tbuckley/cabot-search huggingface dataset:
Inhibitory Effect of Betel Nut Extracts on Endogenous Nitrosation in Humans&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Hans F. Stich, Hiroshi Ohshima, Brigitte Pignatelli, Jocelyne Michelon, Helmut Bartsch
Journal: JNCI Journal of the National Cancer Institute (1983)

Extracts of betel nut (Areca catechu) were tested for their capacity to inhibit the endogenous formation of nitrosamines by measurement of the amount of urinary N-nitroso-L-proline (NPRO) following ingestion of sodium nitrate (300 mg) and L-proline (300 mg) by 2 volunteers. A water extract of the dried nuts, an ether extract containing mainly (+)-catechin and (-)-epicatechin, and a caffeine-precipitated n-butyl alcohol extract containing primarily proanthocyanidins (tannins) strongly reduced the endogenous formation of NPRO. An average of 14.7 and 10.9 micrograms NPRO (8 expts per individual) was excreted in the urine of the 2 volunteers over a 24-hour period following the intake of sodium nitrate and L-proline. The water extract and the proanthocyanidin (tannin)-containing extract, both of which contain the dose equivalent of one-quarter of a nut, reduced the excreted NPRO to background levels, which varied from 0.5 to 3.6 micrograms and from 0.6 to 2.1 micrograms (6 expts) in 24-hour urine samples from the 2 volunteers. These results may exemplify the way in which naturally occurring phenolics, which are ingested daily in relatively large quantities, could affect the endogenous formation of carcinogenic nitrosamines.
Critical Care in Resource-Restricted Settings
Authors: Arjen M. Dondorp, Shivakumar S. Iyer, Marcus J. Schultz
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Error minimization strategy in clinical and translational studies (CTS) through the development of a data management routine (DMR)
Authors: I. Á. Small, D. B. Olmedo, D. Ramalho, J. R. Lapa e Silva, C. G. Ferreira
Journal: Journal of Clinical Oncology (2008)

17567 Background: Clinical studies are the basis for the decision making process in health care. So quality assurance is mandatory. In CTS, of intervention or descriptive nature, the use of spreadsheets as databases is frequent among investigators favoring mistakes during data entry, mainly due to the matricial distribution of data, urging strategies to error minimization. Creation of complex systems by informatics technologists is viable, but expensive and unnecessary for medium and small sized studies. Otherwise, there are systems that allow databases to be built by non-programmers upon training. But the customization of those tools requires knowledge on CTS. Our aim wasto ensure the quality of CTS conducted at Instituto Nacional de Cancer of Brazil (INCA) through the development of a DMR. Methods: DMR is based upon MS Word 2003, MS Access 2003 and SPSS 13.0. Content variables were defined based upon studies running at Clinical and Translational Research Division (CTRD). For its development, 8 different studies (retrospective, molecular correlation, formal clinical trials) were used. Results: We generated a DMR based upon two pillars: a) a multi-step standard operational procedure that includes meetings with the investigators and data collection training; establishment of clinical report forms supported by guidelines for its use; a pivotal pilot data collection for identification and clarification of eventual misunderstanding; a revision of 30% of the cases enrolled; b) a backbone relational database customized for each study by health professionals trained in our service with a friendly easy-to-use interface and several validation rules to reduce data entry mistakes. It stores, organizes, encodes data, filters eligibility criteria, calculates data, generates reports to investigators for proper follow-up and generates spreadsheets easily imported by SPSS for statistical analysis. Since 2004 this routine has been applied to all the studies referred to CTRD, decreasing the intra-mural historical 15% mistake rate in patient inclusion to nearly 0%. Conclusions: In a low-cost and simple manner an effective DMR has been generated, decreasing the likelihood of mistakes with great impact on the quality of the data generated in CTS at INCA. No significant financial relationships to disclose.
Changes in Proto-oncogene Expression Associated With Reversal of Macrophage-Like Differentiation of HL 60 Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: G P Studzinski, Z S Brelvi
Journal: JNCI Journal of the National Cancer Institute (1987)

