Toshiro Miwa

Toyama University, Тояма, Toyama, Japan

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Publications (34)47.99 Total impact

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    ABSTRACT: Aims and background: Amrubicin monotherapy can be an effective treatment option for patients with recurrent small cell lung cancer (SCLC). We conducted this retrospective study to investigate the prognostic factors in patients with recurrent SCLC receiving amrubicin monotherapy. Methods: The associations between survival and clinical data, including the performance status, body mass index (BMI), plasma lactate dehydrogenase (LDH) level, and plasma neuron-specific enolase level, were evaluated in patients with recurrent SCLC, and a subset analysis of patients with platinum-resistant disease was conducted. Results: In all, 37 patients were evaluated. The median survival from the date of initiation of amrubicin monotherapy was 9.1 months (95% confidence interval 4.7-12.0 months). Multivariate analysis using a Cox proportional hazard model identified the plasma LDH level (p = 0.049), BMI (p = 0.031), and platinum resistance (p = 0.032) as independent factors associated with survival. The same associations were also observed in the subset of patients with platinum-resistant disease. Conclusions: Our findings suggest that the plasma LDH level and BMI may be useful prognostic factors in patients with SCLC receiving amrubicin monotherapy, including patients with platinum-resistant disease.
    No preview · Article · Oct 2015
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    ABSTRACT: To determine whether the creatinine/cystatin C (Cr/CysC) ratio, which is influenced by muscle mass, can be used as a predictive marker of the adverse effects of chemotherapy. This single-centre, retrospective, observational study assessed patients with lung cancer. Serum Cr and CysC levels were measured once within 1 month prior the commencement of chemotherapy. A total of 25 patients with lung cancer were enrolled in the study: 22 received first-line therapy; three received second-line therapy. A significant difference was noted regarding the Cr/CysC ratios between patients with nonsmall-cell lung cancer (NSCLC) and those with small-cell lung cancer (0.78 versus 0.92, respectively). A significant difference was also noted in the Cr/CysC ratios of patients with NSCLC with toxicity grades <3 and ≥3 (0.84 versus 0.70, respectively). Similar findings were observed in patients with NSCLC who received platinum-based combination therapy (toxicity grade < 3, 0.85; toxicity grade ≥3, 0.69). The Cr/CysC ratio could serve as a useful predictive marker for chemotherapy-related adverse effects in patients with NSCLC. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
    Full-text · Article · May 2015 · The Journal of international medical research
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    ABSTRACT: Determination of the presence of epidermal growth factor receptor (EGFR) gene mutation is useful for predicting the efficacy of gefitinib. However, the survival rate following the initiation of treatment with gefitinib varies among individuals. A retrospective study was conducted to investigate the associations of the pretreatment serum pro-gastrin-releasing peptide (pro-GRP) and plasma neuron-specific enolase (NSE) levels to the patient survival rate following initiation of treatment with gefitinib in non-small cell lung cancer (NSCLC) patients receiving gefitinib treatment. Patients with NSCLC harboring EGFR gene mutations who received gefitinib therapy between 2004 and 2012 were included in the study. Data from a total of 41 patients were analyzed. The serum pro-GRP level was measured in 31 patients and the plasma NSE in 22 patients. The progression-free survival (PFS) (P=0.013) and overall survival (OS) (P=0.014, log-rank test) rates decreased as the plasma NSE level increased. Statistical analysis using a Cox proportional hazards regression model adjusted for age, gender, performance status (PS) and disease stage showed that higher NSE levels were associated with shorter PFS (P=0.021) and OS (P=0.0024). By contrast, no association was detected between the serum level of pro-GRP and survival rate. The results suggest that pretreatment NSE measurement could be clinically useful in patients with NSCLC scheduled to receive gefitinib treatment.
    Preview · Article · May 2015 · Molecular and Clinical Oncology
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    ABSTRACT: Cortisol plays an important role in the physical status of patients with end-stage lung cancer, but the association of urine cortisol levels with TNM stage/performance status (PS) is unclear in patients with advanced lung cancer receiving chemotherapy. The objective of this study was to examine this association. In this single-center, retrospective, observational study, cortisol concentrations in 24-h pooled urine from 22 patients with advanced lung cancer were measured over 2 days. The mean concentration in each patient was compared with PS, TNM stage, and serum sodium and potassium ion levels. The 24-h urine cortisol levels were higher in PS2 or PS3 cases compared to PS1 (p < 0.05) and increased proportionally with PS. Urine cortisol also increased in N2 or N3 cases compared to N1 (p < 0.01) and also increased in M1 cases (p < 0.05). Urine cortisol levels were negatively correlated with serum sodium (R = -0.49, p < 0.05) and had a tendency for a positive correlation with serum potassium (R = 0.40, p = 0.06). The 24-h urine cortisol level increased in patients with advanced lung cancer undergoing chemotherapy. Low serum levels of potassium and high levels of sodium may indicate relative adrenal insufficiency.
    No preview · Article · Dec 2014 · Supportive Care Cancer
