Diabetes Mellitus and the Development of Lumbar Canal Stenosis: Is There Any Relevance?

Kakadiya Ghanshyam,Saindane Kalpesh,Soni Yogesh,Gohil Kushal,Shakya Akash,Attar Mohhamad Umair 대한척추외과학회 2022 Asian Spine Journal Vol.16 No.3

Study Design: Retrospective study.Purpose: To assess the relationship between the severity of lumbar canal stenosis (LCS) and type-II diabetes mellitus (DM).Overview of Literature: DM is a multiorgan disorder that has an effect on all types of connective tissues. LCS is a narrowing of the spinal canal with nerve root impingement that causes neurological claudication and radiculopathy. Identification of the risk factors of LCS is key in the prevention of its onset or progression.Methods: LCS patients were divided into three groups as per DM status: group A without DM (n=150); group B patients with well-controlled DM; and group C patients with uncontrolled DM. Groups B and C were subdivided into group B1: patients with DM with a duration of ≤10 years (n=76), group B2: DM with duration of >10 years (n=68), group-C1 DM duration ≤10 years (n=56), and group C2 DM duration >10 years (n=48). The severity of LCS was evaluated using the Swiss Spinal Stenosis Scale (SSSS) and Modified Oswestry Disability score (MODS). Operated patients ligamentum flavum sent for histological staining and quantitative immunofluorescence analysis.Results: The demographic data of groups did not show any difference except in age. There was no difference between the mean SSSS and MODS of groups A and B1. Groups B2, C1, and C2 had higher average SSSS and MODS than group A (p<0.05). Groups B2 and C2 had higher SSSS and MODS than groups B1 and C1. Group C1 and C2 had higher scores than groups B1 and B2 (p<0.05). The severity of LCS was significantly related to the duration of DM in groups B and C (p<0.05). Uncontrolled and longer duration of DM had significant elastin fibers loss and also higher rate of disk apoptosis, high matrix aggrecan fragmentation, and high disk glycosaminoglycan content.Conclusions: Longer duration and uncontrolled diabetes were risk factors for LCS and directly correlate with the severity of LCS.

p53 stability is regulated by diverse deubiquitinating enzymes

Kwon, Seul-Ki,Saindane, Madhuri,Baek, Kwang-Hyun Elsevier 2017 Biochimica et biophysica acta, Reviews on cancer Vol.1868 No.2

<P><B>Abstract</B></P> <P>The tumor suppressor protein p53 has a variety of roles in responses to various stress signals. In such responses, p53 activates specific transcriptional targets that control cell cycle arrest, DNA repair, angiogenesis, autophagy, metabolism, migration, aging, senescence, and apoptosis. Since p53 has been identified as the most frequently altered gene in human cancers, regulation and stabilization of its normal functions are important. Stability of p53 is regulated by the ubiquitin-proteasome pathway (UPP). Furthermore, it is readjusted by deubiquitination via deubiquitinating enzymes (DUBs) that can eliminate ubiquitin from p53. Diverse DUBs directly or indirectly affect the ubiquitination of p53 and, consequently, regulate various cellular processes associated with p53. As maintenance of p53 is regulated by a variety of DUBs, the interaction of DUBs and p53 can affect diseases such as cancer. Currently, DUBs have a central role in our understanding of various cancers, and some have potential in the development of effective therapeutic strategies. This review summarizes the current knowledge of p53 and of the interconnection between p53 and DUBs.</P>

Selective inhibition of V600E-mutant BRAF gene induces apoptosis in thyroid carcinoma cell lines

Kyoung Sik Park,Madhuri Saindane,Eun Yeol Yang,TongYi Jin,Harikrishna Reddy Rallabandi,Alexander Heil,Sang Eun Nam,Young Bum Yoo,Jung-Hyun Yang,Jong Bin Kim,Seo-Young Park,Won Seo Park,Yeo-Kyu Youn 대한외과학회 2021 Annals of Surgical Treatment and Research(ASRT) Vol.100 No.3

