Characteristics of early-onset hematotoxicity of sunitinib in Japanese patients with renal cell carcinoma

BACKGROUND: A high incidence of severe hematological adverse events during sunitinib treatment complicates decision making on dose and treatment cycle. We identified the characteristics of early-onset hematotoxicity of sunitinib in Japanese patients with renal cell carcinoma (RCC). METHODS: Seventy-nine patients were treated with sunitinib as 6-week cycles of “4-week on 2-week off” schedule. To evaluate early-onset hematotoxicity, we compared patients with dose reduction during the first cycle (dose-reduced group, n = 57) and those who maintained the initial dose (dose-maintained group, n = 22). ABCG2 and FLT3 genotypes were analyzed for association between hematotoxicity and reported gene polymorphisms. RESULTS: Mean relative dose intensity (RDI) was similar in the two groups during the first 2 weeks of dosing in the first cycle, but was significantly lower in the dose-reduced group during the last 2 weeks. Lymphocytopenia and thrombocytopenia were observed in the dose-reduced group within the first 2 weeks. Genetic analysis indicated a significantly higher frequency of FLT3 738 T/C polymorphism in the dose-reduced group, but no significant difference in the ABCG2 421 C/A polymorphism. CONCLUSIONS: This study showed a high incidence of sunitinib-induced hematotoxicity in Japanese patients with RCC, many of whom need dose adjustment during the first cycle. Further studies should verify whether dose adjustment based on early-onset thrombocytopenia prolongs sunitinib treatment

Dusty ERO Search behind Two Massive Clusters

We performed deep K'-band imaging observations of 2 massive clusters, MS 0451.6-0305 at z = 0.55 and MS 0440.5+0204 at z = 0.19, for searching counterparts of the faint sub-mm sources behind these clusters, which would provide one of the deepest extremely red object(ERO) samples. Comparing our near-infrared images with optical images taken by the Hubble Space Telescope and by the Subaru Telescope, we identified 13 EROs in these fields. The sky distributions of EROs are consistent with the previous results, that there is a sign of strong clustering among detected EROs. Also, the surface density with corrected lensing amplification factors in both clusters are in good agreement with that derived from previous surveys. We found 7 EROs and 3 additional very red objects in a small area (\sim 0.6 arcmin^2) of the MS 0451.6-0305 field around an extended SCUBA source. Many of their optical and near-infrared colors are consistent with dusty star-forming galaxies at high redshifts(z \sim 1.0-4.0), and they may be constituting a cluster of dusty starburst galaxies and/or lensed star-forming galaxies at high redshift. Their red J-K' colors and faint optical magnitudes suggest they are relatively old massive stellar systems with ages(>300 Mega years) suffering from dust obscuration. We also found a surface-density enhancement of EROs around the SCUBA source in the MS 0440.5+0204 field.Comment: 19 pages, 11 figures, Latex(using pasj00.cls). To be published in PASJ vol 55, No. 4(Aug 2003

Acute respiratory distress syndrome following infection of influenza A (H1N1) virus

A 28-year-old man with a history of mental retardation was admitted to our hospital because of dyspnea, cough and high fever. His SpO(2) level at room-environmental conditions was in the eighties, and his chest radiograph showed diffuse infiltrates in both lungs. He was diagnosed as suffering from influenza A by a rapid influenza virus antigen test. The echocardiogram showed no evidence of left cardiac failure; therefore, his symptoms were consistent with acute respiratory distress syndrome (ARDS). Oseltamivir was started, and antibiotics were also given because of the possibility of secondary bacterial infection. Due to respiratory failure and low blood pressure, which suggested septic shock, intensive treatments including mechanical ventilation were performed. Corticosteroid therapy was started for ARDS and sepsis, and these therapies improved his respiratory condition. Polymerase chain reaction of his pharyngeal swab revealed that he had influenza A (H1N1). This is the first case of ARDS following infection by influenza A (H1N1) virus in Japan

