Background: I (the first author) studied DNA methylation in cancer at Johns Hopkins University from December 2013 to July 2016. In this review, we introduce our DNA methylation study in gastric cancer.
Across a diverse spectrum of solid malignancies, Checkpoint with Forkhead and Ring Finger Domains (CHFR) is most frequently inactivated by promoter CpG island methylation and has shown to be a marker of poor prognosis and increased sensitivity to treatment with taxanes. We retrospectively investigated CHFR promoter methylation in gastric cancer as a method for isolating those patients who would derive the most benefit from taxane-based regimens and as an indicator of prognosis.
Materials and Methods: One hundred thirty-six formalin-fixed paraffin-embedded (FFPE) primary tumor samples were collected from patients with gastric cancer who underwent surgery with curative intent at the Juntendo University Shizuoka Hospital between 2005 and 2012. We employed Quantitative Methylation-Specific PCR (qMSP) with bisulfite-modified DNA as a template for fluorescence-based real time PCR. We categorized patients into two groups: the low group (CHFR-relative methylation value (RMV) <10.3%) and the high group (CHFR-RMV ≥10.3%) based on Akaike’s information criteria (AIC).
Results: CHFR-RMVs in cancer tissues were significantly higher than those in normal-appearing adjacent non-cancerous tissues (p=0.0001). The cancer-specific survival among the patients in the high group was significantly worse than that among the patients in the low group (p=0.002).
Conclusions: CHFR promoter methylation is an independent prognostic marker of poor prognosis in gastric cancer.
Sports medicine originates from Europe, and Japan is a developing country in this field. YS experienced medical support as a team physician, both in Japan and Europe. Several differences were observed between sports medicine in Europe and Japan. Firstly, the background of team physicians is different; team physicians in Japan are orthopedists, while they are sports physicians in Europe. Secondly, sports participants have to do periodic health evaluations before they start sports, even at amateur levels, but this is voluntary in Japan. Thirdly, surveillance of injuries and illnesses and injury prevention strategies are well-developed in Europe compared to Japan. Lastly, emergency systems are more advanced in Europe than Japan. Here, we describe these differences based on personal experience and a review of the literature.
Background: Mutations in the recessive genes PINK1 and PARKIN are the most common causes of early-onset Parkinson’s disease (PD). The mitochondrial ubiquitin (Ub) kinase PINK1 mediates, together with the cytosolic E3 Ub ligase PARKIN, mitochondrial quality control. Thereby, damaged mitochondria are identified to prevent their accumulation and eventually cell death. A detailed understanding of PINK1 mutations will help to further our understanding of PD.
Objective: The aim of this study was to examine the exact molecular pathogenic mechanisms of PINK1 p.I368N.
Methods: We investigated molecular mechanisms on the structural and functional level in patients’ fibroblasts and in cell-based, biochemical assays.
Results: Under endogenous conditions, PINK1 p.I368N is expressed, imported in healthy mitochondria similar to PINK1 wild type. Upon mitochondrial damage, however, full-length PINK1 p.I368N is unstable on the outer mitochondrial membrane and consequently mitochondrial quality control declines. We found that stress-induced interaction between PINK1 p.I368N and TOM40 of the mitochondrial protein import machinery is abolished. Analysis of a structural PINK1 p.I368N model additionally suggested impairments of Ub kinase activity. We further confirmed experimentally that the kinase activity of the PINK1 p.I368N mutant is abolished.
Conclusions: We revealed two mechanisms that lead to loss of function of PINK1 upon mutation.
Minimally invasive surgery in children has evolved to the extent that complex procedures can be performed with safety, with comparable outcomes to open surgery and with the advantages of minimal postoperative scarring and lesser pain. In this article, we describe the latest thoracoscopic and laparoscopic techniques used at Juntendo University Hospital, for treating patients with advanced surgery, focusing on esophageal atresia with tracheoesophageal fistula and biliary atresia.
Excretory organs were acquired in the early phase of metazoan evolution, and they play a crucial role in the maintenance of homeostasis of body fluids. In general, these organs consist of two functional components, the primary-urine producing apparatus and the modulating tubule. This basic organization of the excretory organs is conserved among most of the metazoans. Herein, we present an overview of the morphological evolution of the primary urine-producing apparatus in metazoans and describe the acquisition of renal glomerulus, a specialized primary urine-producing apparatus, in vertebrates. We also describe the advancement of the glomerular structure and function in higher vertebrates.
Objective: The clinical manifestations of skin and soft tissue infections, including facial and non-facial cellulitis, have not yet been characterized in detail in children. The purpose of the present study was to elucidate the clinical manifestations of skin and soft tissue infections in children with facial and non-facial cellulitis.
