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Cancer/testis antigens： novel tools for discerning aggressive and non-aggressive prostate cancer

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Asian Journal of Andrology 2012年第3期14卷 400-404,I0006页

作者： Takumi Shiraishi Robert H Getzenberg prakash kulkarni Department of Urology James Buchanan Brady Urological Institute Baltimore M D 21287 USA Department of Urology Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan Department of Oncology James Buchanan Brady Urological Institute Baltimore MD 21287 USA pharmacology and Molecular Sciences The Johns Hopkins University School of Medicine Baltimore MD 21287 USA

The introduction of serum prostate-specific antigen （PSA） in the 1980s has dramatically altered and benefited the initial diagnosis of prostate cancer. However, the widespread use of PSA testing has resulted in overdetection and overtreatment of potentially indolent disease. Thus, a clinical dilemma today in the management of prostate cancer is to discern men with aggressive disease who need definitive treatment from men whose disease are not lethal. Although several serum and tissue biomarkers have been evaluated during the past decade, improved markers are still needed to enhance the accuracy, with which patients at risk can be discerned and treated more aggressively. The cancer/testis antigens （CTAs） are a group of proteins that are restricted to the testis in the normal adult, but are aberrantly expressed in several types of cancers. Because of their restricted expression pattern, the CTAs represent attractive biomarker candidates for cancer diagnosis/prognosis. Furthermore, several studies to date have reported the differential expression of CTAs in prostate cancer. Here, we review recent developments that demonstrate the potential of the CTAs as biomarkers to discern the a^ressive Dhenotvoe of orostate cancer.

关键词： cancer/testis antigens DNA microarrays prostate cancer prostate carcinoma tumor antigen

Cyr61 is a potential prognostic marker for prostate cancer

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Asian Journal of Andrology 2012年第3期14卷 405-408,I0006页

作者： Naoki Terada prakash kulkarni Robert H Getzenberg Department of Urology the James Buchanan Brady Urological Institute The Johns Hopkins University School of Medicine Baltimore M D 21287 USA Department of Urology Oncology The Johns Hopkins University School of Medicine Baltimore Baltimore MD 21287 USA Department of Pharmacology and Molecular Sciences The Johns Hopkins University School of Medicine Baltimore MD 21287 USA

Cysteine-rich angiogenic inducer 61 （Cyr61） is an extracellular matrix protein involved in the transduction of growth factor and hormone signaling that is frequently altered in expression in several types of cancers. In prostate cancer （PCa）, Cyr61 is highly expressed in organ-confined disease. Further, Cyr61 expression levels are associated with a lower risk of disease recurrence, and can be quantitatively measured in the serum. Considered together, these results indicate that Cyr61 is a potential and clinically useful tissue, as well as serum-based biomarker for differentiating lethal and non-lethal PCa.

关键词： Cyr61 lethal prostate cancer non-lethal prostate cancer overdiagnosis overtreatment prostate cancer

Prostate-associated gene 4 （PAGE4）, an intrinsically disordered cancer/testis antigen, is a novel therapeutic target for prostate cancer

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Asian Journal of Andrology 2016年第5期18卷 695-703页

作者： prakash kulkarni A Keith Dunker Keith Weninge John Orban Institute for Bioscience and Biotechnology Research University of Maryland Rockville MD 20850 USA Center for Computational Biology and Bioinformatics Department of Biochemistry and Molecular Biology Indiana University School of Medicine and Informatics Indianapolis IN 46202 USA Department of Physics North Carolina State University Raleigh NC 27695 USA Department of Chemistry and Biochemistry University of Maryland College Park MD 20742 USA.

Prostate-associated gene 4 （PAGE4） is a remarkably prostate-specific Cancer/Testis Antigen that is highly upregulated in the human fetal prostate and its diseased states but not in the adult normal gland. PAGE4 is an intrinsically disordered protein （IDP） that functions as a stress-response protein to suppress reactive oxygen species as well as prevent DNA damage. In addition, PAGE4 is also a transcriptional regulator that potentiates transactivation by the oncogene c-Jun, c-Jun forms the AP-1 complex by heterodimerizing with members of the Fos family and plays an important role in the development and pathology of the prostate gland, underscoring the importance of the PAGE4/c-Jun interaction. HIPK1, also a component of the stress-response pathway, phosphorylates PAGE4 at T51 which is critical for its transcriptional activity. Phosphorylation induces conformational and dynamic switching in the PAGE4 ensemble leading to a new cellular function. Finally, bioinformatics evidence suggests that the PAGE4 mRNA could be alternatively spliced resulting in four potential isoforms of the polypeptide alluding to the possibility of a range of conformational ensembles with latent functions. Considered together, the data suggest that PAGE4 may represent the first molecular link between stress and prostate cancer （PCa）. Thus, pharmacologically targeting PAGE4 may be a novel opportunity for treating and managing patients with PCa, especially patients with low-risk disease.

