tbuckley/cabot-search huggingface dataset:
Abstract 3130: Zoledronic acid inhibits proliferation and metastasis of human pancreatic cancer in the patient-derived orthotopic xenograft (PDOX) model by targeting tumor-educated macrophages
Authors: Yukihiko Hiroshima, Mohamed K. Hassenein, Rhiana Menen, Matthew H.g. Katz, Jason B. Fleming, Sho Sato, Takashi Murakami, Mako Yamamoto, Fuminari Uehara, Shinji Miwa, Shuya Yano, Masashi Momiyama, Ali Maawy, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman
Journal: Cancer Research (2014)

Abstract Macrophages harvested from the peritoneal cavity of nude mice with subcutaneous human pancreatic tumors were defined as “tumor-educated macrophages” (EMϕ) and macrophages harvested from mice without tumors were defined as “naïve macrophages” (NMϕ). EMϕ promote tumor growth and metastasis. The aim of the present study was to determine the efficacy of Zoledronic acid (ZA) on EMϕ in a pancreatic cancer patient derived orthotopic xenograft (PDOX) nude mouse model. In this study, EMϕ and NMϕ were compared for their ability to enhance tumor progression. We initially demonstrated that the cancer cells exposed to the conditioned medium harvested from EMϕ culture significantly increased proliferation (p = 0.016) and had more migration stimulation capability (p &amp;lt; 0.001) compared to cultured cancer cells treated with the conditioned medium from NMϕ. Next, we examined the efficacy of ZA on EMϕ, and NMϕ and found that ZA had the ability to kill both EMϕ and NMϕ in vitro. We then demonstrated that EMϕ promoted tumor growth and metastasis in an orthotopic mouse model of a human pancreatic cancer cell line, ZA reduced the tumor growth (p = 0.006) and metastasis (p = 0.025) promoted by EMϕ. Finally, we examined the efficacy of ZA for pancreatic cancer in the PDOX model, and found that the combination of gemcitabine (GEM) and ZA reduced tumor weight (p = 0.016) and tumor growth (p = 0.005) compared to GEM alone. ZA alone reduced metastasis (p = 0.009). These results suggest that ZA inhibits the proliferation and the metastasis of human pancreatic cancer by targeting EMϕ. Citation Format: Yukihiko Hiroshima, Mohamed K. Hassenein, Rhiana Menen, Matthew H.g. Katz, Jason B. Fleming, Sho Sato, Takashi Murakami, Mako Yamamoto, Fuminari Uehara, Shinji Miwa, Shuya Yano, Masashi Momiyama, Ali Maawy, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman. Zoledronic acid inhibits proliferation and metastasis of human pancreatic cancer in the patient-derived orthotopic xenograft (PDOX) model by targeting tumor-educated macrophages. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3130. doi:10.1158/1538-7445.AM2014-3130
Visfatin induces human endothelial VEGF and MMP-2/9 production via MAPK and PI3K/Akt signalling pathways: novel insights into visfatin-induced angiogenesis
Authors: Raghu Adya, Bee K. Tan, Anu Punn, Jing Chen, Harpal S. Randeva
Journal: Cardiovascular Research (2007)

Visfatin is a novel adipokine whose plasma concentrations are altered in obesity and obesity-related disorders; these states are associated with an increased incidence of cardiovascular disease. We therefore investigated the effect of visfatin on vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP-2, MMP-9) production and the potential signalling cascades. In human umbilical vein endothelial cells (HUVECs), visfatin significantly and dose-dependently up-regulated gene expression and protein production of VEGF and MMPs and down-regulated expression of tissue inhibitors of MMPs (TIMP-1 and TIMP-2). The gelatinolytic activity of MMPs (analysed by zymography) correlated with mRNA and western blot findings. Interestingly, visfatin significantly up-regulated VEGF receptor 2 expression. Inhibition of VEGFR2 and VEGF [by soluble FMS-like tyrosine kinase-1 (sFlt1)] down-regulated visfatin-induced MMP induction. Visfatin induced dose- and time-dependent proliferation and capillary-like tube formation. Importantly, visfatin was noted to have anti-apoptotic effects. In HUVECs, visfatin dose-dependently activated PI3K/Akt (phosphatidylinositol 3-kinase/Akt) and ERK1/2 (extracellular signal-regulated kinase) pathways. The functional effects and MMP/VEGF induction were shown to be dependent on the MAPK/PI3K-Akt/VEGF signalling pathways. Inhibition of PI3K/Akt and ERK1/2 pathways led to significant decrease of visfatin-induced MMP and VEGF production and activation, along with significant reduction in endothelial proliferation and capillary tube formation. Our data provide the first evidence of visfatin-induced endothelial VEGF and MMP production and activity. Further, we show for the first time the involvement of the MAPK and PI3K/Akt signalling pathways in mediating these actions, as well as endothelial cell proliferation. Collectively, our findings provide novel insights into visfatin-induced endothelial angiogenesis.
Selective targeting of the mTORC1/2 protein kinase complexes leads to antileukemic effects in vitro and in vivo
Authors: K Schuster, J Zheng, A A Arbini, C C Zhang, P P Scaglioni
Journal: Blood Cancer Journal (2011)

