Targeting FAPα-positive lymph node metastatic tumor cells suppresses colorectal cancer metastasis

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Erratum: Author correction to "The FAPα-activated prodrug Z-GP-DAVLBH inhibits the growth and pulmonary metastasis of osteosarcoma cells by suppressing the AXL pathway" Acta Pharm Sin B 12 (2022) 1288-1304

[This corrects the article DOI: 10.1016/j.apsb.2021.08.015.].

The FAP α -activated prodrug Z-GP-DAVLBH inhibits the growth and pulmonary metastasis of osteosarcoma cells by suppressing the AXL pathway

Osteosarcoma is a kind of bone tumor with highly proliferative and invasive properties, a high incidence of pulmonary metastasis and a poor prognosis. Chemotherapy is the mainstay of treatment for osteosarcoma. Currently, there are no molecular targeted drugs approved for osteosarcoma treatment, particularly effective drugs for osteosarcoma with pulmonary metastases. It has been reported that fibroblast activation protein alpha (FAPα) is upregulated in osteosarcoma and critically associated with osteosarcoma progression and metastasis, demonstrating that FAPα-targeted agents might be a promising therapeutic strategy for osteosarcoma. In the present study, we reported that the FAPα-activated vinblastine prodrug Z-GP-DAVLBH exhibited potent antitumor activities against FAPα-positive osteosarcoma cells in vitro and in vivo. Z-GP-DAVLBH inhibited the growth and induced the apoptosis of osteosarcoma cells. Importantly, it also decreased the migration and invasion capacities and reversed epithelial-mesenchymal transition (EMT) of osteosarcoma cells in vitro and suppressed pulmonary metastasis of osteosarcoma xenografts in vivo. Mechanistically, Z-GP-DAVLBH suppressed the AXL/AKT/GSK-3β/β-catenin pathway, leading to inhibition of the growth and metastatic spread of osteosarcoma cells. These findings demonstrate that Z-GP-DAVLBH is a promising agent for the treatment of FAPα-positive osteosarcoma, particularly osteosarcoma with pulmonary metastases.

Applycation of laparoscopy in the diagnosis and treatment of obstructive infantile cholestasis / 中华肝胆外科杂志

Objective To study the use of laparoscopy in the diagnosis and treatment of obstructive infantile cholestasis.Methods The clinical data of 106 patients with obstructive infantile cholestasis from January 2012 to June 2017 were studied retrospectively.After two weeks of conservative treatments which failed to decrease the bilirubin levels significantly,these patients were subjected to laparoscopic diagnosis and treatment.Results A correct diagnosis was established in all these 106 patients by laparoscopic biliary tract exploration and cholangiography.Eighty-eight patients were diagnosed to have biliary atresia (83.0％),16 patients inspissated bile syndrome (15.1％) and 2 patients biliary hypoplasia (1.9％).Thirty-eight of the 88 biliary atresia patients gave up operative treatment after laparoscopic biliary tract exploration and cholangiography.The remaining 50 biliary atresia patients were treated with open Kasai portoenterostomy.The prognosis of the biliary atresia patients were different from the non-biliary atresia patients.On follow-up for 4 months to 5 years,all the 18 non-biliary atresia patients were in good condition and there was no recurrence of jaundice after laparoscopic cholecystostomy and biliary tract irrigation.Conclusions The laparoscopic minimally invasive technique helped to establish diagnosis and treatment in patients with obstructive infantile cholestasis.For patients with biliary atresia,this procedure gave a definitive diagnosis and offered an opportunity for surgery.For patients with inspissated bile syndrome and biliary hypoplasia patients,laparoscopic cholecystostomy and biliary tract irrigation established the correct diagnosis and reduced liver damage resulted by cholestasis.

Manufacture and clinical application of a new nasal ice compress cover / 局解手术学杂志

Objective To explore the manufacture methods of a new nasal ice compress cover,and to observe its clinical application effect.Methods The nasal ice compress cover body is a silica gel cover,which contains the upper cover body and the lower cover body.The shape of the upper cover body is consistent to the shape of frontal temporal while the shape of the lower cover body is consistent to the shape of the nose root,and the upper cover body and the lower cover body are integrally formed.The inner surface of the cover body is equipped with a ice pack,and the ice pack is of the same shape with the inner surface.And the cover body is provided with two elastic bands.Patients of the experimental group use the nasal ice compress cover and patients of the control group use the traditional ice hockey ice so as to detect the clinical effect of the new nasal ice compress cover and satisfaction rate and adverse reaction of patients.Results The new nasal ice compress cover has good clinical application effect,and patients consider that it has the advantages of convenient,effective and highly satisfactory. Conclusion The new nasal ice compress cover improves patients’comfort degree and satisfaction rate,and it is worthy of wide promotion.

Image features of ielocecus under colonoscopy in intussusceptions children after successful reduction / 中华消化内镜杂志

Objective To investigate the role of ileocecal valve in children patients with intussus-ceptions by colonoscopy after pneumatic air enema reduction. Methods A total of 106 intussusceptions chil dren patients, who recovered with pneumatic air edema reduction, were recruited to the study. They underwent colonoscopy within 12 hours after reduction. The control group was composed of 103 children patients with both diarrhea and hematochezia. There was no significant difference in age, sex or weight between the two groups.Colonoscopic findings were recorded in terms of slack, swelling, prolapsus, lymphoid hyperplasia and mucosal lesions in ileocecal valve. Results In patients with intussusceptions, the rates of ileocecal valve slack, swelling including prolapsus, lymphoid hyperplasia and mucosal lesions were 61.3%, 33. 9%, 100. 0% and 31.1%, respectively, which were significantly different with those of the control group (P ＞ 0. 05 ). When further divided intussusceptions patients into groups with age more than 1 yr or less, significant differences were also observed in regarding of these features. Conclusion There is a close relationship between morphological and functional changes in ileocecal valve and intussusceptions in children. Ileocolic intussusceptions in patients younger than 1yr is more likely to be due to slack of ileocecal valve, while that in patients older than 1yr is mainly due to swelling or prolapse of ileocecal valve, represented by ileocecal intussuception.

The clinical analysis of 13 children with primary splenic tumor / 临床外科杂志

Objective To discuss the clinical characteristics and treatment of children with primary splenic tumor.Method A retrospective analysis was made on 13 children with primary splenic tumor from January 1970 to December 2001.Results There were splenic hemangioma in 5,splenic lymphoma in 4,splenic cysts in 2 and splenic malignant lymphoma in 2.In the primary splenic benign tumors,4 cases were treated with splenectomy,7 cases were treated with partily splenectomy;2 cases of splenectomy often had respiratory tract infection 1 year postoperatively.2 of the splenic malignant lymphoma were treated with splenectomy and chemotheraphy postoperatively;1 of them died 23 months postoperatively,another is still alive 8 months postoperatively.Conclusions The diagnosis of primary splenic tumor in children is mainly depended on B-ultrasound examination and CT scanning.Children with primary splenic benign tumors should be retained normal spleen as far as possible intraoperatively.It is important for splenectomy to pay more attention to the clinical infection 2 years postoperatively.Splenectomy combined with chemotherapy may provide optimum therapy for children with primary splenic malignant lymphoma.Early detection and treatment are crucial to increase the survival rate of children with primary splenic malignant lymphoma.