Anosmin-1 contributes to brain tumor malignancy through integrin signal pathways

Choy, Catherine T,Kim, Haseong,Lee, Ji-Young,Williams, David M,Palethorpe, David,Fellows, Greg,Wright, Alan J,Laing, Ken,Bridges, Leslie R,Howe, Franklyn A,Kim, Soo-Hyun Bioscientifica Ltd 2014 Endocrine-related cancer Vol.21 No.1

<P>Anosmin-1, encoded by the <I>KAL1</I> gene, is an extracellular matrix (ECM)-associated protein which plays essential roles in the establishment of olfactory and GNRH neurons during early brain development. Loss-of-function mutations of <I>KAL1</I> results in Kallmann syndrome with delayed puberty and anosmia. There is, however, little comprehension of its role in the developed brain. As reactivation of developmental signal pathways often takes part in tumorigenesis, we investigated if anosmin-1-mediated cellular mechanisms associated with brain tumors. Our meta-analysis of gene expression profiles of patients' samples and public microarray datasets indicated that <I>KAL1</I> mRNA was significantly upregulated in high-grade primary brain tumors compared with the normal brain and low-grade tumors. The tumor-promoting capacity of anosmin-1 was demonstrated in the glioblastoma cell lines, where anosmin-1 enhanced cell motility and proliferation. Notably, anosmin-1 formed a part of active β1 integrin complex, inducing downstream signaling pathways. ShRNA-mediated knockdown of anosmin-1 attenuated motility and growth of tumor cells and induced apoptosis. Anosmin-1 may also enhance the invasion of tumor cells within the ECM by modulating cell adhesion and activating extracellular proteases. In a mouse xenograft model, anosmin-1-expressing tumors grew faster, indicating the role of anosmin-1 in tumor microenvironment <I>in vivo</I>. Combined, these data suggest that anosmin-1 can facilitate tumor cell proliferation, migration, invasion, and survival. Therefore, although the normal function of anosmin-1 is required in the proper development of GNRH neurons, overexpression of anosmin-1 in the developed brain may be an underlying mechanism for some brain tumors.</P>

Lowered cutoff of lymph node fine-needle aspiration thyroglobulin in thyroid cancer patients with serum anti-thyroglobulin antibody

Jo, Kwanhoon,Kim, Min-Hee,Lim, Yejee,Jung, So-Lyung,Bae, Ja-Seong,Jung, Chan-Kwon,Kang, Moo-Il,Cha, Bong-Yun,Lim, Dong-Jun BioScientifica Ltd. 2015 European journal of endocrinology Vol.173 No.4

<P><B>Objective</B></P><P>Fine needle aspiration cytology (FNAC) and measurement of thyroglobulin (Tg) in needle washout (FNA-Tg) are recommended for the diagnosis of metastatic or recurrent lymph nodes (LNs) in differentiated thyroid cancer (DTC). However, the effect of serum Tg antibody (TgAb) on FNA-Tg levels still remains unclear in the preoperative setting. We analyze the interference of serum TgAb on FNA-Tg levels as proof of concept in the diagnostic advantage of serum TgAb combined with FNA-Tg.</P><P><B>Subjects and methods</B></P><P>A total of 370 suspicious cervical LNs from 273 patients with DTC were included. The primary tumor was confirmed as DTC on preoperative pathology in all patients. We performed FNA-Tg measurement and FNAC on suspicious LNs and evaluated the diagnostic performance of FNAC and FNA-Tg according to TgAb status. Final diagnoses were confirmed by histological examination of excised specimens or by follow-up ultrasonography for at least 6 months.</P><P><B>Results</B></P><P>Data from 273 subjects with suspicious 370 LNs were evaluated. Fifty-five LNs (14.9%) were from TgAb+ positive serum TgAb (TgAb+) patients. Serum Tg and FNA-Tg levels were significantly lower in patients with TgAb+ than in those with TgAb-negative (TgAb−). Final pathology confirmed 109 LNs (29.5%) asmalignant. Diagnostic performance of FNA-Tg at the same cutoff level was lower in the TgAb+ than TgAb− group. FNA-Tg cutoff levels determined by ROC curve were lower in the TgAb+ group.</P><P><B>Conclusion</B></P><P>The results suggested that the cutoff value of FNA-Tg should be lowered in suspicious LN before thyroidectomy in thyroid cancer patients with TgAb.</P>

Alteration in the intrafollicular thiol–redox system in infertile women with endometriosis

Choi, Young Sik,Cho, SiHyun,Seo, Seok Kyo,Park, Joo Hyun,Kim, Seok Hyun,Lee, Byung Seok BioScientifica Ltd 2015 Reproduction Vol.149 No.2

