Cancer Phenotype Diagnosis and Drug Efficacy within Japanese Health Care

An overview on targeted personalized medicine is given describing the developments in Japan of lung cancer patients. These new targeted therapies with novel personalized medicine drugs require new implementations, in order to follow and monitor drug efficacy and outcome. Examples from IRESSA (Gefitinib) and TARCEVA (Erlotinib) treatments used in medication of lung cancer patients are presented. Lung cancer is one of the most common causes of cancer mortality in the world. The importance of both the quantification of disease progression, where diagnostic-related biomarkers are being implemented, in addition to the actual measurement of disease-specific mechanisms relating to pathway signalling activation of disease-progressive protein targets is summarised. An outline is also presented, describing changes and adaptations in Japan, meeting the rising costs and challenges. Today, urgent implementation of programs to address these needs has led to a rebuilding of the entire approach of medical evaluation and clinical care

Annual change in bone mineral density in COPD

Background: Osteoporosis is a well-known comorbidity in COPD. It is associated with poor health status and prognosis. Although the exact pathomechanisms are unclear, osteoporosis is suggested to be either a comorbidity due to shared risk factors with COPD or a systematic effect of COPD with a cause–effect relationship. This study aimed to evaluate whether progression of osteoporosis is synchronized with that of COPD. Materials and methods: Data from 103 patients with COPD included in the Hokkaido COPD cohort study were analyzed. Computed tomography (CT) attenuation values of thoracic vertebrae 4, 7, and 10 were measured using custom software, and the average value (average bone density; ABD4,7,10) was calculated. The percentage of low attenuation volume (LAV%) for each patient was also calculated for evaluation of emphysematous lesions. Annual change in thoracic vertebral CT attenuation, which is strongly correlated with dual-energy X-ray absorptiometry-measured bone mineral density, was compared with that in FEV1.0 or emphysematous lesions. Results: In the first CT data set, ABD4,7,10 was significantly correlated with age (ρ=–0.331; p=0.0006), body mass index (BMI; ρ=0.246; p=0.0136), St George’s Respiratory Questionnaire (SGRQ) activity score (ρ=–0.248; p=0.0115), eosinophil count (ρ=0.229; p=0.0198), and LAV% (ρ=–0.372; p=0.0001). However, ABD4,7,10 was not associated with FEV1.0. After adjustment for age, BMI, SGRQ activity score, and eosinophil count, no significant relationship was found between ABD4,7,10 and LAV%. Annual change in ABD4,7,10 was not associated with annual change in LAV% or FEV1.0. Conclusion: Progression of osteoporosis and that of COPD are not directly related or synchronized with each other

Bronchiolar chemokine expression is different after single versus repeated cigarette smoke exposure

<p>Abstract</p> <p>Background</p> <p>Bronchioles are critical zones in cigarette smoke (CS)-induced lung inflammation. However, there have been few studies on the <it>in vivo </it>dynamics of cytokine gene expression in bronchiolar epithelial cells in response to CS.</p> <p>Methods</p> <p>We subjected C57BL/6J mice to CS (whole body exposure, 90 min/day) for various periods, and used laser capture microdissection to isolate bronchiolar epithelial cells for analysis of mRNA by quantitative reverse transcription-polymerase chain reaction.</p> <p>Results</p> <p>We detected enhanced expression of keratinocyte-derived chemokine (KC), macrophage inflammatory protein-2 (MIP-2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) by bronchial epithelial cells after 10 consecutive days of CS exposure. This was mirrored by increases in neutrophils and KC, MIP-2, TNF-α, and IL-1β proteins in the bronchoalveolar lavage (BAL) fluid. The initial inhalation of CS resulted in rapid and robust upregulation of KC and MIP-2 with concomitant DNA oxidation within 1 hr, followed by a return to control values within 3 hrs. In contrast, after CS exposure for 10 days, this initial surge was not observed. As the CS exposure was extended to 4, 12, 18 and 24 weeks, the bronchiolar KC and MIP-2 expression and their levels in BAL fluid were relatively dampened compared to those at 10 days. However, neutrophils in BAL fluid continuously increased up to 24 weeks, suggesting that neutrophil accumulation as a result of long-term CS exposure became independent of KC and MIP-2.</p> <p>Conclusion</p> <p>These findings indicate variable patterns of bronchiolar epithelial cytokine expression depending on the duration of CS exposure, and that complex mechanisms govern bronchiolar molecular dynamics <it>in vivo</it>.</p

Propulsive Performance and Heating Environment of Rotating Detonation Engine with Various Nozzles

Geometric throats are commonly applied to rocket combustors to increase pressure and specific impulse. This paper presents the results from thrust measurements of an ethylene/gas-oxygen rotating detonation engine with various throat geometries in a vacuum chamber to simulate varied backpressure conditions in a range of 1.1–104 kPa. For the throatless case, the detonation channel area was regarded to be equivalent the throat area, and three throat-contraction ratios were tested: 1, 2.5, and 8. Results revealed that combustor pressure was approximately proportional to equivalent throat mass flux for all test cases. Specific impulse was measured for a wide range of pressure ratios, defined as the ratio of the combustor pressure to the backpressure in the vacuum chamber. The rotating detonation engine could achieve almost the same level of optimum specific impulse for each backpressure, whether or not flow was squeezed by a geometric throat. In addition, heat-flux measurements using heat-resistant material are summarized. Temporally and spatially averaged heat flux in the engine were roughly proportional to channel mass flux. Heat-resistant material wall compatibility with two injector shapes of doublet and triplet injection is also discussed

Immunological functions of adult T cell leukemia cells of a patient complicated with synchronous double primary gynecologic cancer

A patient with triple malignancies is reported, who presented cervical cancer, vulvar cancer and adult T cell leukemia (ATL). ATL was diagnosed as a smouldering type, because antibody to human T cell leukemia virus associated antigen (ATLA) was positive with a titer of 1 : 160. Although her malignant cells had an OKT 4+8-3+Tac+ phenotype, the cells did not display helper T cell functions. Namely they showed no response to Phytohemagglutinin (PHA) and Interleukin 2 (IL-2) and suppressed the PWM driven IgG synthesis of B cells obtained from healthy donor. They did not produce IL-2 by stimulation with PHA and phorbol myristate acetate (PMA). Furthermore, these ATL cells were producing IL-2 inhibitor like factors. As synchronous triple malignancies are extremely rare, two gynecologic cancers seem to ascribe to the suppressing state of the immunosurveillance mechanism by viral infection