Search

Minimal residual disease of leukemia may reside in the bone marrow (BM) microenvironment and escape the effects of chemotherapeutic agents. This study investigated interactions between B cell precursor (BCP)-acute lymphoblastic leukemia (ALL) cells and BM mesenchymal stromal cells (BM-MSCs) in vitro. Five BCP-ALL cell lines established from pediatric patients and primary samples from a BCP-ALL patient were examined by flow cytometry and immunocytochemistry for expression of specific cell surface markers and cell adhesion proteins. The cell lines developed chemoresistance to commonly used anti-leukemic agents through adhesion to MSC-TERT cells in long-term culture. The change in chemosensitivity after adhering to BM-MSCs was associated with the expression of CD34, CD133, P-glycoprotein and BCRP/ABCG2, and downregulation of CD38. Similar phenotypic changes were observed in primary samples obtained by marrow aspiration or biopsy from a BCP-ALL patient. BM-MSC-adhering leukemia cells also showed deceleration of cell proliferation and expressed proteins in the Cadherin and Integrin pathways. These results suggest that BCP-ALL cells residing in the BM microenvironment may acquire chemoresistance by altering their phenotype to resemble that of cancer stem cells. Our results indicate that cell adhesion could be potentially targeted to improve the chemosensitivity of residual BCP-ALL cells in the BM microenvironment.

All-trans retinoic acid (ATRA) increases the sensitivity to unfolded protein response (UPR) in differentiating leukemic blasts. The downstream transcriptional factors of PERK, a major arm of UPR, regulates muscle differentiation. However, the role of growth arrest and DNA damage-inducible protein 34 (GADD34), one of the downstream factors of PERK, and the effects of ATRA on GADD34 expression in muscle remain unclear. In this study, we identified ATRA increased the GADD34 expression independent of the PERK signal in the gastrocnemius muscle of mice. ATRA up-regulated GADD34 expression through the transcriptional activation of it via inhibiting the interaction of homeobox Six1 and transcription co-repressor TLE3 with the MEF3-binding site on the GADD34 gene promoter in myoblasts. ATRA also inhibited the interaction of TTP, which induces mRNA degradation, with AU-rich element on GADD34 mRNA via p38 MAPK, resulting in the instability of GADD34 mRNA. Overexpressed GADD34 in myoblasts changes the type of myosin heavy chain in myotubes. These results suggest ATRA increases GADD34 expression via transcriptional and post-transcriptional regulation in myoblasts, which changes muscle fiber type in myotubes.

BACKGROUND Social awareness on cancer can be changed with cancer education and proper distribution of cancer information. This study addressed the current situation and historical change of children's perception of cancer. METHODS Questionnaire surveys were conducted among healthy school children aged 10 to 15 years in 2008 and 2018. Knowledge of cancer was questioned and compared with that of asthma, tuberculosis or measles. Furthermore, the children were asked their resources of health information. RESULTS The numbers of participants and collection rates were 438 and 63.9% in 2008, and 320 and 44.7% in 2018. Children's perception of cancer was significantly changed in the last decade. The proportion of respondents answering "cancer affects children" was changed from 78.3 to 89.5% (P=0.0001), "cancer is preventable", from 42.0 to 49.7% (P=0.0425) and "cancer is curable", from 52.4 to 66.0% (P=0.0003). Significantly more junior high school students answered that cancer is preventable than elementary school children in 2018 (55.9 vs. 42.7%, P=0.0028). The major resources of information on health were television, parents and books. The proportion of children choosing the Internet significantly increased from 15.3 to 47.8% (P

The practice of cancer diagnosis disclosure to children has been changed with the times. The regulations of clinical trials in the 2000s might change the practice in Japan. However, the perspective of this topic among children and adults has not been investigated in detail. We studied changes in the practice of information sharing with children with cancer at pediatric cancer centers and the perspective of cancer diagnosis disclosure to children among school children, their parents and pediatric oncologists in the last 20 years by comparing the results of questionnaire surveys conducted in 1998, 2008 and 2018. This study revealed that the performing rate has increased with the times, but the institutions actively performing for children aged 7–9 years were 36.4% even in the 2018 survey. More than 70% of children wished diagnosis disclosure if they suffer from cancer in the series of surveys, while the ratio of parents who tell cancer diagnosis to their children hovered at 34.5 to 53.7% (p

