uthaya kumar - Academia.edu (original) (raw)
Papers by uthaya kumar
Stem cell markers such as NANOG have been implicated in various cancers; however, the functional ... more Stem cell markers such as NANOG have been implicated in various cancers; however, the functional contribution of pluripotency transcription factor NANOG to cancer pathogenesis has remained unclear. Gene profiling, proteomics and metabolomics approaches were combined to identify the pathway(s) altered in tumors. Here, we show that Toll-like receptor 4 (TLR4) signaling phosphorylates E2F1 to transactivate NANOG via TAK1/TBK1. CD133+/CD49f+ TICs isolated from human HCC have tumorigenic activities dependent on TLR4 and NANOG. Down-regulation of Nanog significantly reduces tumor development in obesity-associated HCC mouse model. In the search for the NANOG-dependent mechanisms underlying growth of tumor-initiating stem-like cells (TICs), NANOG ChIP-seq identifies the genes associated with mitochondrial metabolic pathways. The specific pathways, which were examined: oxidative phosphorylation (OXPHOS) and fatty acid oxidation were identified as novel NANOG-mediated oncogenic pathways by NA...
I n this paper, we study some of the properties of interval valued fuzzy subring of a ring and pr... more I n this paper, we study some of the properties of interval valued fuzzy subring of a ring and prove some results on these.
Nature Communications
Tumor-initiating stem-like cells (TICs) are defective in maintaining asymmetric cell division and... more Tumor-initiating stem-like cells (TICs) are defective in maintaining asymmetric cell division and responsible for tumor recurrence. Cell-fate-determinant molecule NUMB-interacting protein (TBC1D15) is overexpressed and contributes to p53 degradation in TICs. Here we identify TBC1D15-mediated oncogenic mechanisms and tested the tumorigenic roles of TBC1D15 in vivo. We examined hepatocellular carcinoma (HCC) development in alcohol Western diet-fed hepatitis C virus NS5A Tg mice with hepatocyte-specific TBC1D15 deficiency or expression of non-phosphorylatable NUMB mutations. Liver-specific TBC1D15 deficiency or non-p-NUMB expression reduced TIC numbers and HCC development. TBC1D15–NuMA1 association impaired asymmetric division machinery by hijacking NuMA from LGN binding, thereby favoring TIC self-renewal. TBC1D15–NOTCH1 interaction activated and stabilized NOTCH1 which upregulated transcription of NANOG essential for TIC expansion. TBC1D15 activated three novel oncogenic pathways to p...
Journal of Testing and Evaluation
Hybrid polymer composites have been used in various applications because of their superior charac... more Hybrid polymer composites have been used in various applications because of their superior characteristics. Conventional cutting techniques in these materials produce poor quality machining because of fiber delamination and surface damage. It is also challenging to produce shapes and cuts in polymer composite materials through conventional machining. Abrasive water jet machining (AWJM) may be suitable for producing quality cuts by controlled machining process. This article investigated the AWJM of red mud–filled sisal polyester hybrid composite. The second order regression model was developed for material removal rate (MRR) and kerf taper (KT) through the experimental data. The developed model predicted the MRR and KT with minimum error at 95 % confidence level. The MRR of the hybrid composite was influenced highly by transverse speed (83.56 %) whereas the KT was influenced mostly by standoff distance (SOD, 45.66 %). Scanning electron microscope (SEM) analysis on the cut surface helps to understand the failure mechanism on AWJM.
Journal of Materials Science: Materials in Electronics
Abstract(E)-2-(benzo[d][1,3]dioxol-5-ylmethylene)hydrazinecarboxamide (BDMHC) molecule has been s... more Abstract(E)-2-(benzo[d][1,3]dioxol-5-ylmethylene)hydrazinecarboxamide (BDMHC) molecule has been synthesized by Schiff base method. A single crystal of BDMHC has been grown by slow evaporation technique. Spectroscopic and computational studies of BDMHC was evaluated using different techniques such as FT-IR, FT-Raman, NMR (1H, 13C), Z-scan and NBO. Density functional theory (DFT) calculations were performed at B3LYP/6-311 ++G (d,p) level to understand vibrational frequency of BDMHC at ground state structure. Hyperconjugative interaction energies of BDMHC was determined by using natural bond orbital (NBO) and non-linear optical (NLO) properties. Furthermore, the 3D Hirshfeld surfaces and the associated 2D fingerprint plots have been analyzed for its intra and inter molecular interactions. The nonlinear optical susceptibility (χ3 = 1.24 × 10−6 esu), nonlinear refractive index (n2) and nonlinear optical absorption coefficient (β = 3.84 × 10−5 cm/W) were estimated by Z-scan technique and these results signify BDMHC has promising NLO applications.
