of these 64 cases had metastatic disease on chest CT (negative predictive value 89%). 8 PET scans were positive - of these, 4 patients were already known to have metastases, 2 were pathologically proven false positives and 1 was a new finding of a pulmonary metastasis (sensitivity 46%). Three patients had indeterminate PET scans (subsequently none developed metastatic disease). Two incidental benign parotid tumors were found. In total, only 1 patient was upstaged by the PET imaging (1.3%). In addition, PET did not alter management of patients already know to have M1 disease (no new organ sites identified). Conclusions: Although PET scans may be of use in specific circumstances, routine use of FDG PET imaging for detection of metastatic disease as part of the initial staging of soft-tissue sarcoma adds little to chest CT scanning and is unlikely to alter management. No significant financial relationships to disclose.
Association between PSA kinetics and cancer-specific mortality in patients with localised prostate cancer: analysis of the placebo arm of the SPCG-6 study
Authors: F.B. Thomsen, K. Brasso, K.D. Berg, T.A. Gerds, J.-E. Johansson, A. Angelsen, T.L.J. Tammela, P. Iversen
Journal: Annals of Oncology (2015)
Importance of Thyroid Hormone and Testosterone in the Induction of Carcinoma and Cirrhosis of the Liver in Female Wistar Rats Ingesting N-2-Fiuorenyldiacetamide23
Authors: Melvin D. Reuber
Journal: JNCI Journal of the National Cancer Institute (1966)

Female Wistar rats were given 0.025 percent N-2-fluorenyldiacetamide, a hepatocarcinogen, in the diet, and the relationship of the thyroid to the adrenals and to sex and sex hormones in carcinogenesis and cirrhosis of the liver was evaluated. Intact, thyroidectomized, adrenalectomized, castrated, thyroidectomized-castrated, and adrenalectomized-castrated female animals fed the carcinogen-containing diet failed to develop tumors or cirrhosis of the liver. Exogenous thyroid hormone did not induce hepatic carcinomas in any of the animals. Testosterone propionate was not effective when administered alone to thyroidectomized or thyroidectomized-castrated animals, but when given simultaneously with thyroid hormone, tumors and cirrhosis of the liver did develop in female animals. Thyroid hormone and testosterone propionate are necessary for the induction of carcinomas and cirrhosis of the liver in both male and female rats.
Establishment and Characterization of an Estrogen-Producing Human Ovarian Granulosa Tumor Cell Line
Authors: I Ishiwata, C Ishiwata, M Soma, N Kobayashi, H Ishikawa
Journal: JNCI Journal of the National Cancer Institute (1984)

Cells designated HTOG and HTOT were established by long-term culture from a human ovarian granulosa cell and a theca cell tumor, respectively. The HTOG line grew well forming colonies and multilayered rapidly without contact inhibition; serial passages of HTOG were performed over 100 times successively within 25 months. HTOG were spindle cells, polygonal or spherical in shape, revealed neoplastic and pleomorphic features, and produced estrone (E1 and 17β-estradiol (E2). The chromosome number varied considerably and showed hyperploidy; the modal chromosome number was in the hypertriploid-tetraploid range. When HTOG cells were heterotransplanted into the subcutis of BALB/c nude mice, they produced a sarcomatous diffuse type of granulosa cell tumors. In contrast, HTOT cells grew slowly while forming monolayers and underwent five successive passages in about 100 days, but a theca cell tumor line could not be established. HTOT cells were fibroblastic in shape and also produced E1 and E2. The majority of the cells showed diploidy and karyologic normality.
Helium or nitrogen: That's the question?
Authors: Lilianne Martin, Silvia Cornelussen, Paul Bongaerts, Chris van der Grinten
Journal: European Respiratory Journal (2014)

There is growing interest in the nitrogen washout technique, especially for cystic fibrosis patients. The aim of our study was to compare conventional FRC measurements (body box and He washin) with 2 commercially available nitrogen washout devices .

Methods: 17 healthy subjects (13F/4M, 25-55 years) performed FRC measurements with He washin and body box (Jaeger) which were compared to 2 nitrogen washout devices (NDD easyone Pro lab and Cosmed Quark PFT). All measurements were done twice. If FRC did not reproduce within 10% a third measurement was done. No fixed breathing pattern was imposed. From all measurements we determined TLC, FRC, RV and VC and from washouts also LCI (Lung Clearance Index).

Results: All VC values were in close range. Compared with He washin FRC NDD was significantly lower and for TLC and RV both washout systems showed lower results. LCI values were for both systems higher than predicted, while the smallest difference was for NDD.

