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MONGRE, RAJ KUMAR,SODHI, SIMRINDER SINGH,SHARMA, NEELESH,GHOSH, MRINMOY,KIM, JEONG HYUN,KIM, NAMEUN,PARK, YANG HO,SHIN, YOUNG GYU,KIM, SUNG JIN,JIAO, ZHANG JIAO,HUYNH, DO LUONG,JEONG, DONG KEE Lychnia 2016 International journal of oncology Vol.48 No.1
<P>Tumor initiating cancer stem-like cells (TICSCs) have recently become the object of intensive study. Human-Lipocalin-2 (h<I>LCN2</I>) acts as a biomarker for cancers. The aim of the present study was to explore new insights regarding the potential role of <I>LCN2</I> in inducing epithelial to mesenchymal transition (EMT) by transfecting <I>LCN2</I> into CD133<SUP>+</SUP>-A549-TICSCs and its cross-talk with the NF-κB signaling pathway in adenocarcinoma of the lung. Furthermore, EMT was confirmed by transcriptomic analysis, immunoblotting and immunocyto/histochemical analyses. Tumorigenesis and metastasis were confirmed by molecular therapeutics tracer 2DG infrared optical probe in BALB/cSIc-nude mice. It was observed that the CD133<SUP>+</SUP>-expressing-<I>LCN2</I>-A549 TICSCs population increased in adenocarcinoma of the lung compared to the normal lung tissue. The expressions of genes involved in stemness, adhesion, motility and drug efflux was higher in these cells than in their non-<I>LCN2</I> expressing counterparts. The present study revealed that elevated expression of <I>LCN2</I> significantly induced metastasis via EMT. Overexpression of <I>LCN2</I> significantly increased stemness and tumor metastasis by modulating NF-κB cellular signaling. BRM270, a novel inhibitor of NF-κB plays a significant role in the EMT reversal. BRM270, a naturaceutical induces cell shrinkage, karyorrhexis and programmed cell death (PCD) which were observed by Hoechst 33342 staining while flow cytometry analysis showed significant (P<0.05) decrease in cell population from G0–G1 phases. Also, 2DG guided <I>in vivo</I> model revealed that BRRM270 significantly (P<0.0003) reduced tumor metastasis and increased percent survival in real-time with complete resection. An elaborate study on the novel concept with respect to linking of naturaceutics as selective and potential anticancer agent that eliminates the elevated <I>LCN2</I> induced EMT and tumor dissemination through cooperation with the NF-κB signaling as the baseline data for the planning of new therapeutic strategies was conducted for the first time. Our results also illustrate a molecular mechanistic approach for 2DG-guided molecular imaging-based cancer therapy using BRM270 as a novel cancer therapeutic drug to enhance the effect of doxorubicin (Dox)-resistant <I>LCN2</I> induced metastasis of solid tumors in nude mice.</P>
Mongre, Raj Kumar,Sodhi, Simrinder Singh,Ghosh, Mrinmoy,Kim, Jeong Hyun,Kim, Nameun,Sharma, Neelesh,Jeong, Dong Kee The Korean Society of Developmental Biology 2014 발생과 생식 Vol.18 No.4
Osteosarcoma (OS) is one of the most common malignant primary bone tumors and NF-${\kappa}B$ appears to play a causative role, but the mechanisms are poorly understood. OS is one of the pleomorphic, highly metastasized and invasive neoplasm which is capable to generate osteoid, osteoclast and osteoblast matrix. Its high incidence has been reported in adolescent and children. Cell signal cascade is the pivotal functional mechanism acquired during the differentiation, proliferation, growth and survival of the cells in neoplasm including OS. The major limitation to the success of chemotherapy in OS is the development of multidrug resistance (MDR). Answers to all such queries might come from the knock-in experiments in which the combined approach of miRNAs with NF-${\kappa}B$ pathway is put into use. Abnormal miRNAs can modulate several epigenetical switching as a hallmark of number of diseases via different cell signaling. Studies on miRNAs have opened up the new avenues for both the diagnosis and treatment of cancers including OS. Collectively, through the present study an attempt has been made to establish a new systematic approach for the investigation of microRNAs, bio-physiological factors and their target pairs with NF-${\kappa}B$ to ameliorate oncogenesis with the "bridge between miRNAs and NF-${\kappa}B$". The application of NF-${\kappa}B$ inhibitors in combination with miRNAs is expected to result in a more efficient killing of the cancer stem cells and a slower or less likely recurrence of cancer.
