BackgroundMagnetic resonance imaging (MRI) plays an irreplaceable role in the preoperative diagnosis of glioma, and its imaging features are the base of making treatment decisions in patients with glioma, but it is still controversial whether peritumoral edema shown by MRI from preoperative routine scans are associated with patient survival. The aim of this study was to assess the prognostic value of preoperative MRI features in patients with glioblastoma.MethodsA retrospective review of 87 patients with newly diagnosed supratentorial glioblastoma was performed using medical records and MRI data from routine scans. The Kaplan-Meier method and COX proportional hazard model were applied to evaluate the prognostic impact on overall survival of pretreatment MRI features (including peritumoral edema, edema shape, necrosis, cyst, enhancement, tumor crosses midline, edema crosses midline, and tumor size).ResultsIn addition to patient age, Karnofsky performance status (KPS) and postoperative chemoradiotherapy, peritumoral edema extent and necrosis on preoperative MRI were independent prognostic indicator for poor survival. Furthermore, patients with two unfavorable conditions (major edema and necrosis) had a shorter overall survival compared with the remainder.ConclusionsOur data confirm that peritumoral edema extent and necrosis are helpful for predicting poor clinical outcome in glioblastoma. These features were easy to determine from routine MRI scans postoperatively and therefore could provide a certain instructive significance for clinical activities.
PurposeComorbid familial nonobstructive azoospermia (NOA) and congenital cataract (CC) have not been reported previously, and no single human gene has been associated with both diseases in humans. Our purpose was to uncover novel human mutations and genes causing familial NOA and CC.MethodsWe performed whole-exome sequencing for two brothers with both NOA and CC from a consanguineous family. Mutation screening of TDRD7 was performed in another similar consanguineous family and 176 patients with azoospermia or CC alone and 520 healthy controls. Histological analysis was performed for the biopsied testicle sample in one patient, and knockout mice were constructed to verify the phenotype of the mutation in TDRD7.ResultsTwo novel loss-of-function mutations (c.324_325insA (T110Nfs*30) and c.688_689insA (p.Y230X), respectively) of TDRD7 were found in the affected patients from the two unrelated consanguineous families. Histological analysis demonstrated a lack of mature sperm in the male patient's seminiferous tubules. The mutations were not detected in patients with CC or NOA alone. Mice with Tdrd7 gene disrupted at a similar position precisely replicated the human syndrome.ConclusionWe identified TDRD7 causing CC as a new pathogenic gene for male azoospermia in human, with an autosomal recessive mode of inheritance.GENETICS in MEDICINE advance online publication, 24 August 2017; doi:10.1038/gim.2017.130.
Glioblastoma multiforme (GBM) has the highest mortality rate among patients with brain tumors, and radiotherapy forms an important part of its treatment. Thus, there is an urgent requirement to elucidate the mechanisms conferring GBM progression and radioresistance. In the present study, it was identified that antisense transcript of hypoxia-inducible factor-1α (AHIF) was significantly upregulated in GBM cancerous tissues, as well as in radioresistant GBM cells. The expression of AHIF was also upregulated in response to radiation. Knockdown of AHIF in GBM cells decreased viability and invasive capacities, and increased the proportion of apoptotic cells. By contrast, overexpression of AHIF in GBM cells increased viability and invasive capacities, and decreased the proportion of apoptotic cells. Furthermore, exosomes derived from AHIF-knockdown GBM cells inhibited viability, invasion and radioresistance, whereas exosomes derived from AHIF-overexpressing GBM cells promoted viability, invasion and radioresistance. Further biochemical analysis identified that AHIF regulates factors associated with migration and angiogenesis in exosomes. To the best of our knowledge, the present study is the first to establish that AHIF promotes glioblastoma progression and radioresistance via exosomes, which suggests that AHIF is a potential therapeutic target for GBM.
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