Purpose: Papillary thyroid cancer (PTC) has a high incidence of BRAF<SUP>V600E</SUP> mutation. The purpose of this study was to evaluate the potential relationship between thyroiditis and BRAF<SUP>V600E</SUP> mutation status in patients with PTC. We investigated how a selective inhibitor of BRAF<SUP>V600E</SUP> PLX4032 affects the proliferation and inflammatory cytokine levels of thyroid cancer. Methods: Two thyroid cancer cell lines TPC1 and 8505C were treated with PLX4032, an analysis was done on cell growth, cell cycle, the degree of apoptosis, and levels of inflammatory cytokines. To identify the functional links of BRAF, we used the STRING database. Results: Docking results illustrated PLX4032 blocked the kinase activity by exclusively binding on the serine/threonine kinase domain. STRING results indicated BRAF is functionally linked to mitogen-activated protein kinase. Both cell lines showed a dose-dependent reduction in growth rate but had a different half maximal inhibitory concentration value for PLX4032. The reaction to PLX4032 was more sensitive in the 8505C cells than in the TPC1 cells. PLX4032 induced a G2/M phase arrest in the TPC1 cells and G0/G1 in the 8505C cells. PLX4032 induced apoptosis only in the 8505C cells. With PLX4032, the TPC1 cells showed decreased levels of vascular endothelial growth factor, granulocyte-macrophage colony-stimulating factor, chemokine (C-C motif) ligand 2/monocyte chemoattractant protein 1, whereas the 8505C cells showed significantly decreased levels of IL-8, serpin E1/plasminogen activator inhibitor-1, and matrix metalloproteinase (MMP)-3. Conclusion: PLX4032 was cytotoxic in both TPC1 and 8505C cells and induced apoptosis. In the 8505C cells, inflammatory cytokines such as IL-8 and MMP-3 were down-regulated. These findings suggest the possibility that the BRAF<SUP>V600E</SUP> mutation needs to target inflammatory signaling pathways in the treatment of thyroid cancer.

Vitamin D receptor (VDR) mRNA overexpression is associated with poor prognosis in breast carcinoma

Sang Eun Nam,TongYi Jin,Kyoung Sik Park,Madhuri Saindane,Woo Chul Noh,Young Bum Yoo,Won Seo Park,Ik Jin Yun 대한외과학회 2022 Annals of Surgical Treatment and Research(ASRT) Vol.103 No.4

Purpose: The prognostic value of vitamin D receptor gene (VDR) expression in breast cancer development is unclear. Here, we aimed to investigate whether VDR expression can be used as a prognostic indicator of breast cancer. Methods: We used various public bioinformatics platforms: Oncomine, GEPIA, UALCAN, Kaplan-Meier plotter, UCSC XENA, bc-GenExMiner, WebGestalt, and STRING database. Results: We found that VDR was upregulated in breast cancer in comparison to normal tissues. Overexpression of VDR was significantly associated with worse overall survival in breast cancer. The expression of VDR was related to age, TNM stages, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, basallike (PAM 50) status, triple-negative breast cancer (TNBC) status, and basal-like (PAM 50) & TNBC status (P < 0.05). Increased VDR expression in breast cancer was significantly associated with older age. The 5 hub genes for VDR were NCOA1, EP300, CREBBP, and RXRA. Conclusion: Our investigation offers hints about the prognostic role of VDR in breast cancer. The findings suggest that VDR expression might be used as a marker to determine a breast cancer patient’s prognosis. Nevertheless, further validation is warranted.

Postthyroidectomy obesity in a Korean population: does the extent of surgery matter?

Min-Young Park,Sang Eun Nam,박경식,Madhuri Saindane,Young-Bum Yoo,Jung-Hyun Yang,Ah-Leum Ahn,Jae-Kyung Choi,박원서 대한외과학회 2019 Annals of Surgical Treatment and Research(ASRT) Vol.97 No.3

Purpose: The purpose of this study was to investigate the prevalence of postthyroidectomy obesity, and the relationship between the extent of thyroidectomy and obesity. Methods: A survey conducted at an outpatient clinic from June to October 2014 and retrospective charts for patients undergoing thyroidectomy at Konkuk University Medical Centers from June 2009 to December 2013 were reviewed. We compared clinical characteristics and pre- and postoperative obesity-related factors in 227 patients who underwent total thyroidectomy or lobectomy. Results: Patients included 39 males and 188 females with a mean age of 46.0 ± 11.0 years; the mean follow-up period was 23.9 ± 16.7 months, and 90 of the 227 patients showed postthyroidectomy obesity. In effect of operative extent on postoperative obesity, patients who underwent TT (48.2 years) than those who underwent lobectomy (43.4 years). TT group had longer follow-up and the frequency of menopause was higher than in the lobectomy group. No differences in postthyroidectomy obesity, body weight change, or body mass index (BMI), change among 2 groups. The predictors of postthyroidectomy obesity were older age, female, heavy alcohol consumption (P = 0.029), higher preoperative BMI (P < 0.001), larger postoperative weight gain (P = 0.024), and larger BMI change. However, the extent of thyroidectomy did not affect postthyroidectomy obesity. Preoperative BMI (P < 0.001) and heavy alcohol consumption (P = 0.03) were independent factors of postthyroidectomy obesity. Conclusion: The extent of thyroidectomy does not affect postthyroidectomy obesity. Preoperative BMI and heavy alcohol consumption are risk factors for postthyroidectomy obesity. Studies are needed to suggest preoperative life style modification to prevent postthyroidectomy obesity