tbuckley/cabot-search huggingface dataset:
The Carcinogenicity of Ethyl Derivatives of &lt;italic&gt;p&lt;/italic&gt;-Aminoazobenzene&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: K SUGIURA, M L CROSSLEY, C J KENSLER
Journal: JNCI Journal of the National Cancer Institute (1954)

The Carcinogenicity of Ethyl Derivatives of p-Aminoazobenzene Kanematsu Sugiura, Kanematsu Sugiura Search for other works by this author on: Oxford Academic PubMed Google Scholar M. L. Crossley, M. L. Crossley Search for other works by this author on: Oxford Academic PubMed Google Scholar Charles J. Kensler Charles J. Kensler Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 1, August 1954, Pages 67–72, https://doi.org/10.1093/jnci/15.1.67 Published: 01 August 1954 Article history Received: 25 February 1954 Published: 01 August 1954
Abstract IA22: CYP3A5 mediates resistance to small molecule inhibitors in a subtype of pancreatic ductal adenocarcinoma
Authors: Elisa M. Noll, Elisa M. Noll, Christian Eisen, Christian Eisen, Elisa Espinet, Elisa Espinet, Albrecht Stenzinger, Wilko Weichert, Martin R. Sprick, Andreas Trumpp, Andreas Trumpp
Journal: Cancer Research (2016)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is clinically still treated as a single disease. We have generated patient-derived models representing the recently identified quasi-mesenchymal, classical and exocrine-like PDAC subtypes, and report a two-marker set facilitating patient stratification by immunohistochemistry. The subtypes show significant differences in overall survival and drug sensitivity, with the exocrine-like subtype being resistant to the tyrosine kinase inhibitors erlotinib, dasatinib, as well as the chemotherapeutic paclitaxel. Highly expressed cytochrome P450 3A5 (CYP3A5) actively metabolizes these compounds in the exocrine-like subtype, and pharmacological or shRNA-mediated CYP3A5 inhibition sensitizes tumor cells in vivo. Additionally, we investigated the transcriptional network underlying the subtype-specific CYP3A5 expression. Hence, these data show that exocrine-like PDAC adopts a highly effective detoxification mechanism akin to that of hepatocytes. High expression of CYP3A5 in other tumor entities suggests this pathway as an important target to overcome drug resistance and to predict response to therapy with small molecule drugs. Citation Format: Elisa M. Noll, Elisa M. Noll, Christian Eisen, Christian Eisen, Elisa Espinet, Elisa Espinet, Albrecht Stenzinger, Wilko Weichert, Martin R. Sprick, Andreas Trumpp, Andreas Trumpp. CYP3A5 mediates resistance to small molecule inhibitors in a subtype of pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr IA22.
Uropathogenic Escherichia coli strain CFT073 disrupts NLRP3 inflammasome activation
Authors: Anna Waldhuber, Manoj Puthia, Andreas Wieser, Christine Cirl, Susanne Dürr, Silke Neumann-Pfeifer, Simone Albrecht, Franziska Römmler, Tina Müller, Yunji Zheng, Sören Schubert, Olaf Groß, Catharina Svanborg, Thomas Miethke
Journal: Journal of Clinical Investigation (2016)

Successful bacterial pathogens produce an array of virulence factors that allow subversion of the immune system and persistence within the host. For example, uropathogenic Escherichia coli strains, such as CFT073, express Toll/IL-1 receptor–containing (TIR-containing) protein C (TcpC), which impairs TLR signaling, thereby suppressing innate immunity in the urinary tract and enhancing persistence in the kidneys. Here, we have reported that TcpC also reduces secretion of IL-1β by directly interacting with the NACHT leucin-rich repeat PYD protein 3 (NLRP3) inflammasome, which is crucial for recognition of pathogens within the cytosol. At a low MOI, IL-1β secretion was minimal in CFT073-infected macrophages; however, IL-1β release was markedly increased in macrophages infected with CFT073 lacking tcpC. Induction of IL-1β secretion by CFT073 and tcpC–deficient CFT073 required the NLRP3 inflammasome. TcpC attenuated activation of the NLRP3 inflammasome by binding both NLRP3 and caspase-1 and thereby preventing processing and activation of caspase-1. Moreover, in a murine urinary tract infection model, CFT073 infection rapidly induced expression of the NLRP3 inflammasome in the bladder mucosa; however, the presence of TcpC in WT CFT073 reduced IL-1β levels in the urine of infected mice. Together, these findings illustrate how uropathogenic E. coli use the multifunctional virulence factor TcpC to attenuate innate immune responses in the urinary tract.
Blue rubber bleb nevus syndrome: combined surgical and endoscopic treatment
Authors: Monica Arena, Matteo Virdis, Elisabetta Morandi, Paolo Viaggi, Andrea Pisani, Enrico Opocher, Enzo Masci
Journal: Endoscopy (2015)