BioResources
Epoxy-based nanocomposites were prepared by incorporating 0.3%, 0.5%, 0.7%, 1%, and 2% cellulose ... more Epoxy-based nanocomposites were prepared by incorporating 0.3%, 0.5%, 0.7%, 1%, and 2% cellulose nanofibers (CNF) through a hand lay-up technique. The influence of the CNF as a reinforcement material on the morphology, and the physical, mechanical, and thermal properties of epoxy-based nanocomposites were investigated using scanning electron microscopy (SEM), density, void content, water absorption, tensile, flexural, impact strength, and thermogravimetric analyses. Compatibility between the nano-reinforcement and epoxy matrix was confirmed using SEM, which demonstrated that the CNF was homogeneously dispersed throughout the epoxy matrix. The mechanical properties were enhanced by increasing the CNF loading up to 1%. Moreover, the incorporation of CNF into the composites reduced the water uptake of the substrates in the water absorption test and resulted in a high thermal stability when exposed to a high temperature. Bamboo-CNF could be used as a potential reinforcement material to improve the properties of epoxy-based nanocomposites.
Oxidative Medicine and Cellular Longevity, 2016
The therapeutic potential ofCassia surattensisin reducing free radical-induced oxidative stress a... more The therapeutic potential ofCassia surattensisin reducing free radical-induced oxidative stress and inflammation particularly in hepatic diseases was evaluated in this study. The polyphenol richC. surattensisseed extract showed good in vitro antioxidant.C. surattensisseed extract contained total phenolic content of 100.99 mg GAE/g dry weight and there was a positive correlation (r>0.9) between total phenolic content and the antioxidant activities of the seed extract.C. surattensisseed extract significantly (p<0.05) reduced the elevated levels of serum liver enzymes (ALT, AST, and ALP) and relative liver weight in paracetamol-induced liver hepatotoxicity in mice. Moreover, the extract significantly (p<0.05) enhanced the antioxidant enzymes and glutathione (GSH) contents in the liver tissues, which led to decrease of malondialdehyde (MDA) level. The histopathological examination showed the liver protective effect ofC. surattensisseed extract against paracetamol-induced histoa...
INTRODUCTION Porous Sponge-like matrices with a specific 3D structural design resembling the actu... more INTRODUCTION Porous Sponge-like matrices with a specific 3D structural design resembling the actual extracellular matrix (ECM) of a particular tissue show significant potential for the regeneration and repair of a broad range of damaged tissues. Generally, the fibrous protein based biomaterials are used for soft tissue repair and provides a template for dermal regeneration. These biomaterials have highly repetitive amino acid sequences that primarily provide mechanical and architectural functions. Most importantly the Collagen Biomaterials are rationally used in the wound healing of burns and as other dermal substitutes. Infection at the site of wound delays regeneration and degrades extra cellular matrix in the skin. Normally, Gelatin and Collagen biomaterials are not used for the dermal regeneration of the infected wound, because microbial pathogens utilize the proteins present in the biomaterials for their microbial growth. The need for incorporation of antimicrobial agents in th...
