Background/aim: Genomic variants can predispose individuals to adverse drug effects (ADEs), implying the potential for personalised therapy based on genetic data to prevent them. However, existing pharmacogenomic databases lack a comprehensive list of such variants due to irregular updates and incomplete literature coverage. To facilitate the assessment of the feasibility of using pharmacogenetic testing on a larger scale and identify existing gaps in the literature, this study sought to compile a comprehensive list of genomic variants associated with ADEs, with a focus on serious ADEs.
Patients and methods: To identify relevant pharmacogenetic studies within randomised controlled trials (RCTs), post-hoc studies of RCTs and meta-analyses, two literature searches were performed across multiple databases. The compiled list of variants associated with ADEs was refined to create a set of variant-drug pairs significantly associated with serious ADEs.
Results: We identified 254 RCTs/post-hoc studies and 207 meta-analyses investigating variants associated with ADEs. Among the 254 RCTs/post-hoc studies identified, 24 meta-analyses were conducted. Among these, only G6PD A- showed a significant association with severe anaemia in patients receiving artemisinin-based treatment for malaria.
Conclusion: This systematic review provides a comprehensive list of variants associated with ADEs and a set of variant-drug pairs significantly associated with serious ADEs. These resources serve as valuable references for regulatory agencies, researchers, and healthcare professionals. This study, however, underscores the need for improved indexing and standardised definitions of ADE seriousness in the literature.
{"title":"Pharmacogenomic Determinants of Adverse Drug Effects: A Systematic Review and Meta-analysis.","authors":"Kinan Mokbel, Michael Weedon, Leigh Jackson","doi":"10.21873/invivo.13671","DOIUrl":"10.21873/invivo.13671","url":null,"abstract":"<p><strong>Background/aim: </strong>Genomic variants can predispose individuals to adverse drug effects (ADEs), implying the potential for personalised therapy based on genetic data to prevent them. However, existing pharmacogenomic databases lack a comprehensive list of such variants due to irregular updates and incomplete literature coverage. To facilitate the assessment of the feasibility of using pharmacogenetic testing on a larger scale and identify existing gaps in the literature, this study sought to compile a comprehensive list of genomic variants associated with ADEs, with a focus on serious ADEs.</p><p><strong>Patients and methods: </strong>To identify relevant pharmacogenetic studies within randomised controlled trials (RCTs), post-hoc studies of RCTs and meta-analyses, two literature searches were performed across multiple databases. The compiled list of variants associated with ADEs was refined to create a set of variant-drug pairs significantly associated with serious ADEs.</p><p><strong>Results: </strong>We identified 254 RCTs/post-hoc studies and 207 meta-analyses investigating variants associated with ADEs. Among the 254 RCTs/post-hoc studies identified, 24 meta-analyses were conducted. Among these, only G6PD A- showed a significant association with severe anaemia in patients receiving artemisinin-based treatment for malaria.</p><p><strong>Conclusion: </strong>This systematic review provides a comprehensive list of variants associated with ADEs and a set of variant-drug pairs significantly associated with serious ADEs. These resources serve as valuable references for regulatory agencies, researchers, and healthcare professionals. This study, however, underscores the need for improved indexing and standardised definitions of ADE seriousness in the literature.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background/aim: Breast cancer is the most predominant type of cancer affecting women worldwide and the current therapeutic treatment for breast cancer patients is not adequately effective. This study aimed to investigate the mechanism of 17-AAG, a heat shock protein (HSP90) inhibitor, as a treatment for inducing breast cancer cell apoptosis.
Materials and methods: The pharmacology network was employed to examine the correlation of 17-AAG with the gene expression profiles of breast cancer, obtained by Gene Expression Profiling Interactive Analysis (GEPIA). MTT and flow cytometry were utilized to investigate cell proliferation and cell apoptosis, respectively. Dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay and western blot analysis were employed to examine the correlation between cellular oxidant levels and protein expression. Immunofluorescence staining was utilized to confirm the protein localization and assess DNA damage.
Results: The pharmacological network analysis revealed that HSP90 serves as the common target connecting 17-AAG and breast cancer genes. Treatment with 17-AAG significantly increased cell apoptosis. Moreover, the treatment resulted in up-regulation of cellular oxidant levels and PERK/eIF2α expression. In line with these, protein localization after treatment revealed an increase in DNA damage, correlating with higher ER stress levels. Furthermore, GEPIA demonstrated that PERK and eIF2α expression were significantly higher in breast invasive carcinoma compared to other tumor types.
