tbuckley/cabot-search huggingface dataset:
Abstract 3256: New retinoid derivatives as backups of adarotene
Authors: Giuseppe Giannini, Walter Cabri, Tiziana Brunetti, Gianfranco Battistuzzi, Domenico Alloatti, Gianandrea Quattrociocchi, Sabrina Dallavalle, Raffaella Cincinelli, Raffaella Nannei, Loredana Vesci, Claudio Pisano
Journal: Cancer Research (2011)

Abstract Adarotene (ST1926) (WO03/011808) belongs to a so-called class of atypical retinoids. It represents a new first-in-class potent proapoptotic and cytodifferentiating agent, and was selected by Sigma-Tau for clinical development as a “chemotherapy enhancer” in solid tumors (ovarian ca.). In pre-clinical models of haematological as well as solid tumors, Adarotene induced a DNA damage response and affected the modulation of cancer cell survival pathways. When used in combination with other anticancer agents, Adarotene showed a significant synergistic effect in most of the combinations and models tested.(1-4) A possible mechanism has also been described.(5-6) The presence of the phenolic hydroxyl group on Adarotene structure, allowed a rapid O-glucuronidation as a major mechanism of elimination of the drug, favoring a fast excretion of its glucuronide metabolite in the urines. In order to protect the phenolic hydroxyl and improve the “drug-like” properties of the drug, a series of new derivatives have been synthesized. According to chemical structure, these can be grouped into three classes: ether-, carbamate- and ester-derivatives. All of them have been studied and evaluated for their stability at different pH (1.2 – 6.8 – 7.4). The cytotoxic activity in vitro on NCI-H460 non-small cell lung carcinoma and A2780 ovarian tumor cells was also tested.(7) A potential back-up of Adarotene has been selected to be evaluated in vivo tumor models. (1) J. Med. Chem. 2003, 46, 909-912 (2) Blood, 2004, 103, 194-207 (3) J. Med. Chem. 2005, 48, 4931-4946 (4) Bioorganic &amp; Medicinal Chemistry, 2007, 15, 4863-4875 (5) J. Med. Chem. 2008, 51, 5650-5662 (6) J. Comput. Aided Mol. Des. 2010, 24, 943-956 (7) WIPO Patent Application WO2010/072727 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 3256. doi:10.1158/1538-7445.AM2011-3256
Abstract 2960: Factor dependent chromatin structure and nucleosome dynamics
Authors: Housheng H. He, Clifford A. Meyer, Shirley X. Liu, Myles Brown
Journal: Cancer Research (2012)

Abstract Transcription factor cistromes are highly cell-type specific. Chromatin accessibility, histone modifications and nucleosome occupancy have all been found to play a role in defining these binding locations. Here, we show that hormone-induced DNase I hypersensitivity changes (≥DHS) are highly predictive of androgen receptor (AR) and estrogen receptor (ER) binding in prostate cancer and breast cancer cells, respectively. The chromatin structure prior to binding and the nucleosome occupancy after binding are strikingly different for ER and AR. AR binding is associated with changes in both the local nucleosome occupancy and the DNase I hypersensitivity. In contrast, while globally ER binding is unrelated to changes in nucleosome occupancy, DNase I hypersensitivity dynamics predict the ER cistrome. These findings suggest that AR and ER have distinct modes of interaction with chromatin and that DNase I hypersensitivity dynamics provides a general approach for predicting cell-type specific cistromes. 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 2960. doi:1538-7445.AM2012-2960
Algorithm for detection of small-bowel metastasis in malignant melanoma of the skin
Authors: J. Albert, M. Fechner, E. Fiedler, W. Voderholzer, H. Lochs, U. Trefzer, W. Sterry, S. Vay, W. Stremmel, A. Enk, W. Marsch, W. Fleig, P. Helmbold
Journal: Endoscopy (2011)

