tbuckley/cabot-search huggingface dataset:
Abstract A05: NKG2D and CD28 receptors differentially activate mTOR to alter murine effector CD8+ T cell differentiation
Authors: Bryan McQueen, Kelsey Trace, Emily Whitman, Amorette Barber
Journal: Cancer Research (2016)

Abstract Memory CD8+ T cells are an essential component of anti-tumor and anti-viral immunity. Activation of the mammalian/mechanistic target of rapamycin (mTOR) pathway has been implicated in regulating the differentiation of effector and memory T cells. However, the mechanisms that control mTOR activity during immunity to tumors and infections are not well known. Activation of costimulatory receptors, including CD28 and NKG2D, activate PI3K and subsequently may activate the mTOR pathway in CD8+ T cells. Therefore this study compared the activation of the mTOR signaling pathway after costimulation through CD28 or NKG2D receptors in murine effector CD8+ T cells. Compared to CD28 costimulation, activation through CD3 and NKG2D receptors had weaker activation of mTORc1 as shown by decreased phosphorylation of mTORc1 targets S6K1, ribosomal protein S6, and 4EBP-1. NKG2D costimulation also showed increased gene expression of TSC2, a negative regulator of mTORc1, whereas CD28 costimulation increased gene expression of Rheb, an activator of mTORc1, and HIF-1α and VEGFα, pro-angiogenic factors downstream of mTORc1. Strong mTORc1 activation in CD28-costimulated cells also increased expression of transcription factors that support effector cell differentiation, namely T-bet, and BLIMP1, whereas low levels of mTORc1 activation allowed for the expression of Eomes and BCL6 during NKG2D stimulation, and increased expression of central memory markers CD62L and CD127. These data show that compared to CD28, costimulation through the NKG2D receptor leads to the differential activation of the mTOR signaling pathway and potentially supports memory CD8+ T cell differentiation. Citation Format: Bryan McQueen, Kelsey Trace, Emily Whitman, Amorette Barber. NKG2D and CD28 receptors differentially activate mTOR to alter murine effector CD8+ T cell differentiation. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr A05.
Angiotensin Inhibition
Authors: Aram V. Chobanian
Journal: New England Journal of Medicine (1974)

Recent advances in pharmacology and peptide chemistry have provided investigators with excellent tools to help dissect out the importance of the renin-angiotensin system in the maintenance of blood pressure and in the pathogenesis of hypertension. Various steps involved in the production of angiotensin II can now be inhibited effectively in man. Renin release from the kidneys can be suppressed with beta blockade; the conversion of angiotensin I to angiotensin II can be decreased considerably with the nonapeptide (SQ 20881)reported on in this issue of the Journal, and the peripheral effects of angiotensin II on blood pressure and aldosterone secretion can . . .
Quantitative DNA Alterations During 5-Azacytidine-Induced Differential Modulation of Benzo(α)pyrene Carcinogenesis in Hamster Bronchi
Authors: W G Hammond, A Yellin, A Gabriel, N Azumi, L R Hill, R L Teplitz, J R Benfield
Journal: Cancer Communications (1990)

Sustained release implants (SRI) containing 10% benzo(a)pyrene (BP) were placed endobronchially into outbred and syngeneic (F1D) hamsters. Randomly selected OB and F1D hamsters also received 5-azacytidine (AZC), 5 mg/kg i.p., twice weekly until death (AZC-CONT); two more groups of F1D hamsters were given the same AZC dose either for the first 75 days of SRI implantation (AZC-EARLY) or from 80 days after SRI placement until death (AZC-LATE). OB Hamsters were sacrificed at regular intervals from 62 to 189 days of SRI exposure. F1D Hamsters were sacrificed in groups after 120, 150, 180, and 220 days of SRI exposure. The bronchial mucosa at the SRI site was examined cytologically and histologically, as were the tumors that developed. Mean quantitative total cellular DNA values (QDNA) were measured by image analysis. For both varieties of hamster given AZC, QDNA values were higher in early carcinogenesis (CG) and lower in the late stage of CG than in hamsters that did not get AZC (P less than 0.001). QDNA values were lower in epidermoid than in non-epidermoid cancers (P less than 0.001); for both types of cancer, QDNA was lower in AZC-treated hamsters (P less than 0.01). Cancers induced under the influence of AZC included more epidermoid cancers (P less than 0.01) and were of a higher degree of differentiation (P less than 0.01) than those induced by BP alone, especially when AZC was given early in CG. There was no consistent relationship between QDNA and degree of differentiation in tumors. These differential effects of AZC given early during CG suggest that 1) for epidermoid bronchial CG, some of the molecular alterations involved in hyperploidy and in differentiation occur early in the sequential progression of carcinogenesis; and 2) for both epidermoid and non-epidermoid bronchial CG, the necessary changes must occur in a fixed sequence instead of as random events, until all needed changes have occurred.
Disrupting Hypoxia-Induced Bicarbonate Transport Acidifies Tumor Cells and Suppresses Tumor Growth
Authors: Alan McIntyre, Alzbeta Hulikova, Ioanna Ledaki, Cameron Snell, Dean Singleton, Graham Steers, Peter Seden, Dylan Jones, Esther Bridges, Simon Wigfield, Ji-Liang Li, Angela Russell, Pawel Swietach, Adrian L. Harris
Journal: Cancer Research (2016)

