tbuckley/cabot-search huggingface dataset:
Alteration of topoisomerase II-alpha gene in human breast cancer: Association with responsiveness to anthracycline-based chemotherapy.
Authors: M. F. Press, G. Sauter, M. E. Buyse, L. Bernstein, W. Eiermann, T. Pienkowski, M. Martin, N. J. Robert, J. Crown, D. J. Slamon
Journal: Journal of Clinical Oncology (2010)

518 Background: Approximately 35% of HER2-amplified breast cancers have coamplification of the topoisomerase II-alpha (TOP2A) gene which encodes an enzyme that is a major target of anthracyclines. This study determines whether TOP2A rather than HER2 gene alterations may be predictive for unique responsiveness to anthracyclines in some breast cancers. Methods: Approximately 5,000 breast cancers were analyzed for alterations in TOP2A and HER2. Using fluorescence in situ hybridization, a test set of tumor tissues from metastatic breast cancer patients treated in a study of chemotherapy with or without trastuzumab and subsequent, large validation set trials were evaluated for amplification or deletion of these genes. Association between these alterations and clinical outcomes was determined. Results: The test set demonstrated that cases containing HER2 amplification treated with doxorubicin, cyclophosphamide (AC) plus trastuzumab had a longer progression-free survival compared to those treated with AC alone (p = 0.03). However, patients treated with AC alone whose tumors contain HER2/TOP2A coamplification experienced a similar significant increase in survival compared to those with only HER2 amplification (p = 0.004). Conversely, in patients treated with paclitaxel, HER2/TOP2A coamplification was not associated with improved outcomes. These observations were confirmed in validation set cases, where HER2/TOP2A coamplification was again associated with longer survival when anthracycline-containing chemotherapy was used compared to cancers lacking TOP2A coamplification. Conclusions: Both the test set and validation set demonstrate that TOP2A coamplification, not HER2 amplification, is the clinically useful predictive marker of a large increment in response to anthracycline-based chemotherapy in a small number of breast cancer patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration IDDI AstraZeneca, Genentech, GlaxoSmithKline, Merck, Novartis, Roche, sanofi-aventis, Ventana Medical Sysems IDDI AstraZeneca, Genentech, Merck, Novartis, Roche, sanofi-aventis Genentech, GlaxoSmithKline, Roche, sanofi-aventis, Ventana Medical Systems
Use of Quantitative Analysis of Urine to Assess Exposure to Asbestos Fibers in Drinking Water in the Puget Sound Region
Authors: Edwin S. Boatman, Tod Merrill, Angela O'Neill, Lincoln Polissar, James R. Millette
Journal: Environmental Health Perspectives (1983)

An earlier epidemiologic and electron microscopy study of drinking water in the Everett area of Washington State indicated large numbers of naturally occurring chrysotile asbestos fibers in the water. The purpose of the present study was to determine whether significant numbers of asbestos fiber could be demonstrated in the urine of donors residing in that area for less than 3 yr and over 20 yr where the tapwater contained about 200 X 10(6) fibers/L. A control group was obtained from Seattle where the tapwater asbestos fiber content was 100 times less. Urine samples, filtered control water, tapwater samples, and additional controls were processed for transmission electron microscopy by the use of the Nuclepore membrane filter-Jaffe wick procedure. Interference by mucus in the urine was reduced by treatment with hydrogen peroxide. Samples were taken over a period of 21 months. At no time during this period did the asbestos content of the urine samples consistently exceed that of the control waters. There was a significant difference (p less than 0.05) in the asbestos content of urine samples from subjects with less than 3 yr residence times versus greater than 20 yr. Asbestos concentration in urine samples from Everett residents as a whole did not differ significantly from that in samples from Seattle residents. Variable degrees of chrysotile contamination of control water samples and of Nuclepore membrane filters presented a problem. At present, the data are inconclusive but would suggest no relationship between high concentrations of fibers in drinking water and the numbers estimated for voided urine.
Regulation of Carbohydrate and Fat Metabolism During and After Exercise
Authors: J. O. Holloszy
Journal: Annual Review of Nutrition (1996)