Kumar Mongre, Raj,Sharma, Neelesh,Singh Sodhi, Simrinder,Ghosh, Mrinmoy,Kumar Singh, Amit,Kim, Nameun,Park, Yang Ho,Shin, Young Gyu,Kim, Sung Jin,Jiao Jiao, Zhang,Huynh, Do Luong,Jeong, Dong Kee EDITIONS SCIENTIFIQUES ELSEVIER 2017 BIOMEDICINE AND PHARMACOTHERAPY Vol.87 No.-
<P><B>Abstract</B></P> <P>Hepatocellular carcinoma (HCC) is a major threat to human health worldwide and development of novel antineoplastic drug is demanding task. BRM270 is a proprietary combination of traditional medicinal herbs, has been shown to be effective against a wide range of stem-like cancer initiating cells (SLCICs). However, the underlying mechanism and antitumor efficacy of BRM270 in human hepatocellular carcinoma (HCC) cells have not been well elucidated till date. Here we studied the tumoricidal effect of BRM270 on human-CD133<SUP>+</SUP> expressing stem-like HepG-2 and SNU-398 cells. Gene expression profiling by qPCR and specific cellular protein expressions was measured using immunocytochemistry/western blot analysis. <I>In vivo</I> efficacy of BRM270 has been elucidated in the SLCICs induced xenograft model. In addition, 2DG-(2-Deoxy-<SMALL>D</SMALL>-Glucose) optical-probe guided tumor monitoring was performed to delineate the size and extent of metastasized tumor. Significant (<I>P</I> <I><</I> 0.05) induction of Annexin-V positive cell population and dose-dependent upregulation of caspase-3 confirmed apoptotic cell death by pre/late apoptosis. In addition, bright field and fluorescence microscopy of treated cells revealed apoptotic morphology and DNA fragmentation in Hoechst33342 staining. Levels of c-Myc, Bcl-2 and c-Jun as invasive potential apoptotic marker were detected using qPCR/Western blot. Moreover, BRM270 significantly (<I>P</I> <I><</I> 0.05) increased survival rate that observed by Kaplan-Meier log rank test. In conclusion, these results indicate that BRM270 can effectively inhibit proliferation and induce apoptosis in hepatoma cells by down-regulating CyclinD1/Bcl2 mediated c-Jun apoptotic pathway.</P>
Raj Kumar Mongre,Simrinder Singh Sodhi,Mrinmoy Ghosh,Jeong Hyun Kim,Nameun Kim,Neelesh Sharma,Dong Kee Jeong 한국발생생물학회 2014 발생과 생식 Vol.18 No.4
Osteosarcoma (OS) is one of the most common malignant primary bone tumors and NF-κB appears to play a causative role, but the mechanisms are poorly understood. OS is one of the pleomorphic, highly metastasized and invasive neoplasm which is capable to generate osteoid, osteoclast and osteoblast matrix. Its high incidence has been reported in adolescent and children. Cell signal cascade is the pivotal functional mechanism acquired during the differentiation, proliferation, growth and survival of the cells in neoplasm including OS. The major limitation to the success of chemotherapy in OS is the development of multidrug resistance (MDR). Answers to all such queries might come from the knock-in experiments in which the combined approach of miRNAs with NF-κB pathway is put into use. Abnormal miRNAs can modulate several epigenetical switching as a hallmark of number of diseases via different cell signaling. Studies on miRNAs have opened up the new avenues for both the diagnosis and treatment of cancers including OS. Collectively, through the present study an attempt has been made to establish a new systematic approach for the investigation of microRNAs, biophysiological factors and their target pairs with NF-κB to ameliorate oncogenesis with the “bridge between miRNAs and NF- κB”. The application of NF-κB inhibitors in combination with miRNAs is expected to result in a more efficient killing of the cancer stem cells and a slower or less likely recurrence of cancer.
Raj Kumar Mongre,정동기,심린더 싱 소디,Mrinmoy Ghosh,김정현,김남은,니레시사르마 한국발생생물학회 2014 발생과 생식 Vol.18 No.4
Osteosarcoma (OS) is one of the most common malignant primary bone tumors and NF-κB appears to play acausative role, but the mechanisms are poorly understood. OS is one of the pleomorphic, highly metastasized and invasiveneoplasm which is capable to generate osteoid, osteoclast and osteoblast matrix. Its high incidence has been reported inadolescent and children. Cell signal cascade is the pivotal functional mechanism acquired during the differentiation,proliferation, growth and survival of the cells in neoplasm including OS. The major limitation to the success of chemotherapyin OS is the development of multidrug resistance (MDR). Answers to all such queries might come from the knock-inexperiments in which the combined approach of miRNAs with NF-κB pathway is put into use. Abnormal miRNAs canmodulate several epigenetical switching as a hallmark of number of diseases via different cell signaling. Studies on miRNAshave opened up the new avenues for both the diagnosis and treatment of cancers including OS. Collectively, through thepresent study an attempt has been made to establish a new systematic approach for the investigation of microRNAs, biophysiologicalfactors and their target pairs with NF-κB to ameliorate oncogenesis with the “bridge between miRNAs and NF-κB”. The application of NF-κB inhibitors in combination with miRNAs is expected to result in a more efficient killing of thecancer stem cells and a slower or less likely recurrence of cancer.
Ghosh, M.,Cho, H. W.,Park, J. W.,Choi, J. Y.,Chung, Y. H.,Sharma, N.,Singh, A. K.,Kim, N. E.,Mongre, R. K.,Huynh, D. Springer Science + Business Media 2016 Applied biochemistry and biotechnology Vol.180 No.3
<P>The athletic abilities of the horse serve as a valuable model to understand the physiology and molecular mechanisms of adaptive responses to exercise. We analyzed differentially expressed genes in triceps brachii muscle tissues collected from Eonjena Taeyang and Jigusang Seryeok Thoroughbred horses and their co-expression networks in a large-scale RNA-sequence dataset comparing expression before and after exercise. High-quality horse transcriptome data were generated, with over 22 million 90-bp pair-end reads. By comparing the annotations, we found that MYH3, MPZ, and PDE8B genes in Eonjena Taeyang and PDE8B and KIF18A genes in Jigusang Seryeok were upregulated before exercise. Notably further, we observed that PPP1R27, NDUFA3, TNC, and ANK1 in Eonjena Taeyang and HIF1A, BDNF, ADRB2, OBSCN, and PER3 in Jigusang Seryeok have shown upregulation at the postexercise period. This investigation suggested that genes responsible for metabolism and oxidative phosphorylations associated with endurance and resistance exercise were highly expressed, whereas genes encoding structural proteins were generally suppressed. The expression profile of racehorses at pre- and postexercise will provide credible reference for further studies on biological effects such as responses to stress and adaption of other Thoroughbred horse, which might be useful for selective breeding for improvement of traits in commercial production.</P>