tbuckley/cabot-search huggingface dataset:
Abstract 2081: NUC 3373 induces endoplasmic reticulum stress in colorectal cancer cells
Authors: Fiona G. McKissock, Asmithaa Prabhakaran, Peter Mullen, David J. Harrison
Journal: Cancer Research (2019)

Abstract Background Although 5-fluorouracil-based (5-FU) chemotherapies remain the cornerstone of combination therapies for colorectal cancer (CRC), their clinical utility is limited by key cancer resistance mechanisms associated with breakdown, transport, and activation. This includes the intracellular conversion of 5-FU into its active metabolite, fluorodeoxyuridine-monophosphate (FUDR-MP), before core anti-cancer activity can be exerted via inhibition of the enzyme thymidylate synthase (TS). NUC-3373, a phosphoramidate transformation of FUDR-MP, is designed to bypass the key resistance mechanisms associated with 5-FU, resulting in a potentially more effective and safer treatment option. In a Phase I dose-finding study, plasma obtained from patients with advanced cancers revealed that NUC-3373 has a longer half-life than 5-FU (9.7 hours vs 8-14 minutes). Herein, we aimed to investigate the potential role of endoplasmic reticulum (ER) stress pathways in the cancer cell response to NUC-3373. Methods IC50 values for NUC-3373 were established in nine CRC cell lines by sulforhodamine B assay, after which one sensitive (HCT116) and one resistant (SW480) cell line were selected for further characterization. Control experiments were conducted with thapsigargin and tunicamycin. Cells were examined by transmission electron microscopy and, using stereological principles, changes in cell ultrastructure were quantified. Expression of the ER chaperone protein binding immunoglobulin protein (BiP) was detected by Western blot analysis. Results Ultrastructural analysis revealed that NUC-3373 had differential effects on ER stress that were dependent on cell line sensitivity to the drug. Following treatment, NUC-3373-sensitive HCT116 cells responded by dilation of their ER, while the SW480 resistant cells responded by lengthening of ER but without dilation. These changes were reflected with the two classical ER stress inducers, thapsigargin and tunicamycin. NUC-3373 activated the unfolded protein response (UPR), as evidenced by upregulation of BiP. Both the magnitude and the duration of the BiP response were higher in SW480 cells. Conclusions This study supports a novel mechanism of action for NUC-3373-induced anti-cancer activity through modulation of cell stress. NUC-3373 induces UPR and ER stress in colorectal cancer cells. Results of the ultrastructural analysis suggest that the sensitivity of cells to NUC-3373 may be determined by the differential adaptation of ER to stress conditions. Citation Format: Fiona G. McKissock, Asmithaa Prabhakaran, Peter Mullen, David J. Harrison. NUC 3373 induces endoplasmic reticulum stress in colorectal cancer cells [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 2081.
Helicobacter pylori
Authors: Pouch-Vaginal Fistula, J Groom, R Nicholls, P Hawley, Rks Phillips
Journal: Gut (1992)

Between 1976 and June 1991, 161 females underwent restorative proctocolectomy.Sixteen (9.9%) developed pouch- vaginal fistula.No difference between inflammatory 14/139 (10.1%) and non-inflammatory 2/22 (9.1%) disease, severity of colitis, or number of stages in operation.All fistula involved the ileo-anal anastomosis.There was no significant difference between hand sewn 9/117 (7.6%) and stapled 7/44 (15.9%) ileo-anal anastomosis, although 3/15 (20%) had double- stapled anastomosis.Of the 16, 8 had pelvic sepsis in the immediate post operative period, only 3 had an anastomotic defect and one who catheterizes had a stricture.In 6 cases there was no apparent reason for PVF.There was no case of Crohn's disease.Three developed PVF before ileostomy closure, 13 after a median interval of 7.5 months (range 0.5 to 33 months).
Microbiology and Molecular Genetics
Authors: J Haug, P Patel, S Khulusi, Tc Mendall, J Bottomley, Clayton Kleanthous
Journal: Gut (1995)

