Ovariectomy Increases Circulating Retinol-Binding Protein Concentrations Independently of Sex-Dependent Differences in Retinol Concentrations in Rats.

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.

Molecular profiling of circulating tumor cells predicts clinical outcome in head and neck squamous cell carcinoma.

OBJECTIVES: The relationship between the molecular profiling of circulating tumor cells (CTCs) and clinical factors is a challenge. In this study, we performed molecular detection and characterization of CTCs in patients with head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: CTCs captured by microfilter were analyzed for the expression of multiple epithelial markers (EPCAM, MET, KRT19, and EGFR) by RT-qPCR. The CTCs-positive samples were further analyzed for the expression of 10 genes (PIK3CA, CCND1, SNAI1, VIM, CD44, NANOG, ALDH1A1, CD47, CD274, and PDCD1LG2). Finally, we analyzed whether the molecular profiling of CTCs was associated with clinical factors. RESULTS: Twenty-eight (63.6%) of the 44 HNSCC patients were positive for at least one epithelial-related gene. CTC-positivity was significantly correlated with treatment resistance (p = 0.0363), locoregional recurrence (p = 0.0151), and a shorter progression-free survival (PFS) (p = 0.0107). Moreover, the expression of MET in CTCs was associated with a shorter PFS (p = 0.0426). Notably, patients with CD274-positive CTC showed prolonged PFS (p = 0.0346) and overall survival (p = 0.0378) compared to those with CD274-negative CTC. CONCLUSION: Our results suggest that molecular profiling characterized by the gene expression of CTCs influences clinical factors in patients with HNSCC.

Expression of immune-regulatory molecules in circulating tumor cells derived from patients with head and neck squamous cell carcinoma.

OBJECTIVES: Circulating tumor cells (CTCs) are cells that have shed from tumor tissue into the bloodstream, and the detection and characterization of CTCs in head and neck squamous cell carcinoma (HNSCC) still remain a challenge. MATERIALS AND METHODS: CTCs were isolated from 30 patients with HNSCC with recurrent and/or distant metastasis, via the depletion of CD45-positive cells with magnetic beads and the expression of multiple epithelial markers (CK19, EpCAM, EGFR, and c-Met) was analyzed by RT-qPCR with a low concentration of RNA from the CTC population. We next investigated the expression of the immune-regulatory molecules, PD-L1, PD-L2, and CD47, in CTC-positive patients and the PD-L1 expression in CTCs was compared with that in tumor tissues. RESULTS: Twenty-four (80.0%) of the 30 patients were positive for at least one epithelial-related gene. Among the 24 CTC-positive patients, 19 (79.2%), 20 (83.3%), and 17 (70.8%) patients were positive for CD47, PD-L1, and PD-L2, respectively. Interestingly, the expression of these three immune-regulatory molecules was positively correlated to each other. As expected, PD-L1 expression in the tumor tissue did not correspond completely with that in the CTCs. CONCLUSION: Although clinical application and/or characterization of CTCs are still developing, our findings suggest that the CTCs are rapidly becoming a powerful tool in cancer treatments that involve the use of immune checkpoint inhibitors.

Impact of a Multidisciplinary Round Visit for the Management of Dysphagia Utilizing a Wi-Fi-Based Wireless Flexible Endoscopic Evaluation of Swallowing.

OBJECTIVES: The management of dysphagia requires a multidisciplinary approach, especially in large-scale hospitals. We introduce a novel protocol using a Wi-Fi-based flexible endoscopic evaluation of swallowing (FEES) system and aim to verify its effectiveness in evaluation and rehabilitation of inpatients with dysphagia. METHOD: We conducted novel Wi-Fi-based FEES at the bedside using 3 iPads as monitors and recorders. Functional outcomes of swallowing in 2 different hospitals for acute care with conventional wired or wireless FEES were compared retrospectively. RESULTS: Using the wireless system, we could visit more patients in a short period of time. Furthermore, a large multidisciplinary team was able to be present at the bedside, which made it easy to hold discussions and rapidly devise appropriate rehabilitation strategies. Aspiration pneumonia recurred in a few cases following our intervention with wireless FEES. Functional oral intake score was significantly increased following the intervention. Moreover, the number of deaths during hospitalization using wireless FEES evaluation was lower than those observed using the conventional system. CONCLUSION: Wi-Fi-based wireless FEES system, the first of its kind, allowed our multidisciplinary team to easily and effectively assess inpatients with dysphagia by facilitating simple examinations and intensive transprofessional discussions for patient rehabilitation.

(18)F-FDG uptake on PET correlates with biological potential in early oral squamous cell carcinoma.

CONCLUSION: The maximum standardized uptake value (SUVmax) of early oral squamous cell carcinoma (OSCC) may have a role as an imaging biomarker for assessment of malignant potential, including cell metabolism and angiogenesis. OBJECTIVE: The usefulness of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been proven in various cancers, including OSCC. Moreover, in several carcinomas, the SUVmax of the tumor has been shown to correlate with the histological type, tumor stage, differentiation, and prognosis. Here, we investigated whether the SUVmax of early OSCC was associated with the biological features. METHODS: Twenty-seven patients with newly diagnosed early OSCC who underwent preoperative FDG-PET and curative surgical resection were included in this study. Tumor sections were stained by immunohistochemistry for glucose transporter 1 (GLUT1), L-type amino acid transporter 1 (LAT1), CD98, microvessels (CD34), cell proliferation marker (Ki-67), and cell cycle regulator (p53). The correlation between SUVmax and clinicopathological findings or the expression level of these molecules was analyzed. RESULTS: SUVmax of primary OSCC was significantly higher in patients with T2 stage. Moreover, patients whose tumors showed vascular invasion had a tendency to show higher SUVmax. A significant correlation was observed between SUVmax and the expression of LAT1 or microvessel density.