Blue rubber bleb nevus syndrome (BRBNS) is a rare disease associated with multiple venous malformations in the skin, gastrointestinal tract, and other organs [1], which usually presents with extensive hemorrhage or anemia [2]. Different therapeutic strategies have been proposed.
Abstract B73: The monoterpene, citral, increases intracellular oxygen radicals and inhibits cancer cell proliferation by inducing apoptosis and endoplasmic reticulum stress .
Authors: Arvinder Kapur, Mildred Felder, Lucas Fass, Justanjyot kaur, Austin Czarnecki, Kavya Rathi, Manish Patankar
Journal: Clinical Cancer Research (2016)

Abstract The terpene-enriched steam distilled extract of ginger rhizomes has potent anti-tumor activity. Screening of the components of ginger extract demonstrated citral, a commonly used food flavoring agent, as the major monoterpene that inhibits proliferation of human and murine cancer cell lines A2780, ECC-1, OVCAR-3, SKOV-3, ID8 and MOVCAR. Citral initiates a rapid decrease in intracellular levels of glutathione and a corresponding increase in oxygen radicals. In wild-type p53-expressing ECC-1 cells, citral treatment increases phosphorylation of the Ser-15 residue of p53 and causes apoptosis. Inhibition of intracellular oxygen radicals by N-acetylcysteine and p53 activity by pifithrin-α inhibits citral-induced apoptosis in ECC-1 cells. Apoptosis in mutant p53 (Arg248Glu) expressing OVCAR-3 cells was also inhibited by N-acetylcysteine and was associated with a decrease in phosphorylation of Ser-15 of p53. Finally, in cells not expressing p53, citral inhibited proliferation, but not through apoptosis. Instead in the p53-negative SKOV-3 cells, citral treatment caused endoplasmic reticulum stress indicated by increase in phosphorylation of eIF2α and the expression of CHOP, GADD45, EDEM, ATF4 and Hsp90 and increased ATG5 and LC3-II suggesting the cells were undergoing autophagy. The study identifies the mechanism that allows citral to produce its cytotoxic effects. Combined with our recent results that nanoparticle-encapsulated citral decreases in vivo growth of 4T1 murine breast tumors, the results from the current study suggest that citral and its analogs be considered as chemotherapeutic agents. Since citral mediates its cytotoxic effects primarily by inducing oxidative stress, it is likely that this monoterpenes and its derivatives can be used for the treatment of a variety of solid tumors including ovarian cancer. Citation Format: Arvinder Kapur, Mildred Felder, Lucas Fass, Justanjyot kaur, Austin Czarnecki, Kavya Rathi, Manish Patankar. The monoterpene, citral, increases intracellular oxygen radicals and inhibits cancer cell proliferation by inducing apoptosis and endoplasmic reticulum stress . [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B73.
&lt;TITLE&gt;Academic Health Centers&lt;/TITLE&gt;
Authors: Lise Stevens, Cassio Lynm, Richard Glass
Journal: JAMA (2001)

The JAMA Patient Page is a public service of JAMA.The information and recommendations appearing on this page are appropriate in most instances, but they are not a substitute for medical diagnosis.For specific information concerning your personal medical condition, JAMA suggests that you consult your physician.This page may be reproduced noncommercially by physicians and other health care professionals to share with patients.Any other reproduction is subject to AMA approval.
Shattuck Lecture -- Misconduct in Medical Research
Authors: D Baltimore
Journal: New England Journal of Medicine (1993)

wards, with caring personnel (who may be staff physicians, physician's assistants, family nurse practitioners, or best, a combination) and superb nurses would be better.Most medical students begin their careers with interest, enthusiasm, and energy.It is our job as teachers and physi- cians to make certain that these qualities are not only preserved but also heightened and transmitted to the care of patients.Each patient should legitimately feel, as should his or her physician, that he or she is a "great case."
Comparing Radical Mastectomy with Quadrantectomy, Axillary Dissection, and Radiotherapy in Patients with Small Cancers of the Breast
Authors: Umberto Veronesi, Roberto Saccozzi, Marcella Del Vecchio, Alberto Banfi, Claudio Clemente, Mario De Lena, Giuseppe Gallus, Marco Greco, Alberto Luini, Ettore Marubini, Giuseppe Muscolino, Franco Rilke, Bruno Salvadori, Annamaria Zecchini, Roberto Zucali
Journal: New England Journal of Medicine (1981)

