tbuckley/cabot-search huggingface dataset:
Abstract 5130: Neuropilin-1 expression in breast, colorectal and lung cancer
Authors: Adrian M. Jubb, Laura A. Strickland, Daniel S. Chen, Maike Schmidt, Hartmut Koeppen
Journal: Cancer Research (2011)

Abstract Neuropilin-1 is a coreceptor for vascular endothelial growth factor, which is expressed by endothelial cells and tumor cells. Preclinical data suggest that targeting neuropilin-1 would directly inhibit tumor cell growth and invasion, in addition to suppressing angiogenesis with indirect suppression of tumor growth. A humanized monoclonal antibody to neuropilin-1 is currently being evaluated in a phase one clinical trial of patients with solid malignancies. The aim of this study was to characterize the in situ expression of neuropilin-1 in normal and neoplastic human tissues. A monoclonal antibody to human neuropilin-1 was generated and validated for immunohistochemistry by comparison with isotopic in situ hybridization data, use of formalin-fixed human embryonic kidney (HEK)-293 cell pellets transfected with neuropilin-1, western blotting and quantitative reverse transcriptase (RT)-PCR on microdissected pure cell populations. Neuropilin-1 expression was assessed in whole sections of 65 primary breast carcinomas, 95 primary colorectal adenocarcinomas and 80 primary non-small cell lung carcinomas. An additional 50 breast, colorectal and lung metastases were also evaluated. The neuropilin-1 monoclonal antibody showed appropriate reactivity by western blotting and in formalin-fixed cell pellet controls, with co-localization of protein (immunohistochemistry) and mRNA (in situ hybridization and laser-capture microdissection followed by quantitative RT-PCR). Immunoreactivity for neuropilin-1 was seen in endothelium from normal tissues adjacent cancer and 98 to 100% of primary and secondary carcinomas. Tumor cell expression of neuropilin-1 was also observed in 34% of primary non-small cell lung carcinomas and 6% of primary breast carcinomas, but no colorectal adenocarcinomas. This is the first comprehensive analysis of neuropilin-1 protein expression in neoplastic human tissue with validated reagents. The assay will inform the likely activity and toxicity of agents that target neuropilin-1 and warrants evaluation as a biomarker of anti-neuropilin-1 activity. 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 5130. doi:10.1158/1538-7445.AM2011-5130
Abstract 1193: Prospective validation of multiple biomarkers for improved clinical decision-making in patients with urothelial carcinoma of the bladder
Authors: Yair Lotan, Ramy Youssef, Shahrokh F. Shariat, Feras Alhalbi, Raheela Ashfaq, Arthur I. Sagalowsky
Journal: Cancer Research (2010)

Abstract Objectives: To prospectively assess the predictive value of a panel of biomarkers (cyclin E1, p53, p21, p27 and pRB/Ki-67) for staging of patients with urothelial carcinoma of the bladder (UCB). Methods: 174 consecutive patients treated with transurethral resection (TUR) and/or radical cystectomy (RC) for UCB were prospectively included in the study starting in January 2007. Standardized, automated immunohistochemical staining and scoring was performed. A prognostic score (PS; ≤2 altered biomarkers=Favorable; &amp;gt;2 altered biomarkers=Unfavorable) was defined and correlated with clinical and pathological data. Results: The study comprised of 102 RC patients and 72 TURBT cases. Unfavorable PS were noted in 36.3 % of RC cases and 16.6 % of TURBT cases matching the more advanced pathological stages of RC patients. In RC group; an unfavorable PS was significantly associated with advanced tumor stage (p=0.02), the presence of LVI (p=0.017), recurrence (p=0.02) and survival (p=0.048). In the subgroup of patients who had biomarker evaluation at TUR and then underwent RC (n=32), 75 % and 50% of the cases with unfavorable PS showed upstaging and LN involvement at RC versus 25 % and 12.5 % in cases with favorable PS. Unfavorable PS at TUR was associated with the presence of LVI (p=0.001) and LN metastasis (p=0.026). Conclusions: The preliminary analysis of our ongoing prospective trial strongly suggests that a panel of five biomarkers improves the identification of patients at risk of upstaging at RC. An unfavorable PS may identify patients who are most likely to benefit from neo-adjuvant and adjuvant chemotherapy combined with RC. 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 1193.
Abstract 3149: MicroRNA-141 inhibits proliferation and invasion by suppressing the Wnt signaling pathway in renal cell carcinoma
Authors: Soichiro Yamamura, Saini Sharanjot, Majid Shahana, Hiroshi Hirata, Koji Ueno, Inik Chang, Takeshi Chiyomaru, Yuichiro Tanaka, Rajvir Dahiya
Journal: Cancer Research (2012)

