In vitro culture with gemcitabine augments death receptor and NKG2D ligand expression on tumour cells

Much effort has been made to try to understand the relationship between chemotherapeutic treatment of cancer and the immune system. Whereas much of that focus has been on the direct effect of chemotherapy drugs on immune cells and the release of antigens and danger signals by malignant cells killed by chemotherapy, the effect of chemotherapy on cells surviving treatment has often been overlooked. In the present study, tumour cell lines: A549 (lung), HCT116 (colon) and MCF-7 (breast), were treated with various concentrations of the chemotherapeutic drugs cyclophosphamide, gemcitabine (GEM) and oxaliplatin (OXP) for 24 hours in vitro. In line with other reports, GEM and OXP upregulated expression of the death receptor CD95 (fas) on live cells even at sub-cytotoxic concentrations. Further investigation revealed that the increase in CD95 in response to GEM sensitised the cells to fas ligand treatment, was associated with increased phosphorylation of stress activated protein kinase/c-Jun N-terminal kinase and that other death receptors and activatory immune receptors were co-ordinately upregulated with CD95 in certain cell lines. The upregulation of death receptors and NKG2D ligands together on cells after chemotherapy suggest that although the cells have survived preliminary treatment with chemotherapy they may now be more susceptible to immune cell-mediated challenge. This re-enforces the idea that chemotherapy-immunotherapy combinations may be useful clinically and has implications for the make-up and scheduling of such treatments

A comparison of body composition assessment methods in climbers: Which is better?

Objective To compare body composition estimations of field estimation methods: Durnin & Womersley anthropometry (DW-ANT), bioelectrical impedance analysis (BIA) and Deborah-Kerr anthropometry (DK-ANT) against dual-energy X-ray absorptiometry (DXA) in a male Chilean sport climbing sample. Methods 30 adult male climbers of different performance levels participated in the study. A DXA scan (Lunar Prodigy (R)) was used to determine fat mass, lean mass and total bone mineral content (BMC). Total muscle mass (MM, kg) was estimated through a validated prediction model. DW-ANT and BIA ("non-athletes" and "athletes" equations) were used to determinate fat mass percentage (FM %), while DK-ANT was utilized to estimate MM and BMC. Results A significant (p<0.01) inter-method difference was observed for all methods analyzed. When compared to DXA, DW-ANT and BIA underestimated FM% and DK-ANT overestimated MM and BMC (All p< 0.01). The inter-method differences was lower for DW-ANT. Discussion We found that body composition estimation in climbers is highly method dependent. If DXA is not available, DW-ANT for FM% has a lower bias of estimation than BIA in young male Chilean climbers. For MM and BMC, further studies are needed to compare and estimate the DK-ANT bias level. For both methods, correction equations for specific climbing population should be considered

Granular cell tumor presenting as a tongue nodule: two case reports

<p>Abstract</p> <p>Introduction</p> <p>Granular cell tumor is an uncommon neoplasm that can occur in any part of the body, including the orofacial region. The tumor is usually benign, but there are reports of cases in which the tumor shows a locally aggressive behavior, malignancy, and distant metastases. The most widely accepted hypothesis is that granular cell tumor arises from the altered metabolism of Schwann cells. The tumor is typically asymptomatic and appears as a nodule that does not exceed 3 cm.</p> <p>Case presentation</p> <p>In case 1, a 26-year-old Caucasian man was seen at the Oral Medicine out-patient clinic of the São José dos Campos Dental School, Universidade Estadual Paulista, with a 'small blister on the tongue', which he had noted approximately three years ago. The nodule was located on the dorsum of the tongue, measured about 1.5 cm in diameter, and was not tender to palpation. Treatment consisted of an excisional biopsy performed on the basis of the diagnostic hypothesis of granular cell tumor, which was confirmed by microscopic analysis. In case 2, a 31-year-old Caucasian woman attended the out-patient clinic of the São José dos Campos Dental School, Universidade Estadual Paulista, with a five-year history of a 'painful lump on the tongue'. Intra-oral examination revealed the presence of a nodular lesion measuring approximately 0.8 cm in diameter, which was located deep in the submucosa of the right lateral margin of the tongue. Treatment consisted of an excisional biopsy performed on the basis of the differential diagnosis of neurofibroma and granular cell tumor. Microscopic analysis defined the final diagnosis of granular cell tumor.</p> <p>Conclusions</p> <p>Granular cell tumor is an uncommon tumor that must be carefully diagnosed and treated correctly.</p

Tuberous sclerosis with pulmonary lymphangioleiomyomatosis and renal angiomyolipomas. Computed tomographic findings: a case report

The authors describe a case of a 31-year-old female with tuberous sclerosis, a genetic, rare, variably expressed disease. Clinical symptoms were chest pain, and progressive dyspnea. Computed tomography scan of the chest showed bilateral, diffuse, small thin-walled cysts scattered throughout the lungs characteristic for pulmonary lymphangioleiomyomatosis. Computed tomography scan of the abdomen revealed enlarged, heterogeneous kidneys, with low density tumors corresponding to angiomyolipomas. Pulmonary lymphangioleiomyomatosis and bilateral renal angiomyolipomas are some presentations of tuberous sclerosis and the coexistence of both conditions may cause devastating morbidity and mortality

Evaluation of CXCL9 and CXCL10 as circulating biomarkers of human cardiac allograft rejection

BACKGROUND: Cardiac allograft rejection remains a significant clinical problem in the early phase after heart transplantation and requires frequent surveillance with endomyocardial biopsy. However, this is an invasive procedure, which is unpleasant for the patient and carries a certain risk. Therefore, a sensitive non-invasive biomarker of acute rejection would be desirable. METHODS: Endomyocardial tissue samples and serum were obtained in connection with clinical biopsies from twenty consecutive heart transplant patients followed for six months. A rejection episode was observed in 14 patients (11 men and 3 women) and biopsies obtained before, during and after the episode were identified. Endomyocardial RNA, from three patients, matching these three points in time were analysed with DNA microarray. Genes showing up-regulation during rejection followed by normalization after the rejection episode were evaluated further with real-time RT-PCR. Finally, ELISA was performed to investigate whether change in gene-regulation during graft rejection was reflected in altered concentrations of the encoded protein in serum. RESULTS: Three potential cardiac allograft rejection biomarker genes, chemokine (C-X-C motif) ligand 9 (CXCL9), chemokine (C-X-C motif) ligand 10 (CXCL10) and Natriuretic peptide precursor A (NPPA), from the DNA microarray analysis were selected for further evaluation. CXCL9 was significantly upregulated during rejection (p < 0.05) and CXCL10 displayed a similar pattern without reaching statistical significance. Serum levels of CXCL9 and CXCL10 were measured by ELISA in samples from 10 patients before, during and after cardiac rejection. There were no changes in CXCL9 and CXCL10 serum concentrations during cardiac rejection. Both chemokines displayed large individual variations in the selected samples, but the serum levels between the two chemokines correlated (p < 0.001). CONCLUSION: We conclude, that despite a distinct up-regulation of CXCL9 mRNA in human hearts during cardiac allograft rejection, this was not reflected in the serum levels of the encoded protein. Thus, in contrast to previous suggestions, serum CXCL9 does not appear to be a promising serum biomarker for cardiac allograft rejection