Progress in molecular-biological technologies has drastically advanced our understanding of tumor molecular biology. As a result, a number of driver genes that promote carcinogenesis have been isolated, and cancers in each organ can now be classified based on the types of driver genes. Furthermore, treatment strategies directed at the driver genes have been established. At present, more than 60 molecular-targeted drugs are already in use throughout the world in clinical settings, and more than 500 drugs against 100 molecular targets are currently under development. Secondary mutations causing tolerance to representative molecular-targeted drugs have also been identified by analyses of repeat biopsy specimens from resistant tumors, and second-line treatments, depending on the mutation profile, are being developed. Here, we provide an outline of the progress of personalized treatments for cancer.
Advanced non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths globally. Systemic chemotherapy using a platinum-based regimen improves overall survival of patients with advanced NSCLC. Furthermore, activating EGFR mutations and ALK fusions were identified, and these gene alterations are associated with favorable response to the tyrosine kinase inhibitors. Recently, many interests are focused on the immunotherapy for NSCLC patients. Herein, we describe cytotoxic chemotherapy, molecular targeted therapy, and immunotherapy for patients with advanced NSCLC.
In chemotherapy for colorectal cancer, the therapeutic effects of anti-epidermal growth factor receptor (EGFR) drugs can be predicted based on the RAS genetic type, while adverse events of irinotecan are predictable based on gene polymorphism of UGT1A1, an enzyme that metabolizes irinotecan. Such personalized medication based on the characteristics of each case of colorectal cancer is referred to as “tailor-made medicine”. This therapeutic approach is likely to improve the efficacy of treatment, decrease adverse events, improve safety, and reduce medical expenses.
I had decided on my life plan of research when I left for my new position (Juntendo University). I gradually became interested in functional sugar chains in the body because the functions of saccharides (particularly, sugar chains and oligosaccharides) had not been elucidated, being considered as just decorations. However, anti-inflammatory effects of glucosamine and chitosan had been described several decades earlier. I found a report on the anti-cancer effect of glucosamine on cancer tissue transplanted in mice in ‘Nature’, and this report gave me an opportunity to consider sugar function research. I repeatedly considered a new idea concerning glucosamine and animal lectin without telling anyone. If lectin existing in many animals and plants proved to be useful for this purpose, glucosamine would exhibit an anti-cancer effect, and the next target which came to my mind was the synthesis of a new sugar chain (galactoseβ1-4/6glucosamine, Galβ1-4/6GlcNH2).
Objective: This study was performed to investigate changes in bacteremia in children at Juntendo University Urayasu Hospital. Materials: A total of 10,487 blood culture specimens were examined from 3,916 children who were admitted to the Department of Pediatrics, Juntendo University Urayasu Hospital and underwent blood cultures from January 2006 to December 2014. Methods: Results for blood culture-positive children were compared before and after introduction of Haemophilus influenzae type b (Hib) vaccine (December 2008) and Streptococcus pneumoniae vaccine (February 2010), based on a retrospective analysis of a bacterial laboratory database. Results: A total of 94 patients had significant bacteria isolated from blood culture, giving a detection rate of 2.4%. Based on annual changes in the number of blood culture-positive patients aged 1 month or older, the number of Streptococcus pneumoniae-positive patients significantly decreased after 2010 and the number of Hib-positive patients reached a peak in 2008 and subsequently decreased. The major cause of fever without source in patients aged 1 month or older was Streptococcus pneumoniae until 2010, but subsequently changed to other bacteria that were unrelated to the vaccines. Conclusions: Introduction of Hib vaccine and Streptococcus pneumoniae vaccine significantly decreased both the number of cases of bacteremia in children and the incidence of invasive infections caused by Hib and Streptococcus pneumoniae. However, serotype replacement should be noted as a growing concern.
Objective: The aim of this study was to investigate the mechanism underlying the increase in intraventricular pressure difference (IVPD) during exercise. Background: Although left ventricular sucking force during early diastole plays an important role in exercise tolerance, the mechanism by which sucking force increases during exercise remains unclear. Methods: Twenty-two healthy men (age range, 22-37 years) underwent echocardiography at rest and while performing “supine bicycle” exercises that included four workload stages at 25 W, 50 W, 75 W, and 100 W. IVPD was calculated with a one-dimensional Euler equation using color Doppler M-mode data, and its relationship with ventricular wall motion patterns was assessed. Results: Peak IVPD observed at early diastole increased from 2.83±0.65 mmHg at rest to 5.31±0.78 mmHg at 100-W loading (p<0.001). Peak IVPD correlated positively with heart rate and cardiac output and negatively with isovolumic relaxation time and diastolic duration (p<0.001 for all). Only lengthening of circumferential strain during early diastole correlated with IVPD at rest (p=0.046). In all loading conditions, all deformation parameters except for left ventricular length strain significantly correlated with IVPD. Conclusions: IVPD plays an important role in generating diastolic sucking force to adjust to loading conditions during exercise. At rest, only circumferential dilatation generated a pressure gradient, but during exercise, torsional deformation also played an important role in causing IVPD. These results provide new insight into diastolic function during exercise.
Anomalous origin of the left coronary artery from the pulmonary artery is a rare disease that may result in occasionally even death during the early infant. We present a successfully treated case of an 8-month-old boy with concomitant severe left ventricular dysfunction. Treatment consisted of simple patch closure to the left coronary artery from inside the pulmonary artery to avoid long duration of cardiopulmonary bypass.
Acute undifferentiated leukemia (AUL) is a rare subset of acute leukemias, being included in the 2008 edition of the World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues as a special category called ‘acute leukemias of ambiguous lineage’, in which the leukemic cells express no more than one membrane marker of any given lineage. We report a rare case of therapy-related acute myeloid leukemia (AML), in which a strict myeloid marker myeloperoxidase (MPO) expression was confirmed by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis but not immunophenotyping. Although the diagnosis of AUL was initially considered, the lineage of leukemic cells was demonstrated by qRT-PCR analysis. Our observations suggest that molecular analysis of lineage markers may help to establish the diagnosis of acute leukemias.
Objective: A few students fail the medical practical examinations every year, due to a lack of practice and academic dishonesty. The present report analyzed practical examination scores received by male and female students, and investigated score differences between the sexes and possible underlying causes, to support development of improvement measures. Materials: The subjects were 351 second- (248 males and 103 females), 346 third- (248 males and 98 females), and 289 fourth- (197 males and 92 females) year students of the Juntendo University Faculty of Medicine as of 2011 to 2013. Methods: Students were assessed using their practical examination performance scores. Students’ grades were expressed as the mean accuracy rate, and the mean comprehensive score. The grades of the male and female students were compared and analyzed. Results: The rate of male students who failed the examination was higher in all school years. The mean accuracy rate and comprehensive score among female students in all school years were significantly higher compared with male students. Conclusions: Female students received higher scores on preclinical phase-practical examinations conducted by the university than male students, because some male students did not sufficiently practice prior to taking the tests. Therefore, as a future challenge, it will be necessary to establish stricter standards for advancement to the next grade, and to develop and implement education methods to increase the motivation of students whose behaviors are unprofessional.
We experienced 3 cases of living renal transplantation in our department since its initiation in April 2015. All three patients made favorable recoveries. Generally, the introduction of renal transplantation requires a specified period of preparation time, not only to meet institutional criteria but also to cooperate with other departments or other related units (e.g., clinical laboratory or pharmacy) and to educate other healthcare professionals. We received support from a variety of departments and units in the hospital, and we were able to prepare for the introduction of living renal transplantation in the short time of only 4 months.