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    ABSTRACT: The usefulness of the Palliative Prognostic Index (PPI) has been successfully validated in a variety of clinical settings. However, while lung cancer is the leading cause of death worldwide, patients with lung cancer accounted for only 6.9-25.8 % of the study populations in these previous studies. We conducted a retrospective study to evaluate the usefulness of the PPI for survival prediction in patients with lung cancer. Patients with lung cancer who were admitted to our hospital between 2009 and 2013 to receive palliative care were enrolled. The association between the Palliative Prognostic Index, determined based on the data recorded in the clinical charts at the last admission to our hospital, and survival was evaluated. The patient group with a PPI of >6 showed a significantly shorter survival time than the patient group with a PPI of ≤6 (P < 0.0001, log-rank test). The sensitivity and specificity of the PPI determined using the cutoff value of 6 for predicting less than 3 weeks of survival were 61.3 and 86.8 %, respectively. However, the sensitivity decreased to 50.0 % when the assessment was carried out in only patients with small cell lung carcinoma. Our findings suggest the existence of a close association between the PPI and survival in patients with lung cancer receiving palliative care. However, the sensitivity of the index for predicting less than 3 weeks of survival was relatively low in patients with small cell lung carcinoma.
    No preview · Article · Sep 2014 · Medical Oncology
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    ABSTRACT: Aims and background: It is reported that about 20% of patients with small cell lung cancer (SCLC) receive third-line chemotherapy. We conducted a retrospective study to investigate the outcome and prognostic factors of patients with SCLC who receive third-line chemotherapy. Methods and study design: The medical records of patients with SCLC who received third-line chemotherapy at our institution were reviewed. Overall survival (OS) from the initiation of third-line chemotherapy was evaluated, and the association between OS and patient characteristics was assessed by the log-rank test. Results: A total of 73 patients with SCLC were treated with cytotoxic drugs between 2004 and 2012, and 19 patients received third-line chemotherapy. Median OS from initiation of third-line chemotherapy was 8.5 months. Patients with higher body mass index (BMI) (P = 0.0071), lower levels of lactate dehydrogenase (LDH) (P = 0.0036), higher levels of hemoglobin (P = 0.048), longer time to progression (TTP) from the initiation of second-line treatment (P = 0.0036), and better response to second-line treatment (P = 0.029) had longer duration of OS. Conclusions: It is suggested that TTP and tumor response in second-line chemotherapy, serum levels of LDH and hemoglobin, and BMI at initiation of third-line chemotherapy could be possible prognostic factors.
    No preview · Article · Sep 2014
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    ABSTRACT: Background: The efficacy of docetaxel, vinorelbine, or gemcitabine monotherapy in previously untreated elderly patients with non-small cell lung cancer has been reported.Pemetrexed monotherapy has shown clinically equivalent efficacy to docetaxel, a standard therapeutic option, in patients with previously treated non-small cell lung cancer and in those with a lower incidence of toxicity such as febrile neutropenia. Objective: In the present study, we aimed to investigate the efficacy and toxicity of pemetrexed in previously untreated elderly patients with non-squamous cell lung cancer and compare the results with those of docetaxel, considered a standard chemotherapeutic agent. Methods: We retrospectively reviewed the medical records of patients with non-squamous cell lung cancer with wild-type(or unknown)epidermal growth factor receptor status who received pemetrexed or docetaxel monotherapy as first-line chemotherapy. Results: We analyzed 6 patients with lung adenocarcinoma in the pemetrexed group and 6 patients with lung adenocarcinoma in the docetaxel group. The median progression-free survival was 3.6 months for patients receiving pemetrexed and 3.1 months for those receiving docetaxel(p=0.45). The median overall survival was 14.8 months in the pemetrexed group and 10.9 months in the docetaxel group(p=0.36).Patients who received docetaxel were more likely to have grade 3 or 4 neutropenia and febrile neutropenia than those receiving pemetrexed.However, 2 patients who received pemetrexed showed grade 3 pneumonitis. Conclusion: Pemetrexed monotherapy is a promising treatment for previously untreated elderly patients with non-squamous cell lung cancer.
    No preview · Article · Jul 2014 · Gan to kagaku ryoho. Cancer & chemotherapy
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    ABSTRACT: A 69-year-old woman was diagnosed with lung adenocarcinoma in the right upper lobe in 2003,and underwent right upper and middle lobectomy. In 2005,she was administered anti-cancer chemotherapy for disease recurrence. In 2008, the patient was hospitalized with fever, general malajse, and a pain in the pubic region during chemotherapy. We suspected the presence of a metastatic lesion in the pubic bone; however, methicillin-resistant Staphyrococcus aureus (MRSA) was detected on blood culture. After the administration of anti-MRSA agents. the pain in the pubic region alleviated. Based on the clinical course and the findings of pelvic magnetic resonance imaging, the patient was diagnosed with septic arthritis of the pubic symphysis. Here, we describe a rare case of septic arthritis of the pubic syrnphysis in a patient undergoing chemotherapy for lung cancer.
    No preview · Article · Mar 2014 · Japanese Journal of Chest Diseases