Introduction: This study comprises 1191 gastral antrum biopsy samples routinely cultured for Helicobacser pylori (Hp) at a single clinical microbiological laboratoin during 27 months since June 1992.Aim: To evaluate 1) diagnostic niethods with regard to the presence of Hp.2) antinucrobial suscetibility rates and 3) the epidemiology of Hp infections in our geographical area (a county of Norway with -240).t(X)inhabitants).Methods: Specimens were incubated nicroaerophilic on selective agar media for up to 12 days.using standard techniques.Microscopy was performed with the Grain and Acridin stains and each specimen was tested for urease production after and 18 hours of incubation In the case of a negative culture.one typical nucroscop and one positive urease test was regarded a Hp-positive case (designated <indirect>> critenon).Antibiotic susceptibility tests were performed with the Epsilometer test.using a MIC > 16 mg/I as breakpoint for metronidazole (MTZ) resistance.Results: The male to female ratio in Hp positive cases was 1.6:1.ln 64.7% of cases.the patients were less than 6(0 years of age.Hp was present in 5(9 (42.5%) of all specimens and of these.a positive culture was achlved in 90.2%.In 72.1% of cases.Hp was cultured within 5 days and the rest after 6-12 days of incubation Our ((indirect)> criterion was not fullfilled in 33.60/0 of the culture-positive cases.hence.the sensitivity and spesificity for the urease test and was 78.7% and 90.5% and for microscopy. 74.0% and 90.9%.respectively.Microscopy and urease test performed significantly better (p<0.001) when Hp grew rapidly i.e after < 5 days, than after a longer periode of incubation.Overall MTZ-resistance was 29.1%.Increased MTZ resistance rates were found for both female sex and for younger patients (i.e.< 60 years of age) with p-values of < ()0.15 and < 0.002.respectively.For tetracycline and ampicillin.susceptibility rates were nearly 100%.Conclusions: In our hands.microscopy and urease test can not replace cultunng as a means of Hp detection.A significant number of the HP culture positive cases in our study (more than 1/ ) w.ere detected after an incubation time of 6 to 12 days.Metronidazole resistance is highly prevalent (29.1%) in our population, especially among the young and female patients.We propose that an earlier use of metronidazole in this particular patient group may be one possible explanation.Serological, histopathological and clinical observations are pending in this on- going study and will be further commented upon. 62Rapid western blotting assay: role in determining which H. pylori patients have duodenal ulceration(DU) .
Correction: Vitamin K Supplementation in Postmenopausal Women with Osteopenia (ECKO Trial): A Randomized Controlled Trial
Authors: Angela M Cheung, Lianne Tile, Yuna Lee, George Tomlinson, Gillian Hawker, Judy Scher, Hanxian Hu, Reinhold Vieth, Lilian Thompson, Sophie Jamal, Robert Josse
Journal: PLoS Medicine (2008)
Fitness Trails
Authors: Robert Buxbaum, Ronald O'Connor
Journal: New England Journal of Medicine (1977)

In a search for ways to control rising medical-care costs, particularly those resulting from end-stage cardiovascular disorders, as well as to promote healthful personal behavior, a number of governments, including Canada,1 Sweden and Switzerland, have initiated comprehensive preventive campaigns emphasizing the need for people to alter habitual practices that lead to ill health. One focus of such programs is the lack of exercise engendered by conditions in the workplace, at home and on the road. Although there are still valid professional questions about the importance of exercise to health,1 much epidemiologic and physiologic evidence suggests that the maintenance of lifetime . . .
Antibiotics in surgical treatment of acute abscesses
Authors: R. Grace
Journal: BMJ (1981)

the health of special "captive" subjects, such as soldiers, prisoners, university under- graduates, and the like, and to protect them from needless physical or mental discomfort.The scientific validation of one of the least intrusive forms of physical culture training is, I believe, a humane and highly ethical thing to have done, and is totally at variance with the tone of Dr Bradshaw's letter.Physical fitness in the accepted sense is not obtained
THE EVILS OF TIGHT LACING.
Journal: JAMA (1900)

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
THE RELATION OF GLYCOSURIA TO DIABETES.
Journal: JAMA (1898)

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
Obituary
Authors: Bob Viator
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
Abstract 2028: CCL18 signaling from breast tumor-associated macrophages fosters the activation of fibroblasts into a chemoresistance-inducing phenotype
Authors: Erwei Song, Jianing Chen, Shicheng Su
Journal: Cancer Research (2019)

