In vivo最新文献

{"title":"Management of the Axilla After Neoadjuvant Chemotherapy: Can Axillary Needle Biopsy Replace Sentinel Node Biopsy?","authors":"Emine Yildirim, Pelin Basim, Nese Ucar, Sibel Bektas, Kutay Iscen, Ebru Karci, Asena Ayca Ozdemir","doi":"10.21873/invivo.13724","DOIUrl":"10.21873/invivo.13724","url":null,"abstract":"<p><strong>Background/aim: </strong>The aim of the study was to investigate whether it is possible to evaluate the axilla after treatment without performing sentinel lymph node biopsy (SLNB) in breast cancer patients with biopsy-proven axillary lymph node metastases who received neoadjuvant chemotherapy (NAC).</p><p><strong>Patients and methods: </strong>This prospective, randomized, clinically designed study included patients with clinical T_1-3 and biopsy-proven N₁ breast cancer. Prior to the surgery scheduled after NAC, the patients were randomized into two groups. A biopsy sample was obtained from the clipped axillary lymph node, which was preoperatively known to be metastatic, using fine needle aspiration (FNAB) in the first group and core needle biopsy (CNB) in the second group. The predictive ability of the two biopsy methods for the SLNB results was evaluated.</p><p><strong>Results: </strong>The study included 50 female patients with breast cancer, with a mean age of 48.4±10.72 years. In both groups, metastasis was detected in nine patients, and no metastasis was seen in 14 patients. In intergroup comparisons, all patients with metastasis in the FNAB group also had metastasis according to SLNB, while 21.4% of the cases without metastasis in this group were metastatic according to SLNB. In the CNB group, metastasis was observed in all patients with metastasis according to SLNB, while no metastasis was detected in those who were reported to have no metastasis by SLNB. The accuracy, specificity, and sensitivity values for the prediction of SLNB results were all found to be 100% for CNB, whereas they were 87%, 100%, and 75%, respectively, for FNAB.</p><p><strong>Conclusion: </strong>Both CNB and FNAB could potentially replace SLNB due to their high accuracy rates in evaluating the axilla after NAC. The sensitivity and accuracy of CNB were determined to be higher.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"38 5","pages":"2523-2530"},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072728","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}

{"title":"Photobiomodulation Effect of Diode Laser on Differentiation of Osteoprogenitor Cells in Rat Bone Marrow.","authors":"Eisuke Iso, Takahide Yamazaki, Norika Kobayashi, Hiroshi Kadokura, Takako Tsuchiya, Yuka Kato, Satoshi Yokose","doi":"10.21873/invivo.13685","DOIUrl":"10.21873/invivo.13685","url":null,"abstract":"<p><strong>Background/aim: </strong>Bone marrow cells contain nonhematopoietic cells with the ability to differentiate into osteogenic, chondrogenic, and adipogenic lineages. Mechanical stress influences osteoblast differentiation of bone marrow cells into osteogenic, chondrogenic, and adipogenic lineages, measurable as the abundance of alkaline phosphatase-positive (ALP⁺) colony-forming unit-fibroblasts (CFU-F); however, the effect of diode laser irradiation on osteoblast differentiation is unknown. The aim of this study was to analyze the effects of photobiomodulation on the osteogenic differentiation of mesenchymal stem cells in the bone marrow, using the CFU-F assay.</p><p><strong>Materials and methods: </strong>Bone marrow cells isolated from rat tibiae were cultured and irradiated with a diode laser (wavelength 808 nm) at a total energy of 0 J (control), 50 J, and 150 J.</p><p><strong>Results: </strong>On day 7 after irradiation, ALP⁺ CFU-F were most abundant in the 50 J group and the least abundant in the 150 J group. Mineralized nodule formation was observed after long-term culture (21 days). Compared with the control group, there were significantly more nodules in the 50 J group and significantly fewer nodules in the 150 J group. Osteocalcin mRNA expression was highest in the 50 J group, and there was no difference between the control and 150 J groups.</p><p><strong>Conclusion: </strong>Irradiation with 50 J was effective in stimulating osteogenesis in bone marrow stem cells. These findings suggest that diode laser irradiation can induce osteogenesis in rat bone marrow cells in an energy-dependent manner, and appears suitable for application in bone regeneration therapy.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"38 5","pages":"2214-2219"},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072733","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}

