tbuckley/cabot-search huggingface dataset:
Abstract 629: MEK inhibition by selumetinib (AZD6244) inhibits progression with a multicentric antiangiogenic effect and enhances the efficacy of cediranib in orthotopic human lung cancer models
Authors: Osamu Takahashi, Ritsuko Komaki, Paul D. Smith, Julian M. Jürgensmeier, Anderson J. Ryan, Benjamin N. Bekele, Ignacio I. Wistuba, Jörg J. Jacoby, Maria V. Korshunova, Anna Biernacka, Baruch Erez, Keiko Hosho, Roy S. Herbst, Michael S. O'Reilly
Journal: Cancer Research (2011)

Abstract Background: Selumetinib is a potent orally available MEK 1/2 inhibitor now in clinical development. We evaluated the therapeutic efficacy of selumetinib alone or with cediranib (RECENTIN™), an orally available inhibitor of all 3 VEGFR tyrosine kinases, in distinct K-ras mutant orthotopic human non-small cell lung cancer models. Methods: NCI-H441 or NCI-H460 cells were injected into the lungs of mice. Mice were randomized to treatment with selumetinib (12.5 or 25 mg/kg/BID po), cediranib (3 mg/kg/qd po), paclitaxel (200 µg/week ip), selumetinib + cediranib, or vehicle. When controls became moribund, all mice were sacrificed and assessed and lung tumors subjected to immunohistochemical analyses. Results: In both models, selumetinib or cediranib were well tolerated and inhibited tumor growth and metastasis with efficacy superior to paclitaxel. The combined antitumor effects of selumetinib and cediranib were markedly enhanced with near complete metastasis suppression. Immunohistochemistry revealed that cediranib or selumetinib reduced microvessel density and tumor cell proliferation and increased apoptosis, with no effect on VEGFR2 expression. The effects were substantially enhanced when they were combined. Cediranib blocked VEGFR2 activation. Selumetinib's antiangiogenic effect, but not cediranib's, was associated with reduced VEGF expression, particularly in the H441 model. Surprisingly, selumetinib reduced tumor and endothelial VEGFR2 activation, which may in part be due to the offset of VEGF expression. Conclusions: The combination of selumetinib and cediranib enhances their antitumor, antimetastatic, and antiangiogenic effects. Selumetinib decreased VEGF and suppressed VEGFR activation, suggesting that MEK inhibition targets VEGF-driven angiogenesis at multiple levels. These data provide a strong basis for clinical trials of selumetinib and cediranib in lung 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 629. doi:10.1158/1538-7445.AM2011-629
MORTALITY, EXPENSE AND LENGTH OF STAY WITH TRANSCATHETER VERSUS SURGICAL AORTIC VALVE REPLACEMENT IN THE FIRST YEAR AFTER APPROVAL IN THE US: AN ANALYSIS OF THE NATIONAL INPATIENT SAMPLE DATABASE
Authors: Saurav Chatterjee, Partha Sardar, Debabrata Mukherjee, Dharam Kumbhani, Jay Giri
Journal: Journal of the American College of Cardiology (2015)
Bayer challenges India's first compulsory licence for generic version of cancer drug
Authors: S. Arie
Journal: BMJ (2012)

An Indian court is to issue a landmark judgment in the coming weeks after German drug company Bayer appealed a decision to over-rule its patent on the cancer drug sorafenib (marketed as Nexavar) so that a local producer could make a much cheaper version.

India’s patent controller issued a compulsory licence in March to local company Natco, which has since made the kidney and liver cancer drug sorafenib tosylate for $175 (£110; €139) per month, 97% less than the cost of sorafenib.

The compulsory licence—the first in India since patent laws were introduced in 2005—was granted to the request of Natco and considered to be in the interests of public health in India where cancer is a growing problem. Natco …
Abstract 4289: Early study on LGR5/GPR49 molecule as a potential colon cancer stem cell target for the antibody conjugated drug treatment
Authors: Weiguang Mao, Janet Tien, David Goldenberg, Scott Stawicki, Rajesh Vij, Xiaoling Xia, Jo-Anne Hongo, Sarajane Ross, Kathy Kozak, Ron Firestein, Yan Wu, Susan Spencer, Paul Polakis
Journal: Cancer Research (2010)

