Effects of deranged metabolism on epigenetic changes in cancer.

Chandra, Vishal,Hong, Kyeong-Man Pharmaceutical Society of Korea 2015 Archives of Pharmacal Research Vol.38 No.3

<P>The concept of epigenetics is now providing the mechanisms by which cells transfer their new environmental-change-induced phenotypes to their daughter cells. However, how extracellular or cytoplasmic environmental cues are connected to the nuclear epigenome remains incompletely understood. Recently emerging evidence suggests that epigenetic changes are correlated with metabolic changes via chromatin remodeling. As many human complex diseases including cancer harbor both epigenetic changes and metabolic dysregulation, understanding the molecular processes linking them has huge implications for disease pathogenesis and therapeutic intervention. In this review, the impacts of metabolic changes on cancer epigenetics are discussed, along with the current knowledge on cancer metabolism and epigenetics.</P>

Therapeutic options for management of endometrial hyperplasia

Vishal Chandra,김종주,Doris Mangiaracina Benbrook,Anila Dwivedi,Rajani Rai 대한부인종양학회 2016 Journal of Gynecologic Oncology Vol.27 No.1

Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH.

Immunohistochemical localization of LLC1 in human tissues and its limited expression in non-small cell lung cancer.

Chandra, Vishal,Choi, Yong-Bock,Hwang, Hai-Li,Lee, Jeong-Hwa,Park, Seong-Yeol,Kim, Hyun-Kyoung,Poojan, Shiv,Koh, Jae-Soo,Kim, Han-Seong,Hong, Kyeong-Man Gutenberg 2015 HISTOLOGY AND HISTOPATHOLOGY Vol.30 No.9

<P>We have shown both LLC1 expression in the lung epithelium by in situ hybridization and its inactivation in lung cancer by epigenetic modification. However, LLC1 protein's cellular localization or its role in normal lung or cancer tissues has not yet been evaluated. In the present study, a monoclonal antibody against recombinant LLC1 was produced, and immunohistochemical staining was performed on arrays including various human tissues, normal lung and non-small cell lung cancer (NSCLC) tissues for LLC1 localization. The immunohistochemical results showed LLC1 expression in the cilia of normal-airway epithelial cells and in the cytoplasm of type II pneumocytes in bronchiectatic patients, but no expression in most of the NSCLC tissues, which is consistent with our previous report positing LLC1 as a tumor suppressor. However, LLC1 over-expression in NSCLC cell lines NCI-H1299 and NCI-H23 did not show any change in proliferation or migration, which does not indicate any LLC1 tumor-suppressor role. As for the other human tissues, LLC1 was localized in renal tubular cells, pancreatic acinar cells, and epithelial cells of the stomach, duodenum, and gallbladder. In summary, our findings suggest that LLC1 is not a tumor suppressor, and that it is localized in the cilia of the normal lung epithelium but is absent in most NSCLC cases, probably due to the loss of cilia during lung carcinogenesis.</P>

Physiological and Functional Evaluation of the Transposed Human Pylorus as a Distal Sphincter

( Abhijit Chandra ),( Uday C Ghoshal ),( Vishal Gupta ),( Ramendra Jauhari ),( Rajendra N Srivastava ),( Asha Misra ),( Ashok Kumar ) 대한소화기기능성질환·운동학회 2012 Journal of Neurogastroenterology and Motility (JNM Vol.18 No.3

Background/Aims Studies evaluating the human pylorus as a sphincter are scanty and contradictory. Recently, we have shown technical feasibility of transposing the human pylorus for end-stage fecal incontinence. This unique cohort of patients provided us an opportunity to study the sphincter properties of the pylorus in its ectopic position. Methods Antro-pylorus transposition on end sigmoid colostomies (n = 3) and in the perineum (n = 15) was performed for various indications. Antro-pylorus was assessed functionally (digital examination, high resolution spatiotemporal manometry, barium retention studies and colonoscopy) and by imaging (doppler ultrasound, MRI and CT angiography) in its ectopic position. Results The median resting pressure of pylorus on colostomy was 30 mmHg (range 28-38). In benign group, median resting pressure in perineum was 12.5 mmHg (range 6-44) that increased to 21.5 mmHg (range 12-29) (P = 0.481) and 31 mmHg (range 16-77) (P = 0.034) on first and second follow-up, respectively. In malignant group, median post-operative pressures were 20 mmHg (range 14-36) and 21 mmHg (range 18-44) on first and second follow-up, respectively. A definite tone and gripping sensation were felt in all the patients on digital examination. On distal loopogram, performed through the diverting colostomies, barium was retained proximal to the neo-pyloric valve. Both perineal ultrasound and MRI showed viable transposed graft. CT angiography and color doppler studies confirmed vascular flow in the transposed position. Conclusions The human pyloric valve can function as a tonic sphincter when removed from the gastroduodenal continuity. (J Neurogastroenterol Motil 2012;18:269-277)

