tbuckley/cabot-search huggingface dataset:
Prognostic value of the microtubule stability index (MTSI), defined by the quantitative ratio of MAP-tau to stathmin expression, for outcome in breast cancer.
Authors: M. T. Baquero
Journal: Journal of Clinical Oncology (2010)

10523 Background: Microtubule associated proteins (MAPs) endogenously regulate microtubule stability, have been reported as prognostic markers, and may predict response to taxane therapy. Previous work in this laboratory has shown that high expression of MAP-tau, a microtubule stabilizer, is prognostic but not predictive for taxane response and that the microtubule destabilizing protein, stathmin, is prognostic with unknown predictive value. We hypothesize that assessing MAPs as ratios of stabilizers to destabilizers, which parallels endogenous cell division activity, may be more informative than single-marker studies. Here we create a microtubule stability index (MTSI) using the ratio of MAP-tau to stathmin expression and quantitatively assess prognostic value using a large retrospective breast cancer cohort. Methods: MAP-tau and stathmin expression was measured in a breast cancer cohort (n = 645) with 20 year follow-up using tissue microarray and quantitative immunofluorescence (AQUA) technology. MTSI, calculated as the ratio of MAP-tau to stathmin expression, was measured for each patient and correlated with clinical and pathological characteristics as well as disease free survival. Median MTSI score served as the pre-defined cutpoint differentiating high versus low patients. Results: MAP-tau and stathmin expression were not correlated (Spearman's Rho = -0.010; p = 0.8311). Prognostic evaluation using Cox univariate analysis indicated positive correlation between MTSI and disease-free survival (HR = 0.744; 95% CI = 0.591-0.856; p = 0.0002). Kaplan Meier analysis showed median 10-year survival of 65.6% for patients with high MTSI versus 59.1% survival rate for low MTSI (log rank, p < 0.001). Cox multivariate showed MTSI (continuous scale) was independent of age, tumor size, nuclear grade, nodal status, ER, PR, HER2, (HR = 0.756; 95% CI = 0.571-0.756; p = 0.004) and was synergistic when compared to either MAP-tau or stathmin. Conclusions: High MTSI shows synergistic and prognostic value for improved outcome in breast cancer. Future studies will determine if this index is valuable for selecting patients for anti-microtubule therapies. No significant financial relationships to disclose.
TCT-466 Long-term outcomes following mini-crush versus culotte stenting for unprotected left main coronary artery disease: a substudy from the Milan and New-Tokyo (MITO) registry
Authors: Hiroyoshi Kawamoto, Alaide Chieffo, Neil Ruparelia, Akihito Tanaka, Yusuke Fujino, Azeem Latib, Mauro Carlino, Matteo Montorfano, Sunao Nakamura, Antonio Colombo
Journal: Journal of the American College of Cardiology (2015)
Safety and Immunogenicity of the 13-Valent Protein-Conjugated Pneumococcal Vaccine(PCV13) Following Related and Unrelated Hematopoietic Stem Cell Transplantation (HCT)
Authors: Trudy N Small, Ann A. Jakubowski, Juliet N Barker, Nancy A. Kernan, Susan E Prockop, Christine Scura Iovino, LeStrange Nicole, Miguel-Angel Perales, Hugo Castro-Malaspina, Guenther Koehne, Sergio Giralt, Esperanza B Papadopoulos
Journal: Blood (2011)
Salvage Therapy with Everolimus Reduces the Severity of Treatment-Refractory Chronic Graft-Versus-Host Disease without Impairing Disease Control: A Dual Center Experience
Authors: Stephan Mielke, Mathias Lutz, Judith Schmidhuber, Markus Kapp, Julia Ammer, Hermann Einsele, Götz Ulrich Grigoleit, Ernst Holler, Daniel Wolff
Journal: Blood (2012)
TCT-539 Scaffold Thrombosis Following Percutaneous Coronary Intervention With Absorb Bioresorbable Vascular Scaffold: A Systematic Review And Meta-Analysis