Cancer Research, 2015
Stem cell markers such as NANOG have been implicated in various cancers; however, the functional ... more Stem cell markers such as NANOG have been implicated in various cancers; however, the functional contribution of pluripotency transcription factor NANOG to cancer pathogenesis has remained unclear. Gene profiling, proteomics and metabolomics approaches were combined to identify the pathway(s) altered in tumors. Here, we show that Toll-like receptor 4 (TLR4) signaling phosphorylates E2F1 to transactivate NANOG via TAK1/TBK1. CD133+/CD49f+ TICs isolated from human HCC have tumorigenic activities dependent on TLR4 and NANOG. Down-regulation of Nanog significantly reduces tumor development in obesity-associated HCC mouse model. In the search for the NANOG-dependent mechanisms underlying growth of tumor-initiating stem-like cells (TICs), NANOG ChIP-seq identifies the genes associated with mitochondrial metabolic pathways. The specific pathways, which were examined: oxidative phosphorylation (OXPHOS) and fatty acid oxidation were identified as novel NANOG-mediated oncogenic pathways by NANOG ChIP-seq analysis and metabolomics. The causal roles of NANOG in mitochondrial metabolic reprogramming occurs through the inhibition of oxidative phosphorylation (OXPHOS) and levels of mitochondrial ROS and activation of fatty acid oxidation (FAO), which are required for both the self-renewal of TICs and their drug resistance. PPARδ physically interacts with NANOG. Restoration of OXPHOS and inhibition of FAO rendered TICs susceptible to drug. Our data showed that NANOG reprogramming of mitochondrial metabolism was responsible for human TIC oncogenicity and chemo-resistance. Together, NANOG-mediated metabolic reprogramming through dysregulation of mitochondrial functions generates TICs and drives tumorigenesis, providing insight into mechanisms of NANOG-mediated metabolic reprogramming and its roles in TIC oncogenic activity and chemo-resistance. NANOG suppresses OXPHOS and activates FAO, thus inhibiting OCR and ROS production, conferring a tumor chemoresistant state. These novel pathways are potential drug targets for the highly malignant TICs found in cancer patients. Reversal of NANOG-dependent effects on OXPHOS and FAO gene may offer a noteworthy strategy of countering therapeutic drug resistance associated with NANOG activation. Citation Format: Chia-Lin Chen, Dinesh Babu Uthaya Kumar, Vasu Punj, Jun Xu, Linda Sher, Sonja Hess, Keigo Machida. NANOG metabolically reprograms tumor-initiating stem-like cells in oxidative phosphorylation and fatty acid metabolism. [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 3040. doi:10.1158/1538-7445.AM2015-3040
Tumor Biology, 2015
Sirtuins belong to the family of class III histone deacetylases; its role in neoplasia is controv... more Sirtuins belong to the family of class III histone deacetylases; its role in neoplasia is controversial as both tumor-suppressive and promoting functions have been reported. There are very few reports available, where expressions of sirtuin isoforms are comprehensively analyzed during neoplasia. Therefore, in the present study, the expression of SIRT1, SIRT2, and SIRT7 during different stages of cervical cancer progression was analyzed. The normal cervical epithelium showed feeble expression of sirtuin isoforms, SIRT1, SIRT2, and SIRT7. A significant increase in SIRT1 expression was noted in the cytoplasm as well as in the nucleus of proliferative layers of cervical epithelium in squamous intraepithelial lesions (SIL); however, in the squamous cell carcinomas (SCC), a heterogeneous pattern of SIRT1 expression varying from low to high was noted. A progressive increase in the expression of both SIRT2 and SIRT7 was noted during cancer progression in the following order: normal &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; preneoplasia &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; cancer. Cervical cancer cell lines, HeLa and SiHa, showed higher levels of SIRT1 and SIRT2 in comparison to the immortalized cell counterpart, HaCaT. Specific inhibitors of SIRT1 (Ex527) and SIRT2 (AGK2) impaired the growth of the cervical cancer cells, SiHa, but not of the HaCaT cells. SIRT1 inhibition caused cell death, while SIRT2 inhibition resulted in cell cycle arrest. In conclusion, we report the overexpression of SIRT2 and SIRT7 proteins in cervical cancer and suggest probable application of sirtuin inhibitors as therapeutic targets. Further, a specific increase in the levels of SIRT1 in intraepithelial lesion makes it a promising candidate for identification of preneoplastic changes.
Journal of Advanced Microscopy Research, 2014
ABSTRACT Redmud is a major waste material generated during the production of alumina from bauxite... more ABSTRACT Redmud is a major waste material generated during the production of alumina from bauxite by the Bayer's process. The present research work is to explore the use of redmud (particle size 4 μm) as a reinforcing material in polymer matrix. General purpose polyester resin (GP) is used as a matrix and banana fiber used as reinforcement. In this investigation the wear behavior on the effect of red mud with banana fiber untreated has been studied. Dry sliding Wear test was carried out by pin on disc wear testing machine as per ASTM G99 standard for the specimens tested. By Taguchi experimental design the effect of redmud percentage, fiber treatment and length of fiber on the wear rate have been analyzed and found the optimal condition.
