Abstract Epithelial sinonasal cancers (SNCs) are rare diseases with overlapping morphological features and a dismal prognosis. We aimed to investigate the expression differences among the histological subtypes for discerning their molecular characteristics. We selected 47 SNCs: (i) 21 nonkeratinizing squamous cell carcinomas (NKSCCs), (ii) 13 sinonasal neuroendocrine cancers (SNECs), and (iii) 13 sinonasal undifferentiated cancers (SNUCs). Gene expression profiling was performed by DASL (cDNA-mediated annealing, selection, extension, and ligation) microarray analysis with internal validation by quantitative RT-PCR (RT-qPCR). Relevant molecular patterns were uncovered by sparse partial-least squares discriminant analysis (sPLS-DA), microenvironment cell type (xCell), CIBERSORT, and gene set enrichment (GSEA) analyses. The first two sPLS-DA components stratified samples by histological subtypes. xCell highlighted increased expression of immune components (CD8+ effector memory cells, in SNUC) and “other cells”: keratinocytes and neurons in NKSCC and SNEC, respectively. Pathway enrichment was observed in NKSCC (six gene sets, proliferation related), SNEC (one gene set, pancreatic β-cells), and SNUC (twenty gene sets, some of them immune-system related). Major neuroendocrine involvement was observed in all the SNEC samples. Our high-throughput analysis revealed a good diagnostic ability to differentiate NKSCC, SNEC, and SNUC, but indicated that the neuroendocrine pathway, typical and pathognomonic of SNEC is also present at lower expression levels in the other two histological subtypes. The different and specific profiles may be exploited for elucidating their biology and could help to identify prognostic and therapeutic opportunities.
BACKGROUND: Peritoneal metastasis is a frequent cause of death in patients with gastric cancer. The aim of this study was to identify molecules responsible for mediating peritoneal metastasis of gastric cancer. METHODS: Transcriptome and bioinformatics analyses were conducted to identify molecules associated with peritoneal metastasis. The therapeutic effects of intraperitoneally administered small interfering (si) RNA were evaluated using mouse xenograft models. Expression of mRNA and protein w...
Last. Frank J. Slack(BIDMC: Beth Israel Deaconess Medical Center)H-Index: 87
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The past decade has witnessed enormous progress, and has seen the noncoding RNAs (ncRNAs) turn from the so-called dark matter RNA to critical functional molecules, influencing most physiological processes in development and disease contexts. Many ncRNAs interact with each other and are part of networks that influence the cell transcriptome and proteome and consequently the outcome of biological processes. The regulatory circuits controlled by ncRNAs have become increasingly more relevant in canc...
Purpose: The Cancer Genome Atlas data resources represent an opportunity to explore commonalities across cancer types involving multiple molecular levels, but tumor lineage and histology can represent a barrier in moving beyond differences related to cancer type. Experimental Design: On the basis of gene expression data, we classified 10,224 cancers, representing 32 major types, into 10 molecular-based “classes.” Molecular patterns representing tissue or histologic dominant effects were first re...
Although immune checkpoint inhibitors have resulted in durable clinical benefits in a subset of patients with advanced cancer, some patients who did not respond to initial anti-PD-1 therapy have been found to benefit from the addition of salvage chemotherapy. However, the mechanism responsible for the successful chemoimmunotherapy is not completely understood. Here we show that a subset of circulating CD8+ T cells expressing the chemokine receptor CX3CR1 are able to withstand the toxicity of che...
The sinonasal cavities harbour a variety of rare tumour types. Many carry a poor prognosis while therapeutic options are limited. Histopathological classification can be difficult, especially for poorly differentiated tumours such as olfactory neuroblastoma (ONB), sinonasal neuroendocrine carcinoma (SNEC) and sinonasal undifferentiated carcinoma (SNUC). We analysed Affymetrix OncoScan genome-wide copy number profiles of these three tumour types, both as originally diagnosed and as regrouped by t...
Last. Guoliang Qing(WHU: Wuhan University)H-Index: 10
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The MYC family oncogene is deregulated in >50% of human cancers, and this deregulation is frequently associated with poor prognosis and unfavorable patient survival. Myc has a central role in almost every aspect of the oncogenic process, orchestrating proliferation, apoptosis, differentiation, and metabolism. Although Myc inhibition would be a powerful approach for the treatment of many types of cancers, direct targeting of Myc has been a challenge for decades owing to its “undruggable” protein ...
