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Association between Subjective Evaluation of Skin Toxicities and Quality of Life in Patients with Lung Cancer Undergoing Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Treatment: A Pilot Study for Developing Skin Toxicity Assessment

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Open Journal of Nursing 2019年第12期9卷 1226-1239页

作者： Kengo Hirayama Ya Su Yasuyuki Ikezawa megumi Chiba Kenichiro Ito Michiko Yuki Faculty of Health Sciences Hokkaido UniversitySapporoJapan Graduate School of Health Sciences Hokkaido UniversitySapporoJapan Department of Respiratory Medicine Oji General HospitalTomakomaiJapan KKR Sapporo Medical Center SapporoJapan

Purposes: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) exert satisfactory therapeutic effects in lung cancer patients. However, the resultant skin toxicity can deteriorate patients’ quality of life (QoL). Differences exist in skin toxicity evaluation between patients and clinicians. We aimed to clarify the association between the subjective evaluation of skin toxicities and QoL in lung cancer patients and to establish a document of scale development in the subjective evaluation of skin toxicity. Methods: We used self-administered questionnaires to evaluate 12 lung cancer patients receiving EGFR-TKI treatment. Indices of QoL were generated using the Functional Assessment of Cancer Therapy-Lung and Hospital Anxiety and Depression Scale, and a subjective evaluation questionnaire concerning skin toxicity was completed. The data were collected immediately before treatment initiation and at 4 weeks post treatment. Results: In the subjective evaluation of skin toxicity, four patients (33.3%) were classified as ≥Grade 2 (painful group), experiencing painful pruritus at the emergence site of the skin rash or xerosis. In this group, the QoL scores of physical and emotional aspects declined after treatment. Conversely, patients in the painless group (Grade 0 - 1) demonstrated an improved emotional QoL following treatment (p = 0.028). Conclusions: Lung cancer patients suffering from painful skin toxicity tended to show a decline in the physical and emotional aspects of QoL following EGFR-TKI treatment. The skin toxicity questionnaire was useful from the point of view of a subjective evaluation and could be a powerful assessment tool in future clinical settings with further modification.

关键词： Lung Cancer EGFR-Tyrosine Kinase Inhibitors Skin Toxicity Quality of Life

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Does Antenatal Fear of Childbirth Predict Postnatal Fear of Childbirth? A Study of Japanese Women

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Open Journal of Nursing 2015年第2期5卷 144-152页

作者： Mizuki Takegata megumi Haruna Masayo Matsuzaki Mie Shiraishi Tadaharu Okano Elisabeth Severinsson Department of Midwifery and Women’s Health Division of Health Sciences & Nursing Graduate School of Medicine The University of Tokyo Tokyo Japan Center of Physical and Mental Health Mie University Tsu City Japan Centre for Women’s Family & Child Health Department of Nursing Science Faculty of Health Sciences Buskerud & Vestfold University College Kongsberg Norway

The study aimed to determine whether antenatal fear of childbirth (expectation) could predict postnatal fear of childbirth (experience) by taking account of other antenatal psychological variables (anxiety and depression) as well as birth outcomes in Japanese women. A longitudinal observational study was conducted at a clinic in Tokyo, Japan, in 2011. Self-report questionnaires were distributed to 240 Japanese women at 37 gestational weeks (Time 1) and on the second day after delivery (Time 2). Regression analyses by means of structural equation modelling were conducted in both the primiparous and the multiparous group. The models exhibited good fit (chisquare value/degree of freedom = 1.10 - 1.62, comparative fit index = 0.92 - 0.99 and root mean square error of approximation = 0.03 - 0.07). Antenatal fear of childbirth was the most predictive variable of postnatal fear of childbirth in both the primiparous (β = 0.58, p = 0.002) and the multiparous group (β = 0.62, p < 0.001). In conclusion, antenatal fear of childbirth was a significant predictor of postnatal fear of childbirth when other antenatal psychological variables and birth outcomes were taken into account. Pregnant women who are strongly afraid of childbirth need special attention before and after delivery.

