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Primary malignant melanoma of the esophagus (PMME) is an extremely rare but highly aggressive malignancy with a poor prognosis. Due to the scarcity of driver gene alterations, there is a need for more clinical data to comprehensively depict its molecular alterations. This study reviewed 26 PMME cases from three medical centers. Hybrid capture‐based targeted sequencing of 295 and 1021 genes was performed in 14 and 12 cases, respectively. We found that PMME patients had a relatively low tumor mutation burden (median, 2.88 mutations per Mb) and were simultaneously accompanied by mutations in genes such as KIT (6/26, 23%), TP53 (6/26, 23%), SF3B1 (4/26, 15%), and NRAS (3/26, 12%). KIT, NRAS, and BRAF were mutually exclusive, and SF3B1 co‐occurred with KIT mutation and amplification. The most common pathways affected were the mitogen‐activated protein kinases and DNA damage response (DDR) pathways. Stage IV was a risk factor for both progression‐free survival (hazard ratio [HR] = 5.14, 95% confidence interval [CI] = 1.32–19.91) and overall survival (OS), HR = 4.33, 95% CI = 1.22–15.30). Treatment with immune‐checkpoint inhibitors (ICIs) was an independent factor for favorable OS (HR = 0.10, 95% CI = 0.01–0.91). Overall, PMME is a complex malignancy with diverse gene alterations, especially with harboring DDR alterations for potentially response from ICIs. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) has the highest metastatic rate among head and neck cancers, with its underlying mechanism not yet fully unveiled. High- versus low-metastasis, NPC cell lines have been established. The footpad-popliteal lymph node metastasis model and other in vivo models have been stably used to study NPC metastasis. The histological appearance and the expression of epithelial-to-mesenchymal transition (EMT) markers might be helpful in selecting high-risk NPC patients for developing post-treatment metastasis. Tested EMT markers and their protein expression levels that correlate with patient disease-free survival in large patient cohorts include E-cadherin, N-cadherin, CD44, Twist, Snail, and Cyclin D1. Epstein-Barr virus (EBV) infection can trigger NPC metastasis from multiple angles via multiple signaling pathways. High endothelial venules are commonly seen in NPC tissues, with their role in NPC metastasis requiring clarification. The molecules that promote and inhibit NPC metastasis are introduced, with a focus on cytokines SPINK6, serglycin, interleukin 8 (IL8), Wnt family member 5A (WNT5A), and chemokine C-C motif ligand 2 (CCL2). Two videos showing NPC cells with and without SPINK6 knocked down are presented. Future directions for studying NPC metastasis are also discussed.

The objective of this work was to investigate the effect of orally administered silybin on the pharmacokinetics of imatinib in rats and the metabolism of imatinib in human liver microsome and rat liver microsomes. Eighteen healthy male SD rats were randomly divided into 3 groups: group A (control group), group B (received multiple doses of 50 mg x [kg.sup.-1] silybin for 15 consecutive days), and group C (received a single dose of 50 mg x [kg.sup.-1] silybin). A single dose of imatinib was administered orally 30 min after administration of silybin (50 mg x [kg.sup.-1]). Imatinib plasma levels were measured by UPLC-MS/MS, and pharmacokinetic parameters were calculated by DAS 3.0 software (Bontz Inc., Beijing, China). In addition, human and rat liver microsome were performed to determine the effects of silybin metabolism of imatinib in vitro. The multiple doses or single dose of 50 mg x [kg.sup.-1] silybin significantly decreased the area under the curve (0-t) of imatinib (p < 0.01). And the half-life ([t.sub.1/2]) of imatinib is significantly increased (p < 0.05 and p < 0.01, respectively). Also, silybin showed inhibitory effect on human and rat microsomes, the [IC.sub.50] of silybin were 26.42 µmol x [L.sup.-1] and 49.12 µmol x [L.sup.-1] in human and rat liver microsomes, respectively. These results indicate that more attention should be paid to when imatinib is administrated combined with silybin. Key words: cytochromes P450, imatinib mesylate, drug interaction, microsomes, UPLC-MS/MS. L'objectif de ce travail etait d'examiner l'effet de la silybine administree par voie orale, sur la pharmacocinetique de l'imatinib chez le rat et son metabolisme dans les microsomes du foie chez l'humain et le rat. Dix-huit rats males sains ont ete repartis au hasard en trois groupes: groupe A (groupe controle), groupe B (doses multiples de 50 mg x [kg.sup.-1] de silybine pendant 15 jours consecutifs), groupe C (une seule dose de 50 mg x [kg.sup.-1] de silybine). Une seule dose d'imatinib a ete administree par voie orale 30 minutes apres l'administration de silybine (50 mg x [kg.sup.-1]). Les niveaux plasmatiques d'imatinib ont ete mesures par UPLC-MS/ MS, et les parametres pharmacocinetiques ont ete calcules au moyen du logiciel DAS 3.0 (Bontz Inc., Beijing, Chine). En outre, les microsomes humains et de rats ont ete utilises pour determiner les effets de la silybine sur le metabolisme de l'imatinib in vitro. De multiples doses ou une dose unique de 50 mg x [kg.sup.-1] de silybine diminuaient significativement l'ASC 0-t de l'imatinib (p < 0.01). La demi-vie ([t.sub.1/2]) de l'imatinib etait significativement accrue (p < 0.05 et p < 0.01, respectivement). La silybine exercait aussi un effet inhibiteur sur les microsomes humains ou de rats, la CI50 de la silybine etant de 26.42 µmol x [L.sup.-1] et 49.12 µmol x [L.sup.-1] pour les microsomes humains et de rats, respectivement. Ces resultats indiquent que l'on devrait etre plus attentif lorsque l'imatinib est administre en meme temps que la silybine. [Traduit par la Redaction] Mots-cles: cytochromes P450, mesilate d'imatinib, interaction medicamenteuse, microsomes, UPLC-MS/MS., Introduction Silybin, the main active flavonoid compound present in silymarin, is a purified extract from Silybum marianum. It has been used as a therapeutic agent in many liver diseases (Buzzeili [...]