Cancer Immunol Immunother

Purpose Through genome-wide expression profile analysis, hypoxia-inducible protein 2 (HIG2) has previously been identified as an oncoprotein involved in development/progression of renal cell carcinoma (RCC). We subsequently identified a highly immunogenic HLA-A*0201/0206-restricted epitope peptide (HIG2-9-4) corresponding to a part of HIG2 and applied it as a therapeutic vaccine. We conducted a phase I clinical trial using the HIG2-9-4 peptide for patients with advanced RCC. Materials and Methods Nine patients having HLA-A*0201 or HLA-A*0206 with metastatic or unresectable RCC after failure of the cytokine and/or tyrosine kinase inhibitor therapies were enrolled in this study. The patients received subcutaneous administration of the peptide as an emulsion form with Montanide ISA-51 VG once a week in a dose-escalation manner (doses of 0.5, 1.0, or 3.0 mg/body, 3 patients for each dose). The primary endpoint was safety, and the secondary endpoints were immunological and clinical responses. Results Vaccinations with HIG2-9-4 peptide could be well tolerated without any serious systemic adverse events. Peptide-specific cytotoxic T lymphocyte (CTL) responses were detected in eight of the nine patients. Doses of 1.0 or 3.0 mg/body seemed to induce a CTL response better than did a dose of 0.5 mg/body, although the number of patients was too small to draw a firm conclusion. The disease control rate (stable disease for ≥4 months) was 77.8 %, and the median progression-free survival time was 10.3 months. Conclusions HIG2-9-4 peptide vaccine treatment was tolerable and effectively induced peptide-specific CTLs in RCC patients. This novel peptide vaccine therapy for RCC is promising

PREDICTION SYSTEMS FOR BLADDER CANCER THERAPY

The present study established systems to predict the chemo‑sensitivity of muscle invasive bladder cancer (MIBC) for neoadjuvant chemotherapy (NAC) with methotrexate, vinblastine, doxorubicin plus cisplatin (M‑VAC) and carboplatin plus gemcitabine (CaG) by analyzing microarray data. The primary aim of the study was to investigate whether the clinical response would increase by combining these prediction systems. Treatment of each MIBC case was allocated into M‑VAC NAC, CaG NAC, surgery, or radiation therapy groups by their prediction score (PS), which was calculated using the designed chemo‑sensitivity prediction system. The therapeutic effect of the present study was compared with the results of historical controls (n=76 patients) whose treatments were not allocated using the chemo‑sensitivity prediction system. In addition, the overall survival between the predicted to be responder (positive PS) group and predicted to be non‑responder (negative PS) group was investigated in the present study. Of the 33 patients with MIBC, 25 cases were positive PS and 8 were negative PS. Among the 25 positive PS cases, 7 were allocated to receive M‑VAC NAC and 18 were allocated to receive CaG NAC according to the results of the prediction systems. Of the 8 negative PS cases, 3 received CaG NAC, 1 received surgery without NAC and 4 received radiation therapy. The total clinical response to NAC was 88.0% (22/25), which was significantly increased compared with the historical controls [56.6% (43/76) P=0.0041]. Overall survival of the positive PS group in the study was significantly increased compared with the negative PS group (P=0.027). In conclusion, the combination of the two prediction systems may increase the treatment efficacy for patients with MIBC by proposing the optimal NAC regimen. In addition, the positive PS group would have a better prognosis compared with the negative PS group. These results suggest that the two prediction systems may lead to the achievement of ‘precision medicine’

Complete Resolution of a Case of Calcific Tendinitis of the Longus Colli with Conservative Treatment

Acute calcific tendinitis of the longuscolli is a self-limiting inflammatory condition caused by calcium hydroxyapatite deposition in the longuscolli tendon. Although several case reports have described its radiological presentation, few reports provide detailed chronological accounts through symptomatic and radiologic resolution. A 59-year-old woman presented with severe neck pain and stiffness of a few days duration as well as moderate discomfort when swallowing. Lateral radiographs revealed a large calcium deposit anterior to the C1.C2 joint and swelling of the prevertebral soft tissue from C1 to C5. CT and magnetic resonance imaging showed fluid in the retropharyngeal gap.A soft collar and non-steroidal anti-inflammatory drug were prescribed, without antibiotics. At 4 months after presentation, the calcium deposit and all symptoms had resolved completely. Although this disease is comparatively rare, physicians should keep it in mind when a patient presents with acute severe neck pain