Abstract MicroRNAs (miRNAs) are highly conserved, single stranded, non-coding RNAs of approximately 22 nucleotides that regulate gene expression by posttranscriptional silencing of specific target mRNAs, by repressing translation or cleaving RNA transcripts. miRNAs regulate diverse cellular processes such as cell-cycle progression, proliferation, apoptosis and development. miRNAs have been shown to function as oncogenes or tumor suppressor genes. MicroRNA-141 has recently been reported to play a role in the epithelial to mesenchymal transition (EMT) process and the expression of miR-141 is inversely correlated with tumorigenicity and invasiveness in several human cancers. The function of miR-141 in renal cell carcinoma has not been studied, therefore we studied the functional effects of miR-141 on renal cell carcinoma. We found that miR-141 was down regulated in human kidney cancer tissues compared with adjacent normal tissues. We also found that miR-141 was down regulated in renal cell carcinoma human cell lines, 769P, 786-O and ACHN compared with normal kidney cell line, HK-2. Transfection of miR-141 into renal cell carcinoma cells promoted apoptosis, inhibited in vitro cell proliferation and inhibited cell invasion. We found that miR-141 has a binding site in 3′UTR of the TCF7L2 (Transcription factor 7-like 2) gene which can activate the canonical Wnt pathway. miR-141 was found to down regulate expression of TCF7L2 by targeting its 3′ UTR as shown by luciferase reporter assays in renal cell carcinoma. Luciferase assays using T cell factor (TCF) reporter plasmids also showed that miR-141 represses TCF/LEF transcriptional activity, indicating that miR-141 suppresses the canonical Wnt pathway in renal cell carcinoma. Our results demonstrate that miR-141 suppresses malignancy by targeting TCF7L2 and inhibiting the Wnt signaling pathway in renal cell carcinoma. Source of Funding: Grants R01CA138642, VA Research Enhancement Award Program (REAP), and VA Merit Review grants 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 3149. doi:1538-7445.AM2012-3149
Abstract 2411: The epithelial-mesenchymal transition of gastric cancer cells was stimulated by TGFβR signaling in hypoxia
Authors: Junko Matsuoka, Masakazu Yashiro, Naoki Aomatsu, Toshiki Hirakawa, Tsuyoshi Hasegawa, Tatsunari Fukuoka, Tamami Morisaki, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Nobuya Yamada, Masaichi Ohira, Tetsuro Ishikawa, Kosei Hirakawa
Journal: Cancer Research (2012)

Abstract Introduction: Epithelial mesenchymal transition (EMT) is a cellular process during which epithelial cells acquire mesenchymal properties while losing cell-cell interactions and apicobasal polarity. EMT is considered to be correlated with malignancy of cancer cells and responsible for cancer invasion and metastasis. Patients with gastric cancer show a poor prognosis because of frequent metastasis. We previously reported that distant metastasis was associated with hypoxia in gastric cancer. Therefore, we investigated the effect of hypoxic condition on EMT of gastric cancer cells. Materials and Methods:Seven gastric cancer cell lines derived from gastric cancer were used. Cells were cultured in normoxia (21% O2) or hypoxia (1% O2) for 24h. EMT rate was evaluated as the percentage of spindle-shaped cells of total cells. The expression level of TGFβ and TGFβ receptor was evaluated by real time RT-PCR. Effect of several inhibitors on the EMT was evaluated by cell morphology. The TGFβ1 level of the cell culture supernate was measured by a quantitative sandwich enzyme immunoassay technique. Results: Hypoxia stimulated EMT of OCUM-2MD3 and OCUM-12 cells, but not that of other cell lines. The level of TGFβ expression was increased significantly (p&amp;lt;0.01) under hypoxia in comparison with normoxia. The level of TGFβ receptor expression was increased in OCUM-2MD3 cells, but not OCUM-2M cells. TGFβR inhibitor, SB431542, significantly suppressed EMT of OCUM-2MD3 (p=0.03) and OCUM-12 (p&amp;lt;0.01). In OCUM-2MD3 and OCUM-12, the quantity of TGFβ1 in cell culture supernatant significantly increased under hypoxia compared to normoxia, but not OCUM-2Mcells. Conclusion: Hypoxia stimulates the EMT of gastric cancer cells via TGFβ/ TGFβ receptor signaling. TGFβ receptor inhibitor might be promising for the treatment of metastasis of gastric cancer. 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 2411. doi:1538-7445.AM2012-2411
Abstract 677: Effects of the vascular disrupting agent ASA404 on tumor growth of gastric cancer in an experimental model
Authors: Christian Moser, Sven A. Lang, Ernst M. Jung, Karin Pfister, Edward K. Geissler, Hans J. Schlitt
Journal: Cancer Research (2011)