The BCR/ABL tyrosine kinase promotes leukemogenesis through activation of several targets that include the phosphoinositide 3-kinase (PI3K). Tyrosine kinase inhibitors (TKIs), which target BCR/ABL, induce striking clinical responses. However, therapy with TKIs is associated with limitations such as drug intolerance, inability to universally eradicate the disease and emergence of BCR/ABL drug-resistant mutants. To overcome these limitations, we tested whether inhibition of the PI3K/target of rapamycin (mTOR) signaling pathway has antileukemic effect in primary hematopoietic stem cells and BA/F3 cells expressing the BCR/ABL oncoprotein. We determined that dual inhibition of PI3K/mTOR causes growth arrest and apoptosis leading to profound antileukemic effects both in vitro and in vivo. We also established that pharmacologic inhibition of the mTORC1/mTORC2 complexes is sufficient to cause these antileukemic effects. Our results support the development of inhibitors of the mTORC1/2 complexes for the therapy of leukemias that either express BCR/ABL or display deregulation of the PI3K/mTOR signaling pathway.
PATHOLOGY AND TREATMENT OF CHRONIC INDURATION OF THE MAMMA
Authors: J. Birkett
Journal: BMJ (1853)

Some experiments which I performed in 1850, with Dr.Glover, may assist in clearing up this difficulty.Conia given to frogs by the mouth, or inserted beneath the skin of 'the lee, produced (besides speedy local parysis in the latter mstance) general flaccidity and prostration, termi- nating in the total abolition of consciousness in from twenty -Minutes to an hour.The heart, however, continued to beat for three or four hours afterwards.A little of the poison was next applied to the outer surface of the ventricle.Im-
How many doctors does Britain need?
Authors: L M Eccles, S J Townsend
Journal: BMJ (1993)

Unlicensed nicotine skin patches EDITOR,-Nicotine skin patches were launched in Britain in June 1992.Three licensed patches (Nicabate, Nicorette, Nicotinell) are now available over the counter from pharmacies.There is convincing evidence from clinical trials that these patches are an effective aid to stopping smoking.'In the past two months there has been a rash of newspaper advertisements for unlicensed patches available by mail order.We are aware of brands going under the names Nicostop, Nicorene, Nicotine Patch, Nicocheck, and Nicoban.The advertisements for two brands, for example, make extravagant claims: "Guaranteed to stop you smoking" (Nicostop); "With Nicoban's help you stop smoking painlessly, simply, permanently....You wear it on your arm, and it releases a measured dosage of nicotine extract throughout the day which really does take away the desire to smoke.So simple, so easy.And above all ... so effective."Common to these patches is the claim that they deliver either nicotine or "nicotine extract" and the promise of great savings over patch products "sold by our competitors."But none of these mail order products has undergone regulatory scrutiny.We
Abstract 2591: Caffeic acid phenethyl ester (CAPE) suppresses melanoma tumor growth by inhibiting AKT/XIAP pathway
Authors: Kartick C. Pramanik, Shashi Kudugunti, Majid Moridani, Sanjay K. Srivastava
Journal: Cancer Research (2012)

