Anticancer research最新文献

{"title":"Robotic-assisted Distal Pancreatectomy Is Associated With Significant Reduction of Morphine Consumption for the Treatment of Acute Postoperative Pain.","authors":"Amelie F Kruse, Andreas Andreou, Haluk Morgul, Mira Kuellmar, Shadi Katou, Mazen A Juratli, Carsten Szardenings, Andreas Pascher, Benjamin Struecker, Jens P Hoelzen","doi":"10.21873/anticanres.18142","DOIUrl":"https://doi.org/10.21873/anticanres.18142","url":null,"abstract":"<p><strong>Background/aim: </strong>Minimal-invasive techniques have been increasingly performed to treat pancreatic lesions. We evaluated the differences between open and robotic approach for distal pancreatectomy (DP) in terms of postoperative analgesic consumption and perioperative outcomes.</p><p><strong>Patients and methods: </strong>Clinicopathological data of patients undergoing DP from 2012-2023 were evaluated. The study compared robotic (RDP) with open distal pancreatectomies (ODP) regarding total postoperative morphine consumption. Secondary endpoints included intensive care unit (ICU) stay and hospital stay.</p><p><strong>Results: </strong>During the study period, 78 DP were performed, including, 24 RDP and 54 ODP. Multivisceral resections including DP and laparoscopic DP were excluded. Patients who underwent RDP required significantly less opioid analgesics compared to those after ODP (113.60 mg; 0,00-516,20 mg morphine milligram equivalents; median; minimum-maximum <i>vs</i>. 253.75 mg; 15,00-3519,45 mg; <i>p</i><0.001). When adjusted for patient weight, the morphine equivalent dose also showed a significant difference between RDP and ODP (1.51; 0,00-6,53 mg/kg <i>vs</i>. 3.19; 0,24-62,85 mg/kg; <i>p</i>=0.004). Additionally, patients who underwent RDP had significantly shorter postoperative ICU stay compared to patients with ODP (0; 0-7 days <i>vs</i>. 4; 1-54 days; <i>p</i><0.001) and shorter hospital stay compared to the open group (10.5; 6-33 days <i>vs</i>. 16; 9-92 days; <i>p</i><0.001).</p><p><strong>Conclusion: </strong>Patients who underwent RDP required significantly lower amounts of opioid analgesics compared to ODP. Furthermore, RDP was associated with significantly shorter length of ICU and hospital stay.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"46 5","pages":"2619-2630"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760274","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}

{"title":"Invasive-Front P21 Expression Is Associated With Tumor Aggressiveness in Head and Neck Squamous Cell Carcinoma.","authors":"Su Il Kim, Minjeong Kim, Jung Woo Lee, Sun Lee, Hyun Jee Lee, Young-Gyu Eun, Young Chan Lee","doi":"10.21873/anticanres.18132","DOIUrl":"https://doi.org/10.21873/anticanres.18132","url":null,"abstract":"<p><strong>Background/aim: </strong>P21 is a key cyclin-dependent kinase inhibitor linked to cellular senescence. However, its spatial expression patterns within tumor compartments and their relationship with tumor aggressiveness remain poorly characterized in head and neck squamous cell carcinoma (HNSCC). This study investigated the spatial distribution of P21 across distinct tumor regions and evaluated its association with tumor aggressiveness, including stage and adverse pathological features, in HNSCC.</p><p><strong>Materials and methods: </strong>Formalin-fixed, paraffin-embedded tissues from patients with HNSCC were assessed using immunohistochemistry for P21. The intensity, percent positivity, and composite scores were quantified in the surface, center, and invasive-front regions. All variables were transformed using log (x+1), and spatial ratios comparing surface-to-center and invasive-front-to-center expressions were calculated. Non-parametric analyses were performed to compare early- and advanced-stage HNSCC, with additional subgroup analyses according to extracapsular extension (ECE), lymphovascular invasion (LVI), perineural invasion (PNI), and tumor subsites.