Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Language
Publication year range
1.
Sci Rep ; 14(1): 14092, 2024 06 18.
Article in English | MEDLINE | ID: mdl-38890401

ABSTRACT

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumours, warranting novel treatments. Here, we examined the therapeutic efficacy of inhibiting p21 activated kinase 4 (PAK4) in OSCC and determined its immunomodulatory effect by focusing on the enhancement of anti-tumour effects. We examined PAK4 expression in OSCC cells and human clinical samples and analysed the proliferation and apoptosis of OSCC cells following PAK4 inhibition in vitro. We also investigated the effects of in vivo administration of a PAK4 inhibitor on immune cell distribution and T-cell immune responses in OSCC tumour-bearing mice. PAK4 was detected in all OSCC cells and OSCC tissue samples. PAK4 inhibitor reduced the proliferation of OSCC cells and induced apoptosis. PAK4 inhibitor significantly attenuated tumour growth in mouse and was associated with increased proportions of IFN-γ-producing CD8+ T-cells. Furthermore, PAK4 inhibitor increased the number of dendritic cells (DCs) and up-regulated the surface expression of various lymphocyte co-stimulatory molecules, including MHC-class I molecules, CD80, CD83, CD86, and CD40. These DCs augmented CD8+ T-cell activation upon co-culture. Our results suggest that PAK4 inhibition in OSCC can have direct anti-tumour and immunomodulatory effects, which might benefit the treatment of this malignancy.


Subject(s)
Carcinoma, Squamous Cell , Cell Proliferation , Immunomodulation , Mouth Neoplasms , p21-Activated Kinases , p21-Activated Kinases/metabolism , p21-Activated Kinases/antagonists & inhibitors , Mouth Neoplasms/drug therapy , Mouth Neoplasms/immunology , Mouth Neoplasms/pathology , Mouth Neoplasms/metabolism , Humans , Animals , Mice , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/metabolism , Immunomodulation/drug effects , Cell Proliferation/drug effects , Cell Line, Tumor , Apoptosis/drug effects , Dendritic Cells/immunology , Dendritic Cells/drug effects , Dendritic Cells/metabolism , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/drug effects , Female , Male
2.
Biomedicines ; 12(5)2024 May 13.
Article in English | MEDLINE | ID: mdl-38791040

ABSTRACT

OBJECTIVES: In this study, we investigated the antitumor immunomodulatory effects of rapamycin in oral cancer. STUDY DESIGN: We examined the proliferation, apoptosis, and migration of cancer cells and investigated the cell surface expression levels of immune accessory molecules and T cell immune responses in vitro. We investigated the effect of in vivo administration of rapamycin on immune cell distribution and T cell immune responses in oral tumor-bearing mice. RESULTS: Rapamycin treatment significantly inhibited OSCC cell proliferation and migration, increased apoptotic cell death, and upregulated cell surface expression of several immune accessory and adhesion molecules, including CD40, CD83, PD-L1, PD-L2, MHC class I, P-selectin, and VCAM-1. These cancer cells augmented T cell proliferation. In vivo rapamycin administration significantly attenuated mouse tumor growth with an increased proportion of immune cells, including CD4+ T cells, CD8+ T cells, and dendritic cells (DCs); decreased the proportion of immune suppressive cells, such as myeloid-derived suppressor cells and regulatory T cells; enhanced DC maturation and upregulated the surface expression of CD40, CD86, and ICAM-1. CONCLUSIONS: Our results suggest that the therapeutic effect of mTOR inhibition in oral cancer can cause direct antitumor and immunomodulatory effects.

3.
Cureus ; 15(11): e49198, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38130517

ABSTRACT

Herein, we report two cases of patients diagnosed with nivolumab-refractory distant metastatic squamous cell carcinoma of the tongue who were successfully treated with a combination of paclitaxel and cetuximab. Case 1 had controllable local recurrence and distant metastasis. Case 2 had controllable distant metastatic disease. Thus, demonstrating that some nivolumab-refractory patients with recurrent or distant metastatic oral squamous cell carcinoma may benefit from subsequent salvage chemotherapy.

4.
Br J Oral Maxillofac Surg ; 60(5): 570-576, 2022 06.
Article in English | MEDLINE | ID: mdl-35422310

ABSTRACT

Preoperative assessment is essential to prevent inferior alveolar nerve (IAN) injury during surgical extraction of the lower third molar (LM3). Here, we aimed to establish an assessment system to predict IAN injury during surgical extraction of the LM3. We conducted a retrospective cohort study on 115 patients diagnosed as 'high-risk' based on our previous risk assessment method involving three anatomical features of the inferior alveolar canal using computed tomographic (CT) images. We evaluated the occurrence of neurosensory impairment in these high-risk patients, and its association with novel anatomic features based on CT images. Neurosensory impairments were observed in 19 patients (16.5%). The inferior alveolar canal major diameter (p < 0.0001) and lingual bone thickness (p = 0.0039) were significantly associated with the occurrence of neurosensory impairment during LM3 extraction. Receiver operating characteristic curves were used to determine cut-off values of these quantitative factors to specifically predict IAN injury. Preoperative risk assessment with quantitative factors based on anatomical features observed on CT images may facilitate more appropriate surgical planning for patients at a high risk of IAN injury.


Subject(s)
Tooth, Impacted , Trigeminal Nerve Injuries , Humans , Mandible/diagnostic imaging , Mandible/innervation , Mandible/surgery , Mandibular Nerve/diagnostic imaging , Molar, Third/diagnostic imaging , Molar, Third/surgery , Radiography, Panoramic/methods , Retrospective Studies , Tomography, X-Ray Computed , Tooth Extraction/adverse effects , Tooth, Impacted/surgery , Trigeminal Nerve Injuries/diagnostic imaging , Trigeminal Nerve Injuries/etiology , Trigeminal Nerve Injuries/prevention & control
SELECTION OF CITATIONS
SEARCH DETAIL
...