tbuckley/cabot-search huggingface dataset:
Clinical characteristics predictive of response to pembrolizumab in advanced melanoma.
Authors: Katy K. Tsai, Kimberly Loo, Neharika Khurana, Alain Patrick Algazi, Jimmy Hwang, Roberto Sanchez, Matthew Krummel, Michael Rosenblum, Paul Tumeh, Adil Daud
Journal: Journal of Clinical Oncology (2015)

9031 Background: Anti-PD-1 therapy has shown significant clinical activity in advanced melanoma and in other cancers. Factors predictive of response remain vaguely defined. We report on clinical characteristics correlated with higher response rates to therapy in a phase I trial of pembrolizumab. Methods: Advanced melanoma patients (n = 110, enrolled Dec 2011 to Oct 2013, data analysis July 2014) received pembrolizumab in 1 of 3 dosing regimens: 2Q3W, 10Q3W, or 10Q2W. Tumor responses were evaluated by RECIST 1.1 criteria. Sites of metastases were determined based on CT imaging, and this analysis was not limited to RECIST target lesions. The overall response rate (ORR) and exact two-sided 95% CI were calculated. Demographic and clinical variables were compared between responders and progressors. Results: In this cohort, ORR to pembrolizumab was 40%. Factors correlated with significantly higher ORR were: LDH ≤ normal (ORR 52.2%), no previous ipilimumab (ORR 48.3%), and presence of lung metastasis (ORR 52.8%). Patients with liver metastasis had worse response (ORR 18.4%), as did those with liver and lung metastases (ORR 31.3%). Data for associations of subgroup variables with ORR in univariate analyses are shown (Table). Conclusions: Normal LDH, no previous ipilimumab, and presence of lung metastasis are correlated with better response to pembrolizumab in advanced melanoma patients. The presence of liver metastasis is correlated with lower response to pembrolizumab, both in the presence and absence of lung metastasis. These correlations were observed regardless of BRAF status, presence of brain metastasis, or site of primary melanoma (cutaneous vs. uveal). Clinical trial information: NCT01295827. Clinical characteristic ORR, % (95% CI) p-value All patients 40 (30.7-49.3) Age <65 36.2 (23.5-49) 0.39 ECOG 0 41.1 (29.5-52.7) 0.741 LDH ≤ normal 52.2 (40-64.5) 0.009 BRAF WT 40.7 (30.1-51.3) 0.416 No previous ipilimumab 48.3 (35.3-61.4) 0.0049 Brain metastasis (met) 38.9 (13.9-63.8) 0.916 Lung met 52.8 (38.9-66.7) 0.008 Liver met 18.4 (5.5-31.3) 0.001 Lung met, no liver met 62.2 (45.8-78.6) 0.001 Lung met and liver met 31.3 (5.7-56.8) 0.001 Liver mets, no lung mets 9.1 (4-22.1) 0.001
Effervescent Mixtures as Adjuvants to the Rapid Absorption of Ingested Drugs
Authors: Giorgio Lolli, Ruth Smith
Journal: New England Journal of Medicine (1946)

ALTHOUGH there are many and obvious advantages to the oral administration of drugs, there are certain equally obvious disadvantages. Of these the most prominent are the uncertain and variable rate of absorption and gastric irritation. It is probable that when irritation occurs, its intensity varies with the duration of the contact of the drug with the gastric mucosa, and that it is least when emptying of the stomach is rapid. Since few drugs are absorbed directly from the stomach, the rate of emptying affects the speed of therapeutic response, and for drugs whose action depends on concentration developed in the . . .
The dual roles of cytokines in Alzheimer’s disease: update on interleukins, TNF-α, TGF-β and IFN-γ
Authors: Cong Zheng, Xin-Wen Zhou, Jian-Zhi Wang
Journal: Translational Neurodegeneration (2016)

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders in the elderly. Although the mechanisms underlying AD neurodegeneration are not fully understood, it is well recognized that inflammation plays a crucial role in the initiation and/or deterioration of AD neurodegeneration. Increasing evidence suggests that different cytokines, including interleukins, TNF-α, TGF-β and IFN-γ, are actively participated in AD pathogenesis and may serve as diagnostic or therapeutic targets for AD neurodegeneration. Here, we review the progress in understanding the important role that these cytokines or neuroinflammation has played in AD etiology and pathogenesis.
Be wary of signing deals for telehealth technologies, conference hears
Authors: M. Limb
Journal: BMJ (2012)

NHS organisations should be wary of bulk buying telehealth technologies and getting locked into unsuitable and costly deals, says a leading campaigner for patients’ interests.

