tbuckley/cabot-search huggingface dataset:
Early- and late-onset psoriasis: a cross-sectional clinical and immunocytochemical investigation
Authors: E. Theodorakopoulou, Z.Z.N. Yiu, C. Bundy, L. Chularojanamontri, M. Gittins, L.A. Jamieson, L. Motta, R.B. Warren, C.E.M. Griffiths
Journal: British Journal of Dermatology (2016)

There is accumulating evidence that early‐onset psoriasis (EOP; presenting at or before 40 years of age) and late‐onset psoriasis (LOP; presenting after 40 years of age) are different diseases. We aimed to identify potential clinical and immunocytochemical differences between EOP and LOP. We assessed immunocytochemistry in involved (PP) skin and uninvolved skin (n = 31) and demographics, psoriasis phenotype and psychological parameters (n = 340) in a cross‐sectional study. Immunocytochemistry revealed (17 EOP, 14 LOP) a greater lymphocytic infiltrate in PP skin of EOP compared with LOP (P = 0·03), with a higher epidermal CD4+ : CD8+ ratio in LOP (1·3) compared with EOP (0·5) (P = 0·002). In 340 patients with psoriasis (278 EOP, 62 LOP), we found an association with a positive first or second degree family history of psoriasis [62·0% vs. 35·6%, adjusted odds ratio (OR) 8·32, 95% confidence interval (CI) 1·90–36·52] and a higher likelihood of having parents with EOP (adjusted OR 10·34, 95% CI 1·32–81·83) in the EOP group. Patients with EOP were more likely to have received biological therapy (13·3% EOP vs. 3·5% LOP, P = 0·042), while patients with LOP had a higher likelihood of having type 2 diabetes (adjusted OR 3·43, 95% CI 1·004–11·691) and autoimmune thyroiditis (adjusted OR 5·05, 95% CI 1·62–15·7). Patients with LOP also had greater anxiety than patients with EOP (mean Hospital Anxiety and Depression Scale‐A score LOP 8 ± 5, EOP 5 ± 5; P = 0·006). Our findings provide further evidence for the difference between EOP and LOP.
Serum Levels of MicroRNA miR-371a-3p: A Sensitive and Specific New Biomarker for Germ Cell Tumours
Authors: Klaus-Peter Dieckmann, Arlo Radtke, Meike Spiekermann, Thomas Balks, Cord Matthies, Pascal Becker, Christian Ruf, Christoph Oing, Karin Oechsle, Carsten Bokemeyer, Johannes Hammel, Sebastian Melchior, Werner Wosniok, Gazanfer Belge
Journal: European Urology (2016)

Clinical management of germ cell tumours (GCTs) relies on monitoring of serum tumour markers. However, the markers α-fetoprotein (AFP), the β-subunit of human chorionic gonadotropin (bHCG), and lactate dehydrogenase (LDH) are expressed in <60% of GCT cases. To test the utility of the microRNAs (miRNAs) miR-371a-3p, miR-372-3p, miR-373-3p, and miR-367-3p as sensitive and specific GCT serum biomarkers. Serum levels of miRNAs were measured in 166 consecutive patients with GCT before and after treatment and in 106 male controls. In the first 50 consecutive patients, all four miRNAs were measured. In the main study, only the most sensitive miRNA was further analysed. The specificity and sensitivity of the four miRNAs were studied using receiver operating characteristic curves. miRNA sensitivities were compared to those of classical markers. Statistical cross-comparisons of miRNA levels for GCT subgroups and controls were performed at various time points during treatment. Overall, miR-371a-3p performed best, with 88.7% sensitivity (95% confidence interval [CI] 82.5–93.3%) and 93.4% specificity (95% CI 86.9–97.3%) and an area under the curve of 0.94, outperforming AFP, bHCG, and LDH (combined sensitivity 50%). According to Kernel density estimation, the sensitivity and specificity were 86.3% and 92.5%, respectively. miR-371a-3p levels dropped to normal after completion of treatment. The miRNA levels correlated with treatment failure and relapse. Teratoma did not express miR-371a-3p. The miRNA miR-371a-3p is a specific and sensitive novel serum GCT biomarker that accurately correlates with disease activity. Validation of this test in a large-scale prospective study is needed. miR-371a-3p is a novel serum marker for germ cell tumours that is expressed by 88.7% of patients and thus is far more sensitive and specific than classical serum markers. It correlates with tumour burden and treatment results. Validation in a large patient cohort is needed.
Abstract 1949: MicroRNA-137 is a putative predictive biomarker and can inhibit cell proliferation and induce apoptosis in colorectal cancer
Authors: YU-CHUAN HUANG.
Journal: Cancer Research (2016)