</p><p><strong>Results: </strong>Advanced-stage HNSCC demonstrated significantly higher invasive-front-to-center log ratios for both percent positivity and composite P21 scores (<i>p</i>=0.0275), indicating relative enrichment of P21 expression at the invasive-front. Among advanced-stage HNSCC, PNI-positive cases showed the most pronounced increases in both surface-to-center and invasive-front-to-center spatial ratios (<i>p</i><0.05), whereas no significant spatial differences were observed for ECE or LVI.</p><p><strong>Conclusion: </strong>P21 expression demonstrated region-specific differences associated with tumor aggressiveness, with PNI-positive tumors showing the clearest enrichment of P21 expression at the invasive-front. These findings suggest that spatial, rather than absolute, P21 expression patterns may reflect progression-related phenotypes in HNSCC. Spatial profiling of P21 may provide exploratory insights into tumor biology and could help identify tumors with a higher invasive potential.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"46 5","pages":"2487-2493"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760277","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}

{"title":"Imipramine Targets Apoptosis, Metastasis, and EGFR/SRC-mediated EMT in Oral Cancer Cells.","authors":"Wei-Chun Wang, Ying-Tzu Chen, Fei-Ting Hsu, Bing-Ru Peng, Hsi-Feng Tu","doi":"10.21873/anticanres.18133","DOIUrl":"https://doi.org/10.21873/anticanres.18133","url":null,"abstract":"<p><strong>Background/aim: </strong>Oral cancer (OC) exhibits aggressive growth and metastatic potential. Imipramine, a tricyclic antidepressant, has been recently explored for its anticancer activity. This study investigated imipramine's therapeutic effects and underlying anti-progression mechanisms in OC.</p><p><strong>Materials and methods: </strong>SAS and MOC1 cell lines were treated with imipramine for cytotoxicity, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT) analyses using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, Transwell assays, and western blotting.</p><p><strong>Results: </strong>Imipramine significantly reduced OC cell viability in a dose-dependent manner and induced apoptosis through both extrinsic (Fas/FasL-caspase-8) and intrinsic (mitochondrial depolarization, ROS/Ca²⁺ elevation, caspase-9) pathways. Anti-apoptotic proteins X-linked inhibitor of apoptosis (XIAP) and cellular FLICE-like inhibitory protein (c-FLIP) and proliferation regulator Cyclin D1 were downregulated. Imipramine also inhibited migration, invasion, and expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor-A (VEGF-A). EMT progression was suppressed, evidenced by decreased zinc-finger-enhancer binding protein 1/2 (ZEB1/2), Snail, Slug, N-cadherin, and re-expression of E-cadherin, accompanied by inactivation of the EGFR/SRC axis.</p><p><strong>Conclusion: </strong>Imipramine exhibits potent anti-OC activity by inducing apoptosis, inhibiting metastasis, and suppressing EMT, supporting its potential as a repurposed therapeutic agent.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"46 5","pages":"2495-2508"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760293","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}

{"title":"Inflammatory Cytokine Genotypic Markers and Ovarian Cancer Risk.","authors":"Wen-Shin Chang, Chia-Wen Tsai, Jaw-Chyun Chen, Yun-Chi Wang, DA-Tian Bau","doi":"10.21873/anticanres.18165","DOIUrl":"https://doi.org/10.21873/anticanres.18165","url":null,"abstract":"<p><p>Ovarian cancer is the most lethal gynecological malignancy worldwide, largely due to late diagnosis and lack of effective population-level screening tools. Inflammatory cytokines regulate proliferation, apoptosis, angiogenesis, and immune surveillance, making inherited variation in cytokine pathways biologically plausible determinants of ovarian cancer susceptibility and progression. Since the early 2000s, numerous candidate-gene studies have evaluated polymorphisms of genes such as the interleukin (<i>IL</i>) families, tumor necrosis factor alpha (<i>TNFA</i>), transforming growth factor beta 1 (<i>TGFB1</i>), and components of the nuclear factor kappa B (<i>NFKB</i>) signaling pathway and adhesion pathways, across diverse populations. In this review, we summarize these potential markers to give readers an overview showing accumulated evidence supports a coherent model in which genetically modulated