Abstract LGR5 (GPR49) is a Wnt pathway downstream target gene. It has already been confirmed that LGR5 gene is up regulated by APC or β-catenin mutation. LGR5 has recently been identified as a biomarker on the human and murine intestinal or colon stem cells. Our gene expression data shows that LGR5 is highly expressed in colon cancer, with minimal expression in normal tissue. Our strategy in this project is to eliminate tumor stem cells by drug conjugated antibody. Our goal is to find a tumor stem cell marker and develop antibody to target the tumor stem cells. Here we developed and characterized both anti-LGR5 phage and monoclonal antibodies by multi molecular techniques. We finally focus on one phage antibody (YW353) and three monoclonal antibodies (2H6, 3G12 and 8E11) as therapeutic drugs for further study. We evaluated antibody drug conjugate (ADC) in vitro and in vivo with different animal tumor models derived from cell lines and human tumor explants. Good efficacy was observed in these animal models following a single dose of 5mg/kg. Conclusion: LGR5 is an attractive colon cancer target for the administration of anti-LGR5 ADC in human cancer. More in vivo models will be tested to confirm the efficacy and evaluate safety. 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 4289.
Abstract 878: Comorbidities in African American and Hispanic/Latina Breast Cancer Patients are associated with IGF-1 and IGFBP3-3 Gene Polymorphisms
Authors: Marianna Sarkissyan, Dhruva Mishra, Yanyuan Wu, Xiying Shang, Suren Sarkissyan, Jaydutt V. Vadgama
Journal: Cancer Research (2010)

Abstract Increase in comorbidities such as diabetes and hypertension in cancer patients lead to poor disease free survival and overall survival. It is probable that risk factors associated with these comorbidities and cancer itself could be linked to alterations in gene polymorphisms associated with hormones and/or growth factors. In this study, we have investigated if (1) comorbidities were associated with our African American and Hispanic breast cancer subjects; and (2) if there was any association between Insulin-Like Growth Factor 1 (IGF-1), and IGF Binding Protein 3 (IGFBP3) gene polymorphisms with breast cancer and comorbidities. We studied 514 subjects (175 African Americans and 339 Hispanic/Latinas), which included 208 cases and 306 controls (no evidence of breast cancer) subjects. DNA was extracted from blood samples and IGF-1 and IGFBP-3 genotyping was performed by PCR-GeneScan and PCR-RFLP methods, respectively. Our results demonstrated that comorbidity is significantly correlated with breast cancer (OR = 2.12; 95% CI = 1.40-3.21; P-value &amp;lt;0.01); especially the comorbidity of hypertension (OR= 2.27; 95% CI = 1.47-3.49; P-value &amp;lt;0.01). Furthermore, there was a significant association between non-19/non-19 IGF-1 (CA)n polymorphisms and breast cancer (OR= 4.80; 95% CI = 1.87, 12.36; P-value &amp;lt;0.01). This study also found a significant association between the non-19/non-19 IGF-1 (CA)n genotype, breast cancer, and comorbidity (OR= 4.65; 95% CI = 1.57, 13.82; P-value &amp;lt;0.01). In summary, our study demonstrated a significant association of IGF-1 polymorphisms and breast cancer with a further link to comorbid diseases. 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 878.
Quantification of Core Antigen Monitors Efficacy of Direct-acting Antiviral Agents in Patients With Chronic Hepatitis C Virus Infection
Authors: Alessio Aghemo, Elisabetta Degasperi, Stella De Nicola, Patrizia Bono, Anna Orlandi, Roberta D’Ambrosio, Roberta Soffredini, Riccardo Perbellini, Giovanna Lunghi, Massimo Colombo
Journal: Clinical Gastroenterology and Hepatology (2016)
Disparities in Uptake Pattern of 123I-MIBG, 18F-FDG, and 99mTc-MDP Within the Same Primary Neuroblastoma
Authors: Ion Codreanu, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2013)

We report an unusual case of primary neuroblastoma in an 11-year-old girl. The superior portion of the tumor accumulated I-MIBG, Tc-MDP, and F-FDG. In contrast, the inferior portion of the tumor showed no abnormal F-FDG or Tc-MDP uptake, which usually indicates tumor necrosis. This inferior portion of the tumor, however, had intense I-MIBG activity, consistent with viable tumor rather than tumor necrosis.
Similar Pelvic Abnormalities on FDG Positron Emission Tomography of Different Origins
Authors: HONGMING ZHUANG, ALVIN J. YAMAMOTO, PARTHA SINHA, MICHAEL POURDEHNAD, YI LIU, ABASS ALAVI
Journal: Clinical Nuclear Medicine (2001)

