Treatment with gefitinib after erlotinib-induced liver injury: a case report

INTRODUCTION: Gefitinib and erlotinib have minor differences in their chemical structures, and thus it remains unclear whether the hepatotoxicity induced by one compound is affected by the other. The case of a patient who developed erlotinib-induced liver injury and was then treated with gefitinib without hepatic toxicity or disease progression is presented. CASE PRESENTATION: A 31-year-old Japanese woman, who never smoked and who was diagnosed as having lung adenocarcinoma with carcinomatous meningitis, was treated with erlotinib. She developed erlotinib-induced liver injury after four weeks of treatment. The treatment was stopped right away, but the symptoms of meningitis re-appeared immediately. Gefitinib treatment was started and continued without recurrence of drug-induced liver injury. CONCLUSION: Gefitinib appears to be a potential treatment option after erlotinib-induced liver injury

Efficacy and safety of amrubicin hydrochloride for treatment of relapsed small cell lung cancer

Long-term survival is quite uncommon in refractory small cell lung cancer (SCLC) patients, with less than 25% of patients with limited-stage disease and 1%–2% of patients with extensive-stage disease remaining alive at five years. Recent clinical studies have demonstrated the promising efficacy of amrubicin for patients with relapsed SCLC. This review presents the results of clinical studies showing the efficacy and safety of amrubicin for the treatment of relapsed SCLC. Amrubicin is a synthetic anthracycline agent with a similar structure to doxorubicin, in which the hydroxyl group at position 9 in amrubicin is replaced by an amino group to enhance efficacy. It is converted to an active metabolite, amrubicinol, which is 5–54 times more active than amrubicin. Amrubicin and amrubicinol are inhibitors of DNA topoisomerase II, exerting their cytotoxic effects by stabilizing a topoisomerase II-mediated cleavable complex. The toxicity of amrubicin is similar to that of doxorubicin, although amrubicin shows almost no cardiotoxicity. In the relevant trials, amrubicin was administered intravenously at a dose of 35–40 mg/m2 on days 1–3 every three weeks. The response rate was 34%–52% and median survival times were 8.1–12.0 months. Common hematologic toxicities included neutropenia, leucopenia, anemia, thrombocytopenia, and febrile neutropenia. Nonhematologic adverse events included Grade 3–4 anorexia, asthenia, hyponatremia, and nausea. The results of the studies which demonstrated the efficacy of monotherapy for relapsed SCLC involved mainly Japanese patients. Therefore, it is necessary to conduct more clinical studies in non-Japanese patients to confirm the efficacy of amrubicin

ER stress response mechanisms in the pathogenic yeast Candida glabrata and their roles in virulence

The maintenance of endoplasmic reticulum (ER) homeostasis is critical for numerous aspects of cell physiology. Eukaryotic cells respond to the accumulation of misfolded proteins in the ER (ER stress) by activating the unfolded protein response (UPR), an intracellular signaling pathway that adjusts the folding capacity of the ER. Recent studies of several pathogenic fungi have revealed that the UPR is important for antifungal resistance and virulence; therefore, the pathway has attracted much attention as a potential therapeutic target. While the UPR is highly conserved among eukaryotes, our group recently discovered that the pathogenic yeast Candida glabrata lacks the typical fungal UPR, but possesses alternative mechanisms to cope with ER stress. This review summarizes how C. glabrata responds to ER stress and discusses the impacts of ER quality control systems on antifungal resistance and virulence

Leukotriene receptor antagonists pranlukast and montelukast for treating asthma

Introduction: The prevalence of bronchial asthma, which is a chronic inflammatory disorder of the airway, is increasing worldwide. Although inhaled corticosteroids (ICS) play a central role in the treatment of asthma, they cannot achieve good control for all asthmatics, and medications such as leukotriene receptor antagonists (LTRAs) with bronchodilatory and anti-inflammatory effects often serve as alternatives or add-on drugs. Areas covered: Clinical trials as well as basic studies of montelukast and pranlukast in animal models are ongoing. This review report clarifies the current status of these two LTRAs in the treatment of asthma and their future direction. Expert opinion: LTRAs could replace ICS as first-line medications for asthmatics who are refractory to ICS or cannot use inhalant devices. Further, LTRAs are recommended for asthmatics under specific circumstances that are closely associated with cysteinyl leukotrienes (cysLTs). Considering the low incidence of both severe adverse effects and the induction of tachyphylaxis, oral LTRAs should be more carefully considered for treating asthma in the clinical environment. Several issues such as predicted responses, effects of peripheral airway and airway remodeling and alternative administration routes remain to be clarified before LTRAs could serve a more effective role in the treatment of asthma

Hybrid male sterility is caused by mitochondrial DNA deletion.

