tbuckley/cabot-search huggingface dataset:
Effects of 17 β-Estradiol and Diethylstilbestrol on Concurrent Development of Hepatic, Mammary, and Pituitary Tumors in WF Rats: Evidence for Differential Effect on Liver&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: C Sumi, K Yokoro, R Matsushima
Journal: JNCI Journal of the National Cancer Institute (1984)

17 beta-Estradiol [(E2) CAS: 50-28-2; estradiol] and diethylstilbestrol [(DES) CAS: 56-53-1; alpha-alpha'-diethyl-4,4'-stilbenediol] were compared to determine their tumor-inducing abilities in tissue. After castration at 40 days of age, inbred male WF rats received a pellet of either 5.0 mg DES or 5.0 mg E2. Approximately half of the rats that had been given DES or E2 were further given at 50-55 days of age 5.0 mg N-nitrosobutylurea [(NBU) CAS: 869-01-2; 1-butyl-1-nitrosourea] in their drinking water each day for 30 days. None of the castrated rats given E2 alone developed hepatic tumors (HT). Even further addition of NBU did not elicit any HT. Conversely, E2 treatment as well as DES treatment, whether administrated alone or in combination with NBU, resulted in an increase in the incidence of pituitary tumors (PT) and in the mean pituitary weight. The data indicate that E2 was ineffective in inducing HT in castrated male rats, whereas E2 showed an ability to induce PT similar to that of DES. In addition, E2 was not as able to induce as many mammary tumors as DES was able to induce. There was no significant synergism between E2 and NBU in contrast to that between DES and NBU in mammary tumorigenesis, whereas these two estrogens had a similar effect in causing an increase in the pituitary weight. This study, therefore, suggests that the carcinogenic effect of estrogens may not always correlate with their estrogenic effect and further confirms the noninvolvement of prolactin in hepatic tumorigenesis.
Monotherapy Administration of Sorafenib in Patients With Non–Small Cell Lung Cancer (MISSION) Trial
Authors: Luis Paz-Ares, Vera Hirsh, Li Zhang, Filippo de Marinis, James Chih-Hsin Yang, Heather A. Wakelee, Takashi Seto, Yi-Long Wu, Silvia Novello, Erszébet Juhász, Osvaldo Arén, Yan Sun, Thomas Schmelter, Teng Jin Ong, Carol Peña, Egbert F. Smit, Tony S. Mok
Journal: Journal of Thoracic Oncology (2015)

Sorafenib monotherapy has shown benefits in phase II trials as third-/fourth-line treatment in patients with non-small-cell lung cancer (NSCLC).The phase III, multinational, double-blind, placebo-controlled Monotherapy admInistration of Sorafenib in patientS wIth nOn-small-cell luNg cancer (MISSION) trial randomized patients with advanced relapsed/refractory NSCLC, following two or three prior treatment regimens, to sorafenib 400 mg twice a day (n = 350) or matching placebo (n = 353) plus best supportive care. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS) and time to progression. Epidermal growth factor receptor and KRAS mutation status was analyzed in archival tumor and/or circulating tumor DNA from blood samples obtained during screening.Median OS was similar in the sorafenib and placebo groups (8.2 versus 8.3 mo; hazard ratio [HR], 0.99; 95% confidence interval [CI], 0.84-1.17; p = 0.47). Median PFS (2.8 versus 1.4 mo; HR, 0.61; 95% CI, 0.51-0.72; p < 0.0001), and time to progression (2.9 versus 1.4 mo; HR, 0.54; 95% CI, 0.45-0.65; p < 0.0001) were significantly greater with sorafenib than with placebo. Among the 89 patients with epidermal growth factor receptor mutations, OS (13.9 versus 6.5 mo; HR, 0.48; 95% CI, 0.30-0.76; p = 0.002) and PFS (2.7 versus 1.4 mo; HR, 0.27; 95% CI, 0.16-0.46; p < 0.001) were significantly higher with sorafenib than placebo. PFS was significantly longer with sorafenib than placebo in patients with either wild-type or mutated KRAS, but OS was similar. Common drug-related adverse events were rash/desquamation, diarrhea, and fatigue, consistent with the safety profile of sorafenib.Third-/fourth-line sorafenib therapy did not significantly increase OS in patients with relapsed/refractory NSCLC, despite significantly increasing PFS.
PTU-051 Does high magnification compared with conventional magnification collagen proportionate area alter its sensitivity in assessing the amount of fibrosis in chronic liver disease?: Abstract PTU-051
Authors: L Andreana, G Isgrò, F Grillo, A Hall, A K Burroughs, A P Dhillon, T Luong
Journal: Gut (2010)

