tbuckley/cabot-search huggingface dataset:
간세포암환자에서 간절제술후 재발된 간암의 치료 및 예후
Authors: 이찬희
Journal: Clinical and Molecular Hepatology (1995)

Background/Aims:The most effective method of improving survival in patients with HCC is early diagnosis and curative hepatic resection. However, longterm survival after curative resection remains low because of high recurrence rate after resection. The purpose of the study is to assess the prognosis and the efficacy of the various treatment modalities on recurrent HCC after curative resection. Methods:The clinical records of 50 patients with recurrent HCC were reviewed retrospectively who underwent curative surgery in Yonsei University, Severance Hospital from Jan. 1987 through Oct. 1994. The cummulative recurrent rate after resection, the response rate of treatment after resection, the median progression free survival and the survival after recurrence according to the treatment modalities were evaluated. Results:The cummulative recurrent rate after resection was 3.9% at 3 month, 8.3% at 6 month, 14.1% at 12 month, 21.5% at 24 month, 23.4% at 36 month and 24.4% at 60 month. The response rate of treatment after recurrence was 23.7% (9 patients). The median progression free survival of the patient with reoperation and hepatic embolization was 13.9 months, that of conservative treatment group was 6.8 months and that of no treatment group was 4 months(p = 0.004). The survival after recurrence of HCC was 19.7 months in reoperation and hepatic embolization group, 11.4 months in multimodality group, 16.9 months in conservative treatment group and 8.4 months in no treatment group(p=0.0998). Conclusions:Reoperation and hepatic embolization for HCC after curative resection was effective in improving progression free survival, but overall survival were not significantly different according to the treatment modalities. This results proposed that reoperation and hepatic embolization for recurrent HCC after curative resection improve progression free survival.
Abstract 2662: A dual PI3K/mTOR inhibitor as potential therapeutic option for vulvar cancer
Authors: Iara Rodrigues, Bruna Rodrigues, Fernanda Giudice, Glauco Baiocchi, Fernando Augusto Soares, Vilma Martins, Rafael Malagoli Rocha
Journal: Cancer Research (2015)

Abstract Introduction: Epithelial to mesenchymal transition (EMT) is an important process during cancer progression by which epithelial cells acquire mesenchymal phenotype and show reduced intercellular adhesion as well as increased motility. Interfering PI3K/AKT pathway has been considered an anti-EMT target therapy, due to its effect in restoration of E-cadherin function and inhibition of transcription factors that repress the E-cadherin promoter, such as Snail, Slug, and Twist. Aim: Investigate the antitumor effects of treatment with PI3K/mTOR dual inhibitor, NVP-BEZ235, in biological behavior of lymph node metastatic vulva cancer cell line (SW962), as a potential anti-EMT agent in vulvar tumor. Methods: we performed in vitro assays and evaluated the expression of proteins related to PI3K/Akt/mTOR pathway as well as Vimentin and E-cadherin, relevant EMT biomarkers. All results were presented as mean standard deviation and were compared using the unpaired t test or ANOVA followed by the Bonferroni post test using Graph Pad InStat v3.02 software. P values &amp;lt; 0.05 were considered statistically significant. Results: Treatment with NVP-BEZ235 resulted in a significant decrease in cell migration (p&amp;lt; 0.001), proliferation (p&amp;lt; 0.01) and invasion (p&amp;lt;0.05). The phosphorylation of AKT, S6K, 4E-BP1 and p70S6 was markedly reduced by NVP-BEZ235 treatment. In contrast, the levels of p-GSK3β (Ser9) were increased. Our qualitative results demonstrated that the localization pattern of E-cadherin and Vimentin protein was similar between control and treatment groups. We observed Vimentin protein only in isolated cells and, E-cadherin protein was found exclusively in cell clusters, demonstrating EMT-like events in SW962 cells. The expression of E-cadherin in SW962 cells treated was slightly increased and the levels of Vimentin was reduced in these cells. Conclusion: The present study suggests that NVP-BEZ235 is an effective inhibitor of PI3K/mTOR pathway, resulting in the decrease of Vimentin expression, an important EMT marker, as well as of other essential tumor events, such as proliferation, migration and invasion of vulva cancer. Taken together, these findings not only provide a novel insight into the actions of NVP-BEZ235 as inhibitor of EMT process in cancer progression, but also highlight a novel potential therapeutic option for the treatment of aggressive tumors such as vulvar carcinoma. Citation Format: Iara Rodrigues, Bruna Rodrigues, Fernanda Giudice, Glauco Baiocchi, Fernando Augusto Soares, Vilma Martins, Rafael Malagoli Rocha. A dual PI3K/mTOR inhibitor as potential therapeutic option for vulvar cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2662. doi:10.1158/1538-7445.AM2015-2662
Abstract 4603: Male pattern baldness in relation to prostate cancer-specific mortality: A prospective analysis in the NHANES I Epidemiologic Followup Study (NHEFS)
Authors: Cindy Ke Zhou, Paul H. Levine, Sean D. Cleary, Heather J. Hoffman, Barry I. Graubard, Michael B. Cook
Journal: Cancer Research (2015)

