FSTL5 expression is a marker of Group C metastatic medulloblastomas

INTRODUCTION: Medulloblastoma (MB) is the most commonmalignant brain tumor in children. Four different molecular subgroups are recognized, which differ in gene expression, genomic aberrations, histology, demographics and survival:WNT and SHH groups, having specific mutations in the homonymous pathway, and groups C and D having several genetic alternations not specific to a single pathway. The gene for follistatin-like protein 5, FSTL5, is overexpressed in nonSHH/nonWNT MBs poorly characterized. Highexpression of FSTL5 is significantly associated with reduced event-free and overall survival in non-WNT/non-SHHMBs. The major aim of this project is to study the FSTL5 expression level in pediatric MBs with metastasis at the onset. METHOD: We investigated the protein expression of biomarkers involved in metastatic pathways by IHC and FSTL5 expression level by RT-PCR in 26 metastatic MBs samples and correlated these data with the outcomes by Kaplan-Meier statistic analysis. RESULTS: 83% of Group C MBs showed high level of FSTL5 while none of these presented down-expression. Low-expression level of FSTL5 was find in 60% of SHH MBs and none showed over-expression. Kaplan-Meier test revealed that, in our cohort, highexpression ofFSTL5didnot correlatewithworse outcomewhile lowexpression of FSTL5 was associated with good prognosis and the co-presence of FSTL5 with other biomarkers correlated with poorer prognosis. CONCLUSION: FSTL5 is a marker of Group C in medulloblastomas with metastasis at the onset and the results highlighted decreased FSTL5 expression as a marker of good prognosis. Group C MBs have characteristic molecular features that confirm the poorest outcome also inMBs with metastasis at the onset

Expanding the spectrum of "mesenchymal" tumors of the central nervous system

: In this review, we summarize the clinical, histopathological, and molecular features of central nervous system (CNS) tumors with BCOR internal tandem duplication, intracranial mesenchymal tumor with FET/CREB fusion, CNS CIC-rearranged sarcomas and primary intracranial sarcoma DICER1-mutant, now included in the 2021 WHO classification of CNS tumors. Possible relationships between tumors occurring in the CNS and their systemic counterparts are discussed

PEMILIHAN METODE PERAMALAN UNTUK MENGURANGI BULLWHIP EFFECT PADA SISTEM RANTAI PASOK PRODUK SIDE VISOR DXXN (STUDI KASUS DI PERUSAHAAN PLASTIC INJECTION CIKARANG)

ABSTRAKPerusahaan Plastic Injection, Cikarang tempat dilakukannya penelitian ini adalah salah satu perusahaan yang bergerak di bidang injection molding dengan produk utamanya yaitu side visor untuk kendaraan roda empat. Dalam memenuhi permintaan customer seringkali terjadi variasi pada demand dan order yang diterima dari customer. Ketika terjadi variasi dalam permintaan pasar yang pada awalnya relatif stabil dengan persediaan di tingkat downstream berubah fluktuatif semakin besar hingga ke tahap upstream, variasi persediaan akan semakin membesar, sehingga membentuk pola seperti cambuk. Fenomena ini kemudian dinamakan bullwhip effect. Bullwhip effect tersebut menyebabkan tidak akuratnya keputusan dalam penentuan tingkat persediaan dan kapasitas produksi yang dibutuhkan, yang berdampak pada terganggunya aliran rantai pasok. Dengan tujuan untuk mengurangi bullwhip effect di level delivery, maka penulis menggunakan metode Autoregressive Integrated Moving Average (ARIMA) dan Single Exponential Smoothing (ES) untuk pemilihan metode peramalan yang tepat guna mengurangi bullwhip effect di level delivery. Hasil yang didapat menunjukan terjadi penurunan nilai bullwhip effect di level delivery sebesar 0,0171 poin

Patrimônio cultural e revolução tecnológica: os meios digitais para ampliação das práticas culturais

Divulgação dos SUMÁRIOS das obras recentemente incorporadas ao acervo da Biblioteca Ministro Oscar Saraiva do STJ. Em respeito à Lei de Direitos Autorais, não disponibilizamos a obra na íntegra.Localização na estante: 351.853:004(81) N441