Jeremy Taylor, chief executive of the National Voices coalition of health and social care charities, said there were risks associated with the spread of telehealth and telecare initiatives and patients’ needs must come first.

Although some technologies could help people with long term conditions live independently, they must not be a substitute for effective services and must be “wired in” to well coordinated support, he said.

Mr Taylor, who is a member of the NHS Future Forum, said health technologies were “usually designed by young, fitter people for use by older, sicker” ones.

He said the NHS had spent lots of money in recent years on “kit” that had failed to live up to expectations.

“We have to avoid the trap of having technology driven solutions in search of problems,” he said. “It leads …
Tc-99m Hexamethylpropylene Amine Oxime Leukocyte Pinhole Imaging of the Scrotum in Patients with Epididymitis Showing Equivocal Clinical and Scintigraphic Findings
Authors: KYOUNG MIN SOHN, BONG RYOUL OH, SOO BANG RYU, YANG IL PARK, HO-CHUN SONG, HEE-SEUNG BOM
Journal: Clinical Nuclear Medicine (2001)

MIN SOHN, KYOUNG M.D.; RYOUL OH, BONG M.D.; BANG RYU, SOO M.D.; IL PARK, YANG M.D.; SONG, HO-CHUN M.D.; BOM, HEE-SEUNG M.D. Author Information
Abstract 1827: Ethnic differences in the association between body mass and risk of colorectal cancer in the multiethnic cohort
Authors: Unhee Lim, Abraham M. Y. Nomura, Lynne R. Wilkens, Loic Le Marchand, Kristine R. Monroe, Suzanne P. Murphy, Cheryl L. Albright, Brian E. Henderson, Laurence N. Kolonel
Journal: Cancer Research (2010)

Abstract Introduction. Higher body mass has been associated with elevated risk of developing colorectal cancer. However, limited prospective data are available as to whether the association differs among ethnic groups with varying degrees of susceptibility for central obesity and obesity-related metabolic diseases. We investigated potential ethnic heterogeneity in the body mass-colorectal cancer association in the Multiethnic Cohort. Methods. Baseline self-reported data were obtained on height, weight, physical activity, diet, and other risk factors from a population-based sample of over 96,810 men and 118,441 women in Hawaii and Los Angeles who were of Caucasian, African, Japanese, Latino, and Native Hawaiian ancestry and were 45-75 years old in 1993. By December 2006, 1,575 male and 1,316 female incident colorectal cancer cases were ascertained from linkage with SEER registries. The associations of interest were estimated by multivariable-adjusted Cox proportional hazards models with age as the time metric. Results. Prevalence of obesity at baseline (body mass index (BMI) ≥ 30) ranged from 8% in Japanese to 36% in Native Hawaiian men and from 6% in Japanese to 35-37% in African American and Native Hawaiian women. Baseline BMI was positively associated with colorectal cancer risk in men (hazard ratio (HR) for BMI ≥ 30 compared with 18.5-22.9 = 1.50 (95% confidence interval: 1.32, 1.70)) and women (HR = 1.50 (1.33, 1.70)). When examined by sex and ethnicity, men of Caucasian (HR = 1.80 (1.36, 2.39)), African (HR = 2.17 (1.48, 3.16)), and Japanese (HR = 1.80 (1.44, 2.25)) ancestry showed a positive association, whereas Latino and Native Hawaiian men showed a null association (p-interaction = 0.11). In women, the association was strongest among Native Hawaiians (HR = 2.39 (1.24, 4.60)) and Japanese Americans (HR = 2.21 (1.75, 2.79)), followed by Latinas (HR = 1.67 (1.15, 2.41)) and Caucasians (HR = 1.38 (1.07, 1.77)), while it was null among African Americans (p-interaction = 0.12). Conclusions. These findings from a large follow-up study of diverse ethnic make-up suggest sex- and ethnicity-related heterogeneity in the body mass-colorectal cancer association, which would be important to consider for understanding the etiology and identifying higher-risk groups for intervention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1827.
A CASE OF DIDELPHIC UTERUS WITH LATERAL HEMATOCOLPOS, HEMATOMETRA AND HEMATOSALPINX, WITH SOME REMARKS ON THE TREATMENT OF THESE CONDITIONS.Read in the Section on Obstetrics and Diseases of Women, at the Forty-fifth Annnal Meeting of the American Medical Association, held at San Francisco, June 5-8, 1894.
Authors: X. O. WERDER
Journal: JAMA (1894)