Abstract Background: Androgenic action underlies prostate gland development and prostate cancer progression. However, the role of such in prostate carcinogenesis remains unclear. Results from studies that have quantitated pre-diagnostic, circulating androgens at a single time-point in relation to prostate cancer are inconsistent, possibly due to the failure to capture cumulative or relevant age-specific hormone exposure. Therefore, we used male pattern baldness as a proxy of long-term androgen exposure, and investigated the association between dermatologist-assessed male pattern baldness and prostate cancer-specific mortality in the NHANES-I Epidemiologic Followup Study (NHEFS). Methods: We included 4,316 men from NHEFS, who were 25-74 years, received dermatologic exams, and had no prior cancer diagnosis at baseline. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) were estimated using Cox proportional hazards regression with age as the time-metric and baseline hazard stratified by age at baseline. A hybrid model was used to account for stratification and clustering of the survey design, while adjusting for variables used to calculate sample weights. Results: During follow-up (median = 21 years), 3,284 deaths occurred, 107 of which had the underlying cause of prostate cancer. Any degree of baldness was associated with a 56% increased risk of prostate cancer-specific mortality (HR = 1.56; 95%CI = 1.02, 2.37) and, specifically, moderate balding was associated with an 83% increased risk of the outcome (HR = 1.83; 95%CI = 1.15, 2.92), each compared with no balding. Conversely, male pattern baldness was not statistically significantly associated with all-cause mortality. Conclusion: Our analysis suggests that male pattern baldness is associated with an increased risk of fatal prostate cancer, and supports the hypothesis of overlapping pathophysiological mechanisms. Impact: If the association between male pattern baldness and fatal prostate cancer is substantiated in future studies, male pattern baldness may contribute to predictive algorithms of prostate cancer risk, helping guide individuals as to whether they should opt to undergo cancer screening. Citation Format: Cindy Ke Zhou, Paul H. Levine, Sean D. Cleary, Heather J. Hoffman, Barry I. Graubard, Michael B. Cook. Male pattern baldness in relation to prostate cancer-specific mortality: A prospective analysis in the NHANES I Epidemiologic Followup Study (NHEFS). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4603. doi:10.1158/1538-7445.AM2015-4603
Unrelated Cord Blood Transplantation (UCBT) in Children with Sickle Cell Disease (SCD): US Centers Experience.
Authors: Tom V. Adamkiewicz, Ann Haight, Melissa A. Mazur, K. Scott Baker, Paul Szabolcs, Amos Kedar, K.Y. Chiang, Lakshmanan Krishnamurti, John E. Wagner, John R. Wingard, Andrew M. Yeager
Journal: Blood (2005)
The “Bandalarga” project: School's concerts in oncology
Authors: D. Pezzuolo, L. Scarabelli, F. Giovanardi, G. Prati, S. Montanari, R. Vernizzi, S. Darecchio, G. Maramotti, M. Codispoti, F. Sforacchi, E. Gervasi, G. Codeluppi, G. Carpi, C. Manara, M. Cavalca, C. Brozzi, R. Alberini, C. Verona, L. Scaltriti
Journal: Annals of Oncology (2015)
187. TFEB-Mediated Clearance of the Lipofuscin Fluorophore A2E
Authors: Ivana Trapani, Elisabetta Toriello, Renato Minopoli, Alberto Auricchio
Journal: Molecular Therapy (2016)