Abstract MicroRNA-137 (miR-137) is a potential tumor suppressor in many kinds of cancers, including colorectal cancer (CRC). However, the role of miR-137 in CRC remains unclear. Our study showed that miR-137 is silenced in human colorectal cancer tissues and colon polyps. The methylation of miR-137 promoter is determined by methylation-specific PCR (MSP) and quantified by pyrosequencing analysis. By bioinformatics analysis and Q-PCR assay, we confirmed that miR-137 can target COX2, CDC42, CDK6, and Aurora-A. The negative expression of miR-137 and Aurora-A is confirmed in human colorectal cancer tissues and colon polyps, as well as colon polyps from the AOM/DSS-treated mouse model. Enforcing expression of miR-137 in colorectal cancer cells resulted in G2/M arrest, reduced cell proliferation, and finally led to apoptosis. Those effects can be rescued by overexpressed Aurora-A. By xenograft animal model, the growth of tumors was attenuated in miR-137-overexpressing colorectal cancer cells, in which the tissues show an increased Annexin V signal. Additionally, the AOM/DSS-induced colorectal adenocarcinoma can be restored by demethylation drug treatment. Taken together, our study suggests that epigenetic silence of miR-137 may contribute to early CRC formation through inhibiting the expression of Aurora-A, and loss of miR-137 expression in colon polyps may serve as a potential biomarker to predict the tendency towards to CRC formation. The investigation of the regulatory mechanism of miR-137 in CRC progression may shed new light on early prognosis or cancer therapy for CRC in the future. Citation Format: YU-CHUAN HUANG. MicroRNA-137 is a putative predictive biomarker and can inhibit cell proliferation and induce apoptosis in colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1949.
Prognostic impact of stem cell marker CD133 in 61 glioblastoma patients treated with concomitant chemoradiation: A prospective study.
Authors: P. Metellus, I. Nanni-Metellus, C. Delfino, C. Colin, B. Coulibaly, F. Fina, O. L. Chinot, D. Figarella-Branger, L. Ouafik
Journal: Journal of Clinical Oncology (2010)

2027 Background: Cancer stem cells (CSC) are thought to represent the population of tumorigenic cells responsible for tumor development. The CD133 antigen has been described as a putative stem cell marker in malignant brain tumor that could identify such a tumorogenic population in a subset of glioblastoma multiforme (GBM). To date, the correlation between CD133 expression in primary GBM and patients' prognosis is not clearly established. To address this question we investigated the relationship between the expression of CD133 marker and glioblastoma patients outcome. Methods: The quantittative expression of CD133 stem cell antigen mRNA was assesszed using real-tima quantitative RT-PCR in a prospective cohort of 61 primary GBM patients treated with radiotherapy combined with concomitant and adjuvant therapy with temozolomide. Results: On multivariate survival analysis, CD133 stem cell antigen expression was a significant (p = 0.007) prognostic factor for adverse overall survival independent of extent of resection (p = 0.012), patient age (p = 0.037) and MGMT status (p = 0.002). Furthermore, according to the conjoined expression of CD 133 and MGMT status, the patients were categorized into three groups. Among these three groups, patients with methylated tumors and low expression level of CD 133 (group I) had the best prognosis, patients with unmethylated tumors and high expression level of CD 133 (group III) had the poorest prognosis and others (group II) had an intermediate outcome. Conclusions: These findings constitute conclusive evidence that the measurement of the mRNA expression of CD133 stem cell antigen carried by some GBM cancer stem cells actually impact the survival of GBM patients, lending support to the current brain tumor stem cell hypothesis. No significant financial relationships to disclose.
구연 : 간세포암에서 N-cadherin의 과발현 : 근치적 간절제술후 조기 재발을 예견할 수 있는가?
Authors: 김선영, 이한주, 장명국, 김인숙, 임영석, 정영화, 이영상, 서동진, 유은실, 전선영
Journal: Clinical and Molecular Hepatology (2003)
Abstract 4184: Pre-clinical study using KRAS mutant mouse models for lung cancer immunotherapy together with MEK inhibition
Authors: Jiehui Deng, Shuai Li, Grit Herter-Sprie, Paul D. Smith, Gordon J. Freeman, Jeffrey A. Engelman, Peter Hammerman, Kwok-Kin Wong
Journal: Cancer Research (2016)

