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TCAB1?A Potential Target for Diagnosis and Therapy in Head and Neck Cancers

ABSTRACT: Previous studies indicated TCAB1, also known as WRAP53, had oncogenic feature in a certain extend. However, there is none direct study on the function of TCAB1 in tumorigenesis and development of head and neck cancers. First of all, we verified the function of TCAB1 in head and neck cancers. Knockdown TCAB1 would inhibit cell proliferation in Vitro as well as in Vivo, meanwhile, depletion TCAB1 would decrease the invasion potential of OSCC Cal-27 cells. cDNA microarray analysis showed many pathways and factors associated with occurrence and development of carcinomas were implicated in this process. Our study indicated TCAB1 might be a potential target for prognosis and therapy in head and neck cancers. Immunohistochemistry assay and western blot showed TCAB1 was overexpressed in clinical nasopharyngeal carcinoma and head and neck cell lines. Depletion endogenous TCAB1 by shRNA lentivirus in Cal-27 would verify the function of TCAB1 in cells proliferation and invasion. Furthermore, cDNA microarray was performed to detect some pathways or factors involved in the process.

ORGANISM(S): Homo sapiens

SUBMITTER: sun chongkui

PROVIDER: S-ECPF-GEOD-54224 | biostudies-other |

REPOSITORIES: biostudies-other

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TCAB1：A Potential Target for Diagnosis and Therapy in Head and Neck Cancers

2014-06-15 | GSE54224 | GEO

TCAB1M-oM-<M-^ZA Potential Target for Diagnosis and Therapy in Head and Neck Cancers

Project description:Previous studies indicated TCAB1, also known as WRAP53, had oncogenic feature in a certain extend. However, there is none direct study on the function of TCAB1 in tumorigenesis and development of head and neck cancers. First of all, we verified the function of TCAB1 in head and neck cancers. Knockdown TCAB1 would inhibit cell proliferation in Vitro as well as in Vivo, meanwhile, depletion TCAB1 would decrease the invasion potential of OSCC Cal-27 cells. cDNA microarray analysis showed many pathways and factors associated with occurrence and development of carcinomas were implicated in this process. Our study indicated TCAB1 might be a potential target for prognosis and therapy in head and neck cancers. Immunohistochemistry assay and western blot showed TCAB1 was overexpressed in clinical nasopharyngeal carcinoma and head and neck cell lines. Depletion endogenous TCAB1 by shRNA lentivirus in Cal-27 would verify the function of TCAB1 in cells proliferation and invasion. Furthermore, cDNA microarray was performed to detect some pathways or factors involved in the process.

2014-06-15 | E-GEOD-54224 | biostudies-arrayexpress

RRM2 regulates Bcl-2 in head and neck and lung cancers: a potential target for cancer therapy.

Project description:PurposeRibonucleotide reductase subunit M2 (RRM2) plays an active role in tumor progression. Recently, we reported that depletion of RRM2 by systemic delivery of a nanoparticle carrying RRM2-specific siRNA suppresses head and neck tumor growth. The aim of this study is to clarify the underlying mechanism by which RRM2 depletion inhibits tumor growth.Experimental designsiRNA-mediated gene silencing was carried out to downregulate RRM2. Immunoblotting, reverse-transcriptase PCR, confocal microscopy, tissue fractionation, gene overexpression and knockdown were employed to analyze critical apoptosis signaling. Conventional immunohistochemistry and quantum dot-based immunofluorescence were applied to detect RRM2 and Bcl2 expression and localization in tissue samples from patients and mice.ResultsKnockdown of RRM2 led to apoptosis through the intrinsic pathway in head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC) cell lines. We showed that Bcl-2 is a key determinant controlling apoptosis, both in vitro and in vivo, and that RRM2 depletion significantly reduces Bcl-2 protein expression. We observed that RRM2 regulates Bcl-2 protein stability, with RRM2 suppression leading to increased Bcl-2 degradation, and identified their colocalization in HNSCC and NSCLC cells. In a total of 50 specimens each from patients with HNSCC and NSCLC, we identified the colocalization of Bcl-2 and RRM2 and found a significant positive correlation between their expression in HNSCC (R = 0.98; P < 0.0001) and NSCLC (R = 0.92; P < 0.0001) tumor tissues.ConclusionsOur novel findings add to the knowledge of RRM2 in regulating expression of the antiapoptotic protein Bcl-2 and reveal a critical link between RRM2 and Bcl-2 in apoptosis signaling.

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ALKBH overexpression in head and neck cancer: potential target for novel anticancer therapy.

Project description:The nine identified human homologues of E. coli AlkB 2-oxoglutarate (2OG) and Fe(II)-dependent dioxygenase, ALKBH1-8 and FTO, display different substrate specificities and diverse biological functions. Here we discovered the combined overexpression of members of the ALKBH family in head and neck squamous cell carcinomas (HNSCC). We found direct correlation of ALKBH3 and FTO expression with primary HNSCC tumor size. We observed unidentified thus far cytoplasmic localization of ALKBH2 and 5 in HNSCC, suggesting abnormal role(s) of ALKBH proteins in cancer. Further, high expression of ALKBHs was observed not only in HNSCC, but also in several cancerous cell lines and silencing ALKBH expression in HeLa cancer cells resulted in dramatically decreased survival. Considering the discovered impact of high expression of ALKBH proteins on HNSCC development, we screened for ALKBH blockers among newly synthetized anthraquinone derivatives and demonstrated their potential to support standard anticancer therapy.

| S-EPMC6744417 | biostudies-literature

Immune-checkpoint molecules on regulatory T-cells as a potential therapeutic target in head and neck squamous cell cancers.