关键词： Antenatal Fear of Childbirth Japanese Women Postnatal Fear of Childbirth Relationship

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Clinical Significance of Platelet-Derived Growth Factor-C Expression in Colorectal Cancer

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Journal of Cancer Therapy 2014年第1期5卷 11-20页

作者： Shinichi Yamauchi Satoru Iida megumi Ishiguro Toshiaki Ishikawa Hiroyuki Uetake Kenichi Sugihara Department of Surgical Oncology Graduate School Tokyo Medical and Dental University Tokyo Japan Department of Translational Oncology Graduate School Tokyo Medical and Dental University Tokyo Japan

Platelet-derived growth factors (PDGFs) are known to be associated with tumor growth and angiogenesis through their activation of the receptor tyrosine kinases, PDGF receptors alpha and beta. Several studies revealed the participation of the PDGF family in colorectal cancer (CRC). However, the role of platelet derived growth factor-C (PDGFC) in CRC is less well studied. This study aimed to determine the correlation between PDGFC expression and the prognosis of patients with CRCs. Tumor samples were obtained from patients with CRC who underwent surgical resection between 2002 and 2006. The mRNA expression of PDGFC was investigated by quantitative reverse transcription-polymerase chain reaction in 85 patients with stage I-IV CRC. PDGFC protein expression was analyzed by immunohistochemistry, and the relationship between PDGFC protein expression and clinicopathologic features was investigated in 245 patients with stage I-III CRC. PDGFC mRNA expression in cancer tissues was significantly higher in patients with distant metastases than in those without metastases (P = 0.016). PDGFC protein overexpression was associated with significantly worse overall and relapse-free survival (P P < 0.0001, respectively). Moreover, PDGFC protein overexpression was an independent risk factor for CRC recurrence (relative risk = 3.395, 95% confidence interval = 1.895 - 6.081, P < 0.001). In the present study, PDGFC overexpression appeared to be predictive of recurrence and poor prognosis in patients with CRC.

关键词： Platelet-Derived Growth Factor-C Colorectal Cancer Prognosis mRNA Expression Immunohistochemistry

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Anesthetic Management for a Patient of Gorham’s Syndrome: The Vanishing Bone Disease

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Open Journal of Anesthesiology 2017年第6期7卷 147-151页

作者： Aiji Sato-Boku Eisuke Kako megumi Harima Jun Harada Kazuya Sobue Department of Anesthesiology Aichi Gakuin University School of Dentistry Nagoya Japan Department of Anesthesiology and Intensive Care Medicine Nagoya City University Graduate School of Medical Sciences Nagoya Japan

Gorham-Stout (GS) syndrome or the vanishing bone disease is a very rare chronic disease characterized by the destruction of the osseous matrix and proliferation of vascular structures. Review of the general anesthesia showed only a few cases till date. We report general anesthesia for tooth extraction in a 21-year-old male patient with Gorham-Stout syndrome. In this case, the most concerning issue was limited mouth opening due to mandible osteolysis and difficult intubation was anticipated. To anticipate difficult airway management, it is very important to consider the preoperative airway assessment including the cervical spine screening. In this case, the McGrath video laryngoscope prevented the anticipated difficult intubation due to the limited mouth opening due to mandible osteolysis.

关键词： Gorham’s Syndrome Massive Osteolysis General Anesthesia Airway Evaluation

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Allergic Contact Dermatitis from Diethyl Sebacate in a Topical Antimycotic Medicament

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Journal of Cosmetics, Dermatological Sciences and Applications 2012年第3期2卷 216-218页

作者： Ayaka Hirao Naoki Oiso megumi Hama Noriko Higashimori Yoichi Tatsumi Akira Kawada Departments of Dermatology Kinki University Faculty of Medicine Osaka Japan Departments of Patient Safety and Management Kinki University Faculty of Medicine Osaka Japan

Diethyl sebacate is used in topical medicaments in United States and Japan. We described a case of allergic contact dermatitis from diethyl sebacate in a topical antimycotic medicament. Allergic reaction to diethyl sebacate is likely more common because our group has found three of eight sensitized cases. We believe that an investigation regarding the sensitized frequency to diethyl sebacate would conduct to improve the safety of products in United States and Japan.

关键词： Allergic Contact Dermatitis Patch Test Allergen Diethyl Sebacate Safety Evaluation

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Prognostic Factors in Geriatric Patients with Metastatic Colon Cancer

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Journal of Cancer Therapy 2019年第10期10卷 779-788页

作者： Kenji Ina megumi Kabeya Shu Yuasa Yuko Kato Satoshi Kayukawa Takae Kataoka Ryuichi Furuta Department of Medical Oncology Nagoya Memorial Hospital Nagoya Japan Department of Phamacy Nagoya Memorial Hospital Nagoya Japan Medical Social Work Consultation Room Nagoya Memorial Hospital Nagoya Japan Department of Clinical Oncology Nagoya Memorial Hospital Nagoya Japan.

