Project description:The resistance of hypoxic cells to radiotherapy and chemotherapy is a major problem in the treatment of cancer. Recently, an additional level of Hypoxia Inducible Factor (HIF) dependent transcriptional regulation has emerged involving modulation of a specific set of miRNAs including miR-210. We have recently shown that HIF-1 induction of miR-210 also stabilizes HIF-1 through a positive regulatory loop. We therefore hypothesized that by stabilizing HIF-1 in normoxia, miR-210 may protect cancer cells from radiation. We developed Non-Small Cell Lung Cancer (NSCLC)-derived cell lines (A549 and H1975) stably expressing miR-210 (pmiR-210) or a control miRNA (pmiR-Ctl). MiR-210 expressing cells showed a significant stabilization of HIF-1 associated with mitochondrial defects and a glycolytic phenotype. The cells were subjected to radiation levels ranging from 0 to 10Gy in normoxia and hypoxia. Cells expressing miR-210 in normoxia had the same level of resistance than control cells in hypoxia. pmiR-210 cells under hypoxia showed a low mortality rate due to a decrease in apoptosis and an ability to grow even at 10Gy. We have established that radioresistance was independent of p53 and cell cycle status. In addition, we show here that genomic double strand breaks (DSB) foci disappeared faster in pmiR-210 than in pmiR-Ctl cells, suggesting that miR-210 expression promotes a more efficient DSB repair. Finally, HIF-1 invalidation in pmiR-210 cells (pmiR-210/HIF-1-) abolished radioresistance of cells showing that this mechanism was dependent upon HIF-1. In conclusion, miR-210 appears to be a major component in the radioresistance of hypoxic cancer cells. Given the high stability of most miRNAs, this advantage could even be used by tumor cells in conditions where hypoxia may not be present anymore and strongly suggests that strategies targeting miR-210 would enhance tumor radiosensitization. To identify the set of transcripts targeted by miR-210, we overexpressed has-miR-210 or a control miRNA (ce-miR-67) in human lung adenocarcinoma A549 cells by transduction using lentivirus. The resulting pmiR-67 and pmiR-210 that stably overexpress miR-210 were selected by puromycin. RNA samples were harvested at 2 different times following cell plating (24 hours or 48 hours). Experiments were performed in dye-swap.

Project description:BackgroundAvailable research about the anatomic patterns of intertrochanteric fractures is lacking, and fracture mapping has not previously been performed on intertrochanteric fractures. This study aimed to determine the major trajectories of intertrochanteric fracture lines using computed tomography data from a series of surgically treated patients.MethodsIn this study, 504 patients with intertrochanteric fractures were retrospectively analyzed. Fracture patterns were graded according to Arbeitsgemeinschaft für Osteosynthesefragen (AO) classification. Fracture lines were transcribed onto proximal femoral templates and graphically superimposed to create a compilation of fracture maps that were subsequently divided into anterior, posterior, lateral, and medial fracture maps to create a three-dimensional (3D) pattern by reducing fragments in the 3D models. The fracture maps were then converted into frequency spectra. The major fracture patterns were assessed by focusing on the lateral femoral wall, lesser trochanter, intertrochanteric crest, and inner cortical buttress.ResultsAnterior, posterior, lateral, and medial fracture maps were created. The majority of fracture lines (85.9%, 433/504) on the anterior maps were along the intertrochanteric line where the iliofemoral ligament was attached. In the medial plane, the majority of fracture lines (49.0%, 247/504) shown on the frequency spectrum included the turning point involving the third quadrant. In the posterior plane, the majority of fracture lines (52.0%, 262/504) involved the intertrochanteric crest from the greater to the lesser trochanter. In the lateral plane, the majority of fracture lines (62.7%, 316/504) involved the greater trochanter at the gluteus medius attachment.ConclusionsThe fracture patterns observed in the present study might be used to describe morphologic characteristics and aid with management strategies. Further classifications or modifications that incorporate the fracture patterns identified in this study may be used in future research.

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Three dimensional cultivation increases chemo- and radioresistance of colorectal cancer cell lines.

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Three dimensional cultivation increases chemo- and radioresistance of colorectal cancer cell lines.

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