Abstract The incidence of melanoma is constantly on the rise indicating that current available therapies are not very effective. Moreover, melanoma is highly metastatic and resistant to chemotherapeutic drugs. Our previous studies have demonstrated that caffeic acid phenethyl ester (CAPE) suppress the growth of melanoma cells and induce ROS generation. However, the exact mechanism of the growth suppressive effects of CAPE was not clear. Here we determined the potential mechanism of CAPE against melanoma in vitro and in vivo. In a concentration and time-dependent study, CAPE treatment suppressed the activating phosphorylation of PI3K at Tyr-458, PDK1 at Ser-241, mTOR at Ser-2448 and AKT at Ser-473 in B16F0 and SK-MEL-28 melanoma cells. Furthermore, the expression of XIAP, survivin and BCl2 were down-regulated by CAPE treatment in both the cell lines. Significant apoptosis was observed in both the cell lines by CAPE treatment as indicated by cleavage of caspase-3 and PARP. AKT kinase activity was inhibited by CAPE in a concentration-dependent manner. Since Akt regulates XIAP, their interaction was examined by immunoprecipitation studies. Our results show that CAPE treatment decreased the interaction of AKT with XIAP. To establish the involvement of Akt in the apoptosis-inducing effects of CAPE, cells were transfected with Akt. Our results reveal that AKT over-expression attenuated the decrease in XIAP and significantly blocked CAPE-mediated apoptosis. Similarly, over-expression of XIAP further decreased CAPE-induced apoptosis. To confirm the involvement of ROS in the inhibition of AKT/XIAP pathway, cells were treated with antioxidant NAC prior to CAPE treatment. Our results indicate that NAC blocked CAPE mediated AKT/XIAP inhibition and protected the cells from apoptosis. In addition, oral administration of 10mg/kg/day CAPE substantially suppressed the growth of B16F0 tumor xenografts in C57BL/6 mice. Tumors from CAPE treated mice showed reduced phosphorylation of PI3K, AKT, mTOR and protein level of XIAP and enhanced the cleavage of caspase-3 and PARP. Taken together, our results suggest that CAPE suppresses AKT/XIAP pathway leading to apoptosis in melanoma tumor cells in vitro and in vivo. [Supported in part by R01 grant CA129038 (to S.K.S) awarded by the National Cancer Institute]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2591. doi:1538-7445.AM2012-2591
Ultrasoundwave Treatment of Chronic Disorders of the Locomotor System
Authors: A. Sonnenschein
Journal: Annals of the Rheumatic Diseases (1951)

Treatment with ultrasoundwaves is the latest method of physical therapy to attract attention in many countries.Langevin and others (1923) first proved the existence of biological effects of ultrasoundwaves in experiments in which they killed small fishes.Pohlman and his co-workers (1939) used ultrasoundwaves in the treatment of sciatic pain and other neuralgias.But only since 1945 has it become possible to build and distribute ultrasoundwave apparatus so that their effects could be studied on a wider scale.These results have been acclaimed as successful, besides being subjected to severe criticism.Definition.-The name ultrasound (U.S.) is given to a "sound " produced by more than 18,000 mechanical vibrations per sec.which is not audible to the human ear.into the air, and is therefore altogether lost for therapeutic purposes.To prevent this, a fluid can be inserted between the sound-head and the body surface which reduces reflection to some 30 per cent.In therapeutic work liquid AA42
'Do Not Resuscitate' Orders
Authors: Valerie D. Raskin
Journal: JAMA (1985)

<h3>To the Editor.—</h3> As a house officer, I welcome the recent<i>JAMA</i>discussion of "do not resuscitate" (DNR) orders. In view of Dr Youngner's findings that resident physicians, albeit in consultation with attending physicians in the medical intensive care unit, are primarily responsible for writing DNR orders,<sup>1</sup>it is ironic that the same issue reports that a mere 8% of physicians received training in medical ethics as part of their residency programs.<sup>2</sup>If only 15% of DNR orders are written at the request of the patient or his family, it seems that the decision to resuscitate is being made by those of us with the least experience and training in such matters. Perhaps the question of who makes decisions about DNR orders should separate patients' decisions from those of their families. Talking about DNR orders may be as uncomfortable for the inexperienced physician as it is for the
Publish and be pampered
Authors: C. White
Journal: BMJ (2003)

How freelance health journalists are under increased pressure from PR firms

A“message” reported in the news media is eight times more likely to be trusted than an advertisement, according to a survey of 850 US and European opinion leaders, published earlier this year. An article in a news magazine is 10 times more likely to be trusted than a product advertisement, the survey, Building Trust , by public relations giant Edelman, showed (/www.edelman.com/

Credibility depends on repeated exposure to the message, the survey indicated. No surprise, then, that the pharmaceutical industry, and nutriceutical and lifestyle product manufacturers court health journalists as eagerly as they do doctors. This courtship is not restricted to journalists writing for specialist medical publications; consumer media are also on the agenda.

