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Quantitative Evaluation of Urine Protein-to-Creatinine Ratio in Dogs With Sporadic Bacterial Cystitis. 散发性细菌性膀胱炎犬尿蛋白与肌酐比值的定量评价。
IF 1.8 4区 医学
In vivo Pub Date : 2026-11-01 DOI: 10.21873/invivo.14488
Jungmin Lym, Yeon Chae, Yoonhoi Koo, Hakhyun Kim, Byeong-Teck Kang, Taesik Yun
{"title":"Quantitative Evaluation of Urine Protein-to-Creatinine Ratio in Dogs With Sporadic Bacterial Cystitis.","authors":"Jungmin Lym, Yeon Chae, Yoonhoi Koo, Hakhyun Kim, Byeong-Teck Kang, Taesik Yun","doi":"10.21873/invivo.14488","DOIUrl":"https://doi.org/10.21873/invivo.14488","url":null,"abstract":"<p><strong>Background/aim: </strong>Proteinuria is a key indicator of canine renal disease. While bacterial cystitis causes post-renal proteinuria, the extent to which sporadic bacterial cystitis increases the urine protein-to-creatinine ratio (UPC) is not well defined. This study aimed to quantitatively evaluate the effect of sporadic bacterial cystitis on the canine UPC and determine whether the UPC can distinguish sporadic infection from renal proteinuria.</p><p><strong>Materials and methods: </strong>A retrospective study was conducted on dogs evaluated between 2016 and 2025. The study included healthy dogs (n=37), dogs with sporadic bacterial cystitis (n=13), bacterial cystitis with comorbidities (n=65), chronic kidney disease (CKD; n=26), and hyperadrenocorticism (HAC; n=15).</p><p><strong>Results: </strong>The median UPC in the sporadic bacterial cystitis group (0.20) showed no significant difference compared to healthy dogs (0.20; <i>p</i>=0.392). Conversely, dogs with bacterial cystitis with comorbidities (0.62) and those with CKD or HAC (0.73) exhibited significantly higher UPCs than the sporadic infection group (<i>p</i><0.001). Distinguishing sporadic infection from renal proteinuria yielded an area under the curve of 0.9373, with an optimal cut-off of 0.425 (100% specificity, 73.2% sensitivity).</p><p><strong>Conclusion: </strong>Sporadic bacterial cystitis alone does not cause clinically significant increases in the UPC in dogs. A UPC exceeding 0.32 in dogs with cystitis should prompt further investigation for underlying diseases, and a UPC greater than 0.425 suggests renal proteinuria. This approach prevents the misattribution of proteinuria and supports the timely diagnosis of renal diseases.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"40 6","pages":"3445-3456"},"PeriodicalIF":1.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149297047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Newly Synthesized S4MA Inhibits Inflammatory Responses Through STAT3/NF-κB Pathways in Human Colon Cancer HCT 116 Cells In Vitro. 新合成的S4MA体外通过STAT3/NF-κB通路抑制人结肠癌HCT 116细胞的炎症反应
IF 1.8 4区 医学
In vivo Pub Date : 2026-11-01 DOI: 10.21873/invivo.14480
Jin-Cherng Lien, Yi-Shih Ma, Fu-Shin Chueh, Yi-Ping Huang, Jaw-Chyun Chen, Jiun-Long Yang, Yung-Lin Chu, An-Cheng Huang, Chiung-Ju Chen, Shu-Mi Chen, Shu-Fen Peng
{"title":"Newly Synthesized S4MA Inhibits Inflammatory Responses Through STAT3/NF-κB Pathways in Human Colon Cancer HCT 116 Cells <i>In Vitro</i>.","authors":"Jin-Cherng Lien, Yi-Shih Ma, Fu-Shin Chueh, Yi-Ping Huang, Jaw-Chyun Chen, Jiun-Long Yang, Yung-Lin Chu, An-Cheng Huang, Chiung-Ju Chen, Shu-Mi Chen, Shu-Fen Peng","doi":"10.21873/invivo.14480","DOIUrl":"https://doi.org/10.21873/invivo.14480","url":null,"abstract":"<p><strong>Background/aim: </strong>This study aimed to investigate the impacts and underlying molecular mechanisms of E-4-(2-chloro-1-(4-methylbenzyl)-1H-indol-3-yl)but-3-en-2-one, C<sub>20</sub>H<sub>18</sub>ClNO (S4MA), a newly synthesized compound, on inflammation-associated cytokine responses in human colon cancer HCT 116 cells <i>in vitro</i>.</p><p><strong>Materials and methods: </strong>Phase-contrast microscopy was utilized to detect the changes in cell morphology, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to analyze cell proliferation. Cytokine secretion was measured by enzyme-linked immunosorbent assay (ELISA), and mRNA levels were assessed by reverse transcriptase polymerase chain reaction (RT-PCR). Western blotting and confocal laser microscopy were employed to investigate the associated protein expression. Furthermore, the interaction of nuclear factor kappa-B (NF-κB) with specific DNA sequences in HCT 116 cells was evaluated using electrophoresis mobility shift assay (EMSA).