<P>The aim of this study was to compare intrafollicular biomarkers of thiol–redox system and chronic inflammation in infertile patients with and without endometriosis, and examine correlations between biomarkers and IVF outcomes. The study included 65 patients receiving IVF: 31 patients with endometriosis vs 34 patients without endometriosis. Follicular fluid (FF) was obtained from a single-dominant follicle during oocyte retrieval and stored at −70 °C. Malondialdehyde, superoxide dismutase, glutathione (GSH), glutathione peroxidase 3 (GPX3), thioredoxin (TRX), TRX-binding protein 2 (TBP2), and peroxiredoxin-4 levels were measured in the FF samples by ELISAs as biomarkers of oxidative stress. The inflammatory cytokines interleukin 1 beta (IL1β), IL6, IL8, and tumor-necrosis factor alpha (TNFα) were also measured by ELISAs. GSH levels were significantly lower in the endometriosis group compared with the controls. TBP2 levels were significantly higher in the endometriosis group. IL6, IL8, and TNFα levels were significantly higher in the endometriosis group. The levels of all of the inflammatory cytokines positively correlated with the levels of TRX. GSH levels positively correlated with the number of high-quality embryos. GPX3 and TRX levels negatively correlated with the percentage of mature oocytes. TNFα levels negatively correlated with the cumulative embryo score per embryo. Logistic regression analysis revealed that the number of high-quality embryos was an independent factor predicting clinical pregnancy. In conclusion, there may be an imbalance in the thiol–redox system and increased levels of inflammatory cytokines in the intrafollicular microenvironment of infertile patients with endometriosis, which may affect the qualities of the oocyte and embryo.</P>

Expression of the rhesus glycoproteins, ammonia transporter family members, RHCG and RHBG in male reproductive organs

Lee, Hyun-Wook,Verlander, Jill W,Handlogten, Mary E,Han, Ki-Hwan,Cooke, Paul S,Weiner, I David BioScientifica Ltd 2013 Reproduction Vol.146 No.3

<P>The rhesus glycoproteins, Rh B glycoprotein (RHBG) and Rh C glycoprotein (RHCG), are recently identified ammonia transporters. Rhcg expression is necessary for normal male fertility, but its specific cellular expression is unknown, and Rhbg has not been reported to be expressed in the male reproductive tract. This study sought to determine the specific cellular expression of Rhcg, to determine whether Rhbg is expressed in the male reproductive tract, and, if so, to determine which cells express Rhbg using real-time RT-PCR, immunoblot analysis, and immunohistochemistry. Both Rhbg and Rhcg were expressed throughout the male reproductive tract. In the testis, high levels of Rhbg were expressed in Leydig cells, and Rhcg was expressed in spermatids during the later stages of their maturation (steps 13–16) in stages I–VIII of the seminiferous epithelium cycle. In the epididymis, basolateral Rhbg was present in narrow cells in the initial segment, in principal cells in the upper corpus, and in clear cells throughout the epididymis. Apical Rhcg immunolabel was present in principal cells in the caput and upper corpus epididymidis and in clear cells in the middle and lower corpus and cauda epididymidis. In the vas deferens, apical Rhcg immunolabel and basolateral Rhbg immunolabel were present in some principal cells and colocalized with H<SUP>+</SUP>-ATPase immunolabel. We conclude that both Rhbg and Rhcg are highly expressed in specific cells in the male reproductive tract where they can contribute to multiple components of male fertility.</P>

Decrement of postprandial insulin secretion determines the progressive nature of type-2 diabetes

Shim, W. S.,Kim, S. K.,Kim, H. J.,Kang, E. S.,Ahn, C. W.,Lim, S. K.,Lee, H. C.,Cha, B. S. BioScientifica Ltd. 2006 European journal of endocrinology Vol.155 No.4

Preproghrelin Leu72Met polymorphism predicts a lower rate of developing renal dysfunction in type 2 diabetic nephropathy

Lee, D.-Y.,Kim, S.-Y.,Jo, D.-S.,Hwang, P. H.,Kang, K. P.,Lee, S.,Kim, W.,Park, S. K. BioScientifica Ltd. 2006 European journal of endocrinology Vol.155 No.1

Low PR in ER(+)/HER2(−) breast cancer: high rates of <i>TP53</i> mutation and high SUV

Ahn, Sung Gwe,Yoon, Chang Ik,Lee, Jae Hoon,Lee, Hye Sun,Park, So Eun,Cha, Yoon Jin,Cha, Chihwan,Bae, Soong June,Lee, Kyung-A,Jeong, Joon Bioscientifica Ltd 2018 Endocrine-related cancer Vol.26 No.2