inflammation is an integral driver of epithelial ovarian carcinogenesis. Collectively, studies reveal recurrent patterns of risk-increasing and risk-protective variants. Risky genotypes predicted to enhance pro-inflammatory, pro-angiogenic, or immunosuppressive signaling include <i>IL1B</i> rs16944 CC, <i>IL6</i> rs1800795, <i>IL8</i> rs2227306 TT, <i>IL8</i> rs1126647 TT, <i>IL16</i> rs11556218 GT/GG, <i>IL16</i> rs4778889 CT/CC, <i>IL23R</i> rs10889677 AC/CC, <i>IL31</i> rs4758680 CA/AA, <i>IL32</i> rs28372698 TT, <i>TNFA</i> rs1800629 GA/AA, and peroxisome proliferator-activated receptor gamma (<i>PPARG</i>) rs1801282 CG genotypes. Conversely, protective variants tend to dampen inflammatory tone or rebalance cytokine networks, including <i>IL1A</i> rs17561 GT/TT, <i>IL1A</i> rs4848300 CT/CC, <i>IL1A</i> rs3783553 insertion/insertion, <i>IL1B</i> rs7596684 CT/CC, <i>IL6</i> rs1880242 GT/TT, <i>IL31</i> rs7977932 CG/GG, <i>TGFB1</i> rs1800469 CT/TT, selectin E (<i>SELE</i>) rs5361 AC, intercellular adhesion molecule 1 (<i>ICAM1</i>) rs5498 AG genotypes and specific <i>IL6</i> haplotypes. Beyond risk <i>per se</i>, several polymorphisms appear predictive of clinical features, including tumor stage, cytoreductive resectability and recurrence, highlighting potential prognostic relevance. Notably, associations are often population-specific, reflecting differences in allelic frequencies and linkage disequilibrium across ethnic groups, underscoring the need for cross-ethnic replication. Further investigations may ultimately enable further improved the prevention, early detection, and personalized management of ovarian cancer.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"46 5","pages":"2863-2876"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760316","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}

{"title":"Identification of Risk Factors for the Local Recurrence of Hepatocellular Carcinoma Post-radiofrequency Ablation.","authors":"Kosuke Tanaka, Akifumi Kuwano, Masayoshi Yada, Hideo Suzuki, Kenta Motomura","doi":"10.21873/anticanres.18141","DOIUrl":"https://doi.org/10.21873/anticanres.18141","url":null,"abstract":"<p><strong>Background/aim: </strong>Radiofrequency ablation (RFA) is a mainstay curative treatment for unresectable hepatocellular carcinoma (HCC). Despite the success of RFA, however, some patients with HCC continue to experience local recurrence (LR). The aim of the present study was to identify risk factors for LR post-RFA, considering cases of repeated RFA for LR-HCC separately.</p><p><strong>Patients and methods: </strong>This study initially included 829 patients who underwent RFA for HCC at our institution between January 2013 and December 2022. From these, 447 patients with single HCC were selected based on the selection criteria, and they were further classified into a new HCC lesion group (n=400, NL group) and repeated RFA for LR-HCC post-first RFA group (n=47, LR group). The two groups were retrospectively analyzed to identify factors related to LR post-RFA.</p><p><strong>Results: </strong>In the NL and LR groups, the median observation period after treatment was 36.9 months and 33.7 months, respectively. The cumulative LR rates were 5.1%, 11.0%, and 14.2% in the NL group, and 12.8%, 34.2%, and 40.8% in LR group at 1, 3, and 5 years post-RFA, respectively. The Cox proportional hazard test showed that HCC tumors >1.5 cm [hazard ratio (HR)=3.606; <i>p</i>=0.001] and tumor site (adjacent to blood vessels) (HR=1.932; <i>p</i>=0.035) were identified as independent risk factors for LR post-RFA in the NL group, while only TACE prior to RFA was identified in the LR group.</p><p><strong>Conclusion: </strong>Tumor size and site of HCC were independent risk factors for LR post-RFA. Moreover, repeated RFA for LR-HCC post-first RFA had quite a high rate of LR post-RFA. For these cases, the selection of modalities other than RFA should be considered.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"46 5","pages":"2609-2618"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760340","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}