</p><p><strong>Results: </strong>High concentrations of S4MA triggered cell morphological alterations in HCT 116 cells. Therefore, we reduced the concentration of S4MA to 1 μM for the inflammation-associated cytokine assay. S4MA at 0.5 and 1 μM inhibited cell proliferation. S4MA at 0.1 and 1 μM reduced the secretion of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) cytokines, and S4MA at 1 μM diminished the mRNA expression of <i>IL-6</i> and <i>TNF-α</i>, as determined by ELISA and RT-PCR assays, respectively. Western blotting and confocal laser microscopy demonstrated that S4MA reduced the levels of signal transducer and activator of transcription 3 (STAT3)- and NF-κB-associated proteins in HCT 116 cells. Furthermore, S4MA reduced the interaction between NF-κB and its target DNA sequences within the nucleus, as determined by EMSA.</p><p><strong>Conclusion: </strong>S4MA inhibited inflammation-associated responses by regulating the STAT3/NF-κB pathways in human colon cancer HCT 116 cells. Therefore, S4MA may be a promising agent for suppressing inflammatory responses in future therapies for human colon cancer.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"40 6","pages":"3322-3337"},"PeriodicalIF":1.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149297223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Incidence and Predictors of Systemic Complications in Hospitalized Patients With Cervical Traumatic Spinal Cord Injury. 颈外伤性脊髓损伤住院患者全身并发症的发生率及预测因素
IF 1.8 4区 医学
In vivo Pub Date : 2026-11-01 DOI: 10.21873/invivo.14512
Shih-Hsiang King, Meng-Hsuan Hsieh, Ting-Lin Yen, Cheng-Ta Hsieh
{"title":"Incidence and Predictors of Systemic Complications in Hospitalized Patients With Cervical Traumatic Spinal Cord Injury.","authors":"Shih-Hsiang King, Meng-Hsuan Hsieh, Ting-Lin Yen, Cheng-Ta Hsieh","doi":"10.21873/invivo.14512","DOIUrl":"https://doi.org/10.21873/invivo.14512","url":null,"abstract":"<p><strong>Background/aim: </strong>Traumatic spinal cord injury (tSCI) is accompanied by systemic physiological vulnerability due to autonomic dysregulation and impaired organ function. Although acute systemic complications are common and may compromise early outcomes, their independent predictors remain unclear, particularly in Asian health-care settings, in which prolonged acute hospitalization is common. This study aimed to determine the incidence and independent predictors of systemic complications among surgically treated patients with cervical tSCI.</p><p><strong>Patients and methods: </strong>This retrospective study included adults with acute cervical tSCI who underwent surgery at a single tertiary center between 2010 and 2025. Demographic characteristics, injury characteristics, clinical course variables, and in-hospital systemic complications were evaluated. Outcomes assessed included in-hospital mortality and neurological improvement, defined as an increase of ≥1 American Spinal Injury Association grade at discharge. Multivariable logistic regression was performed to identify independent predictors of major complications.</p><p><strong>Results: </strong>Data on 92 patients were analyzed. Urinary tract infection (UTI; 35.9%), pneumonia (22.8%), and ileus (18.5%) were the most frequent complications. In-hospital mortality rate was 8.7%. Approximately 41.3% of the patients exhibited neurological improvement. Initial American Spinal Injury Association grade was significantly associated with both neurological recovery and mortality. Pneumonia and UTI were strongly associated with in-hospital death. Longer hospital stay was independently associated with UTI and ileus, whereas advanced age and lower body mass index were independently associated with ileus. Longer ventilator exposure was independently associated with respiratory complications.</p><p><strong>Conclusion: </strong>Systemic complications are common after surgical treatment of cervical tSCI and are closely associated with early mortality. Care-related factors, particularly prolonged hospitalization and ventilator exposure, were associated with systemic complications. These variables may represent markers of a more complicated clinical course rather than direct causal factors and should be interpreted accordingly.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"40 6","pages":"3753-3762"},"PeriodicalIF":1.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149297240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