Abstract Activating KRAS mutations are identified as the most common driver oncogene for lung adenocarcinomas, accounts for 20∼30% of lung cancer patients. The development of therapeutic strategy for KRAS mutant lung cancer patients remains to be an unmet need, due to poor prognosis and therapeutic resistance to conventional therapy. The purpose of our study is through utilizing different types of genetically engineered mouse models (GEMMs), to understand the molecular heterogeneity of KRAS mutant lung cancer, to define the immune microenvironment, and to determine the feasibility and strategy of using MEK inhibition in combination with immune checkpoint inhibitors for the treatment of KRAS mutant lung cancer. We generated two different types of GEMMs with KRAS mutations that develop tumor in the lung: Kras with G12D mutation or KRAS with G12C mutation. Continuous treatment of either KrasG12D or KRASG12C mice with MEK inhibitor Selumetinib (AZD6244, ARRY-142886) shows short-term response followed by drug resistance to single regimen treatment. The immuno-profiling shows that Selumetinib can increase cytotoxic T cells percentage and decrease PD-L1 expression on both myeloid cells and lymphocytes. Prolonged treatment of Selumetinib on KRAS mutant mice will lead to down-regulation of the expression of immune-checkpoint inhibitory factors Ctla-4 and Pd-1 on both CD4+ and CD8+ T cells. When KRAS mutant mice are treated with Selumetinib intermittently, they show improved response comparing with continuous treatment. When combining MEK inhibition with immune checkpoint blockade by using Selumetinib together with Pd-1 antibody treatment, Tim3 and Ctla-4 expression on T cells is increased potentially leading to T cell exhaustion and immune suppression in lung cancer. These pre-clinical results provide molecular insight for the immune response to MEK inhibition in KRAS driven lung cancer. Furthermore, these data support our hypothesis that MEK inhibition combination with immune checkpoint blockade treatment will have better outcome for lung cancer patients that have KRAS mutation through activating T cell response. Citation Format: Jiehui Deng, Shuai Li, Grit Herter-Sprie, Paul D. Smith, Gordon J. Freeman, Jeffrey A. Engelman, Peter Hammerman, Kwok-Kin Wong. Pre-clinical study using KRAS mutant mouse models for lung cancer immunotherapy together with MEK inhibition. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4184.
Abstract 3512: Cyclopamine enhances TRAIL-induced apoptosis by induction of DR5 via ER stress in gastric cancer cells
Authors: Yoo Jin Na, Dae-Hee Lee, Jung Lim Kim, Bo Ram Kim, Seong Hye Park, Byung-Wook Min, Sun Il Lee, SangHee Kang, Sung Yup Joung, Suk Young Lee, Hong-Jun Kim, Sang Cheul Oh
Journal: Cancer Research (2016)

Abstract Activation of sonic hedgehog (Shh) signaling has been involved in progression of various cancers. Cyclopamine uses as effective treatment for cancers in which hedgehog signaling is overexpressed. In this study, we elucidated that cyclopamine sensitizes to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in gastric cancer cells. Single treatment with cyclopamine or TRAIL could not induce significant cytotoxicity in gastric cancer cells. However, combination treatment of TRAIL with cyclopamine effectively led to caspase dependent apoptosis. We found that cyclopamine increased ER (Endoplasmic Reticulum) stress level in gastric cancer cells, and using ER stress inhibitor attenuated the cell death by cyclopamine. As further underlying mechanism, induction of ER stress by cyclopamine caused upregulation of JNK (c-Jun N-terminal kinases) protein, and then accumulation of p53 protein. We conducted experiment using p53 wild-type and p53-mutated gastric cancer cells, and this of particular importance since p53 wild-type gastric cancer cells had more significant efficacy than p53-mutated cells by cyclopamine. Accumulation of p53 increased DR5 protein. Taken together, we showed that cyclopamine sensitizes to TRAIL-induced apoptosis in gastric cancer cells. Citation Format: Yoo Jin Na, Dae-Hee Lee, Jung Lim Kim, Bo Ram Kim, Seong Hye Park, Byung-Wook Min, Sun Il Lee, SangHee Kang, Sung Yup Joung, Suk Young Lee, Hong-Jun Kim, Sang Cheul Oh. Cyclopamine enhances TRAIL-induced apoptosis by induction of DR5 via ER stress in gastric cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3512.
Abstract 4348: A prospective study of smoking habit and risk of synchronous colorectal cancers
Authors: David A. Drew, Reiko Nishihara, Paul Lochhead, Aya Kuchiba, Zhi Rong Qian, Kosuke Mima, Katsuhiko Nosho, Kana Wu, Molin Wang, Donna Spiegelman, Edward L. Giovannucci, Charles S. Fuchs, Shuji Ogino, Andrew T. Chan
Journal: Cancer Research (2016)