From 1973 to 1980, we carried out a controlled study at the National Cancer Institute in Milan to consider the value of a conservative procedure in patients with breast cancer of small size. We randomized 701 patients with breast cancer measuring less than 2 cm in diameter and with no palpable axillary lymph nodes to Halsted radical mastectomy or to "quadrantectomy" with axillary dissection and radiotherapy to the ipsilateral residual breast tissue. We treated 349 patients with Halsted mastectomy and 352 with quadrantectomy. The two groups were comparable in age distribution, size and site of primary tumor, menopausal status, and frequency of axillary metastases. There were three local recurrences in the Halsted group and one in the quadrantectomy group. Actuarial curves showed no difference between the two groups in disease-free or overall survival. From these results, mastectomy appears to involve unnecessary mutilation in patients with breast cancer of less than 2 cm and no palpable axillary nodes. (N Engl J Med. 1981; 305:6–11.)
Lipocalin-2 deficiency or blockade protects against aortic abdominal aneurysm development in mice
Authors: Carlos Tarín, Carlos Ernesto Fernandez-Garcia, Elena Burillo, Carlos Pastor-Vargas, Patricia Llamas-Granda, Borja Castejón, Priscila Ramos-Mozo, Mónica M. Torres-Fonseca, Thorsten Berger, Tak W. Mak, Jesús Egido, Luis M. Blanco-Colio, Jose L. Martín-Ventura
Journal: Cardiovascular Research (2016)

To study the role of lipocalin-2 (Lcn2) and the effect of Lcn2 blockade via anti-Lcn2 antibody in the development of abdominal aortic aneurysm (AAA). Expression mRNA and protein levels of Lcn2 and its human orthologue neutrophil gelatinase-associated lipocalin (NGAL) in aortic wall samples from experimental mouse and human AAA samples, respectively, were analysed by real-time PCR and immunohistochemistry. Experimental AAA was induced by aortic elastase perfusion in wild-type mice (WT) and Lcn2-deficient mice (Lcn2−/−). NGAL/Lcn2 mRNA and protein levels in human and murine AAA samples were increased compared with healthy aortas. Decreased AAA incidence and reduced aortic expansion were observed in Lcn2−/− mice or mice preoperative treated with a polyclonal anti-Lcn2 antibody compared with WT mice or mice treated with control IgG, respectively, at Day 14 after elastase perfusion. Moreover, immunohistochemical analysis of AAA tissues from Lcn2−/− or anti-Lcn2-treated mice showed diminished elastin damage, reduced microvessels and polymorphonuclear neutrophil (PMN) infiltration, and enhanced preservation of vascular smooth muscle cells compared with WT aortas. Fluorescent molecular tomography revealed decreased MMP activity in AAA of Lcn2−/− mice compared with WT controls. Therapeutic administration of anti-Lcn2 antibody to WT mice 3 days after elastase perfusion decreased aortic dilatation and PMN infiltration compared with WT mice treated with control IgG. Either Lcn2 deficiency or anti-Lcn2 antibody blockade limits AAA expansion in mice by decreasing PMN infiltration in the aorta. Lcn2 modulation may therefore be a viable new therapeutic option for the treatment of AAA.
Letters
Authors: J. E Enstrom
Journal: BMJ (2003)