The aim of this study was to develop an algorithm to detect small-bowel metastasis (SBM) of melanoma by sequential laboratory parameters and pan-intestinal endoscopy (PIE) including video capsule endoscopy (VCE).A total of 390 melanoma patients (AJCC stage I/II/III/IV, 140/80/121/49) were screened for signs of intestinal blood loss (fecal occult blood test [FOBT] or overt bleeding) in an open, multicenter, prospective study, and those who were positive underwent PIE. Independent of the presence of intestinal bleeding, all stage IV patients were offered PIE. Follow-up was obtained in 357 patients (91.5 %) for a median of 16 months. We undertook to identify possible associations between SBM and clinical and laboratory data. Survival data were analyzed with regard to clinical and laboratory data and small-bowel findings.Intestinal blood loss was suspected in 49 of 390 patients (12.6 %), 38 of whom (77.6 %) agreed to undergo endoscopy. In 10 patients, SBM was detected by VCE (intention-to-diagnose, 20.4 %; AJCC III, n = 2; AJCC IV, n = 8). The SBM was resected in five patients. Total detection rates of SBM were 14 of 49 patients in stage IV (28.6 %, intention-to-diagnose), 2 of 121 in stage III (1.7 %), and 0 in stage I/II. In FOBT-positive patients, SBM detection rates were 72.7 %, 14.3 %, and 0 % in tumor stages IV, III, and I/II, respectively. Positive FOBT proved to be an independent negative prognostic factor for total survival in stage III and IV melanoma.SBMs are frequent in advanced melanoma. In stage III patients, screening for intestinal blood loss by PIE may help to identify SBMs. In stage IV, indication for PIE should depend on the individual consequences of detecting SBM, but not on bleeding symptoms alone.
MDR1/ABCB1 single nucleotide polymorphism (SNP) as a possible prognostic factor in breast cancer patients receiving docetaxel and doxorubicin neoadjuvant chemotherapy.
Authors: H. Kim, B. Keam, S. Im, H. Ham, S. Han, D. Oh, W. Han, T. Kim, D. Noh, Y. Bang
Journal: Journal of Clinical Oncology (2010)