Fluorodeoxyglucose positron emission tomography (FDG PET) has been used extensively to detect and stage various cancers. However, normal variation and inflammatory lesions may lead to false-positive interpretations of PET findings. The authors report three cases of increased pelvic FDG uptake with differing origins. Although the findings are similar, a postpartum uterus, lymphoma, and a bleeding uterus caused pelvic FDG uptake in these patients. Interestingly, of these three patients, the patient with lymphoma had the lowest level of FDG uptake. Clinical correlation is needed for the accurate interpretation of FDG-PET findings.
Case 33-2003
Authors: Oscar Soto, E. Tessa Hedley-Whyte
Journal: New England Journal of Medicine (2003)

Presentation of CaseA 37-year-old man was admitted to the hospital because of collapse.The patient was unmarried and unemployed and was a former smoker. He had abused alcohol since the age of 13 years and had been admitted for detoxification on numerous occasions because of alcohol abuse and use of illicit drugs. Since his early teens, he had had an eating disorder that led to obesity. During the 10 years before admission, he had asthma, proteinuria, and hypertension. Six years before admission, he began to use intermittent doses of colchicine and indomethacin for gouty arthritis.Three years before admission, . . .
Case 26-2006
Authors: Nagagopal Venna, Katherine B. Sims, P. Ellen Grant
Journal: New England Journal of Medicine (2006)

A 19-year-old woman had difficulty walking and painful spasms in her legs and arms, worse at night than in the morning, which had slowly worsened since the age of 8 years. Tremors occurred in her arms, and she had insomnia, anxiety, and irritability. There was no weakness or cognitive impairment. A diagnostic test was performed.
Abstract 2905: The HMGA1-MMP-2 pathway in poorly differentiated uterine tumors
Authors: Joelle Hillion, Francescopaolo Di Cello, David Huso, Linda Resar
Journal: Cancer Research (2011)

Abstract Uterine cancer is the most common cancer of the female genital tract and the fourth most frequent cause for cancer death in women in the United States. Thus, further study has the potential to significantly benefit women's health worldwide. Despite the high prevalence of this disease, the molecular events that lead to uterine cancers are poorly understood. We are studying the role of the high mobility group A1 (HMGA1) gene in the pathogenesis of uterine cancer. The HMGA1 gene encodes the HMGA1a and HMGA1b chromatin remodeling proteins, which function in modulating gene expression. In a previously published pilot study, we showed that HMGA1 is overexpressed in poorly differentiated uterine cancers, but not in normal uterine tissue, benign tumors, or most low-grade neoplasms of the uterus. We also engineered HMGA1 transgenic mice and found that all females develop uterine sarcomas by 9 months of age. In lung cancer, we reported that HMGA1 induces expression of the matrix metalloproteinase-2 (MMP-2) gene, but only in poorly differentiated tumors, suggesting that this pathway could drive tumor progression and a poorly differentiated state. Here, we investigated the role of the HMGA1-MMP-2 pathway in the pathogenesis of uterine tumorigenesis. Using a genetic approach, we crossed our HMGA1 transgenic mice with mice that are null for the MMP-2 gene. We found that the uterine tumors were significantly smaller in the HMGA1 transgenic mice that are also null for MMP-2. To determine if this pathway is involved in human uterine tumorigenesis, we assessed expression of the HMGA1 and MMP-2 genes in primary, human uterine tumors. We studied: 1.) endometrioid tumors, which are derived from the endometrial epithelium and tend to be low-grade (well-differentiated), 2.) serous tumors, which are also derived from the endometrial epithelium, but tend to be high-grade (poorly differentiated), and, 3.) carcinosarcomas (or mixed malignant, mullerian tumors), which are derived from the endometrial epithelium and stroma and tend to by high-grade. We found that HMGA1 expression was highest in the high-grade serous tumors and carcinosarcomas, with lower levels in the endometrioid tumors. Moreover, we found that there was a significant correlation between HMGA1 and MMP-2, but only in the high-grade carcinosarcomas and serous tumors. Taken together, our studies demonstrate that HMGA1 induces expression of MMP-2 during uterine tumorigenesis and suggest that this pathway is important in aggressive, poorly differentiated tumors. Although further studies are needed, our findings also suggest that the HMGA1-MMP-2 pathway could serve as a rational therapeutic target in poorly differentiated uterine 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 2905. doi:10.1158/1538-7445.AM2011-2905
P21 Hypoxia-induced Neutrophil Survival Is Dependent On Phosphoinositide 3-kinase (pi3-k)-mediated Signalling
Authors: S. Palazzo, L. Porter, J. Juss, E. Hessel, A. Amour, D. House, M. Begg, E. Chilvers
Journal: Thorax (2014)