关键词： prostate-associated Gene 4 cancer/testis antigen intrinsically disordered protein prostate cancer c-Jun AP-1 proteininteraction networks homeodomain-interacting protein 1

Phenotypic plasticity in prostate cancer： role of ntrinsically disordered proteins

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Asian Journal of Andrology 2016年第5期18卷 704-710页

作者： Steven M Mooney Mohit Kumar Jolly Herbert Levine prakash kulkarni Department of Biology University of Waterloo Waterloo ON N2L 3G1 Canada Center for Theoretical Biological Physics Rice University Houston TX 77005 USA Department of Bioengineering Rice University Houston TX 77005 USA Department of Physics and Astronomy Rice University Houston TX 77005 USA institute for Bioscience and Biotechnology Research University of Maryland Rockville Maryland 20850 USA

A striking characteristic of cancer ceLls is their remarkable phenotypic plasticity, which is the ability to switch states or phenotypes in response to environmental fluctuations. Phenotypic changes such as a partial or complete epithelial to mesenchymal transition （EMT） that play important roles in their survival and proliferation, and development of resistance to therapeutic treatments, are widely believed to arise due to somatic mutations in the genome. However, there is a growing concern that such a deterministic view is not entirely consistent with multiple lines of evidence, which indicate that stochasticity may also play an important role in driving phenotypic plasticity. Here, we discuss how stochasticity in protein interaction networks （PINs） may play a key role in determining phenotypic plasticity in prostate cancer （PCa）. Specifically, we point out that the key players driving transitions among different phenotypes （epithelial, mesenchymal, and hybrid epithelial/mesenchymal）, including ZEB1, SNAIl, OVOL1, and OVOL2, are intrinsically disordered proteins （IDPs） and discuss how plasticity at the molecular level may contribute to stochasticity in phenotypic switching by rewiring PINs. We conclude by suggesting that targeting iDPs implicated in EMT in PCa may be a new strategy to gain additional insights and develop novel treatments for this disease, which is the most common form of cancer in adult men.

关键词： epithelial to mesenchymal transition intrinsically disordered proteins prostate cancer state-switching

Cancer/testis antigens and obligate participation in multiple hallmarks of cancer： an update

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Asian Journal of Andrology 2016年第5期18卷 711-712页

作者： Steven M Mooney Krithika Rajagopalan Govindan Rangarajan prakash kulkarni Department of Biology University of Waterloo Waterloo ON N2L 3G1 Canada Department of Biological Sciences Columbia University NY 10027 USA Department of Mathematics and Centre for Neuroscience Indian Institute of Science Bengaluru Karnataka India Institute for Bioscience and Bietechnology Research University of Maryland Rockville. Marvland 20850. USA.

The Cancer/Testis Antigens （CTAs） are a group of so-called tumor antigens that exhibit provocative expression patterns in most types of cancer. However, because most CTAs appear to be intrinsically disordered, they ... 详细信息

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TRPM8 and prostate cancer:to overexpress or repress,that is the question-comment on“Effects of TRPM8 on proliferation and motility of prostate cancer PC-3 cells”by Yang ZH et *** Asian Journal of Andrology

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Asian Journal of Andrology 2009年第2期11卷 150-151页

作者： prakash kulkarni James Buchanan Brady Urological Institute Department of UrologyJohns Hopkins University School of medicineBaltimoreMD 21287USA

The progression of cells from a normal differentiated state in which the rates of proliferation and apoptosis are in check,to a tumorigenic and metastatic state where these rates are imbalanced,likely involves the accumulation of mutations in multiple genes,and the evolution and clonal selection of more aggressive *** events are associated with changes in the expression of numerous gene products including the transient receptor potential(TRP)proteins.