Authors: Michael J. Lipinski, Ricardo O. Escarcega, Nevin C. Baker, Hadiya A. Benn, Michael A. Gaglia, Rebecca Torguson, Ron Waksman
Journal: Journal of the American College of Cardiology (2015)
TCT-400 2-Year Clinical Follow-up of the TRYTON IDE Randomized Trial Comparing a Dedicated Bifurcation Stent to Provisional Stenting in the Treatment of Coronary Bifurcations
Authors: Indulis Kumsars, Philippe Genereux, Annapoorna Kini, Maciej Lesiak, Geza Fontos, Ton Slagboom, Imre Ungi, D. Christopher Metzger, Joanna J. Wykrzykowska, Pieter R. Stella, Antonio L. Bartorelli, William F. Fearon, Thierry Lefevre, Robert L. Feldman, Giuseppe Tarantini, Linn L. Laak, Donald Cutlip, Aaron Kaplan, Patrick W. Serruys, Martin Leon
Journal: Journal of the American College of Cardiology (2015)
TCT-708 Progressive Mitral Annuloplasty with Implantation of an Adjustable Complete Circumferential Ring: A Method for Chronic Cinching and Annular Reduction
Authors: Yanping Cheng, Juan Grau, Gerard B. Conditt, Adrienne D. Meyers, Patricia Mount, Athanasios Peppas, Greg L. Kaluza, Juan Granada, Geng-Hua Yi
Journal: Journal of the American College of Cardiology (2015)
GW27-e0256 Panax quinquefolium saponin combined with dual antiplatelet drugs inhibits platelet adhesion to injured HUVECs via PI3K/AKT and COX pathways
Authors: Wang Mingming, Mei Xue, Yu Miao, Na Kou, Yonggang Xu, Lin Yang, Ying Zhang, Dazhuo Shi
Journal: Journal of the American College of Cardiology (2016)
Incidence, Treatment and Outcome of Isolated Extramedullary Relapses after Allogeneic Hematopoietic Stem Cell Transplantation for Acute Lymphoblastic and Myeloid Leukemias: Single-Center Experience with 324 Patients
Authors: Dariusz Kata, Slawomira Kyrcz-Krzemien, Tomasz Czerw, Maria Sadus-Wojciechowska, Marek Seweryn, Grzegorz Helbig
Journal: Blood (2008)
Side Effects on the Heart and Skeleton of Growing Mice Attributed to Chronic Imatinib Exposure.
Authors: Meinolf Suttorp, Julia Boehme, Johannes Vaitl, Birgit Mosch, Stefan Pursche, Roland Jung, Ralf Bergmann, Rainer Fischer, Jens Pietzsch, Martin Bornhaeuser, Juerg A. Gasser
Journal: Blood (2008)
Detecting Adaptation in Protein-Coding Genes Using a Bayesian Site-Heterogeneous Mutation-Selection Codon Substitution Model
Authors: Nicolas Rodrigue, Nicolas Lartillot
Journal: Molecular Biology and Evolution (2016)

Codon substitution models have traditionally attempted to uncover signatures of adaptation within protein-coding genes by contrasting the rates of synonymous and non-synonymous substitutions. Another modeling approach, known as the mutation–selection framework, attempts to explicitly account for selective patterns at the amino acid level, with some approaches allowing for heterogeneity in these patterns across codon sites. Under such a model, substitutions at a given position occur at the neutral or nearly neutral rate when they are synonymous, or when they correspond to replacements between amino acids of similar fitness; substitutions from high to low (low to high) fitness amino acids have comparatively low (high) rates. Here, we study the use of such a mutation–selection framework as a null model for the detection of adaptation. Following previous works in this direction, we include a deviation parameter that has the effect of capturing the surplus, or deficit, in non-synonymous rates, relative to what would be expected under a mutation–selection modeling framework that includes a Dirichlet process approach to account for across-codon-site variation in amino acid fitness profiles. We use simulations, along with a few real data sets, to study the behavior of the approach, and find it to have good power with a low false-positive rate. Altogether, we emphasize the potential of recent mutation–selection models in the detection of adaptation, calling for further model refinements as well as large-scale applications.