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    ABSTRACT: Background and objective: In asthma, reduced histone deacetylase activity and enhanced histone acetyltransferase activity in the lungs have been reported. However, the precise function of Sirtuin 1 (Sirt1), a class III histone deacetylase, and the effect of the Sirt1 activator SRT1720 on allergic inflammation have not been fully elucidated. Methods: The effect of SRT1720, a synthetic activator of Sirt1, in an ovalbumin (OVA)-induced asthma mouse model was investigated. The effect of SRT1720 and resveratrol on OVA stimulation in splenocytes from OVA-sensitized and challenged mice was also examined. Results: In OVA-sensitized and challenged mice (OVA mice) compared with saline-sensitized and challenged mice (control mice), Sirt1 messenger RNA expression in the lungs was decreased (P = 0.02), while cellular infiltration, airway eosinophilia and bronchoalveolar lavage (BAL) fluid levels of interleukin (IL)-4, IL-5 and IL-13 were increased (P < 0.01). In OVA mice, SRT1720 treatment decreased total and eosinophil cell counts and IL-5 and IL-13 levels in the BAL fluid compared with the vehicle treatment (P < 0.05). In OVA mice, SRT1720 treatment also decreased inflammatory cell lung infiltrates histologically (P = 0.002). Both SRT1720 and resveratrol suppressed OVA-induced cell proliferation and IL-6 (P < 0.05) and tumour necrosis factor-α (TNF-α) (P < 0.05) production in splenocytes (P < 0.01). Conclusions: The Sirt1 activator SRT1720 suppressed inflammatory cell infiltration and cytokine production in an OVA-induced mouse model of asthma. SRT1720 and resveratrol suppressed OVA-induced splenocyte proliferation and TNF-α and IL-6 production. Sirt1 activators might have beneficial effects in asthmatics by suppressing inflammation.
    No preview · Article · Oct 2012 · Respirology
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    ABSTRACT: Miliary brain metastasis is an extremely rare form of brain metastasis which can present with atypical imaging findings. We report the case of a patient with miliary brain metastasis of lung cancer showing calcification in metastatic lesions. A 68-year-old Japanese woman was diagnosed with lung adenocarcinoma. Brain computed tomography revealed multiple small calcified lesions in both cerebral hemispheres. Mutation of the epidermal growth factor receptor gene (exon 21, L858R) in lung cancer cells was detected, and treatment with gefitinib was initiated. A partial response was observed; however, the patient was readmitted to our hospital because of regrowth of the primary lesion and complaints of nausea, headache, and difficulty walking. Brain magnetic resonance imaging revealed scattered tiny nodules enhanced by gadolinium. A diagnosis of leptomeningeal carcinomatosis was made on the basis of cerebrospinal fluid cytology. The patient's general status worsened, and she died 356 days after the day of first medical examination. Upon autopsy, the brain was found to be edematous and swollen. Lung carcinoma cells were diffusely disseminated on the meningeal surface. Metastatic foci of small nodular form, accompanied by calcifications, were also found in the brain parenchyma. We diagnosed miliary metastasis of lung carcinoma. To the best of our knowledge, this is the third report of calcified miliary brain metastasis confirmed by autopsy. We describe calcified lesions that increased in size during the clinical course of nine months. Brain computed tomography findings that reveal multiple small calcified lesions in patients with malignancy should raise suspicion of miliary brain metastasis.
    Full-text · Article · Sep 2012 · Journal of Medical Case Reports
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    ABSTRACT: Chronic necrotizing pulmonary aspergillosis usually occurs in mildly immune-compromised hosts or those with underlying pulmonary disease. The radiographic pattern of chronic necrotizing pulmonary aspergillosis is typically a progressive upper lobe cavitary infiltrate with pleural thickening. We report here an atypical case of chronic necrotizing pulmonary aspergillosis mimicking lung cancer, which developed into a disseminated fatal disease in an older woman with no comorbidity. An 80-year-old Japanese woman was referred to our hospital for a chest roentgenogram abnormality. Repeated fiber-optic bronchoscopy could not confirm any definite diagnosis, and she refused further examinations. Considering the roentgenogram findings and her age, she was followed-up as a suspected case of lung cancer without any treatment. Then, 10 months later, she complained of visual disturbance and was admitted to our department of ophthalmology. She was diagnosed as having endophthalmitis. After treatment with corticosteroids for 20 days, she developed acute encephalitis and died four weeks later. Autopsy revealed dissemination of Aspergillus hyphae throughout her body, including her brain. In older patients, even if they do not have any comorbidity, chronic necrotizing pulmonary aspergillosis should be added to the differential diagnosis of solitary pulmonary lesions in a chest roentgenogram.
    Full-text · Article · Aug 2012 · Journal of Medical Case Reports
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    ABSTRACT: Silent information regulator 2 (SIR2) is a highly conserved protein, the mammalian orthologue of which, SIRT1, exhibits histone deacetylase activity. SIRT1 is involved not in only longevity due to caloric restriction but in a variety of diseases such as diabetes, cardiovascular dysfunction and neurodegeneration. However, accumulating evidence shows that SIRT1 is overexpressed in various types of malignant cells, and its inhibitors suppress the growth of tumor cells. The relationship between SIRT1 and metastasis remains to be clarified. Here, we examined the effect of SRT1720, a SIRT1 activator, on lung metastasis of breast cancer cells. 4T1 breast cancer cells were subcutaneously implanted into syngeneic BALB/c mice and SRT1720 was administered alone or with an antitumor agent, cisplatin. As expected, cisplatin decreased the lung metastasis score, whereas SRT1720 increased metastasis irrespective of cisplatin. In the primary tumors, cisplatin suppressed the mRNA level of angiopoietin-like protein 4 (angptl4), a lung metastasis-promoting gene product of breast cancer, but SRT1720 reduced the effectiveness of cisplatin. The results obtained with animal experiments were in accordance with those in human cancer cells; SRT1720 significantly increased the amount of VEGF secreted from MDA-MB-231 cells. Moreover, a transendothelial cell migration assay showed that SRT1720 promotes the migration of MDA-MB-231 cells across an endothelial cell layer despite the presence of cisplatin. These findings imply that SRT1720 promotes the pulmonary metastasis of breast cancer cells and SIRT1 may be an important target for suppressing metastasis to the lung.
    Preview · Article · Jun 2012 · Oncology Reports

