Phase 3 Randomized Study Comparing Vadadustat with Darbepoetin Alfa for Anemia in Japanese Patients with Nondialysis-Dependent CKD

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Phase II Study of the EGFR-TKI Rechallenge With Afatinib in Patients With Advanced NSCLC Harboring Sensitive EGFR Mutation Without T790M: Okayama Lung Cancer Study Group Trial OLCSG 1403

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as first-line therapy for patients with EGFR-mutated non–small-cell lung cancer (NSCLC) have shown a significantly better objective response rate and progression-free survival than platinum doublet therapy. However, acquired resistance often occurs within 12 months. One of the potential strategies for treating acquired resistance in NSCLC is the readministration of EGFR-TKIs, a strategy that has mainly been evaluated using gefitinib or erlotinib. The aim of the present study is to investigate the efficacy and safety of EGFR-TKI readministration with afatinib in patients with advanced NSCLC harboring activating EGFR mutations without T790M. The primary endpoint is progression-free survival. The secondary endpoints include the objective response rate, disease control rate, overall survival, toxicity, and quality of life. A total of 12 patients will be enrolled in this trial.     

Long Survival of a Small-Cell Lung Cancer Patient Who Received Maintenance Chemotherapy with Irinotecan

Lung cancer is the leading cause of cancer-related death worldwide. Small-cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers. It is characterized by rapid tumor growth and early metastasis to multiple organs. Response to initial chemotherapy is generally good; however, the majority of patients develop recurrence and the prognosis of such patients is reportedly 2–4 months. Evolution of the treatment for SCLC has stagnated, and cisplatin + etoposide has been the standard chemotherapy for decades. Meanwhile, the combination of cisplatin + irinotecan has demonstrated equivalent efficacy to cisplatin + etoposide. Recently, maintenance chemotherapy has been extensively investigated in non-small-cell lung cancer (NSCLC), and is currently recommended as a standard treatment in clinical guidelines. On the contrary, a maintenance strategy has not been established for SCLC. Here, we describe an SCLC patient who received maintenance chemotherapy with irinotecan for more than 2 years after induction chemotherapy with cisplatin + irinotecan, and survived long term with no recurrence.Key Words: Small-cell lung cancer, Irinotecan, Maintenance, Long survivor, Extensive disease     

Sun exposure is an aggravating factor responsible for the recalcitrant facial erythema in adult patients with atopic dermatitis

BACKGROUND: In Japan, a considerable number of adult patients with atopic dermatitis suffer from recalcitrant facial erythema that resists common treatment with topical corticosteroids and antihistamines. OBJECTIVE: Our purpose was to investigate the potential role of sun exposure in the aggravation of these facial lesions. METHODS: The history of photoaggravation was taken from 74 adult patients with atopic dermatitis who suffered from recalcitrant facial erythema. Repeated UVB and UVA phototests were performed in 36 patients. Surface markers of infiltrating cells in UVB-provoked lesions were characterized immunohistochemically. RESULTS: Forty-one of 74 patients experienced an exacerbation of the facial lesions after sun exposure. UVB testing revealed an abnormal, papular response in 14 of 36 patients. All of the 14 patients complained of clinical aggravation after sun exposure. No abnormal reactions were observed at UVA testing. In UVB-provoked lesions, CD4+ cells were predominant to CD8+ cells. CONCLUSION: Exposure to UVB radiation may be responsible for the recalcitrant facial erythema in at least some of the patients with atopic dermatitis.     

The association of endothelial cell signaling,severity of illness,and organ dysfunction in sepsis

Introduction  

Previous reports suggest that endothelial activation is an important process in sepsis pathogenesis. We investigated the association between biomarkers of endothelial cell activation and sepsis severity, organ dysfunction sequential organ failure assessment (SOFA) score, and death.     