<P>On the basis of <I>TP53</I> mutations and standardized uptake values (SUVs) from 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET), we sought to enhance our knowledge of the biology underlying low progesterone receptor (PR) expression in estrogen receptor (ER)-positive/human epidermal growth factor receptor-2 (HER2)-negative tumors. This study included 272 patients surgically treated for ER-positive, HER2-negative breast cancer and who had undergone <I>TP53</I> gene sequencing. Of these, 229 patients also underwent 18F-FDG PET or PET/CT. Mutational analysis of exons 5–9 of the <I>TP53</I> gene was conducted using PCR amplification and direct sequencing. The SUVs were measured using 18F-FDG-PET scan images. Twenty-eight (10.3%) tumors had a somatic <I>TP53</I> mutation. The <I>TP53</I> mutation rate was significantly higher in low-PR tumors than in high-PR tumors (17.1% vs 7.9%, <I>P</I> = 0.039). Low-PR tumors had significantly higher median SUVs than high-PR tumors (<I>P</I> = 0.046). The multivariable analysis revealed that SUV and age remained independent variables associated with low PR expression. An adverse impact of low PR expression on recurrence-free survival was observed in the multivariable Cox regression hazard model. We provide clinical evidence that genetic alteration of the <I>TP53</I> gene and dysregulated glucose metabolism partly involve low PR expression in ER-positive and HER2-negative breast cancer.</P>

Evaluation of estrogenic potential by herbal formula, HPC 03 for <i>in vitro</i> and <i>in vivo</i>

Chang, Bo Yoon,Kim, Dae Sung,Kim, Hye Soo,Kim, Sung Yeon BioScientifica Ltd 2018 Reproduction Vol.155 No.2

<P>HPC 03 is herbal formula that consists of extracts from Angelica gigas, Cnidium officinale Makino and Cinnamomum cassia Presl. The present study evaluated the estrogenic potential of HPC 03 by using in vitro and in vivo models. The regulatory mechanisms of HPC 03 in estrogen-dependent MCF-7 cells were assessed. HPC 03 induced the proliferation of estrogen receptor-positive MCF-7 cells, and the proliferation was blocked by the addition of the estrogen antagonist tamoxifen. The estrogen receptora(alpha/beta) luciferase activities were significantly increased by HPC 03 treatment, which also increased the mRNA expression of the estrogen-responsive genes Psen2, Pgr and Ctsd. Also, we evaluated the ameliorative effects of HPC 03 on menopausal symptoms in ovariectomized rats. HPC 03 treatment in OVX rats significantly affected the uterine weight, increased the expression of estrogen-responsive genes Pgr and Psen2 in uterus, increased bone mineral density loss in the femur and inhibited body weight increase. Serum E2, collagen type 1 and osteocalcin were significantly increased, while serum LH, FSH and ALP were decreased compared with OVX rats. HPC 03 may be a promising candidate for the treatment of menopause, but further research is necessary to determine whether the observed effects also occur in humans.</P>

Clinical outcomes after delayed thyroid surgery in patients with papillary thyroid microcarcinoma

Jeon, Min Ji,Kim, Won Gu,Kwon, Hyemi,Kim, Mijin,Park, Suyeon,Oh, Hye-Seon,Han, Minkyu,Sung, Tae-Yon,Chung, Ki-Wook,Hong, Suck Joon,Kim, Tae Yong,Shong, Young Kee,Kim, Won Bae BioScientifica Ltd. 2017 European journal of endocrinology Vol.177 No.1

<P>Conclusions: In PTMC patients, delayed surgery was not associated with higher risk of structural recurrent/persistent disease compared to immediate surgery. These findings support the notion that surgical treatment can be safely delayed in patients with PTMC under close monitoring.</P>

Metabolic profiling of cholesterol and sex steroid hormones to monitor urological diseases

Moon, Ju-Yeon,Choi, Man Ho,Kim, Jayoung Bioscientifica Ltd 2016 Endocrine-related cancer Vol.23 No.10

<P>Cholesterol and sex steroid hormones including androgens and estrogens play a critical role in the development and progression of urological diseases such as prostate cancer. This disease remains the most commonly diagnosed malignant tumor in men and is the leading cause of death from different cancers. Attempts to understand the role of cholesterol and steroid metabolism in urological diseases have been ongoing for many years, but despite this, our mechanistic and translational understanding remains elusive. In order to further evaluate the problem, we have taken an interest in metabolomics; a discipline dedicated to the systematic study of biologically active metabolites in cells, tissues, hair and biofluids. Recently, we provided evidence that a quantitative measurement of cholesterol and sex steroid metabolites can be successfully achieved using hair of human and mouse models. The overall goal of this short review article is to introduce current metabolomic technologies for the quantitative biomarker assay development and also to provide new insight into understanding the underlying mechanisms that trigger the pathological condition. Furthermore, this review will place a particular emphasis on how to prepare biospecimens (e.g., hair fiber), quantify molecular profiles and assess their clinical significance in various urological diseases.</P>