Lenalidomide and Rituximab Are a Promising Combination in Vitro, in Vivo Preclinically and in a Phase I/II Clinical Trial in Relapsed/Refractory Mantle Cell Lymphoma
Authors: Michael Wang, Liang Zhang, Luis Fayad, Fredrick Hagemeister, Sattva Neelapu, Felipe Samaniego, Barbara Pro, Anas Younes, Scott Miller, Robert D. Knight, Jerome B. Zeldis, Qing Yi, Jorge Romaguera
Journal: Blood (2008)
Risk of Pregnancy in Moderate and Severe Aortic Stenosis
Authors: Stefan Orwat, Gerhard-Paul Diller, Iris M. van Hagen, Renate Schmidt, Daniel Tobler, Matthias Greutmann, Regina Jonkaitiene, Amro Elnagar, Mark R. Johnson, Roger Hall, Jolien W. Roos-Hesselink, Helmut Baumgartner
Journal: Journal of the American College of Cardiology (2016)
Temozolomide (TMZ) 3 weeks on/1 week off in the treatment of progressive low grade gliomas: A phase II GICNO study
Authors: A. A. Brandes, A. Tosoni, G. Cavallo, L. Scopece, M. Gardiman, F. Berti, L. M. Pasetto, F. Ferrarese, V. Blatt, M. Ermani
Journal: Journal of Clinical Oncology (2006)

1514 Background: Encouraging results have been obtained inlow grade glioma (LGG) patients (pts) following TMZ therapy at the standard schedule of 200 mg/m 2 for five-days every 28 days. A continuous dose TMZ schedule leads to DNA repair enzyme AGAT level depletion in tumor cells. By removing TMZ-produced methyl adducts, AGAT contributes to the development of resistance to alkylating agents. Methods: Pts with a diagnosis of LGG received TMZ 75 mg/m 2 /d for 21 days every 28 days at clinical or radiological progression. MiniMax Simon’s design with P 0 =0.2, P 1 =0.4, α=0.1, β=0.1 was used and a sample size of 36 pts was planned. The primary end-point was to assess the response rate (RR=CR+PR), and the secondary end-point to investigate the correlations between 1p/19q deletions by FISH and MGMT promoter methylation by methylation specific PCR (MSP). Results: 22 oligodendroglioma (O), 4 oligoastrocytoma (OA) and 10 astrocytoma pts (A) were enrolled (median age of pts 47 years, range 24–69 years; median KPS 90, range 50–100). Eleven pts were pre-treated with radiotherapy; 5 (13.5%) had enhancing lesion at MRI scan. RR was 30.5% (11 PR), all RR being obtained in pts with non-enhancing lesions; 20 pts (55.5%) had disease stabilization; 8/11 responders were assessable for 1p/19 q deletions and, of these, 6 pts (75%) had combined 1p/19q deletion. Median PFS was 17.4 months (interquartile ranges, 9.3–25). PFS at 1 year was 73% (SE 8%). Preliminary data on molecular assessment are: 29 pts were assessable for 1p and 19q deletions, both being present in 19 pts (65.5%). 1p/19 q loss was significantly greater in pts with O/OA than A (p=0.01). Of 11 assessable pts, 7 (63.6%) presented MGMT promoter gene methylation and all 7 pts presented 1p and 19q deletions (p=0.03). Grade 3 lymphopenia was observed in 4 pts (11.1%) and 1 patient had G2 reversible renal toxicity. Conclusion: TMZ for 21 days every 28 is an active and well tolerated regimen in pts with LGG. The analysis to verify any correlation between molecular markers and clinical outcome is ongoing. [Table: see text]
TCT-507 Edge Vascular Response After Resorption of Everolimus-Eluting Bioresorbable Vascular Scaffold: A 5-Year Serial Optical Coherence Tomography Study
Authors: Hiroki Tateishi, Shimpei Nakatani, Yuki Ishibashi, Pannipa Suwannasom, Maik J. Grundeken, Yohei Sotomi, Yaping Zeng, Erhan Tenekecioglu, Susan Veldhof, Yoshinobu Onuma, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (2015)
TCT-311 The comparison of myocardial perfusion imaging with fractional flow reserve to detect ischemic territory for patients with multi-vessel disease
Authors: Hiroshi Aoki, Yasutsugu Shiono, Makoto Orii, Akio Kuroi, Takeyoshi Kameyama, Yamano Takashi, Tomoyuki Yamaguchi, Yoshiki Matsuo, Yasushi Ino, Takashi Kubo, Atsushi Tanaka, Takeshi Hozumi, Takashi Akasaka
Journal: Journal of the American College of Cardiology (2015)
Time to Post-Remission Therapy (PRT) Is an Independent Prognostic Factor for Relapse and Overall Survival in Adults with Acute Lymphocytic Leukemia (ALL).