585 Background: Drug resistance is a limitation of chemotherapy. Efflux transporters of the ATP-binding cassette family such as ABCB1 (p-glycoprotein) has been identified as a major determinant of chemoresistance. The objective of this study was to explore the correlation between the single nucleotide polymorphisms (SNP) in MDR1/ABCB1 gene and the clinical outcome of patients receiving neoadjuvant chemotherapy (NAC) consists of the substrates of p-glycoprotein. Methods: Stage II or III breast cancer patients who received NAC were enrolled. Patients were treated with 3 cycles of docetaxel and doxorubicin NAC. The clinical response was determined by RECIST criteria after 3 cycles of NAC, after which the patients received curative surgery. Patients who had not experience progression during the NAC, underwent additional 3 cycles of adjuvant chemotherapy with the same regimen. SNPs of MDR1/ABCB1 gene (C3435T, G2677T/A, and C1236T) were genotyped. The correlation of genetic polymorphisms of MDR1/ABCB1 and clinical outcome was analyzed. Results: A total of 216 patients were enrolled. The median age was 44 years and the median primary tumor size was 5.7 cm with 71.8% ≥ stage IIIA, 50.5 % of T3/T4, and 56.5% of N2 or 3 stage. The overall radiologic response rate (RR) was 80.1%, while 8.3% of patients achieved a pathologically complete response. After a follow-up duration of 37.3 months, median relapse-free survival (RFS) and overall survival (OS) were not reached. There was a trend toward longer OS (p = 0.051) and lower relapse rate (p = 0.160) in patients with TT genotype than in those with CC/CT genotype, although which did not reach statistical significance. Polymorphisms of G2677T/A or C1236T were not associated with clinical outcomes in terms of RR and survival. Conclusions: Our study suggested that genetic polymorphism of MDR1/ABCB1 C3435T might be associated with clinical outcomes in patients treated with neoadjuvant docetaxel/doxorubicin for stage II and III breast cancer. Further research including functional analysis and longer follow- up duration is warranted to clarify the clinical impact of MDR1 gene polymorphisms. No significant financial relationships to disclose.
SAT0193 Low Serum Prealbumin as a Prognostic Factor in Systemic Sclerosis
Authors: V. Codullo, E. Cereda, C. Klersy, R. Caccialanza, C. Bonardi, L. Quarleri, S. Breda, R. Caporali, C. Montecucco
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Malnutrition is a frequent complication of Systemic Sclerosis (SSc). Its presence is predicted by an active disease (according to Valentini score) and low serum prealbumin levels. <h3>Objectives</h3> The aim of the present study is to investigate the prognostic value of this latter serum marker of malnutrition in a cohort of SSc outpatients <h3>Methods</h3> Outpatients who satisfied LeRoy’s classification criteria for SSc and admitted to a single University Hospital were screened for malnutrition (defined as a body mass index&lt;20 kg/m<sup>2</sup>, spontaneous weight loss ≥10% of body weight in the previous 6 months or both) and subsequently followed-up according to EUSTAR recommendations for clinical and instrumental parameters and for survival. The Valentini’s disease activity score was calculated at baseline. Presence of other comorbidities (such as diabetes, arterial hypertension, cancer, HCV infection) was also recorded. Statistical analysis was performed with STATA software. <h3>Results</h3> Out of 160 patients evaluated at baseline, 158 (20:138 M:F) had complete follow-up data. Mean age was 60.5±11.1 years, diffuse and limited cutaneous patients were 24 and 134 respectively. Main autoantibody reactivities were anticentromere (n=83, 52%) and anti-topoisomerase I (n=29, 18%). An active disease was present in 27 (17%) patients, malnutrition in 24 (15%). Low prealbumin serum concentrations (&lt;20 mg/dl) were detected in 23 (14.5%). Lung involvement (interstitial or vascular) was present in 43 subjects (27%), gastroenteric tract abnormalities in 82 (52%). After a mean follow-up of 3.8 (2.6-4.5) years, 11 (7%) patients had died (9 of SSc-related causes, 2 of cancer complications). Low prealbumin serum levels were significantly associated to a worse survival (univariate HR= 4.89, 1.36-17.56, p=0.015), even when corrected for other significant predictors of mortality in bivariate analyses (lung involvement, g-i involvement, presence of other comorbidities). When evaluated in combination with disease activity, low prealbumin was strongly predictive of survival in patients with an inactive disease (HR=7.3, 1.22-43.64, p=0.03), but not in patients with active disease. In this analysis, presence of malnutrition conferred increased risk of mortality (HR=2.52, 0.65-9.75; p=0.18) although not reaching statistical significance. <h3>Conclusions</h3> Low prealbumin values are an important marker of malnutrition in SSc patients and represent a poor prognostic factor in terms of mortality, especially in patients with an inactive disease. Prealbumin levels should be investigated and aimed to be restored to normal in SSc cohorts. <h3>Disclosure of Interest</h3> None Declared
Comparison of the diagnostic accuracy of EUS, MDCT, MRCP and ERCP in intraductal papillary mucinous neoplasm (IPMN) of the pancreas
Authors: H Imazu, Y Uchiyama, H Kakutani, K Goda, S Omar, M Kawamura, H Tajiri
Journal: Endoscopy (2006)

Background: Multidiagnostic imaging consisting of EUS, MDCT, MRCP and ERCP are utilised for diagnosing IPMN. The diameter of main pancreatic duct (MPD), size of cystic lesions and mural nodules are very important factors in determining further management for patients with IPMN. However, the role of each diagnostic modality has yet to be defined. We investigated the diagnostic ability of EUS, MDCT, MRCP and ERCP for detection of IPMN.
Genomewide Association Studies and Common Disease — Realizing Clinical Utility
Authors: Lars Fugger, Gil McVean, John I. Bell
Journal: New England Journal of Medicine (2012)