Abstract Background: A functional vascular system is essential for growth of solid malignancies including gastric cancer. For establishment and maintenance of such a vascular system endothelial cells (ECs) and pericytes (e.g. vascular smooth muscle cells, VSMC) are required. We hypothesized that targeting tumor vasculature with the vascular disrupting agent (VDA) ASA404 reduces tumor growth in a model of gastric cancer. Methods: Gastric cancer (GC) cell lines, ECs and VSMCs were used for experiments. Effects of ASA404 on growth of GC, EC and VSMC were assessed by MTT assays. Impact of ASA404 (20 mg/kg on day 1, 5, 9) in combination with paclitaxel (10 mg/kg on day 1 and 7) on tumor growth was assessed in a subcutaneous tumor model. Treatment was started when tumors reached a size of approximately 200 mm3. Tumors were measured and harvested on day 23 for IHC analyses. Effect of ASA404 on blood perfusion of tumors during therapy was monitored by contrast-enhanced ultrasound (CEUS). Results: In vitro ASA404 impaired growth of ECs and VSMCs upon stimulation with condition media from gastric cancer cells. No direct effect on tumor cells was observed. In vivo, treatment with ASA404 led to marked decrease of tumor perfusion and an increase of necrosis as determined by CEUS. Furthermore, combination of ASA404 with paclitaxel showed significant reduction of tumor growth compared to controls (P&amp;lt;0.05). In addition, tumor vascularisation and tumor cell proliferation were significantly reduced as determined by CD31-positive vessel area and BrdU-positive cells (P&amp;lt;0.05). Conclusion: Combination of the VDA ASA404 with paclitaxel impairs tumor growth and perfusion of gastric cancer in an experimental model. Hence, targeting tumor vasculature with ASA404 appears to be a promising strategy for therapy of gastric cancer. 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 677. doi:10.1158/1538-7445.AM2011-677
Acenocoumarol and Heparin Compared with Acenocoumarol Alone in the Initial Treatment of Proximal-Vein Thrombosis
Authors: Dees P.M. Brandjes, Harriët Heijboer, Harry R. Büller, Monique de Rijk, Henriëtte Jagt, Jan Wouter ten Cate
Journal: New England Journal of Medicine (1992)

In most countries, heparin is used in the initial treatment of patients with deep-vein thrombosis. Well-designed studies establishing the efficacy of heparin therapy are lacking, however. Treatment with acenocoumarol alone, according to the hypothesis that high dosages of oral anticoagulants obviate the need for heparin, is considered an effective alternative in some countries.
Abstract 311: Phosphorylation of RalB by PKC regulates its intracellular distribution and promotion of bladder tumor growth
Authors: Hong Wang, Xuejiao Wang, Charles Owens, Nidhi Chandra, Mark R. Conaway, David L. Brautigan, Dan Theodorescu
Journal: Cancer Research (2010)

