Fas,FasL, and cleaved caspases 8 and 3 in glioblastomas: A tissue microarray-based study

This investigation analyzed the immunoexpression of FasL, Fas, cleaved caspase-8, and cleaved caspase-3 in glioblastomas. Formalin-fixed and paraffin-embedded glioblastoma tissues and control brain tissues from 97 patients were analyzed by tissue microarrays and immunohistochemistry. Patients with glioblastomas that were negative or weakly stained (<50% of cells positive) for cleaved caspase-8 had worse cancer-specific overall survival (median = 8.5 months) than did patients with tumors that highly expressed cleaved caspase-8 (median = 11.7 months; P = 0.0325), independent of clinical variables. There was no association of other markers with survival, treatment, sex, age, tumor size, and primary site. Among the tumors, there were reasonable to good positive correlations between the expression of FasL and Fas (r = 0.47) and between Fas and cleaved caspase-8 (r = 0.41), and there were poor positive correlations between Fas and cleaved caspase-3 (r = 0.26), FasL and cleaved caspase-8 (r = 0.22), and cleaved caspase-8 and -3 (r = 0.31). Our results suggest that Fas-Fas-ligand signal transduction could be inhibited, especially at the stage of caspase-8 activation, thereby establishing a major mechanism for evasion of apoptosis by these tumors. The absence or low expression of cleaved caspase-8 in the tumors was a negative prognostic indicator for patient survival.     

Micromorphology of the Dental Pulp Is Highly Preserved in Cancer Patients Who Underwent Head and Neck Radiotherapy

Introduction

Teeth are often included in the radiation field during head and neck radiotherapy, and recent clinical evidence suggests that dental pulp is negatively affected by the direct effects of radiation, leading to impaired sensitivity of the dental pulp. Therefore, this study aimed to investigate the direct effects of radiation on the microvasculature, innervation, and extracellular matrix of the dental pulp of patients who have undergone head and neck radiotherapy.

Methods

Twenty-three samples of dental pulp from patients who finished head and neck radiotherapy were analyzed. Samples were histologically processed and stained with hematoxylin-eosin for morphologic evaluation of the microvasculature, innervation, and extracellular matrix. Subsequently, immunohistochemical analysis of proteins related to vascularization (CD34 and smooth muscle actin), innervation (S-100, NCAM/CD56, and neurofilament), and extracellular matrix (vimentin) of the dental pulp was performed.

Results

The morphologic study identified preservation of the microvasculature, nerve bundles, and components of the extracellular matrix in all studied samples. The immunohistochemical analysis confirmed the morphologic findings and showed a normal pattern of expression for the studied proteins in all samples.

Conclusions

Direct effects of radiotherapy are not able to generate morphologic changes in the microvasculature, innervation, and extracellular matrix components of the dental pulp in head and neck cancer patients.     

Histochemistry and Immunohistochemistry Evaluation of the Abrikossoff’s Tumour of the Tongue: a Case Report

Abrikossoff’s tumour is a rare benign soft tissue neoplasm that can occur in any part of the body, including the orofacial region. The tumour is usually benign, but there are reports of cases in which the tumour shows a locally aggressive behaviour, malignancy, and distant metastases. The aetiology is unknown, since several studies have shown that different cells are involved. In the present case, a 36-year-old Dominican woman was referred to the Department of Oral and Maxillofacial Surgery in Policlinico Federico II, Naples with a circumscribed lesion and sessile nodule on the dorsum of the tongue measuring about 17 mm in diameter. The treatment consisted of an excisional biopsy performed on the basis of the diagnostic hypothesis of Abrikossoff’s tumour, which was confirmed by histopathological analysis and histochemistry and immunohistochemistry evaluation. Abrikossoff’s tumour is an uncommon neoplasm which must be carefully diagnosed considering all the histological and clinical aspects in order to be treated correctly.Key words: Granullar Cell Tumour, Soft Tissue Neoplasm, Tongue     

Platelet‐rich plasma counteracts detrimental effect of high‐glucose concentrations on mesenchymal stem cells from Bichat fat pad

Diabetic patients display increased risk of periodontitis and failure in bone augmentation procedures. Mesenchymal stem cells (MSCs) and platelet‐rich plasma (PRP) represent a relevant advantage in tissue repair process and regenerative medicine. We isolated MSCs from Bichat's buccal fat pad (BFP) and measured the effects of glucose and PRP on cell number and osteogenic differentiation potential. Cells were cultured in the presence of 5.5‐mM glucose (low glucose [LG]) or 25‐mM glucose (high glucose [HG]). BFP–MSC number was significantly lower when cells were cultured in HG compared with those in LG. Following osteogenic differentiation procedures, calcium accumulation, alkaline phosphatase activity, and expression of osteogenic markers were significantly lower in HG compared with LG. Exposure of BFP–MSC to PRP significantly increased cell number and osteogenic differentiation potential, reaching comparable levels in LG and in HG. Thus, high‐glucose concentrations impair BFP–MSC growth and osteogenic differentiation. However, these detrimental effects are largely counteracted by PRP.     