Feasibility of Neurovascular Antropylorus Perineal Transposition With Pudendal Nerve Anastomosis Following Anorectal Excision: A Cadaveric Study for Neoanal Reconstruction

Abhijit Chandra,Ashok Kumar,M Noushif,Nitish Gupta,Vijay Kumar,Navneet Kumar Chauhan,Vishal Gupta 대한대장항문학회 2013 Annals of Coloproctolgy Vol.29 No.1

Purpose: Perineal transposition of the antropyloric valve following an anorectal excision as a substitute for a permanent colostomy has recently been reported in humans. However, the problem of neural control still remains in these patients. Our aim herein was to study the anatomical feasibility of an anastomosis between the pudendal nerve branches (inferior rectal nerve) innervating the external anal sphincter and the anterior vagal branches of the perineally-transposed antropyloric segment in cadavers. Methods: The antropyloric segment, along with its carefully dissected branch of the anterior vagus, was mobilized based on the left gastroepiploic pedicle in six fresh human cadavers. The antropyloric valve was then transposed in the perineum after the pudendal nerve branches had been dissected out, and an approximation of these two nerves was performed to ascertain the technical feasibility of their neural anastomosis. Results: The anterior vagus innervating the antropylorus could be harvested in all cadavers below the hepatic division of the main vagus trunk. The inferior rectal nerve or its branches were found consistently around the 3 or the 9 o’clock position in the ischioanal fossa. An anatomical tension-free approximation of the anterior vagus branch (of the transposed antropyloric segment) to the inferior rectal nerve in the perineum was feasible in all the cadavers studied. Conclusion: An inferior rectal nerve anastomosis with the anterior vagal branch of the perineally-transposed antropyloric segment can be achieved anatomically. This preliminary step can be the basis for future animal studies and subsequent clinical application of the procedure for possible neural control of the transposed antropyloric segment in the perineum.

Role of Arbitrary Intensity Profile Laser Beam in Trapping of RBC for Phase-imaging

Ranjeet Kumar,Vishal Srivastava,Dalip Singh Mehta,Chandra Shakher 한국광학회 2016 Current Optics and Photonics Vol.20 No.1

Red blood cells (RBCs) are customarily adhered to a bio-functionalised substrate to make them stationaryin interferometric phase-imaging modalities. This can make them susceptible to receive alterations in innatemorphology due to their own weight. Optical tweezers (OTs) often driven by Gaussian profile of a laserbeam is an alternative modality to overcome contact-induced perturbation but at the same time a steeplyfocused laser beam might cause photo-damage. In order to address both the photo-damage and substrateadherence induced perturbations, we were motivated to stabilize the RBC in OTs by utilizing a laser beamof ‘arbitrary intensity profile’ generated by a source having cavity imperfections per se. Thus the immobilizedRBC was investigated for phase-imaging with sinusoidal interferograms generated by a compact and robustMichelson interferometer which was designed from a cubic beam splitter having one surface coated withreflective material and another adjacent coplanar surface aligned against a mirror. Reflected interferogramsfrom bilayers membrane of a trapped RBC were recorded and analyzed. Our phase-imaging set-up is limitedto work in reflection configuration only because of the availability of an upright microscope. Due to RBC’smembrane being poorly reflective for visible wavelengths, quantitative information in the signal is weakand therefore, the quality of experimental results is limited in comparison to results obtained in transmissionmode by various holographic techniques reported elsewhere.

A Hyaluronic Acid-Rich Node and Duct System in Which Pluripotent Adult Stem Cells Circulate

Rai, Rajani,Chandra, Vishal,Kwon, Byoung S. Mary Ann Liebert 2015 STEM CELLS AND DEVELOPMENT Vol.24 No.19

<P>Regenerative medicine is in demand of adult pluripotent stem cells (PSCs). The 'Bonghan System (BHS)' was discovered and suggested to contain cells with regenerative capacity in the early 1960s. It had been ignored for a long time due to the lack of sufficient details of experiments, but about 37 years after the initial report, the BHS was rediscovered and named as the 'primo vascular system.' Recently, we have discovered a similar structure, which contained a high level of hyaluronic acid, and hence, named the structure as hyaluronic acid-rich node and duct system (HAR-NDS). Here we discuss the HAR-NDS concept starting from the discovery of BHS, and findings pointing to its importance in regenerative medicine. This HAR-NDS contained adult PSCs, called node and duct stem cells (NDSCs), which appeared to circulate in it. We describe the evidence that NDSCs can differentiate into hemangioblasts that further produced differentiated blood cells. The NDSCs had a potential to differentiate into neuronal cells and hepatocytes; thus, NDSCs had a capability to become cells from all three germ layers. This system appears to be a promising alternative source of adult stem cells that can be easily delivered to their target tissues and participate in tissue regeneration.</P>

