Optimized protocol to derive germline stem-cell-like cells from mouse pluripotent stem cells

Male germ-cell development comprises primordial germ-cell (PGC) development, spermatogonium differentiation, and ensuing spermatogenesis. We present a step-by-step protocol for differentiation of mouse pluripotent stem cells (PSCs) into germline stem-cell-like cells (GSCLCs) via PGC-like cell and spermatogonium-like cell intermediates. The differentiation protocol has higher fidelity than our previous protocol. Upon transplantation into testes in vivo or culture for testis transplants, GSCLCs robustly contribute to spermatogenesis, providing a paradigm for PSC-based reconstitution of mammalian male germ-cell development

Pathophysiology of Tumor Neovascularization

Neovascularization is essential to the process of development and differentiation of tissues in the vertebrate embryo, and is also involved in a wide variety of physiological and pathological conditions in adults, including wound repair, metabolic diseases, inflammation, cardiovascular disorders, and tumor progression. Thanks to cumulative studies on vasculature, new therapeutic approaches have been opened for us to some life-threatening diseases by controlling angiogenesis in the affected organs. In cancer therapy, for example, modulation of factors responsible for tumor angiogenesis may be beneficial in inhibiting of tumor progression. Several antiangiogenic approaches are currently under preclinical trial. However, the mechanisms of neovascularization in tumors are complicated and each tumor shows unique features in its vasculature, depending on tissue specificity, angiogenic micromilieu, grades and stages, host immunity, and so on. For better understanding and effective therapeutic approaches, it is important to clarify both the general mechanism of angiogenic events and the disease-specific mechanism of neovascularization. This review discusses the general features of angiogenesis under physiological and pathological conditions, mainly in tumor progression. In addition, recent topics such as contribution of the endothelial progenitor cells, tumor vasculogenic mimicry, markers for tumor-derived endothelial cells and pericytes, and angiogenic/angiostatic chemokines are summarized

Advanced moderately differentiated neuroendocrine carcinoma of the rectum with favorable prognosis by postoperative chemoradiation

Rectal neuroendocrine carcinoma is rare with poor prognosis. We report herein a case of advanced moderately differentiated neuroendocrine carcinoma of the rectum with relatively favorable prognosis treated by postoperative adjuvant chemoradiation therapy. A 58-year-old Japanese female was referred and colonofiberscopy revealed an easy-bleeding irregular tumor in the lower rectum, which was pathologically diagnosed as a neuroendocrine carcinoma. Surgical treatment consisted of abdominoperineal resection and lymph node dissection. The tumor invaded deeply into perirectal tissues, and 9 of 11 lymph node metastases were observed. Immunohistochemically, chromogranin A showed diffuse and strong staining, and the MIB-1 labeling index was 18.3 ± 5.6, supporting the high proliferation of the tumor. Some nucleus of the tumor showed positive staining for p21/WAF1. A total dose of 46 Gy of radiotherapy was delivered with 800 mg of daily oral doxifluridine. At 5 years post-surgery, the patient demonstrated no clinical evidence of intrapelvic recurrence or distant metastases

Impact of pre-Treatment C-reactive protein level and skeletal muscle mass on outcomes after stereotactic body radiotherapy for T1N0M0 non-small cell lung cancer: A supplementary analysis of the Japan Clinical Oncology Group study JCOG0403

This study aimed to evaluate the impact of pretreatment C-reactive protein (CRP) and skeletal muscle mass (SMM) on outcomes after stereotactic body radiotherapy (SBRT) for T1N0M0 non-small cell lung cancer (NSCLC) as a supplementary analysis of JCOG0403. Patients were divided into high and low CRP groups with a threshold value of 0.3 mg/dL. The paraspinous musculature area at the level of the 12th thoracic vertebra was measured on simulation computed tomography (CT). When the area was lower than the sex-specific median, the patient was classified into the low SMM group. Toxicities, overall survival (OS) and cumulative incidence of cause-specific death were compared between the groups. Sixty operable and 92 inoperable patients were included. In the operable cohort, OS significantly differed between the CRP groups (log-rank test p = 0.009; 58.8% and 83.6% at three years for high and low CRP, respectively). This difference in OS was mainly attributed to the difference in lung cancer deaths (Gray’s test p = 0.070; 29.4% and 7.1% at three years, respectively). No impact of SMM on OS was observed. The incidence of Grade 3–4 toxicities tended to be higher in the low SMM group (16.7% vs 0%, Fisher’s exact test p = 0.052). In the inoperable cohort, no significant impact on OS was observed for either CRP or SMM. The toxicity incidence was also not different between the CRP and SMM groups. The present study suggests that pretreatment CRP level may provide prognostic information in operable patients receiving SBRT for early-stage NSCLC

