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Early apoptosis and cell death induced by ATX-S10Na(Ⅱ)-mediated photodynamic therapy are Bax- and p53-dependent in human colon cancer cells

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World Journal of Gastroenterology 2007年第5期13卷 692-698页

作者： Makoto Mitsunaga Akihito Tsubota Kohichi Nariai yoshihisa namiki Makoto Sumi Tetsuya Yoshikawa Kiyotaka Fujise Institute of Clinical Medicine and Research Jikei University School of Medicine Kashiwa Chiba Japan Division of Gastro-enterology and Hepatology Department of Internal Medicine Jikei University School of Medicine Tokyo Japan Institute of Clinical Medicine and Research Jikei University School of Medicine Kashiwa Chiba Japan

AIM： To investigate the roles of Bax and p53 proteins in photosensitivity of human colon cancer cells by using lysosome-localizing photosensitizer, ATX-S10Na （Ⅱ）. METHODS： HCT116 human colon cancer cells and Bax-null or p53-null isogenic derivatives were irradiated with a diode laser. Early apoptosis and cell death in response to photodynamic therapy were determined by MTT assays, annexin Ⅴ assays, transmission electron microscopy assays, caspase assays and western blotting. RESULTS： Induction of early apoptosis and cell death was Bax- and p53-dependent. Bax and p53 were required for caspase-dependent apoptosis. The levels of anti-apoptotic Bcl-2 family proteins, Bcl-2 and Bcl-xL, were decreased in Bax- and p53-independent manner. CONCLUSION： Our results indicate that eady apoptosis and cell death of human colon cancer cells induced by photodynamic therapy with lysosome-localizing photosensitizer ATX-S10Na （Ⅱ） are mediated by p53- Bax network and low levels of Bcl-2 and Bcl-xL proteins. Our results might help in formulating new therapeutic approaches in photodynamic therapy.

关键词： Photodynamic therapy ATX-S10Na (Ⅱ) Apoptosis Bax p53

Four-week pegylated interferon a-2a monotherapy for chronic hepatitis C with genotype 2 and low viral load:A pilot,randomized study

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World Journal of Gastroenterology 2008年第47期14卷 7220-7224页

作者： Akihito Tsubota Ken-ichi Satoh Mashu Aizawa Seishi Takamatsu yoshihisa namiki Toshifumi Ohkusa Kiyotaka Fujise Hisao Tajiri Institute of Clinical Medicine and Research Jikei University School of MedicineChiba 277-8567Japan Department of Gastroenterology and Hepatology Kashiwa HospitalJikei University School of MedicineChiba 277-8567Japan Division of Gastroenterology and Hepatology Department of Internal MedicineJikei University School of MedicineTokyo 105-8461Japan

AIM:To assess the efficacy and advantages of 4-wk pegylated interferon a-2a(peg-IFN-a2a) monotherapy for chronic hepatitis C patients with strong predictors of sustained virologic response(SVR).METHODS:Patients(n = 33) with genotype 2 and low viral load(< 100 KIU/mL),who became HCV RNA negative after 1 wk of IFN treatment,were randomly allocated to receive a 4-or 12-wk treatment course at a ratio of 2:1,respectively,with a subsequent 24-wk follow-up ***-IFN-a2a was administered subcutaneously at a dose of 180 μg or 90 μg once *** was defined as absence of serum HCV RNA at the end of the follow-up ***:All patients completed the treatment schedule,and more than half were symptom-free during the *** the 4-wk treatment group,20 of 22(91%) patients achieved *** patients relapsed,but achieved SVR following re-treatment with peg-IFN-a2a *** the 12-wk treatment group,11 of 11(100%) patients attained ***:Our results show that a 4-wk course of peg-IFN-a2a monotherapy can achieve a high SVR rate in "IFN-sensitive" patients,without negatively affecting outcome.