<h3>Introduction</h3> We have recently shown that CPA assessed in histological section can be used to quantify collagen 1 and has prognostic significance.2 CPA has been evaluated using 4× magnification image capturing, but this conventional CPA technique has limits in sensitivity such that pericellular fibrosis is not captured in these images. A more sensitive image capturing for CPA can validates the conventional CPA. <h3>Methods</h3> From a series of 250 trans-jugular liver biopsies in 115 patients transplanted for hepatitis C virus related cirrhosis, 20 slides were randomly selected. After staining with sirius red, they were analysed in random order by 4× (conventional) CPA and 20× (high magnification) CPA by two different authors. The data of previous studies correlating conventional CPA, Ishak score and hepatic venous pressure gradient (HVPG) have been matched with the values of the high magnification CPA. Data have been analysed using linear regression and logistic analysis as appropriate. <h3>Results</h3> High magnification CPA and conventional CPA had a good correlation, with a more strict correlation when considering overall fibrosis compared to that performed excluding pericellular fibrosis (R<sup>2</sup> 0.81 vs 0.79). Results of both CPA techniques are related to the Ishak stages, whereas only high magnification CPA shows significant correlation with the HVPG values in this small series (Abstract 011). <h3>Conclusion</h3> A more sensitive image capturing validates the conventional, 4× magnification CPA. Conventional CPA for the easy usability and clinical implications can become part of routine histological liver assessment. Moreover high magnification CPA appears to be an interesting tool to describe liver fibrosis with more details compared to the conventional one.
Tumor Progression in Nude Mice and Its Representation in Cell Culture&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: H Rubin, P Arnstein, B M Chu
Journal: JNCI Journal of the National Cancer Institute (1986)

Varying dilutions containing from 10(6) to 10(3) spontaneously transformed Balb/3T3 cells were inoculated into nude mice [N:NIH(S)II]. Less than half the mice inoculated with 10(3) cells developed tumors. The higher concentrations of cells produced visible tumors in all mice within 2-3 weeks, and these tumors grew rapidly to large sizes. Some tumors initiated by the lower concentrations of cells arose quickly, but others were greatly delayed in onset, then grew slowly, if at all, for several weeks before a rapid acceleration. The delayed acceleration can be considered a form of tumor progression. When first explanted into culture, cells from the early tumors multiplied somewhat more slowly than the parental cells that initiated the tumors, but narrowed the gap in a few weekly passages. By contrast, only a small fraction (less than or equal to 0.001) of cells from the longest delayed tumors could sustain multiplication in culture, although flow cytometry revealed them to have been a rapidly multiplying population when explanted. A relatively large fraction of these explanted tumor cells incorporated a 1-hour pulse of [3H]thymidine into DNA, although at a low rate. The shift to culture apparently slowed progress through the S-period of the cell cycle. The multiplication rate of cell populations from the delayed tumors increased in successive passages in culture. There was great heterogeneity in growth capacity among clones of the tumor cells. The growth rates of some clones declined to the point of extinction, those of others remained constant for several weeks, while those of still others steadily increased in growth rate. The low initial cloning efficiency of cells from the delayed tumors and the heterogeneity of growth rates among the clonable cells indicate that selection plays a major role in the increase of the growth capacity of the cell population. The steady increase in growth rates within clones suggests that physiological adaptation also contributes to the progressive growth of the tumor populations in culture. The results constitute a rationale for using the progressive growth of cells in culture as a model system for discriminating the types of cellular changes that underlie tumor progression.
Leukemic Stem Cell Quantification in Newly Diagnosed Patients With Chronic Myeloid Leukemia Predicts Response to Nilotinib Therapy
Authors: Noortje Thielen, Johan Richter, Matthias Baldauf, Gisela Barbany, Thoas Fioretos, Francis Giles, Bjørn-Tore Gjertsen, Andreas Hochhaus, Gerrit Jan Schuurhuis, Sieghart Sopper, Leif Stenke, Sarah Thunberg, Dominik Wolf, Gert Ossenkoppele, Kimmo Porkka, Jeroen Janssen, Satu Mustjoki
Journal: Clinical Cancer Research (2016)

