Veterinary and comparative oncology最新文献

{"title":"Critical Questions in Genomic Diagnostics for Veterinary Oncology: What We Need to Know.","authors":"Sharadha Sakthikumar, Giulia Siravegna, Michelle E White, Douglas H Thamm, Esther Chon","doi":"10.1111/vco.70068","DOIUrl":"10.1111/vco.70068","url":null,"abstract":"<p><p>Genomic diagnostics are increasingly integrated into veterinary oncology practice, offering the possibility of refined approaches to tumour classification, risk stratification and therapeutic guidance through high-throughput sequencing technologies. In human medicine, the clinical utility of genomic testing is underpinned by rigorous analytical and clinical validation, robust regulatory oversight and an expanding evidence base linking specific genomic alterations to disease phenotypes and therapeutic responses. In contrast, genomic testing in veterinary oncology remains underdeveloped, with limited standardisation, sparse species-specific validation and frequent reliance on extrapolation from human data. This review delineates the current landscape of genomic testing in veterinary oncology, emphasising methodological considerations in assay design, validation requirements, and clinical interpretation. We highlight the need for analytical rigour, including the use of in silico and orthogonal validation strategies, and advocate for the establishment of performance benchmarks that account for assay sensitivity, specificity and reproducibility in relevant canine populations. In addition, we address the interpretive challenges posed by variants of uncertain significance and the limitations of inferring clinical actionability from human oncology frameworks. A critical, question-driven approach is proposed to guide clinicians in evaluating the validity and applicability of genomic tests, focusing on test validation, intended clinical use and the functional relevance of identified alterations. Advancing genomic diagnostics in veterinary oncology will require coordinated efforts to improve transparency, expand validation cohorts and align clinical expectations with the current evidentiary base. These steps are essential to realising the full potential of precision medicine in veterinary oncology while maintaining scientific and clinical integrity.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"657-664"},"PeriodicalIF":1.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147718374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic Profiling of Canine Mammary Tumours Reveals Significant Heterogeneity Between and Within Histological Classes.","authors":"Ingrid Marie Moberg, Nina Hansen, Helga Bergholtz, Kaja Sverdrup Borge, Gjermund Gunnes, Ellen Frøysadal Arnet, Ole Albert Guttersrud, Monica Hongrø Solbakken, Frode Lingaas","doi":"10.1111/vco.70067","DOIUrl":"10.1111/vco.70067","url":null,"abstract":"<p><p>This study presents a comprehensive transcriptomic analysis of 128 canine mammary tumours (CMTs), aiming to characterize their molecular landscape. Differential gene expression analysis (DGE), gene set enrichment analysis (GSEA) and clustering based on the human PAM50 gene panel were applied to explore molecular differences between the different histological categories. The analysis revealed transcriptomic differences between benign and malignant tumours as well as between tumours with high and low mitotic count. Malignant tumours were significantly enriched for gene sets associated with cell cycle regulation, proliferation, inflammatory response, signalling pathways and metabolic processes. Of the malignant tumours, purely epithelial tumours were enriched in gene sets related to proliferation, signalling and metabolic processes when compared to mixed tumours harbouring myoepithelial or mesenchymal components. To assess the relevance of human classification systems, CMTs were clustered on the PAM50 genes. The analysis revealed two clusters resembling human basal-like and luminal A subtypes, while the remaining tumours did not display expression patterns similar to human breast cancer subtypes. This suggests that there are limitations to applying the human molecular classification systems to canine tumours without adaptation. Additionally, CMTs displayed intragroup heterogeneity, where not all tumours within a histopathological category clustered together, indicating that the molecular aspect of CMTs is not necessarily reflected in the pathology. Together, this study highlights the need to develop canine-specific molecular markers based on gene expression, which could enable diagnosis prior to surgical removal of tumours, and ultimately improve treatment strategies and outcomes for dogs with mammary tumours.