{"title":"Restoration of Spatial Learning Through Oral Administration of Lipopolysaccharides in Diabetes-related Cognitive Dysfunction.","authors":"Hiroyuki Inagawa, Masataka Oda, Vindy Tjendana Tjhin, Chie Kohchi, Gen-Ichiro Soma","doi":"10.21873/invivo.13682","DOIUrl":"10.21873/invivo.13682","url":null,"abstract":"<p><strong>Background/aim: </strong>In a previous report, our group showed that oral administration of lipopolysaccharides (LPS) from Pantoea agglomerans can prevent the progression of streptozotocin (STZ)-induced diabetes-related cognitive dysfunction (DRCD) in mice without causing significant side-effects. However, the treatment effects of oral administration of LPS to DRCD remain unknown.</p><p><strong>Materials and methods: </strong>We modified our previous animal experimental model to investigate whether oral administration of LPS can recover cognitive function after DRCD onset.</p><p><strong>Results: </strong>The Morris water maze (MWM) revealed a significant decrease in learning and memory abilities at 13 days after intracerebroventricular administration of STZ, thereby providing evidence of the occurrence of DRCD in the animal model. Oral administration of LPS (1 mg/kg per day) started after cognitive impairment was observed. After 28 days of treatment, mice receiving LPS via the oral route showed significant recovery of spatial learning ability, a symptom of early dementia, while only a trend toward recovery was seen for spatial memory compared to the untreated group.</p><p><strong>Conclusion: </strong>These results, limited to MWM, suggest that oral administration of LPS is a promising therapeutic strategy for restoring decreased spatial learning ability.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"38 5","pages":"2190-2196"},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072739","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}

{"title":"The Effect of Hypoxia on Irisin Expression in HL-1 Cardiomyocytes.","authors":"Maciej Grzeszczuk, Monika Mrozowska, Alicja Kmiecik, Agnieszka Rusak, Karolina Jabłońska, Urszula Ciesielska, Piotr Dzięgiel, Katarzyna Nowińska","doi":"10.21873/invivo.13675","DOIUrl":"10.21873/invivo.13675","url":null,"abstract":"<p><strong>Background/aim: </strong>Cardiovascular diseases (CVD) are the leading cause of death worldwide. In 2019, 523 million people were diagnosed with CVD, with 18.6 million deaths. Improved treatment and diagnostics could reduce CVD's impact. Irisin (Ir) is crucial for heart function and may be a biomarker for heart attack. Ir is a glycoprotein with sugar residues attached to its protein structure. This glycosylation affects Ir stability, solubility, and receptor interactions on target cells. Its secondary structure includes a fibronectin type III domain, essential for its biological functions. Ir helps cardiomyocytes to respond to hypoxia and protects mitochondria. The aim of the study was to determine the FNDC5 gene expression level and the Ir level in HL-1 cardiomyocytes subjected to hypoxia.</p><p><strong>Materials and methods: </strong>We examined the effect of hypoxia on the expression levels of the FNDC5 gene and those of Ir in mouse cardiomyocytes of the HL-1 cell line. Real-time PCR (RT-PCR) was used to estimate the expression levels of the FNDC5 gene. Western blot and immunofluorescence methods were used to analyze the Ir protein levels.</p><p><strong>Results: </strong>Analyses showed an increased Ir level in HL-1 cardiomyocytes in response to hypoxia. This is the first study to confirm the presence of Ir in HL-1 cells.</p><p><strong>Conclusion: </strong>The observed increase in Ir expression in murine cardiomyocytes is associated with the hypoxic environment and can be potentially used to diagnose hypoxia and CVD.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"38 5","pages":"2126-2133"},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072667","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}