Leukemic stem cells (LSCs) may harbor important resistance to tyrosine kinase inhibitors in chronic myelogenous leukemia (CML). We identified Philadelphia chromosome (Ph)-positive CD34(+)CD38(-) bone marrow cells (here denoted LSCs) and addressed their response-predictive value in patients with CML (n = 48) subjected to nilotinib in the ENEST1st trial (NCT01061177).Two flow cytometry-based cell sorting methods were used with multiparameter-directed CD45- (MPFC) and BCR-ABL1 probe-linked (FISH) identification of Ph-positive cells, respectively.We observed a positive correlation between the proportion of LSCs at diagnosis and established prognostic markers (blast count, spleen size, Sokal score, and hemoglobin). Conversely, a high LSC burden predicted for an inferior molecular response at 3 (MPFC and FISH), 6 (MPFC), 9 (FISH), and 15 months (FISH). During nilotinib therapy, the proportion of LSCs decreased rapidly. At 3 months, a median of only 0.3% LSCs remained among CD34(+)CD38(-) cells, and in 33% of the patients the LSC clone was not detectable anymore (FISH). The response kinetics was similar in LSC fractions as it was in the progenitor and unseparated bone marrow cell fractions.The proportion of LSCs at diagnosis, as analyzed by two independent methodologies, reflects the biology of the disease and appeared as a prognostic and response-predictive marker in patients with CML subjected to first-line nilotinib therapy. Clin Cancer Res; 22(16); 4030-8. ©2016 AACR.
NIH Scientists Identify Chemical DNA Signature of 5 Cancers
Authors: Julie A. Jacob
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Utilization management of mental health services by private third parties
Authors: G L Tischler
Journal: American Journal of Psychiatry (1990)

The author describes approaches to utilization management and the growth of this segment of the health care industry. Issues posed for the mental health field by introducing a third party as the arbiter of care include professional uncertainty and the discretionary behavior of practitioners and third parties, the availability of clinically appropriate alternative services, shifting of costs between the public and private sectors, safeguarding privacy, accountability and the integrity of the review process, financial risk versus professional responsibility, and the impact of utilization management on the outcome of care.
O-020 Quality-of-life results from RAISE: randomized, double-blind phase III study of FOLFIRI plus ramucirumab or placebo in patients with metastatic colorectal carcinoma after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine
Authors: R. Garcia-Carbonero, R. Obermannova, G. Bodoky, J. Prausova, T.-E. Ciuleanu, P. Garcia Alfonso, D. Portnoy, A. Cohn, E. Van Cutsem, K. Yamazaki, S.-E. Al-Batran, P. Rougier, A. Liepa, L. Yang, Y. Zhang, F. Nasroulah, S.-C. Chang, J. Tabernero
Journal: Annals of Oncology (2015)
Enhancing Cardiac Rehabilitation With Stress Management Training
Authors: James A. Blumenthal, Andrew Sherwood, Patrick J. Smith, Lana Watkins, Stephanie Mabe, William E. Kraus, Krista Ingle, Paula Miller, Alan Hinderliter
Journal: Circulation (2016)

