A5006471040- Prostate Cancer Treatment and Research
- DNA Repair Mechanisms
- Cancer-related molecular mechanisms research
- Berberine and alkaloids research
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- PARP inhibition in cancer therapy
- RNA Research and Splicing
- Genetic factors in colorectal cancer
- Cervical Cancer and HPV Research
- Sirtuins and Resveratrol in Medicine
- Prostate Cancer Diagnosis and Treatment
- RNA and protein synthesis mechanisms
- Genetic and Environmental Crop Studies
- Cancer, Lipids, and Metabolism
- Computational Drug Discovery Methods
- Traditional and Medicinal Uses of Annonaceae
- Ubiquitin and proteasome pathways
- Plant tissue culture and regeneration
- Toxin Mechanisms and Immunotoxins
- Cancer-related Molecular Pathways
- Tannin, Tannase and Anticancer Activities
- 14-3-3 protein interactions
- Phytochemicals and Antioxidant Activities
- RNA Interference and Gene Delivery
Memorial Sloan Kettering Cancer Center
2018-2025
The University of Texas Health Science Center at Houston
2015-2021
The University of Texas Health Science Center at San Antonio
2015-2021
Urology San Antonio
2017
The University of Texas System
2015
Significance Cancers associated with the human papillomavirus, including oropharyngeal, anal canal, cervical, and vulvar carcinomas, constitute about 4.5% of all solid tumors. In many cases, they can be readily cured radiotherapy, which is mainstay treatment. HPV-associated cancers are more radiosensitive than HPV-negative cancers, but mechanism this radiosensitivity unknown. Across oncology, HPV association one only validated molecular biomarker radiosensitivity. Here, we demonstrate that...
Double strand break (DSB) repair primarily occurs through 3 pathways: non-homologous end-joining (NHEJ), alternative (Alt-EJ), and homologous recombination (HR). Typical methods to measure pathway usage include integrated cassette reporter assays or visualization of DNA damage induced nuclear foci. It is now well understood that Cas9-induced breaks also involves NHEJ, Alt-EJ, HR pathways, providing a new format usage. Here, we have developed simple Cas9-based system with validated outcomes...
In this study we have identified POLθ-S6K-p62 as a novel druggable regulator of radiation response in prostate cancer. Despite significant advances delivery, radiotherapy continues to negatively affect treatment outcomes and quality life due resistance late toxic effects the surrounding normal tissues such bladder rectum. It is essential develop new effective strategies achieve better control tumor. We found that ribosomal protein S6K (RPS6KB1) elevated human tumors, contributes radiation....
Double-strand breaks (DSBs) are toxic lesions that lead to genome instability. While canonical DSB repair pathways typically operate independently of RNA, emerging evidence suggests RNA:DNA hybrids and transcripts near damaged sites can influence outcomes. However, a direct role for transcript RNA as template during in human cells is yet be established. In this study, we designed fluorescent- sequencing-based assays, which demonstrated RNA-containing oligonucleotides messenger serve...
Abstract Double-strand breaks (DSBs) are toxic lesions that lead to genome instability. While canonical DSB repair pathways typically operate independently of RNA, growing evidence suggests RNA:DNA hybrids and nearby transcripts can influence outcomes. However, whether transcript RNA directly serve as a template for in human cells remains unclear. In this study, we develop fluorescence sequencing-based assays show RNA-containing oligonucleotides messenger templates during repair. We conduct...
The NAD+-dependent deacetylase, Sirtuin 1 (SIRT1) is involved in prostate cancer pathogenesis. However, the actual contribution unclear as some reports propose a protective role while others suggest it harmful. We provide evidence for contextual SIRT1 cancer. Our data show that (i) mice orthotopically implanted with SIRT1-silenced LNCaP cells produced smaller tumors; (ii) suppression mimicked AR inhibitory effects hormone responsive cells; and (iii) caused significant reduction gene...