During vigorous exercise, carbohydrate, in the form of muscle glycogen and blood glucose, is the primary energy source, whereas fatty acids play a secondary, carbohydrate-sparing role. In the postabsorptive state, nearly all of the carbohydrate used during exercise comes from muscle and liver glycogen. The size of these glycogen stores plays a major role in determining how long vigorous endurance exercise can be performed if other causes of fatigue, such as dehydration or heat exhaustion, are avoided. In a "fight or flight" situation, individuals whose muscles are glycogen depleted are helpless, as they are unable to either run or fight. The same is true of someone who has become markedly hypoglycemic as a result of liver glycogen depletion.
Abstract 3684: The TGFβ2-Snail1-miRNATGFβ2 circuitry is critical for the development of aggressive functions in breast cancer
Authors: Zhimin He, Guopei Zheng, Zhijie Zhang, Hao Liu, Binhua Peter Zhou
Journal: Cancer Research (2019)

Abstract There have been contradictory reports on the biological role of transforming growth factor-βs (TGFβs) in breast cancer, especially with regard to their ability to promote epithelial-mesenchymal transition. Here, we show that TGFβ2 is preferentially expressed in mesenchymal-like breast cancers and maintains the epithelial-mesenchymal transition phenotype, correlating with cancer stem cell -like characteristic, growth, metastasis and chemo-resistance and predicting worse clinical outcome. However, this is only true in ERα- breast cancer. In ERα+ luminal-type breast cancer, estrogen receptor interacts with p-Smads to block TGFβ signaling. Furthermore, we also identify a microRNAs (miRNAs) signature (miRNAsTGFβ2) that is weakened in TGFβ2-overexpressing breast cancer cells. We discover that TGFβ2-Snail1 recruits EZH2 and BMI1 to convert miRNAsTGFβ2 promoters from an active to repressive chromatin configuration and then repress miRNAsTGFβ2 transcription, forming a negative feedback loop. On the other hand, miRNAsTGFβ2 overexpression reverses the mesenchymal-like traits in agreement with inhibition of TGFβ2-Snail1 signaling in breast cancer cells. These findings clarify the roles of TGFβ2 in breast cancer and suggest novel therapeutic strategies based on the TGFβ2-Snail1-miRNATGFβ2loop for a subset type of human breast cancers. Keywords: TGFβ, EMT, miRNA, Snail1, feedback loop This study was supported by grants from the National Natural Science Foundation of China (No.81672616, 81872197, 81402196, 81272450 and 81772825); Guangdong Natural Science Funds for Distinguished Young Scholars (2016A030306003); Guangdong Special Support Program (2017TQ04R809). Note: This abstract was not presented at the meeting. Citation Format: Zhimin He, Guopei Zheng, Zhijie Zhang, Hao Liu, Binhua Peter Zhou. The TGFβ2-Snail1-miRNATGFβ2 circuitry is critical for the development of aggressive functions in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3684.
THE REQUIREMENT FOR CALCIUM
Journal: JAMA (1941)

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
Acute cholecystitis
Authors: R. E. Hermann
Journal: JAMA (1975)

FOR MANY years, the management of acute cholecystitis has been a controversial issue: should cholecystectomy be performed as an emergency procedure, should it be performed after a short period of diagnostic evaluation and medical treatment, or should the acute inflammatory process be treated medically and cholecystectomy delayed six to eight weeks until the inflammation has subsided? The principal arguments in favor of early operation are as follows: (1) In acute cholecystitis, the gallbladder is frequently obstructed and distended, and there is a 5% to 10% risk of ischemic necrosis of the wall of the gallbladder or of perforation. This is more likely to occur in the elderly, in patients with diabetes, and in those with atherosclerosis. (2) Early operation removes the inflamed organ promptly and avoids the need for a second hospitalization. (3) Recent studies have shown that if the operation is performed within 24 to 72 hours after the
PWE-372 Impact of type of surgery (Laparoscopic vs Open) on the time to initiation of adjuvant chemotherapy in operable rectal cancers
Authors: S Sinukumar, S Mehta, V Ostwal, S Jatal, A Saklani
Journal: Gut (2015)