The uterus didelphys is undoubtedly one of the rarest malformations met by the gynecologist. Until recently it was thought to exist only in connection with deformity of other organs of such serious nature as to interfere with the life of the fetus; at present, however, there are on record a number of well authenticated cases in adults; in a cursory examination of the recent literature I have been able to find ten or eleven, a few of them with lateral retention of menstrual blood in vagina, uterus and tube, as in my own case. By uterus didelphys we understand two well formed and entirely separated uteri, with no partition wall, which have either no connection with each other at all, or at least a very loose one, but with only one cornu and, therefore only one tube and ovary accompanying each organ; in other words, two complete uteri unicornes. In
The Secure Anonymised Information Linkage (SAIL) system in Wales has privacy protection at its heart
Authors: R. Lyons, D. Ford, K. Jones
Journal: BMJ (2014)

We would like to comment on the recently published article on the use of general practice data for research.1 The article is correct in its general description of the Secure Anonymised Information Linkage (SAIL) system in Wales. However, some of the phrases used, such as: “The Welsh system does not hold any fully identifiable data, and researchers need consent from individual patients to access red data” …
PWE-152 Primary Sclerosing Cholangitis-inflammatory Bowel Disease Is Associated With An Increased Frequency Of Post-transplant Colonic Lymphoma
Authors: PJ Trivedi, T Wright, J Robinson, K-K Li, B Gunson, D Adams, J Ferguson, G Hirschfield
Journal: Gut (2014)

<h3>Introduction</h3> Post-transplant lymphoproliferative disease (PTLD) is a recognised complication of liver transplantation (LT). Although small intestinal involvement is common, factors predisposing to colonic disease are not well characterised. <h3>Methods</h3> A case-note review of all patients undergoing liver transplantation (1982–2013) was performed, and subsequently cross-referenced with an institutional lymphoma database comprising all biopsy-proven PTLD cases to date. Putative risk factors for development of colonic lymphoma were analysed using SPSSv21. <h3>Results</h3> Over a 31-year adult 'first liver' transplant experience (No. of recipients=2872), 72 cases of post-LT lymphoproliferative disease were identified and most commonly observed in the context of primary biliary cirrhosis (PBC; n = 20) and primary sclerosing cholangtitis (PSC; n = 14). Overall, intestinal involvement was observed in 18/72 patients, representing predominantly small bowel disease (n = 12). Colonic lymphoma occurred only in individuals transplanted for PSC (n = 6; median 5.0yrs post-transplant; IQR: 3.2–11.7), all of who had underlying colitis. In all cases, disease was a diffuse large B-cell lymphoma; however, only 2 patients had EBV-(LMP)-positive tumours, from which only 1 a detectable serum EBV-titre (qPCR). There were no significant associations with age at transplantation, male gender, treatment with azathioprine or tacrolimus, duration of azathioprine or calcineurin inhibitor exposure, or onset of colitis post-LT. Only one patient (each) with PTLD occurring in the context of cardiothoracic (n = 6) and renal (n = 32) transplantation developed large bowel disease, and under these circumstances was part of a disseminated lymphomatous process. <h3>Conclusion</h3> PSC/colitis is associated with development of colonic lymphoma post-LT. Additional risk factors have yet to be identi, UKfied. <h3>Disclosure of Interest</h3> None Declared.
House Legislators Sponsor New Breast Cancer Bills
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article House Legislators Sponsor New Breast Cancer Bills Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 21, 1 November 1989, Pages 1609–1610, https://doi.org/10.1093/jnci/81.21.1609 Published: 01 November 1989
Abstract 4445: Novel antibody-dendrimer conjugates efficiently complex plasmid DNA
Authors: Yang Wang, Bill McBride, David M. Goldenberg, Chien-Hsing Chang
Journal: Cancer Research (2011)