L-Glutamine for Pediatric Sickle Cell Disease: Pharmacology, Mechanism of Action, Safety and Efficacy. l -谷氨酰胺治疗小儿镰状细胞病:药理学、作用机制、安全性和有效性。
IF 1.8 4区 医学
In vivo Pub Date : 2026-11-01 DOI: 10.21873/invivo.14475
Eduard H Panosyan
{"title":"L-Glutamine for Pediatric Sickle Cell Disease: Pharmacology, Mechanism of Action, Safety and Efficacy.","authors":"Eduard H Panosyan","doi":"10.21873/invivo.14475","DOIUrl":"https://doi.org/10.21873/invivo.14475","url":null,"abstract":"<p><strong>Background/aim: </strong>L-Glutamine (L-Gln) has been approved for the treatment of sickle cell disease (SCD) since 2017. Clinical and pharmacological data in pediatric patients remain limited. This review summarizes studies of L-Gln use in SCD including pharmacokinetics (PK), pharmacodynamics (PD), safety, and efficacy in pediatrics, alongside <i>in-vitro</i> and pre-clinical data elucidating primary and supplemental mechanisms of action (MOA). Pharmacoeconomics (PE) is addressed briefly.</p><p><strong>Materials and methods: </strong>Literature search included keywords of SCD, L-Gln, and pediatrics - targeting papers with PK, PD, PE, clinical and preclinical studies. Thirty-two articles meeting the selection criteria were included for descriptive and analytical review.</p><p><strong>Results: </strong>Two mouse studies were identified. The remaining articles included translational, Phase-2 and Phase-3 trials and studies containing pharmacological data. Pharmacokinetics showed serum L-Gln levels to peak at 800-1000 μM within 1 h after oral intake of clinically relevant doses. Thereafter, approximately 500-600 μM levels were shown to last 4-8 h post-dose. Pharmacodynamic data suggest that antioxidant effects may represent an important mechanism of action mainly <i>via</i> increased NADH, but additional contributors may include increased glutathione, decreased cell adhesion, and up-regulated autophagy of peripheral blood mononuclear cells. Five papers compared L-Gln with other SCD-modifying therapies. Indirect comparisons suggest that L-Gln, hydroxyurea, and crizanlizumab can each reduce vaso-occlusive events with significant decrease of pain crises and hospitalizations. However, direct comparative efficacy cannot be established in the absence of head-to-head trials. Overall safety profile was also comparable; however L-Gln may cause more gastrointestinal (GI) side effects such as constipation and abdominal pain. Annual cost of L-Gln is lower than crizanlizumab, however insurance denials and high co-pays were reported as barriers to initiating the therapy.</p><p><strong>Conclusion: </strong>Oral L-Gln is an effective SCD-modifying therapy for patients with sickle cell disease 5 years and older. Gastrointestinal adverse effects, including abdominal pain and constipation, are reported. PK supports twice daily regimen, and PD suggests that anti-oxidative effect is the dominant MOA. Cost reductions may result in wider use of L-Gln.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"40 6","pages":"3253-3261"},"PeriodicalIF":1.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149297249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CRP-Albumin-Lymphocyte (CALLY) Index Is an Independent Prognostic Factor for Recurrent Esophageal Cancer After Curative Treatment. crp -白蛋白淋巴细胞(CALLY)指数是食管癌治愈后复发的独立预后因素。
IF 1.8 4区 医学
In vivo Pub Date : 2026-11-01 DOI: 10.21873/invivo.14518
Maki Takagi, Toru Aoyama, Itaru Hashimoto, Taiichi Kawabe, Yukio Maezawa, Sho Sato, Kanechika DEN, Takashi Kosaka, Tsutomu Sato, Yosuke Atsumi, Miki Kayashima, Kohei Sekiguchi, Ayako Tamagawa, Keisuke Kazama, Nobuhiro Sugano, Haruhiko Cho, Norio Yukawa, Takaki Yoshikawa