<h3>Objective</h3> Patients with increased PD-L1<sup>+</sup> host cells in tumours are more potent to benefit from antiprogrammed death-1/programmed death ligand-1 (PD-L1) treatment, but the underlying mechanism is still unclear. We aim to elucidate the nature, regulation and functional relevance of PD-L1<sup>+</sup> host cells in hepatocellular carcinoma (HCC). <h3>Design</h3> A total of untreated 184 HCC patients was enrolled randomly. C57BL/6 mice are given injection of Hepa1-6 cells to form autologous hepatoma. ELISpot, flow cytometry and real-time PCR are applied to analyse the phenotypic characteristics of PD-L1<sup>+</sup> cells isolated directly from HCC specimens paired with blood samples or generated from ex vivo and in vitro culture systems. Immunofluorescence and immunohistochemistry are performed to detect the presence of immune cells on paraffin-embedded and formalin-fixed samples. The underlying regulatory mechanisms of metabolic switching are assessed by both in vitro and in vivo studies. <h3>Results</h3> We demonstrate that PD-L1<sup>+</sup> host macrophages, which constructively represent the major cellular source of PD-L1 in HCC tumours, display an HLA-DR<sup>high</sup>CD86<sup>high</sup> glycolytic phenotype, significantly produce antitumourigenic IL-12p70 and are polarised by intrinsic glycolytic metabolism. Mechanistically, a key glycolytic enzyme PKM2 triggered by hepatoma cell derived fibronectin 1, via a HIF-1α-dependent manner, concurrently controls the antitumourigenic properties and inflammation-mediated PD-L1 expression in glycolytic macrophages. Importantly, although increased PKM2<sup>+</sup> glycolytic macrophages predict poor prognosis of patients, blocking PD-L1 on these cells eliminates PD-L1-dominant immunosuppression and liberates intrinsic antitumourigenic properties. <h3>Conclusions</h3> Selectively modulating the ‘context’ of glycolytic macrophages in HCC tumours might restore their antitumourigenic properties and provide a precise strategy for anticancer therapy.
Abstract P5-13-06: Concurrent gonadotropin-releasing hormone (GnRH) agonist administration with chemotherapy improves neoadjuvant chemotherapy responses in young premenopausal breast cancer patients
Authors: TI Yoon, HJ Kim, JH Yu, G Sohn, BS Ko, JW Lee, BH Son, SH Ahn
Journal: Cancer Research (2016)

Abstract Background Gonadotropin-releasing hormone (GnRH) agonist therapy for ovarian function preservation shows promising results. This study aimed to determine the oncologic efficacy of GnRH agonist treatment concurrent with chemotherapy in a neoadjuvant setting. Patients and Methods A retrospective analysis was performed on 332 cases of invasive breast cancer in patients who were &amp;lt;40 years old at diagnosis and received GnRH agonists concurrent with neoadjuvant chemotherapy (GnRH agonist group) or neoadjuvant chemotherapy alone (neochemotherapy-alone group) at Asan Medical Center from December 2010 to September 2014. Pathologic complete response rates (pCR) and Ki-67 changes were evaluated between the two groups. For hormone receptor (HR)-positive tumors, the clinical response and preoperative endocrine prognostic index (PEPI) score also were evaluated. Results The median age was 32 ± 3.9 and 36 ± 3.0 years old in the GnRH agonist group and neochemotherapy-alone group, respectively (P &amp;lt; .001). Adjusted for tumor size, grade, lymph node metastasis, HR status, and chemotherapy regimen, the GnRH agonist group exhibited a higher pCR rate with an odds ratio (OR) of 2.98 (95% CI, 1.37–6.34) and more decreased Ki-67 expression during treatment (P = 0.05) than the neochemotherapy-alone group. In HR-negative tumors, the GnRH agonist group showed a higher pCR rate (multivariate OR = 3.50; 95% CI, 1.37–8.95) and more decreased Ki-67 expression (P = 0.047). In HR-positive breast cancer, the pCR rate, change in Ki-67 index, and clinical response were higher and preoperative prognostic index (PEPI) scores were lower in the GnRH agonist group, but not significant between the two treatment groups. Conclusion Concurrent administration of GnRH agonists during neoadjuvant chemotherapy improved pCR rates and suppressed Ki-67 expression especially in HR-negative tumors. Citation Format: Yoon TI, Kim HJ, Yu JH, Sohn G, Ko BS, Lee JW, Son BH, Ahn SH. Concurrent gonadotropin-releasing hormone (GnRH) agonist administration with chemotherapy improves neoadjuvant chemotherapy responses in young premenopausal breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-13-06.
Clinical and psychobiological characteristics of simultaneous panic disorder and major depression
Authors: L Grunhaus
Journal: American Journal of Psychiatry (1988)