Abstract Background: Synchronous colorectal cancers (CRC) (2 or more distinct primary carcinomas simultaneously identified in one patient) may arise as a result of a “field effect” or shared etiologic factors. Synchronous CRC has been associated with somatic epigenetic changes; cigarette smoking has been associated with DNA methylation in CRC. Thus, we examined the association between cigarette smoking and risk of synchronous CRC. Methods: Among men and women enrolled in the Health Professionals Follow-up Study and Nurses’ Health Study over 24 and 32 years, respectively, we examined the association of smoking with CRC. We examined the differential risk of developing synchronous CRC compared with solitary CRC, classified based on review of pathology reports, through duplication-method Cox proportional hazards regression. Results: During 3,477,211 person-years of follow-up of 45,691 men and 88,614 women, we documented 1,960 individuals with solitary CRC and 45 individuals with synchronous CRC. The association of smoking with CRC differed significantly according to the presence of synchronous compared with solitary tumors (Pheterogeneity = 0.0008). Compared with never smokers, current smokers experienced a higher risk of synchronous CRC (multivariable HR = 5.26; 95% CI, 2.08-13.32). In contrast, current smokers did not experience an elevated risk of solitary cancer (multivariable HR = 0.97; 95% CI, 0.83-1.13). Similar differences in the association of cumulative pack-years smoked with CRC according to tumor synchronicity status were also observed (Pheterogeneity = 0.006). Smoking cessation for ≥10 years was significantly associated with reduced risk of synchronous tumors (multivariable HR = 0.44; 95% CI, 0.20-1.00), but not solitary tumors (multivariable HR = 1.07; 95% CI, 0.91-1.25) (Pheterogeneity = 0.003). Conclusion: Current cigarette smoking is associated with an increased risk of synchronous but not solitary CRC. These data support a model in which smoking contributes to an etiologic field effect predisposing individuals to the development of synchronous CRC. Citation Format: David A. Drew, Reiko Nishihara, Paul Lochhead, Aya Kuchiba, Zhi Rong Qian, Kosuke Mima, Katsuhiko Nosho, Kana Wu, Molin Wang, Donna Spiegelman, Edward L. Giovannucci, Charles S. Fuchs, Shuji Ogino, Andrew T. Chan. A prospective study of smoking habit and risk of synchronous colorectal cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4348.
Abstract 4684: Modulating the function of multidrug resistance ABCG2 transporter by tyrosine kinases receptor inhibitor cabozantinib
Authors: Guannan Zhang, Yun-Kai Zhang, Yi-Jun Wang, Zhe-Sheng Chen
Journal: Cancer Research (2016)

Abstract Cabozantinib (XL184) is an oral tyrosine kinases receptor inhibitor which inhibits MET and vascular endothelial growth factor receptor 2 (VEGFR2). Cabozantinib has been approved by Food and Drug Administration for treating advanced medullary thyroid cancer and it is also tested in clinical trials on other solid tumors, including prostate, bladder, ovarian and breast cancer. In the present study, we evaluated the ability of cabozantinib in modulating the function of ABCG2 transporter in drug-selected H460/MX20 cell line and ABCG2 stable transfected cell lines ABCG2-482-R2, ABCG2-482-G2 and ABCG2-482-T7. Cabozantinib at non-toxic level can sensitize the ABCG2-overexpressing cells to antineoplastic drugs mitoxantrone, SN-38 and topotecan. Our results indicated that cabozantinib reversed ABCG2 mediated multi-drug resistance by antagonizing the drug efflux function of ABCG2. However, this reversal effect was not attributed to reduced expression of ABCG2 protein, because ABCG2 protein level was unchanged after treatment of 4μM cabozantinib for 72 hours. Immunofluorescence result showed that cabozantinib did not alter the cellular localization of ABCG2 transporter. Docking analysis indicated that cabozantinib binds to the drug-binding site of ABCG2 transporter. Finally, cabozantinib at 4μM did not significantly change the resistance of ABCB1 overexpressing cell line SW620/AD300 to antineoplastic drug paclitaxel. Overall, our finding demonstrated that cabozantinib potentiates the cytotoxic effects of various antineoplastic drugs that are substrates of ABCG2 and that this is due to modulating the function of ABCG2 transporter. Keyword: Cabozantinib; ABCG2; Multidrug resistance; Citation Format: Guannan Zhang, Yun-Kai Zhang, Yi-Jun Wang, Zhe-Sheng Chen. Modulating the function of multidrug resistance ABCG2 transporter by tyrosine kinases receptor inhibitor cabozantinib. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4684.
A Simple Scoring System for Identifying Relapsed/Refractory Lymphoma Patients Prematurely Withdrawn from Phase I Trials: The Gustave Roussy Experience
Authors: Lina Benajiba, Capucine Baldini, Laura Faivre, Jean-Marie Michot, Andrea Varga, Christophe Willekens, Camille Bigenwald, Rastislav Bahleda, Anas Gazzah, Jean-Charles Soria, Vincent Ribrag
Journal: Blood (2014)
Abstract 1791: Effects of calcium and vitamin D supplementation on circulating markers of inflammation
Authors: Veronika Fedirko, Julia Latash, Roberd M. Bostick, Elizabeth L. Barry
Journal: Cancer Research (2016)