Abstract Carcinoma-associated fibroblasts (CAFs) are abundant and heterogeneous stromal cells in tumor microenvironment critically involved in cancer progression. Our recent study identified a specific CAFs subset by two cell-surface molecules, CD10 and GPR77. We proved that CD10+GPR77+CAFs could promote tumor formation and chemoresistance by providing a survival niche for cancer stem cells (CSCs). However, their origin and underlying activating initiation mechanism are unclear. Tumor-associated macrophages (TAMs) are the most abundant immune-related stromal cells and the important source of inflammatory cytokine. Here, we demonstrated that CCL18 secreted by TAMs could induces the activation of normal breast fibroblasts into a CD10+GPR77+CAFs phenotype, which are not only resistant to chemotherapy themselves, but also can induce chemoresistance in cancer cells by abundantly producing IL-8 and IL-6 and enriching the population of cancer stem cells. In conclusion, our studies have identified an inflammatory signaling network in the interaction of different kind of stroma cells in tumor microenvironment and highlighted its potential values as predictive markers and therapeutic targets to abrogate tumor formation and improve chemotherapeutic efficacy. Note: This abstract was not presented at the meeting. Citation Format: Erwei Song, Jianing Chen, Shicheng Su. CCL18 signaling from breast tumor-associated macrophages fosters the activation of fibroblasts into a chemoresistance-inducing phenotype [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 2028.
Prospective evaluation of a simplified approach for common atrial flutter radiofrequency ablation with only two catheters Didier Klug, Dominique Lacroix, Bernard d'Hautefeuille, Max Pecheux, St�phane Denneti�re, Claude Kouakam, Christelle Marqui�, Salem Kacet. University of Lille, Lille, France
Journal: Journal of the American College of Cardiology (2001)
Measles immunization: new recommendation
Authors: S. Krugman
Journal: JAMA (1977)

Live, attenuated measles virus vaccine was licensed for use in the United States in 1963. During the past 13 years, more than 80 million children have been immunized. During the prevaccine era, major epidemics occurred in most cities at two- or threeyear intervals, and the number of reported cases in the United States was approximately 500,000 each year. The extensive use of measles vaccine during the past decade has had a profound effect on the epidemiology of the disease in this country. The number of reported cases has declined to levels of approximately 35,000 per year, a decrease exceeding 90%. In addition, there has been a corresponding reduction in the number of cases of encephalitis following measles cases, and major nationwide epidemics have not occurred. However, despite this encouraging trend, outbreaks of measles have been observed in adolescents as well as in young children during the past four or five
Neuropsychiatric manifestations of human leukocyte interferon therapy in patients with cancer
Authors: F. Adams
Journal: JAMA (1984)

The conditions of ten patients with metastatic renal cell carcinoma were serially evaluated by neuropsychiatric examination to determine the nature of the fatigue-asthenia symptoms resulting from human leukocyte interferon alpha therapy. The majority of the patients had moderate to severe behavioral changes and mild to moderate cognitive, affective, and personality changes within the first week of daily intramuscular administration of 3×10<sup>6</sup>units of interferon. This descriptive clinical study suggests that the intense fatigue may be a manifestation of a complex neurotoxicity, most suggestive of frontal lobe changes, and resulting in neurasthenia syndrome with reversible impairment of some higher mental functions. (<i>JAMA</i>1984;252:938-941)
From the Centers for Disease Control. Investigations of patients who have been treated by HIV-infected health-care workers
Journal: JAMA (1992)

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
Medicine and the Laity
Journal: JAMA (1969)

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
Risk of Second Cancer in Patients With Hairy Cell Leukemia: Long-Term Follow-Up
Authors: M. Federico
Journal: Journal of Clinical Oncology (2002)