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"444-457"},"PeriodicalIF":1.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147700261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Definitive-Intent 10-Fraction Radiotherapy Protocol ('The Zurich Protocol') Yields Lasting Tumour Control and Survival in Dogs With Intracranial Meningiomas.","authors":"Carlotta Ahrens, Sergejs Unterkirhers, Carla Rohrer Bley","doi":"10.1111/vco.70081","DOIUrl":"10.1111/vco.70081","url":null,"abstract":"<p><p>Moderately hypofractionated definitive-intent radiotherapy protocols can be used for canine intracranial meningiomas to shorten overall treatment time while maintaining tumour control and limiting normal tissue toxicity. This retrospective study evaluated oncologic outcomes, toxicity, and radiation dose-volume-related prognostic factors in dogs with imaging-based intracranial meningiomas treated with a 10-fraction definitive-intent protocol. Medical records from 2015 to 2025 were reviewed. All dogs received 10 daily fractions of 4 Gy delivered with a homogeneous dose prescription, risk-adapted heterogeneous dose distributions, or an 11% simultaneously integrated boost (SIB) to the gross tumour volume. One hundred and ten dogs were included, with a median follow-up of 498 days. Median time to progression was 873 days (95% CI: 552-1195), median overall survival after first radiotherapy was 756 days (95% CI: 474-1039), and median DSS was 1078 days (95% CI: 915-1242). Time to progression differed among treatment subgroups (p = 0.024). Larger volumes of normal brain receiving ≥ 32 Gy (> 11.5 cm³) were associated with shorter overall (p < 0.001) and disease-specific survival (p = 0.002). Use of an SIB was associated with shorter disease-specific survival (HR 2.47; p = 0.012), and post-radiotherapy seizures were associated with reduced time to progression (HR 2.01; p = 0.026). Tumour location was not identified as a prognostic factor. Acute or early delayed neurologic toxicity occurred in 10% of dogs and was generally transient and generally corticosteroid responsive. In conclusion, the definitive-intent, moderately hypofractionated 10-fraction radiotherapy protocol achieves long lasting tumour control and survival outcomes in dogs with intracranial meningiomas, provided that evidence-based brain dose-volume constraints are respected.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"601-610"},"PeriodicalIF":1.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148266328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-Species Transcriptomic and Network Analysis of Human and Canine Diffuse Large B-Cell Lymphoma Identifies a Conserved Replication-DNA Damage Module for Drug Repurposing.","authors":"Soroush Akbari-Ardabili, Safiyeh Aghazadeh","doi":"10.1111/vco.70079","DOIUrl":"10.1111/vco.70079","url":null,"abstract":"<p><p>Rational, mechanism-based drug selection for canine diffuse large B-cell lymphoma (DLBCL) remains limited, despite extensive molecular work in human DLBCL. We asked whether human and canine DLBCL share a conserved transcriptional network that could anchor therapeutic hypotheses for dogs. Using public human and canine DLBCL transcriptomes, we derived a 409-gene cross-species module defined by concordant tumour-normal dysregulation and projected it onto pathway and protein-protein interaction (PPI) networks. The module was dominated by DNA replication, cell-cycle checkpoint and DNA damage-response programmes and contained a compact PPI core centred on TOP2A and PARP1. Querying the Connectivity Map/LINCS library with the human component of the module highlighted anthracycline-like topoisomerase II poisons (valrubicin, etoposide, amsacrine) and the PARP inhibitor rucaparib among the ~0.2% most negative connectivity scores, while directly targeting TOP2A and/or PARP1. A simple up-down module score strongly separated tumour from normal lymph nodes in both species and was associated with outcome: higher scores predicted longer progression-free survival in CHOP-treated dogs and better overall survival in an independent human cohort, with a similar but underpowered trend in TCGA-DLBC. Finally, extracellular-vesicle microRNA (EV-miRNA) profiling in human DLBCL showed that differentially expressed EV-miRNAs, including let-7 family members, miR-21-5p, miR-124-3p and miR-205-5p, converge on the same TOP2A/PARP1-centred core. These cross-species, multi-layer data support topoisomerase II poisons and PARP inhibition as coherent, network-anchored candidate therapies for canine DLBCL, with module scores and EV-miRNAs as candidate biomarkers.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"578-592"},"PeriodicalIF":1.