Conclusion: HSP90 emerges as a potential target for inducing apoptosis in breast cancer cells by disrupting protein homeostasis in the endoplasmic reticulum, possibly through PERK/eIF2α up-regulation. 17-AAG, an HSP90 inhibitor, may therefore potentially hold an alternative therapeutic strategy for breast cancer treatment.
背景/目的:乳腺癌是全球女性最主要的癌症类型,目前对乳腺癌患者的治疗效果不佳。本研究旨在探讨热休克蛋白(HSP90)抑制剂17-AAG诱导乳腺癌细胞凋亡的机制:采用药理学网络研究 17-AAG 与乳腺癌基因表达谱的相关性。MTT 和流式细胞术分别用于研究细胞增殖和细胞凋亡。二氯二氢荧光素二乙酸酯(DCFH-DA)测定和 Western 印迹分析用于检测细胞氧化剂水平与蛋白质表达之间的相关性。免疫荧光染色用于确认蛋白质定位和评估 DNA 损伤:药理学网络分析显示,HSP90 是连接 17-AAG 和乳腺癌基因的共同靶点。用 17-AAG 治疗可明显增加细胞凋亡。此外,治疗还导致细胞氧化水平和 PERK/eIF2α 表达上调。与此相一致,处理后的蛋白质定位显示 DNA 损伤增加,与较高的 ER 应激水平相关。此外,GEPIA表明,与其他肿瘤类型相比,乳腺浸润癌中PERK和eIF2α的表达明显更高:结论:HSP90 可能通过上调 PERK/eIF2α 来破坏内质网中的蛋白质平衡,从而成为诱导乳腺癌细胞凋亡的潜在靶点。因此,HSP90 抑制剂 17-AAG 有可能成为治疗乳腺癌的另一种疗法。
{"title":"17-AAG Induces Endoplasmic Reticulum Stress-mediated Apoptosis in Breast Cancer Cells, Possibly Through PERK/eIF2α Up-regulation.","authors":"Prasit Suwannalert, Pimchanok Panpinyaporn, Pitchapa Wantanachaisaeng, Teerapat Teeppaibul, Thanaphat Worawichitchaikun, Thidarat Koomsang, Chonnapat Naktubtim, Witchuda Payuhakrit","doi":"10.21873/invivo.13687","DOIUrl":"10.21873/invivo.13687","url":null,"abstract":"<p><strong>Background/aim: </strong>Breast cancer is the most predominant type of cancer affecting women worldwide and the current therapeutic treatment for breast cancer patients is not adequately effective. This study aimed to investigate the mechanism of 17-AAG, a heat shock protein (HSP90) inhibitor, as a treatment for inducing breast cancer cell apoptosis.</p><p><strong>Materials and methods: </strong>The pharmacology network was employed to examine the correlation of 17-AAG with the gene expression profiles of breast cancer, obtained by Gene Expression Profiling Interactive Analysis (GEPIA). MTT and flow cytometry were utilized to investigate cell proliferation and cell apoptosis, respectively. Dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay and western blot analysis were employed to examine the correlation between cellular oxidant levels and protein expression. Immunofluorescence staining was utilized to confirm the protein localization and assess DNA damage.</p><p><strong>Results: </strong>The pharmacological network analysis revealed that HSP90 serves as the common target connecting 17-AAG and breast cancer genes. Treatment with 17-AAG significantly increased cell apoptosis. Moreover, the treatment resulted in up-regulation of cellular oxidant levels and PERK/eIF2α expression. In line with these, protein localization after treatment revealed an increase in DNA damage, correlating with higher ER stress levels. Furthermore, GEPIA demonstrated that PERK and eIF2α expression were significantly higher in breast invasive carcinoma compared to other tumor types.</p><p><strong>Conclusion: </strong>HSP90 emerges as a potential target for inducing apoptosis in breast cancer cells by disrupting protein homeostasis in the endoplasmic reticulum, possibly through PERK/eIF2α up-regulation. 17-AAG, an HSP90 inhibitor, may therefore potentially hold an alternative therapeutic strategy for breast cancer treatment.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background/aim: Transanal endoscopic local excision requires fine operation in a very narrow space in the rectum. We report a case in which the use of surgical instruments with a multi-jointed structure allowed safe resection of a lesion with a stable field of view, resulting in preservation of postoperative function.
