The molecular pathogenesis of craniopharyngiomas

ABSTRACT Research from the last 20 years has provided important insights into the molecular pathogenesis of craniopharyngiomas (CPs). Besides the well-known clinical and histological differences between the subtypes of CPs, adamantinomatous (ACP) and papillary (PCP) craniopharyngiomas, other molecular differences have been identified, further elucidating pathways related to the origin and development of such tumors. The present minireview assesses current knowledge on embryogenesis and the genetic, epigenetic, transcriptomic, and signaling pathways involved in the ACP and PCP subtypes, revealing the similarities and differences in their profiles. ACP and PCP subtypes can be identified by the presence of mutations in CTNNB1 and BRAF genes, with prevalence around 60% and 90%, respectively. Therefore, β-catenin accumulates in the nucleus-cytoplasm of cell clusters in ACPs and, in PCPs, cell immunostaining with specific antibody against the V600E-mutated protein can be seen. Distinct patterns of DNA methylation further differentiate ACPs and PCPs. In addition, research on genetic and epigenetic changes and tumor microenvironment specificities have further clarified the development and progression of the disease. No relevant transcriptional differences in ACPs have emerged between children and adults. In conclusion, ACPs and PCPs present diverse genetic signatures and each subtype is associated with specific signaling pathways. A better understanding of the pathways related to the growth of such tumors is paramount for the development of novel targeted therapeutic agents.

Mutations in K ATP channel genes and congenital hyperinsulinemic hypoglycemia / 国际儿科学杂志

Congenital hyperinsulinemic hypoglycemia(CHH)is a group of rare heterogeneous diseases with hypoglycemia as the main clinical manifestation caused by insulin imbalance and excessive secretion.It is the most common cause of persistent hypoglycemia in infants and children.Related gene mutations were detected in about 40% of patients, among which inactivating mutations in ABCC8 or KCNJ11 genes are the most common.Delay in diagnosis and improper treatment can cause permanent brain damage in infants and children with CHH.Therefore, early identification and correct diagnosis and treatment are important and essential to prevent brain damage in infants and children with CHH.This article reviews the molecular pathogenesis of CHH caused by K ATP gene inactivation mutations, the impact of ABCC8 or KCNJ11 gene mutations on the pathological types of pancreas, the severity of hypoglycemia and the choice of clinical treatment options in children with CHH, as well as the latest progress in clinical diagnosis and treatment of CHH, in order to improve clinicians′ awareness of CHH.

From Driver Mutations to Genomic Classification: Current & Future Perspectives on Myeloproliferative Neoplasms

@#Myeloproliferative neoplasms (MPNs) encompass a heterogeneous group of chronic, clonal haematopoietic stem cell neoplasms that harbor the propensity to undergo leukaemic transformation. Epidemiological data on MPNs especially pertaining to non-Caucasian populations is limited, and the molecular pathogenesis of MPN remains unclear. Although the discovery of MPN driver mutations in JAK2, MPL and CALR in the last decade has revolutionised disease management, the mutations are not specific for any MPN subtype. The management of MPNs is further challenged by substantial genetic and phenotypic heterogeneity that exist between and within MPN subtypes as well as other myeloid diseases. In this review, we focus on the classical Philadelphia chromosome (Ph)-negative MPNs – polycythaemia vera (PV), essential thrombocythaemia (ET), and primary myelofibrosis (PMF); providing an overview on the current understanding of the disease at a clinical and molecular standpoint while discussing the present challenges and future opportunities in the management of MPNs.

Progress of molecular pathogenesis of extranodal natural killer/T-cell lymphoma / 白血病·淋巴瘤

Extranodal nature killer/T cell lymphoma (ENKTCL) is a highly aggressive non-Hodgkin lymphoma (NHL) with a high mortality. ENKTCL is epidemic in Asia and Latin America, especially in China, Japan and South Korea. EBV has been proved to be associated closely with ENKTCL; however, specific molecular mechanism which can explain how the neoplasm develops is still unclear. Chinese population seems to be more susceptible to this lymphoma and Chinese scientists have made great contributions to the pathogenesis and the treatments of ENKTCL. This review mainly introduces the recent progress of molecular pathogenesis of ENKTCL.

Management of an internal root resorption on a permanent tooth: a case report / Manejo de una reabsorción radicular interna en una pieza permanente: reporte de caso

Internal root resorption (IRR) is a rare pulp disease. Its etiology involves late pulpal inflammations and trauma, among others. IRR may also show some symptoms, and is usually detected by X-rays. However, its diagnosis is significantly improved by the use of cone beam computed tomography (CBCT). The objective of this case report was to account for the diagnosis and management of an internal root resorption without perforation. The patient, a 26-year-old male, went to the School of Dentistry at Universidad Andres Bello, Concepción, without having symptoms in the tooth 1.1. Anamnesis revealed the presence of previous symptoms. CBCT examination showed absence of bowl-shaped calcified dentin tissue on the inner walls of the root canal with apical lesion but without perforation of surrounding tissues. Endodontic treatment was performed using the following methods: irrigation of the root canal with 2 percent chlorhexidine (CHX) using a Max-i-probe cannula and simultaneous cavitation of the irrigant Then calcium hydroxide (CH) was applied as intracanal medication for a week and Schilder’s technique for vertical compaction was used. The patient was checked after one week and then after six months. He did not have any symptoms. Early diagnosis using modern imaging equipment, appropriate use of ultrasound for chemomechanical debridement and thermoplastic filling techniques contribute to a more favorable prognosis of patients with internal root resorption...