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147983538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Response of Canine and Human Osteosarcoma Tumour Cell Lines to Molecularly Targeted Anticancer Agents at Clinically Relevant Exposures With Analysis of Genomic Biomarkers.","authors":"Daniel L Gustafson, Kala A Early, Maritza A Morales, Klaudia A Poplawski, Sunetra Das, Dawn L Duval","doi":"10.1111/vco.70074","DOIUrl":"10.1111/vco.70074","url":null,"abstract":"<p><p>Osteosarcoma (OSA) is a primary bone tumour occurring in children but is also prevalent in large breed dogs. Canine OSA (cOSA) has long been viewed as analogous to human OSA (hOSA) with cOSA serving as a surrogate for development of therapeutic approaches to treat the rarer human form. Drug therapy of OSA has remained virtually unchanged over the last four decades and drug testing is challenging due to the genomic heterogeneity of OSA as well as the limited number of patients for clinical trials. Thus, an approach that includes a suitable clinical surrogate at the early stage of therapeutic development may be beneficial. Therefore, to address these challenges, a phenotypic drug screen of 12 targeted anticancer drugs was carried out using 13 cOSA and 6 hOSA cell lines and responses compared at clinically relevant exposures (CRE) estimated from human data. The results identified four drugs (alisertib, crizotinib, onvansertib and sorafenib) with significant responses at the CRE in cOSA and hOSA cell lines and demonstrated that drug responses were indistinguishable across species. Correlations of drug response with genomic biomarkers in the cOSA cell line panel identified Myc and Hedgehog signalling as potential predictors of crizotinib response and Myc, epithelial markers and anti-apoptotic signalling for onvansertib response. The conclusions of these findings are that cOSA and hOSA cell lines show the same range of response to targeted agents and identify potential biomarker pathways for further investigation in OSA tumours for use in future comparative oncology studies including clinical trials in pet dogs.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"532-544"},"PeriodicalIF":1.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Novel Therapeutic Agent Candidates Through High Throughput Screening With Chemical Library Based on Molecular Subclassification in Canine Histiocytic Sarcoma Cell Lines.","authors":"Hiroki Sakuma, Hirotaka Tomiyasu, Mari Takamiya, Yuko Goto-Koshino, Atsushi Tsukamoto, Makoto Bonkobara, Masaru Okuda","doi":"10.1111/vco.70077","DOIUrl":"10.1111/vco.70077","url":null,"abstract":"<p><p>Effective chemotherapy for canine histiocytic sarcoma (CHS) has yet to be established. In our previous study, CHS cell lines were subclassified into two groups based on their gene expression profiles: Group A and Group B. This study aimed to identify novel therapeutic agents that are effective against each CHS subgroup, and we performed high throughput screening, which examined the effects of 1824 chemical compounds on the 10 CHS cell lines. Among the compounds examined, 73 compounds were identified as candidates to show antiproliferative effects in all CHS cell lines examined, and the median IC₅₀ values of 5-fluorouracil and sunitinib were 7.49 μM and 608 nM, respectively, across all CHS cell lines. While there was no compound that was specifically effective for Group B CHS cell lines, duvelisib was identified as a selective antitumor agent for CHS cell lines in Group A (median IC₅₀ = 287 nM), with minimal effects on the other group (median IC₅₀ > 5 μM) and normal peripheral blood mononuclear cells (IC₅₀ = 7.46 μM). The amount of phosphorylated Akt protein decreased following duvelisib treatment in all eight CHS cell lines in Group A, but not in cell lines in Group B. Furthermore, duvelisib induced cell cycle arrest and increased cell death in a subset of Group A cell lines. These findings demonstrated that duvelisib exerted antiproliferative effects through inhibition of the Akt pathway in a subset of CHS cell lines while causing minimal cytotoxicity to normal cells.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"554-567"},"PeriodicalIF":1.