Search

Objective: Unusual setting of medical care Background: Subacute lower limb ischemia occurs more than 14 days and less than 3 months from symptom onset. Although endovascular procedures are the preferred treatment choice for a viable and not immediately threatened limb in patients with acute lower limb ischemia (<14 days), percutaneous catheter-directed thrombolysis, percutaneous mechanical thrombectomy, or percutaneous thromboaspiration are not recommended, and no treatment strategy has yet been established for nonacute lower limb ischemia (>14 days). A percutaneous Fogarty thrombectomy, an endovascular thrombus removal procedure with the use of a large-caliber sheath and a Fogarty balloon catheter, has recently been reported as a less invasive alternative to open surgery in patients with acute lower limb ischemia. In this report, we use this technique for a case of subacute lower limb ischemia caused by a resistant thrombus. Case Report: A 73-year-old man with a diagnosis of essential thrombocythemia presented with symptoms of right lower limb ischemia, which started about a month before. The diagnosis was subacute lower limb ischemia due to a resistant thrombus in the popliteal artery. First, we attempted percutaneous thromboaspiration and prolonged dilation with a large-caliber balloon catheter, but there were still severe residual stenoses with delayed blood flow. Although vascular scaffold implantation might have achieved complete revascularization, we avoided it because of a high probability of stent fracture in the popliteal artery. Thus, we performed a subsequent percutaneous Fogarty thrombectomy immediately after the conventional endovascular recanalization failed, achieving complete revascularization and next-day discharge without any complications. Conclusions: A percutaneous Fogarty thrombectomy could be a new treatment option for subacute lower limb ischemia due to a resistant thrombus, which can be performed immediately after failure of the conventional endovascular recanalization. [ABSTRACT FROM AUTHOR]

Catechol-estrogens can cause genetic mutations and to counteract their oncogenicity, the catechol-O-methyltransferase (COMT) gene is capable of neutralizing these reactive compounds. In this study, we determined the functional effects and regulation of COMT in prostate cancer. Both the Cancer Genome Atlas (TCGA) and immunohistochemical analysis of clinical specimens demonstrated a reduction of COMT expression in prostate cancer. Also, western analyses of prostate cancer cell lines show COMT levels to be minimal in DuPro and DU145 and thus, these cells were used for further analyses. Re-expression of COMT led to suppressed migration ability (wound healing assay) and enhanced apoptosis (flow cytometric analyses), and when challenged with 4-hydroxyestradiol, a marked reduction of cell proliferation (MTT assay) was observed. Xenograft growth in athymic mice also resulted in inhibition due to COMT. As a mechanism, western analyses show cleaved CASP3 and BID were increased whereas XIAP and cIAP2 were reduced due to COMT. As COMT expression is low in prostate cancer, its regulation was determined. Databases identified several miRNAs capable of binding COMT and of these, miR-195 was observed to be increased in prostate cancer according to TCGA. Real-time PCR validated upregulation of miR-195 in clinical prostate cancer specimens as well as DuPro and DU145 and interestingly, luciferase reporter showed miR-195 capable of binding COMT and overexpressing miR-195 could reduce COMT in cells. These results demonstrate COMT to play a protective role by activating the apoptosis pathway and for miR-195 to regulate its expression. COMT may thus be a potential biomarker and gene of interest for therapeutic development for prostate cancer. [ABSTRACT FROM AUTHOR]

This study aimed to compare lower limb events associated with preplanned and finally selected treatment strategies-the validity and usefulness of the physician-chosen strategy were verified.We examined the data of 1003 patients in the registry of multicenter endovascular treatment for superficial femoral and popliteal artery disease study and prospectively enrolled patients who underwent endovascular treatment (EVT) of the femoropopliteal (FP) artery between February 2017 and June 2018 from 67 Japanese institutes. The outcome measures were major adverse limb events (MALE) and target vessel revascularization.The EVT strategies were classified into balloon angioplasty-alone (37.3%), primary stenting (26.7%), and provisional stenting (36.0%) groups. In the initial strategy analysis for the balloon angioplasty-alone, primary stenting, and provisional stenting groups, two-year rates of freedom from MALE (95% confidence interval) were 0.680 (0.620-0.732), 0.754 (0.688-0.808), and 0.798 (0.746-0.840), respectively. Additionally, the rate of MALE was significantly higher among patients in the balloon angioplasty-alone group than among those in the primary or provisional stenting groups in the initial strategy analysis (P = 0.007). Changes in treatment strategy were more frequent in the primary stenting group than in the other groups. Furthermore, the rate of MALE did not significantly differ among the three groups in the final strategy analysis (P = 0.56).Limb outcomes for the final applied strategy did not differ among the three strategies. Additionally, the physician's selection bias was mostly appropriate in the EVT of the FP artery.