Case report: The patient was a 49-year-old man who had a rectal neuroendocrine tumor (NET) (G1) with erosive changes in the lower rectum. Preoperative imaging showed no evidence of surrounding lymph node or distant metastasis; thus, we performed a transanal endoscopic local excision of the tumor. After positioning the patient under general anesthesia and securing the field of view in the intra-rectal cavity, the flexion of the surgical instruments with a multi-jointed structure was used to secure the operating space to not interfere with the camera and the surgeon's right hand. The operating field was developed, and the tumor was incised by stable traction. After the excision, the needle was advanced in the direction of the intestinal axis using the multi-jointed holder, and continuous suturing was performed. The patient has no recurrence without any defecation disorder.
Conclusion: The use of multi-jointed surgical instruments in transanal endoscopic excision of rectal tumors can provide a stable operative field and preserve postoperative function. The advanced flexibility of these instruments allows precise manipulation in the narrow rectal space, resulting in successful tumor resection with minimal invasiveness and no postoperative complications. These findings suggest that multi-jointed instruments are valuable for enhancing the safety and efficacy of minimally invasive rectal surgery.
{"title":"A Case of Transanal Endoscopic Excision for Rectal Tumor Using Surgical Instruments With Multi-jointed Structures.","authors":"Yuki Toyoda, Rie Hayashi, Norikatsu Miyoshi, Rie Mizumoto, Kengo Haruna, Shinya Kato, Soichiro Minami, Mitsunobu Takeda, Yuki Sekido, Shiki Fujino, Tsuyoshi Hata, Atsushi Hamabe, Takayuki Ogino, Hidekazu Takahashi, Mamoru Uemura, Hirofumi Yamamoto, Yuichiro Doki, Hidetoshi Eguchi","doi":"10.21873/invivo.13732","DOIUrl":"10.21873/invivo.13732","url":null,"abstract":"<p><strong>Background/aim: </strong>Transanal endoscopic local excision requires fine operation in a very narrow space in the rectum. We report a case in which the use of surgical instruments with a multi-jointed structure allowed safe resection of a lesion with a stable field of view, resulting in preservation of postoperative function.</p><p><strong>Case report: </strong>The patient was a 49-year-old man who had a rectal neuroendocrine tumor (NET) (G1) with erosive changes in the lower rectum. Preoperative imaging showed no evidence of surrounding lymph node or distant metastasis; thus, we performed a transanal endoscopic local excision of the tumor. After positioning the patient under general anesthesia and securing the field of view in the intra-rectal cavity, the flexion of the surgical instruments with a multi-jointed structure was used to secure the operating space to not interfere with the camera and the surgeon's right hand. The operating field was developed, and the tumor was incised by stable traction. After the excision, the needle was advanced in the direction of the intestinal axis using the multi-jointed holder, and continuous suturing was performed. The patient has no recurrence without any defecation disorder.</p><p><strong>Conclusion: </strong>The use of multi-jointed surgical instruments in transanal endoscopic excision of rectal tumors can provide a stable operative field and preserve postoperative function. The advanced flexibility of these instruments allows precise manipulation in the narrow rectal space, resulting in successful tumor resection with minimal invasiveness and no postoperative complications. These findings suggest that multi-jointed instruments are valuable for enhancing the safety and efficacy of minimally invasive rectal surgery.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background/aim: The overexpression of matrix metalloproteinase-9 (MMP9) has been observed in asthmatic patients, yet the role of MMP9 genotype in determining asthma susceptibility remains unresolved. This study aimed to elucidate the contribution of MMP9 promoter rs3918242 genotype to asthma risk in Taiwan.
Materials and methods: A cohort comprising 453 non-asthmatic healthy controls and 198 asthmatic cases was assembled, and the MMP9 rs3918242 genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism methodology.
Results: Our findings indicated that people carrying the variant CT or TT genotype of MMP9 rs3918242 did not demonstrate an elevated risk of asthma compared to wild-type CC carriers (odds ratio=1.28 and 1.72, 95% confidence interval=0.87-1.87 and 0.72-4.13; p=0.2417 and 0.3201, respectively). Furthermore, individuals carrying the T allele at MMP9 rs3918242 did not exhibit a higher risk of asthma than those carrying the C allele (odds ratio=1.31, 95% confidence interval=0.96-1.79, p=0.0869). Interestingly, a positive association was observed between MMP9 rs3918242 CT or TT genotypes and the severity of asthma symptoms among asthmatic patients (p=0.0035).
Conclusion: Although the T allele at MMP9 rs3918242 was not associated with asthma risk, it may serve as a predictor for asthma symptom severity. These findings warrant validation in larger and more diverse populations to further elucidate the significance of MMP9 in asthma etiology.