Simultaneous major depression and panic disorder appears to be a common occurrence in psychiatric patients. Patients with this condition present with more severe symptoms than patients with major depression only, respond less well to conventional antidepressants, and in general exhibit greater psychopathology over the course of their illness. Evidence suggesting a possible "dual diathesis," depression and panic, in these patients is reviewed from epidemiological, clinical, and biological perspectives. The importance of taking into account the combined symptoms in treatment planning and physiopathological studies is discussed.
Follow-up of children treated in psychiatric hospitals: a review of studies
Authors: M J Blotcky, T L Dimperio, J T Gossett
Journal: American Journal of Psychiatry (1984)

Approximately 15,000 children are currently in residential psychiatric treatment in the United States. Their response to treatment and their long-term adaptation remain only partially understood. The authors review 24 child inpatient follow-up studies and discuss their methodologies. Findings are presented along 10 dimensions relevant to long-term outcome. Good prognosis was positively correlated with adequate intelligence, nonpsychotic and nonorganic diagnoses, absence of antisocial features and bizarre symptoms, healthy family functioning, adequate length of stay, and involvement in aftercare. The authors discuss factors suggesting caution in the interpretation of these findings. They emphasize the importance of longitudinal research in developing empirically based, increasingly effective treatment programs.
Mental health services and the elderly: needs and options
Authors: G D Cohen
Journal: American Journal of Psychiatry (1976)

The author examines mental health issues related to the elderly from the perspective of the options for immediate impact on treatment. He stresses the potential for creative collaboration between public and private mental health care systems. Myths, stereotypes, and misinformation about the aged are discussed, as are the positive. The author also describes an innovative model of service delivery in the treatment of older individuals.
Renal tubular function in patients on long-term lithium therapy
Authors: G W Viol, P Grof, L Daigle
Journal: American Journal of Psychiatry (1975)

The authors conducted a study in which 10 patients with recurrent affective disorders who responded completely to long-term lithium therapy but who were otherwise unselected were tested for renal tubular concentrating and acidification ability. Despite frequent symptoms of thirst, polyuria, and nocturia, all patients were able to concentrate urine normally and all showed normal renal tubular acidification ability. A significant correlation was found between erythrocyte lithium concentration and maximum urinary osmolality.
EpCAM-regulated intramembrane proteolysis induces a cancer stem cell-like gene signature in hepatitis B virus-infected hepatocytes
Authors: Saravana Kumar Kailasam Mani, Hao Zhang, Ahmed Diab, Pete E. Pascuzzi, Lydie Lefrançois, Nadim Fares, Brigitte Bancel, Philippe Merle, Ourania Andrisani
Journal: Journal of Hepatology (2016)
Elimination of clonogenic Burkitt's lymphoma cells from human bone marrow using 4-hydroperoxycyclophosphamide in combination with monoclonal antibodies and complement
Authors: P De Fabritiis, M Bregni, J Lipton, J Greenberger, L Nadler, L Rothstein, M Korbling, J Ritz, RC Jr Bast
Journal: Blood (1985)
SP0018 OX40 Stimulation and Blockade in Cancer and Inflammatory Disease
Authors: M. Croft
Journal: Annals of the Rheumatic Diseases (2015)

The Tumor Necrosis Factor Receptor (TNFR) superfamily consists of 29 membrane and soluble proteins with similar structural features. Many of these molecules are expressed on cells of the immune system and are potential targets for therapeutic intervention in a number of immune based diseases. OX40 (CD134, TNFRSF4) is one TNFR family member that can act as a co-stimulatory receptor for both effector CD4 and CD8 T cells driving proliferation and clonal expansion when ligated by its TNF family ligand, OX40L (CD252, TNFSF4). OX40 signaling can also inhibit the development of suppressive peripheral regulatory T cells (pTreg), as well as promote the activity of innate lymphoid cells such as NK and NKT cells, further amplifying its ability to help an effective immune response. In accordance, many studies in animal models of inflammatory disease, autoimmunity, and transplantation have now shown that blocking OX40/OX40L interactions can reduce the activity of pathogenic T cells and dampen inflammation. Conversely, stimulation of OX40 signaling with agonist antibodies in animals can promote T cell activity that protects against tumor growth as well as T cells that can reduce viral replication. The potential of targeting OX40 or OX40L as a therapy for human immune disease will be discussed, as well as recent and ongoing clinical trials. <h3>Disclosure of Interest</h3> None declared