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Neoadjuvant use of oncolytic herpes virus G47Δ prevents local recurrence after insufficient resection in tongue cancer models

ABSTRACT: Mice with orthotopic tongue cancer received neoadjuvant G47Δ therapy. Neoadjuvant G47Δ and resection led to 10/10 survival even with insufficient resection margins.

ORGANISM(S): Mus musculus

PROVIDER: GSE227813 | GEO | 2023/04/13

REPOSITORIES: GEO

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Neoadjuvant use of oncolytic herpes virus G47Δ prevents local recurrence after insufficient resection in tongue cancer models

Project description:Neoadjuvant use of oncolytic herpes virus G47Δ prevents local recurrence after insufficient resection in tongue cancer models

| PRJNA947121 | ENA

Neoadjuvant use of oncolytic herpes virus G47Δ prevents local recurrence after insufficient resection in tongue cancer models.

Project description:A complete resection of tongue cancer is often difficult. We investigate the usefulness of administering G47Δ (teserpaturev), a triple-mutated oncolytic herpes simplex virus type 1, prior to resection. G47Δ exhibits good cytopathic effects and replication capabilities in all head and neck cancer cell lines tested. In an orthotopic SCCVII tongue cancer model of C3H/He mice, an intratumoral inoculation with G47Δ significantly prolongs the survival. Further, mice with orthotopic tongue cancer received neoadjuvant G47Δ (or mock) therapy with or without "hemilateral" resection, the maximum extent avoiding surgical deaths. Neoadjuvant G47Δ and resection led to 10/10 survival (120 days), whereas the survivals for G47Δ alone and resection alone were 6/10 and 5/10, respectively: all control animals died by day 11. Furthermore, 100% survival was achieved with neoadjuvant G47Δ therapy even when the resection area was narrowed to "partial," providing insufficient resection margins, whereas hemilateral resection alone caused death by local recurrence in half of the animals. G47Δ therapy caused increased number of tumor-infiltrating CD8+ and CD4+ cells, increased F4/80+ cells within the residual tongues, and increased expression of immune-related genes in and around the tumor. These results imply that neoadjuvant use of G47Δ is useful for preventing local recurrence after tongue cancer surgery.

| S-EPMC10423690 | biostudies-literature

Integrated proteomics and phosphoproteomics revealed druggable kinases in neoadjuvant chemotherapy resistant tongue cancer

Project description:Tongue squamous cell carcinoma is characterised by poor prognosis and high metastatic events. Patients with unresectable tumors are benefiting from neoadjuvant chemotherapy (NACT) which surgical resection, and controls distant metastasis, and locoregional recurrence. However, resistance to NACT limit the success of the treatment regimen. In this study, we investigated the altered proteome and phosphoproteome of NACT resistant and sensitive cohort using Mass spectrometry-based proteomics. We carried out proteomic as well as phosphoproteomic analysis of treatment naïve tongue cancer patients whose response to NACT is recorded. Proteomic analysis revealed distinct protein expression between the responders and non-responders. The Phosphoproteomic analysis revealed kinases and the pathways associated with NACT resistance in tongue cancer.

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Transcription profiling by array of Paneth cells and whole ileum from human Crohn's disease patient ileo-colic resection tissue

Project description:Transcriptional profiling of microscopically laser dissected Paneth cells and whole thickness ileum tissue from the proximal margins of archived formalin-fixed, paraffin-embedded ileo-colic resection samples.

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A gene signature in histologically normal surgical margins is predictive of oral carcinoma recurrence

Project description:Samples were prospectively collected from patients with histologically normal surgical resection margins. 96 tissue samples (histologically normal margins, oral carcinoma and adjacent normal tissues) from 24 patients comprised the training set. Our study design was guided by the hypothesis that the expression of genes present in oral squamous cell carcinoma (OSCC) but not in healthy oral tissues would be indicative of recurrence in advance of histological alteration. We used meta-analysis of five published microarray data sets (GEO accession GDS2520, Kuriakose et al. 2004; GDS1584, Toruner et al. 2004; GSE6791, Pyeon et al. 2007; GSE9844, Ye et al. 2008; and GSE10121, Sticht et al. 2008), in conjunction with the current training set, to identify genes reliably over-expressed in OSCC. This reduced gene set was used to train a risk model to predict recurrence based on over-expression of a subset of these genes in histologically normal surgical resection margins. Validation of the risk signature was performed using quantitative real-time reverse-transcription PCR in an independent set of 136 samples from an independent cohort of 30 patients. This was a case-only design involving a training set of 23 tumors and 73 margins from 24 patients with squamous cell carcinoma of the tongue.