Journal of Hepatology, 2015
Stem cell markers such as NANOG have been implicated in various cancers; however, the functional ... more Stem cell markers such as NANOG have been implicated in various cancers; however, the functional contribution of pluripotency transcription factor NANOG to cancer pathogenesis has remained unclear. Gene profiling, proteomics and metabolomics approaches were combined to identify the pathway(s) altered in tumors. Here, we show that Toll-like receptor 4 (TLR4) signaling phosphorylates E2F1 to transactivate NANOG via TAK1/TBK1. CD133+/CD49f+ TICs isolated from human HCC have tumorigenic activities dependent on TLR4 and NANOG. Down-regulation of Nanog significantly reduces tumor development in obesity-associated HCC mouse model. In the search for the NANOG-dependent mechanisms underlying growth of tumor-initiating stem-like cells (TICs), NANOG ChIP-seq identifies the genes associated with mitochondrial metabolic pathways. The specific pathways, which were examined: oxidative phosphorylation (OXPHOS) and fatty acid oxidation were identified as novel NANOG-mediated oncogenic pathways by NA...
I n this paper, we study some of the properties of interval valued fuzzy subring of a ring and pr... more I n this paper, we study some of the properties of interval valued fuzzy subring of a ring and prove some results on these.
Nature Communications
Tumor-initiating stem-like cells (TICs) are defective in maintaining asymmetric cell division and... more Tumor-initiating stem-like cells (TICs) are defective in maintaining asymmetric cell division and responsible for tumor recurrence. Cell-fate-determinant molecule NUMB-interacting protein (TBC1D15) is overexpressed and contributes to p53 degradation in TICs. Here we identify TBC1D15-mediated oncogenic mechanisms and tested the tumorigenic roles of TBC1D15 in vivo. We examined hepatocellular carcinoma (HCC) development in alcohol Western diet-fed hepatitis C virus NS5A Tg mice with hepatocyte-specific TBC1D15 deficiency or expression of non-phosphorylatable NUMB mutations. Liver-specific TBC1D15 deficiency or non-p-NUMB expression reduced TIC numbers and HCC development. TBC1D15–NuMA1 association impaired asymmetric division machinery by hijacking NuMA from LGN binding, thereby favoring TIC self-renewal. TBC1D15–NOTCH1 interaction activated and stabilized NOTCH1 which upregulated transcription of NANOG essential for TIC expansion. TBC1D15 activated three novel oncogenic pathways to p...
Journal of Testing and Evaluation
Hybrid polymer composites have been used in various applications because of their superior charac... more Hybrid polymer composites have been used in various applications because of their superior characteristics. Conventional cutting techniques in these materials produce poor quality machining because of fiber delamination and surface damage. It is also challenging to produce shapes and cuts in polymer composite materials through conventional machining. Abrasive water jet machining (AWJM) may be suitable for producing quality cuts by controlled machining process. This article investigated the AWJM of red mud–filled sisal polyester hybrid composite. The second order regression model was developed for material removal rate (MRR) and kerf taper (KT) through the experimental data. The developed model predicted the MRR and KT with minimum error at 95 % confidence level. The MRR of the hybrid composite was influenced highly by transverse speed (83.56 %) whereas the KT was influenced mostly by standoff distance (SOD, 45.66 %). Scanning electron microscope (SEM) analysis on the cut surface helps to understand the failure mechanism on AWJM.
Journal of Materials Science: Materials in Electronics
Abstract(E)-2-(benzo[d][1,3]dioxol-5-ylmethylene)hydrazinecarboxamide (BDMHC) molecule has been s... more Abstract(E)-2-(benzo[d][1,3]dioxol-5-ylmethylene)hydrazinecarboxamide (BDMHC) molecule has been synthesized by Schiff base method. A single crystal of BDMHC has been grown by slow evaporation technique. Spectroscopic and computational studies of BDMHC was evaluated using different techniques such as FT-IR, FT-Raman, NMR (1H, 13C), Z-scan and NBO. Density functional theory (DFT) calculations were performed at B3LYP/6-311 ++G (d,p) level to understand vibrational frequency of BDMHC at ground state structure. Hyperconjugative interaction energies of BDMHC was determined by using natural bond orbital (NBO) and non-linear optical (NLO) properties. Furthermore, the 3D Hirshfeld surfaces and the associated 2D fingerprint plots have been analyzed for its intra and inter molecular interactions. The nonlinear optical susceptibility (χ3 = 1.24 × 10−6 esu), nonlinear refractive index (n2) and nonlinear optical absorption coefficient (β = 3.84 × 10−5 cm/W) were estimated by Z-scan technique and these results signify BDMHC has promising NLO applications.