Conclusions: FRC measurements using NDD device were significantly lower than other FRC measurements with concomitant decreases in RV and TLC. The lower values for TLC and RV using the Cosmed device may be due to separation of VC and FRC measurements. Both devices use indirect measurement of FN2 which may deviate especially at low FN2 values.

View this table:

average values for different devices ± SD. * indicates P<0.001
Computerized tomography measured liver fat is associated with low levels of N-terminal pro-brain natriuretic protein (NT-proBNP). Multi-Ethnic Study of Atherosclerosis
Authors: Otto A. Sanchez, Mariana Lazo-Elizondo, Irfan Zeb, Russell P. Tracy, Ryan Bradley, Daniel A. Duprez, Hossein Bahrami, Carmen A. Peralta, Lori B. Daniels, João A. Lima, Alan Maisel, David R. Jacobs, Mathew J. Budoff
Journal: Metabolism (2016)
Secondary hyperparathyroidism and vitamin D receptor binding to vitamin D response elements in rats with incipient renal failure.
Authors: B P Sawaya, N J Koszewski, Q Qi, M C Langub, M C Monier-Faugere, H H Malluche
Journal: Journal of the American Society of Nephrology (1997)

The pathogenesis of secondary hyperparathyroidism in early renal failure is poorly understood. In the study presented here, parathyroid hormone and GFR in rats with mild renal failure of various durations are evaluated. Parathyroid hormone increased significantly 3 days after nephrectomy and peaked at 2 wk, despite reduction in GFR of < 50%. Parathyroid hormone remained elevated, but there was no difference in serum levels of calcium, phosphorus, and calcitriol between the nephrectomized and sham-operated rats. There were also no differences in both intestinal and kidney vitamin D receptor concentrations between the two groups. Histomorphometric analysis of bone at 6 wk revealed significant increase in osteoid thickness, osteoblast number, erosion surface with osteoclasts, and erosion depth. Employing electrophoretic mobility shift assay, we consistently observed a significant reduction in kidney calcitriol-receptor complex binding to mouse osteopontin vitamin D response element (-70.2 +/- 4.9%, P < 0.001). Western blot analysis also revealed a significant reduction in at least one retinoid X receptor isoform. In conclusion, biochemical and histological evidence of secondary hyperparathyroidism develops in rats with mild renal failure, despite normal calcium, phosphorus, calcitriol, and vitamin D receptor concentrations. These rats also have evidence of reduced renal vitamin D receptor binding to nuclear response elements. This finding, possibly an important early factor in the pathogenesis of secondary hyperparathyroidism, could also play a role in the development of compensatory renal growth of the remnant kidney.
Lumiliximab (anti-CD23 antibody) mediates apoptosis and antitumor activity in chronic lymphocytic leukemia (CLL) cells and CD23<sup>+</sup> lymphoma cell lines
Authors: N. Pathan, J. Byrd, K. Hariharan, P. Chu, A. Molina
Journal: Journal of Clinical Oncology (2007)

3039 Background: Given the success of treating CLL with antibody therapies, interest in those directed at alternative B-cell antigens remains high. Lumiliximab is a chimeric macaque and human anti-CD23 monoclonal antibody whose antigen is expressed on almost all CLL cells. Methods: We examined lumiliximab’s ability to mediate direct apoptosis, antibody-dependent cellular cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC) against primary CLL cells and CD23+ B-cell lines. Apoptosis was measured with a flow-cytometry based assay for active caspase-3. ADCC was determined by 51 Cr-release assay. CDC assays were performed in the presence of 30% autologous plasma from patients and quantified by propidium iodide staining. Western blotting analysis was used to monitor protein expression before and after treatment with lumiliximab. The CD23+ human lymphoma SKW6.4 cell line was used for in vivo evaluation of lumiliximab in a disseminated human lymphoma model. Results: Lumiliximab mediates apoptosis, ADCC, and CDC in CD23+ B-cell lines. However, in primary CLL cells, the primary mechanism of cell killing appears to be mediated via apoptosis. Apoptosis induced by lumiliximab occurs mainly through the intrinsic pathway used by other CLL therapies. Lumiliximab decreased expression of Bcl-2 and XIAP and inhibited Akt activation in CLL cells. Lumiliximab when combined in vitro or in vivo with rituximab or fludarabine effectively mediates synergistic cytotoxicity against primary CLL cells and CD23+ B-cell lines. Significant antitumor activity was also observed with lumiliximab vs a control antibody in a SCID mouse model of human B-cell lymphoma (P &lt;.01). More importantly, lumiliximab + rituximab or lumiliximab + fludarabine results in prolonged survival vs lumiliximab, rituximab, or fludarabine single-agent treatment. Conclusions: These results indicate that lumiliximab induces apoptosis by activating caspases and downregulating antiapoptotic proteins, and suggest that in combination with rituximab or chemotherapy, lumiliximab synergistically enhances antitumor activity in CLL or other B-cell malignancies in which this antigen is overexpressed. No significant financial relationships to disclose.
Clinical Interest of Digital Pcr for Routine Detection of Circulating Dna in Metastatic Colorectal Cancer
Authors: D. Sefrioui, C. Vasseur, R. Sesboué, F. Blanchard, A. Gangloff, M. Baretti, L. Beaussire, F. Clatot, C. Dolfus, J. Sabourin, P. Michel, T. Frebourg, F. Di Fiore
Journal: Annals of Oncology (2014)
Role of conserved peptide in taurine transporter inactivation modulated by protein kinase C.
Authors: X Han, A M Budreau, R W Chesney
Journal: Journal of the American Society of Nephrology (1996)