The Administration of Xultophy for Diabetic Patients on Hemodialysis

Background: Recent diabetic treatments include Insulin Degludec/ liraglutide (IDeg/Lira, Xultophy) in clinical practice. Authors have continued clinical research concerning diabetes, chronic renal failure, dialysis, and others. Subjects and Methods: Ten patients with type 2 diabetes mellitus (T2DM) undergoing hemodialysis were investigated. They showed that ages 74.5 ± 5.9 years, M/F=6/4, BMI 21.1± 3.8kg/m2, hemodialysis duration 8.1 ± 5.7 years. At the beginning, fundamental data were Cre 8.2 ± 1.9 mg/dL, HbA1c 6.5 ± 0.8%. Xultophy was started on 5-12 doses and continued for 6 months with the same or 1-4 increased doses for better glycemic variability. Results: Out of 10 subjects, the changes in HbA1c showed a decrease in 7, stable in 2, and an increase in 1. HbA1c value was 6.2 ± 0.8% in average at 6 months. There were no remarkable adverse effects by Xultophy for 6 months. Discussion and Conclusion: Xultophy was started at 5-12 doses, which were remarkably lower doses than usual doses with satisfactory efficacy. One of the reasons may be from the characteristic of the patients, who were diabetic with undergoing hemodialysis. Another factor is possibly from liraglutide, which has hepatic clearance with potential vascular protective effects. These results are expected to become reference data for future research

Carnitine for Body Composition in Hemodialysis Patients

Background: Authors and colleagues have continued clinical research for hemodialysis patients. Currently, a pilot study presents intervention of carnitine for changes of the body composition. Subjects and Methods: Subjects were six patients on hemodialysis with intervention of carnitine (group 1). Average data were 74.3 years, 65.4 kg, 22.6 in BMI. As levocarnitine, L-Cartin FF injection 1000 mg was administered three times a week for six months. Group 2 has six control patients for age-, sex-, body weight, BMI-matched (group 2). Body composition of muscle and fat tissues were measured by InBody 770 on 0 and 6 months. Results: In group 1, muscle volume and skeletal muscle showed increasing tendency without statistical significance. In contrast, there were significant decreases of body fat volume (22.3 kg vs 20.5 kg, 39.0% vs 35.8%) (p<0.05). No significant differences were found in hemoglobin, total protein, albumin and Cardio-Thoracic Ratio (CTR) of chest X-ray. Group 2 showed no significant changes. Discussion and Conclusion: Hemodialysis patients often have muscular reduction. Previous reports showed improved lean body mass by carnitine administration, which may support our result. These results from current pilot study would be expected to become useful reference data in the pathophysiological investigation in patients on hemodialysis

ホウシャセン チリョウ ガ コウカテキ デ アッタ チョクチョウナイ ブンピツ サイボウ ガン ノ 1 レイ

A 54-year-old woman was seen at the hospital because of anal bleeding. Colonoscopy examination showed a type 2 tumor in the lower rectum and the histological diagnosis from the biopsy specimen was undifferenciated adenocarcinoma. Abdomino-perineal amputation of the rectum were performed. The resected specimen was positive for synaptophysin stain immunohistochemically and we diagnosed it as an endocrine cell carcinoma. We underwent adjuvant chemotherapy by bolus CPT-11, and the post operative course was uneventful. Intra-pelvic recurrence was observed 15 months after operation, and further 4 months later, metastasis developed around the pancreas. And we noticed the tumor in supraclavicular region 21 months after operation. The tumor was sensitive to chemotherapy, but continued to progress. So we underwent radiotherapy for each lesion. The lesion treated with radiotherapy were controlled until she died of cancer, 31 months after the operation. As a result of autopsy, an exellent effect of radiotherapy was confirmed

Effects of Metoclopramide Hydrochloride, a D2-Selective Dopamine Receptor Antagonist, on the Fast Oscillation of the Electrooculogram

Fast oscillation (FO) of an electrooculogram (EOG) was recorded in both eyes of 10 healthy volunteers before and after administration of metoclopramide hydrochloride (MTCL), a D2-selective dopamine receptor antagonist, paying particular attention to sex concerning sensitivity to dopamine in young subjects. Healthy volunteers were divided into male and female groups; 5 males (10 eyes) aged 21 to 23 years (average, 21.8 years) and 5 females (10 eyes) aged 19 to 25 years (average, 21.8 years). As an FO parameter, the dfFO (the averaged difference in ?V between maximum amplitude in the dark period and minimum amplitude in the light period during FO measurement) was evaluated. The mean level of dfFO significantly increased between phase A (the initial 10 min before intravenous injection of 10 mg of MTCL) and phase B (10 min after the injection) in the male and female groups (P < 0.01 and P < 0.025) and between phase A and phase C (the additional 10 min after the injection) in both groups (P < 0.01 and P < 0.05). The mean level of dfFO in the female group was significantly higher than that of the male group in phase B (P < 0.05). As a control, the experimental procedure was performed with physiological saline administration, and no changes were observed. The data suggest that there exists some difference between young males and females generation concerning sensitivity to dopamine and that young females may show a higher-than-male sensitivity to dopamine in the occurrence of FO potential

キョウセン ヒテイケイテキ カルチノイド ノ 1セツジョレイ

Background. Thymic carcinoids are rare disease to account for ２-４％ of anterior mediastinal tumors. So, the clinicopathologic characters are not known enough. Case. A ６７ years old man was followed up old myocardial infarction, and he was taken chest CT scan for evaluate coronary artery. It revealed three anterior mediastinal tumors and we diagnosed thymoma by needle biopsy. We treated by neoadjuvant chemotherapy（CAMP therapy）, but it was ineffective. We performed thoracoscopic thymothymomectomy, and the pathological diagnosis was thymic atypical carcinoid. He is free of clinically event recurrence one year and a half after treatment. Conclusions. When we found an anterior mediastinal tumor, and if the clinical course is usually different, we should consider the possibility of a thymic carcinoid