{"title":"Impacts of Matrix Metalloproteinase-9 Promoter Genotypes on Asthma Risk.","authors":"Kuo-Liang Chiu, Jie-Long He, Guan-Liang Chen, Te-Chun Shen, Li-Hsiou Chen, Jaw-Chyun Chen, Chia-Wen Tsai, Wen-Shin Chang, Te-Chun Hsia, DA-Tian Bau","doi":"10.21873/invivo.13677","DOIUrl":"10.21873/invivo.13677","url":null,"abstract":"<p><strong>Background/aim: </strong>The overexpression of matrix metalloproteinase-9 (MMP9) has been observed in asthmatic patients, yet the role of MMP9 genotype in determining asthma susceptibility remains unresolved. This study aimed to elucidate the contribution of MMP9 promoter rs3918242 genotype to asthma risk in Taiwan.</p><p><strong>Materials and methods: </strong>A cohort comprising 453 non-asthmatic healthy controls and 198 asthmatic cases was assembled, and the MMP9 rs3918242 genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism methodology.</p><p><strong>Results: </strong>Our findings indicated that people carrying the variant CT or TT genotype of MMP9 rs3918242 did not demonstrate an elevated risk of asthma compared to wild-type CC carriers (odds ratio=1.28 and 1.72, 95% confidence interval=0.87-1.87 and 0.72-4.13; p=0.2417 and 0.3201, respectively). Furthermore, individuals carrying the T allele at MMP9 rs3918242 did not exhibit a higher risk of asthma than those carrying the C allele (odds ratio=1.31, 95% confidence interval=0.96-1.79, p=0.0869). Interestingly, a positive association was observed between MMP9 rs3918242 CT or TT genotypes and the severity of asthma symptoms among asthmatic patients (p=0.0035).</p><p><strong>Conclusion: </strong>Although the T allele at MMP9 rs3918242 was not associated with asthma risk, it may serve as a predictor for asthma symptom severity. These findings warrant validation in larger and more diverse populations to further elucidate the significance of MMP9 in asthma etiology.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background/aim: Chronic lower limb ischaemia is a peripheral arterial disease (PAD) which is typically instigated by atherosclerotic plaques in the peripheral vasculature. This article reports on a unique case of chronic ischaemia in the lower limb, presenting in a distinctive manner as a fungal toenail infection.
Case report: An 82-year-old frail woman with multimorbidity presented with toenail symptoms in her right foot. While initial examination had shown onychomycosis, further investigation was unexpectedly consistent with chronic ischaemia in the lower limb. We explored the clinical presentation, diagnostic challenges encountered, and the subsequent management of this unique manifestation in the context of the patient's multimorbidity.
Conclusion: This case report highlights the need to consider chronic limb ischemia as a differential diagnosis in toenail infections when no alternative causes or predisposing factors are identified.
{"title":"Lower Limb Chronic Ischaemia Presenting Exclusively as Fungal Toenail Infection: Case Report and Brief Literature Review.","authors":"Kinan Mokbel, Rob Daniels, Mohammad Alallan","doi":"10.21873/invivo.13725","DOIUrl":"10.21873/invivo.13725","url":null,"abstract":"<p><strong>Background/aim: </strong>Chronic lower limb ischaemia is a peripheral arterial disease (PAD) which is typically instigated by atherosclerotic plaques in the peripheral vasculature. This article reports on a unique case of chronic ischaemia in the lower limb, presenting in a distinctive manner as a fungal toenail infection.</p><p><strong>Case report: </strong>An 82-year-old frail woman with multimorbidity presented with toenail symptoms in her right foot. While initial examination had shown onychomycosis, further investigation was unexpectedly consistent with chronic ischaemia in the lower limb. We explored the clinical presentation, diagnostic challenges encountered, and the subsequent management of this unique manifestation in the context of the patient's multimorbidity.</p><p><strong>Conclusion: </strong>This case report highlights the need to consider chronic limb ischemia as a differential diagnosis in toenail infections when no alternative causes or predisposing factors are identified.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background/aim: Oral squamous cell carcinoma (OSCC) presents a significant health challenge, requiring effective treatments. Magnolol, a compound with potential anticancer properties, warrants investigation in OSCC treatment. Here, we aimed to assess the efficacy of magnolol in inhibiting progression of OSCC and to explore the underlying mechanisms of its action.