关键词： Chronic hepatitis C Pegylated interferonalpha-2a monotherapy Genotype 2 Low viral load Randomized pilot study

Several factors including ITPA polymorphism influence ribavirin-induced anemia in chronic hepatitis C

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World Journal of Gastroenterology 2012年第41期18卷 5879-5888页

作者： Akihito Tsubota Noritomo Shimada Hiroshi Abe Kai Yoshizawa Rie Agata Yoko Yumoto Makiko Ika yoshihisa namiki Keisuke Nagatsuma Hiroshi Matsudaira Kiyotaka Fujise Norio Tada Yoshio Aizawa Institute of Clinical Medicine and Research The Jikei University School of Medicine163-1 Kashiwa-shitaKashiwaChiba 277-8567Japan Division of Gastroenterology and Hepatology Kashiwa HospitalThe Jikei University School of Medicine163-1 Kashiwa-shitaKashiwaChiba 277-8567Japan Department of Gastroenterology Shinmatsudo Central General Hospital1-380 ShinmatsudoMatsudoChiba 270-0034Japan Division of Gastroenterology and Hepatology Katsushika Medical CenterThe Jikei University School of Medicine6-41-2 AotoKatsushika-kuTokyo 125-8506Japan

AIM： To construct formulae for predicting the likelihood of ribavirin-induced anemia in pegylated interferon plus ribavirin for chronic hepatitis C. METHODS： Five hundred and sixty-one Japanese patients with hepatitis C virus genotype lb who had received combination treatment were enrolled and as- signed randomly to the derivation and confirmatory groups. Single nucleotide polymorphisms at or nearby ITPA were genotyped by real-time detection poly- merase chain reaction. Factors influencing significant anemia （hemoglobin concentration 〈 10.0 g/dL at week 4 of treatment） and significant hemoglobin decline （declining concentrations 〉 3.0 g/dL at week 4） were analyzed using multiple regression analyses. Prediction formulae were constructed by significantly independent factors. RESULTS： Multivariate analysis for the derivation group identified four independent factors associated with significant hemoglobin decline： hemoglobin decline at week 2 [P = 3.29× 10^4, odds ratio （OR） = 7.54 （g/dL）], estimated glomerular filtration rate [P = 2.16× 10^4, OR = 0.962 （ml/min/1.73 m2）], rs1127354 （P = 5.75 × 10^4, OR = 10.94） and baseline hemoglobin [P = 7.86 × 10^4, OR = 1.50 （g/alL）]. Using the model constructed by these factors, positive and negative predictive values and predictive accuracy were 79.8%, 88.8% and 86.2%, respectively. For the confirmatory group, they were 83.3%, 91.0% and 88.3%. These factors were closely correlated with significant anemia. However, the model could not be constructed, because no patients with rs1127354 minor genotype CA/AA had significant anemia. CONCLUSION： Reliable formulae for predicting the likelihood of ribavirin-induced anemia were constructed. Such modeling may be useful in developing individual tailoring and optimization of ribavirin dosage.

关键词： Chronic hepatitis C virus infection Ribavi-rin Pegylated interferon Prediction model Hemolyticanemia Single nucleotide polymorphism

A mutation of the start codon in the X region of hepatitis B virus DNA in a patient with non-B,non-C chronic hepatitis

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World Journal of Hepatology 2011年第2期3卷 56-60页

作者： Kiyotaka Fujise Keiko Tatsuzawa Midori Kono Sadayori Hoshina Akihito Tsubota Minoru Niiya yoshihisa namiki Norio Tada Hisao Tajiri Division of Gastroenterology and Hepatology Department of Internal MedicineKashiwa HospitalThe Jikei University School of MedicineChiba277-8567Japan Institute of Clinical Medicine and Research The Jikei University School of Medicine Chiba277-8567Japan Department of Laboratory Medicine The Jikei University School of MedicineTokyo 105-8461Japan