All-trans retinoic acid (ATRA) increases the sensitivity to unfolded protein response in differentiating leukemic blasts. The downstream transcriptional factor of PERK, a major arm of unfolded protein response, regulates muscle differentiation. However, the role of growth arrest and DNA damage-inducible protein 34 (GADD34), one of the downstream factors of PERK, and the effects of ATRA on GADD34 expression in muscle remain unclear. In this study, we identified ATRA increased the GADD34 expression independent of the PERK signal in the gastrocnemius muscle of mice. ATRA up-regulated GADD34 expression through the transcriptional activation of GADD34 gene via inhibiting the interaction of homeobox Six1 and transcription co-repressor TLE3 with the MEF3-binding site on the GADD34 gene promoter in skeletal muscle. ATRA also inhibited the interaction of TTP, which induces mRNA degradation, with AU-rich element on GADD34 mRNA via p-38 MAPK, resulting in the instability of GADD34 mRNA. Overexpressed GADD34 in C2C12 cells changes the type of myosin heavy chain in myotubes. These results suggest ATRA increases GADD34 expression via transcriptional and post-transcriptional regulation, which changes muscle fiber type.

Arthritis has been reported as an acute pattern, generally evanescent with oligoarthritis, mostly affecting knees and ankles in childhood systemic polyarteritis nodosa. However, chronic polyarthritis with morning stiffness mimicking juvenile idiopathic arthritis has not been reported. We describe the case of a 4-year old girl who had additive and chronic polyarthritis with edema, tenderness, pain on motion and morning stiffness for 2 months. After 45 days, she also presented painful subcutaneous nodules and erythematous-violaceous lesions in the extensor region of upper and lower limbs. She was admitted to university hospital due to high fever, malaise, myalgia, anorexia, loss of weight (1kg), painful skin lesions and severe functional disability. She was bedridden by chronic polyarthritis with limitation on motion. Systolic and diastolic blood pressures were greater than 95th percentile for height. Urine protein/creatinine ratio was 0.39g/day, and immunological tests were negative. Anti-streptolysin O was 1,687UI/mL. Skin biopsy revealed necrotizing vasculitis in medium- and small-sized vessels compatible with polyarteritis nodosa. Therefore, we had the diagnosis of systemic polyarteritis nodosa. Prednisone 2mg/kg/day was administered with complete resolution of skin lesions and arthritis, and improvement of proteinuria (0.26g/day) after 15 days. The diagnosis of childhood systemic polyarteritis nodosa should be considered for patients with chronic polyarthritis associated to cutaneous vasculitis triggered by streptococcal infection. RESUMO Na poliarterite nodosa sistemica pediatrica, a artrite caracteriza-se pelo padrao agudo, geralmente evanescente, com oligoartrite, e afeta principalmente joelhos e tornozelos. No entanto, a poliartrite cronica com rigidez matinal e simulando artrite idiopatica juvenil ainda nao foi relatada. Descrevemos o caso de uma menina de 4 anos que apresentou poliartrite cronica aditiva com edema, dor a palpacao e movimento, e rigidez matinal por 2 meses. Apos 45 dias, tambem apresentou nodulos subcutâneos dolorosos e lesoes eritemato-violaceas na regiao extensora dos membros superiores e inferiores. Foi internada no hospital universitario por conta de febre alta, mal-estar, mialgia, anorexia, perda de peso (1kg), lesoes de pele muito dolorosas e incapacidade funcional grave. Estava restrita ao leito devido a poliartrite cronica com limitacao do movimento. Pressoes sistolica e diastolica foram maiores que percentil 95 para altura. Relacao proteina/creatinina urinaria estava 0,39g/dia, e os testes imunologicos foram negativos. Antiestreptolisina O era 1.687UI/mL. A biopsia de pele revelou vasculite necrosante de vasos de pequeno e medio calibre, compativel com poliarterite nodosa. Portanto, foi realizado o diagnostico de poliarterite nodosa sistemica. Foi administrada prednisona 2mg/kg/dia com resolucao completa das lesoes de pele e da artrite, alem de melhora da proteinuria (0,26g/dia) apos 15 dias. O diagnostico de poliarterite nodosa sistemica pediatrica deve ser considerado em pacientes com poliartrite cronica associado a lesoes cutâneas vasculiticas, sendo a infeccao estreptococica um importante fator desencadeante.

The remote haptic collaboration system between operating and assistant surgeons causes both shift and step delays of force feedback, and then makes users feel coarse reaction forces and different hardness of the object. In this study, we propose a haptic interface protocol for finite-element-method based deformable objects, in order to achieve a high update rate of force calculation. The method exports the necessary information for calculation of reaction forces from the simulation loop to the haptic loop. The experimental results indicated that the proposed method improved the fineness of force feedback and subjective hardness significantly.