Materials and methods: We evaluated the effect of magnolol on tumor progression using the MOC1-bearing orthotopic model. We examined its impact on pathology and toxicity through hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and biochemical analysis. We also investigated the immunoregulatory effects of magnolol in the MOC1-bearing model using flow cytometry.
Results: At high doses, magnolol significantly reduced tumor volume (p<0.0001 for comparisons between treated with magnolol and untreated groups) and weight loss by 70% in vivo. It also induced caspase-dependent apoptosis, evidenced by 2.42-, 2-, and 2.2-fold increases in the expression of caspase-3, -8, and -9, respectively, in mouse tumors treated with high 60 mg/kg of magnolol compared to untreated (p<0.0001 for all comparisons). Magnolol demonstrated no toxicity, maintaining body weight and normal biochemical parameters, including liver and kidney function. Pathological evaluations showed no adverse effects on organs in all treatment groups. Moreover, high doses of magnolol enhanced natural killer cells (by 3%), dendritic cells (20-25%), and cytotoxic T cells (20-40%) while reducing myeloid-derived suppressor cells and regulatory T cells by 1.5 times.
Conclusion: Magnolol demonstrates potential as a therapeutic agent for OSCC, offering antitumor efficacy and immunomodulatory benefits.
{"title":"Magnolol's Therapeutic Efficacy and Immunomodulatory Effects in Oral Squamous Cell Carcinoma.","authors":"Chien-Fu Tseng, Hsin-Ming Chen, Tsai-Lan Liao, Fei-Ting Hsu, Chi-Jung Yeh, Wei-Ting Chen, Sang-Heng Kok","doi":"10.21873/invivo.13678","DOIUrl":"10.21873/invivo.13678","url":null,"abstract":"<p><strong>Background/aim: </strong>Oral squamous cell carcinoma (OSCC) presents a significant health challenge, requiring effective treatments. Magnolol, a compound with potential anticancer properties, warrants investigation in OSCC treatment. Here, we aimed to assess the efficacy of magnolol in inhibiting progression of OSCC and to explore the underlying mechanisms of its action.</p><p><strong>Materials and methods: </strong>We evaluated the effect of magnolol on tumor progression using the MOC1-bearing orthotopic model. We examined its impact on pathology and toxicity through hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and biochemical analysis. We also investigated the immunoregulatory effects of magnolol in the MOC1-bearing model using flow cytometry.</p><p><strong>Results: </strong>At high doses, magnolol significantly reduced tumor volume (p<0.0001 for comparisons between treated with magnolol and untreated groups) and weight loss by 70% in vivo. It also induced caspase-dependent apoptosis, evidenced by 2.42-, 2-, and 2.2-fold increases in the expression of caspase-3, -8, and -9, respectively, in mouse tumors treated with high 60 mg/kg of magnolol compared to untreated (p<0.0001 for all comparisons). Magnolol demonstrated no toxicity, maintaining body weight and normal biochemical parameters, including liver and kidney function. Pathological evaluations showed no adverse effects on organs in all treatment groups. Moreover, high doses of magnolol enhanced natural killer cells (by 3%), dendritic cells (20-25%), and cytotoxic T cells (20-40%) while reducing myeloid-derived suppressor cells and regulatory T cells by 1.5 times.</p><p><strong>Conclusion: </strong>Magnolol demonstrates potential as a therapeutic agent for OSCC, offering antitumor efficacy and immunomodulatory benefits.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background/aim: Although nutritional risk factors for developing complications in type 2 diabetes mellitus (T2DM) have been examined, the effect of protein intake on nephropathy is debated, and there is little research on retinopathy. This cross-sectional case-series study aimed to examine the risk factors, including nutritional status, for complications in patients newly diagnosed with T2DM.
Patients and methods: Fifty-four patients were recruited, based on the results of examinations of blood glucose and/or glycated hemoglobin level for T2DM. To evaluate nutritional status, blood and urine examinations were performed and the Food Frequency Questionnaire was administered. Two-way analysis of variance, Fisher's exact test and logistic regression analyses were performed.
Results: The patients were categorized into four groups: 24 without albuminuria and without retinopathy, four without albuminuria with retinopathy, 21 with albuminuria without retinopathy, and five with albuminuria with retinopathy. Logistic analysis of albuminuria revealed that estimated sodium intake was significantly independent as the explanatory factors of age, sex, and body mass index. Patients with retinopathy had significantly higher blood urea nitrogen, and significantly lower plasma total protein levels than patients without retinopathy, suggesting that retinopathy is related to a higher catabolic state. Through a questionnaire on food intake, patients with retinopathy had a significantly lower intake of fat and monounsaturated fatty acids and a significantly higher intake of iodine based on intake of seaweed, corrected for energy intake, than patients without retinopathy.