Last. James R. Howe(Roy J. and Lucille A. Carver College of Medicine)H-Index: 67
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Background Small bowel neuroendocrine tumors (SBNETs) present frequently with metastases, yet little is known about the molecular basis of this progression. This study sought to identify the serial differential expression of genes between normal small bowel, primary small bowel neuroendocrine tumors, and liver metastases. Methods RNA isolated from matched normal small bowel tissue, primary small bowel neuroendocrine tumors, and liver metastases in 12 patients was analyzed with whole transcriptom...
#1Eleni Anastasiadou(BIDMC: Beth Israel Deaconess Medical Center)H-Index: 17
#2Leni S. Jacob(BIDMC: Beth Israel Deaconess Medical Center)H-Index: 12
Last. Frank J. Slack(BIDMC: Beth Israel Deaconess Medical Center)H-Index: 87
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Non-coding RNAs (ncRNAs) are functional molecules that regulate physiological programmes in developmental and disease contexts. This Review article discusses the complex networks of interactions that ncRNAs engage in and how these confer oncogenic or tumour-suppressive effects in cancer.
Abstract miR-758-3p plays an important role via regulting ABCA1-mediated cholesterol efflux in atherosclerosis. However, the mechanism of miR-758-5p in cholesterol metabolism is still unclear. Here, we revealed that miR-758-5p decreased total cholesterol accumulation in THP-1 macrophage derived foam cells through markedly reducing cholesterol uptake, and no effect on the cholesterol efflux. Interestingly, computational analysis suggests that CD36 may be a target gene of miR-758-5p. Our study fur...
Primary neuroendocrine tumors of the breast are a rare and underrecognized subtype of mammary carcinoma. Neuroendocrine tumors of the breast occur predominately in postmenopausal women. The tumors are subclassified into well-differentiated and poorly differentiated neuroendocrine tumors, and invasive breast carcinoma with neuroendocrine features. Well-differentiated tumors show architectural similarity to carcinoids of other sites but lack characteristic neuroendocrine nuclei. Poorly differentia...
Sinonasal squamous cell carcinoma is a rare tumor affecting the nasal cavity and paranasal sinuses. Several aspects of this disease, ranging from epidemiology to biology, pathology, diagnosis, staging, treatment, and post-treatment surveillance are controversial, and consensus on how to manage this sinonasal cancer is lacking. A narrative literature review was performed to summarize the current evidence and provide the reader with available data supporting the decision-making process in patients...
#1Diana Bell(University of Texas MD Anderson Cancer Center)H-Index: 31
#2Achim H. Bell(University of Texas MD Anderson Cancer Center)H-Index: 3
Last. Ehab Y. Hanna(University of Texas MD Anderson Cancer Center)H-Index: 62
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Abstract The skull base is the location of a wide variety of malignant tumors. Among them is sinonasal undifferentiated carcinoma (SNUC), a highly aggressive sinonasal neoplasm that was recently reclassified into subgroups of high-grade carcinomas with unique genomic events (e.g., SMARC-deficient carcinoma, nuclear protein in testis NUT carcinoma). Other high-grade carcinomas in this location are neuroendocrine carcinomas, sinonasal adenocarcinomas, and teratocarcinosarcomas. Given the rarity of...
#2J Chan(QMUL: Queen Mary University of London)H-Index: 1
Last. P.M. Clarke(Imperial College Healthcare)H-Index: 11
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BACKGROUND: Advances in immunohistochemistry have spearheaded major developments in our understanding and classification of sinonasal tumours. In the last decade, several new distinct histopathological entities of sinonasal cancer have been characterised. OBJECTIVES: This review aims to provide a clinical update of the major emerging subtypes for the ENT surgeon and an overview of the management strategies available for this heterogeneous group of pathologies. CONCLUSION: Although rare, knowledg...
Background:We evaluated the prognostic role of gross tumor volumes (GTVs) of primary tumor and positive lymph nodes on overall survival (OS) and progression-free survival (PFS) in locally advanced ...