La reabsorción radicular interna (RRI) es una condición pulpar poco común, cuyo origen etiológico incluye procesos inflamatorios tardíos de la pulpa, traumatismos, entre otros; por otra parte ésta podría presentar sintomatología. Generalmente es detectada por hallazgo radiográfico, sin embargo, requiere de un mejor método de diagnóstico por imagen como es la tomografía computarizada cone beam (TCCB). El objetivo de este reporte de caso fue detallar el diagnóstico y manejo de una reabsorción radicular interna sin perforación. El paciente de sexo masculino, 26 años de edad acudió a la Facultad de Odontología de la Universidad Andrés Bello sede Concepción, sin presentar síntomas en el diente 1.1. La anamnesis refirió presencia de sintomatología con anterioridad. La evaluación mediante la TCCB demostró ausencia de tejido dentinario calcificado en forma de cuenco en las paredes internas del conducto radicular con presencia de lesión apical sin evidenciar perforación hacia tejidos circundantes. Se realizó el tratamiento endodóntico, usando los siguientes métodos: el conducto radicular se irrigó con Clorhexidina (CHX) al 2 por ciento usando cánula Max-i-probe y simultáneamente fue realizada la cavitación del irrigante, luego se colocó Hidróxido de Calcio (HC) como medicación intraconducto por una semana. Se usó la técnica de compactación vertical de Schilder más un control del paciente a la semana y a los 6 meses. El paciente no presentó sintomatología. El diagnóstico temprano mediante herramientas imaginológicas contemporáneas, la utilización del ultrasonido para el desbridamiento químico-mecánico y las técnicas de obturación termoplásticas usadas acorde al caso hacen que las piezas con reabsorción radicular interna tengan un pronóstico más favorable...

Research progress of the molecular pathogenesis in myelodysplastic syndromes / 白血病·淋巴瘤

The pathogenesis-related genes of myelodysplastic syndrome (MDS) has became a hot spot in the whole world.The common genetic mutations in MDS include epigenetic regulator mutations (TET2,ASXL1,DNMT3A),RNA splicing mutations (SF3B1,SRSF2,U2AF1,ZRSR2),signal transduction regulators (NRAS,JAK2),transcription factors mutations (RUNX1,TP53) and so on.Each mutation plays an important role in the molecular mechanisms of the pathogenesis of MDS and is closely related with clinical phenotype,efficacy and prognosis.Further study of the molecular pathogenesis of MDS-related genes can promote exploring the mechanisms and new therapeutic strategies for MDS.

Update on the molecular pathogenesis of intrauterine growth retardation / 中华实用儿科临床杂志

The causes of intrauterine growth retardation (IUGR) remains a challenge due to the complicated embryonic and fetal growth.More and more researches put their insights into the molecular pathogenesis.In this review,provide recent advances in the molecular pathogenesis of IUGR aimed at further understanding of this vexing medical problem.

Molecular pathogenesis and the role of tumor markers in cholangiocarcinoma / 대한내과학회지

Cholangiocarcinoma is a devastating cancer originating from the epithelial cell lining of the bile duct, whose prognosis is poor due to suboptimal response to therapy despite the fact that the incidence is increasing. Hence surgery still remains the only curative treatment option for cholangiocarcinoma. Recent investigations into the underlying biochemical and molecular mechanisms in biliary carcinogenesis and tumor growth, may illuminate new therapeutic modalities and suggest some new serum and bile markers that could be useful for the diagnosis of cholangiocarcinoma. In this review, we discuss the molecular mechanisms of pathogenesis in cholangiocarcinoma and the role of new tumor makers for the diagnosis of cholangiocarcinoma.

Molecular Pathogenesis of Pancreatic Cancer / 한양의대학술지

Applying the growing body of knowledge of the molecular basis of pancreatic cancer to effective strategies for early diagnosis and treatment is a challenge for both clinicians and scientists. Although our knowledge of the molecular alterations in pancreatic cancer has grown significantly using genomic high-throughput technology, there is still much to learn. Molecular studies of pancreatic cancer have revealed that this cancer is associated with several genetic mutations. The genes targeted in pancreatic cancer include tumor-suppressor genes (p16, TP53 and SMAD4), oncogenes (K-RAS, BRAF, AKT2 and Shh), and genome-maintenance genes (MLH1, MSH2 and BRAC2). However, a better understanding of the relative contribution of each of these molecular alterations is necessary. Mutant mice that develop pancreatic intraepithelial neoplasms (PanIN), the preinvasive stage of pancreatic cancer, were produced and demonstrated promise in the pursuit of biomarkers of early pancreatic cancer. Mutant mice that develop PanIN also facilitate explorations of the cellular origins of pancreatic cancer and the development of treatment strategies.