关键词： TRPM8 al. motility

Restless head syndrome:A retrospective study

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World Journal of Methodology 2025年第1期15卷 51-59页

作者： Sanjay prakash Varoon Vadodaria Niraj Chawda Chetsi S Shah Anurag prakash Department of Neurology Smt.B.K.Shah Medical Institute and Research CentreSumandeep VidyapeethVadodara 391760GujarātIndia Department of Medicine Smt.B.K.Shah Medical Institute and Research CentreSumandeep VidyapeethVadodara 391760GujarātIndia Department of Medicine Parul Institute of Medical Sciences and Research CentreParul University WaghodiaVadodara 391760India

BACKGROUND Restless legs syndrome(RLS)is characterized by an urge to move with an unpleasant sensation in the lower *** typically affects the ***,it can also affect several other body regions,such as the arms,abdomen,face,neck,head,and genital *** are only a few reports of the RLS variant affecting the *** To assess the epidemiological,clinical,and other aspects of the RLS variant affecting the *** We conducted a retrospective study of 17 adult patients(>18 years)who met the RLS criteria and simultaneously experienced RLS-like symptoms in the *** The median age at which symptoms appeared was 41.6 *** and females were equally affected(1.1:1).All 17 patients had uncomfortable sensations in the lower *** or disturbed sleep was the most common comorbidity(n=16,88.2%).However,headache was the most common presenting or primary symptom(n=10,70.5%).Dizziness or an abnormal sensation in the head was the second most common presenting symptom(5 patients,29.4%).Other presenting features were leg pain,backache,and generalized body *** patients responded favorably to dopaminergic *** If RLS-related unpleasant sensations and pain are felt in the head,they may be misinterpreted as headache,dizziness,or psychosomatic *** and headaches in a subset of patients may be two phenotypic manifestations of the same disorder.

关键词： Restless legs syndrome Restless head syndrome Dopamine Headache Migraine Tension-type headache

Landslide Susceptibility Mapping Using RBFN-Based Ensemble Machine Learning Models

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 467-500页

作者： Landslide Susceptibility Mapping Using RBFN-Based Ensemble Machine Learning Models Duc-Dam Nguyen Nguyen Viet Tiep Quynh-Anh Thi Bui Hiep Van Le Indra prakash Romulus Costache Manish Pandey Binh Thai Pham Faculty of Civil Engineering University of Transport TechnologyThanh XuanHa Noi100000Vietnam Faculty of Hydraulic Engineering Hanoi University of Civil EngineeringHa Noi100000Vietnam DDG(R)Geological Survey of India Gandhinagar382010India Research Institute of the University of Bucharest Bucharest050663Romania National Institute of Hydrology and Water Management Bucharest013686Romania Department of Civil Engineering Transilvania University of BrasovBrasov500152Romania Danube Delta National Institute for Research and Development Tulcea820112Romania Marwadi University Research Center(MURC) Marwadi UniversityRajkotGujaratBharat360003India Department of Civil Engineering Faculty of Engineering&TechnologyMarwadi UniversityRajkotGujaratBharat360003India

This study was aimed to prepare landslide susceptibility maps for the Pithoragarh district in Uttarakhand,India,using advanced ensemble models that combined Radial Basis Function Networks(RBFN)with three ensemble learning techniques:DAGGING(DG),MULTIBOOST(MB),and ADABOOST(AB).This combination resulted in three distinct ensemble models:DG-RBFN,MB-RBFN,and ***,a traditional weighted method,Information Value(IV),and a benchmark machine learning(ML)model,Multilayer Perceptron Neural Network(MLP),were employed for comparison and *** models were developed using ten landslide conditioning factors,which included slope,aspect,elevation,curvature,land cover,geomorphology,overburden depth,lithology,distance to rivers and distance to *** factors were instrumental in predicting the output variable,which was the probability of landslide *** analysis of the models’performance indicated that the DG-RBFN model,with an Area Under ROC Curve(AUC)of 0.931,outperformed the other *** AB-RBFN model achieved an AUC of 0.929,the MB-RBFN model had an AUC of 0.913,and the MLP model recorded an AUC of *** results suggest that the advanced ensemble ML model DG-RBFN was more accurate than traditional statistical model,single MLP model,and other ensemble models in preparing trustworthy landslide susceptibility maps,thereby enhancing land use planning and decision-making.

关键词： Landslide susceptibility map spatial analysis ensemble modelling information values(IV)

A dysregulated calcium homeostasis as the earliest pathological sign in stem cell-derived Parkinson's disease neurons?

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Neural Regeneration Research 2024年第7期19卷 1421-1422页

作者： Nilima prakash Working Group Human Stem Cell Research Department Hamm 2Hamm-Lippstadt University of Applied SciencesHammGermany

Parkinson’s disease(PD) is characterized by the slow and progressive demise of dopamine(DA)-synthesizing neurons in the substantia nigra pars compacta(SNc),a nucleus located in the human ventral *** death also affects other regions in the brain at later stages of *** concomitant lack of DA in the human forebrain(striatum) leads to the typical motor symptoms of this still uncurable neurodegenerative disorder.

关键词： homeostasis dopamine death