<h3>Introduction and objectives</h3> Neutrophils (PMNs) are a key component of the innate immune response to invading pathogens. They accumulate at sites of inflammation and infection, which are typically characterised by low oxygen tensions (e.g. in the acute respiratory distress syndrome (ARDS)). Human PMNs undergo constitutive apoptosis, their survival contingent upon pro-survival and pro-apoptotic signals derived from their microenvironment. Hypoxia profoundly delays PMN apoptosis, resulting in persistence of PMNs at inflammatory foci and this may perpetuate hypoxia-mediated lung injury. Given the importance of phosphoinositide 3-kinase (PI3-K) signalling in cytokine-mediated neutrophil survival, we hypothesised that hypoxia-induced PMN survival may also involve PI3-K-mediated signalling. <h3>Methods</h3> Highly pure PMNs isolated from healthy volunteers were incubated for 20 h under normoxic (20 kPa) and physiologically relevant hypoxic (3 kPa) conditions with a pan-PI3-K inhibitor (LY294002 at 10 μM), a novel pan-Class I PI3-K inhibitor (ZSTK474 at 1 μM, 3 μM and 10 μM) or novel PI3-K Class I isoform-selective inhibitors (PI3-Kδ at 1 μM; PI3-Kγ at 3 μM and 10 μM, or PI3-Kδγ at 3 μM). PMNs were also incubated in normoxia and hypoxia in the presence of GM-CSF (1 ng/ml) with the same panel of inhibitors, allowing comparison with GM-CSF mediated survival, which is largely PI3-K dependent. PMN apoptosis was assessed using two complementary techniques – morphology and flow cytometry following annexin V-FITC and propidium iodide staining. <h3>Results</h3> Compared with normoxia, hypoxia promoted PMN survival (mean% ± SEM apoptotic cells at 20 h; 30.9 ± 1.9 vs. 59.0 ± 1.8 respectively, p &lt; 0.0001). Both pan-PI3-K inhibitors reversed the pro-survival effect of hypoxia in a concentration-dependent manner, LY294002 (10 μM; 60.3 ± 4.0, p &lt; 0.0001) and ZSTK474 (10 μM; 58.3 ± 2.6, p &lt; 0.0001) without affecting the basal rate of apoptosis. This effect was not seen with the dual PI3-Kδγ inhibitor (3 μM; 43.8 ± 7.6) or individual PI3-Kδ (1 μM; 43.0 ± 5.8) and γ inhibitors (3 μM; 34.9 ± 4.5 and 10 μM; 32.6 ± 3.6). <h3>Conclusions</h3> Our results indicate that hypoxia-induced PMN survival is PI3-K dependent. Targeting this pathway may accelerate PMN apoptosis, resulting in resolution of inflammation.
A case of gastric ischemic necrosis
Authors: I. Papanikolaou, P. Foukas, A. Sioulas, I. Beintaris, P. Panagopoulos, G. Karamanolis, I. Panayiotides, G. Dimitriadis, K. Triantafyllou
Journal: Endoscopy (2011)

Gastric ischemic necrosis (GIN) is a rare condition, usually seen postoperatively or after therapeutic embolizations [1]; in the absence of such surgical interventions, diagnosis can be delayed, a delay that can be fatal [2]. Patients are treated conservatively unless signs of perforation or sepsis develop,in which casegastrectomy is warranted [3].
1350 GRANULOCYTE APHERESIS FOR STEROID-NAIVE PATIENTS WITH SEVERE ALCOHOLIC HEPATITIS: A CASE SERIES
Authors: S. Hasuike, K. Nagata, Y. Yamada, Y. Ohzono, S. Takeda, S. Hirata, M. Hidaka, S. Natsuda, M. Tsuchimochi, K. Hashimoto, T. Yamaji, K. Nakamura, H. Abe, T. Miike, K. Kusumoto, H. Iwakiri, S. Yamamoto, K. Shimoda
Journal: Journal of Hepatology (2012)
Abstract 4713: Serum thyroglobulin, a biomarker for iodine deficiency, and risk of upper gastrointestinal cancers
Authors: Shih-Wen Lin, Jin-Hu Fan, Sanford M. Dawsey, Xiu-Di Sun, Philip R. Taylor, You-Lin Qiao, Christian C. Abnet
Journal: Cancer Research (2010)