Conclusion: The present study may lead to planning a large cohort study for examining nutritional risk factors related to complications in patients newly diagnosed with T2DM in Japan.
{"title":"Nutritional Risk Factors in Albuminuria and Retinopathy in Patients Newly Diagnosed With Type 2 Diabetes: A Cross-sectional Case Series Study.","authors":"Emi Arimura, Yukiko Maruguti, Yaoko Nakao, Miharu Ushikai, Koji Yotsueda, Shoko Kajiya, Yoshihiko Nishio, Masahisa Horiuchi","doi":"10.21873/invivo.13722","DOIUrl":"10.21873/invivo.13722","url":null,"abstract":"<p><strong>Background/aim: </strong>Although nutritional risk factors for developing complications in type 2 diabetes mellitus (T2DM) have been examined, the effect of protein intake on nephropathy is debated, and there is little research on retinopathy. This cross-sectional case-series study aimed to examine the risk factors, including nutritional status, for complications in patients newly diagnosed with T2DM.</p><p><strong>Patients and methods: </strong>Fifty-four patients were recruited, based on the results of examinations of blood glucose and/or glycated hemoglobin level for T2DM. To evaluate nutritional status, blood and urine examinations were performed and the Food Frequency Questionnaire was administered. Two-way analysis of variance, Fisher's exact test and logistic regression analyses were performed.</p><p><strong>Results: </strong>The patients were categorized into four groups: 24 without albuminuria and without retinopathy, four without albuminuria with retinopathy, 21 with albuminuria without retinopathy, and five with albuminuria with retinopathy. Logistic analysis of albuminuria revealed that estimated sodium intake was significantly independent as the explanatory factors of age, sex, and body mass index. Patients with retinopathy had significantly higher blood urea nitrogen, and significantly lower plasma total protein levels than patients without retinopathy, suggesting that retinopathy is related to a higher catabolic state. Through a questionnaire on food intake, patients with retinopathy had a significantly lower intake of fat and monounsaturated fatty acids and a significantly higher intake of iodine based on intake of seaweed, corrected for energy intake, than patients without retinopathy.</p><p><strong>Conclusion: </strong>The present study may lead to planning a large cohort study for examining nutritional risk factors related to complications in patients newly diagnosed with T2DM in Japan.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sotirios Sachanas, Christina Stefanaki, Leonidas Marinos, Xanthi Yiakoumis, Maria Moschogiannis, Efstathios Koulieris, Maria Efstathopoulou, Gerassimos A Pangalis
Background/aim: Hairy cell leukemia (HCL) is a well-known lymphoproliferative disease with very effective treatment approaches primarily relying on purine analogues. However, these treatments are associated with profound and prolonged immunosuppression. Merkel cell carcinoma (MCC) is a rare and extremely aggressive skin tumor with an increased incidence in immunocompromised patients.
Case report: We report a case of a patient with HCL who was diagnosed with MCC, while in remission following retreatment with pentostatin, which induced a profound decrease in CD4 (+) T-cells.
Conclusion: Our case provides further evidence supporting the hypothesis of a significant association between immunosuppression and MCC pathogenesis.