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Transcription profiling of human head and neck squamous cell carcinomas to identify metastasis predictors and descriptors, and differentiation classifiers

Project description:A "Cartes d'Identite des Tumeurs" (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net). 81 samples on Affymetrix HG-U133 Plus 2.0 GeneChips arrays for 81 patients with primary Head and Neck Squamous Cell Carcinoma (HNSCC; oral cavity, tongue, oro- or hypopharynx); metastases as first recurrent event in a 36-month follow up; histologically tumor-free margins (?3 mm); patients had undergone surgical resection as the first treatment and had no clinically evident distant metastases.

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Project description:Tongue squamous cell carcinoma is a tumour type with rather low five year survival, around 60%. The poor survival rate has been ascribed to late detection, a high frequency of locoregional recurrence, the occurrence of secondary primary tumours and death due to comorbidity. One reason for development of recurrence is thought to be the existence of transformed cells in areas adjacent to the primary tumour, cancerization field effect. The aim of this study was to map the changes in the tumour free tongue tissue adjacent to tongue tumours compared with healthy control tongue tissue to better understand the cancerization field effect. Tissue biopsies were collected from tumour (T) and tumour free tissue adjacent to the tumour (TF) from patients with tongue squamous cell carcinoma. Control tissue was collected from latter border of the tongue of tumour free healthy volunteers (C). All samples were homogenized and RNA was extracted. The RNA was biotin labelled and run on Illumina HT-12 bead chip array.

2016-12-21 | E-MTAB-4678 | biostudies-arrayexpress

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Project description:This SuperSeries is composed of the following subset Series: GSE34105: Gene expression profiling of archival tongue carcinoma and normal tongue tissue (all samples) GSE34106: Gene expression profiling of archival tongue carcinoma and normal tongue tissue (subset) Refer to individual Series

2012-05-10 | E-GEOD-34115 | biostudies-arrayexpress

Tongue tissue gene profile in 4NQO induced tongue carcinogenesis before and after IL-1Ra interference

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Oncolytic herpes virus G47Δ injected into tongue cancer swiftly traffics in lymphatics and suppresses metastasis.

Project description:The prognosis of oral squamous cell carcinoma (OSCC) largely depends on the control of lymph node metastases. We evaluate the therapeutic efficacy of G47Δ, a third-generation oncolytic herpes simplex virus type 1 (HSV-1), in mouse tongue cancer models. Intratumoral injection with G47Δ prolonged the survival in all orthotopic models investigated. In both athymic and immunocompetent models, G47Δ injected into the tongue cancer swiftly traffics to the draining cervical lymph nodes and suppresses lymph node metastases. In the immunocompetent KLN205-MUC1 model, in which the metastatic cascade that tongue cancer patients commonly experience is reproduced, intratumoral G47Δ injection even immediately prior to a tumor resection prolonged survival. Cervical lymph nodes 18 h after G47Δ treatment showed the presence of G47Δ infection and an increase in CD69-positive cells, indicating an immediate activation of T cells. Furthermore, G47Δ injected directly into enlarged metastatic lymph nodes significantly prolonged the survival at an advanced stage. Whereas intratumorally injected oncolytic HSV-1 does not readily circulate in the blood stream, G47Δ is shown to traffic in the lymphatics swiftly. The use of G47Δ can lead to entirely new treatment strategies for tongue cancer and other OSCC at all clinical stages.

| S-EPMC8430046 | biostudies-literature

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