Tumor hypoxia is associated clinically with therapeutic resistance and poor patient outcomes. One feature of tumor hypoxia is activated expression of carbonic anhydrase IX (CA9), a regulator of pH and tumor growth. In this study, we investigated the hypothesis that impeding the reuptake of bicarbonate produced extracellularly by CA9 could exacerbate the intracellular acidity produced by hypoxic conditions, perhaps compromising cell growth and viability as a result. In 8 of 10 cancer cell lines, we found that hypoxia induced the expression of at least one bicarbonate transporter. The most robust and frequent inductions were of the sodium-driven bicarbonate transporters SLC4A4 and SLC4A9, which rely upon both HIF1α and HIF2α activity for their expression. In cancer cell spheroids, SLC4A4 or SLC4A9 disruption by either genetic or pharmaceutical approaches acidified intracellular pH and reduced cell growth. Furthermore, treatment of spheroids with S0859, a small-molecule inhibitor of sodium-driven bicarbonate transporters, increased apoptosis in the cell lines tested. Finally, RNAi-mediated attenuation of SLC4A9 increased apoptosis in MDA-MB-231 breast cancer spheroids and dramatically reduced growth of MDA-MB-231 breast tumors or U87 gliomas in murine xenografts. Our findings suggest that disrupting pH homeostasis by blocking bicarbonate import might broadly relieve the common resistance of hypoxic tumors to anticancer therapy. Cancer Res; 76(13); 3744-55. ©2016 AACR.
Serum Oxaloacetic Transaminase Levels Following Renal Infarction
Authors: Charles J. Frahm
Journal: JAMA (1962)

Serial determinations of serum glutamic-oxaloacetic transaminase (SGO-T) were recorded during the entire course of a patient, a woman 51 years of age. who survived unilateral renal arterial infarction. SGO-T levels were also studied in 10 dogs with surgically induced renal infarctions. The values rose to a maximum on the first day after infarction and returned to normal by the third day. The maximum elevations ranged from 62 to 155 units per milliliter.
Comparison of intensity modulated radiation therapy (IMRT) with conventional radiotherapy (CRT) for cervical cancer with concurrent cisplatin (CDDP)
Authors: N. Thawani, J. M. Vainshtein, R. Hannan, S. Kalnicki, R. Yaparpalvi, S. Mutyala
Journal: Journal of Clinical Oncology (2008)