Backgrounds: Colorectal cancer is an important contributor to cancer morbidity and mortality. Given that many older adult patients often have concomitant diseases and impairments in organ function, they are at increased risk for chemotherapy toxicity. Therefore, it is important to identify prognostic factors in older patients undergoing chemotherapy. Methods: We performed a retrospective chart review of colorectal cancer patients treated at Nagoya Memorial Hospital between 2012 and 2017 and selected those who received chemotherapy for metastatic colon cancer. Overall survival was calculated from the beginning of chemotherapy until death or the most recent follow-up date. We used the Kaplan-Meier method to plot survival curves and performed a statistical comparison using a log-rank test. In addition, multivariate analysis was performed using stepwise Cox proportional hazards models. Finally, a comprehensive geriatric assessment was conducted for older patients. The chart review was approved by the ethics committee of Nagoya Memorial Hospital. Results: The overall survival of metastatic colon cancer patients was not markedly different between patients aged ≥ 65 years of age (N = 37). Neither lesion site nor the RAS status affected survival, whereas the usage of three kinds of cytotoxic agents prolonged longevity. In a multivariate analysis of patients ≥ 65 years of age, the only independent prognostic factor for survival was the functional capacity, as measured by the Tokyo Metropolitan Institute of Gerontology (TMIG) index of competence. Conclusions: A combination of the comprehensive geriatric assessment and TMIG index was useful for predicting the longevity in patients with metastatic colon cancer ≥ 65 years of age.

关键词： Metastatic Colon Cancer Chemotherapy Comprehensive Geriatric Assessment TMIG Index of Competence

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Fatal hemophagocytic lymphohistiocytosis presenting as Reye’s syndrome: Report of two cases

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Open Journal of Pediatrics 2012年第2期2卷 161-164页

作者： Shinji Kounami Koichi Minami megumi Yoshiyama Genkichi Izumi Noriyuki Aoyagi Norishige Yoshikawa Department of Pediatrics Wakayama Medical University Kimiidera Wakayama City Japan

We report two cases of rapidly fatal hemophagocytic lymphohistiocytosis (HLH) that presented as Reye’s syndrome (RS). The patients were referred to our hospital because of altered level of consciousness with hyperammonemia and hypoglycemia. The first patient, a 24-month-old girl (Case 1), died soon after arrival and was clinically diagnosed as having RS, but a diagnosis of HLH was established on the basis of autopsy findings. The other patient, a 4-month-old boy (Case 2), was diagnosed as having HLH in view of the bone marrow findings on admission, but immunosuppressive therapy failed to prevent a rapidly fatal course. Marked hypercytokinemia was found in both patients, and liver pathology demonstrated panlobular microvesicular steatosis of hepatocytes, resembling that in RS. Mononuclear cell infiltration with hemophagocytosis in the liver was evident in case 2, but not in case 1. In both cases, hypercytokinemia was thought to have caused mitochondrial dysfunction, resulting in RS-like microvesicular steatosis of hepatocytes. HLH is an important differential diagnosis of children presenting with RS-like picture.

关键词： Hemophagocytic Lymphohistiocytosis Reye’s Syndrome Cytokine Mitochondria Encephalopathy

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Pelvic floor function and advanced maternal age at first vaginal delivery

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Open Journal of Obstetrics and Gynecology 2013年第4期3卷 28-34页

作者： Mikako Yoshida Ryoko Murayama Maki Nakata megumi Haruna Masayo Matsuzaki Mie Shiraishi Hiromi Sanada Department of Advanced Nursing Technology Graduate School of Medicine The University of Tokyo Tokyo Japan Department of Gerontological Nursing/Wound Care Management Graduate School of Medicine The University of Tokyo Tokyo Japan Department of Midwifery and Women’s Health Graduate School of Medicine The University of Tokyo Tokyo Japan Department of Obstetrics and Gynecology Mitsui Memorial Hospital Tokyo Japan

Purpose: The study aimed to show differences in temporal recovery of pelvic floor function within 6 months postpartum between women having their first delivery at an advanced age and those having their first delivery at a younger age. Methods: Seventeen women (age: 35.5 ± 3.5, BMI: 21.1 ± 3.2) were studied at about 6 weeks, 3 months, and 6 months after vaginal delivery. Urinary incontinence was assessed by the International Consultation on Incontinence Questionnaire-Short Form. Pelvic floor function was assessed by the anteroposterior diameter of the levator hiatus using transperineal ultrasound. Women who delivered for the first time at 35 years and/or older were defined as being of advanced maternal age. Results: Nine of 17 women (52.9%) were of advanced maternal age and 5 experienced postpartum stress urinary incontinence. Four of these 5 women (80.0%) were of advanced maternal age. The anteroposterior diameter of the levator hiatus at rest was significantly greater in the advanced maternal age women than in the younger maternal age women at 3 and 6 months postpartum (p < 0.01). Among the continent women, the anteroposterior diameter of the levator hiatus at rest was significantly greater in the advanced maternal age women than in the younger maternal age women at 6 months postpartum (p = 0.004). However, among the advanced maternal age women, all parameters of the anteroposterior diameter of the levator hiatus were not significantly different between the women with and without stress urinary continence. Conclusion: Recovery of pelvic floor function following delivery may be delayed in women of advanced maternal age at first delivery because of the damage to the pelvic floor during pregnancy and vaginal delivery, resulting in increase in the incidence of stress urinary incontinence.