{"title":"CRP-Albumin-Lymphocyte (CALLY) Index Is an Independent Prognostic Factor for Recurrent Esophageal Cancer After Curative Treatment.","authors":"Maki Takagi, Toru Aoyama, Itaru Hashimoto, Taiichi Kawabe, Yukio Maezawa, Sho Sato, Kanechika DEN, Takashi Kosaka, Tsutomu Sato, Yosuke Atsumi, Miki Kayashima, Kohei Sekiguchi, Ayako Tamagawa, Keisuke Kazama, Nobuhiro Sugano, Haruhiko Cho, Norio Yukawa, Takaki Yoshikawa","doi":"10.21873/invivo.14518","DOIUrl":"https://doi.org/10.21873/invivo.14518","url":null,"abstract":"<p><strong>Background/aim: </strong>The C-reactive protein-albumin-lymphocyte (CALLY) index is a promising biomarker. We investigated the prognostic significance of the CALLY index in patients with recurrent esophageal cancer (EC).</p><p><strong>Patients and methods: </strong>Consecutive patients who developed recurrent EC after curative esophagectomy and received treatment for recurrence at Yokohama City University from 2005 to 2022 were selected based on medical records. The CALLY index was calculated as follows: serum albumin level (g/dl) × peripheral lymphocyte count (/μl)/[C-reactive protein level (mg/dl) × 10<sup>4</sup>]. The primary endpoint was overall survival after recurrence. The secondary endpoint was the association between the CALLY index and the clinical course after recurrence, including the administration of first-, second-, and third- line treatments.</p><p><strong>Results: </strong>One hundred patients were included in this retrospective study. The cut-off value for the CALLY index was set at 5. The 5-year overall survival rates were 11.2% and 46.9% for the low and high CALLY index groups, respectively (<i>p</i><0.001). Multivariate analysis demonstrated that a low CALLY index was an independent prognostic factor for poor overall survival (hazard ratio=4.271, 95% confidence interval=2.370-7.696, <i>p</i><0.001). Patients with a high CALLY index were significantly more likely to receive first-, second-, and third-line treatments than those with a low CALLY index.</p><p><strong>Conclusion: </strong>The CALLY index may serve as a useful prognostic biomarker and may also be associated with the ability to receive subsequent lines of treatment in patients with recurrent esophageal cancer.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"40 6","pages":"3821-3829"},"PeriodicalIF":1.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149296964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Salvage Chemotherapy After Pembrolizumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Pembrolizumab治疗复发或转移性头颈部鳞状细胞癌后的补救性化疗。
IF 1.8 4区 医学
In vivo Pub Date : 2026-11-01 DOI: 10.21873/invivo.14503
Chihiro Fushimi, Isaku Okamoto, Takashi Matsuki, Takuro Okada, Yuri Ueda, Hideaki Takahashi, Hiroki Sato, Takahito Kondo, Kunihiko Tokashiki, Kenji Hanyu, Tatsuya Ito, Yukiomi Kushihashi, Tatsuo Masubuchi, Yuichiro Tada, G O Omura, Taku Yamashita, Nobuhiko Oridate, Kiyoaki Tsukahara
{"title":"Salvage Chemotherapy After Pembrolizumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.","authors":"Chihiro Fushimi, Isaku Okamoto, Takashi Matsuki, Takuro Okada, Yuri Ueda, Hideaki Takahashi, Hiroki Sato, Takahito Kondo, Kunihiko Tokashiki, Kenji Hanyu, Tatsuya Ito, Yukiomi Kushihashi, Tatsuo Masubuchi, Yuichiro Tada, G O Omura, Taku Yamashita, Nobuhiko Oridate, Kiyoaki Tsukahara","doi":"10.21873/invivo.14503","DOIUrl":"https://doi.org/10.21873/invivo.14503","url":null,"abstract":"<p><strong>Background/aim: </strong>Pembrolizumab-based therapy is widely used for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, clinical outcomes after subsequent salvage chemotherapy (SCT) remain insufficiently defined. This study evaluated the efficacy of SCT after pembrolizumab in patients with R/M HNSCC.</p><p><strong>Patients and methods: </strong>This multicenter retrospective study included 36 evaluable patients with R/M HNSCC who received SCT after pembrolizumab between December 2019 and February 2022. The primary endpoint was the objective response rate. Secondary endpoints included the disease control rate, progression-free survival, overall survival, and exploratory clinical factors associated with treatment outcomes.</p><p><strong>Results: </strong>The best overall response to SCT was a complete response in 2 patients, partial response in 8, stable disease in 12, and progressive disease in 14. The overall response rate was 27.8%, and the disease control rate was 61.1%. Median progression-free and overall survival were 4.6 months and 11.5 months, respectively. The overall response rate was significantly higher (>4-fold) in patients with prior surgery and in platinum-naive patients. A combined positive score of 20 or higher for tumor programmed cell death-ligand 1, initial M1 status, and prior surgery were associated with longer progression-free survival in exploratory analyses.