Prolonged exposure to 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] of 2 sublines (AB-2 and AB-26) of human pro-myelocytic HL 60 leukemia cells produced increased adherence of the cells to the culture substratum. Advantage was taken of this property to separate physically a population of cells highly enriched in macrophage-like forms. When these differentiated cells were placed in culture medium free of 1,25(OH)2D3, there was a rapid reversal of the features of the differentiated phenotype, monitored by the loss of α-naphthyl butyrate esterase activity and the loss of adherence to the substrate. The reversal was accompanied by the resumption of normal rates of DNA synthesis, mitosis, and reaccumulation of c-myc and c-myb transcripts. The levels of transcripts of oncogenes c-fos and c-fms, which became abundant in the phenotypically differentiated cultures, declined along with the loss of adhesiveness and reversion to more primitive myeloblasts forms. These changes in proto-oncogene expression became evident before cell proliferation resumed, thereby excluding the diluting effect of the outgrowth of undifferentiated cells. It is concluded that in this system there is no firm commitment to terminal, as opposed to early, differentiation in the great majority of the cells and that the expression of the monocytic maturation-associated genes c-fos and c-fms is down-regulated when macrophage-like cells dedifferentiate. This strengthens the case for an association between macrophage differentiation and the expression of oncogenes c-fos and c-fms.
In vitro susceptibility of mycobacterium bovis against moxifloxacin
Authors: Timo Weiss, Torsten Blum, Jens Kollmeier, Harald Mauch, Holger Russmann, Nicolas Schönfeld, Torsten T. Bauer
Journal: European Respiratory Journal (2011)

Introduction:  Mycobacterium bovis, the causative agent of bovine tuberculosis is also responsible for diseases in humans. To date there are no data available on the in vitro susceptibility of M. bovis strains to moxifloxacin, an established second line drug in the treatment of disease caused by M. tuberculosis.   Methods:  From M. bovis-positive cultures from BAL, sputum, pleural effusion or cerebrospinal fluid of 34 pts from the years 1993-2010, we retrospectively evaluated the sensitivity in vitro and the minimum inhibitory concentrations of moxifloxacin. Culturing and resistance testing was performed on solid Middlebrook agar plates.   Results:  Out of 34 tested M. bovis-positive cultures 33 showed a sensitivity to moxifloxacin at 2 or 4 mcg/ml. Only one strain showed resistance.   Conclusion:  Our study of a small group of patients shows a high sensitivity rate of moxifloxacin against M. bovis strains. Despite the absence of clinical treatment studies, we see a potential use of moxifloxacin as a second line drug, with regular ineffectiveness of the first-line drug pyrazinamide in M. bovis.
Association of concurrent AURKA and MYCN amplification in primary prostate adenocarcinoma with the development of lethal neuroendocrine prostate cancer (NEPC).
Authors: Himisha Beltran, Kyung Park, Scott T. Tagawa, Theresa Macdonald, David M. Nanus, Juan Miguel Mosquera, Mark A. Rubin
Journal: Journal of Clinical Oncology (2012)