{"title":"Thyroiditis and Thyroid Cancer: Bioinformatics Analysis of Gene Expression Data.","authors":"Szu-I Yu, Yu-Kang Chang, Meei-Ling Sheu, Yao-Hsien Tseng","doi":"10.21873/invivo.13684","DOIUrl":"10.21873/invivo.13684","url":null,"abstract":"<p><strong>Background/aim: </strong>Hashimoto thyroiditis (HT) association with thyroid lymphoma is well established; however, the association with papillary thyroid cancer (PTC) is still unclear. Thyroid cancer incidence has shown an increasing trend in recent years. It is characterized by slow growth, making it generally amenable to successful treatment.</p><p><strong>Materials and methods: </strong>We aimed to identify genes considered as promising biomarkers of the progression from thyroiditis to thyroid cancer in public gene expression datasets.</p><p><strong>Results: </strong>We identified 70 differentially expressed genes (DEGs) and used them to prioritize biological risk genes for thyroiditis and thyroid cancer. Statistics and a scoring system based on six functional annotations of significant biological impact identified four genes of interest: CXCR4, IL6ST, PPARG and TP53. Kaplan-Meier plots were used to assess the expression levels related to overall survival. Furthermore, a manual bibliographic search was carried out for each gene, and a protein-protein interaction (PPI) network was built to verify their known associations.</p><p><strong>Conclusion: </strong>The results showed that all four genes (CXCR4, IL6ST, PPARG, TP53) were highly relevant to thyroiditis and thyroid cancer, thus making them worthy of further investigation to understand their relationship with these two diseases.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"38 5","pages":"2205-2213"},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072673","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}

{"title":"Impact of PD-L1 Expression on the Overall Survival of Patients With Non-small Cell Lung Cancer Treated With Single-agent Pembrolizumab.","authors":"Martin Svaton, Magdalena Knetki-Wroblewska, Sylwia Tabor, Petr Domecky, Ondrej Venclicek, Jana Krejci, Marie Drosslerova, Michal Hrnciarik, Daniel Hricisak, Alzbeta Bejckova, Ondrej Fischer, Martina Vitkova, Maciej Krzakowski","doi":"10.21873/invivo.13712","DOIUrl":"10.21873/invivo.13712","url":null,"abstract":"<p><strong>Background/aim: </strong>Cemiplimab in patients with non-small cell lung cancer (NSCLC) with PD-L1 (programmed death ligand type 1) expression ≥50% showed a significant improved overall survival (OS) with increasing expression of PD-L1. To our knowledge there exist no similar data published for pembrolizumab regarding the increased OS in relation to the PD-L1 expression. Therefore, the objective of our study was to determine whether improvement in OS reflects increased expression levels of PD-L1 (≥50%) in patients with NSCLC.</p><p><strong>Patients and methods: </strong>Retrospective data from 9 Czech and 1 Polish comprehensive oncology Centers were used. All patients with stage IV NSCLC and PD-L1 expression ≥50% treated with pembrolizumab in daily practice were included. The groups of patients according to the expression of PD-L1 were determined as follows: PD-L1 50-59%, 60-69%, 70-79%, 80-89% and 90-100%. The log-rank test and the Cox regression model were used to compare survival between study groups.</p><p><strong>Results: </strong>A total of 617 patients were included in the study. We did not observe a statistically significant difference in OS between groups of patients with different levels of PD-L1 expression in the pooled comparison (p=0.445). Furthermore, we did not observe a statistically significant difference even when comparing OS in patients with PD-L1expression of 50-59% (reference) with the group of other patients according to the level of expression of PD-L1 in the Cox regression model including the effect covariates.</p><p><strong>Conclusion: </strong>PD-L1 expression showed no significant effect on OS in patients with NSCLC with PD-L1≥50% treated with pembrolizumab.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"38 5","pages":"2434-2440"},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072718","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}

