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For unresectable recurrent/metastatic head and neck cancer, pembrolizumab alone or pembrolizumab combined with cisplatin and 5-fluorouracil is the first-line therapy, depending on the PD-L1 combined positive score (CPS). However, this is based on clinical studies of head and neck cancer, and few similar studies have been conducted on oral cancer alone. This study aimed to investigate the current status of pharmacotherapy for unresectable, recurrent, or metastatic oral cancer. Patients with unresectable or recurrent/metastatic oral cancer who received cetuximab, nivolumab, or pembrolizumab as first-line treatment were reviewed. Overall survival (OS), progression-free survival (PFS), PFS 2 (PFS2), overall response rate (ORR), disease control rate (DCR), and immune-related adverse events were obtained from medical records. A total of 155 patients were enrolled from six hospitals. The ORR in the nivolumab, pembrolizumab, and cetuximab groups was 17.2 %, 4.2 %, and 21.6 %, respectively, and the DCR was 37.9 %, 41.7 %, and 58.8 %, respectively. Median OS in nivolumab, pembrolizumab, and cetuximab groups was 10.3, 9.5, and 11.1 months, respectively. No significant differences were observed in survival among the three groups. The small number of cases and the retrospective nature of the study precluded the determination of the more effective first-line treatment among the three drugs. The current statuses of nivolumab, pembrolizumab, and cetuximab in unresectable recurrent metastatic oral cancer was reported. [ABSTRACT FROM AUTHOR]

Objectives: The progression level of extracapsular spread (ECS) for cervical lymph node metastasis of oral squamous cell carcinoma (OSCC) was previously divided into three types, and their relationships with the prognosis of patients were re-examined.Patients and methods: The Kaplan-Meier method was used to examine overall survival (OS) and relapse-free survival (RFS) curves. Prognosis factor for recurrence was analyzed with univariate and multivariate analysis.Results: ECS was detected in 216 cases of OSCC and analyzed. The 5-year overall survival and RFS rates of patients with type C, which was microscopically defined as tumor invasion to perinodal fat or muscle tissue, were significantly poor at 40.6 and 37.8%, respectively. The results of a univariate analysis suggested that the prognosis of ECS in OSCC patients is associated with its progression level, particularly type C. The 5-year RFS rate of type C with tumor budding was significantly poor at 31.5%. Type C with tumor budding correlated with local and regional recurrence as well as distant metastasis. In a multivariate analysis, tumor budding was identified as an independent prognostic factor.Conclusions: These results suggest that the progression level of ECS and tumor budding are useful prognostic factors in OSCC patients.Clinical relevance: This study indicated that the progression level and tumor budding of ECS for cervical lymph node metastasis were useful prognostic factors in OSCC patients. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the prognostic factor in salivary gland carcinoma patients. Clinical and pathological data of 211 consecutive patients who treated with curative intent were analyzed. The overall survival (OS) rate, local control rate, and distant metastasis rate were calculated. To examine a prognostic factor in salivary gland carcinoma patients, a multivariate analysis was performed. The 5-year-OS rate was 84.0%, and 10-year was 69.2%. The 5-year-local control rate was 84.6%, and 10-year was 70.1%. The 5-year-distant metastasis rate was 16.9%, and 10-year was 21.1%. In a multivariate analysis, the OS rate was affected by pN(+), high-grade malignancy, and primary tumor size. The local control was affected by the primary tumor size, high-grade malignancy, and the status of the surgical margin. The primary tumor size and pN(+) were associated with the distant metastasis. The results of this study suggested that pN(+), malignancy grade, primary tumor size, and the margin status might affect the prognosis of salivary gland carcinoma patients. Postoperative radiotherapy and adjuvant chemotherapy were suggested the possibility of contribution to the good prognosis of salivary gland carcinoma patients. [ABSTRACT FROM AUTHOR]