PURPOSE: The purpose of the present study was to assess the risk of second cancers in patients with hairy cell leukemia (HCL). PATIENTS AND METHODS: We investigated the incidence of additional cancers in those patients registered in the nationwide registry of the Italian Cooperative Group for the Study of HCL, asking the cooperating centers for additional information on initial and subsequent therapies and on time and type of second malignancies, if they developed. Here we report the final results of this survey, consisting of 54 cases of second malignancies (excluding nine cases of epithelial skin cancer) which developed in 54 patients of 1,022 with adequate follow-up. RESULTS: The cumulative risk of development of a second cancer was 5%, 10%, and 14% at 5, 10, and 15 years, respectively. The incidence of second malignancies was not significantly higher than the expected rate (standardized incidence ratio [SIR], 1.01; 95% confidence interval [CI], 0.74 to 1.33; P = 1.0). However, the SIR of non-Hodgkin's lymphoma in the entire cohort was 5.3 (95% CI, 1.9 to 11.5). Second malignancies occurred in eight (4.7%) of 386 patients who never received interferon (IFN), nine (5.9%) of 495 patients treated with IFN at the time of diagnosis, and seven (6.9%) of 102 patients who received IFN as second-line therapy. These differences were not statistically significant. Analysis of the separate calendar periods did not reveal any particular trends with respect to variations in SIR. CONCLUSION: The present study does not support the suspicion that patients with HCL are at increased risk of additional second malignancies, although the incidence of lymphoid neoplasms was significantly higher than expected. In addition, our data indicate that IFN therapy did not exert an oncogenic effect in such patients.
CBMT-11. HIGH MITOCHONDRIAL DNA COPY NUMBER IS ASSOCIATED WITH LONGER SURVIVAL IN YOUNG PATIENTS WITH GLIOBLASTOMA
Authors: Audrey Rousseau, Laure-Marie Dardaud, Céline Bris, Valérie Desquiret-Dumas, Blandine Boisselier, Emeline Tabouret, Karima Mokhtari, Dominique Figarella-Branger, Vincent Procaccio
Journal: Neuro-Oncology (2019)

Abstract Young patients (&lt; 40 years-old) with glioblastoma (GB) may carry IDH1/2 mutations or rarely, H3F3A/HIST1H3B mutations. Some instead harbor chromosome (chr) 7 gain, chr 10 loss, and EGFR amplification (amp). IDH1/2 mutations are associated with longer survival in contrast to H3F3A/HIST1H3B mutations. Novel reliable prognostic factors are needed in GB. Mitochondria (mt) are responsible for ATP production through oxidative phosphorylation. High mtDNA copy number (CN) has been associated with variable outcomes in cancer. The mtDNA-CN was assessed by RT Q-PCR in 66 GB from patients 18 to 40 years-old. Whole mitochondrial genome sequencing was performed in 18/66 GB. 17/66 (25.8%) cases harbored IDH1-R132H mutation; 29/66 (44%) had chr 7 gain/chr 10 loss and/or EGFRamp; 4/66 (6%) harbored H3F3A/HIST1H3B mutations. The remaining cases (24.2%) had no key genetic alterations. The mtDNA/nuclearDNA ratio was subdivided into groups: Low and High according to the median (mtDNA-CN median 194.9). 33 patients displayed a low ratio (≤ median) whereas 33 displayed a high ratio (&gt; median). The overall survival in the High vs Low group was significantly longer in the whole cohort (Log-rank test, 31.8 vs 14.2 months, p= 0.019) and the chr7+/chr10-/EGFRamp subgroup (37.8 vs 12.1 months; p= 0.0117). There was still a trend towards longer survival in the High vs Low group within the other genetic subgroups (IDH-mutant; no genetic alteration) except for the H3-mutant GB (4 patients). Analyses on 232 patients 18 to 84 years-old showed that among patients &lt; 56 years-old, the High group (58 cases) had a longer survival compared to the Low group (59 cases) (27.3 vs 15 months; p= 0.023). High mtDNA level is linked to oxidative metabolism (which decreases tumor aggressiveness) and cell differentiation. Increasing mtDNA-CN might induce tumor cell differentiation and slow disease progression. In conclusion, mtDNA-CN may be a novel prognostic biomarker in GB.
Editorial Board
Authors: Andrew Schachat, Henry Jampel, Douglas Anderson, James Miami, Wiley Brandt Sacramento, I Chambers, Susan Washington, San Day, William Francisco, La Freeman, David Friedman Baltimore, Glenn Durham, Yoshiaki Kitazawa, Ronald Madison, Richard Alan, Lewis Houston, Maureen Maguire Philadelphia, Steven Mccormick, New York, Joel Mindel, Arthur Mueller, David Musch, Ann Arbor, Steven Charlottesville, Joan O'brien, San Francisco, Denis O', Day Nashville, Roger Steinert Boston, Richard Stone Philadelphia, Alan Sugar, M Rohit Varma, Thomas Weingeist, Richard London, Veronica Doyle, Miranda Walker, Anika Trahan, Richard Zorab Vp, Ophthalmic Knowledge, Hal Straus, Thomas Los, Debra Shetlar
Journal: Ophthalmology (2006)