Interview with Dr. David Hunter on genomewide association studies and their potential clinical utility in common diseases. (13:08)Download The value of GWAS for finding therapies for complex disease may seem dubious. But even if genetic variants confer modest risk and subtly alter biologic function, drugs mimicking their activity can have much more powerful effects. GWAS data analysis could identify key leads.
Abstract P2-05-03: Mouse double minute 2 nuclear expression as a prognostic marker in patients with breast cancer
Authors: HS Park, S Park, JS Koo, JH Cho, JM Park, S-I Kim, B-W Park
Journal: Cancer Research (2012)

Abstract BACKGROUND: Mouse double minute 2 (Mdm2) is a negative regulator of tumor suppressor, p53, thus Mdm2 expression may play a role in cancer development and prognosis, however, the definite role of Mdm2 in breast cancer is unclear. The aim of the study is to evaluate the correlation between Mdm2 expression and prognosis of breast cancer. METHODS: Mdm2 expression was determined from immunohistochemistry of tissue microarrays of 865 patients with breast cancer who underwent surgery. Clinicopathologic characteristics and survival data were analyzed using a univariate and multivariate analysis. Mdm2 expression was categorized into 3 groups: negative; no Mdm2 expression in nucleus and cytoplasm, cytoplasm-positive; cytoplasmic expression of Mdm2, nucleus-positive; nuclear with or without cytoplastimc expression of Mdm2. RESULTS: Negative, cytoplasm-positive, and nucleus-positive groups were observed in 59.2%, 10.9%, and 29.9% of patients, respectively. Nucleus-positive group was associated with young age, high grade, negativity of estrogen and progesterone receptor, HER2 positivity, and high Ki-67 index. With median 86.0 follow-up months, nucleus-positive group showed poorer disease-free survival and overall survival than negative and cytoplasm-positive groups. In multivariate analysis, cytoplsmic expression of Mdm2 was not significantly associated with survival, whereas nuclear expression of Mdm2 was related to poor prognosis. (HR, 1.44; 95% CI, 1.041–1.993 for DFS; HR, 1.546; 95% CI, 1.060–2.255 for OS) CONCLUSIONS: Nuclear expression of Mdm2 was an independent prognostic factor in patients with breast cancer. Patterns of Mdm2 expression in tumor cell should be rendered in the evaluation of Mdm2 in breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-03.
607 DEFECTIVE MONOCYTE PHAGOCYTOSIS MAY EXPLAIN SUSCEPTIBILITY TO SEPSIS AND BE A TARGET FOR IMMUNOTHERAPY IN ACUTE-ON-CHRONIC LIVER FAILURE
Authors: R. Tidswell, R. Gadhok, N. Vergis, M.J. McPhail, N. Selvapatt, G.K.M. Vijay, A. Quaglia, W. Bernal, G. Auzinger, M. Heneghan, Y. Ma, M. Thursz, J. Wendon, W. Khamri, C.G. Antoniades
Journal: Journal of Hepatology (2013)
Bleeding hepaticojejunostomy anastomotic varices successfully treated with Histoacryl injection, using single-balloon enteroscopy
Authors: V. Prachayakul, P. Aswakul, U. Kachintorn
Journal: Endoscopy (2011)