120 Background: NEPC is an aggressive variant of prostate cancer that most commonly arises from prostate adenocarcinoma (PCA), with likely clonal origin. There is currently no effective therapy with most patients surviving &lt; 1 yr. Recent work identified overexpression and amplification of Aurora kinase A (AURKA) and N-myc (MYCN) in metastatic NEPC, evidence that they cooperate to directly induce a NE phenotype in PCA, and are targetable with Aurora kinase inhibitor therapy (AKI) (Beltran et al). NEPC xenografts demonstrate dramatic and preferential sensitivity to AKI therapy with complete reversal of NE marker expression. We evaluated primary prostate tumors of patients that later developed lethal NEPC for presence of AURKA and MYCN alterations. Methods: 226 primary PCA tumors were evaluated, of which 57 tumors were from patients with NEPC. 22 benign prostate and 57 metastatic NE carcinomas from prostate (38) or other primary site were also evaluated. Histology, immunohistochemistry (IHC), Fluorescence In Situ Hybridization (FISH) were performed and correlated with clinical variables (ie, Gleason, PSA, OS). Results: AURKA and concurrent MYCN amplification were identified by FISH in 75% of primary PCA of patients with NEPC (&gt; 95% cells). In contrast, in an unselected PCA cohort, AURKA and MYCN amplifications were identified in 5% of 169 cases. These results are independent of NE marker expression by IHC. In only one case did MYCN gain occur in absence of AURKA amplification. When metastatic NEPC was compared to primary PCA in same patient, there was 100% concordance of AURKA and MYCN amplification. In prostate tumors with mixed features, there was 94% concordance between NEPC and PCA. 0% benign prostate and 40% metastatic NEPC harbored AURKA and MYCN amplifications. Conclusions: AURKA and MYCN amplification occurs early and are nearly always concurrent despite separate chromosomes. Their presence in primary PCA identifies patients predisposed to the development of an aggressive lethal NEPC variant. These patients may benefit from early intervention with AKI therapy. Therefore, AURKA and MYCN amplification may be new prognostic and predictive biomarkers.
Time to abandon three-phase trials?
Authors: Andrew V Metcalfe
Journal: BMJ (2016)

Emmanuel and colleagues conclude that “concerns about the high risks of serious harm in non-oncology phase I trials do not seem to be borne out.”1 But, although the risk may be small, the consequences can be tragic.2 3 

Nevertheless, randomised controlled trials (RCTs) are widely considered the gold standard for clinical research, …
Preliminary results of treatment of Ewing's sarcoma of bone in children and young adults: six months of intensive combined modality therapy without maintenance.
Authors: J S Miser, T J Kinsella, T J Triche, M Tsokos, R Forquer, R Wesley, K Horvath, J Belasco, D L Longo, R Steis
Journal: Journal of Clinical Oncology (1988)

Thirty-one previously untreated patients with Ewing's sarcoma were treated with an intensive chemotherapy program of vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cyclosphosphamide (VADRIAC) in combination with radiation therapy to the primary site (greater than 50 Gy) and bone metastases (45 to 50 Gy). An intensified regimen with one further cycle of chemotherapy (VADRIAC), total body irradiation (TBI), and autologous bone marrow transplantation was given to patients with primary tumors of the pelvis, humerus, femur, and chest wall without metastases and to all patients with metastases at diagnosis. Patients with primary tumors of the distal extremity and other sites without metastases at diagnosis were treated on a less intensive chemotherapy regimen of VADRIAC without the intensification. Therapy was completed within 6 to 7 months in all patients. Thirteen patients had metastatic disease at diagnosis; only two of these had the lung as the sole site of metastatic disease. Eighteen patients had no evidence of metastatic disease at diagnosis: ten of these patients had tumors that arose in central axis and proximal extremity sites, and eight had tumors that arose in distal extremity and other sites. Thirty of the 31 patients achieved a complete remission, although two patients underwent amputation: one before chemotherapy and radiation and one after chemotherapy and radiation because of persistent local disease. Seventeen remain in their first complete remission at a median time on study of 30 months and a median time after completion of therapy of 24 months. Fourteen patients have relapsed (13) or progressed (1): ten in metastatic sites and four in the primary site. One patient had persistent local disease after radiation requiring amputation. Nine of the 13 patients with metastatic disease at diagnosis have relapsed compared with five of the 18 patients without metastatic disease. For the entire group, the actuarial survival is 78% (65% to 87%) at 30 months, and the actuarial disease-free survival is 58% (46% to 69%) at 30 months.
Abstract 17173: Reduced Bleeding Rates and Improved Clinical Outcomes With the Use of Radial Access in Octogenarians Undergoing Percutaneous Coronary Intervention
Authors: Jean P Dery, Helena Tizon-Marcos, Gerald Barbeau, Josep Rodes-Cabau, Stephane Rinfret, Eric Larose, Karen P Alexander, Sunil Rao, Can M Nguyen, Bernard Noel, Guy Proulx, Louis Roy, Onil Gleeton, Robert De Larochelliere, Olivier F Bertrand
Journal: Circulation (2010)
<italic>Brief Communication:</italic> Blood Group MN Antigens and Precursors in Normal and Malignant Human Breast Glandular Tissue<xref ref-type="fn" rid="fn2">2</xref>
Authors: G F Springer, P R Desai, I Banatwala
Journal: JNCI Journal of the National Cancer Institute (1975)