BioResources
Epoxy-based nanocomposites were prepared by incorporating 0.3%, 0.5%, 0.7%, 1%, and 2% cellulose ... more Epoxy-based nanocomposites were prepared by incorporating 0.3%, 0.5%, 0.7%, 1%, and 2% cellulose nanofibers (CNF) through a hand lay-up technique. The influence of the CNF as a reinforcement material on the morphology, and the physical, mechanical, and thermal properties of epoxy-based nanocomposites were investigated using scanning electron microscopy (SEM), density, void content, water absorption, tensile, flexural, impact strength, and thermogravimetric analyses. Compatibility between the nano-reinforcement and epoxy matrix was confirmed using SEM, which demonstrated that the CNF was homogeneously dispersed throughout the epoxy matrix. The mechanical properties were enhanced by increasing the CNF loading up to 1%. Moreover, the incorporation of CNF into the composites reduced the water uptake of the substrates in the water absorption test and resulted in a high thermal stability when exposed to a high temperature. Bamboo-CNF could be used as a potential reinforcement material to improve the properties of epoxy-based nanocomposites.
Oxidative Medicine and Cellular Longevity, 2016
The therapeutic potential ofCassia surattensisin reducing free radical-induced oxidative stress a... more The therapeutic potential ofCassia surattensisin reducing free radical-induced oxidative stress and inflammation particularly in hepatic diseases was evaluated in this study. The polyphenol richC. surattensisseed extract showed good in vitro antioxidant.C. surattensisseed extract contained total phenolic content of 100.99 mg GAE/g dry weight and there was a positive correlation (r>0.9) between total phenolic content and the antioxidant activities of the seed extract.C. surattensisseed extract significantly (p<0.05) reduced the elevated levels of serum liver enzymes (ALT, AST, and ALP) and relative liver weight in paracetamol-induced liver hepatotoxicity in mice. Moreover, the extract significantly (p<0.05) enhanced the antioxidant enzymes and glutathione (GSH) contents in the liver tissues, which led to decrease of malondialdehyde (MDA) level. The histopathological examination showed the liver protective effect ofC. surattensisseed extract against paracetamol-induced histoa...
INTRODUCTION Porous Sponge-like matrices with a specific 3D structural design resembling the actu... more INTRODUCTION Porous Sponge-like matrices with a specific 3D structural design resembling the actual extracellular matrix (ECM) of a particular tissue show significant potential for the regeneration and repair of a broad range of damaged tissues. Generally, the fibrous protein based biomaterials are used for soft tissue repair and provides a template for dermal regeneration. These biomaterials have highly repetitive amino acid sequences that primarily provide mechanical and architectural functions. Most importantly the Collagen Biomaterials are rationally used in the wound healing of burns and as other dermal substitutes. Infection at the site of wound delays regeneration and degrades extra cellular matrix in the skin. Normally, Gelatin and Collagen biomaterials are not used for the dermal regeneration of the infected wound, because microbial pathogens utilize the proteins present in the biomaterials for their microbial growth. The need for incorporation of antimicrobial agents in th...