Characterization of a Parkinson’s disease rat model using an upgraded paraquat exposure paradigm

Animal models of human diseases are crucial experimental tools to investigate the mechanisms involved in disease pathogenesis and to develop new therapies. In spite of the numerous animal models currently available that reproduce several neuropathological features of Parkinson disease (PD), it is challenging to have one that consistently recapitulates human PD conditions in both motor behaviors and biochemical pathological outcomes. Given that, we have implemented a new paradigm to expose rats to a chronic low dose of paraquat (PQ), using osmotic minipumps and characterized the developed pathologic features over time. The PQ exposure paradigm used lead to a rodent model of PD depicting progressive nigrostriatal dopaminergic neurodegeneration, characterized by a 41% significant loss of dopaminergic neuron in the substantia nigra pars compacta (SNpc), a significant decrease of 18% and 40% of dopamine levels in striatum at week 5 and 8, respectively, and a significant 1.5‐fold decrease in motor performance. We observed a significant increase of microglia activation state, sustained levels of α‐synucleinopathy and increased oxidative stress markers in the SNpc. In summary, this is an explorative study that allowed to characterize an improved PQ‐based rat model that recapitulates cardinal features of PD and may represent an attractive tool to investigate several mechanisms underlying the various aspects of PD pathogenesis as well as for the validation of the efficacy of new therapeutic approaches that targets different mechanisms involved in PD neurodegeneration.     

Parenchymal abnormalities associated with cerebral venous sinus thrombosis: assessment with diffusion-weighted MR imaging

BACKGROUND AND PURPOSE: The common entity cerebral venous sinus thrombosis is associated with the poorly characterized imaging finding of parenchymal abnormalities; diffusion-weighted imaging has offered some insight into these manifestations. We assessed the relationship between the diffusion constant from apparent diffusion coefficient (ADC) maps in patients with cerebral venous thrombosis (CVT) with follow-up imaging findings and clinical outcome. METHODS: We evaluated the medical records and T2-weighted MR images of 13 patients with CVT complicated by intraparenchymal abnormality. Diffusion-weighted (DW) images and ADC maps were evaluated for increased, decreased, or unchanged signal intensity and were compared with signal intensity of contralateral, normal-appearing brain. In addition, ADCs were obtained in nine pixel regions of interest in abnormal regions in eight of the 13 patients. RESULTS: Eight patients had superficial CVT, and five had superficial and deep CVT. CVT of deep veins was associated with deep gray nucleus and deep white matter abnormalities, whereas superficial CVT was associated with cortical and subcortical abnormalities. Twenty-four nonhemorrhagic lesions were identified in 10 of 13 patients on the basis of follow-up imaging findings. Four patients without seizures had lesions with decreased diffusion that appeared hyperintense on follow-up T2-weighted images, three patients with seizures had lesions with decreased diffusion that resolved, and seven patients had lesions with increased diffusion that resolved. Three of 10 patients had more than one lesion type. No difference was noted in mean ADCs for lesions with decreased diffusion that resolved compared with lesions with decreased diffusion that persisted. CONCLUSION: DW imaging in these patients disclosed three lesion types: lesions with elevated diffusion that resolved, consistent with vasogenic edema; lesions with low diffusion that persisted, consistent with cytotoxic edema in patients without seizure activity; and lesions with low diffusion that resolved in patients with seizure activity. This information may be important in prospectively determining severity of irreversible injury and in patient treatment.     

Lymph Node Retrieval after Preoperative Chemoradiotherapy for Rectal Cancer

Background

Current guidelines recommend the assessment of at least 12 lymph nodes for rectal cancer staging. Preoperative chemoradiotherapy may affect lymph node yield in this malignancy. This study investigated the impact of neoadjuvant chemoradiotherapy on the number of lymph nodes retrieved from rectal cancer patients.

Methods

An analysis of 162 rectal cancer patients who underwent curative surgery between 2005 and 2010. Seventy-one patients with stage II or III tumors received preoperative chemoradiotherapy. Using multivariate analysis, we assessed the correlation between clinicopathologic variables and number of retrieved lymph nodes. We also evaluated the association between survival and number of lymph nodes obtained.

Results

On multivariate analysis, preoperative chemoradiotherapy was the only variable to independently affect the number of lymph nodes obtained. The mean number of lymph nodes was 14.2 in patients treated with preoperative chemoradiotherapy and 19.4 in those not treated (P?P?=?0.003). After chemoradiation, the number of retrieved lymph nodes was inversely correlated with tumor regression grade. Results showed that 5-year overall and disease-free survival were similar whether the patient had 12 or more nodes retrieved or not.

Conclusions

Preoperative chemoradiotherapy reduces the lymph node yield in rectal cancer. The number of retrieved lymph nodes is affected by degree of histopathologic response of the tumor to chemoradiation. Thus, number of lymph nodes should not be used as a surrogate for oncologic adequacy of resection after neoadjuvant chemoradiotherapy for rectal cancer.