{"title":"Impact of PEG-GCSF in Breast Cancer Patients Undergoing Chemotherapy During the COVID-19 Pandemic: Single Center Experience and Literature Review.","authors":"Kioto Yokoyama, Nobuyasu Yoshimoto, Satoru Takayama, Masaki Sakamoto, Keisuke Tomoda, Ken Ishikawa, Masakatsu Yamashita, Hiroto Suzuki, Ryosuke Hosogi, Masahiro Takahashi, Mari Fukuda, Hisanori Kani","doi":"10.21873/invivo.13699","DOIUrl":"10.21873/invivo.13699","url":null,"abstract":"<p><strong>Background/aim: </strong>The COVID-19 pandemic brought many challenges in healthcare systems globally. Pegylated granulocyte colony stimulating factor (PEG-GCSF) is recommended to reduce febrile neutropenia (FN), however there are a few reports that G-CSF might worsen COVID-19 disease, and its appropriate use during the COVID-19 pandemic remains uncertain. This retrospective study aimed to analyze the association between PEG-GCSF use and COVID-19 infection and severity.</p><p><strong>Patients and methods: </strong>Breast cancer patients who received chemotherapy at the Nagoya Tokushukai General Hospital between October 2020 and April 2023 were included. Patients with suspected COVID-19 symptoms during each chemotherapy cycle underwent COVID-19 antigen testing. To assess the potential impact of PEG-GCSF on COVID-19 severity, we collected data on patient background, chemotherapy regimens, PEG-GCSF use, COVID-19 antigen tests, and COVID-19 infection from their medical records.</p><p><strong>Results: </strong>Thirty patients received chemotherapy. In total, 71 cycles were administered comprising adriamycin and cyclophosphamide (AC; 37 cycles), docetaxel (DTX; 26 cycles) and docetaxel and cyclophosphamide (TC; eight cycles). Among those patients, suspected COVID-19 symptoms were observed in only one of 62 cycles of the three regimens (1.6%) with PEG-GCSF compared to two of nine cycles (22.2%) without PEG-GCSF (p=0.0405). However, because none developed COVID-19 infection during chemotherapy, we could not assess COVID-19 severity and PEG-GCSF use.</p><p><strong>Conclusion: </strong>A potential role of PEG-GCSF in reducing suspected COVID-19 symptoms during chemotherapy, reducing the anxiety and need for hospital visits, thus improving patients' quality of life, is suggested. These insights could contribute to optimizing the care of breast cancer patients in situations like the current pandemic.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"38 5","pages":"2335-2340"},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072719","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}

{"title":"Short Term Exposure of Sheep Tracheal Epithelium to Cigarette Smoke Extract Reduces ENaC Current: A Pilot Study.","authors":"Rajesh M Jagirdar, Alexandros Grammatikopoulos, Maria Ioannou, Evgeniy Solenov, Konstantinos I Gourgoulianis, Chrissi Hatzoglou, Anastasios D Giannou, Baris Mercanoglu, Sotirios G Zarogiannis","doi":"10.21873/invivo.13694","DOIUrl":"10.21873/invivo.13694","url":null,"abstract":"<p><strong>Background/aim: </strong>Cigarette smoke has been shown to induce a phenotype in humans known as \"acquired cystic fibrosis\". This occurs because the cystic fibrosis transmembrane conductance regulator (CFTR) functions are impaired systemically due to the deleterious effects of smoke components. Elucidation of cigarette smoke effects on the tracheal epithelium is important. The aim of this study was to develop an ex vivo sheep tracheal model to investigate tracheal ion function. In this model, the epithelial sodium channel (ENaC) is inhibited after exposure to cigarette smoke extract (CSE) as a proof of principle.</p><p><strong>Materials and methods: </strong>Tracheas were isolated from healthy sheep and the tracheal epithelium was surgically excised. Tissues were mounted in Ussing chambers and the short circuit current (I_sc) was measured after incubation with 5% CSE in PBS or PBS alone for 30 min. The function of ENaC was investigated by the addition of amiloride (10^-5M) apically. Western blot analysis was performed to assess differences in ENaC quantity after CSE exposure. Some specimens were stained with H&E for detection of histological alterations.</p><p><strong>Results: </strong>The amiloride effect on normal epithelium led to a significant decrease in I_sc [ΔI=33±5.92 μA/cm²; p<0.001 versus control experiments (ΔI=1.44±0.71 μA/cm²)]. After incubation with CSE, ENaC I_sc was significantly reduced (ΔI=14.80±1.96 μA/cm²; p<0.001). No differences in αENaC expression were observed between CSE-exposed and normal tracheal epithelium. Histological images post CSE incubation revealed decreases in the height of the epithelium, with basal cell hyperplasia and loss of ciliated cells.</p><p><strong>Conclusion: </strong>Reduced ENaC inhibition by amiloride after CSE incubation could be due to alterations in the tracheal epithelium.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"38 5","pages":"2294-2299"},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072742","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}

