Infrared spectroscopic imaging study of BV-2 microglia altering tumor cell biological activity and cellular fraction.

Tumor brain metastasis is a severe threat to patients' neurological function, in which microglia may be involved in the process of tumor cell metastasis among nerve cells. Our study focused on the interaction between microglia and breast and lung cancer cells. Changes in the proliferation and migration ability of cocultured tumor cells were examined; synchrotron radiation-based fourier transform infrared microspectroscopy (SR-FTIR) was used to detect changes in the structures and contents of biomolecules within the tumor cells. The experimental results showed that the proliferation and migration ability of tumor cells increased after coculture, and the structures and contents of biological macromolecules in tumor cells changed. The absorption peak positions of the amide Ⅱ and amide Ⅰ bands observed for the four kinds of tumor cells changed, and the absorption intensities were significantly enhanced, indicating changes in the secondary structures and contents of proteins in tumor cells, which may be the root cause of the change in tumor cell characteristics. Therefore, the metabolites of microglia may be involved in the progression of tumor cells in the nervous system. In this study, we focused on the interaction between microglia and tumor cells by using SR-FTIR and provided a new understanding of the mechanism of brain metastasis.

Tumor budding correlates with occult cervical lymph node metastasis and poor prognosis in clinical early-stage tongue squamous cell carcinoma.

BACKGROUND: Tumor budding has been suggested to be a prognostic factor in various human cancers. However, the prognostic value of tumor budding for early-stage (cT1/2N0) tongue squamous cell carcinoma remains inconclusive. This study analyzed the correlation of tumor budding with the clinicopathologic features, and its prognostic significance for cT1/2N0 stage tongue squamous cell carcinoma. METHODS: One hundred and ninety-five patients with T1/2 stage tongue squamous cell carcinoma enrolled in the retrospective study. Tumor invasive depth, the intensity of tumor budding, and other clinicopathological features were reviewed. Overall survivals were evaluated by the Kaplan-Meier method. For multivariable analysis, Cox's proportional hazards regression models were performed. RESULTS: The frequency of tumor buds in tongue squamous cell carcinoma is about 85.6% in this study. The intensity of tumor budding showed strong correlations with occult lymph node metastasis (P < 0.05), local relapse (P < 0.01), worse invasive pattern (P < 0.01), and invasive depth (P < 0.05). The invasive depth was significantly associated with T classification (P < 0.01) and lymph node metastasis (P < 0.01). And both high intensity of tumor budding and deeper invasive depth correlated with reduced overall survival. Cox's regression models proved tumor budding to be an independent prognostic factor in clinical early-stage tongue squamous cell carcinoma. Tumor local relapses were also a predictor of tongue squamous cell carcinoma progression. CONCLUSIONS: Tumor budding is a frequent event in tongue squamous cell carcinoma. It independently predicted prognosis of patients with T1/2 stage tongue squamous cell carcinoma and may be used for routing pathological diagnosis and the decision of elective lymph node dissection.

Disclosure of a stem cell phenotype in an oral squamous cell carcinoma cell line induced by BMP-4 via an epithelial-mesenchymal transition.

A small subset of cells within a malignant neoplasm, named cancer stem cells (CSCs) or tumour initiating cells, are thought to be capable of initiating the neoplasm itself, and of driving its growth and recurrence after treatment. It is unclear whether CSCs can be identified and experimentally induced within oral squamous cell carcinoma (OSCC), although this has been reported for a number of other tumour types. In this study, we aimed to determine whether BMP-4 (bone morphogenetic protein-4) could induce epithelial-mesenchymal transition (EMT) with acquisition of stem cell-like phenotypes in a cell-culture model. Furthermore, the differential expression of ABCG2, a putative CSC marker, was determined in human normal oral mucosa and OSCC tissues at mRNA and protein level. The results showed that after treatment with BMP-4, most Tca8113 cells (a human tongue OSCC cell line) changed their morphology from slabstone to spindle-shaped, and demonstrated enhanced expression of ABCG2 compared with non-treated cells. Expression of Oct-4 was induced in cell nuclei with up-regulation of EMT markers (Snail, Slug and vimentin), and down-regulation of E-cadherin. Interestingly, the expression of hTERT, CD44 and Bmi-1 (generally accepted as markers of CSCs) were up-regulated, but this was not synchronous with the expression of EMT markers. Tumour spheres were formed after stimulation with BMP-4, with high expression of CD44 and ABCG2. In human tissues, ABCG2 was strongly expressed in OSCC, but not in normal mucosa. This study suggests that BMP-4-mediated EMT constitutes one possible pathway for the development of CSCs in oral cancer, implying a transient therapeutic opportunity if EMT can be interrupted early in the evolution of such a neoplasm.