Ghost probiotics with a combined regimen: a novel therapeutic approach against the Zika virus, an emerging world threat

Bajpai, Vivek K.,Chandra, Vishal,Kim, Na-Hyung,Rai, Rajni,Kumar, Pradeep,Kim, Kangmin,Aeron, Abhinav,Kang, Sun Chul,Maheshwari, D. K.,Na, MinKyun,Rather, Irfan A.,Park, Yong-Ha Informa UK (TaylorFrancis) 2018 Critical reviews in biotechnology Vol.38 No.3

Genome-wide identification and analysis of Subtilisin-like serine protease gene family in banana (Musa accuminta L.) and their expression under abiotic stresses

Purwar Shalini,Chugh Vishal,Singh Poornima,Srivastava Akhilesh Kumar,Singh Akhilesh Kumar,Mishra Akhilesh Chandra,Singh Ashutosh,Singh Chandra Mohan 한국식물생명공학회 2024 Plant biotechnology reports Vol.18 No.1

Subtilisin-like serine proteases (SBT), a serine proteolytic enzymes play an important role in plant growth function and during different stresses responses. The systematic analysis of the SBT gene family in Musa acuminate (MaSBT) has been done and their responses to abiotic stresses in banana variety cv. G-9 were also analyzed. Total of 67 MaSBT genes were identified and based on phylogeny these were grouped into five districted subgroups. Cis-acting element analysis indicated that almost all MaSBT promoters contain regulatory elementary related to growth and development, hormonal regulation, and stress responses. The gene structure and domain analysis showed a maximum of seventeen exons and four functional domains in MaSBT. The 42 orthologous genes, 07 MaSBT paralogous genes were also identified through synteny analysis. The Ka /Ks study indicated that four MaSBT paralogous gene pairs were tandemly duplicated, while the other three were segmental duplications. Further, the expression pattern via RNA-seq data revealed that MaSBTs exhibited differential expres- sion specifically in response to the abiotic stress of low nitrogen. and also during the flowering time. The MaSBT-1.7 gene was found involved in the response to salt stress and flowering. These findings establish a cornerstone for future research on banana's salt stress mechanism. The study offers valuable insights into SBT encoding genes, shedding light on their roles in growth, development, and abiotic stress responses

Clinical implications of proliferation activity in T1 or T2 male gastric cancer patients

김영우,엄방울,Myeong-Cherl Kook,김한성,김미경,Hai-Li Hwang,Vishal Chandra,Shiv Poojan,송유라,고재수,배창대,노정실,홍경만 생화학분자생물학회 2015 Experimental and molecular medicine Vol.47 No.-

Proliferation activity has already been established as a prognostic marker or as a marker for anticancer drug sensitivity. In gastric cancer, however, the prognostic significance of proliferation activity is still being debated. Several studies evaluating proliferation activity using Ki-67 have shown controversial results in terms of the relationship between proliferation activity and overall survival (OS) or drug sensitivity in gastric cancer patients. Because cytoskeleton-associated protein 2 (CKAP2) staining has recently been introduced as a marker of proliferation activity, we analyzed 437 gastric cancer tissues through CKAP2 immunohistochemistry, and we evaluated the chromatin CKAP2-positive cell count (CPCC) for proliferation activity. Although the CPCC did not show any significant correlation with OS in the male, female or total number of cases, it did show a significant correlation in the T1 or T2 male patient subgroup, according to log-rank tests (P=0.001) and univariate analysis (P=0.045). Additionally, multivariate analysis with the Cox proportional hazard regression model showed a significant correlation between the CPCC and OS (P=0.039) for the co-variables of age, gender, T stage, N stage, histology, tumor location, tumor size and adjuvant chemotherapy. In male gastric cancer cell lines, faster-growing cancer cells showed higher sensitivity to cisplatin than slow-growing cells. Thus our study indicates that CPCC-measured proliferation activity demonstrates a significantly worse prognosis in T1 or T2 male gastric cancer patients. The CPCC will help to more precisely classify gastric cancer patients and to select excellent candidates for adjuvant chemotherapy, which in turn will facilitate further clinical chemotherapeutic trials.