背景/目的:毛细胞白血病(HCL)是一种众所周知的淋巴细胞增生性疾病,主要依靠嘌呤类似物进行有效治疗。然而,这些治疗方法都会带来深刻而持久的免疫抑制。梅克尔细胞癌(MCC)是一种罕见的侵袭性极强的皮肤肿瘤,在免疫力低下的患者中发病率较高:我们报告了一例 HCL 患者的病例,该患者在接受喷司他丁再治疗后病情得到缓解,但却被诊断为 MCC,而喷司他丁会导致 CD4 (+) T 细胞大量减少:我们的病例为免疫抑制与 MCC 发病机制之间存在显著关联的假设提供了进一步的证据支持。
{"title":"A Rapidly Developing Nodule in a Patient With Hairy Cell Leukemia in Remission: Merkel Cell Carcinoma: A Case Report.","authors":"Sotirios Sachanas, Christina Stefanaki, Leonidas Marinos, Xanthi Yiakoumis, Maria Moschogiannis, Efstathios Koulieris, Maria Efstathopoulou, Gerassimos A Pangalis","doi":"10.21873/invivo.13727","DOIUrl":"10.21873/invivo.13727","url":null,"abstract":"<p><strong>Background/aim: </strong>Hairy cell leukemia (HCL) is a well-known lymphoproliferative disease with very effective treatment approaches primarily relying on purine analogues. However, these treatments are associated with profound and prolonged immunosuppression. Merkel cell carcinoma (MCC) is a rare and extremely aggressive skin tumor with an increased incidence in immunocompromised patients.</p><p><strong>Case report: </strong>We report a case of a patient with HCL who was diagnosed with MCC, while in remission following retreatment with pentostatin, which induced a profound decrease in CD4 (+) T-cells.</p><p><strong>Conclusion: </strong>Our case provides further evidence supporting the hypothesis of a significant association between immunosuppression and MCC pathogenesis.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ryo Miyata, Masaya Aoki, Shoichiro Morizono, Tadashi Umehara, Aya Harada-Takeda, G O Kamimura, Toshiyuki Nagata, Kazuhiro Ueda
Background/aim: The prognostic impact of adjuvant cytotoxic chemotherapy for patients with resectable locally advanced non-small cell lung cancer (NSCLC) who underwent surgery after neoadjuvant chemotherapy remains unclear.
Patients and methods: A retrospective chart review was performed to identify patients who underwent surgery following neoadjuvant therapy for clinical T3N0 or N1-N2 resectable NSCLC between 2011 and 2016 at our hospital. Survival outcomes were analyzed with the Kaplan-Meier method and a Cox proportional hazard model.
Results: Thirty-eight patients were identified. The median recurrence-free survival (RFS) was 50.6 months and overall survival (OS) was 75.2 months. Patients who had undergone adjuvant chemotherapy were not associated with a favorable RFS (hazard ratio=1.01, p=0.98) or OS (hazard ratio=0.72, p=0.55), as compared with those who had not. However, subgroup analysis revealed that hazard ratio based on RFS and OS varied greatly between subgroups, suggesting that selected patients might benefit from adjuvant therapy, while others might be harmed by it. For example, in surgical-pathological stage III disease, adjuvant therapy showed a favorable RFS (HR=0.22, 95%CI=0.02-2.57, p=0.23) and OS (HR=0.36, 95%CI=0.03-4.01, p=0.40). Conversely, in surgical-pathological stage 0-II disease, adjuvant therapy showed an unfavorable RFS (HR=1.40, 95%CI=0.49-3.96, p=0.53) and OS (HR=0.95, 95%CI=0.29-3.12, p=0.93).
Conclusion: Regardless of the negative findings in our overall patient cohort, our results may be beneficial in identifying patients who may likely benefit from adjuvant therapy. This contribution could assist the planning of large-scale prospective studies.
{"title":"Adjuvant Chemotherapy in Addition to Neoadjuvant Chemotherapy for Locally Advanced Non-small Cell Lung Cancer.","authors":"Ryo Miyata, Masaya Aoki, Shoichiro Morizono, Tadashi Umehara, Aya Harada-Takeda, G O Kamimura, Toshiyuki Nagata, Kazuhiro Ueda","doi":"10.21873/invivo.13723","DOIUrl":"10.21873/invivo.13723","url":null,"abstract":"<p><strong>Background/aim: </strong>The prognostic impact of adjuvant cytotoxic chemotherapy for patients with resectable locally advanced non-small cell lung cancer (NSCLC) who underwent surgery after neoadjuvant chemotherapy remains unclear.</p><p><strong>Patients and methods: </strong>A retrospective chart review was performed to identify patients who underwent surgery following neoadjuvant therapy for clinical T3N0 or N1-N2 resectable NSCLC between 2011 and 2016 at our hospital. Survival outcomes were analyzed with the Kaplan-Meier method and a Cox proportional hazard model.</p><p><strong>Results: </strong>Thirty-eight patients were identified. The median recurrence-free survival (RFS) was 50.6 months and overall survival (OS) was 75.2 months. Patients who had undergone adjuvant chemotherapy were not associated with a favorable RFS (hazard ratio=1.01, p=0.98) or OS (hazard ratio=0.72, p=0.55), as compared with those who had not. However, subgroup analysis revealed that hazard ratio based on RFS and OS varied greatly between subgroups, suggesting that selected patients might benefit from adjuvant therapy, while others might be harmed by it. For example, in surgical-pathological stage III disease, adjuvant therapy showed a favorable RFS (HR=0.22, 95%CI=0.02-2.57, p=0.23) and OS (HR=0.36, 95%CI=0.03-4.01, p=0.40). Conversely, in surgical-pathological stage 0-II disease, adjuvant therapy showed an unfavorable RFS (HR=1.40, 95%CI=0.49-3.96, p=0.53) and OS (HR=0.95, 95%CI=0.29-3.12, p=0.93).</p><p><strong>Conclusion: </strong>Regardless of the negative findings in our overall patient cohort, our results may be beneficial in identifying patients who may likely benefit from adjuvant therapy. This contribution could assist the planning of large-scale prospective studies.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background/aim: Although studies on senescence-related genes using human islets of Langerhans have been performed, the expression of senescence-related genes and their association with functional genes in islets remain insufficiently investigated. We aimed to determine whether and what types of senescent-related genes are expressed in islets and identify their correlations with pancreatic function-related genes by using islets isolated for transplantation from individuals of various ages.