Long non-coding RNA (lncRNA) plays an important role in the regulation of gene expression in normal and cancer cells. We previously discovered a novel tumor-suppressive lncRNA, DRAIC , in prostate cancer cells. Subsequent studies have demonstrated that DRAIC is dysregulated in various malignancies and exhibits a tumor-suppressive or pro-oncogenic function. However, details regarding its expression pattern in normal and cancerous tissues remain largely unknown. In this study, we performed chromogenic in situ hybridization (CISH) using RNAscope technology to assess DRAIC expression in formalin-fixed paraffin-embedded (FFPE) specimens. In the neuroendocrine-differentiated cancer cell line VMRC-LCD, CISH revealed a diffuse localization of DRAIC in the cytoplasm as well as specific accumulation in the nuclear compartment. DRAIC expression was comprehensively analyzed using tissue microarrays containing 89 normal and 155 tumor tissue samples. DRAIC was weakly expressed in normal epithelial cells of the colon, bronchiole, kidney, prostate, and testis. Conversely, DRAIC was moderately to highly expressed in some cancer tissues, including prostate adenocarcinoma, invasive ductal carcinoma of the breast, neuroendocrine carcinoma of the esophagus, lung adenocarcinoma, and small cell lung carcinoma. While DRAIC knockdown did not affect VMRC-LCD cellular viability and invasive ability, gene expression related to the neuroendocrine and cancer-related pathways was altered. Our expression analysis revealed the specific expression pattern of DRAIC in normal and cancerous FFPE tissues. The results presented here may lead to the elucidation of additional novel functions of DRAIC ., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background/aim: We aimed to evaluate the changes of androgen receptor (AR) signaling-related long non-coding RNAs (lncRNAs) in serum extracellular vesicles (EVs) from prostate cancer (PC) patients, in order to identify novel biomarkers for AR axis-targeted therapy (ARAT)-resistance among castration-resistant PC (CRPC) patients., Patients and Methods: EVs were isolated from 2 patients before and after acquiring ARAT-resistance. RNA profiling of EVs was performed by RNA-sequencing. The expression levels of selected lncRNAs in EVs were analyzed by digital droplet PCR (ddPCR) in 58 localized and 14 metastatic PC patients at diagnosis, 7 ARAT-naïve and 6 ARAT-resistant CRPC patients. LncRNA H19 expression in PC tissue was examined using published data. In order to analyze the role of H19, the prognosis was analyzed in PC patients and proteomic analysis was performed in 22Rv1 PC cells., Results: RNA-sequencing revealed that AR-regulated RNAs were most enriched in EVs after acquiring ARAT-resistance. Among them, up-regulation of AR signaling-related lncRNAs (PCAT1, H19, HOXA-11AS, ZEB1-AS1, ARLNC1, PART1, CTBP1-AS and PCA3) was confirmed by ddPCR. H19 contained in EVs (EV-H19) was significantly increased among ARAT-resistant patients compared to ARAT-naïve CRPC or metastatic PC patients. In PC tissue, H19 was negatively correlated with AR protein and AR-activity score and up-regulated in neuroendocrine CRPC tissue with low AR expression. Furthermore, EV-H19 expression was significantly associated with worse outcome to androgen-deprivation therapy. Proteomic analysis demonstrated that H19 knockdown enhanced PC-related protein expression., Conclusion: EV-H19 may negatively correlate with AR-signaling activity and could be a marker to diagnose ARAT-resistance among CRPC patients., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: There is a sex-dependent difference in blood retinol and RBP concentrations, and plasma RBP is associated with insulin resistance., Objectives: We aimed to clarify sex-dependent variations in body concentrations of retinol and RBPs and their