There are cases of hepatitis involving occult hepatitis B virus(HBV)infection in which,even though the HB surface antigen(HBsAg)is negative,HBV-DNA is detected by a polymerase chain reaction(PCR).We con-ducted a sequence analysis of the entire HBV region in a case of non-B non-C chronic hepatitis in a 46-yearold female.A diagnosis of non-B non-C chronic hepatitis was *** HBV markers,such as HBs antibody(anti-HBs),anti-HBc,HBeAg and anti-HBe,were negative,HBV-DNA was *** PCR was performed to amplify the precore region of HBV-DNA and all remaining regions by long nested *** analysis of the two obtained bands was conducted by direct *** with the control strains,the ATG(Methionine)start codon in the X region had mut ated to GTG(Valine).It is assumed that a mutation at the start codon in the X region may be the reason why HBV markers are negative in some cases of hepatitis that involve occult HBV infection.

关键词： Hepatitis B virus X region Mutation Non-B non-C chronic hepatitis Occult infection

Knockout of a rice K5.2 gene increases Ca accumulation in the grain

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Journal of Integrative Plant Biology 2024年第2期66卷 252-264页

作者： Peitong Wang Naoki Yamaji namiki Mitani-Ueno Jun Ge Jian Feng Ma National Key Laboratory of Crop Genetics&Germplasm Enhancement and Utilization College of Resources and Environmental SciencesNanjing Agricultural UniversityNanjing 210095China Institute of Plant Science and Resources Okayama UniversityKurashiki 710-0046Japan

Rice is a staple food for half of the world’s population,but it is a poor dietary source of calcium(Ca)due to the low *** is an important issue to boost Ca concentration in this grain to improve Ca deficiency risk,but the mechanisms underlying Ca accumulation are poorly ***,we obtained a rice(Oryza sativa)mutant with high shoot Ca *** mutant exhibited 26%-53% higher Ca in shoots than did wild-type rice(WT)at different Ca *** concentration in the xylem sap was 36% higher in the mutant than in the *** was no difference in agronomic traits between the WT and mutant,but the mutant showed 25% higher Ca in the polished grain compared with the ***-based cloning combined with a complementation test revealed that the mutant phenotype was caused by an 18-bp deletion of a gene,OsK5.2,belonging to the Shaker-like K+channel ***5.2 was highly expressed in the mature region of the roots and its expression in the roots was not affected by Ca levels,but upregulated by low *** showed that OsK5.2 was mainly expressed in the pericycle of the *** together,our results revealed a novel role for OsK5.2 in Ca translocation in rice,and will be a good target for Ca biofortification in rice.

关键词： accumulation biofortification calcium OsK5.2 pericycle rice translocation

Immunotherapy for colorectal cancer

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World Journal of Gastroenterology 2013年第46期19卷 8531-8542页

作者： Shigeo Koido Toshifumi Ohkusa Sadamu Homma yoshihisa namiki Kazuki Takakura Keisuke Saito Zensho Ito Hiroko Kobayashi Mikio Kajihara Kan Uchiyama Seiji Arihiro Hiroshi Arakawa Masato Okamoto Jianlin Gong Hisao Tajiri Division of Gastroenterology and Hepatology Department of Internal Medicine The Jikei University School of Medicine Department of Oncology Institute of DNA Medicine The Jikei University School of Medicine Institute of Clinical Medicine and Research The Jikei University School of Medicine Department of Endoscopy The Jikei University School of Medicine Division of Cellular Signaling Institute for Advanced Medical Research Keio University School of Medicine Department of Medicine Boston University School of Medicine Boston

The incidence of colorectal cancer(CRC)is on the rise,and the prognosis for patients with recurrent or metastatic disease is extremely *** chemotherapy and radiation therapy can improve survival rates,it is imperative to integrate alternative strategies such as immunotherapy to improve outcomes for patients with advanced *** this review,we will discuss the effect of immunotherapy for inducing cytotoxic T lymphocytes and the major immunotherapeutic approaches for CRC that are currently in clinical trials,including peptide vaccines,dendritic cell-based cancer vaccines,whole tumor cell vaccines,viral vector-based cancer vaccines,adoptive cell transfer therapy,antibody-based cancer immunotherapy,and cytokine *** possibility of combination therapies will also be discussed along with the challenges presented by tumor escape mechanisms.