  • No preview · Conference Paper · May 2012
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    ABSTRACT: A 76-year-old man was diagnosed with advanced lung adenocarcinoma and received treatment with gefitinib. In addition, prednisolone was started for severe appetite loss. However, the patient complained of dyspnea and a chest CT revealed bilateral ground glass opacity. Gefitinib-induced lung injury was suspected, and the drug was discontinued. However, it was found that the serum level of beta-D glucan was higher than 300 pg/ml. After further detailed investigation, a diagnosis of Pneumocystis jiroveci pneumonia (PCP) was made. Treatment with trimethoprim-sulphamethoxazole was started and the abnormal shadows and dyspnea disappeared. Treatment with gefitinib could be resumed without any adverse effect. The present case highlights the need for appropriate investigation and diagnosis in patients developing abnormal shadows on chest imaging during treatment with gefitinib.
    No preview · Article · Sep 2011

  • No preview · Conference Paper · May 2011
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    ABSTRACT: A 23-year-old man was admitted for examination of an abnormal shadow in the right lower lung field. A chest CT scan revealed a nodule in the right lower lobe and a calcified nodule in the right upper lobe. A diagnosis of lung adenocarcinoma in the right lower lobe was made by transbronchial cytology. After resection of the right lower lobe and partial resection of the nodule in the right upper lobe were performed, we diagnosed lung adenocarcinoma in the right lower lobe (pathological stage IIIA) and hamartoma in the right upper lobe. Although several authors have reported cases of synchronous pulmonary hamartoma and lung cancer, it is uncommon in young patients. Since patients with hamartoma could also have lung carcinoma, careful observation is needed.
    Full-text · Article · May 2011