<h3>Introduction</h3> Over the last decade, minimally invasive modalities have been adopted for the management of colorectal cancers. The COREAN and the MRC-CLASICC trial have established the benefits of laparoscopic surgery in rectal cancers in terms of decreased postoperative pain, shortened hospital stay and speedy recovery. A rapid post operative recovery is essential for initiation of adjuvant chemotherapy especially in stage II-III rectal cancers. The aim of this study was to evaluate whether the type of surgery (Laparoscopic or Open) had any bearing on the time to initiation of adjuvant chemotherapy (TIAC) after complete radical surgical proctectomy. <h3>Method</h3> A subset of 181 consecutive patients of operable rectal cancer, who underwent curative resection (laparoscopic or open) and who received postoperative adjuvant chemotherapy between July 2013 and Dec 2014 at the Tata memorial Centre, were studied. The time of initiation of adjuvant chemotherapy (TIAC) after curative resection of rectal cancers and the factors determining the same were studied in an univariate as well as a multivariate analysis. The factors that were analysed were type of surgery (Laparoscopic or open), age, gender, presence of complications and BMI. <h3>Results</h3> Fivety seven patients underwent laparoscopic and 124 patients underwent open resection of rectal tumours. 88.4% of the tumours were cT3+ and 61.3% of the tumours were N+ at initial staging. Overall, 90.6% of patients received neoadjuvant chemoradiotherapy prior to surgical resection. After surgery, 6–8 cycles of Single agent Capacetabine (CAP)(8.3%) or Capacetabine with Oxaliplatin (CAPEOX)(91.7%) were the chemotherapeutic agents administered. The median duration of hospital stay was (7.17days vs 10.64 days; p = 0.89) in the laparoscopic and open groups respectively. Overall complications were seen in 17.6% (32/181) of patients, eight in the laparoscopic arm and 24 in the open groups. The median time to start adjuvant chemotherapy after surgery was (21.6days vs. 23.73days; p = 0.94) in the laparoscopic and open groups respectively nor did it influence the duration of postoperative hospital stay. The presence of a surgical complication, however, was associated with a longer TIAC (p = 0.001). On univariate and multivariate analysis, the type of surgery (p = 0.398) did not influence the time of initiation of adjuvant chemotherapy. The only factor that influenced the TIAC was the presence of post operative complications (p = 0.001). <h3>Conclusion</h3> To conclude, while laparoscopic surgery has its benefits of shorter hospital stay, fewer complications, our study shows that laparoscopic surgery does not lead to an earlier start of adjuvant chemotherapy. <h3>Disclosure of interest</h3> None Declared.
Medical Emergencies
Authors: R. Greene
Journal: BMJ (1966)

Both the anticancer agent 2-chloro-2′-deoxy-adenosine (Cladribine) and its derivative 2-chloro-adenosine induce apoptosis of human astrocytoma cells (<i>J Neurosci Res</i><b>60:</b>388–400, 2000). In this study, we have analyzed the involvement of caspases in these effects. Both compounds produced a gradual and time-dependent activation of “effector” caspase-3, which preceded the appearance of the nuclear signs of apoptosis, suggesting a temporal correlation between these two events. Moreover, the caspase inhibitor <i>N</i>-benzyloxycarbonyl-Val-Ala-dl-Asp-fluoromethylketone (fmk) suppressed both caspase-3 activation and apoptosis induction. “Initiator” caspase-9 and caspase-8 were only marginally activated at later times in the apoptotic process. Accordingly, at concentrations that selectively inhibit these caspases, neither <i>N</i>-benzyloxycarbonyl-Leu-Glu-His-Asp-fmk nor <i>N</i>-benzyloxycarbonyl-Ile-Glu-Thr-Asp-fmk could prevent adenosine analog-induced cell death. To definitively rule out a role for the caspase-9/cytochrome <i>c</i>-dependent mitochondrial pathway of cell death, neither adenosine analog had any effect on mitochondrial membrane potential, which was instead markedly reduced by other apoptotic stimuli (e.g., deoxyribose, NaCN, and betulinic acid). Consistently, although the latter triggered translocation of mitochondrial cytochrome <i>c</i> to the cytoplasm, no cytosolic accumulation of cytochrome <i>c</i> was detected with adenosine analogs. Conversely, 1 to 7 h after addition of either adenosine analog (i.e., before the appearance of caspase-3 activation), caspase-2 activity was surprisingly and markedly increased. The selective caspase-2 inhibitor <i>N</i>-benzyloxy carbonyl-Val-Asp-Val-Ala-Asp-fmk significantly reduced both adenosine analogs-induced caspase-2 activation and the associated cell death. We conclude that adenosine analogs induce the apoptosis of human astrocytoma cells by activating an atypical apoptotic cascade involving caspase-2 as an initiator caspase, and effector caspase-3. Therefore, these compounds could be effectively used in the pharmacological manipulation of tumors characterized by resistance to cell death via either the mitochondrial or caspase-8/death receptor pathways.
Genomic Rearrangements Involving Programmed Death Ligands Are Recurrent In Primary Mediastinal Large B-Cell Lymphoma
Authors: David D. W. Twa, Fong Chun Chan, Susana Ben-Neriah, Bruce W. Woolcock, King L. Tan, Graham W. Slack, Jay Gunawardana, Raymond S. Lim, Andrew W. McPherson, Robert Kridel, Adele Telenius, David W. Scott, Kerry J. Savage, Sohrab P. Shah, Randy D. Gascoyne, Christian Steidl
Journal: Blood (2013)
Chronic Conjunctivitis Since Infancy
Journal: JAMA (1988)