Abstract Objectives: Gastric cancer is the second leading cause of cancer death worldwide and has been hypothesized to be associated with iodine deficiency. While iodine concentrations are highest in the thyroid, iodine also concentrates in gastric tissue where it may act as an antioxidant for the stomach and possibly the esophagus. We previously showed that self-reported goiter was associated with significantly increased risk of gastric noncardia adenocarcinoma (GNCA) and non-significantly increased risks of gastric cardia adenocarcinoma (GCA) and esophageal squamous cell carcinoma (ESCC). Iodine deficiency is correlated with increased serum thyroglobulin, and this study aimed to determine whether serum thyroglobulin is associated with GNCA, GCA, and ESCC in a Chinese population with very high rates of upper gastrointestinal (UGI) cancers. Methods: We examined the association between serum thyroglobulin levels and the three UGI cancers in a study nested in the Linxian General Population Nutrition Intervention Trial. At baseline, blood was drawn from participants, ages 40-69 years, and outcomes were identified during 15 years of follow-up. Approximately 200 subjects of each case type and 400 non-case controls were selected for serum thyroglobulin concentration measurements. All samples were first screened for thyroglobulin antibody, and thyroglobulin concentrations were then measured by radioimmunoassay (RIA) for thyroglobulin-antibody-positive samples or by immunometric assay (IMA) for thyroglobulin-antibody-negative samples. Thyroglobulin concentrations were analyzed as quartiles using logistic regression models adjusted for numerous potentially confounding factors. Results: 25% of females and 5% of males in the controls were thyroglobulin-antibody-positive. Compared to participants in the lowest quartile, those in the highest quartile of serum thyroglobulin had adjusted odds ratios of 0.82 (95% confidence interval 0.50-1.36) for GNCA, 1.12 (0.66-1.90) for GCA, and 0.73 (0.44-1.21) for ESCC. Conclusions: Using serum thyroglobulin, a sensitive biomarker of iodine deficiency, we found no association between serum thyroglobulin concentrations and risk of UGI cancer in the overall study population. Our results do not support the hypothesis that iodine deficiency is associated with an increased risk of UGI cancers in this population. 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 4713.
A fatal case of a colonic fistula communicating with a walled-off area of pancreatic necrosis
Authors: Rungsun Rerknimitr, Narisorn Lakananurak, Piyapan Prueksapanich, Sasipim Sallapant, Phonthep Angsuwatcharakon, Pradermchai Kongkam, Pinit Kullavanijaya
Journal: Endoscopy (2014)

A 28-year-old woman with chronic glomerulonephritis who was treated with prednisolone for many years developed pneumonia due to Nocardia that required treatment with co-trimoxazole. She subsequently developed acute necrotizing pancreatitis and her hospital course was complicated by a prolonged fever. In the fourth week, a computed tomography (CT) scan of the abdomen to evaluate the severity of the pancreatitis demonstrated a walled-off area of pancreatic necrosis (5 × 6 cm) that was extending via the transverse mesocolon to the edematous wall of the transverse colon. In addition, an air pocket was seen in the necrotic cavity ([Fig. 1]). This raised the suspicion of infected pancreatic necrosis and/or fistula formation.
Faisabilité, tolérance et qualité de la gastroscopie sous mélange équimolaire oxygène-protoxyde d'azote
Authors: L de Galleani, G Vanbiervliet, M Montoya, P Staccini, M Raucoules, X Hébuterne
Journal: Endoscopy (2011)

Introduction: Aucune étude n'a évalué de manière prospective le Mélange Equimolaire d'Oxygène et de Protoxyde d'Azote (MEOPA) pour la réalisation de la gastroscopie en alternative à l'anesthésie locale seule ou à l'anesthésie générale chez les patients adultes. L'objectif de notre travail est d'étudier de manière prospective la faisabilité, la tolérance et la qualité de la gastroscopie sous MEOPA.