Background— Cardiac rehabilitation (CR) is the standard of care for patients with coronary heart disease. Despite considerable epidemiological evidence that high stress is associated with worse health outcomes, stress management training (SMT) is not included routinely as a component of CR. Methods and Results— One hundred fifty-one outpatients with coronary heart disease who were 36 to 84 years of age were randomized to 12 weeks of comprehensive CR or comprehensive CR combined with SMT (CR+SMT), with assessments of stress and coronary heart disease biomarkers obtained before and after treatment. A matched sample of CR-eligible patients who did not receive CR made up the no-CR comparison group. All participants were followed up for up to 5.3 years (median, 3.2 years) for clinical events. Patients randomized to CR+SMT exhibited greater reductions in composite stress levels compared with those randomized to CR alone ( P =0.022), an effect that was driven primarily by improvements in anxiety, distress, and perceived stress. Both CR groups achieved significant, and comparable, improvements in coronary heart disease biomarkers. Participants in the CR+SMT group exhibited lower rates of clinical events compared with those in the CR-alone group (18% versus 33%; hazard ratio=0.49; 95% confidence interval, 0.25–0.95; P =0.035), and both CR groups had lower event rates compared with the no-CR group (47%; hazard ratio=0.44; 95% confidence interval, 0.27–0.71; P &lt;0.001). Conclusions— CR enhanced by SMT produced significant reductions in stress and greater improvements in medical outcomes compared with standard CR. Our findings indicate that SMT may provide incremental benefit when combined with comprehensive CR and suggest that SMT should be incorporated routinely into CR. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00981253.
Prescribing of quinine and drugs that induce cramp
Authors: H. D Simpson
Journal: BMJ (1996)

Digoxin comes from Digitalis lanataEDrroR,-Gregory Y H Lip and colleagues say that the purple foxglove, Digitalis purpurea, con- tains digoxin.'This is wrong.Digoxin is obtained from the leaf of the woolly or Balkan foxglove, D lanata,2 from which it was first isolated by Dr Sydney Smith at Burroughs Wellcome in Britain in 1930.It is still extracted from the plant because, although it can be made synthetically, this is a difficult and expensive process.Soon after the war the Dutch realised that plants would still be essential for the production of important drugs, and with funds from the Marshall Plan they cultivated the foxglove on a large scale.By selective breeding of D lanata they improved the yield of digoxin, and this drug is currently chiefly obtained from plants grown on a cooperative farm at Elburg in the Netherlands.D purpurea yields digitoxin,3 which is now seldom used in Britain.
Racial/Ethnic Differences in Adverse Outcomes Among Childhood Cancer Survivors: The Childhood Cancer Survivor Study
Authors: Qi Liu, Wendy M. Leisenring, Kirsten K. Ness, Leslie L. Robison, Gregory T. Armstrong, Yutaka Yasui, Smita Bhatia
Journal: Journal of Clinical Oncology (2016)

Childhood cancer survivors carry a high burden of treatment-related morbidity; however, race/ethnicity-specific risks of adverse outcomes are not well understood.Data from the Childhood Cancer Survivor Study, a cohort of survivors of at least 5 years, were used to compare Hispanic (n = 750, 5.4%) and non-Hispanic black (NHB: n = 694, 5.0%) survivors to non-Hispanic white patients (NHW: n = 12,397, 89.6%) for late mortality, subsequent neoplasms, and chronic health conditions.NHBs and Hispanics reported lower socioeconomic status (SES) and higher prevalence of obesity, and NHBs reported higher prevalence of hypertension. NHBs had higher rate of all-cause mortality (relative rate [RR], 1.4; 95% CI, 1.1 to 1.9; P = .008), which was abrogated (RR, 1.0; 95% CI, 0.8 to 1.4; P = .9) after adjusting for SES. Nonmelanoma skin cancer was not observed among irradiated NHBs, and the risk was lower among Hispanic survivors (RR, 0.3; 95% CI, 0.1 to 0.7) compared with NHWs. Both NHBs and Hispanics demonstrated elevated risks for diabetes; these risks persisted after adjusting for SES and obesity (NHBs: RR, 2.8; 95% CI, 1.1 to 6.7; Hispanics: RR, 3.1; 95% CI, 1.5 to 6.4). NHBs were more likely to report cardiac conditions (RR, 1.8; 95% CI, 1.1 to 2.7), but the risk was attenuated after adjusting for cardiovascular risk factors. Therapeutic exposures did not affect racial/ethnic differences in mortality (all cause or cause specific), chronic health conditions, or subsequent neoplasms.By and large, NHB and Hispanic childhood cancer survivors experience a comparable burden of morbidity and mortality to their NHW counterparts. The few differences in risk were explained by the racial/ethnic differences in socioeconomic status and/or cardiovascular risk factors.
Whole-brain spectroscopic MRI biomarkers identify infiltrating margins in glioblastoma patients
Authors: James S. Cordova, Hui-Kuo G. Shu, Zhongxing Liang, Saumya S. Gurbani, Lee A. D. Cooper, Chad A. Holder, Jeffrey J. Olson, Brad Kairdolf, Eduard Schreibmann, Stewart G. Neill, Constantinos G. Hadjipanayis, Hyunsuk Shim
Journal: Neuro-Oncology (2016)