{"title":"Cancer Cachexia Predicts Benefit of Immunotherapy Plus Chemotherapy in <i>EGFR</i>-mutant NSCLC After TKI Resistance.","authors":"Haruka Nakatani, Hayato Kawachi, Tadaaki Yamada, Naoki Furuya, Hisashi Tanaka, Akihiro Yoshimura, Tomohiro Oba, Makoto Hibino, Takahito Fukuda, Yasuhiro Goto, Akira Nakao, Shinsuke Ogusu, Yuta Okazaki, Taishi Harada, Takayo Ota, Ken Masubuchi, Koji Mikami, Tae Hata, Kenji Morimoto, Koichi Takayama","doi":"10.21873/anticanres.18159","DOIUrl":"https://doi.org/10.21873/anticanres.18159","url":null,"abstract":"<p><strong>Background/aim: </strong>Cancer cachexia, characterized by weight loss and systemic inflammation, has been associated with poor prognosis in non-small cell lung cancer (NSCLC). However, its impact on treatment outcomes in tumors with mutant epidermal growth factor receptor (<i>EGFR</i>) remains unclear. This multicenter retrospective cohort study evaluated the impact of cancer cachexia on treatment selection after the development of resistance to EGFR tyrosine kinase inhibitors (TKIs).</p><p><strong>Patients and methods: </strong>This study included 439 patients with advanced <i>EGFR</i>-mutant NSCLC who received chemotherapy (n=304) or immune checkpoint inhibitors (ICIs) combined with chemotherapy (n=135) after EGFR-TKI failure. Cancer cachexia was diagnosed based on specific weight loss criteria and laboratory data. Propensity score matching was performed to adjust for baseline differences, and survival outcomes were compared.</p><p><strong>Results: </strong>Overall, significant differences in treatment outcomes were observed between the groups. In the chemotherapy group, cancer cachexia was an independent predictor of overall survival (hazard ratio=1.53; <i>p</i>=0.004), whereas it was not associated with survival in the ICIs/chemotherapy group. Among patients with cachexia, overall survival was significantly longer with ICIs/chemotherapy than with chemotherapy alone (13.8 <i>vs</i>. 11.2 months; <i>p</i>=0.049).</p><p><strong>Conclusion: </strong>Although no significant survival difference was found between chemotherapy and ICIs/chemotherapy in the overall population, ICIs/chemotherapy conferred a survival benefit to patients with cancer cachexia. These findings suggest that the presence of cachexia may serve as a potential biomarker for treatment selection in EGFR-TKI-resistant, <i>EGFR</i>-mutant NSCLC.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"46 5","pages":"2789-2806"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760181","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}

{"title":"Therapeutic Efficacy of PB101 and Chemotherapy Combination in Preclinical Gastric Cancer Models.","authors":"Minsung Park, Cheng Hyun Lee, Kui-Jin Kim, Sung-Hyun Hwang, Ji Hea Sung, Milang Nam, Minsu Kang, Woochan Park, Ji-Won Kim, Jin Won Kim, Se Hyun Kim, Jeongmin Seo, Eun Hee Jung, Koung Jin Suh, Yu Jung Kim, Jee Hyun Kim, Hye Seong Lim, Hyun Gul Yang, Eun Byul Cho, Keun-Wook Lee","doi":"10.21873/anticanres.18128","DOIUrl":"https://doi.org/10.21873/anticanres.18128","url":null,"abstract":"<p><strong>Background/aim: </strong>Gastric cancer (GC) remains a leading cause of cancer-associated deaths globally, particularly in East Asia. Although anti-angiogenic therapies have yielded therapeutic benefit in GC, their efficacy is limited, as current vascular endothelial growth factor-A (VEGF-A) and VEGF receptor-2 (VEGFR-2) targeted therapies eventually fail due to compensatory pathways involving VEGF-B and placental growth factor (PlGF). PB101, a VEGFR-1 decoy receptor, inhibits VEGF-A, VEGF-B, and PlGF, potentially offering broader anti-angiogenic effects. This study evaluated the efficacy of PB101 alone and in combination with cytotoxic chemotherapeutic agents in GC models.</p><p><strong>Materials and methods: </strong><i>In vitro</i> assays including CellTiter-Glo cell viability, tube formation, transwell and chemotaxis migration were conducted to evaluate PB101's effects on cell survival, migration, and endothelial angiogenesis. An <i>in vivo</i> NCI-N87 xenograft model was used to evaluate antitumor efficacy. Tumor angiogenesis was assessed by CD31 immunohistochemistry.