Blood group M and N active substances were demonstrated in human mammary gland tissue in both benign and malignant lesions. The precursor T (Thomsen-Friedenreich) antigen occurred only in cancerous tissue, where it was found regularly in the 15 gross cancers tested. The precursor Tn antigen also was found regularly in cancerous breast tissue; Both antigens were reactive in breasts with in situ carcinoma. The T antigen was not demonstrable in the 6 benign mammary glands studied; similarly, the Tn antigen was unmasked by sialidase treatment of healthy breast tissues. Anti-T antibody, present in all human sera, was severely depressed in many breast cancer patients compared to controls.
Abstract P112: Vivasure: An Oxygen-Carrying Lipid Emulsion for Resuscitation
Authors: Cuthbert O Simpkins, Juan Rodriguez
Journal: Circulation (2009)

Oxygen (O2) and mediators of hemorrhagic shock are lipophilic and should be preferentially taken up by lipid micelles(LM). Also, LM are colloids that can fill intravascular space. These facts sugge...
Safety and pharmacokinetics of intravenous VEGF Trap plus FOLFOX4 in a combination phase I clinical trial of patients with advanced solid tumors
Authors: M. Mulay, S. A. Limentani, M. Carroll, E. S. Furfine, D. P. Cohen, L. S. Rosen
Journal: Journal of Clinical Oncology (2006)

13061 Background: VEGF Trap is a potent angiogenesis inhibitor comprising portions of human VEGF receptor VEGFR1 (Flt-1) and VEGFR2 (KDR) extracellular domains fused to the Fc portion of human IgG. VEGF Trap binds VEGF and neutralizes all VEGF-A isoforms plus placental growth factor. FOLFOX4 is an approved chemotherapy regimen for the treatment of colorectal cancer. This study was designed to evaluate the safety and pharmacokinetics (PK) of VEGF Trap plus FOLFOX4 administered intravenously. Methods: Successive cohorts of 3–6 patients (pts) with advanced solid tumors received intravenous VEGF Trap plus FOLFOX4 every 2 weeks. Study endpoints included safety, PK, and immunogenicity. Antitumor activity was assessed by CT scan. Results: Six pts (3 male/3 female), median age 55 (25–74), ECOG PS 0/1/2: 2/4/0, with a variety of advanced solid tumors, including 2 gastric and 2 neuroendocrine tumors, have received a total of 19 cycles of VEGF Trap plus FOLFOX4 across 2 VEGF Trap dose levels (2.0 mg/kg, 4.0 mg/kg) to date. Three of these 6 pts had grade 3 AEs (hypertension [n=2], neutropenia [n=2]), which were manageable and reversible. However, no dose-limiting toxicities or grade 4 AEs have been encountered so far. Preliminary mean free VEGF Trap clearance was 17.1 mL/kg/day. No pts have developed anti-VEGF Trap antibodies. Conclusions: VEGF Trap may be safely combined with FOLFOX4 at the dose levels studied. Preliminary free VEGF Trap clearance did not differ significantly from that seen with single-agent exposure; chemotherapy PK analysis is pending. The maximum tolerated dose has not yet been reached, and dose escalation continues. Updated safety, pharmacokinetic, and preliminary efficacy results from this ongoing study will be presented. [Table: see text]
Prognostic Factors in Canine Mammary Cancer
Authors: W. Misdorp, A. A. M. Hart
Journal: JNCI Journal of the National Cancer Institute (1976)