Although it is known that the hybrid male mouse is sterile just like any other animal\u27s heterogametic sex, the reason why only the male germ cells are impaired has yet to be discovered. TdT-mediated dUTP nick end labeling assay using a confocal fluorescence microscope and DNA fragmentation assay of hybrid testis indicated destruction of the mitochondrial DNA (mtDNA) rather than the nuclear DNA. Previously we reported that maternal mtDNA inheritance is through selective sperm mtDNA elimination based on the sperm factor and two egg factors, and expression of these three factors was recognized in the hybrid testis. It was thereby assumed that mtDNA destruction caused by the expression of maternal mtDNA inheritance system in male germ cells is implicated in the hybrid male sterility of mice

Respiratory Bronchiolitis-associated Interstitial Lung Disease with Unusual Histopathological Findings

Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) is a mild inflammatory reaction commonly seen in asymptomatic young male cigarette smokers. This report describes unusual pathological findings in a 63-yearold Japanese female with RB-ILD. She had a 40 pack-year smoking history. Chest computed tomography showed multiple patchy shadows, especially in the right lower lobe. Diagnosis could not be established by bronchoalveolar lavage and transbronchial lung biopsy. Thoracoscopic lung biopsy was performed from right S5 and S9, which demonstrated the typical pathological findings of RB-ILD, including the presence of pigmented macrophages within respiratory bronchioles, thickening of alveolar septa by fibrosis, accumulation of intrapulmonary blue bodies and lack of granulomatous changes. Our patient had atypical RB-ILD based on old age at presentation (commonly -40 years of age), marked fibrosis and presence of numerous blue bodies

Progressive Retrograde Acute Coronary Occlusion after Gianturco-Roubin Stenting

We report a case of progressive retrograde acute coronary occlusion after Gianturco-Roubin (GR) stenting in a patient with two vessel diseases. A GR stent was implanted in the proximal part of the left anterior descending artery (LAD) because of suboptimal results of percutaneous transluminal coronary angioplasty (PTCA). More than 90% stenosis occurred in the non-stented region just distal to the edge of the GR stent. Another stenosis ensued mid-stent after PTCA was performed for that lesion. Acute occlusion from the mid- LAD to the main trunk progressed immediately after PTCA for the LAD. The patient died of cardiogenic shock despite repeated bail-out PTCA procedures for both the main trunk and the proximal LAD. Acute retrograde occlusion might be caused by in-stent thrombosis, or acute recoil of GR stent associated with insufficient stent dilatation and acute coronary arterial elastic recoil

Efficacy and safety of amrubicin hydrochloride for treatment of relapsed small cell lung cancer

Long-term survival is quite uncommon in refractory small cell lung cancer (SCLC) patients, with less than 25% of patients with limited-stage disease and 1%-2% of patients with extensive-stage disease remaining alive at five years. Recent clinical studies have demonstrated the promising efficacy of amrubicin for patients with relapsed SCLC. This review presents the results of clinical studies showing the efficacy and safety of amrubicin for the treatment of relapsed SCLC. Amrubicin is a synthetic anthracycline agent with a similar structure to doxorubicin, in which the hydroxyl group at position 9 in amrubicin is replaced by an amino group to enhance efficacy. It is converted to an active metabolite, amrubicinol, which is 5-54 times more active than amrubicin. Amrubicin and amrubicinol are inhibitors of DNA topoisomerase II, exerting their cytotoxic effects by stabilizing a topoisomerase II-mediated cleavable complex. The toxicity of amrubicin is similar to that of doxorubicin, although amrubicin shows almost no cardiotoxicity. In the relevant trials, amrubicin was administered intravenously at a dose of 35-40 mg/m2 on days 1-3 every three weeks. The response rate was 34%-52% and median survival times were 8.1-12.0 months. Common hematologic toxicities included neutropenia, leucopenia, anemia, thrombocytopenia, and febrile neutropenia. Nonhematologic adverse events included Grade 3-4 anorexia, asthenia, hyponatremia, and nausea. The results of the studies which demonstrated the efficacy of monotherapy for relapsed SCLC involved mainly Japanese patients. Therefore, it is necessary to conduct more clinical studies in non-Japanese patients to confirm the efficacy of amrubicin

Interleukin 5 Levels in Bronchoalveolar Lavage Fluid from Patients with Interstitial Lung Disease

Bronchiolitis obliterans organizing pneumonia (BOOP) is clinically and histologically difficult to differentiate from chronic eosinophilic pneumonia (CEP). The common histological feature of these diseases is an infiltration of mononuclear cells into the small airway, interstitial tissue and alveoli. Activation of T cells and secretion of lymphokines play a crucial role in the regulation and coordination of immune responses and inflammatory processes. In this study, we demonstrated the distribution of lymphocyte subpopulations and their stage of activation and T cellderived cytokine, IL-5 level in bronchoalveolar lavage (BAL) fluid obtained from patients with BOOP and CEP by comparison with sarcoidosis and diffuse panbronchiolitis (DPB). Flow cytometric analysis of T cell activation markers revealed that BOOP and sarcoidosis are characterized by increased absolute numbers of HLA-DR-bearing T cell subsets, while the relative numbers were increased in CEP and DPB. IL-5 in BAL fluids from BOOP and CEP was significantly high levels, and CEP patients with the high level of IL-5 showed the marked elevation of BAL eosinophils. Furthermor, it is of interest that the absolute numbers of HLA-DR T cells correlated with IL-5 levels in BAL fluid. These results suggest that activated T cells and secretion of IL-5 may be important factors in the pathogenetic processes of BOOP and CEP