</p><p><strong>Results: </strong>PB101 exerted no direct cytotoxicity on GC cells, either alone or in combination with chemotherapy. However, it demonstrated potent anti-angiogenic properties by significantly inhibiting endothelial cell migration and tube formation. As 2D culture cannot recapitulate the tumor microenvironment (TME), <i>in vivo</i> studies were conducted. <i>In vivo</i> studies revealed that mice receiving PB101 plus paclitaxel or irinotecan exhibited greater tumor volume suppression compared to each single-agent treatment group. Harvested tumors from PB101 and combination groups showed reduced CD31 expression, indicating reduced angiogenesis.</p><p><strong>Conclusion: </strong>PB101, blocking VEGF-A/B and PlGF, showed broad anti-angiogenic activity and enhanced chemotherapy efficacy in GC xenograft models when used in combination.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"46 5","pages":"2429-2443"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760296","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}

{"title":"Macroscopic Tumor Color as a Surrogate for Biological Diversity in Clear Cell Renal Cell Carcinoma.","authors":"Nozomi Tsujio, Chisato Ohe, Masanori Shiohara, Nao Yukimatsu, Takeshi Yamasaki, Masahiro Kato, Rena Uno, Junji Uchida, Kenichi Kohashi","doi":"10.21873/anticanres.18148","DOIUrl":"https://doi.org/10.21873/anticanres.18148","url":null,"abstract":"<p><strong>Background/aim: </strong>Clear cell renal cell carcinoma (ccRCC) exhibits marked intratumoral heterogeneity, reflected in its macroscopic color variation. As limited tissue sampling often underrepresents aggressive tumor components, macroscopic appearance may serve as an accessible, integrative indicator of intratumoral heterogeneity. However, its oncologic relevance has not been systematically investigated. This study evaluated a macroscopic color scoring system and its correlation with pathological prognostic factors and histological parameters linked to therapeutic response-related gene signatures.</p><p><strong>Patients and methods: </strong>Macroscopic color in 309 surgically treated ccRCC cases was retrospectively analyzed and scored as 1 (golden yellow), 2 (yellow/pale tan), or 3 (grey/white). Correlations with pathological prognostic factors, histological features (cytological phenotype/vascularity-based architectural classification/immunophenotype), and recurrence-free survival (RFS) were evaluated. Survival analyses were performed using the Kaplan-Meier method with log-rank tests and Cox proportional hazards regression models.</p><p><strong>Results: </strong>Macroscopic color score was significantly correlated with TNM stage (<i>p</i>=0.009), tumor size (<i>p</i>=0.001), and histological parameters, including World Health Organization (WHO)/International Society of Urologic Pathology (ISUP) nucleolar grade, sarcomatoid/rhabdoid features, tumor-type necrosis, cytological phenotype, vascularity-based architectural classification, and immunophenotype (<i>p</i><0.001). Higher scores were associated with adverse histological parameters, decreased vascularity, and increased immune infiltration. The strongest correlations were observed with WHO/ISUP grade and vascularity-based architectural classification. Although its C-index was lower than that of histological parameters, macroscopic color score effectively stratified RFS into three distinct groups [hazard ratio (HR)=2.69; <i>p</i>=0.022 for score 2; HR=6.53; <i>p</i><0.001 for score 3].</p><p><strong>Conclusion: </strong>Macroscopic intratumoral heterogeneity in ccRCC may offer a readily accessible surrogate for biological diversity and tumor microenvironmental features linked to therapeutic response. Systemic gross evaluation may improve tissue sampling, reduce pathological underestimation, and support personalized treatment strategies.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"46 5","pages":"2683-2692"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760307","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}