Embryonal tumors in the WHO CNS5 classification: a review

Embryonal tumors are a heterogenous group of neoplasms mostly defined by recurrent genetic driver events. They have been, previously, broadly classified as either medulloblastoma or supratentorial primitive neuroectodermal tumors (PNETs). However, the application of DNA methylation/gene expression profiling in large series of neoplasms histologically defined as PNET, revealed tumors, which showed genetic events associated with glial tumors. These findings led to the definitive removal of the term "PNET" in the 2016 World Health Organization (WHO) classification of CNS tumors. Moreover, further studies on a large scale of methylation profiling have allowed the identification of new molecular-defined entities and have largely influenced the 5th edition of the WHO classification of CNS tumors (WHO CNS5) for both medulloblastomas and other CNS embryonal tumors. The importance of molecular characteristics in CNS embryonal tumors is well represented by the identification of different molecular groups and subgroups in medulloblastoma. So, in the CNS5, the emerged group 3 and group 4 belong to the classification, and the four molecular and morphologic types are now combined into a unique section. Among other embryonal tumors, two new recognized entities are introduced in CNS5: CNS neuroblastoma, FOXR2-activated, and CNS tumor with BCOR internal tandem duplication (ITD). Embryonal tumor with multilayered rosettes (ETMR), already present in the previous classification now has a revised nomenclature as a result of the new DICER1 alteration, additional to the formerly known C19MC. Regarding atypical teratoid/rhabdoid tumor (AT/RT), three molecular subgroups are recognized in CNS5. The combination of histopathological and molecular features reflects the complexity of all these tumors and gives critical information in terms of prognosis and therapy. This encourages the use of a layered diagnostic report with the integrated diagnosis at the top, succeeded by layers including the histological, molecular, and other essential details

Sonic hedgehog medulloblastoma cancer stem cells mirnome and transcriptome highlight novel functional networks

Molecular classification has improved the knowledge of medulloblastoma (MB), the most common malignant brain tumour in children, however current treatments cause severe side effects in patients. Cancer stem cells (CSCs) have been described in MB and represent a sub population characterised by self-renewal and the ability to generate tumour cells, thus representing the reservoir of the tumour. To investigate molecular pathways that characterise this sub population, we isolated CSCs from Sonic Hedgehog Medulloblastoma (SHH MB) arisen in Patched 1 (Ptch1) heterozygous mice, and performed miRNA-and mRNA-sequencing. Comparison of the miRNA-sequencing of SHH MB CSCs with that obtained from cerebellar Neural Stem Cells (NSCs), allowed us to obtain a SHH MB CSC miRNA differential signature. Pathway enrichment analysis in SHH MB CSCs mirnome and transcriptome was performed and revealed a series of enriched pathways. We focused on the putative targets of the SHH MB CSC miRNAs that were involved in the enriched pathways of interest, namely pathways in cancer, PI3k-Akt pathway and protein processing in endoplasmic reticulum pathway. In silico analysis was performed in SHH MB patients and identified several genes, whose expression was associated with worse overall survival of SHH MB patients. This study provides novel candidates whose functional role should be further investigated in SHH MB

Primary cutaneous alk positive anaplastic large cell lymphoma in a melanoma patient

Primary cutaneous anaplastic large cell lymphoma (PCALCL) is a raresubset of CD30+ lymphoproliferative disorder, characterized by the presenceof large anaplastic cells, which express CD30, CD2, CD3, CD4, and CD5. A 62 year-old male patient presented to our Institute with a history of a fastgrowing and pinkish-brown asymptomatic cutaneous nodule. His medical past history was positive for a malignant melanoma (MM) of the abdomen (0.7 mm Breslow thickness; pT1a). Histologically the lesion showed a diffuse infiltrate consisting in cohesive sheets of large cells with anaplastic morphology with a kidney-shaped nucleus, also known as hallmark cells. Immunohistochemical studies revealed a CD30 expression, and a positivity to perforin and anaplastic lymphoma kinase (ALK). The laboratory and instrumental investigations were all normal and a final diagnosis of PCALCL was made. The patient showed a good response to radiotherapy. Usually PCALCL shares with systemic anaplastic large cell lymphoma (ALCL) the presence of neoplastic CD30+ large T cells, but lack ALK translocations and protein expression. However, the detection of ALK expression in PCALCL should be considered highly suspicious of a cutaneous manifestation of an underlying systemic disease (not detected in our patient). We recommend to exclude a systemic involvement in this kind of disease, with a strict follow-up, especially in patients with double malignancies

Sporadic High-Grade Malignant Peripheral Nerve Sheath Tumor of the Hypoglossal Nerve

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Sporadic high-grade malignant peripheral nerve sheath tumor of the hypoglossal nerve

Malignant tumors of peripheral nerve sheaths (MPNSTs) are rare malignant soft tissue tumors arising either from a peripheral nerve or from a pre-existing benign nerve sheath tumor. They occur most often in the context of Neurofibromatosis type-1 (NF-1) and are characterized by poor prognosis and aggressive behavior with a high rate of recurrence and distant metastases. We describe a 50-year-old woman who presented with right neck swelling, progressive dysphagia and tongue paresis. Imaging analysis revealed a mass involving the right parapharyngeal space. The tumor was excissed through a transcervical approach. At surgery, the tumor was strictly adherent to the hypoglossal nerve. Pathologic evaluation of the mass revealed a high-grade MPNST. Based on the pathological diagnosis, a clinical work-up for NF-1 was performed but it resulted negative. Occurrence of sporadic high-grade MPNST in the parapharyngeal space is rare and development from the hypoglossal nerve exceptional. As far as we know, only in two cases, both with clinical features consistent with NF1, the tumor was reported to be arised from the hypoglossal nerve