Authors: Anjali Advani, Tao Jin, Ramon Tiu, Giridharan Ramsingh, Christopher Lowe, Wael Saber, Ronald Sobecks, Mikkael Sekeres, Shawnda Sungren, Matt Kalaycio
Journal: Blood (2006)
Occurrence and Prognostic Significance of Cytogenetic Evolution in Patients with Multiple Myeloma
Authors: Moritz Binder, S. Vincent Rajkumar, Rhett P. Ketterling, Angela Dispenzieri, Martha Q. Lacy, Morie A. Gertz, Francis Buadi, Suzanne R. Hayman, Yi L. Hwa, Steven R. Zeldenrust, John A. Lust, Stephen J. Russell, Nelson Leung, Prashant Kapoor, Ronald S. Go, Wilson I. Gonsalves, Robert A. Kyle, Shaji K. Kumar
Journal: Blood (2015)
Rituximab Treatment in Childhood Chronic Immune Thrombocytopenic Purpura (ITP).
Authors: Ji Yoon Kim, Kun Soo Lee, Hyoung Jin Kang, Hoon Kook, Hong Hoe Koo, Sun Young Kim, Byung-Kiu Park, Hyeon Jin Park, Hee-Jo Baek, Jong Jin Seo, Ki Woong Sung, Hee Young Shin, Hyo Seop Ahn, Keon Hee Yoo, Soo Hyun Lee, Ho Joon Im, Yong-Mook Choi, Dong kyun Han, Tai Ju Hwang
Journal: Blood (2009)
Exploratory covariate analysis for phase II clinical trial of sorafenib (S) in metastatic castrate-resistant prostate cancer (mCRPC)
Authors: L. Jain, J. B. Aragon-Ching, P. M. Arlen, J. L. Gully, J. Venitz, J. J. Wright, W. L. Dahut, W. D. Figg
Journal: Journal of Clinical Oncology (2008)

14690 Background: S has been associated with high inter-individual variability in systemic exposure, efficacy & toxicities. To identify potential genetic and non-genetic covariates contributing to this variability, we performed an exploratory analysis of data from phase II clinical trial of S in mCRPC. Methods: In an open label single arm study, 46 patients (pt) were given S at a dose of 400 mg orally BID in 28-day cycles. Pharmacokinetics (PK), after initial doses, was characterized by non-compartmental analysis. Genetic polymorphism in metabolic enzymes (CYP3A4*1B, CYP3A5*3C, UGT1A9*3 & UGT1A9*5), drug target (VEGFR2Val297Ile & VEGFR2Gln472His) for S, baseline age, ethnicity, body weight, body surface area (BSA) and measures of liver function were examined as covariates. For each pt, most severe grade of toxicity (diarrhea, hypertension, hand-foot reaction, skin rash & fatigue) and duration of progression free survival (PFS) were evaluated as response parameters. One-way ANOVA, linear regression and Chi-square tests were performed as covariate analysis. Results: The PK metrics, area under the curve (AUC0–12, exposure) and maximum plasma concentration (Cmax) were significantly inter-related (r=0.98, p<0.0001) for available data from 38 pt. No significant exposure-response (PFS & severity of toxicity) relationship was observed. Age (direct correlation, p=0.0263, r2=0.13) and BSA (inverse correlation, p=0.0347, r2=0.12) were statistically significant covariates for AUC0–12. Age and BSA were inter-related (r=−0.58, p<0.0001). Interestingly, the pt (only 1) with UGT1A9*3/*3 genotype had highest AUC0–12, and grade 3 skin rash; which needs to be confirmed in more pt. Total protein was also found to be a predictor of PFS (direct correlation, p=0.0131, r2=0.15). Conclusion: These exploratory analyses suggest that dosing based on BSA may reduce inter-pt variation in disposition of S. The UGT1A9*3 may be an important predictor of S exposure and severity of skin rash. Studies with larger sample size are needed to confirm these findings and to avoid the skewed genotype distribution. No significant financial relationships to disclose.