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147933902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing EGFR Inhibition: Monensin and Erlotinib Synergize to Eliminate Cancer Stem Cells in Canine Mammary Tumours.","authors":"Tian Fang, Mengxing Zhang, Chang Ma, Min Dong, Xinhao Song, Junqi Wang, Runan Zuo, Jinwei You, Yingfeng Zhao, Shanxiang Jiang, Dawei Guo","doi":"10.1111/vco.70085","DOIUrl":"10.1111/vco.70085","url":null,"abstract":"<p><p>Canine mammary tumours (CMTs) and human breast cancer (HBC) share highly similar pathological characteristics. Cancer stem cells (CSCs) are critical to breast cancer invasion, metastasis, drug resistance, and recurrence. The experiment utilised CMT cell line CMT-U27 and HBC cell line MDA-MB-231. Cancer stem cell spheres were isolated from the two cell lines by serum-free culture respectively, named as CMT-U27 microspheres (CMT-U27S) and MDA-MB-231 microspheres (MDA-MB-231S), and the proportion of CSCs with the CD44⁺/CD24^- phenotype was identified by flow cytometry. Monensin (MON), one of Polyether ionophore antibiotics, has been demonstrated to effectively suppress various types of CSCs, while erlotinib (ERL), as a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR), effectively inhibits cancer cell growth. This study investigates the synergistic inhibitory effects of MON-ERL combination on CSCs derived from CMTs. Cell viability was analysed by CCK-8 assay, while cell invasion and mammosphere formation assays were conducted to evaluate changes. An orthotopic tumour model in nude mice using CMT-U27S was established for in vivo validation. The results suggested that MON and ERL combination synergistically inhibited CSCs viability and significantly suppress their invasion and mammosphere formation abilities. The expression of key proteins of the EGFR pathway-p-EGFR, PI3K, and p-AKT was significantly reduced. In animal experiments, tumour volumes in the combination treatment group were markedly reduced compared to those in all other groups (p < 0.05), and no lung metastases were observed only in the combination group. Immunofluorescence and immunohistochemistry results indicated a marked reduction of CD44⁺/CD24^- cells in the combination group, along with suppressed expression of stem cell markers and proliferation/apoptosis proteins. In conclusion, MON combined with ERL effectively inhibits the proliferation, self-renewal, and metastatic capabilities of CSCs from CMTs by synergistically downregulating the EGFR/PI3K pathway, demonstrating promising antitumor potential and offering a new strategy for CMTs treatment.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"643-656"},"PeriodicalIF":1.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148449651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surgical Margins Required for the Complete Excision of Canine Oral Melanomas.","authors":"Jonathon Richard Chinner, Jovene Jia Wen Lee, Jonathan Tuke, Fui Wen Yap","doi":"10.1111/vco.70069","DOIUrl":"10.1111/vco.70069","url":null,"abstract":"<p><p>Oral malignant melanoma (OMM) is the most common canine oral neoplasm. Complete excision is recognised as the mainstay of treatment in the absence of distant metastasis, but recommended surgical margins are unvalidated. This study investigates the surgical margins required for complete excision of canine OMMs. We hypothesised that surgical margins 10-15 mm wide and a qualitative deep margin (bone, fascia or full-thickness tissue excision) would be adequate for complete local excision of OMMs. Margins required to excise canine oral melanocytomas are also unknown; a secondary objective was to investigate this. Cases were retrospectively collected from two referral centres and a veterinary pathology laboratory. Histologic diagnosis, en bloc excision of gross tumour, surgical margin and histologic margins were required for inclusion. Tumours were categorised based on surgical margin width (Group A < 10 mm, Group B 10-15 mm and Group C > 15 mm). A qualitative deep margin was required for Groups B and C, but not Group A, to include marginal excision cases. Histologic margins were classified by the R tumour classification scheme. Twenty-eight tumours were included, comprising 25 OMMs and three melanocytomas. R0 rates for OMMs were 56% (10/17) in Group A, 100% (7/7) in Group B and 100% (2/2) in Group C. Surgical margins ≥ 10 mm were significantly (p = 0.03) more likely to result in R0 classification. The three melanocytomas were all classified as R0, with < 10 mm surgical margins. Results suggest that surgical margins 10-15 mm wide and a qualitative deep margin may be adequate for complete excision of OMMs.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"458-467"},"PeriodicalIF":1.