Abnormal accumulation of various by-products of the visual cycle, including the diretinoid-pyridinium-ethanolamine (A2E), in retinal pigment epithelium (RPE) is an hallmark of both Stargardt disease (STGD) and age-related macular degeneration (AMD). This is responsible for RPE and, consequently, photoreceptor (PR) cell death. A2E storage in RPE lysosomes has been shown to reduce both the capacity of RPE to degrade phagocytized PR outer segments and autophagosome biogenesis, trafficking and autophagic flux. The transcription factor EB (TFEB) is a master regulator of cellular clearance. Here we tested if TFEB overexpression induces A2E clearance from the RPE cells. We have generated a plasmid encoding for a double-serine mutant (S142A, S211A) form of TFEB, which is constitutively active. We have transfected this plasmid in the human RPE-derived ARPE19 cells to evaluate TFEB activation of its transcriptional targets and ability to clear A2E after loading. We found that TFEB overexpression in ARPE19 cells results in the induction of TFEB transcriptional targets involved in cellular clearance. Importantly, TFEB overexpression in ARPE19 cells was associated with reduction of intracellular A2E accumulation. Taken together these results suggest that TFEB overexpression is an effective strategy to promote A2E clearance in vitro. Further studies will clarify if this holds true in vivo. These results may have implications for the therapy of both STGD and the more common AMD.
Abstract 2137: The effect of the transcription factor MAZ on kRAS transcription: a role for the G-quadruplex
Authors: Harshul Batra, Tracy A. Brooks
Journal: Cancer Research (2015)

Abstract kRAS is a GTPase protein affecting normal cell proliferation, division, and apoptosis. It is mutated in &amp;gt;30% of all cancers, particularly in 60-90% of pancreatic cancers. Mutated kRAS leads to continuous activity and uncontrolled proliferation. To date there have been no successful clinical agents targeting mutant kRAS activity. Modulating kRAS expression has shown anti-proliferative promise as an approach in pancreatic cancer models, but is not a main avenue of pursuit for clinical development due to lack of a molecular target. Our lab is focused on the regulation of kRAS transcription through a variety of G-rich regions of DNA in the promoter capable of forming non-B-DNA structures termed G-quadruplexes (G4s). In the current study, we sought to determine the effect of the transcription factor MAZ on the regulation of kRAS, with a particular focus on the three putative G4-forming regions (herein termed near, mid, and far in reference to their relative proximity to the transcriptional start site). In a study of the kRAS promoter using a series of luciferase plasmids, MAZ expression led to a concentration-dependent decrease in promoter activity. This action was localized to interactions with the mid-G4-forming region. In the context of a more multifaceted intracellular mileu as found in the pancreatic cancer cell lines MiaPaCa-2, Panc-1, and BxPc3, the effects of MAZ were much more complex. In particular, 48 hr post-transfection with MAZ expression plasmids, monitoring of kRAS transcription revealed a cell line-specific modulation with an increase in kRAS expression in Panc-1 cells only, confirming a previous study, and no changes noted in either the MiaPaCa-2 or the Bx-Pc3 cells. Further studies are ongoing evaluating the direct binding of MAZ to the various G-rich regions in those cell lines, as well as determining the DNA structure (single-stranded, double-stranded, or G4-DNA) to which the MAZ protein is binding. Ultimately, an understanding of the regulation of this G-rich region of DNA, by MAZ or any other transcription factors such as Sp1 or p53, is an important part of the larger puzzle leading to a targeted drug discovery program focused on G4-regulation. Ultimately, G4-stabilization-mediated down regulation of kRAS has high potential for anti-cancer efficacy in pancreatic cancers, where there is a dire need for novel therapeutic development. Citation Format: Harshul Batra, Tracy A. Brooks. The effect of the transcription factor MAZ on kRAS transcription: a role for the G-quadruplex. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2137. doi:10.1158/1538-7445.AM2015-2137
Generation of HIV Resistant and Functional Macrophages From Hematopoietic Stem Cell Derived Induced Pluripotent Stem Cells
Authors: Amal Kambal, Gaela Mitchell, Whitney Cary, William Gruenloh, Yunjoon Jung, Catherine Nacey, Stefanos Kalomoiris, Matt Lindsey, Gerhard Bauer, Jan A. Nolta, Joseph S. Anderson
Journal: Blood (2010)
Epithelial-mesenchymal transition: A mechanism of resistance to VEGF pathway inhibition in genitourinary cancers.
Authors: Hans Hammers, Chenglai Fu, Stephanie Gerber, Susan Van Den Berg, Frans Steenwinkel, Whei Moriarty, Daniel Keizman, Sushant Kachhap, Michael Anthony Carducci
Journal: Journal of Clinical Oncology (2012)