Materials and methods: Islets from deceased donors of both sexes and different ages were used for analysis. The expression status of senescence-related genes (glutaminase 1, interleukin 6, interleukin 8, cyclin-dependent kinase inhibitor 2A, cyclin-dependent kinase inhibitor 1A, and senescence-associated beta-galactosidase) and pancreatic function-related genes (glucagon and insulin) was examined by reverse transcription-quantitative polymerase chain reaction, and their relationships with age were investigated.
Results: We obtained isolated human islets from 18 deceased multiorgan donors. There was no correlation between donor age and expression of any of the senescence-related genes. Regarding correlations between donor age and pancreatic function-related genes, age was positively correlated only with INS (r=0.49, p=0.03). INS expression was not correlated with that of GLS1 (r=0.23, p=0.34), IL6 (r=-0.06, p=0.79), or IL8 (r=-0.1, p=0.12), but positively related with p16 (r=0.89, p<0.0001), p21 (r=0.51, p=0.02), and SA-β-gal (r=0.52, p=0.02).
Conclusion: We showed the functional potential even of aged islets, which were originally thought to be functionally impaired. We were unable to identify any senescence-related genes expressed in islets from donors of different ages. Therefore, a new index is needed to evaluate not only actual chronological age but also organ- and cell-specific age.
{"title":"Analysis of Expression Status and Relationship Between Senescence-related Genes and Pancreatic Function-related Genes in Human Islets of Langerhans from Donors of Various Ages.","authors":"Hajime Imamura, Tomohiko Adachi, Daisuke Miyamoto, Tatsuya Kin, Mampei Yamashita, Hajime Matsushima, Takanobu Hara, Akihiko Soyama, Susumu Eguchi","doi":"10.21873/invivo.13679","DOIUrl":"10.21873/invivo.13679","url":null,"abstract":"<p><strong>Background/aim: </strong>Although studies on senescence-related genes using human islets of Langerhans have been performed, the expression of senescence-related genes and their association with functional genes in islets remain insufficiently investigated. We aimed to determine whether and what types of senescent-related genes are expressed in islets and identify their correlations with pancreatic function-related genes by using islets isolated for transplantation from individuals of various ages.</p><p><strong>Materials and methods: </strong>Islets from deceased donors of both sexes and different ages were used for analysis. The expression status of senescence-related genes (glutaminase 1, interleukin 6, interleukin 8, cyclin-dependent kinase inhibitor 2A, cyclin-dependent kinase inhibitor 1A, and senescence-associated beta-galactosidase) and pancreatic function-related genes (glucagon and insulin) was examined by reverse transcription-quantitative polymerase chain reaction, and their relationships with age were investigated.</p><p><strong>Results: </strong>We obtained isolated human islets from 18 deceased multiorgan donors. There was no correlation between donor age and expression of any of the senescence-related genes. Regarding correlations between donor age and pancreatic function-related genes, age was positively correlated only with INS (r=0.49, p=0.03). INS expression was not correlated with that of GLS1 (r=0.23, p=0.34), IL6 (r=-0.06, p=0.79), or IL8 (r=-0.1, p=0.12), but positively related with p16 (r=0.89, p<0.0001), p21 (r=0.51, p=0.02), and SA-β-gal (r=0.52, p=0.02).</p><p><strong>Conclusion: </strong>We showed the functional potential even of aged islets, which were originally thought to be functionally impaired. We were unable to identify any senescence-related genes expressed in islets from donors of different ages. Therefore, a new index is needed to evaluate not only actual chronological age but also organ- and cell-specific age.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}