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
Colonic Polyps
Authors: F. Ackroyd
Journal: Annual Review of Medicine (1985)

Carcinoma of the large bowel arises almost exclusively in neoplastic polyps, which are present in 5-10% of the population over age 40. These polyps may be of three histologic types: (a) tubular adenoma (adenomatous polyp), (b) tubulovillous adenoma (villoglandular polyp), and (c) villous adenoma. The tendency for malignant change is greatest in the villous adenoma (41%) and in tubulovillous (villoglandular polyps–23%). In tubular adenomas (simple adenomatous polyps), the incidence of malignancy is 5% over all. The tendency toward malignant change is determined by histologic type, size, and degree of atypicality of adenoma. Early detection and complete removal of neoplastic polyps of the colon are essential to the prevention of cancer of the large bowel, and this may usually be done in most cases with the colonoscope.
Experimental Radiation Pneumenitis
Journal: JAMA (1963)

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
Clonal identities and multiple isotype transcripts in hematological diseases revealed by a single‐strand conformation polymorphism analysis of the immunoglobulin heavy chain messenger signals
Authors: Satoshi Shiokawa, Junji Nishimura, Naokuni Uike, Yoshio Saburi, Tomoki Suehiro, Kazuhiko Yamamoto
Journal: American Journal of Hematology (1999)

A single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction (PCR)-amplified products of immunoglobulin (Ig) heavy chain rearrangements can be used to analyze B cell clonalities and clonal identities of B cells from different samples. However, the usefulness of the PCR-SSCP analysis is not fully assessed in B cell malignancies. For example, we did not know whether the PCR-SSCP method can be used to detect tumor-related clones in peripheral blood of patients with multiple myeloma and Waldenström's macroglobulinemia. In addition, because genomic DNA is used in the PCR-SSCP method, we could obtain no information about the isotype of the expanded B cell clone. In this study, we combined the reverse transcriptase (RT)-PCR of immunoglobulin heavy chain transcripts with an SSCP analysis and thus analyzed eight healthy individuals, five patients with B chronic lymphocytic leukemia, four patients with multiple myeloma and three patients with Waldenström's macroglobulinemia. Clonal B cell populations were detected as discrete bands in the RT-PCR-SSCP analysis that can be readily detected over the background of polyclonal rearrangements. Circulating tumor-related clones were detected in all but one peripheral blood sample from multiple myeloma and Waldenström's macroglobulinemia patients and B cell clones in peripheral blood and bone marrow from these patients showed a similar mobility on SSCP gel. Because the transcripts of different isotypes were separately analyzed, we could thus determine the isotype of B cell clones as well. When monoclonal Igs of different isotypes were detected in the individual samples, we analyzed the relationship of each monoclonal band by excising the band and then further analyzing it by a PCR-SSCP analysis. RT-PCR amplification in conjunction with the SSCP analysis is thus considered to be a useful method to detect and characterize the B cell clones in hematological diseases. Am. J. Hematol. 62:74–81, 1999. © 1999 Wiley-Liss, Inc.
Dementia. Council on Scientific Affairs
Journal: JAMA (1986)

Dementia has emerged as a national health concern. The demographics of our aging population suggest that this concern can only become more acute. For families that have a member with a primary dementing illness, this concern often becomes an all-consuming one. At present, our understanding of the primary dementias, especially Alzheimer's disease, is incomplete, and thus, most cases of primary dementia progress irreversibly. Nevertheless, there is much in the way of treatment, care, and support that can be provided by the practicing medical community to sustain the viability and vitality of patient and family.
Organ donation.
Authors: G R Park, K E Gunning, M J Lindop, P G Roe
Journal: BMJ (1993)

general practice tutor who now visits and assesses practices applying to employ a retained doctor and who meets the retained doctors annually to assess whether their educational needs are being met.Toynton also recommends a system whereby retained doctors can be given a free pass for educational activities.At this postgraduate centre, and many others in this region, this has been the system for some time.Fees are charged only to doctors who require a postgraduate education allowance certificate.Doctors on the retainer scheme, and trainees, assistants, retired doctors, and anyone else who does not require a certificate, are welcome to contact our postgraduate administrator for details of our educational programmes, to which they will be admitted free of charge.