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147700238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic and microRNA Profiling Suggest a Candidate RIPPLY1-cfa-miR-187 Relationship in Canine Mammary Gland Tumours From Dogs With Confirmed Metastasis.","authors":"Shaohsu Wang, Masashi Takahashi, Hui-Wen Chen, Nobuhiro Nozaki, Mohammad Arif, Yutaro Ide, Yoshiyuki Akiyama, Sirazul Islam, Tatsuro Hifumi, Shinji Hirano, Noriaki Miyoshi, Osamu Yamato, Daiki Kato, Takayuki Nakagawa, Naoki Miura","doi":"10.1111/vco.70084","DOIUrl":"10.1111/vco.70084","url":null,"abstract":"<p><p>Canine mammary gland tumours (MGT) represent a common malignancy in intact female dogs, with a high metastasis rate approaching 50% and a poor prognosis. However, metastasis-related genes remain largely unelucidated. Accordingly, we aimed to identify differentially expressed mRNAs and miRNAs in primary canine MGT tissues from dogs with or without confirmed metastasis. We compared mRNA and microRNA (miRNA) expression profiles between malignant MGT tissue samples with and without metastasis. Differentially expressed genes and miRNAs were identified using next-generation sequencing and analysed using the Empirical Analysis of DEGs tool within CLC Genomics Workbench. We identified 119 genes and eight miRNAs as differentially expressed in primary MGTs from dogs with confirmed metastasis. The RIPPLY1 gene was significantly downregulated in primary MGT samples with confirmed metastasis and this result was validated by RT-qPCR. The Cancer Genome Atlas (TCGA) database showed decreased RIPPLY1 expression in human breast cancer, supporting its possible relevance to tumour biology. In silico analysis (miRWalk) revealed that miR-187 is a predicted candidate miRNA that may interact with RIPPLY1 and both NGS data and RT-qPCR showed increased cfa-miR-187 expression in primary tumour samples from dogs with confirmed metastasis. The inverse expression pattern of RIPPLY1 and cfa-miR-187, together with RNAhybrid binding prediction, suggests a possible candidate miRNA-mRNA relationship. STRING analysis suggested a possible pathway context involving beta-catenin/TCF-related proteins, but this computational result requires further validation. Based on these findings, we identified RIPPLY1 and cfa-miR-187 as potential candidate transcripts associated with primary canine MGTs from dogs with confirmed metastasis but functional validation is required.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"631-642"},"PeriodicalIF":1.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148377403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokine-Enhanced Vaccine as Surgery Adjuvant Treatment for Spontaneous Canine Melanoma: Comparison of Two Intralesional Procedures for Local Disease Control.","authors":"Liliana M E Finocchiaro, Marcela S Villaverde, Gerardo C Glikin","doi":"10.1111/vco.70072","DOIUrl":"10.1111/vco.70072","url":null,"abstract":"<p><p>We present here the feasibility, safety, and efficacy results of a 7-year study that included 337 canine melanoma patients undergoing surgery with adjuvant intralesional therapies combined with immunogenic therapy. After complete (CS) or partial (PS) surgery, the patients received post-surgical bed injections of (i) lipoplexes carrying canine interferon-β (cIFNβ) gene combined with bleomycin (CT_IF/B) or (ii) 5-fluorouracil (CT_5FU). This surgery adjuvant therapy (SAT) also included the periodic administration of subcutaneous genetic vaccines composed of tumour extracts and lipoplexes carrying cIFNβ, human interleukin-2, and human granulocyte-macrophage colony-stimulating factor genes. Compared at the end of their individual follow-ups with controls treated with complete surgery alone (CSo), CS-CT_IF/B and CS-CT_5FU treatments quadrupled the fraction of local disease-free (from 19% to 81% and 85%), and increased the percentage of metastasis-free patients (M0: from 47% to 82% and 81%). Both PS arms (PS-CT_IF/B and PS-CT_5FU) also significantly increased the fraction of metastatic-free disease (M0: from 48% to 75% and 73%). In addition, SAT produced a significant 11- (CS-CT_IF/B: p < 0.0001, HR_{95% CI} = 0.155 [0.109-0.222]), 9- (CS-CT_5FU: p < 0.0001, HR_{95% CI} = 0.172 [0.123-0.242]), 6- (PS-CT_IF/B: p < 0.0001, HR_{95% CI} = 0.204 [0.132-0.315]), and 7- (PS-CT_5FU: p < 0.0001, HR_{95% CI} = 0.203 [0.132-0.311]) fold increase of overall survival as compared to their respective CSo and PSo controls. The respective median follow-up days for each group were: 695.5 (28-2516), 542.5 (46-2554), 458 (29-1273), and 521 (30-1659). In general terms, this SAT transformed a lethal disease into a manageable condition where 25% (CS-CT_IF/B), 24% (CS-CT_5FU), 22% (PS-CT_IF/B), and 22% (PS-CT_5FU) of patients were still alive at the end of the study, while 53%, 60%, 16%, and 17%, respectively, died from causes unrelated to melanoma. Both surgery adjuvant treatments delayed or prevented post-surgical recurrence and metastases, improved disease-free and overall survival while maintaining quality of life. These successful outcomes encourage assaying a similar scheme for human melanoma.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"499-514"},"PeriodicalIF":1.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}