GW27-e0163 One - year cohort study about changes in fasting blood sugar and incidence of diabetes mellitus after liver transplantation
Authors: Seyed Jalil Massoumi, Zohreh Mazloom, Abbas Rezaianzadeh, Saman Nikeghbalian, Seyed Ali Malek-Hosseini, Heshmatollah Salahi
Journal: Journal of the American College of Cardiology (2016)
Prognostic Significance of Cytogenetic Abnormalities, Serum P53 Protein Concentration, Staging, Patient Factors in Chinese Patients with Non–Hodgkin Lymphomaprognostic Significance of Cytogenetic Abnormalities, Serum P53 Protein Concentration, Staging, Patient Factors in Chinese Patients with Non–Hodgkin Lymphoma
Authors: Min Zhou, Ling Cen, Jianhe Yang, Jianyong Li
Journal: Blood (2011)
TCT-631 Comparison of the second generation Edwards Sapien 3 valve with the Edwards Sapien XT for transfemoral aortic valve implantation (TAVI)
Authors: Julia Seeger, Birgid Gonska, Christoph Rodewald, Sinisa Marcovic, Dominik Scharnbeck, Wolfgang Rottbauer, Jochen Wöhrle
Journal: Journal of the American College of Cardiology (2015)
A Phase 1 Study of Venetoclax (ABT-199 / GDC-0199) Monotherapy in Patients with Relapsed/Refractory Non-Hodgkin Lymphoma
Authors: John F. Gerecitano, Andrew W. Roberts, John F. Seymour, William G. Wierda, Brad S. Kahl, John M. Pagel, Soham Puvvada, Thomas J. Kipps, Mary Ann Anderson, Martin Dunbar, Ming Zhu, Lori Gressick, Lindsay Wagner, Su Young Kim, Sari Heitner Enschende, Rod A. Humerickhouse, Matthew S. Davids
Journal: Blood (2015)
ORP4L Facilitates Macrophage Survival via G-Protein–Coupled Signaling
Authors: Wenbin Zhong, Guoping Pan, Lin Wang, Shiqian Li, Jingsong Ou, Mengyang Xu, Jiwei Li, Biying Zhu, Xiuye Cao, Hongling Ma, Chaowen Li, Jun Xu, Vesa M. Olkkonen, Bart Staels, Daoguang Yan
Journal: Circulation Research (2016)

Macrophage survival within the arterial wall is a central factor contributing to atherogenesis. Oxysterols, major components of oxidized low-density lipoprotein, exert cytotoxic effects on macrophages.To determine whether oxysterol-binding protein-related protein 4 L (ORP4L), an oxysterol-binding protein, affects macrophage survival and the pathogenesis of atherosclerosis.By hiring cell biological approaches and ORP4L-/- mice, we show that ORP4L coexpresses with and forms a complex with Gαq/11 and phospholipase C (PLC)-β3 in macrophages. ORP4L facilitates G-protein-coupled ligand-induced PLCβ3 activation, IP3 production, and Ca2+ release from the endoplasmic reticulum. Through this mechanism, ORP4L sustains antiapoptotic Bcl-XL expression through Ca2+-mediated c-AMP responsive element binding protein transcriptional regulation and thus protects macrophages from apoptosis. Excessive stimulation with the oxysterol 25-hydroxycholesterol disassembles the ORP4L/Gαq/11/PLCβ3 complexes, resulting in reduced PLCβ3 activity, IP3 production, and Ca2+ release, as well as decreased Bcl-XL expression and increased apoptosis. Overexpression of ORP4L counteracts these oxysterol-induced defects. Mice lacking ORP4L exhibit increased apoptosis of macrophages in atherosclerotic lesions and a reduced lesion size.ORP4L is crucial for macrophage survival. It counteracts the cytotoxicity of oxysterols/oxidized low-density lipoprotein to protect macrophage from apoptosis, thus playing an important role in the development of atherosclerosis.