{"title":"Analysis of Single Nucleotide Polymorphisms (SNPs) rs2234693 and rs9340799 of the <i>ESR1</i> Gene and the Risk of Breast Cancer.","authors":"Beata Smolarz, Anna Zadrożna Nowak, Magdalena Bryś, Ewa Forma, Honorata Łukasiewicz, Dariusz Samulak, Sara Langner, Hanna Romanowicz","doi":"10.21873/invivo.13676","DOIUrl":"10.21873/invivo.13676","url":null,"abstract":"<p><strong>Background/aim: </strong>The aim of this study was to analyze rs2234693 and rs9340799 polymorphisms of the ESR1 gene in the context of breast cancer risk in Polish patients.</p><p><strong>Materials and methods: </strong>The study involved a group of 117 patients with breast cancer and 106 controls. The analyses were carried out using the polymerase chain reaction - restriction fragments length polymorphism technique.</p><p><strong>Results: </strong>The presence of the CC genotype in rs2234693 more than doubled the risk of breast cancer (p=0.04), whereas the presence of the TT genotype in rs2234693 significantly reduced the risk of developing this type of cancer (p=0.0002). The presence of the GG genotype in rs9340799 more than doubled the risk of breast cancer (p=0.04), which was confirmed by the analysis of the recessive model (p=0.04).</p><p><strong>Conclusion: </strong>The polymorphisms rs2234693 and rs9340799 of the ESR1 gene may be associated with the risk of breast cancer among Polish women.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"38 5","pages":"2134-2143"},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072654","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}

{"title":"Anti-Tumor and Chemosensitizing Effects of the CDK Inhibitor Dinaciclib on Cholangiocarcinoma <i>In Vitro</i> and <i>In Vivo</i>.","authors":"Prin Sungwan, Sonexai Kidoikhammouan, Unchalee Thonsri, Charupong Saengboonmee, Sopit Wongkham, Seiji Okada, Wunchana Seubwai","doi":"10.21873/invivo.13693","DOIUrl":"10.21873/invivo.13693","url":null,"abstract":"<p><strong>Background/aim: </strong>Cholangiocarcinoma (CCA) is a highly aggressive disease. Most of CCA patients are diagnosed in an advanced stage of the disease, when it is unresectable and there is chemoresistance, resulting in poor prognosis. However, effective therapeutic regimens and molecular targets for CCA remain poor. Cyclin-dependent kinases (CDKs) are key regulatory enzymes in cell cycle progression. Aberrant CDK activation is a hallmark of cancer. Dinaciclib is a small molecule inhibitor of multiple CDKs, currently under clinical evaluation for treating advanced malignancies. The efficacy of anti-tumor activity of dinaciclib against chemotherapy resistant CCA cells was examined in vitro and in vivo.</p><p><strong>Materials and methods: </strong>In this study, the effect of dinaciclib on growth and cell cycle in CCA cell lines were determined using the MTT assay and cell cycle analysis. The anti-tumor activity of dinaciclib was investigated in CCA-inoculated mice. In addition, the chemosensitizing effect of dinaciclib was investigated in gemcitabine-treated CCA cell lines.</p><p><strong>Results: </strong>Dinaciclib significantly suppressed cell proliferation, induced G₁/S phase cell cycle arrest and apoptosis of CCA cell lines. It significantly suppressed the growth of CCA cells in xenograft mouse models. We also found that dinaciclib significantly inhibited the growth of gemcitabine-resistant CCA cell lines (KKU-213A-GemR and KKU-100-GemR). Furthermore, dinaciclib significantly enhanced the anti-tumor activity of gemcitabine in CCA cell lines.</p><p><strong>Conclusion: </strong>Dinaciclib has the potential to be an effective therapeutic agent to control tumor cell growth of both parental and gemcitabine-resistant CCA cells.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"38 5","pages":"2284-2293"},"PeriodicalIF":1.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072655","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}