Targeting CD133 improves chemotherapeutic efficacy of recurrent pediatric pilocytic astrocytoma following prolonged chemotherapy

Quantification of western blot results showing overexpression of pAKT(S473, T308) and pNF-ƙB/p65 in recurrent PAs with chemotherapy, compared to matched primary tumors. (TIF 52 kb

Alternative lengthening of telomeres, ATRX loss and H3â K27M mutations in histologically defined pilocytic astrocytoma with anaplasia

Anaplasia may be identified in a subset of tumors with a presumed pilocytic astrocytoma (PA) component or piloid features, which may be associated with aggressive behavior, but the biologic basis of this change remains unclear. Fiftyâ seven resections from 36 patients (23 M, 13 F, mean age 32 years, range 3â 75) were included. A clinical diagnosis of NF1 was present in 8 (22%). Alternative lengthening of telomeres (ALT) was assessed by telomereâ specific FISH and/or CISH. A combination of immunohistochemistry, DNA sequencing and FISH were used to study BRAF, ATRX, CDKN2A/p16, mutant IDH1 p.R132H and H3â K27M proteins. ALT was present in 25 (69%) cases and ATRX loss in 20 (57%), mostly in the expected association of ALT+/ATRXâ (20/24, 83%) or ALTâ /ATRX+ (11/11, 100%). BRAF duplication was present in 8 (of 26) (31%). H3â K27M was present in 5 of 32 (16%) cases, all with concurrent ATRX loss and ALT. ALT was also present in 9 (of 11) cases in the benign PA precursor, 7 of which also had ATRX loss in both the precursor and the anaplastic tumor. In a single pediatric case, ALT and ATRX loss developed in the anaplastic component only, and in another adult case, ALT was present in the PAâ A component only, but ATRX was not tested. Features associated with worse prognosis included subtotal resection, adult vs. pediatric, presence of a PA precursor preceding a diagnosis of anaplasia, necrosis, presence of ALT and ATRX expression loss. ALT and ATRX loss, as well as alterations involving the MAPK pathway, are frequent in PA with anaplasia at the time of development of anaplasia or in their precursors. Additionally, a small subset of PA with anaplasia have H3â K27M mutations. These findings further support the concept that PA with anaplasia is a neoplasm with heterogeneous genetic features and alterations typical of both PA and diffuse gliomas.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147190/1/bpa12646_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147190/2/bpa12646.pd

Anti-bacterial activity of inorganic nanomaterials and their antimicrobial peptide conjugates against resistant and non-resistant pathogens

This review details the antimicrobial applications of inorganic nanomaterials of mostly metallic form, and the augmentation of activity by surface conjugation of peptide ligands. The review is subdivided into three main sections, of which the first describes the antimicrobial activity of inorganic nanomaterials against gram-positive, gram-negative and multidrug-resistant bacterial strains. The second section highlights the range of antimicrobial peptides and the drug resistance strategies employed by bacterial species to counter lethality. The final part discusses the role of antimicrobial peptide-decorated inorganic nanomaterials in the fight against bacterial strains that show resistance. General strategies for the preparation of antimicrobial peptides and their conjugation to nanomaterials are discussed, emphasizing the use of elemental and metallic oxide nanomaterials. Importantly, the permeation of antimicrobial peptides through the bacterial membrane is shown to aid the delivery of nanomaterials into bacterial cells. By judicious use of targeting ligands, the nanomaterial becomes able to differentiate between bacterial and mammalian cells and, thus, reduce side effects. Moreover, peptide conjugation to the surface of a nanomaterial will alter surface chemistry in ways that lead to reduction in toxicity and improvements in biocompatibility

Histopathology of Polymicrogyria

Investigators from Sainte Justine Hospital (Montreal), Montreal Neurological Hospital and Institute, King's College Hospital (London), and John Radcliffe Hospital (Oxford) retrospectively reviewed medical records, autopsy reports, and genetic studies containing “Polymicrogyria.

PI3K/AKT pathway and brain malformations

Investigators from Seattle Children's Research Institute, University of Washington, and collaborating institutions sought to evaluate 10 genes in the PI3K/AKT pathway as it relates epileptogenic brain malformations in patients with megalencephaly, hemimegalencephaly, and focal cortical dysplasia

Maternal to fetal transmission of cervical carcinoma.

Reported cases of metastases to the placenta are uncommon, and maternal transmission of tumor to the fetus is even more infrequent. However, vertical transmission of tumor can occur and should be considered as a potential etiology of malignancy in newborns and infants born to mothers with a history of cancer during gestation. Here, we present the imaging findings and clinical course of an unusual case of maternal cervical neuroendocrine carcinoma presenting as bilateral petrous temporal bone lesions in an infant

Hepatobiliary cystadenoma: a rare pediatric tumor.

Hepatobiliary cystadenoma is a rare hepatic neoplasm that has been reported only 10 times in the pediatric population. Although considered a benign cystic tumor of the liver, hepatobiliary cystadenoma has a high risk of recurrence with incomplete excision and a potential risk for malignant degeneration. Complete tumor excision with negative margins is the mainstay in treatment. Unfortunately, due to the paucity of cases and its vague presentation, hepatobiliary cystadenoma is rarely diagnosed preoperatively. Therefore, in patients with hepatic cystic masses without a clear diagnosis, total resection of the lesion with negative margins is indicated to adequately evaluate for malignant potential and limit the risk of recurrence. We describe a 2-year-old girl with an asymptomatic abdominal mass that was found to be hepatobiliary cystadenoma. In addition, the pathogenic, histopathologic and clinical features of hepatobiliary cystadenoma are reviewed

Type I interferon signaling does not alter mortality or control viral replication in the neonatal mouse brain after HSV infection.

<p>(A) Survival of 7-day-old (neonatal) WT mice inoculated with 10³ PFU HSV-1 F (n = 5), neonatal IFNAR KO mice (n = 9) inoculated with 10³ PFU of HSV-1 F, or neonatal WT mice inoculated with 100 PFU HSV-1 F (n = 6). Results shown represent survival data combined from 6 independent inoculations. Log-rank analysis showed no difference in time to mortality between groups of mice inoculated with 10³ PFU HSV-1 (<i>P</i> = 1.00) or between groups of WT mice inoculated with different amounts of virus (<i>P</i> = 0.17, median survival = 3 days in all groups). (B) HSV-1 titer in brain tissue of neonatal WT (10³ or 100 PFU) or IFNAR KO (10³ PFU) mice at death or post-inoculation day 14. Log-transformed mean titer at death did not differ between IFNAR KO and WT mice inoculated with 10³ PFU of HSV-1 (10^7.2 PFU/g vs 10^7.1 PFU/g, respectively, <i>P</i> = 0.67, <i>t</i> test). Log-transformed mean titer at death in brain homogenates from WT neonates inoculated with 100 PFU were statistically higher than those inoculated with 10³ PFU (10^7.3 PFU/g vs 10^7.1 PFU/g, respectively, <i>P</i> = 0.01).</p