Cancer Research, 2015
Stem cell markers such as NANOG have been implicated in various cancers; however, the functional ... more Stem cell markers such as NANOG have been implicated in various cancers; however, the functional contribution of pluripotency transcription factor NANOG to cancer pathogenesis has remained unclear. Gene profiling, proteomics and metabolomics approaches were combined to identify the pathway(s) altered in tumors. Here, we show that Toll-like receptor 4 (TLR4) signaling phosphorylates E2F1 to transactivate NANOG via TAK1/TBK1. CD133+/CD49f+ TICs isolated from human HCC have tumorigenic activities dependent on TLR4 and NANOG. Down-regulation of Nanog significantly reduces tumor development in obesity-associated HCC mouse model. In the search for the NANOG-dependent mechanisms underlying growth of tumor-initiating stem-like cells (TICs), NANOG ChIP-seq identifies the genes associated with mitochondrial metabolic pathways. The specific pathways, which were examined: oxidative phosphorylation (OXPHOS) and fatty acid oxidation were identified as novel NANOG-mediated oncogenic pathways by NANOG ChIP-seq analysis and metabolomics. The causal roles of NANOG in mitochondrial metabolic reprogramming occurs through the inhibition of oxidative phosphorylation (OXPHOS) and levels of mitochondrial ROS and activation of fatty acid oxidation (FAO), which are required for both the self-renewal of TICs and their drug resistance. PPARδ physically interacts with NANOG. Restoration of OXPHOS and inhibition of FAO rendered TICs susceptible to drug. Our data showed that NANOG reprogramming of mitochondrial metabolism was responsible for human TIC oncogenicity and chemo-resistance. Together, NANOG-mediated metabolic reprogramming through dysregulation of mitochondrial functions generates TICs and drives tumorigenesis, providing insight into mechanisms of NANOG-mediated metabolic reprogramming and its roles in TIC oncogenic activity and chemo-resistance. NANOG suppresses OXPHOS and activates FAO, thus inhibiting OCR and ROS production, conferring a tumor chemoresistant state. These novel pathways are potential drug targets for the highly malignant TICs found in cancer patients. Reversal of NANOG-dependent effects on OXPHOS and FAO gene may offer a noteworthy strategy of countering therapeutic drug resistance associated with NANOG activation. Citation Format: Chia-Lin Chen, Dinesh Babu Uthaya Kumar, Vasu Punj, Jun Xu, Linda Sher, Sonja Hess, Keigo Machida. NANOG metabolically reprograms tumor-initiating stem-like cells in oxidative phosphorylation and fatty acid metabolism. [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 3040. doi:10.1158/1538-7445.AM2015-3040
Tumor Biology, 2015
Sirtuins belong to the family of class III histone deacetylases; its role in neoplasia is controv... more Sirtuins belong to the family of class III histone deacetylases; its role in neoplasia is controversial as both tumor-suppressive and promoting functions have been reported. There are very few reports available, where expressions of sirtuin isoforms are comprehensively analyzed during neoplasia. Therefore, in the present study, the expression of SIRT1, SIRT2, and SIRT7 during different stages of cervical cancer progression was analyzed. The normal cervical epithelium showed feeble expression of sirtuin isoforms, SIRT1, SIRT2, and SIRT7. A significant increase in SIRT1 expression was noted in the cytoplasm as well as in the nucleus of proliferative layers of cervical epithelium in squamous intraepithelial lesions (SIL); however, in the squamous cell carcinomas (SCC), a heterogeneous pattern of SIRT1 expression varying from low to high was noted. A progressive increase in the expression of both SIRT2 and SIRT7 was noted during cancer progression in the following order: normal &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; preneoplasia &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; cancer. Cervical cancer cell lines, HeLa and SiHa, showed higher levels of SIRT1 and SIRT2 in comparison to the immortalized cell counterpart, HaCaT. Specific inhibitors of SIRT1 (Ex527) and SIRT2 (AGK2) impaired the growth of the cervical cancer cells, SiHa, but not of the HaCaT cells. SIRT1 inhibition caused cell death, while SIRT2 inhibition resulted in cell cycle arrest. In conclusion, we report the overexpression of SIRT2 and SIRT7 proteins in cervical cancer and suggest probable application of sirtuin inhibitors as therapeutic targets. Further, a specific increase in the levels of SIRT1 in intraepithelial lesion makes it a promising candidate for identification of preneoplastic changes.
Journal of Advanced Microscopy Research, 2014
ABSTRACT Redmud is a major waste material generated during the production of alumina from bauxite... more ABSTRACT Redmud is a major waste material generated during the production of alumina from bauxite by the Bayer's process. The present research work is to explore the use of redmud (particle size 4 μm) as a reinforcing material in polymer matrix. General purpose polyester resin (GP) is used as a matrix and banana fiber used as reinforcement. In this investigation the wear behavior on the effect of red mud with banana fiber untreated has been studied. Dry sliding Wear test was carried out by pin on disc wear testing machine as per ASTM G99 standard for the specimens tested. By Taguchi experimental design the effect of redmud percentage, fiber treatment and length of fiber on the wear rate have been analyzed and found the optimal condition.
Journal of Hepatology, 2015