Abstract Introduction: Cationic polymers, such as polylysine, polyethylenimine, or polyamidoamine (PAMAM)-based dendrimers, form complexes with nucleic acids. However, their potential applications in nanomedicne as non-viral vectors for delivering therapeutic genes or siRNAs remain a challenge. One approach to improve selectivity and potency of a dendrimeric nanoparticle may be achieved by conjugation with an antibody that internalizes upon binding to target cells. In this study, we describe the synthesis and initial characterization of a novel immunoconjugate, designated E1-G5/2, which was made by the modular Dock-and-Lock (DNL) method to comprise half of a generation 5 (G5) PAMAM dendrimer (G5/2) site-specifically linked to a stabilized dimer of Fab derived from hRS7, a humanized antibody that is rapidly internalized upon binding to the Trop-2 antigen expressed on various solid cancers. Methods: E1-G5/2 was prepared by combining two self-assembling modules, AD2-G5/2 and hRS7-Fab-DDD2, under mild redox conditions, followed by purification on a Protein L column. To make AD2-G5/2, we derivatized the AD2 peptide with a maleimide group to react with the single thiol generated from reducing a G5 PAMAM with a cystamine core and used reversed-phase HPLC to isolate AD2-G5/2. We produced hRS7-Fab-DDD2 as a fusion protein in myeloma cells. The molecular size, purity and composition of E1-G5/2 were analyzed by size-exclusion HPLC, SDS-PAGE, and Western blotting. The biological functions of E1-G5/2 were assessed by binding to an anti-idiotype antibody against hRS7, a gel retardation assay, and a DNase protection assay. Results: E1-G5/2 was shown by size-exclusion HPLC to consist of a major peak (&amp;gt;90%) flanked by several minor peaks. The three constituents of E1-G5/2 (Fd-DDD2, the light chain, and AD2-G5/2) were detected by reducing SDS-PAGE and confirmed by Western blotting. Anti-idiotype binding analysis revealed E1-G5/2 contains a population of antibody-dendrimer conjugates of different size, all of which are capable of recognizing the anti-idiotype antibody, thus suggesting structural imperfections in the commercial supply of the G5 dendrimer. Gel retardation assay showed E1-G5/2 was able to maximally condense plasmid DNA at a charge ratio of 6:1 (+/-), with the resulting dendriplexes completely protecting the complexed DNA from degradation by DNase I. Conclusion: The DNL method can be used to build dendrimer-based nanoparticles that are targetable with antibodies. Such agents may have improved properties as carriers of drugs, plasmids, or siRNAs for diverse applications in vitro and in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4445. doi:10.1158/1538-7445.AM2011-4445
THE EFFICACY OF PACLITAXEL-COATED BALLOON FOR DRUG-ELUTING STENT RESTENOSIS LESIONS ACCORDING TO THE RESTENOSIS PATTERNS
Authors: Takenobu Shimada, Kazushige Kadota, Hidewo Amano, Yu Izawa, Tahei Ichinohe, Takenori Kanazawa, Shunsuke Kubo, Yusuke Hyodo, Koshi Miyake, Suguru Otsuru, Daiji Hasegawa, Seiji Habara, Takeshi Tada, Hiroyuki Tanaka, Yasushi Fuku, Harumi Katoh, Tsuyoshi Goto, Kazuaki Mitsudo
Journal: Journal of the American College of Cardiology (2015)
Migration of a Metallic Pin from the Humerus into the Lung
Authors: Theodore A. Tristan, T. Giffin Daughtridge
Journal: New England Journal of Medicine (1964)

THIS presentation describes the migration of a Steinmann pin from the right humerus into the right lung of a twelve-year-old child, followed by its successful removal. Although previously reported, such cases are sufficiently unusual to merit reiterating.Case ReportA 12-year-old girl was admitted for the 7th time to the Hospital of the University of Pennsylvania on March 17, 1963, with a history of poliomyelitis at 3 years of age and residual paralysis of the right upper extremity. The previous 6 admissions had been for surgical procedures designed to allow more useful function of the right arm. These admissions are . . .
Abstract 1704: Linking mitochondrial epigenetics to tumorigenesis and the cancer theory of Warburg.
Authors: Thomas N. Seyfried
Journal: Cancer Research (2013)