{"title":"Imbalance Between CD44 and STAT3 Enhances Spheroid Viability and Impairs Pembrolizumab Response in Urothelial Cancer.","authors":"Keita Goto, Kiyohiro Ando, Noriko Motoi, Toshihiko Iizuka, Hirotaka Fuchizawa, Yuki Nakamura, Yuta Sano, Shotaro Matsuoka, Hisanori Takenobu, Masayuki Haruta, Ritsuko Onuki, Yoh Matsuoka, Takehiko Kamijo, Yukio Kageyama","doi":"10.21873/anticanres.18129","DOIUrl":"https://doi.org/10.21873/anticanres.18129","url":null,"abstract":"<p><strong>Background/aim: </strong>Cancer cell plasticity is tightly linked to therapeutic resistance in urothelial carcinoma (UC). Signal transducer and activator of transcription 3 (STAT3) and CD44 play crucial roles in plasticity, but their potential crosstalk in the therapeutic context has not yet been fully elucidated. This study aimed to unveil the shared and distinct roles of STAT3 and CD44 and obtain a better understanding of targeted therapy in UC.</p><p><strong>Materials and methods: </strong>T24 bladder cancer cells were genetically ablated for STAT3 and CD44 and their plasticity was subsequently assessed. Phosphorylated-STAT3 (pSTAT3) and CD44 expression was determined using tissue microarrays in 16 patients who received pembrolizumab therapy for UC, and the association of their expression levels with patient prognosis was investigated.</p><p><strong>Results: </strong>Ablation of STAT3 or CD44 expression resulted in the dysregulation of vimentin expression and promotion of cell spheroid viability. Patients with imbalanced pSTAT3 and CD44 expression had significantly shorter progression-free survival and overall survival.</p><p><strong>Conclusion: </strong>Functional imbalance of STAT3 and CD44 may promote cancer cell plasticity and result in impaired pembrolizumab response in patients with advanced UC.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"46 5","pages":"2445-2453"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760327","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}

{"title":"Ubiquitin Ligase RNF149 Promotes Head and Neck Cancer Growth <i>via</i> Downregulation of CDKN2C.","authors":"Yu-Hsuan Hung, Min-Hong Wang, Li-Tzong Chen, Mei-Ren Pan, Hui-Ching Wang, Sin-Hua Moi, Chi-Wen Luo","doi":"10.21873/anticanres.18137","DOIUrl":"https://doi.org/10.21873/anticanres.18137","url":null,"abstract":"<p><strong>Background/aim: </strong>Head and neck squamous cell carcinoma (HNSC) remains one of the main causes of cancer-related deaths among male patients with cancer. Although surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy are available, their success in controlling the disease remains limited. Novel targets and therapeutics for HNSC therefore await identification, which is frequently pursued using bioinformatics approaches.</p><p><strong>Materials and methods: </strong>Bioinformatics analyses were conducted to evaluate prognosis, differential gene expression, pathways, therapeutics, immunohistochemistry, and expression correlations. Experimental procedures included gene knockdown, proliferation assays, cell cycle analysis, drug treatment, 3D assays, proximity ligation assays, immunoprecipitation, and immunohistochemistry.</p><p><strong>Results: </strong>In the present study, a prognostic factor for HNSC with concordant expression changes was identified. Ring finger protein 149 (RNF149) was shown to predict poor prognosis and to be upregulated during tumorigenesis. Pathway and therapeutic analyses revealed that RNF149-high HNSCs were enriched for cell cycle dysregulation, which might be counteracted by cyclin-dependent kinase inhibitors (CDKi). Cell line experiments validated that RNF149 knockdown in HNSC decreased proliferation and altered the response to CDKi in both 2D and 3D environments. Multi-omics analysis and tissue staining revealed that this ubiquitin ligase might ubiquitinate cyclin-dependent kinase inhibitor 2C (CDKN2C) in HNSC. This regulation was experimentally verified using proximity ligation assays (PLA) and immunoprecipitation. Finally, tissue array staining confirmed a negative correlation between RNF149 and CDKN2C expression in HNSC.</p><p><strong>Conclusion: </strong>This study provides insights into RNF149-mediated proteolysis in HNSC.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"46 5","pages":"2551-2564"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760331","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}