GLI1-induced mammary gland tumours are transplantable and maintain major molecular features

Increased expression of GLI1, the main Hedgehog signalling pathway effector, is related to unfavourable prognosis and progressive disease of certain breast cancer subtypes. We used conditional transgenic mice induced to overexpress GLI1 in the mammary epithelium either alone or in combination with deletion of one Trp53 allele to address the role of elevated GLI1 expression in breast tumour initiation and progression. Induced GLI1 expression facilitates mammary gland tumour formation and this was further increased upon heterozygous deletion of Trp53. The GLI1-induced primary tumours were of different murine molecular subtypes, including Normal-like^Ex, Class8^Ex, Claudin-Low^Ex and Erbb2-like^Ex. The gene expression profiles of some of the tumours correlated well with the PAM50 subtypes for human breast cancer. Whole-exome sequencing revealed somatic mutation profiles with only little overlap between the primary tumours. Orthotopically serially transplanted GLI1-induced tumours maintained the main morphological characteristics of the primary tumours for ≥10 generations. Independent of Trp53 status and molecular subtype, the serially transplanted GLI1-induced tumours were able to grow both in the absence of transgenic GLI1 expression and in the presence of the GLI1 inhibitor GANT61. These data suggest that elevated GLI1 expression has a determinant role in tumour initiation; however, additional genetic events are required for tumour progression.     

Elevated Serum Cytokines and Trichomonas vaginalis Serology at Diagnosis Are Not Associated With Higher Gleason Grade or Lethal Prostate Cancer

Background

Inflammation and infections have been associated with prostate cancer progression. We assessed whether elevated serum cytokines or T. vaginalis seropositivity at the time of diagnosis was associated with higher grade or lethal prostate cancer.

First report of Mortierella wolfii causing fungal keratitis from a tertiary eye hospital in India

A young 33 year old male presented with non-resolving corneal infiltrate for 2 month duration in the right eye. KOH/ Calcoflour wet mount revealed sparsely septate fungal hyphae. Post therapeutic penetrating keratoplasty 3 doses of intracameral voriconazole(100μg/0.1ml) was administered suspecting recurrence. Fungal culture revealed non sporulating mould on SDA. PCR based DNA sequencing targeting the ITS region identified the fungal isolate as Mortierella wolfii (M. wolfii) belonging to zygomycetes. To the best of our knowledge, this is the first report of human fungal keratitis caused by M. wolfii.     

Positron emission tomography visualized stimulation of the vestibular organ is localized in Heschl's gyrus

The existence of a human primary vestibular cortex is still debated. Current knowledge mainly derives from functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) acquisitions during artificial vestibular stimulation. This may be problematic as artificial vestibular stimulation entails coactivation of other sensory receptors. The use of fMRI is challenging as the strong magnetic field and loud noise during MRI may both stimulate the vestibular organ. This study aimed to characterize the cortical activity during natural stimulation of the human vestibular organ. Two fluorodeoxyglucose (FDG)‐PET scans were obtained after natural vestibular stimulation in a self‐propelled chair. Two types of stimuli were applied: (a) rotation (horizontal semicircular canal) and (b) linear sideways movement (utriculus). A comparable baseline FDG‐PET scan was obtained after sitting motion‐less in the chair. In both stimulation paradigms, significantly increased FDG uptake was measured bilaterally in the medial part of Heschl's gyrus, with some overlap into the posterior insula. This is the first neuroimaging study to visualize cortical processing of natural vestibular stimuli. FDG uptake was demonstrated in the medial‐most part of Heschl's gyrus, normally associated with the primary auditory cortex. This anatomical localization seems plausible, considering that the labyrinth contains both the vestibular organ and the cochlea.