</p><p><strong>Conclusion: </strong>SCT after pembrolizumab showed clinically meaningful activity in selected patients with R/M HNSCC. These findings support SCT as a reasonable post-pembrolizumab option, although prospective validation is warranted.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"40 6","pages":"3648-3656"},"PeriodicalIF":1.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149296990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Renal and Vascular Effects of Selective FGFR4 Inhibition in Folic Acid-induced Kidney Injury in Rats. 选择性抑制FGFR4在叶酸诱导的大鼠肾损伤中的肾和血管作用。
IF 1.8 4区 医学
In vivo Pub Date : 2026-11-01 DOI: 10.21873/invivo.14498
Zeliha Rumanli, Emre Avci, Ülkü Irem Yilmaz, Bariş Baykal, Beyhan Karli Yildirim, Okan Ali Aksoy, Berk Alp Göksel, Ismail Mert Vural
{"title":"Renal and Vascular Effects of Selective FGFR4 Inhibition in Folic Acid-induced Kidney Injury in Rats.","authors":"Zeliha Rumanli, Emre Avci, Ülkü Irem Yilmaz, Bariş Baykal, Beyhan Karli Yildirim, Okan Ali Aksoy, Berk Alp Göksel, Ismail Mert Vural","doi":"10.21873/invivo.14498","DOIUrl":"https://doi.org/10.21873/invivo.14498","url":null,"abstract":"<p><strong>Background/aim: </strong>Fibroblast growth factor-23 (FGF-23) has been implicated in chronic kidney disease (CKD)-associated cardiovascular dysfunction, potentially through fibroblast growth factor receptor 4 (FGFR4). This study investigated renal and vascular alterations in folic acid-induced CKD and evaluated the effects of selective FGFR4 inhibition.</p><p><strong>Materials and methods: </strong>Male Sprague-Dawley rats were assigned to healthy control, CKD control, vehicle, and roblitinib-treated groups. CKD was induced by a single intraperitoneal dose of folic acid. Serum creatinine, FGF-23, tumor necrosis factor-α, interleukin-1β, and asymmetric dimethylarginine levels were measured. Vascular reactivity was evaluated in isolated aortic rings using phenylephrine, carbachol, and sodium nitroprusside. Renal fibrosis, carotid calcification, and medial thickness were assessed histologically.</p><p><strong>Results: </strong>Folic acid administration increased serum creatinine and relative kidney weight and impaired both endothelium-dependent and endothelium-independent vascular relaxation. Relative kidney weight was lower in the roblitinib-treated group than in the CKD control group. However, changes in vascular responses observed in both the treatment and vehicle groups prevented these effects from being attributed specifically to FGFR4 inhibition. FGF-23 and inflammatory marker levels did not differ significantly among the groups. Carotid medial thickness was significantly greater in the treatment group than in the CKD-control group (<i>p</i><0.05), whereas no other significant between-group differences were detected.</p><p><strong>Conclusion: </strong>Folic acid-induced renal injury was associated with early functional vascular impairment despite limited structural and inflammatory alterations. Selective FGFR4 inhibition did not demonstrate a clear therapeutic effect. Further <i>in vivo</i> studies using complementary CKD models, direct assessment of FGFR4 signaling, and vehicle formulations without intrinsic vascular activity are required to validate these findings.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"40 6","pages":"3591-3606"},"PeriodicalIF":1.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149296999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hepatobiliary Adverse Events Associated With Avacopan: Analysis of the JADER Database. Avacopan相关肝胆不良事件:JADER数据库分析。
IF 1.8 4区 医学
In vivo Pub Date : 2026-11-01 DOI: 10.21873/invivo.14510
Masaki Fujiwara, Kazumasa Kotake, Yuki Uemichi, Tadashi Shimizu