Abstract: Cortactin stimulates cell migration, invasion, and experimental metastasis. Overexpression of cortactin has been reported in several human cancers. CRK was originally identified as an oncogene product of v-CRK in a CT10 chicken retrovirus system. Overexpression of CRKII has been reported in several human cancers. CRKII regulates cell migration, morphogenesis, invasion, phagocytosis, and survival; however, the underlying mechanisms are not well understood. We evaluated the possibility of the combination of cortactin and CRKII as an appropriate molecular target for cancer gene therapy. The expression of cortactin and CRKII in 70 primary oral squamous cell carcinomas and 10 normal oral mucosal specimens was determined immunohistochemically, and the correlation of cortactin and CRKII co-overexpression with clinicopathological factors was evaluated. Co-overexpression of cortactin and CRKII was detected in 31 of 70 oral squamous cell carcinomas, the frequency being significantly greater than in normal oral mucosa. In addition, cortactin and CRKII co-overexpression was more frequent in higher-grade cancers according to the T classification, N classification, and invasive pattern. RNAi-mediated co-suppression of cortactin and CRKII expression reduced the migration and invasion potential of an oral squamous cell carcinoma cell line, OSC20. Downregulation of cortactin and CRKII expression also reduced the expression of vimentin, fibronectin, and N-cadherin. These results indicate that the co-overexpression of cortactin and CRKII may be tightly associated with an aggressive phenotype of oral squamous cell carcinoma. Therefore, we propose that the combination of cortactin and CRKII could be a potential molecular target of gene therapy by RNAi-targeting in oral squamous cell carcinoma. [Copyright &y& Elsevier]

Abstract: Carcinoma ex pleomorphic adenoma (CEPA) is defined as a pleomorphic adenoma from which an epithelial malignancy is derived. Most cases of CEPA occur in parotid glands, and CEPA arising in minor salivary glands is rare. We report an extremely rare case of CEPA arising in the minor salivary glands of the anterior tongue in a 64-year-old man. The mass of the left anterior surface of tongue was a 30mm×20mm×20mm, relatively well-defined, elastic, hard, and tender. Biopsy was performed and the histological diagnosis was adenocarcinoma, not otherwise specified (NOS). Benign PA was not included in the biopsy specimen. A wide local excision of the tongue, with left upper neck dissection, and local flap repair were performed. The removed tumor was composed of adenocarcinoma, NOS accompanied with small foci of pre-existing chondroid areas of PA. A diagnosis of CEPA was finally made. There were no signs of recurrence and metastasis 22 months after the surgery. [Copyright &y& Elsevier]

Abstract: CT10 regulator of kinase (CRK) was originally identified as an oncogene product of v-CRK in a CT10 chicken retrovirus system. Overexpression of CRKII has been reported in several human cancers. CRKII regulates cell migration, morphogenesis, invasion, phagocytosis, and survival; however, the underlying mechanisms are not well understood. In the present study, we evaluated the possibility of CRKII as an appropriate molecular target for cancer gene therapy. The expression of CRKII in 71 primary oral squamous cell carcinomas and 10 normal oral mucosal specimens was determined immunohistochemically, and the correlation of CRKII overexpression with clinicopathological factors was evaluated. Overexpression of CRKII was detected in 41 of 70 oral squamous cell carcinomas, the frequency being more significant than in normal oral mucosa. In addition, CRKII overexpression was more frequent in higher-grade cancers according to the T classification, N classification, and invasive pattern. Moreover, RNAi-mediated suppression of CRKII expression reduced the migration and invasion potential of an oral squamous cell carcinoma cell line, OSC20. Downregulation of CRKII expression also reduced the expression of Dock180, p130Cas, and Rac1, and the actin-associated scaffolding protein cortactin. These results indicate that the overexpression of CRKII is tightly associated with an aggressive phenotype of oral squamous cell carcinoma. Therefore, we propose that CRKII could be a potential molecular target of gene therapy by RNAi-targeting in oral squamous cell carcinoma. [Copyright &y& Elsevier]

The aim of the present study was to clarify the association of mTORC2 expression with the cancer progression and the anti-tumor effects of Torin-1 alone and combined treatment with Cetuximab in OSCC cells. The expressions of Rictor and SGK1 were immunohistochemically evaluated and the relationships between the expressions of molecular markers and clinicopathological factors were determined. Moreover, OSCC cells were treated with Torin-1, Cetuximab or combined agents, and anti-tumor effects of OSCC cells were examined in vitro and in vivo. Rictor and SGK1 expressions were significantly associated with tumor stage and pattern of invasion in OSCC sections (P<0.05 and P<0.01, respectively). Treatment of OSCC cell lines with Torin-1 resulted in dose and time-dependent inhibition of proliferation with decrease of phosphorylation on downstream molecules. Combined treatment with Torin-1 and Cetuximab resulted in enhanced anti-tumor effects in vitro compared with either agent alone. Furthermore, treatment of mice bearing OSCC xenografts with Torin-1 and Cetuximab also demonstrated a remarked growth inhibition of tumor volumes. The results suggested that new regimens of systemic therapy combined with Cetuximab and Torin-1 may be useful for very advanced OSCC patients. [ABSTRACT FROM AUTHOR]