And there's a lot more of it on the way. “Health is a growth area for PR,” says Ann Mealor, …
P957 FINAL ANALYSIS OF AETIOLOGY/COMORBIDITIES IN EUROPEAN PATIENTS FROM THE GIDEON (GLOBAL INVESTIGATION OF THERAPEUTIC DECISIONS IN HEPATOCELLULAR CARCINOMA AND OF ITS TREATMENT WITH SORAFENIB) STUDY
Authors: V. Ratziu, P.I. Stal, J.-P. Bronowicki, F. Serejo, G.M. Bodoky, A.E. Criotoru, B. Daniele, C. Papandreou, J. Turnes, M. Cox, P. Mathurin
Journal: Journal of Hepatology (2014)
A phase 2 study of the farnesyltransferase inhibitor tipifarnib in poor-risk and elderly patients with previously untreated acute myelogenous leukemia
Authors: Jeffrey E. Lancet, Ivana Gojo, Jason Gotlib, Eric J. Feldman, Jacqueline Greer, Jane L. Liesveld, Laura M. Bruzek, Lawrence Morris, Youn Park, Alex A. Adjei, Scott H. Kaufmann, Elizabeth Garrett-Mayer, Peter L. Greenberg, John J. Wright, Judith E. Karp
Journal: Blood (2006)
Management of diabetes: are doctors framing the benefits from the wrong perspective?
Authors: H. A Wolpert, B. J Anderson
Journal: BMJ (2001)

<h3>Introduction</h3> Vedolizumab. (VDZ) is an α4β7 integrin antagonist licensed to treat moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD). We provide long-term real-world data on outcomes after VDZ discontinuation. <h3>Methods</h3> A consecutive cohort of 193 adult IBD patients initiated on VDZ between May 2015 and June 2019 was retrospectively reviewed up to June 2020. Primary outcomes were post-VDZ relapse, biologic and surgical event rates. VDZ discontinuation for remission was classified as treatment for at least 6 months with 3 months corticosteroid-free clinical remission pre-discontinuation. Statistics: Continuous variables (median, interquartile ranges (IQR), Mann–Whitney U- test); categorical variables (frequency, percentages, chi-square test). <h3>Results</h3> Data from 90 CD and 103 UC patients was analysed. Prior biologic exposure (Adalimumab 57.5% (111/193); Infliximab 46.6% (90/193); Ustekinumab in CD 42.2% (38/90)) was high overall. Total all-cause VDZ discontinuation rate was 74.4% (67/90) in CD and 56.3% (58/103) in UC with the majority discontinuing within year 1 (CD: <i>n</i> = 44; UC: <i>n</i> = 35) as compared to years 2, 3 or greater (CD: <i>n</i> = 13, 8, 2; UC: <i>n</i> = 11, 6, 7). Of these patients, 77.6% (52/67) with CD and 63.8% (37/58) with UC required another biologic. A majority with CD persisted on subsequent Ustekinumab (68%; 30/44) or anti-TNF (71%; 5/7) by the end of the study period. In UC, 26% (7/27) persisted on an anti-TNF and 64% (7/11) on Tofacitinib (Table 1). 17 patients were retreated with VDZ having discontinued it for remission (CD: <i>n</i> = 7; UC:<i> n</i> = 10). The median duration of VDZ retreatment was 164 [IQR: 87-189] weeks for CD and 165 [IQR: 126-205] weeks for UC (duration follow-up from first VDZ discontinuation for CD: 46 [IQR: 30-56] weeks; UC: 46 [IQR: 16-77] weeks). Of this larger cohort, there was no significant difference in relapse rate on VDZ retreatment between CD and UC (14% (<i>n</i> = 1) vs. 30% (<i>n</i> = 3), <i>p</i> = 0.6029)). A large minority of patients underwent subsequent surgery (CD: 38.8% (26/67); UC: 29.3% (17/59) with the median interval to surgery greatest in UC (CD: 21 (IQR: 9-71) vs. UC 63 (IQR: 12-84) weeks, <i>p</i> = 0.2409). Most CD patients who had surgery post VDZ (61.5%, 16/26) had had 2 prior biologics as compared to none who had VDZ first line (<i>p</i> = 0.184) whereas in UC, biologic exposure had less impact on surgery rate (<i>p</i> = 0.592). <h3>Conclusions</h3> Our data suggests VDZ recapture for relapse following discontinuation of therapy for remission, sequencing Ustekinumab after VDZ in complex/refractory CD and anti-TNF therapy before or after VDZ in UC are options in the management algorithm of IBD.
PROTEOSE INTOXICATIONS AND INJURY OF BODY PROTEIN
Authors: G. H. Whipple, Donald D. Van Slyke
Journal: The Journal of Experimental Medicine (1918)