390 Background: There is emerging clinical data that epithelial-mesenchymal-transition (EMT), a cellular phenotype observed with aggressive disease and metastasis, is associated with resistance to angiogenesis inhibitors targeting the VEGF pathway. To better study and characterize this clinical observation we set out to generate well-defined preclinical prostate and kidney cancer models of EMT mediated resistance to the angiogenesis inhibitor sunitinib with the overarching goal to develop more effective antiangiogenic therapies in genitourinary malignancies. Methods: We screened a library of prostate and kidney cancer xenografts models for their response to the angiogenesis inhibitor sunitinib. By applying strict clinical criteria we identified models, which were refractory, resistant and also unambiguously sensitive to sunitinib. The sensitive cell lines were used to stably overexpress the EMT inducing transcription factors Twist1, Snail and ZEB1. The cell lines were then injected to form xenografts and their response to sunitinib was assessed. Correlative studies for microvascular density and cellularly mediated resistance through blood vessel maturation and myeloid cell recruitment were performed. Results: EMT mediated resistance to sunitinib was seen in both, prostate and kidney cancer models. Interestingly, EMT mediated resistance was primarily associated with an increase in blood vessel maturation. Conclusions: We present for the first time defined preclinical prostate and kidney cancer model of EMT mediated resistance to a multitargeted VEGF pathway inhibitor. These model could prove useful in our efforts to develop more effective antiangiogenic approaches in prostate cancer and kidney cancer and aid to predict response or the lack thereof to VEGF based therapies.
Effects of Physician-targeted Pay for Performance on Use of Spontaneous Breathing Trials in Mechanically Ventilated Patients
Authors: Ian J. Barbash, Francis Pike, Scott R. Gunn, Christopher W. Seymour, Jeremy M. Kahn
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Pay for performance is an increasingly common quality improvement strategy despite the absence of robust supporting evidence.To determine the impact of a financial incentive program rewarding physicians for the completion of daily spontaneous breathing trials (SBTs) in three academic hospitals.We compared data from mechanically ventilated patients from 6 months before to 2 years after introduction of a financial incentive program that provided annual payments to critical care physicians contingent on unit-level SBT completion rates. We used Poisson regression to compare the frequency of days on which SBTs were completed among eligible patients and days on which patients were excluded from SBT eligibility among all mechanically ventilated patients. We used multivariate regression to compare risk-adjusted duration of mechanical ventilation and in-hospital mortality.The cohort included 7,291 mechanically ventilated patients with 75,621 ventilator days. Baseline daily SBT rates were 96.8% (hospital A), 16.4% (hospital B), and 74.7% (hospital C). In hospital A, with the best baseline performance, there was no change in SBT rates, exclusion rates, or duration of mechanical ventilation across time periods. In hospitals B and C, with lower SBT completion rates at baseline, there was an increase in daily SBT completion rates and a concomitant increase in exclusions from eligibility. Duration of mechanical ventilation decreased in hospital C but not in hospital B. Mortality was unchanged for all hospitals.In hospitals with low baseline SBT completion, physician-targeted financial incentives were associated with increased SBT rates driven in part by increased exclusion rates, without consistent improvements in outcome.
Depletion of SAG/RBX2 E3 ubiquitin ligase suppresses prostate tumorigenesis via inactivation of the PI3K/AKT/mTOR axis
Authors: Mingjia Tan, Jie Xu, Javed Siddiqui, Felix Feng, Yi Sun
Journal: Molecular Cancer (2016)