关键词： Colorectal cancer Cytotoxic T lymphocyte Dendritic cell Immunotherapy vaccine

Literature Review on Support for Children and Families Experiencing Parental Bereavement

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Open Journal of Nursing 2024年第4期14卷 139-163页

作者： Rurie namiki Keita Sasaki Iku Taniguchi Rie Wakimizu Department of Nursing Science Graduate School of Comprehensive Human Sciences University of Tsukuba Ibaraki Japan Department of Child Health Care Nursing Division of Health Innovation and Nursing Faculty of Medicine University of Tsukuba Ibaraki Japan

Purpose: This study aimed to understand the actual nursing support in a wide perspective by reviewing overseas literature on support for children who have experienced parental bereavement and their families. The goal was to identify future challenges in nursing support in clinical practice in Japan. Method: Literature searchable as of May 2023 was retrieved using PubMed, resulting in 11 relevant articles. Result: The results revealed the following: 1) For support provided to children, 13 codes were condensed into 5 subcategories and 4 categories. 2) For support provided to families, 36 codes were condensed into 11 subcategories and 4 categories. Conclusion: Open communication was found to be essential for supporting children and their families who have experienced parental bereavement. Moreover, involvement of multiple professions facilitated the provision of specialized support to address diverse needs of children and families, playing a crucial role in overcoming grief. Additionally, the effectiveness of support systems for bereaved families highlighted the need for nursing professionals in Japan to gain knowledge through learning opportunities and to establish a multi-disciplinary approach to support, thus indicating future challenges in nursing support.

关键词： Terminal Care Family Support Child Parental Death Palliative Care

Prostate-specific antigen-based population screening for prostatecancer： current status in Japan and future perspective in Asia

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Asian Journal of Andrology 2015年第3期17卷 475-480页

作者： Yasuhide Kitagawa Mikio namiki Department of Integrative Cancer Therapy and Urology Kanazawa University Graduate School of Medical Science Kanazawa 920-8640 Japan

In Western countries, clinical trials on prostate cancer screening demonstrated a limited benefit for patient survival. In the Asia-Pacific region, including Japan, the rate of prostate-specific antigen （PSA） testing remains very low compared with Western countries, and the benefits of population-based screening remain unclear. This review describes the current status of population screening and diagnosis for prostate cancer in Japan and discusses the efficacy of population screening for the Asian population. Since the 1990s, screening systems have been administered by each municipal government in Japan, and decreases in the prostate cancer mortality rate are expected in some regions where the exposure rate to PSA screening has increased markedly. A population-based screening cohort revealed that the proportion of metastatic disease in cancer detected by screening gradually decreased according to the increased exposure rate, and a decreasing trend in the proportion of cancer with high serum PSA levels after population screening was started. The prognosis of the prostate cancer detected by population screening was demonstrated to be more favorable than those diagnosed outside of the population screening. Recent results in screening cohorts demonstrated the efficacy of PSA. These recent evidences regarding population-based screening in Japan may contribute to establishing the optimal prostate cancer screeninK system in Asian individuals.

关键词： free prostate-specific antigen pro-prostate-specific antigen prostate cancer prostate cancer gene 3 prostate-specificantigen-based population screening serum prostate-specific antigen distribution

What is appropriate neoadjuvant/adjuvant androgen deprivation for high-risk/locally advanced prostate cancer？

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Asian Journal of Andrology 2011年第4期13卷 624-625页

作者： Mikio namiki Hiroyuki Konaka Department of Integrative Cancer Therapy and Urology Kanazawa University Graduate School of Medica Science Ishikawa 920-8640 Japan

The majority of low-risk patients with clinically localized prostate cancer have a high likeliihood of disease-free survival, regardless of the treatment option chosen.

关键词： neoadjuvantladjuvant androgen deprivation prostate