Abstract Otto Warburg first proposed that respiratory insufficiency was the common metabolic hallmark of all tumor cells. Respiratory insufficiency is the precursor to aerobic fermentation (Warburg effect), and can also be linked to dysregulated proliferation and to the genomic abnormalities seen in the majority of cancers. It is well documented that tumorigenicity can be suppressed in a broad range of tumor types when cytoplasm from enucleated normal cells, containing normal mitochondria, is fused with nucleated tumor cells to form cybrids. Tumorigenicity is also suppressed in a broad range of tumors following transplantation of the nucleus from tumor cells into enucleated eggs or somatic cells, indicating that tumor nuclei are capable of directing development despite the persistence of tumor-associated mutations. Tumor cell mutations seem to abort development, rather than induce tumorigenesis. In contrast to the tumor suppressive effects of cytoplasm containing normal mitochondria, either cell death or tumor cells arise when nuclei from non-tumorigenic normal cells are fused with cytoplasm from tumor cells. The results from these studies indicate that nuclear genomic defects alone cannot produce tumors, and that normal mitochondria can suppress tumorigenesis. The findings, when viewed collectively, support Warburg's central theory and suggest that mitochondrial epigenetics drives tumorigenesis. Supported in part from the Boston College Res. Expense Fund. Citation Format: Thomas N. Seyfried. Linking mitochondrial epigenetics to tumorigenesis and the cancer theory of Warburg. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1704. doi:10.1158/1538-7445.AM2013-1704
A4.20 Viral expression of TSG-6 can stimulate osteophyte formation in experimental osteoarthritis
Authors: MGA Broeren, MB Bennin, OJ Arntz, AB Blom, WB van den Berg, FAJ van de Loo
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Tumour necrosis factor-inducible gene 6 (TSG-6, also named TNFAPI6) is upregulated during experimental arthritis in mice (Geurts <i>et al</i>. 2009). The therapeutic efficacy of TSG-6 has been shown in multiple animal models for rheumatoid arthritis, reducing both inflammation and cartilage damage. Recent studies suggest that inflammation can also play a role in early osteoarthritis (OA) pathogenesis (Ayral <i>et al</i>. 2005). Therefore, TSG-6 therapy might also be an effective treatment in inflammatory OA. In this study, we analysed the expression of TSG-6 during experimental arthritis and explored the effects of TSG-6 gene therapy in a murine model of inflammatory osteoarthritis. <h3>Materials and methods</h3> TSG-6 gene expression was determined in microarrays of collagenase-induced osteoarthritis at day 7 and day 14 after induction. The murine TSG-6 gene was cloned in a lentiviral and adenoviral vector. Freshly isolated bone marrow-derived dendritic cells (BMDCs) were transduced with the lentiviral vector and subsequently differentiated into osteoclasts on bone slices with M-CSF and RANKL. After 10 days, bone slices were washed and stained using Coomassie Blue and bone resorption was determined using the Leica Application Suite software. To study the effects of TSG-6 in experimental knee osteoarthritis, mice received two intra-articular injections of collagenase. Four days prior to and 20 days after arthritis induction, mice were injected intra-articularly with TSG-6 adenovirus. At day 7, inflammation was assessed using fluorescent Prosense probes. At day 42, knee joints were analysed by X-ray and histological assessment. <h3>Results</h3> TSG-6 was upregulated in collagenase-induced OA (2,6x at day 7 (P &lt; 0.05) and 2.5x at day 14 (P = 0.55)). BMDCs transduced with TSG-6 lentivirus showed strong expression of TSG-6. Bone resorption by BMDC-derived osteoclasts was significantly reduced (20.1% surface erosion with control virus to 10.4%, p = 0.01), providing a possible mechanism for the therapeutic effects in rheumatoid arthritis models. At day 7 of collagenase-induced osteoarthritis, no difference in inflammation was detected using the Prosense probes. At day 42, no improvement on cartilage damage was seen, but X-ray analysis showed strong osteophyte formation at the femur/tibia region in the knee joint. Histological analysis showed that the osteophytes contained both bone and cartilage. <h3>Conclusions</h3> Viral expression of TSG-6 can reduce the bone resorption activity by BMDC-derived osteoclasts. The expression of TSG-6 by synovial cells during experimental osteoarthritis results in the formation of osteophytes. These results imply a causative role for TSG-6 in osteophyte formation, supporting the recent finding that TSG-6 activity is associated with radiographic progression of OA (Wisniewski <i>et al</i>. 2014).