5562 Background: The current standard of care for locally advanced cervical cancer, concurrent CDDP and radiation therapy, has shown high cure rates, but with substantial acute toxicity. IMRT has shown the promise of sparing normal tissues while delivering high doses to the tumor which may translate into high local control with potential decrease in morbidity. We compare the acute toxicity of concurrent CDDP chemoradiotherapy delivered with IMRT versus CRT. Methods: Between Jan 2000 to date, 96 consecutive patients with histologically proven cancer cervix received radiation at our institution. Acute toxicity was assessed according to RTOG criteria and analyzed. All patients received 45 Gy to the whole pelvis (53- IMRT and 43- CRT), 52 treated to extended paraortic field (28-CRT and 24- IMRT) and 62 received a parametrial boost. All patients except one received HDR brachytherapy to the cervix. 79 patients were treated definitively (42 CRT, 39 IMRT) and 17 postoperatively(16-IMRT, 1 CRT). 96% patients received concurrent chemotherapy with CDDP at 40 mg/m2 weekly or 20 mg/m2 /day for weeks 1, 4 and with second fraction HDR. Both groups were statistically similar for age and stage of disease. Toxicity was compared using Student's t-test. Results: All patients completed the prescribed radiation course. No patients in the IMRT group had any grade 3 or 4 weight loss or skin toxicity. Severe toxicity (grade 3 and 4) are summarized in table. Conclusions: There was significantly less GI, GU and skin toxicity in IMRT group, most probably secondary to IMRT's ability to constrain radiation doses to the bladder, rectum and small bowel. Bone marrow radiation was not strictly constrained which might have lead to similar myelotoxicity in both groups. We are currently evaluating the effects of dose constraining for bone marrow. Further follow-up and prospective study is warranted. Technique GI GU Skin Neutropenia Anemia Thrombocytopenia CRT 21% 11% 9% 46.5% 16% 11% IMRT 4% 2% 0 45% 6% 13% p-value <0.01 <0.01 <0.01 0.68 0.18 0.99 No significant financial relationships to disclose.
Creutzfeldt-Jakob disease and related diseases in France from 1998 to 2000
Authors: L Capek, V Vaillant
Journal: Eurosurveillance (2003)

In France, the number of reports of suspected CJD increased from 1998 to 2000, probably due to the increase in the requests for biological tests: respectively 459 in 1998, 590 in 1999, and 823 in 2000. For all three years, the distribution by sex is similar, with a sex ratio (M/F) of 1.05. The proportion of suspected cases aged under 50 remained stable (16% of all reports in 1998–2000). The number of sporadic CJD, confirmed or probable, was stable, with a mortality ratio of 1.38 per one million in 1998, 1.56 in 1999, and 1.41 in 2000.
FINGERTIP DIAGNOSIS OF AMYLOIDOSIS
Authors: W S HOFFMAN, W L FISHBEIN, M B ANDELMAN
Journal: JAMA (1964)

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
Imbalance in Alternative Splicing of MCL-1 Inhibits Apoptosis in Diffuse Large B-Cell Lymphoma
Authors: Nicolle H Rekers, Laura M Moesbergen, Nathalie J Hijmering, Wim Vos, Joost Oudejans, Gert J. Ossenkoppele, Chris JLM Meijer, Saskia AGM Cillessen
Journal: Blood (2014)
Induction of Mammary Tumors by Injection of &lt;italic&gt;N&lt;/italic&gt;-2-Fluorenylacetamide into Artificial Cecal Pouches in Rats&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Harlan J. Spjut, M.D., Ernst J. Eichwald, M.D.
Journal: JNCI Journal of the National Cancer Institute (1957)

Induction of Mammary Tumors by Injection of N-2-Fluorenylacetamide into Artificial Cecal Pouches in Rats Get access Harlan J. Spjut, M.D., Harlan J. Spjut, M.D. Department of Surgical Pathology, Washington University School of Medicine and Barnes Hospital, St. Louis, Missouri, and Montana Deaconess Hospital, Great Falls, Montana Search for other works by this author on: Oxford Academic PubMed Google Scholar Ernst J. Eichwald, M.D. Ernst J. Eichwald, M.D. Department of Surgical Pathology, Washington University School of Medicine and Barnes Hospital, St. Louis, Missouri, and Montana Deaconess Hospital, Great Falls, Montana Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 18, Issue 3, March 1957, Pages 473–479, https://doi.org/10.1093/jnci/18.3.473 Published: 01 March 1957 Article history Received: 14 November 1956 Published: 01 March 1957
Persistence and Clinical Outcome of Hepatitis G Virus Infection in Pediatric Bone Marrow Transplant Recipients and Children Treated for Hematological Malignancy
Authors: Maki Yamada-Osaki, Ryo Sumazaki, Masahiro Tsuchida, Kazutoshi Koike, Takashi Fukushima, Akira Matsui
Journal: Blood (1999)
Is stress response a new link between adipose tissue and atherogenesis? The role of HSPs/HSF1
Authors: Ioannis Akoumianakis, Charalambos Antoniades
Journal: Cardiovascular Research (2016)

This editorial refers to ‘Heat shock factor-1 knockout enhances cholesterol 7α-hydroxylase (CYP7A1) and multidrug transporter (MDR1) gene expressions to attenuate atherosclerosis’, by K. Krishnamurthy et al. , pp. 74–83. 