Dystrophin–glycoprotein complex: Its role in the molecular pathogenesis of muscular dystrophies

Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene, is associated with a large oligomeric complex of sarcolemmal glycoproteins, including dystroglycan which provides a linkage to the extracellular matrix component, laminin. In patients with DMD, the absence of dystrophin leads to the loss in all of the dystrophin-associated proteins, causing the disruption of the linkage between the subsarcolemmal cytoskeleton and the extracellular matrix. This may render the sarcolemma vulnerable to physical stress. These recent developments in the research concerning the function of the dystrophin–glycoprotein complex pave a way for the better understanding of the pathogenesis of muscular dystrophies. © 1994 John Wiley & Sons, Inc.     

Increased met-enkephalin plasma levels in hemodialysis patients with or without pruritus

Met-enkephalin plasma levels were measured in 21 hemodialysis patients with or without pruritus. The mean value was significantly increased in the total of the patients compared with that in ten healthy subjects. There was, however no correlation between met-enkephalin levels and the degree of pruritus. The findings suggest that the opioid system may be activated in this condition, although the relevance of this endogenous opioid peptide to pruritus remains to be determined.     

Longitudinal change in youth suicide mortality in Okinawa after World War II: A comparative study with mainland Japan

Abstract Okinawa prefecture has a unique socio-cultural status in Japan including the experience of having been occupied by the USA from the end of World War II to 1972. In this study, the longitudinal change in youth suicide mortality for those aged 10–29 years in Okinawa (1960–90) was compared with that for the same sex-age groups in mainland Japan (1950–90). In contrast with mainland Japan, no dramatic change in the youth suicide mortality was observed in Okinawa in the 1960s. The rise and fall of teenage suicide mortality in Okinawa during the 1970–80s might be associated with 'reversion anxiety', rather than with the traumatic experience of World War II itself. This seems to be inconsistent with previous speculation regarding the change in youth suicide mortality in mainland Japan. The suicide mortality for men aged 20–29 in Okinawa was significantly higher than that for the same sex-age group in mainland Japan through the observed period. The possible effects of the USA occupation, economic anomie or migration on the suicide in Okinawa should be further examined.     

Combined effect of cabozantinib and gefitinib in crizotinib‐resistant lung tumors harboring ROS1 fusions

The ROS1 tyrosine kinase inhibitor (TKI) crizotinib has shown dramatic effects in patients with non‐small cell lung cancer (NSCLC) harboring ROS1 fusion genes. However, patients inevitably develop resistance to this agent. Therefore, a new treatment strategy is required for lung tumors with ROS1 fusion genes. In the present study, lung cancer cell lines, HCC78 harboring SLC34A2‐ROS1 and ABC‐20 harboring CD74‐ROS1, were used as cell line‐based resistance models. Crizotinib‐resistant HCC78R cells were established from HCC78. We comprehensively screened the resistant cells using a phosphor‐receptor tyrosine kinase array and RNA sequence analysis by next‐generation sequencing. HCC78R cells showed upregulation of HB‐EGF and activation of epidermal growth factor receptor (EGFR) phosphorylation and the EGFR signaling pathway. Recombinant HB‐EGF or EGF rendered HCC78 cells or ABC‐20 cells resistant to crizotinib. RNA sequence analysis by next‐generation sequencing revealed the upregulation of AXL in HCC78R cells. HCC78R cells showed marked sensitivity to EGFR‐TKI or anti‐EGFR antibody treatment in vitro. Combinations of an AXL inhibitor, cabozantinib or gilteritinib, and an EGFR‐TKI were more effective against HCC78R cells than monotherapy with an EGFR‐TKI or AXL inhibitor. The combination of cabozantinib and gefitinib effectively inhibited the growth of HCC78R tumors in an in vivo xenograft model of NOG mice. The results of this study indicated that HB‐EGF/EGFR and AXL play roles in crizotinib resistance in lung cancers harboring ROS1 fusions. The combination of cabozantinib and EGFR‐TKI may represent a useful alternative treatment strategy for patients with advanced NSCLC harboring ROS1 fusion genes.