SAG (Sensitive to Apoptosis Gene), also known as RBX2, ROC2 or RNF7, is a RING component of CRL (Cullin-RING ligase), required for its activity. Our recent study showed that SAG/RBX2 co-operated with Kras to promote lung tumorigenesis, but antagonized Kras to inhibit skin tumorigenesis, suggesting a tissue/context dependent function of Sag. However, it is totally unknown whether and how Sag would play in prostate tumorigenesis, triggered by Pten loss. Sag and Pten double conditional knockout mice were generated and prostate specific deletion of Sag and Pten was achieved by PB4-Cre, and their effect on prostate tumorigenesis was evaluated by H&E staining. The methods of immunohistochemistry (IHC) staining and Western blotting were utilized to examine expression of various proteins in prostate cancer tissues or cell lines. The effect of SAG knockdown in proliferation, survival and migration was evaluated in two prostate cancer cell lines. The poly-ubiquitylation of PHLPP1 and DEPTOR was evaluated by both in vivo and in vitro ubiquitylation assays. SAG is overexpressed progressively from early-to-late stage of human prostate cancer with the highest expression seen in metastatic lesion. Sag deletion inhibits prostate tumorigenesis triggered by Pten loss in a mouse model as a result of suppressed proliferation. SAG knockdown in human prostate cancer cells inhibits a) proliferation in monolayer and soft agar, b) clonogenic survival, and c) migration. SAG is an E3 ligase that promotes ubiquitylation and degradation of PHLPP1 and DEPTOR, leading to activation of the PI3K/AKT/mTOR axis, whereas SAG knockdown caused their accumulation. Importantly, growth suppression triggered by SAG knockdown was partially rescued by simultaneous knockdown of PHLPP1 or DEPTOR, suggesting their causal role. Accumulation of Phlpp1 and Deptor with corresponding inactivation of Akt/mTOR was also detected in Sag-null prostate cancer tissues. Sag is an oncogenic cooperator of Pten-loss for prostate tumorigenesis. Targeting SAG E3 ligase may, therefore, have therapeutic value for the treatment of prostate cancer associated with Pten loss.
Determinants of bile acids.
Authors: Bonnie LaFleur, Weiqun Tong, Junmei Liu, M Peter Lance, Patricia Thompson
Journal: Journal of Clinical Oncology (2012)

632 Background: Several epidemiological studies have demonstrated an association between bile acids (BA) and colorectal cancer. Despite this evidence, there are limited studies that examine the determinants of bile acids in humans. We conducted a secondary, cross-sectional analysis on 735 adenoma formers from a phase III adenoma prevention trial of ursodeoxycholic acid (URSO) who provided a fecal sample at their baseline visit. Methods: Fecal measures of primary bile acids cholic acid (CA) and chenodoxycholic acid (CDCA), as well as secondary bile acids, deoxycholic acid (DCA), lithocholic (LCA) were the outcome variables of interest. Dietary, non-dietary, medication use, genetic variation in the CYP7A1 gene (as single nucleotide polymorphisms (SNPs) and haplotypes), and physical activity, and characteristics of baseline adenoma were evaluated as correlates of fecal BAs. We used maximum likelihood methods to incorporate left-censoring in the BAs that had concentrations below the detection limit (BDL). These log-normal parametric survival models were used to fit potential predictors of fecal BA levels, stratifying by sex. The Akaike information criterion (AIC) was used to choose the best predictive model from each BA outcome. Model accuracy was assessed using leave-one-out cross validation and a likelihood-based measure of R 2 and the Brier score. Results: LDL and cholesterol were predictors for primary bile acid CDCA in men and women, as was the use of pain medication (use of medication lowered BA levels). Genetic variation in CYP7A1 (as haplotypes and individual SNP's) was a significant determinant of CA level in both men and women. BMI was an important predictor for both men and women for DCA and CA. Presentation with tubular-villous histology was associated with LCA levels whereas proximal adenoma was an important predictor for CA levels, in men and women. Conclusions: This secondary analysis of a uniquely large dataset validates previous studies that suggest lifestyle and genetic factors influence colonic exposure to carcinogenic BAs. These findings also importantly highlight gender-specific differences in BA determinants that may explain colorectal cancer incidence differences between men and women.
Cerebellar Metastases From Prostate Cancer on 68Ga-PSMA PET/CT
Authors: Mico Chan, Edward Hsiao, Jennifer Turner
Journal: Clinical Nuclear Medicine (2016)

68Ga prostate-specific membrane antigen PET/CT is increasingly used to evaluate extent of disease in prostate carcinoma. Parenchymal brain metastases originating from prostate cancer have highly variable imaging appearance. We present a 77-year-old man with cerebellar metastasis from prostate cancer showing focal uptake on prostate-specific membrane antigen PET/CT.