A 29-year-old, 31-week pregnant woman presented to our department with recurrent lower gastrointestinal bleeding. Her past history was remarkable for a choledochal cyst excision with hepaticojejunostomy 2 years ago. Intermittent massive bleeding started 6 months after the surgery for which the patient received blood transfusions as the source of the bleeding was not identified. On examination the stools were maroon colored stool but there was no hematemesis. The blood tests were negative for hypercoagulable factors. Esophagogastroduodenoscopy revealed few small esophageal varices and one small gastric varix, without bleeding stigmata, while a colonoscopy was normal. The patient's pregnancy was terminated at 34 weeks because of the recurrent lower gastrointestinal bleeding. Anastomotic varices were suspected to be the source of the bleeding, and thus, single-balloon enteroscopy was carried out. The enteroscopy revealed multiple varices with white and red nipple signs around the hepaticojejunostomy anastomotic site ([Fig. 1]). A total of 3 mL of glue mixture (0.5 mL of N-butyl-2-cyanoacrylate [Histoacryl] and 0.8 mL of Lipiodol) was injected at the varices under fluoroscopic guidance ([Figs. 2], [3]). The patient underwent computed tomography (CT) for portal vein evaluation, which showed embolic glue material in liver parenchyma, small portal vein branches, and multiple filling defects in branches of the superior mesenteric vein (SMV) that were hyperdense in the contrast phase, suggestive of acute SMV branch thrombosis. The patient developed moderate abdominal discomfort without elevation of liver enzymes, but the pain disappeared within few days of conservation management. The patient continues to be free from abdominal pain and bleeding, and a 3-month follow-up single-balloon enteroscopy revealed no residual anastomotic varices ([Fig. 4]).
Abstract 3298: Neotargeting HER2 negative cancer cells with Trastuzumab-based photoimmunotherapy by viral transduction of HER2-extracellular domain.
Authors: Michihiro Ishida, Shunsuke Kagawa, Kyoko Shimoyama, Shinichiro Watamabe, Kazuhiro Noma, Hiroshi Tazawa, Yuuri Hashimoto, Junji Matsuoka, Hisataka Kobayashi, Toshiyoshi Fujiwara
Journal: Cancer Research (2013)

Abstract The prognosis of HER2 positive breast cancer has been improved by Trastuzumab which features high specificity and limited side effects. Numerous randomized trials have confirmed the efficacy and safety of Trastuzumab in HER2-overexpressing cancers. However, many patients who initially respond to Trastuzumab ultimately develop disease progression. Strategies to overcome Trastuzumab-refractory cancer are sought, and drug-conjugation is one of candidates. Trastuzumab-IR700 which is Trastuzumab conjugated with a near-infrared (NIR) photosensitizer, phthalocyanine dye, IR700, has recently been developed as a new type of molecular-target photoimmunotherapy(PIT). This PIT can induce target-selective necrotic cell death only at the place which have Trastuzumab's target part and where exposure of NIR light. Disappointingly, HER2-targeting therapy is applicable to only Her2-expressig tumors which consist of approximately 20-25% of primary breast cancers. In previous study, we developed the adenoviral vector to express HER2-extracellular domain (HER2-ECD), Ad/HER-ECD, and confirmed that it efficiently induced HER2 expression for HER2 negative and HER2-downregulated human cancer cells. So, we hypothesized that Ad/HER-ECD expand the range of tumor entities suitable for Trastuzumab-based PIT. By using Ad/HER-ECD and Trastuzumab-IR700 with PIT we revealed that the direct cell membrane destruction are induced at HER2 negative cancer cells, similarly at HER2 positive cancer cells, in vitro. These results suggest that combination of virally-transduction of target antigen and an antibody-based PIT would expand and potentiate target therapy even for target-negative or attenuated cancer cells. Citation Format: Michihiro Ishida, Shunsuke Kagawa, Kyoko Shimoyama, Shinichiro Watamabe, Kazuhiro Noma, Hiroshi Tazawa, Yuuri Hashimoto, Junji Matsuoka, Hisataka Kobayashi, Toshiyoshi Fujiwara. Neotargeting HER2 negative cancer cells with Trastuzumab-based photoimmunotherapy by viral transduction of HER2-extracellular domain. [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 3298. doi:10.1158/1538-7445.AM2013-3298
Simultaneous Rectal Schwannoma and Prostatic Adenocarcinoma Detected on FDG PET/CT
Authors: Yu-Chin Wu, Te-Chun Hsieh, Chia-Hung Kao, Kuo-Yang Yen, Shung-Shung Sun
Journal: Clinical Nuclear Medicine (2011)