Motion of methanol adsorbed in porous coordination polymer with paramagnetic metal ions

Molecular motions of methanol adsorbed in 1D nano-channels of pillared-layer coordination polymer with paramagnetic metal ions have been studied by 2H NMR together with X-ray crystallography

Analysis of Expression Patterns of MicroRNAs That Are Closely Associated With Renal Carcinogenesis

Background: MicroRNAs (miRNA) are frequently dysregulated in clear cell renal cell carcinoma (ccRCC).Objective: This study aimed to elucidate the role of miRNA expression patterns in renal carcinogenesis and to identify the specific miRNAs that exhibit expression patterns closely associated with patient outcomes.Methods: We examined the expression patterns of selected miRNAs, including miRNA-155-5p, miRNA-122-5p, miRNA-21-5p, miRNA-185-5p, miRNA-106a-5p, miRNA-106b-3p, miRNA-34b-3p, miRNA-210-3p, miRNA-141-3p, miRNA-200c-3p, miRNA-135a-5p, miRNA-30a-5p, miRNA-218-5p, miRNA-429, miRNA-200a-3p and miRNA-200b-3p, in 96 samples of ccRCCs using the TaqMan real-time PCR method. In addition, cluster analysis was performed to stratify expression patterns of multiple miRNAs.Results: In the present study, three distinct subgroups could be clearly stratified in ccRCCs. Subgroup 1 was characterized by upregulation of miRNA-155-5p, miRNA-122-5p, miRNA-21-5p, miRNA-185-5p, miRNA-106a-5p, miRNA-106b-3p, miRNA-34b-3p and miRNA-210-3p. Subgroup 2 was closely associated with downregulation of miRNA-141-3p, miRNA200c-3p, miRNA-30a-5p, miRNA-218-5p, miRNA-429, miRNA-200a-3p and miRNA-200b-3p. Moreover, significant lower expression of miRNA-135a-5p was a distinctive feature of subgroup 3, which was correlated with metachronous metastasis. Among the individual markers in subgroup 3, miRNA-135a-5p was retained in multivariate analysis. The cutoff value of miRNA-135a-5p expression to identify the association of an altered level of miRNA-135a-5p with metachronous metastasis in ccRCCs was determined and showed excellent specificity.Conclusion: We suggest that the expression pattern of the chosen miRNAs is useful to identify renal carcinogenesis and to help identify the association of such expression patterns with metachronous metastasis in ccRCCs. In addition, miRNA-135a-5p was an excellent marker for prediction of metachronous metastasis

Complex orbital state in manganites

The $e_g$-orbital states with complex coefficients of the linear combination of $x^2-y^2$ and $3z^2-r^2$ are studied for the ferromagnetic state in doped manganites. Especially the focus is put on the competition among uniform complex, staggered complex, and real orbital states. As the hole-doping $x$ increases, the real, the canted complex, and the staggered complex orbital states appears successively. Uniform complex state analoguous to Nagaoka ferromagnet does not appear. These complex states can be expressed as a resonating state among the planer orbitals as the orbital liquid, accompanied by no Jahn-Teller distortion.Comment: 14 pages, 6 figure

Elucidation of flow characteristics in honeycomb structure to design nanobubble generating apparatus

A nanobubble generator with honeycomb structures producing a large amount of water including large nanobubble density in a short time is described. The nanobubble‐generating performance is investigated for large and small apparatus having different honeycomb cell dimensions by applying computational fluid dynamics (CFD) coupled with a population balance model (PBM). The CFD simulation shows that a significant pressure drop and shear stress occur in the bubbly flow in the honeycomb cell. The numerical model is based on the Eulerian multiphase model and the PBM is used to calculate the bubble size distribution. The obtained CFD‐PBM results are compared with the experimental results for large and small apparatus. Bubble size distributions in the honeycomb structure under different inlet absolute pressure can be predicted by the PBM. The maximum shear stress is determined as the main controlling factor for nanobubble generation