Project description:Immune-checkpoint inhibitors improve the survival of head and neck squamous cell carcinoma (HNSCC) patients. Although recent studies have demonstrated that the tumor immune microenvironment (TIME) has critical roles in immunotherapy, the precise mechanisms involved are unclear. Therefore, further investigations of TIME are required for the improvement of immunotherapy. The frequency of effector regulatory T-cells (eTregs) and the expression of immune-checkpoint molecules (ICM) on eTregs and conventional T-cells (Tconvs) both in peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) from HNSCC patients were analyzed by flow cytometry and their distributions were evaluated by multi-color immunofluorescence microscopy. High frequency eTreg infiltration into HNSCC tissues was observed and high expressions of CD25, FOXP3, stimulatory-ICM (4-1BB, ICOS, OX40 and GITR) and inhibitory-ICM (programmed cell death-1 [PD-1] and cytotoxic T-lymphocyte-associated protein-4 [CTLA-4]) were found on invasive eTregs. In contrast, the expression of stimulatory-ICM on Tconvs was low and the expression of inhibitory-ICM was high. In addition, ICM-ligands (programmed cell death-1 [PD-L1], galectin-9 and CEACAM-1) were frequently expressed on cancer cells. PD-L1 and galectin-9 were also expressed on macrophages. PD-1+ T-cells interacted with PD-L1+ cancer cells or PD-L1+ macrophages. This suggested that in TIL, eTregs are highly activated, but Tconvs are exhausted or inactivated by eTregs and immune-checkpoint systems, and ICM and eTregs are strongly involved in the creation of an immunosuppressive environment in HNSCC tissues. These suggested eTreg targeting drugs are expected to be a combination partner with immune-checkpoint inhibitors that will improve immunotherapy of HNSCC.

| S-EPMC7293074 | biostudies-literature

Head and Neck Cancers, Version 1.2015.

Project description:These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Head and Neck (H&N) Cancers. These Insights describe the different types of particle therapy that may be used to treat H&N cancers, in contrast to traditional radiation therapy (RT) with photons (x-ray). Research is ongoing regarding the different types of particle therapy, including protons and carbon ions, with the goals of reducing the long-term side effects from RT and improving the therapeutic index. For the 2015 update, the NCCN H&N Cancers Panel agreed to delete recommendations for neutron therapy for salivary gland cancers, because of its limited availability, which has decreased over the past 2 decades; the small number of patients in the United States who currently receive this treatment; and concerns that the toxicity of neutron therapy may offset potential disease control advantages.

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Dermatologic Toxicities of Targeted Therapy and Immunotherapy in Head and Neck Cancers.

Project description:Treatment of head and neck cancers requires multidisciplinary collaboration to reduce morbidity and mortality associated with the tumor burden, as well as to preserve function of organs and structures. With the use of various new targeted therapies come new adverse events including dermatologic toxicities, which may consist of xerosis, nail and hair changes, morbilliform or papulopustular rashes, to more severe eruptions such as Stevens-Johnson syndrome. We describe the dermatologic toxicities and corresponding grades of severity and associated pathophysiology resulting from seven therapeutics used to treat head and neck cancers: cetuximab, trastuzumab, pembrolizumab, nivolumab, lentatinib, larotrectinib, and entrectinib. Being familiar with these dermatologic toxicities allows clinicians to provide comprehensive counseling for patients, encourage preventative measures, and to know when it is appropriate to hold therapy or permanently stop treatment.

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Role of Epstein-Barr Virus in the Pathogenesis of Head and Neck Cancers and Its Potential as an Immunotherapeutic Target.

Project description:The role of Epstein-Barr virus (EBV) infection in the development and progression of tumor cells has been described in various cancers. Etiologically, EBV is a causative agent in certain variants of head and neck cancers such as nasopharyngeal cancer. Proteins expressed by the EVB genome are involved in invoking and perpetuating the oncogenic properties of the virus. However, these protein products were also identified as important targets for therapeutic research in the past decades, particularly within the context of immunotherapy. The adoptive transfer of EBV-targeted T-cells as well as the development of EBV vaccines has opened newer lines of research to conceptualize novel therapeutic approaches toward the disease. This review addresses the most important aspects of the association of EBV with head and neck cancers from an immunological perspective. It also aims to highlight the current and future prospects of enhanced EBV-targeted immunotherapies.

| S-EPMC6043647 | biostudies-literature

Imaging in head and neck cancers.

Project description: Not available

| S-EPMC7808093 | biostudies-literature

Nanoparticles for Diagnosis and Target Therapy in Pediatric Brain Cancers.

Project description:Pediatric brain tumors represent the most common types of childhood cancer and novel diagnostic and therapeutic solutions are urgently needed. The gold standard treatment option for brain cancers in children, as in adults, is tumor resection followed by radio- and chemotherapy, but with discouraging therapeutic results. In particular, the last two treatments are often associated to significant neurotoxicity in the developing brain of a child, with resulting disabilities such as cognitive problems, neuroendocrine, and neurosensory dysfunctions/deficits. Nanoparticles have been increasingly and thoroughly investigated as they show great promises as diagnostic tools and vectors for gene/drug therapy for pediatric brain cancer due to their ability to cross the blood-brain barrier. In this review we will discuss the developments of nanoparticle-based strategies as novel precision nanomedicine tools for diagnosis and therapy in pediatric brain cancers, with a particular focus on targeting strategies to overcome the main physiological obstacles that are represented by blood-brain barrier.

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