The acute intoxication following an injection of a toxic proteose is usually associated with a large increase (40 per cent or more) in the non-protein nitrogen of the blood. This increase is found chiefly in the blood urea nitrogen, but the amino and peptide nitrogens also may show small increases. The changes observed in the blood non-protein nitrogen are identical with those which follow the feeding of large amounts of meat (8). These facts indicate that the proteose intoxication causes an abnormally rapid autodigestion of tissue proteins, but that the nitrogenous end-products are, in chief part at least, the same that result from normal catabolism of food proteins. There is no evidence that the autolytic products play any part in causing the intoxication. The possibility of such a part and a resultant vicious circle is not excluded, but from the available facts the autolysis appears more as a result rather than cause of the intoxication. It appears possible that in disease or intoxication tissue catabolism may be enormously accelerated and yet yield the end-products of normal protein metabolism.
Defective B cell development and function in Btk-deficient mice
Authors: Wasif N. Khan, Frederick W. Alt, Rachel M. Gerstein, Barbara A. Malynn, Irene Larsson, Gary Rathbun, Laurie Davidson, Sussane Müller, Aaron B. Kantor, Leonora A. Herzenberg, Fred S. Rosen, Paschalis Sideras
Journal: Immunity (1995)
Virtual teaching offers practitioners new style of radiotherapy training
Authors: Zosia Kmietowicz
Journal: BMJ (2007)

s health secretary, has said that some Muslim GPs may be divulging details of the sexual health of female Muslim patients to family members.Her comments drew an angry response from Muslim GPs, who said that her claims were based only on anecdotal evidence.However, Mrs Hewitt, who represents a constituency in Leicester with a large ethnic minority community, said, "I have had Muslim women give me chapter and verse on very distressing breaches of confidentiality by Muslim GPs."Some women patients in some Muslim communities are feeling they can't trust their own GP, who is from the same community and knows their extended family."If they go for particular situations, such as a sexual health problem or domestic violence, they fear they will share that information with other members of the family or community."Mrs Hewitt made her comments in an interview with the magazine for GPs Pulse (29 Mar, p 2).Vijoy Singh, chairman of the Leicestershire and Rutland local medical committee, which covers Ms Hewitt's constituency, said, "No GP would break confidentiality, because if they break it they are liable to be sued.She's out of touch."Mrs Hewitt cited a report published in November last year by the Muslim Women's Network, which was based on conversations with Muslim women throughout the country, as further evidence of her concerns.The report, She Who Disputes (www.thewnc.org.uk/pubs/shewhodisputesnov06.pdf),noted: "Health services were criticised for being insensitive and there was repeated concern that GPs from within the community could not be trusted to maintain patient confidentiality." Hewitt says some Muslim GPs breach confidentialityUK NEWS Safety agency prioritises better use of anticoagulants, p714 World NEWS drugs are as goo�� as ���� in stable coronary artery ��isease, stu��y s�o�s, p71� drugs are as goo�� as ���� in stable coronary artery ��isease, stu��y s�o�s, p71� , p71� bmj.com o�for�� ra��cliffe �ospitals tol�� to impro�e team�or� o�for�� ra��cliffe �ospitals tol�� to impro�e team�or�
Prevalence and Causes of Low Vision and Blindness in a Rural Chinese Adult Population
Authors: Yuan Bo Liang, David S. Friedman, Tien Yin Wong, Si Yan Zhan, Lan Ping Sun, Jie Jin Wang, Xin Rong Duan, Xiao Hui Yang, Feng Hua Wang, Qiang Zhou, Ning Li Wang
Journal: Ophthalmology (2008)