  • No preview · Conference Paper · May 2010
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    ABSTRACT: We report 2 cases of pulmonary sarcomatoid carcinoma mimicking malignant mesothelioma. Case 1: A 69 year-old man presented, complaining of right chest pain. The chest X ray film and CT showed tumors in the right chest wall and pleura. Histological findings of specimens obtained from a percutaneous biopsy revealed spindle tumor cells, and the immunohistochemistry showed that the tumor cells were positive for CK-7, AE1/AE3, and vimentin and negative for calretinin, D2-40, and WT-1. We diagnosed pulmonary sarcomatoid carcinoma and started chemotherapy with carboplatin and paclitaxel, but it was ineffective. Case 2: A 68 year-old man was admitted complaining of general malaise. The chest X ray film and CT revealed tumors in the right chest wall. Histological findings showed necrosis and spindle tumor cells which were positive for AE1/AE3 and vimentin, and negative for calretinin, D2-40, and WT-1. We diagnosed pulmonary sarcomatoid carcinoma and started chemotherapy with carboplatin and paclitaxel. However the disease continued to progress and he died 2 months after admission. The pulmonary sarcomatoid carcinoma was reported to have spred to the pleural and chest wall. The present two cases showed prominent chest wall and pleural tumors with obscure primary lung tumors. Therefore, we needed to differentiate sarcomatoid carcinoma from malignant pleural mesothelioma.
    No preview · Article · Jan 2010
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    ABSTRACT: A 23-year-old Japanese man was admitted to our hospital because of dry cough and lacrimal gland swelling. Laboratory findings showed hypergammaglobulinemia (4859 mg/dl), hypocomplementemia (CH50 13 U/ml), and hyperamylasemia. CT revealed a marked swelling of the bilateral lacrimal glands, diffuse patchy infiltration in the bilateral lung fields, and enlargement of the whole pancreas. Gallium citrate scintigraphy showed abnormal accumulation in the bilateral lacrimal glands, submandibular glands, and both lung fields. Biopsy specimens from the salivary gland revealed dense lymphoplasmacytic infiltration and abundant IgG4-positive plasma cells. Furthermore, open lung biopsy showed a marked peribronchial lymphoplasmacytic and eosinophilic infiltration with IgG4-positive plasma cells. These findings fulfilled the criteria of Mikulicz's disease and autoimmune pancreatitis, and support the recently proposed concept of IgG4-related systemic disease.
    Full-text · Article · Mar 2009
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    ABSTRACT: Adenosylhomocysteine hydrolase (SAHase)-like protein 1 (SAH-L), also called inositol 1,4,5-triphosphate receptor-binding protein (IRBIT) is a novel protein involved in fish embryo development and calcium release in mammalian cells through protein-protein interactions. To better understand its reaction mechanism, purified protein is indispensable. Here we describe a simple purification procedure and the unique properties of SAH-L. The cDNA was isolated from mouse kidney by RT-PCR and inserted into various pETtrade mark vectors. Escherichia coli harboring a plasmid coding for SAH-L with a C-terminal His-tag could solely produce a soluble protein. SAH-L purified through a Ni(2+) column gave M(r)s of 59,000 and 190,000 by SDS-PAGE and gel filtration, respectively, which is suggestive of a trimer, but chemical cross-linking experiments demonstrated a dimer. The incompatible M(r) values implicate an irregular structure of SAH-L. In fact, SAH-L was partially purified in a form lacking the 31 N-terminal residues, and was found to be extremely susceptible to proteases in the region around residue 70. The N-terminal polypeptide (residues 1-98) was also expressed as a soluble form and was trypsin-sensitive. Circular dichroism revealed a low alpha-helix content but not a randomly extended structure. Interestingly, SAH-L contained tightly bound NAD(+) despite showing no SAHase activity. The characterized properties of SAH-L and its N-terminal fragment present the notion that the structure of the protease-sensitive N-terminal region is relatively loose and flexible rather than compact, and which protrudes from the major SAHase-like domain. This structure is supposed to be favorable to interact with the IP(3) receptor.
    Full-text · Article · Oct 2008 · Biochimica et Biophysica Acta

Publication Stats

103 Citations
47.99 Total Impact Points

Institutions

  • 2008-2015
    • Toyama University
      Тояма, Toyama, Japan
  • 2006-2012
    • University of Toyama
      • • Department of Internal Medicine 3
      • • Faculty of Medicine
      Тояма, Toyama, Japan
  • 2001-2006
    • Toyama Medical and Pharmaceutical University
      Тояма, Toyama, Japan