Castrate-resistant prostate cancer (CRPC) is the fatal form of cancer. Although reactivation androgen receptor (AR) occurs following deprivation, precise mechanism involved unclear. Here we show that tyrosine kinase, RON alters mechanical properties cells to influence epithelial mesenchymal transition and functions as a transcription factor differentially regulate AR signaling. inhibits activation subset AR-regulated transcripts in responsive LNCaP cells. However C4-2B, castrate-resistant...
Abstract Radiation Therapy (RT) is curative for most localized prostate cancer (PCA) patients, but limited by dose-related toxicities and radioresistance. Administration of Nexrutine® (Nx), an inexpensive supplement from Phellodendron amurense bark extract prior to RT inhibited progression poorly differentiated carcinoma in transgenic adenocarcinoma the mouse (TRAMP) mice. However, precise molecular mechanism underlying Nx-mediated tumor growth inhibitory effects combination with unclear....
Abstract Radiation Therapy (RT) is a definitive treatment for early-localized prostate cancer (PCA), but associated with side effects which impair quality of life in addition to development radioresistance. PI3K/Akt/mTOR signaling one the contributors therapeutic resistance, including Ribosomal protein S6 (rpS6), downstream effector signaling, mediates radioresistance by increasing synthesis, cell survival and epithelial mesenchymal transition. Also, increased activation rpS6 correlated poor...
Radiation Therapy (RT) is a curative treatment for localized prostate cancer (PCA), but limited by dose‐related toxicities and radioresistance. Ribosomal protein S6 (rpS6), downstream effector of PI3K/Akt/mTOR signaling, can mediate radioresistance tempering with translation, survival, cell cycle progression DNA repair. Analysis from the Oncomine® database showed that carcinoma prostatic intraepithelial neoplasia had higher rpS6 expression compared to normal prostate. Similarly, PCA lines...
You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology III1 Apr 2017MP87-15 INHIBITION OF RPS6KB1 AS A POTENTIAL ADJUVANT FOR PROSTATE CANCER RADIATION THERAPY Suleman Hussain, Roble Bedolla, Hiroshi Miyamoto, Paul Rivas, Joseph Basler, Gregory Swanson, Nikos Papanikolaou, Robert Reddick, Rita Ghosh, and Addanki Kumar HussainSuleman Hussain More articles by this author , BedollaRoble Bedolla MiyamotoHiroshi Miyamoto RivasPaul Rivas BaslerJoseph Basler...
Abstract SIRT1, a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, is member of multigene family Sirtuins. Traditionally SIRT1 known player in enhancing longevity. can target both histone and non-histone proteins to regulate diverse activities including cellular stress resistance, genomic stability, energy metabolism tumorigenesis. Disruption the prostate results formation prostatic intraepithelial neoplasia (PIN) lesions, suggesting role for development PIN, precursor lesion...
Radiation therapy (RT) is a standard treatment for organ confined prostate cancer (PCa). Although dose escalation increases local control, further hampers effectiveness due to toxicity. Additionally, intrinsic and acquired resistance radiation causes progression advanced metastatic PCa. Therefore, there an urgency addition of adjuvant therapies that synergize with improve therapeutic efficacy. We have identified novel combination regimen (Nexrutine, Nx, natural compound plus radiation)...
Double strand break (DSB) repair mainly occurs through 3 pathways: non-homologous end-joining (NHEJ), alternative (Alt-EJ), and homologous recombination (HR). We present an assay system that enables simultaneous measurement of all three pathways using Cas9-generated DSBs next generation sequencing to profile quantify pathway choice. The has provided several insights. First, absence the key Alt-EJ factor Pol q only abrogates ~50% total Alt-EJ. Second, single-strand templated (SSTR) requires...
Abstract Radiation therapy (RT) is a standard treatment for organ confined prostate cancer (PCa). Given that both intrinsic and acquired resistance to radiation causes progression advanced metastatic PCa, there an unmet need adjuvant therapies synergize with improve therapeutic efficacy. Previously, we demonstrated strong synergistic tumor growth inhibitory activities Phellodendron amurense bark extract in combination part through downregulation of ribosomal protein S6K (encoded by RPS6KB1)....