Abstract Chronic inflammation plays a major role in colon carcinogenesis. Recent evidence from experimental models suggests that vitamin D and calcium may reduce systemic inflammation and local inflammation in the colorectum, thus contributing to reducing risk for colorectal neoplasia. However, human experimental evidence to support these purported anti-inflammatory effects remains inconclusive, coming from very few, small, mainly short-term clinical studies with a variety of doses and administration regimens, with and without calcium supplementation in very different patient populations, and with a limited number of inflammatory biomarkers measured. To address this, we tested the effects of calcium (1.2 g/d) and/or vitamin D3 (1,000 IU/d) supplementation for 3 or 5 years on circulating pro- (IFNγ, TNFα, IL-6, IL-8, IL-12p40) and anti-inflammatory (IL-10) cytokines in 471 participants with previous colorectal adenoma in a recently completed, multi-center, randomized, double-blind, placebo-controlled, modified 2 × 2 factorial chemoprevention clinical trial (NCT00153816). The cytokines were measured in plasma using multiplex electrochemiluminescence detection-based immunoassays. Over a 3- or 5-year treatment period, we found no appreciable effects of calcium and/or vitamin D supplementation on pro-inflammatory cytokines (all P-values &amp;gt; 0.3). However, there was a suggestion that vitamin D may favorably modulate concentrations of IL-10, an anti-inflammatory cytokine. In the calcium, vitamin D, and calcium plus vitamin D groups, the relative increase vs. placebo in IL-10 from baseline to end of follow-up was 3% (P = 0.78), 15% (P = 0.15), 13% (P = 0.35). Our preliminary results indicate no considerable effects of calcium and vitamin D treatment on circulating pro-inflammatory cytokines, and might suggest that vitamin D may increase circulating levels of anti-inflammatory cytokine IL-10, which plays an important role in the Th2-type immune response. Citation Format: Veronika Fedirko, Julia Latash, Roberd M. Bostick, Elizabeth L. Barry, John A. Baron on behalf of Investigators in the PPS4 Study. Effects of calcium and vitamin D supplementation on circulating markers of inflammation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1791.
Abstract 25: SCAP links glucose to lipids for tumor growth
Authors: Chunming Cheng, Feng Geng, Jeffrey Yunhua Guo, Xiaoning Wu, Xiang Cheng, Arnab Chakravarti, Deliang Guo
Journal: Cancer Research (2016)

Abstract Increased glucose consumption and elevated lipogenesis are co-occurred in malignancies. But the molecular mechanism of the link between glucose and lipid metabolism remains elusive. Our previous studies have uncovered that sterol regulatory element-binding protein (SREBP-1), an endoplasmic reticulum-bound transcription factor with a central role in lipid metabolism, is highly upregulated in glioblastoma (GBM), the most deadly brain tumor. In the current study, we found that SREBP-cleavage activating protein (SCAP), a key player regulating SREBP trafficking from ER to the Golgi and subsequent SREBP activation, links oncogenic signaling and glucose consumption to lipid metabolism. Our data showed that glucose is a critical activator for SREBP function via N-glycosylation of SCAP. N-glycosylation is a key signal to promote SCAP/SREBP complex move from ER to the Golgi and SREBP activation. Moreover, we found that EGFR/PI3K/Akt signaling activates SREBP-1 via upregulation of SCAP N-glycosylation and its protein levels through enhancing glucose uptake. Genetically silencing SCAP or mutation of the N-glycosylation sites on SCAP downregulates SREBP-1 activity and impairs GBM tumor growth. Taken together, our study revealed that glucose is a critical activator for SREBP-1 function and lipid metabolism, and SCAP integrates oncogenic signaling and fuel availability to SREBP-1-mediated lipogenesis for tumor growth. Our study also demonstrated that targeting SCAP N-glycosylation represents a promising therapeutic strategy to treat malignancies. Citation Format: Chunming Cheng, Feng Geng, Jeffrey Yunhua Guo, Xiaoning Wu, Xiang Cheng, Arnab Chakravarti, Deliang Guo. SCAP links glucose to lipids for tumor growth. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 25.