From a follow-up study of dogs surgically treated for mammary cancer, ten characteristics were analyzed statistically with special reference to their association with prognosis (expressed as survival for 2 years). The interrelations among five of the characteristics were also tested. The histologic type (descending range in malignancy: sarcomas greater than simple carcinomas greater than complex carcinomas), mode of growth (highly infiltrating greater than moderately infiltrating greater than expansive), clinical stage of complex carcinomas (large tumors and/or tumors involving the skin or underlying tissue greater than small, well-defined tumors), and size (greater than 15 cm greater than 11-15 cm greater than 5-10 cm greater than 0-5 cm) were of definite prognostic importance. The histologic grade was of possible prognostic importance. Localization, type of surgical therapy (mastectomy, block-dissection), growth in lymph vessels, involvement of regional lymph nodes, and duration of symptoms before treatment were not important to prognosis. A comparison between the factors associated with the prognosis of canine and human mammary cancer showed many similarities. However, the involvement of regional lymph nodes, important in women, was not so in bitches.
Predictors of pathologic response and correlation with long-term outcomes in a trial of neoadjuvant concurrent paclitaxel radiation in locally advanced breast cancer (LABC).
Authors: S. Adams, S. C. Lymberis, A. B. Chakravarthy, D. V. Spicer, T. Hochman, M. Donach, J. D. Goldberg, R. Schneider, J. A. Pietenpol, S. Formenti
Journal: Journal of Clinical Oncology (2010)

589 Background: The association of hormone receptor (HR) status of the original tumor with pathologic response and correlation with DFS and OS from a multi-institutional trial of concurrent paclitaxel (P) and radiation (RT) are reported. Methods: 105 LABC patients were treated with neoadjuvant concurrent P and RT (P: 30 mg/m2 2x/week for 10-12 weeks; RT: 1.8 Gy daily to breast, axillary and supraclavicular LN weeks 2-7 to total of 45 Gy followed by a tumor boost of 14 Gy at 2 Gy/fraction). Pathologic response was defined as absence of invasive cancer in breast and LN (pCR) or persistence of less than 10 microscopic foci of invasive cancer in breast or LN (pPR). Logistic regression methods were used to predict response status, logrank tests and Cox proportional hazards methods to evaluate DFS and OS in relation to HR status and pathologic response. Results: Pathologic response (pCR+pPR) for the entire cohort was achieved in 36/105 patients (34%, 95% CI: 25-44%). For all patients, lack of a pathologic response conveyed 4.4 times greater death rate than for pathologic responders (95% CI 1.5-12.7). Nonresponders have a median survival time of 84 months; median not reached for responders. A significantly greater rate of pathologic response occurred in patients with HR negative cancers compared with HR positive cancers (p < 0.001): 54% (95% CI 39-69%) compared to 18% (95% CI of 9-30%). HR status was the only predictor of pathologic response after concurrent P-RT. As expected, HR negative tumors had a worse prognosis than HR positive ones; this feature remained despite the achievement of a pathologic response. However, pathologic response and HR status jointly predicted DFS (likelihood ratio p < 0.001). The clinical benefit from achieving a pathologic response was most pronounced in patients with HR negative tumors with a reduction in recurrence or death rate of 75% as compared with HR negative nonresponders. Conclusions: Conclusions: HR status is highly predictive of response to neoadjuvant concurrent paclitaxel and radiation; more than half of the patients with HR negative tumors achieved a pathologic response, which translates into superior DFS and OS. No significant financial relationships to disclose.
Risque de sténose après dissection sous-muqueuse de larges néoplasies rectales
Journal: Endoscopy (2015)

Le développement de la technique de dissection sous-muqueuse (DSM) a rendu possible la résection de lésions circonférentielles rectales. Ce geste peut néanmoins se compliquer de sténose cicatricielle. L’objet de cette étude est d’analyser la fréquence et les facteurs de risques de survenue d’une sténose qui sont peu décrits dans la littérature.