A case of an 84-year-old man with suspicious rectal cancer has been reported. The patient underwent FDG PET/CT for whole-body survey. Unexpectedly, FDG PET/CT demonstrated abnormally increased FDG uptake in rectum (SUVmax: 3.33) and prostate (SUVmax: 5.66) simultaneously. Ultimately, biopsies of rectal tumor and prostatic gland confirmed diagnoses of synchronous schwannoma in the rectum and adenocarcinoma in the prostate. To our best knowledge, this is the first case of rectal schwannoma with representative FDG PET/CT scan in the literature.
TNF <b>α</b> and IL-6 Responses to Particulate Matter <i>in Vitro</i> : Variation According to PM Size, Season, and Polycyclic Aromatic Hydrocarbon and Soil Content
Authors: Natalia Manzano-León, Jesús Serrano-Lomelin, Brisa N. Sánchez, Raúl Quintana-Belmares, Elizabeth Vega, Inés Vázquez-López, Leonora Rojas-Bracho, Maria Tania López-Villegas, Felipe Vadillo-Ortega, Andrea De Vizcaya-Ruiz, Irma Rosas Perez, Marie S. O’Neill, Alvaro R. Osornio-Vargas
Journal: Environmental Health Perspectives (2015)

Observed seasonal differences in particulate matter (PM) associations with human health may be due to their composition and to toxicity-related seasonal interactions.We assessed seasonality in PM composition and in vitro PM pro-inflammatory potential using multiple PM samples.We collected 90 weekly PM10 and PM2.5 samples during the rainy-warm and dry-cold seasons in five urban areas with different pollution sources. The elements, polycyclic aromatic hydrocarbons (PAHs), and endotoxins identified in the samples were subjected to principal component analysis (PCA). We tested the potential of the PM to induce tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6) secretion in cultured human monocytes (THP-1), and we modeled pro-inflammatory responses using the component scores.PM composition varied by size and by season. PCA identified two main components that varied by season. Combustion-related constituents (e.g., vanadium, benzo[a]pyrene, benzo[a]anthracene) mainly comprised component 1 (C1). Soil-related constituents (e.g., endotoxins, silicon, aluminum) mainly comprised component 2 (C2). PM from the rainy-warm season was high in C2. PM (particularly PM2.5) from the dry-cold season was rich in C1. Elevated levels of cytokine production were associated with PM10 and C2 (rainy-warm season), whereas reduced levels of cytokine production were associated with PM2.5 and C1 (dry-cold season). TNFα secretion was increased following exposure to PM with high (vs. low) C2 content, but TNFα secretion in response to PM was decreased following exposure to samples containing ≥ 0.1% of C1-related PAHs, regardless of C2 content. The results of the IL-6 assays suggested more complex interactions between PM components and particle size.Variations in PM soil and PAH content underlie seasonal and PM size-related patterns in TNFα secretion. These results suggest that the mixture of components in PM explains some seasonal differences in associations between health outcomes and PM in epidemiologic studies.Manzano-León N, Serrano-Lomelin J, Sánchez BN, Quintana-Belmares R, Vega E, Vázquez-López I, Rojas-Bracho L, López-Villegas MT, Vadillo-Ortega F, De Vizcaya-Ruiz A, Rosas Perez I, O'Neill MS, Osornio-Vargas AR. 2016. TNFα and IL-6 responses to particulate matter in vitro: variation according to PM size, season, and polycyclic aromatic hydrocarbon and soil content. Environ Health Perspect 124:406-412; http://dx.doi.org/10.1289/ehp.1409287.