ABSTRACT
Radical gastrectomy with D2 lymphadenectomy has been widely performed as the standard surgery for patients with gastric cancer in major medical centers in China and abroad. However, the exact extent of lymph node dissection is still controversial. In the latest version of the Japanese Gastric Cancer Treatment Guidelines, No. 14v lymph nodes (along the root of the superior mesenteric vein) are again defined as loco-regional lymph nodes, and it is clarified that distal gastric cancer presenting with infra-pyloric regional lymph node (No.6) metastasis is recommended for D2+ superior mesenteric vein (No. 14v) lymph node dissection. To explore the relevance and clinical significance of No.6 and No.14v lymphadenectomy in radical gastric cancer surgery, a review of the national and international literature revealed that No.6 lymph node metastasis was associated with No.14v lymph node metastasis, that No.6 lymph node status was a valid predictor of No.14v lymph node negative status and false negative rate, and that for gastric cancer patients with No. 14v lymph node negative and No.6 lymph node positive, the dissection of No.14v lymph node may also have some significance. The addition of No. 14v lymph node dissection in radical gastrectomy is safe, but it is more important to distinguish the patients who can benefit from it. Professor Liang Han of Tianjin Medical University Cancer Hospital is currently leading a multicenter, large-sample, prospective clinical trial (NCT02272894) in China, which is expected to provide higher level evidence for the clinical significance of lymph node dissection in No.14v.
Subject(s)
Humans , Stomach Neoplasms/pathology , Lymphatic Metastasis/pathology , Prospective Studies , Retrospective Studies , Lymph Nodes/pathology , Lymph Node Excision , Gastrectomy , Multicenter Studies as TopicABSTRACT
This study aimed to investigate the effect of methyl eugenol(ME) on hypoxia/reoxygenation(H/R)-induced injury of human renal tubular epithelial HK-2 cells and its mechanism. The viability of HK-2 cells cultured with different concentrations of ME and exposed to H/R was detected by cell counting kit-8(CCK-8) assay. The effect of ME on the morphology of HK-2 cells was observed under an inverted microscope. The content of intracellular reactive oxygen species in different groups was detected after 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA) fluorescence staining. Cell apoptosis was determined by flow cytometry. Changes in mitochondrial membrane potential were monitored by JC-1 dye. The concentrations of nuclear factor erythroid 2 related factor 2(Nrf2), heme oxygenase-1(HO-1), and nicotinamide adenine dinucleotide phosphatase oxidase 4(Nox4) were measured by Western blot, followed by the assay of Nrf2 concentration changes in cytoplasm and nucleus by confocal fluorescence staining. The results showed that when the concentration of ME was 0-40 μmol·L~(-1), the activity of HK-2 cells was not affected. Compared with the model group, ME enhanced the activity of HK-2 cells and the cell morphology was normal. As revealed by further experiments, ME inhibited the release of reactive oxygen species and the decline in mitochondrial membrane potential of HK-2 cells after H/R injury, promoted Nrf2/HO-1 expression and Nrf2 translocation to the nucleus, and down-regulated the expression of Nox4, thereby significantly reducing apoptosis. This protective effect of ME could be reversed by the specific Nrf2 inhibitor ML385. These findings have preliminarily proved that ME effectively protected HK-2 cells against H/R injury, which might be related to its promotion of Nrf2/HO-1 signaling pathway and inhibition of Nox4. Such exploration on the possible mechanism of ME in the treatment of renal ischemia-reperfusion injury(IRI) and protection of organ function from the perspective of antioxidant stress has provided reference for related research on the treatment of acute kidney injury with traditional Chinese medicine.