关键词： Advanced Maternal Age Pelvic Floor Stress Urinary Incontinence Ultrasound Vaginal Delivery

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Optimization of siRNA Delivery Method into the Liver by Sequential Injection of Polyglutamic Acid and Cationic Lipoplex

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Pharmacology & Pharmacy 2015年第7期6卷 302-310页

作者： Yoshiyuki Hattori Shohei Arai Takuto Kikuchi megumi Hamada Ryou Okamoto Yoko Machida Kumi Kawano Department of Drug Delivery Research Hoshi University Tokyo Japan

Previously, we developed a novel siRNA transfer method to the liver by sequential intravenous injection of poly-L-glutamic acid (PGA) and cationic liposome/siRNA complex (cationic lipoplex). In this study, we examined the effects of the charge ratio (+/-) of cationic liposome/siRNA, molecular weight of PGA and cationic lipid of cationic liposome on the biodistribution of siRNA after sequential injection of PGA plus cationic lipoplex. When 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/cholesterol (Chol) lipoplex was intravenously injected into mice, the accumulation of siRNA was mainly observed in the lungs. In contrast, when DOTAP/Chol lipoplex was intravenously injected at 1 min after intravenous injection of PGA, siRNA was largely accumulated in the liver. The charge ratio (+/-) of DOTAP/Chol liposome/siRNA did not affect the biodistribution of siRNA after sequential injection. As regards the molecular weight of PGA, the accumulation of siRNA was observed mainly in the liver after the sequential injection of PGA of 20.5, 38, 64 or 200 kDa plus DOTAP/Chol lipoplex. Furthermore, to examine the effect of cationic lipid of cationic liposome on the biodistribution of siRNA, we prepared other cationic liposomes composed of 1,2-di-O-octadecenyl-3-trimethylammonium propane chloride (DOTMA)/Chol, dimethyldioctade-cylammonium bromide (DDAB)/Chol and O,O’-ditetradecanoyl-N-(α-trimethylammonioacetyl)di-ethanolamine chloride (DC-6-14)/Chol. For the cationic liposomes, the accumulation of siRNA was observed mainly in the liver when their cationic lipoplexes were sequentially injected after injection of PGA into mice. From these findings, sequential injection of PGA plus cationic lipoplex could deliver siRNA efficiently into the liver regardless of the charge ratio (+/-) of lipoplex, lengths of PGA and cationic lipid of liposome.

关键词： Cationic Liposome siRNA Delivery Polyglutamic Acid Liver Targeting Sequential Injection

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Porcine Placenta Extract Enhances Ceramide Synthase 3 Expression through the PPARδ/ILK/Akt/mTOR/STAT3 Pathway

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Journal of Cosmetics, Dermatological Sciences and Applications 2022年第3期12卷 131-144页

作者： Akihiro Aioi Ryuta Muromoto Jun-ichi Kashiwakura Sho Mogami megumi Nishikawa Shigeyuki Ogawa Tadashi Matsuda Septem-Soken 2-4-27 Dojima Kita-ku Osaka Japan Laboratory of Immunology Faculty of Pharmaceutical Sciences Hokkaido University Sapporo Japan

Porcine placenta extract (PPE) is widely accepted as an ingredient in complementary and alternative medicine and previous studies have reported its availability, however, its underlying action mechanism remains unclear. In this study, we investigated the underlying mechanism of PPE-induced ceramide synthase 3 upregulation. PPE enhanced the expression of ceramide synthase 3 at both the mRNA and protein levels in HaCaT cells. Moreover, PPE-induced ceramide synthase3 upregulation was suppressed by the Akt inhibitor, suggesting the involvement of Akt in the underlying mechanism. As the PI3K inhibitor did not affect PPE-induced ceramide synthase 3 upregulation, the factors upstream of Akt were estimated. Inhibition and small interfering RNA experiments demonstrated that the peroxisome proliferator-activated receptors δ (PPARδ) and integrin-linked kinase (ILK) are involved in the phosphorylation of Akt. Next, we explored the factors downstream of Akt and found that PPE induced phosphorylation of the STAT3 while PPE-induced upregulation of ceramide synthase 3 was significantly suppressed by the inhibitor of the mTOR, suggesting that the mTOR/STAT3 pathway is involved in the downstream of Akt. These results demonstrate that PPE upregulates CerS3 expression via the PPARδ/ILK/Akt/mTOR/STAT3 pathway.

关键词： Porcine Placenta Ceramide Synthase 3 Signaling Pathway

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