GW27-e0085 Accelerated Thymic Involution in Experimental Model of Atherosclerosis
Authors: Huang Shuaibo, Xianliang Dai, Zhiqing He, Ru Ding, Qiheng Li, Xiaofeng Zhao, Jiyuan Su, Yanda Zhang, Sidi Ai, Feng Wu, Zonggui Wu, Chun Liang
Journal: Journal of the American College of Cardiology (2016)
TCT-37 The Prognostic Value of the Residual SYNTAX Score after “Functionally” Complete Revascularization: Insights from the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) Trial
Authors: Yuhei Kobayashi, Chang-Wook Nam, Pim A. Tonino, Bernard De Bruyne, Nico H. Pijls, William F. Fearon
Journal: Journal of the American College of Cardiology (2015)
Management of Early Leukemia Relapse after Allogeneic Hematopoietic Stem Cell Transplantation by Donor’s Dendritic Cell-Primed Cytokine- Induced Killer Cells
Authors: Jing-Bo Wang, Tong Wu, Jun-Fang Yang, Jian-Ping Zhang, Xing-Yu Cao, Yu-Ming Yin, Yuan Sun, Rong-Mu Luo, Dao-Pei Lu, Chun-Rong Tong
Journal: Blood (2008)
Prognostic Factors of Response and Overall Survival (OS) in Higher-Risk MDS (including RAEB-t) Treated with Azacytidine (AZA): Results of the French ATU Program.
Authors: Raphael Itzykson, Sylvain Thépot, Bruno Quesnel, Odile Beyne-Rauzy, Francois Dreyfus, Norbert Vey, Pascal Turlure, Laurence Legros, Caroline Dartigeas, Jacques Delaunay, Stephane de Botton, Emmanuel Raffoux, Anne-Laure Taksin, Aspasia Stamatoullas, Anne Marfaing Koka, Eric Wattel, Sorin Visanica, Célia Salanoubat, Pierre Morel, Pascale Cony Makhoul, Stéphane Cheze, Laurence Sanhes, Isabelle Plantier, Gerard Tertian, Mehdi Dahoun, Agnes Guerci, Claude Gardin, Lionel Ades, Pierre Fenaux
Journal: Blood (2009)
TCT-478 Comparison of Five-year Outcomes of Percutaneous Versus Surgical Coronary Revascularization: A Meta-analysis
Authors: Alok Saurav, Ajay K. Kaja, Manu Kaushik, Venkata M. Alla, Ruby Satpathy, Aiman Smer, Michael D. White, Mark Woodruff, Aryan Mooss, Michael DelCore
Journal: Journal of the American College of Cardiology (2015)
The role of Beclin 1 interacting proteins and Beclin 1 post-translational modification in autophagy regulation.
Authors: Rebecca Baerga, Markus Kalkum, Shengkan Jin
Journal: Cancer Research (2007)

2765  The process of autophagy is a complex catabolic program for lysosomal degradation of proteins and other subcellular constituents. It is important for normal growth control and is defective in a number of cancers. Beclin 1 gene is the first mammalian gene identified involved in autophagy. Mono-allelic deletions of Beclin 1 gene are identified in 40-75% of human sporadic breast, ovarian and prostate cancers. Beclin 1 knockout mice were recently generated. Homozygous Beclin 1 knockout mice are embryonic lethal, while the heterozygous Beclin 1 knockout mice develop various tumors. These mouse genetic results provide compelling evidence that autophagy plays an important role in preventing tumorigenesis. This work also defined a novel class of tumor suppressor genes which are involved in autophagy and its regulation. However, exactly why the Beclin 1 gene and autophagy are critical for tumor suppression remains unknown.  In order to understand the molecular mechanism of how Beclin 1 is involved in autophagy, we created a cell line expressing a flag-tag Beclin 1 protein. Western blot analysis revealed that after the induction of autophagy resulting from starvation, Beclin 1 underwent a molecular weight shift. These results suggest that the protein undergoes a post-translational modification when autophagy is activated. We then opted to purify the Beclin 1 protein and its interacting partners by immunoprecipitation. Two proteins that interact specifically with Beclin 1 were purified and further identified by mass spectrometry. They are two kinases homologous to yeast Vps34 and Vps15. Furthermore, the region of the post-translational modification site was defined with a monoclonal antibody that specifically recognizes the non-modified form of Beclin-1, but not the modified one. This post-translational modification is inhibited by okadaic acid, a specific inhibitor of protein phosphatase 2A and known inhibitor of autophagy. Site-directed mutagenesis revealed the region of the post-translational modification of Beclin 1. Expression of a subset of the mutants of Beclin 1 resulted in the constitutive activation of autophagy. Current experiments are underway to address the role of Beclin 1 on autophagy activation. In addition, these mutants provide a molecular tool to study the impact of autophagy activation on cancer therapy and cancer prevention.