{"title":"Hepatobiliary Adverse Events Associated With Avacopan: Analysis of the JADER Database.","authors":"Masaki Fujiwara, Kazumasa Kotake, Yuki Uemichi, Tadashi Shimizu","doi":"10.21873/invivo.14510","DOIUrl":"https://doi.org/10.21873/invivo.14510","url":null,"abstract":"<p><strong>Background/aim: </strong>Avacopan, a selective C5a receptor antagonist approved for anti-neutrophil cytoplasmic antibody-associated vasculitis, has been associated with hepatobiliary disorders including vanishing bile duct syndrome (VBDS). These events have been reported more frequently in Japanese patients than in Western populations. To address this population-specific safety concern, we characterized the reporting patterns of avacopan-associated hepatobiliary disorders using the Japanese Adverse Drug Event Report (JADER) database.</p><p><strong>Patients and methods: </strong>We analyzed reports submitted to JADER between April 2004 and January 2026 in which avacopan was registered as a suspect drug. Hepatobiliary adverse events were defined as a composite set comprising preferred terms (PTs) under the System Organ Class (SOC) \"Hepatobiliary disorders\" (code 10019805) of Medical Dictionary for Regulatory Activities (MedDRA)/J version 29.0 and two liver-related PTs classified under the SOC \"Investigations\" (code 10022891): Liver function test increased (10077692) and hepatic enzymes increased (10060795). Disproportionality was assessed using the reporting odds ratio with 95% confidence intervals (CIs); a signal was defined as three or more reports with a lower CI limit exceeding 1.0. Time to onset was calculated from treatment start to hepatobiliary adverse events onset, and post-event outcomes were categorized based on available JADER outcome data.</p><p><strong>Results: </strong>Among 685 avacopan-related reports, disproportionality signals were detected for all hepatobiliary adverse events evaluated. The median time to onset of hepatobiliary adverse events ranged from 33 to 56.5 days, with most events occurring within one to two months after avacopan treatment. Of 226 reports with outcome data, 19 (8.4%) recorded death. Notably, 13 of 27 VBDS reports (48.1%) recorded death as the outcome, a markedly higher proportion than that for other hepatobiliary adverse events.</p><p><strong>Conclusion: </strong>These findings support the importance of continued post-marketing surveillance and monitoring of hepatobiliary events during avacopan treatment.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"40 6","pages":"3716-3724"},"PeriodicalIF":1.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149297006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Definitive Hypofractionated Radiotherapy in Elderly Patients With Non-melanoma Skin Cancer: Predicting Complete Response Using a Machine Learning-based Approach. 老年非黑色素瘤皮肤癌患者的明确低分割放疗:使用基于机器学习的方法预测完全缓解。
IF 1.8 4区 医学
In vivo Pub Date : 2026-11-01 DOI: 10.21873/invivo.14507
Francesca DE Felice, Lavinia Spinelli, Paola Critelli, Melissa Scricciolo, Daniela Musio, Annalisa Magnante, Stefania Martini, Giuseppe Minniti, Anna Merlotti
{"title":"Definitive Hypofractionated Radiotherapy in Elderly Patients With Non-melanoma Skin Cancer: Predicting Complete Response Using a Machine Learning-based Approach.","authors":"Francesca DE Felice, Lavinia Spinelli, Paola Critelli, Melissa Scricciolo, Daniela Musio, Annalisa Magnante, Stefania Martini, Giuseppe Minniti, Anna Merlotti","doi":"10.21873/invivo.14507","DOIUrl":"https://doi.org/10.21873/invivo.14507","url":null,"abstract":"<p><strong>Background/aim: </strong>This study aimed to develop a classification tree model to predict clinical complete response (cCR) after definitive hypofractionated RT in elderly patients with non-melanoma (basal and squamous cell carcinoma) skin cancer based on pre-treatment clinical parameters.</p><p><strong>Patients and methods: </strong>Data from elderly patients (aged ≥ 70 years) with histologically proven non-melanoma skin cancer lesion(s) were reviewed. All lesions were treated with definitive hypofractionated RT. A decision tree methodology was applied to define significant pre-treatment parameters influencing the cCR rate. The data set included seven predictor variables (location, histology, T stage, diameter, bleeding, pain, previous treatment) and a dependent variable (cCR). The analysis was conducted using open-source R software. Important explanatory variables were selected using the random forest approach. A classification tree that optimally partitioned patients according to cCR was then built.