Materials and Methods: This retrospective study reviewed the management of children with skin and soft tissue infections, including cellulitis, who were admitted to Sagamihara Kyodo Hospital between January 2001 and December 2013. Exclusion criteria were patients with immunosuppression, surgical site infections, and missing medical records.
Results: Data from twenty patients (10 males and 10 females) in the facial group and 25 (16 males and 9 females) in the non-facial group were analyzed. No significant differences were observed in the median age (interquartile range) at admission between the groups: 3.9 years (1.6-7.7 years) and 4.2 years (0.9-7.9 years) in the facial and non-facial groups, respectively. In the facial group, most patients were admitted between October and April (85%), whereas those in the non-facial group were mainly admitted between April and August (72%). No significant differences were observed in blood examination findings between the groups. Pus cultures were performed on discharges collected using needle aspiration in 14 patients. Methicillin-sensitive Staphylococcus aureus (MSSA) was isolated from 7 patients and Streptococcus pyogenes and coagulase-negative staphylococci from 2 patients. Penicillin-sensitive S. pneumoniae was isolated from 1 out of 24 patients (4%) for whom blood cultures were performed.
Conclusions: These results suggest seasonal differences in admissions, but minimal differences in clinical manifestations between the groups.
Objective: To assess the efficacy of preoperative chemoradiation therapy (CRT) for clinical T4 (cT4) esophageal cancer.
Materials and Methods: From November 1998 to November 2008, 57 patients with cT4 esophageal cancer (any N) without distant metastases underwent preoperative CRT. All but 2 patients received a total dose of 40 Gy administered in 20 fractions over 4 weeks. Eleven patients received 5-fluorouracil and cisplatin, and 46 were treated with docetaxel. All patients underwent reassessment of their response to CRT 1 month after completion of treatment. Surgery was performed within 4 to 6 weeks of completing CRT if the tumor was diagnosed as operable.
Results: One patient discontinued preoperative treatment at 30.6 Gy, and four stopped planned chemotherapy. One patient developed grade 4 thrombocytopenia, and six developed grade 3 leukocytopenia. One patient developed a grade 3 esophagobronchial fistula. Of the 57 patients, 36 (63%) were diagnosed with operable tumors and underwent curative intent surgery. A complete pathological response (grade 3, Japanese Classification of Esophageal Cancer The 11th edition) was achieved in 3 patients. The other responses were grade 2 (The number of proliferating cells is 1/3 or less) in 16 patients, grade 1a (Proliferable cells are 2/3 or more) in 6, grade 1b (Proliferable cells are 1/3 or more and less than 2/3) in 10, and unknown in 1. The 2-year overall survival rate was 21%. The 2-year survival rates for the curative intent surgery group and the inoperable group were 46% and 0%, respectively. In the surgery group, there was no significant difference in overall survival between patients who underwent R0 (no residual tumor) resection and those who underwent R1 (microscopic residual tumor) or R2 (macroscopic residual tumor) resection.
Conclusion: Preoperative CRT for cT4 esophageal cancer was relatively safe but did not improve overall survival (OS) compared to treatment solely with CRT.
The Tropical Medicine Association of Juntendo University (TMAJU) is a student group of Juntendo University founded by many of medical students (Youji Ono, Tadamitu Yamazaki, Mikio Mori et al.) including chief executive officer (CEO) of Juntendo University, Prof. Hideoki Ogawa, nearly 60 years ago. We have been active in learning about tropical medicine abroad every year through our study abroad programs, gaining friends in many countries in the South East Asia area. Over a 12-day period from March 18-29, 2017, the TMAJU sent their 53 rd South East Asia research team to learn about medicine in Thailand and Singapore. Ten students in their second to fifth years of university were accompanied by professors from Juntendo and studied the valuable experience of learning about foreign healthcare systems. We hope this experience will inspire future members of TMAJU on their next trip in March 2018.
The prevalence of childhood obesity has risen over the last three decades and has become worldwide public health problem. Childhood obesity causes a range of complications including the risk of adulthood obesity and obesity-related chronic diseases that lead to premature death. South-Asian countries (India, Sri-Lanka, Pakistan and Bangladesh) have high rates of childhood obesity, despite the continuing high level of under-nutrition. The co-occurrence of nutrition transition and obesity in these middle and low-income countries presents unique challenges. This systemic review presents a summary of published research on the causes and effective prevention strategies in South Asian countries. We searched for published studies in Pub Med, Google scholar and the Cochrane Library. We also reviewed the reference lists of published studies. Thirteen studies met the inclusion criteria. The selected studies considered childhood obesity complications, and risk factors, including energy-rich and nutrition-poor foods were identified as key factors influencing rapid weight gain in children. Some articles focused on prevention and weight reduction strategies. Childhood obesity is a crucial issue and to overcome, changing in dietary habits, nutrition policies are needed along with physical interventions. Regular physical activities and nutritional interventions can be maintained through home or school.