Abstract RalA and RalB are members of the Ras family of monomeric G proteins that are 83% identical in amino acid sequence, but have paralog-specific effects on cancer cell proliferation, metastasis and apoptosis. Using in vitro kinase assays and phosphosite specific antibodies, here we show paralog-specific phosphorylation of RalA by PKA and RalB by PKC. Mutagenesis identified Ser194 as the single PKA phosphorylation site in RalA and S198 as the primary PKC phosphorylation site in RalB. Phorbol ester treatment of human bladder carcinoma cells induced phosphorylation of S198 in both stably expressed FLAG-RalB and endogenous RalB. Compared to activated RalB(G23V) that localized at plasma membrane, phosphosite mutant RalB(G23V-S198A) colocalized with GFP-Rab11, a recycling endosome marker. Phorbol ester treatment enhanced anchorage independent growth of UMUC3 human bladder carcinoma cells stably transfected with wild type RalB or activated RalB(G23V), but not with phosphosite mutants RalB(S198A) or RalB(G23V-S198A). Furthermore, UMUC3 cells transfected with RalB(G23V) exhibited enhanced subcutaneous tumor growth compared to vector transfected cells, but cells expressing RalB(G23V-S198A) had growth indistinguishable from the controls. Our data demonstrate that RalA and RalB are specifically phosphorylated by different kinases, and RalB phosphorylation regulates its intracellular localization and in vivo tumor growth promotion. Phosphorylation of RalA and RalB by different kinases may contribute to the biological specificity of these closely related proteins. 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 311.
The Contribution of Specialists to the Delivery of Primary Care
Authors: Linda H. Aiken, Charles E. Lewis, John Craig, Robert C. Mendenhall, Robert J. Blendon, David E. Rogers
Journal: New England Journal of Medicine (1979)

Despite increased numbers of medical-school graduates and opportunities for "primary-care" specialty training since the mid-1960's, many believe that the shortage of physicians delivering generalist care will continue through the 1980's. Missing, however, is solid information on the role of physician specialists in providing such care. Two national studies have shown that one of every five Americans now receives continuing general medical care from a specialist physician. Our study suggests that, despite the current shortage of generalist-physician services, continuing specialist participation in primary care will lead to sufficient generalist medical services by the mid-1980's. Whether specialist participation is the most appropriate or cost-effective way to improve access to such care is unclear. However, until this question is resolved, more governmental regulation of graduate medical education may be unwise. Offering all physicains, regardless of specialty, more primary-care experience during residency training might better deal with this aspect of American medical practice.
Abstract 3678: Reducing non-specific toxicity of cisplatin in head and neck cancer by targeted therapy using cisplatin-heparin-folic acid nanoparticles
Authors: Xianghong Peng, Yiqing Wang, Donghai Huang, Yuxiang Wang, Zuo Georgia Chen, Shuming Nie, Dong M. Shin
Journal: Cancer Research (2010)

Abstract Cisplatin(DDP) is a platinum-based chemotherapy drug which was widely used to treat various types of cancer including Head and Neck Squamous Cell Carcinoma (HNSCC). However, very little DDP reaches the tumor tissue due to poor specificity and it induces dose-limiting toxicities. The delivery of DDP selectively into a tumor mass has the potential to minimize toxicity to normal tissues and to improve the antitumor efficiency. We have developed novel nanoparticles by conjugating folic acid to modified heparin, then loaded cisplatin (DDP) into the targeted nanoparticles via the exchange of reaction of Pt from the chloride to the carboxylates on the nanoparticles. Uptake and biodistribution of DDP delivered by the nanoparticles or the free DDP form in vitro and in vivo was quantified by inductively coupled plasma-mass spectrometry (ICP-MS). We showed that DDP-Heparin-Folic Acid (FA) Nanoparticles are specifically internalized by FR-expressing HNSCC KB cells in vitro (17 fold higher than free DDP). Systemic delivery of DDP-Heparin-FA nanoparticles (2.5 mg/kg; 4 times treatment at 3 days intervals) into nude mice bearing KB cell tumors (6 mice/group) lead to selective accumulation of the DDP in subcutaneous tumor lesions (74 ppb/mg tissue for HFDDP, 16.5 ppb/mg tissue for DDP, P&amp;lt;0.05), and have significant antitumor activity. Furthermore, mice receiving DDP-Heparin-FA nanoparticles showed no significant body weight loss or damage to liver or spleen, whereas mice that received free DDP had significant weight loss and massive organ damage. Our results suggest that DDP-Heparin-FA nanoparticles have the potential to be used for delivery of this highly toxic chemotherapeutic agent with reduced side effects in HNSCC. (This research was supported by the National Cancer Institute award 5 P50 CA128613) 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 3678.
COMPARISON OF BASELINE CHARACTERISTICS, TREATMENT, AND OUTCOMES OF HISPANIC AND NON-HISPANIC WHITE PATIENTS IN ACUTE CORONARY SYNDROMES: A META-ANALYSIS OF REGISTRIES FROM THE UNITED STATES FROM 1982 TO 2007
Authors: Senthil Anand, Justin Lee, Sridhar Reddy, Carol Howe, Prakash Suryanarayana, Vijay Doraiswamy, Kwan Lee
Journal: Journal of the American College of Cardiology (2016)
<b>Journal article questions the use of ayurvedic therapies for diabetes</b>
Authors: Cheryl Travasso
Journal: BMJ (2016)