The role of lipids in atherogenesis is well established; subendothelial deposition of oxidized low-density lipoprotein (ox-LDL) initiates atherosclerotic plaque formation.1 Circulating cholesterol is regulated by its dietary intake and endogenous synthesis on one hand, and its elimination from the circulation via LDL-receptors/excretion in the bile on the other hand.2 Various lipid-lowering therapies targeting these regulatory mechanisms are used in patients with dyslipidaemias, significantly impacting cardiovascular risk. However, the residual risk after applying existing lipid-lowering strategies highlights the complexity of lipid metabolism and the necessity for broader understanding of the links between lipids and the cardiovascular system.

Over the last decade, it became clear that adipose tissue is an active endocrine organ producing various adipocytokines, the secretory profile of which is dysregulated in cardiovascular and metabolic disease. Adipocyte differentiation, a process whereby small pre-adipocytes with little lipid content transform into large, differentiated lipid-rich adipocytes, is altered in cardiometabolic disease.3 Obesity-related diseases are characterized by adipose inflammatory infiltration, which prevents pre-adipocyte differentiation, affecting lipid and energy consumption/expenditure and modifying the secretory profile of the tissue.3 The literature on the roles …
Mentorship Malpractice
Authors: Vineet Chopra, Dana P. Edelson, Sanjay Saint
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
S29 Predictors of continuous positive airways pressure usage at six months in minimally symptomatic patients. Further data from the MOSAIC trial: Abstract S29 Table 1
Authors: CD Turnbull, DJ Bratton, SE Craig, M Kohler, JR Stradling
Journal: Thorax (2015)

<h3>Introduction</h3> Severity of OSA and early patterns of CPAP usage have previously been shown to determine subsequent long term CPAP use in patients with symptomatic moderate-to-severe disease.<sup>1</sup> We wished to see if different factors influenced compliance in minimally symptomatic patients. <h3>Methods</h3> Patients were randomised to 6-months of CPAP or standard care if they had an ODI of &gt;7.5 h due to OSA on a baseline sleep study, but had insufficient daytime OSA symptoms to mandate CPAP.<sup>2</sup> Baseline characteristics (Table 1), medical history, ESS, SAQLI and SF-36 were recorded. Repeat overnight pulse oximetry was performed after entry for uniformity of trial ODI across recruiting centres. CPAP usage data were downloaded at the 2–4 week assessment, and at the 6 month assessment. Those who withdrew were assumed to have 0:00 h/n usage. Correlations were calculated between CPAP usage at the 6 month assessment and both the baseline characteristics and to the 2–4 week CPAP usage data. <h3>Results</h3> Median CPAP usage at 2–4 week follow-up was low at 2:49 h/n (n = 174, IQR 0:44, 5:13). Median usage at 6 month follow-up was 2:17 h/n (n = 195, IQR 0:08, 4:54). At 6 months males had significantly greater mean usage at 2:56 h/n compared to 1:47 h/n in females (95% confidence intervals of the difference, -1:49 to -0:09 h/n, p = 0.02). There were no other significant predictors of 6 month usage (age, BMI, ODI, ESS, sleep symptoms, smoking status, ethnicity, SAQLI, SF-36). Average usage of CPAP at 2–4 week assessment was moderately correlated with the average usage at the 6 month assessment (r = 0.76, p &lt; 0.001). <h3>Conclusions</h3> Male gender predicted greater CPAP usage at 6 months, but no other baseline characteristics were predictive of CPAP usage in these minimally symptomatic patients with generally mild OSA. 2–4 week CPAP usage was predictive of 6 month usage, but by no means could all patients’ usage be predicted at such an early stage. Thus in clinical practice, trials of CPAP are necessary in patients with minimally symptomatic OSA but it may be necessary for patients to try CPAP for longer than one month to determine those benefitting from treatment in the long term. <h3>References</h3> 1 <i>Thorax</i> 2010;<b>65</b>:829–32 2 <i>Thorax</i> 2012;<b>67</b>:1090-66
Three-Dimensional Breast Cancer Models Mimic Hallmarks of Size-Induced Tumor Progression
Authors: Manjulata Singh, Shilpaa Mukundan, Maria Jaramillo, Steffi Oesterreich, Shilpa Sant
Journal: Cancer Research (2016)