</p><p><strong>Results: </strong>A total of 121 patients with 145 non-melanoma skin cancer lesions were identified between January 2015 and December 2023. The cCR rate after treatment was 78.6%. The three most important variables identified were T stage, location and pain at diagnosis. Based on these explanatory variables, patients were partitioned in five groups. Of these groups, three experienced cCR rates ranging from 69% to 88% and two experienced cCR rates lower than 15%.</p><p><strong>Conclusion: </strong>The proposed classification tree could serve as a valuable tool to guide future research in the field of non-melanoma skin cancer. The decision tree method may be an effective approach to partition elderly patients with non-melanoma skin cancer based on key clinical parameters.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"40 6","pages":"3685-3691"},"PeriodicalIF":1.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149297042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Galectin-3 as a Candidate Marker of Endocrine-modulator-associated Endometrial Remodeling During Breast Cancer Endocrine Therapy. 乳腺癌内分泌治疗中半乳糖凝集素-3作为内分泌调节剂相关子宫内膜重塑的候选标志物
IF 1.8 4区 医学
In vivo Pub Date : 2026-11-01 DOI: 10.21873/invivo.14494
Adamantia Kontogeorgi, Ioannis Boutas, Dimitrios Kalaitzis, Tatiana S Driva, George Agrogiannis, Emmanouil Zoumakis, Sophia N Kalantaridou, Antonios Makrigiannakis
{"title":"Galectin-3 as a Candidate Marker of Endocrine-modulator-associated Endometrial Remodeling During Breast Cancer Endocrine Therapy.","authors":"Adamantia Kontogeorgi, Ioannis Boutas, Dimitrios Kalaitzis, Tatiana S Driva, George Agrogiannis, Emmanouil Zoumakis, Sophia N Kalantaridou, Antonios Makrigiannakis","doi":"10.21873/invivo.14494","DOIUrl":"https://doi.org/10.21873/invivo.14494","url":null,"abstract":"<p><strong>Background/aim: </strong>Breast cancer endocrine therapies may induce endometrial alterations, but the endometrial effects of antiprogestins remain incompletely defined. This study evaluated the effects of tamoxifen, mifepristone, and ulipristal acetate on endometrial morphology and galectin-3 expression, with the aim of exploring galectin-3 as a candidate marker of endocrine-modulator-associated endometrial remodeling.</p><p><strong>Materials and methods: </strong>Endometrial effects were examined in a rat mammary carcinogenesis model treated with tamoxifen, mifepristone, ulipristal acetate, or vehicle control. Uterine tissues were assessed by histology and galectin-3 immunohistochemistry. Complementary in vitro experiments in Ishikawa endometrial adenocarcinoma cells evaluated agent- and dose-associated galectin-3 protein-expression patterns by western blotting. Histological outcomes and in vitro fold-change values were summarized descriptively.</p><p><strong>Results: </strong>In the analyzed cohort, tamoxifen-treated animals showed the highest descriptive proportion of complex endometrial hyperplasia, whereas mifepristone and ulipristal acetate were associated predominantly with simple hyperplastic changes. Normal endometrial morphology was retained in selected mifepristone- and ulipristal acetate-treated animals and in all control animals. Galectin-3 immunoreactivity was low but detectable in morphologically normal endometrium, whereas hyperplastic lesions showed no detectable galectin-3 immunoreactivity under the staining conditions used. In Ishikawa cells, galectin-3 expression showed agent-specific fold-change patterns: tamoxifen and mifepristone were associated with reduced expression at higher concentrations, while ulipristal acetate showed a non-monotonic pattern with increased expression at low and intermediate concentrations and return toward baseline at the highest concentration.</p><p><strong>Conclusion: </strong>In this exploratory model, endocrine-modulator-associated hyperplastic endometrial remodeling was accompanied by reduced or undetectable galectin-3 immunoreactivity, while low-level expression was retained in morphologically normal endometrium. These findings support further investigation of galectin-3 as a candidate marker of endocrine-associated endometrial remodeling, but validation in larger animal cohorts and human endometrial samples from treated patients is required.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"40 6","pages":"3519-3539"},"PeriodicalIF":1.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149297045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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