[Radiation-induced maxillary malignancies: complications of radiotherapy treatment for head-neck malignant tumors].

OBJECTIVE: To investigate the incidence of radiation-induced maxillary malignancy after radiotherapy for head and neck cancer. METHODS: A total of 273 patients who suffered from osteoradionecrosis after radiotherapy for head and neck cancer were evaluated. Among them, 6 patients were presented with carcinoma and sarcoma arising from maxillary area after radiotherapy. RESULTS: Radiation-induced maxillary cancers happened at a rate of 2.2% in the patients with osteoradionecrosis. There were no statistically significant differences in age, sex and the time interval between the radiotherapy and the cancer occurrence. CONCLUSIONS: Radiation-induced malignancy after radiotherapy for head and neck cancer is mainly located in maxilla, presenting as squamous cell carcinoma or sarcoma of the maxillary sinus.

Assessment of local angiogenesis and vascular endothelial growth factor in the patients with atrophic-erosive and reticular oral lichen planus.

OBJECTIVES: The objective of this study was to assess local angiogenesis and expression of VEGF in atrophic-erosive and reticular oral lichen planus (OLP). STUDY DESIGN: Microvessel density (MVD) and VEGF level in 30 OLP subjects and 7 matched controls were detected by immunohistochemistry and ELISA. RESULTS: MVD and VEGF levels in whole OLP group were significantly elevated (P = .033, P < .0001, respectively), and there was a positive correlation between MVD and VEGF (correlation coefficient = 0.84, P < .0001). MVD in atrophic-erosive OLP was significantly higher than that in controls (P = .001) and reticular OLP (P = .042), and the expression of VEGF in both subgroups was significantly higher (P < .0001, P = .008, respectively) compared to control group. CONCLUSION: These results indicated that angiogenesis and VEGF expression were closely correlated to the different clinical forms of OLP lesions, which may give new insights into the mechanisms and treatment strategy of OLP.

Epstein-Barr virus infected lymphoepithelial carcinomas of the salivary gland in the Russia-Asia area: a clinicopathologic study of 160 cases.

In order to determine the prevalence of the Epstein-Barr virus (EBV) infection in salivary gland lymphoepithelial carcinomas (LEC), we have collected 160 cases from Asian countries and Russia. All the cases examined by PCR for EBV DNA BamHI fragment and in-situ hybridization for EBER-1, EBV encoded small RNA, showed positivity for EBV infection in LEC cells, while no positive signals were found in any other salivary neoplasm examined. The incidence of LEC was highest in Guanzhou, followed by Shanghai and Chengdu and lowest in the northern parts of China, Seoul, Niigata, and Moscow. The mean age of the patients with LEC was 43.9 years with no sex predilection. The Chinese patients were of the Han race, only including minor races. There were ninety-five cases found with LEC in the parotid gland (75%), 20 in the submandibular gland (5%), and 28 in the minor salivary gland (20%). Histologically, the LECs were classified into two types: small nest type and large nest type. The latter type consisted of large-sized tumor cell nests and dense lymphocytic stromata and more frequently occurred in the minor salivary gland. The former consisted of small-sized tumor cell nests with fibrous and lymphocyte-depleted stromata, which were more frequently found in the parotid gland. The results indicated that EBV infection and certain geographic factors play important roles in the pathogenesis of the salivary LEC.