Tumor size is strongly correlated with breast cancer metastasis and patient survival. Increased tumor size contributes to hypoxic and metabolic gradients in the solid tumor and to an aggressive tumor phenotype. Thus, it is important to develop three-dimensional (3D) breast tumor models that recapitulate size-induced microenvironmental changes and, consequently, natural tumor progression in real time without the use of artificial culture conditions or gene manipulations. Here, we developed size-controlled multicellular aggregates ("microtumors") of subtype-specific breast cancer cells by using non-adhesive polyethylene glycol dimethacrylate hydrogel microwells of defined sizes (150-600 μm). These 3D microtumor models faithfully represent size-induced microenvironmental changes, such as hypoxic gradients, cellular heterogeneity, and spatial distribution of necrotic/proliferating cells. These microtumors acquire hallmarks of tumor progression in the same cell lines within 6 days. Of note, large microtumors of hormone receptor-positive cells exhibited an aggressive phenotype characterized by collective cell migration and upregulation of mesenchymal markers at mRNA and protein level, which was not observed in small microtumors. Interestingly, triple-negative breast cancer (TNBC) cell lines did not show size-dependent upregulation of mesenchymal markers. In conclusion, size-controlled microtumor models successfully recapitulated clinically observed positive association between tumor size and aggressive phenotype in hormone receptor-positive breast cancer while maintaining clinically proven poor correlation of tumor size with aggressive phenotype in TNBC. Such clinically relevant 3D models generated under controlled experimental conditions can serve as precise preclinical models to study mechanisms involved in breast tumor progression as well as antitumor drug effects as a function of tumor progression. Cancer Res; 76(13); 3732-43. ©2016 AACR.
Preliminary report on the dexamethasone suppression test for psychiatrically disturbed adolescents
Authors: F E Crumley, J Clevenger, D Steinfink, D Oldham
Journal: American Journal of Psychiatry (1982)

Of 100 adolescents who showed evidence of a depressive disorder and were given the dexamethasone suppression test (DST), 42% had abnormal results. Several had mixed or contradictory symptoms and the DST helped in diagnosis of an affective disorder and in treatment planning.
Targeted sequencing of BRCA1 and BRCA2 across a large unselected breast cancer cohort suggests that one-third of mutations are somatic
Authors: C. Winter, M.P. Nilsson, E. Olsson, A.M. George, Y. Chen, A. Kvist, T. Törngren, J. Vallon-Christersson, C. Hegardt, J. Häkkinen, G. Jönsson, D. Grabau, M. Malmberg, U. Kristoffersson, M. Rehn, S.K. Gruvberger-Saal, C. Larsson, Å. Borg, N. Loman, L.H. Saal
Journal: Annals of Oncology (2016)

A mutation found in the BRCA1 or BRCA2 gene of a breast tumor could be either germline or somatically acquired. The prevalence of somatic BRCA1/2 mutations and the ratio between somatic and germline BRCA1/2 mutations in unselected breast cancer patients are currently unclear.Paired normal and tumor DNA was analyzed for BRCA1/2 mutations by massively parallel sequencing in an unselected cohort of 273 breast cancer patients from south Sweden.Deleterious germline mutations in BRCA1 (n = 10) or BRCA2 (n = 10) were detected in 20 patients (7%). Deleterious somatic mutations in BRCA1 (n = 4) or BRCA2 (n = 5) were detected in 9 patients (3%). Accordingly, about 1 in 9 breast carcinomas (11%) in our cohort harbor a BRCA1/2 mutation. For each gene, the tumor phenotypes were very similar regardless of the mutation being germline or somatically acquired, whereas the tumor phenotypes differed significantly between wild-type and mutated cases. For age at diagnosis, the patients with somatic BRCA1/2 mutations resembled the wild-type patients (median age at diagnosis, germline BRCA1: 41.5 years; germline BRCA2: 49.5 years; somatic BRCA1/2: 65 years; wild-type BRCA1/2: 62.5 years).In a population without strong germline founder mutations, the likelihood of a BRCA1/2 mutation found in a breast carcinoma being somatic was ∼1/3 and germline 2/3. This may have implications for treatment and genetic counseling.