A letter in a leading journal has sparked controversy by claiming that Indian alternative medicines for diabetes are “maximum hype, minimum science.”1

Published in the Lancet Diabetes & Endocrinology and targeting ayurvedic medicine, the letter stated that “there is scant scientific basis for the use of these products in the management of diabetes.” But proponents of ayurveda have defended the traditional therapy.

Ayurveda is an ancient system of medicine practised in India. In 2014 the Ministry of Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homoeopathy (AYUSH) was set up by the Indian government to encourage research and education into these disciplines.

To evaluate whether ayurvedic medicines were effective and …
An Assessment of Participatory Integrated Vector Management for Malaria Control in Kenya
Authors: Clifford Maina Mutero, Charles Mbogo, Joseph Mwangangi, Susan Imbahale, Lydia Kibe, Benedict Orindi, Melaku Girma, Annah Njui, Wilber Lwande, Hippolyte Affognon, Charity Gichuki, Wolfgang Richard Mukabana
Journal: Environmental Health Perspectives (2015)

The World Health Organization (WHO) recommends integrated vector management (IVM) as a strategy to improve and sustain malaria vector control. However, this approach has not been widely adopted.
PWE-113 Low Risk for Hepatocellular Cancer (HCC) in Hepatitis B Virus (HBV) Infected Asian Migrants: Implications for Cancer Surveillance
Authors: K-K Li, S Von Heimendahl, T Bruns, S Ward, P Trivedi, Y Oo, D Mutimer
Journal: Gut (2013)

<h3>Introduction</h3> The global incidence of HCC is rising and it is the third most common cause of cancer-related death worldwide. Surveillance of at risk patients has been recommended by expert guidelines to detect early cancers that are amenable to curative treatments. AASLD has recommended HCC surveillance for non-cirrhotic HBV-positive Asian males over 40 and females over 50yrs of age. However, the evidence to support this recommendation is limited and is derived from studies conducted in Asia. Results from such studies may not be applicable in the West, due to differences in environmental risk factors and availability of HBV treatment. Implementation of such a recommendation would place a burden on healthcare resources, and may not be justified if the risk for HCC is substantially lower than previous estimates in this population. <h3>Methods</h3> A retrospective study was carried out of all Asian patients undergoing follow up for HBV infection from 1990 to 2012. Patients were classified as cirrhotic or non-cirrhotic according to clinical, biochemical, radiological and histological results. Follow-up was until September 2012, and was censored at time of death, development of cirrhosis or loss to follow-up. <h3>Results</h3> Among 316 identified Asian patients with HBV, 73 non-cirrhotic patients fulfilled the proposed AASLD surveillance criteria, either at time of initial referral or during the period of follow-up. The median at-risk follow up period (as defined by AASLD guidelines for non-cirrhotic Asians) was 57 months (range: 0–354 months). HCC was diagnosed in one non-cirrhotic patient after 77 months of follow up (male, 60yrs), two patients became cirrhotic after 49 and 89 months (male, age 46 and 55yrs) and no deaths occurred. The overall incidence of HCC in the non-cirrhotic cohort meeting the AASLD surveillance criteria was 1 per 429.5 patient-years of follow-up (0.23% per patient-year). <h3>Conclusion</h3> The incidence of HCC in Asian patients with non-cirrhotic HBV is low in our cohort. This low incidence challenges the rationale for surveillance in this group of patients. More studies are needed to assess the benefit of such approach. <h3>Disclosure of Interest</h3> None Declared.
Phase II study of carboplatin plus weekly nab-paclitaxel in elderly patients with NSCLC:NJLCG1301
Authors: Kazuhiro Usui, Eisaku Miyauchi, Shunichi Sugawara, Tatsuro Fukuhara, Heisuke Saito, Yuka Fujita, Terufumi Kato, Toshiro Suzuki, Akira Inoue, Masakazu Ishinose
Journal: Annals of Oncology (2015)