association with sex hormones in rats., Methods: Plasma and liver retinol concentrations and hepatic mRNA and plasma concentrations of RBP4 were analyzed in 3- and 8-wk-old male and female Wistar rats before and after sexual maturity (experiment 1) and in orchiectomized male Wistar rats (experiment 2) and ovariectomized female Wistar rats (experiment 3). Furthermore, the mRNA and protein concentrations of RBP4 in adipose tissue were measured in ovariectomized female rats (experiment 3)., Results: There were no sex-dependent differences in liver retinyl palmitate and retinol concentrations; however, the plasma retinol concentration was significantly higher in male rats than that in female rats after sexual maturity. Furthermore, the plasma retinol concentrations did not differ between the ovariectomized or orchiectomized rats and the control rats. Plasma Rbp4 mRNA concentrations were higher in male rats than those in female rats but not in castrated and control rats, a change consistent with plasma retinol concentration. Plasma RBP4 concentrations were also higher in male rats than those in female rats; however, unlike liver Rbp4 gene expression, plasma RBP4 concentrations were 7-fold higher in the ovariectomized rats than those in the control rats. Moreover, the Rbp4 mRNA concentrations in inguinal white adipose tissue was significantly higher in the ovariectomized rats than those in the control rats and correlated with plasma RBP4 concentrations., Conclusions: Hepatic Rbp4 mRNA is higher in male rats through a sex hormone-independent mechanism, which may contribute to sex differences in blood retinol concentrations. Furthermore, ovariectomy leads to an increase in adipose tissue Rbp4 mRNA and blood RBP4 concentrations, which may contribute to insulin resistance in ovariectomized rats and postmenopausal women., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background/aim: Cancer cells with high anchorage independence can survive and proliferate in the absence of adhesion to the extracellular matrix. Under anchorage-independent conditions, cancer cells adhere to each other and form aggregates to overcome various stresses. In this study, we investigated the cytomorphology and gene expression signatures of oral cancer cell aggregates., Materials and Methods: Two oral cancer-derived cell lines, SAS and HSC-3 cells, were cultured in a low-attachment plate and their cytomorphologies were observed. The transcriptome between attached and detached SAS cells was examined using gene expression microarrays. Subsequently, gene enrichment analysis and Ingenuity Pathway Analysis were performed. Gene expression changes under attached, detached, and re-attached conditions were measured via RT-qPCR., Results: While SAS cells formed multiple round-shaped aggregates, HSC-3 cells, which had lower anchorage independence, did not form aggregates efficiently. Each SAS cell in the aggregate was linked by desmosomes and tight junctions. Comparative transcriptomic analysis revealed 1,698 differentially expressed genes (DEGs) between attached and detached SAS cells. The DEGs were associated with various functions and processes, including cell adhesion. Moreover, under the detached condition, the expression of some epithelial genes (DSC3, DSP, CLDN1 and OCLN) were up-regulated. The changes in both cytomorphology and epithelial gene expression under the detached condition overall returned to their original ones when cells re-attached., Conclusion: The results suggest specific cytomorphological and gene expression changes in oral cancer cell aggregates. Our findings provide insights into the mechanisms underlying anchorage-independent oral cancer cell aggregation and reveal previously unknown potential diagnostic and therapeutic molecules., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)