The standard of care for glioblastoma (GBM) is maximal safe resection followed by radiation therapy with chemotherapy. Currently, contrast-enhanced MRI is used to define primary treatment volumes for surgery and radiation therapy. However, enhancement does not identify the tumor entirely, resulting in limited local control. Proton spectroscopic MRI (sMRI), a method reporting endogenous metabolism, may better define the tumor margin. Here, we develop a whole-brain sMRI pipeline and validate sMRI metrics with quantitative measures of tumor infiltration. Whole-brain sMRI metabolite maps were coregistered with surgical planning MRI and imported into a neuronavigation system to guide tissue sampling in GBM patients receiving 5-aminolevulinic acid fluorescence-guided surgery. Samples were collected from regions with metabolic abnormalities in a biopsy-like fashion before bulk resection. Tissue fluorescence was measured ex vivo using a hand-held spectrometer. Tissue samples were immunostained for Sox2 and analyzed to quantify the density of staining cells using a novel digital pathology image analysis tool. Correlations among sMRI markers, Sox2 density, and ex vivo fluorescence were evaluated. Spectroscopic MRI biomarkers exhibit significant correlations with Sox2-positive cell density and ex vivo fluorescence. The choline to N-acetylaspartate ratio showed significant associations with each quantitative marker (Pearson's ρ = 0.82, P < .001 and ρ = 0.36, P < .0001, respectively). Clinically, sMRI metabolic abnormalities predated contrast enhancement at sites of tumor recurrence and exhibited an inverse relationship with progression-free survival. As it identifies tumor infiltration and regions at high risk for recurrence, sMRI could complement conventional MRI to improve local control in GBM patients.
Equity in Cancer Care and Outcomes of Treatment
Authors: Ralph I. Horwitz
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Phase II evaluation of weekly docetaxel and gemcitabine combination chemotherapy in recurrent ovarian cancer
Authors: P. Hanjani, M. S. Shahin, S. A. Nolte
Journal: Journal of Clinical Oncology (2004)

5115 Background: The aim of this trial was to investigate the efficacy and toxicity of weekly combination of docetaxel and gemcitabine in the management of recurrent ovarian cancer. Methods: Patients with recurrent ovarian, primary peritoneal and fallopian tube cancer (platinum sensitive and resistant), who had up to 2 prior regimen of chemotherapy received docetaxel (30 mg/m2) and gemcitabine (650 mg/m2) on days 1, 8 and 15 every 28 days. Results: To date, a total of 16 patients (median age 73; range 50–85) have been treated. Nine (56%) were platinum sensitive and 7(44%) were platinum resistant. A total of 53 cycles of chemotherapy were administered (median=2.5, range 2–6). Toxicity included grade 3 and 4 granulocytopenia (25% and 37.5% respectively), grade 3 thrombocytopenia (6.25%), grade 2 asthenia (25%), grade 2 hepatic toxicity (12.5%), and grade 2 edema (12.5%). One dose level reduction was necesary in 7(43.75%) patients. No neutropenic fever, grade 4 thrombocytopenia, or grade 3 or 4 anemia was encountered. Among the 15 evaluable patients, overall response rate was 20% (3 partial responses). Six patients (40%) had stable disease, and 6 (40%) demonstrated progression. Median time to progression and over all survival was 11 and 24 weeks respectively. Conclusions: Weekly docetaxel plus gemcitabine appears to be a tolerable regimen with minimal toxicity in this older population of patients (7 age > 80 years of age). No complete response was observed. Response rates appear to be comparable with single agent docetaxel given every 21 days with significantly less (p=0.0019) grade 3 or 4 neutropenia. No significant difference in response between platinum sensitive and resistant patients has been observed to date. Administration of weekly docetaxel and gemcitabine is feasible and tolerable in advanced ovarian cancer patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis Pharmaceutical