Activation of protein kinase C (PKC) by the active phorbol ester 12-myristate 13-acetate (PMA, 100 nM) or phorbol-12, 13-dibutyrate (100 nM) reduced taurine uptake by 80% in oocytes given injections with cRNA from and expressing the Madin-Darby canine kidney cell taurine transporter pNCT. Inhibition of PKC by calphostin C or staurosporine increased taurine uptake by 20% and 400%, respectively. The inhibitory effect of PMA on taurine uptake was blocked by calphostin C, a specific inhibitor of PKC. Modulation by PMA mainly affected the apparent affinity K(m) (from 5.6 microM to 18.1 microM) with minimal effect on the maximal velocity (25% decrease) of the transporter. A polyclonal antibody (AbS4) directed against a conserved intracellular segment (S4) of the Madin-Darby canine kidney cell taurine transporter enhanced taurine uptake by pNCT cRNA-treated oocytes. The effect of AbS4 was blocked by incubation with the corresponding peptide antigen. Preimmune IgG and peptide antigen had no effect on taurine transporter activity expressed in oocytes. Modulation seemed to occur through phosphorylation of a consensus PKC site located on segment S4 of the transporter, because downregulation of the transporter by PMA (100 nM) was abolished by preinjection of AbS4 (12 ng/ oocyte). In contrast, downregulation of the transporter by PMA could not be restored by AbS4 when pNCT-expressing oocytes were pretreated with PMA (50 nM). In conclusion, the peptide segment recognized by this antibody appears to participate directly in taurine transporter inactivation that is modulated by PKC phosphorylation.
Protective effect of pulmonary surfactant on elastase-induced emphysema in mice
Authors: CJ Otto-Verberne, AA Ten Have-Opbroek, C Franken, J Hermans, JH Dijkman
Journal: European Respiratory Journal (1992)

The aim of this study was to obtain some evidence of a protective role for pulmonary surfactant in the pathogenesis of emphysema. Firstly, we developed a quick and easy method to treat mice with a series of intratracheal instillations. Subsequently, three groups of mice were treated as follows: two groups received intratracheal instillations with pancreatic elastase (1.8 mg.kg-1 BW) followed after 3, 48 and 96 h in one group (El/Surf group) by intratracheal administration of surfactant (100 mg phospholipid.kg-1 BW), and in the other group by instillations with saline (El/s group). The third group of control mice was treated with saline followed by three doses of surfactant (s/Surf group). After eight weeks, the mice were killed and emphysema was measured by calculating the mean linear intercepts (Lm) of airspaces. The Lm values in the different groups were statistically tested for differences by the Mann-Whitney test. Instillation of pancreatic elastase (El/s group) resulted in an evenly distributed increase in Lm compared with the control group. Administration of surfactant in elastase-treated mice (El/Surf group) resulted in a statistically significant inhibition of airspace enlargement. Although the Lm in the El/Surf group was still higher than in the control group, analysis of histograms of Lm values per field of examination revealed that the Lm distribution in the former group was similar to that of the s/Surf group. The El/s group, on the contrary, showed the presence of many fields with enlarged air spaces. Repeated instillations with saline and/or surfactant had no effect on the Lm.(ABSTRACT TRUNCATED AT 250 WORDS)