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.

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

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.

Objective: To analyze the application of accelerated rehabilitation surgery in elderly patients with gastric cancer surgery and its influence on inflammation and nutritional indicators. Methods: From October 2017 to October 2018, 80 elderly patients with gastric cancer who underwent gastrectomy in Shaoxing People's Hospital were selected.According to random number table method, they were randomly divided into traditional control group and ERAS group, with 40 cases in each group.The traditional control group was treated by traditional perioperative treatment + operation, while ERAS group was treated with ERAS perioperative treatment + operation.The recovery and complications, inflammation and nutritional changes before operation, 1 day after operation and 3 days after operation, and the improvement of quality of life after operation were compared and analyzed between the two groups. Results: In the ERAS group, the first exhaust time[(2.3±0.8)d] and defecation time[(2.5±0.4)d]were shorter than those in the traditional control group[(3.5±0.5)d and (3.7±0.6)d], and the incidence rate of complications (7.5%) was lower than that in the traditional control group (35.0%), the differences were statistically significant (t=8.72, 10.52, χ²=9.04, all P<0.05). On the first day after operation, the serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6(IL-6) in the ERAS group were (28.3±4.9)μg/L and (23.1±5.8)μg/L, respectively, which were lower than those in the traditional control group[(39.8±6.7)μg/L and (34.5±8.1)μg/L](t=8.76, 7.24, all P<0.05). The serum TNF-α and IL-6 levels in the ERAS group on the 3rd day after operation were (18.4±6.2)μg/L and (18.3±3.2)μg/L, respectively, which were lower than those in the traditional control group[(26.2±5.1)μg/L and (26.5±4.8)μg/L](t=6.14, 8.99, all P<0.05). The serum levels of albumin (Alb) and prealbumin (PRE) in the ERAS group on the first day after operation were (31.1±0.7)g/L and (161.3±7.2) mg/L, respectively, which were lower than those in the traditional control group[(30.2±0.9)g/L and (154.3±4.8)mg/L](t=4.99, 5.12, all P<0.05). The serum levels of Alb and PRE in the ERAS group on the 3rd day after operation were (33.4±0.5)g/L and (172.1±5.0)mg/L, respectively, which were lower than those in the traditional control group[(31.9±0.8)g/L and (165.3±3.2)mg/L](t=10.06, 7.24, all P<0.05). The WHOQOL-BREF score of the ERAS group[(91.4±6.5)points]was higher than that of the traditional control group[(80.3±7.8)points](P<0.05). Conclusion Accelerated rehabilitation surgery has good effect for elderly gastric cancer surgery.It can maintain the inflammation and nutritional status of patients after operation.It is worthy of clinical reference.

OBJECTIVETo investigate the effect of mTOR signal transduction pathway and down-regulating anti-oncogene PTEN on the growth of breast cancer MCF-7 cells.

METHODSMCF-7 cells were transfected with the eukaryotic expression plasmid pcDNA3.1-mTOR and non-loaded plasmid, and the expression of mTOR in the cells was detected using Western blotting. Flow cytometry was used to analyze apoptosis and cell cycle of the transfected cells, and the expression of PTEN was detected after transfection.

RESULTSThe cells transfected with pcDNA3.1-mTOR showed a increased growth rate than those transfected with the non-loaded plasmid and those without transfection. The expression of the protein PTEN decreased obviously in the cells after mTOR trasnfection.

CONCLUSIONmTOR can regulate the expression of PTEN via PI3K/AKT/PTEN pathways through a negative feedback mechanism. Increased mTOR expression promotes MCF-7 cell growth, suggesting the potential value of mTOR specific inhibitor in the treatment of breast cancer.

Apoptosis ; Breast Neoplasms ; pathology ; Cell Cycle ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; PTEN Phosphohydrolase ; metabolism ; Plasmids ; Signal Transduction ; TOR Serine-Threonine Kinases ; genetics ; Transfection

Objective To investigate the effect of mTOR signal transduction pathway and down-regulating anti-oncogene PTEN on the growth of breast cancer MCF-7 cells. Methods MCF-7 cells were transfected with the eukaryotic expression plasmid pcDNA3.1-mTOR and non-loaded plasmid, and the expression of mTOR in the cells was detected using Western blotting. Flow cytometry was used to analyze apoptosis and cell cycle of the transfected cells, and the expression of PTEN was detected after transfection. Results The cells transfected with pcDNA3.1-mTOR showed a increased growth rate than those transfected with the non-loaded plasmid and those without transfection. The expression of the protein PTEN decreased obviously in the cells after mTOR trasnfection. Conclusion mTOR can regulate the expression of PTEN via PI3K/AKT/PTEN pathways through a negative feedback mechanism. Increased mTOR expression promotes MCF-7 cell growth, suggesting the potential value of mTOR specific inhibitor in the treatment of breast cancer.

Objective To investigate the effect of mTOR signal transduction pathway and down-regulating anti-oncogene PTEN on the growth of breast cancer MCF-7 cells. Methods MCF-7 cells were transfected with the eukaryotic expression plasmid pcDNA3.1-mTOR and non-loaded plasmid, and the expression of mTOR in the cells was detected using Western blotting. Flow cytometry was used to analyze apoptosis and cell cycle of the transfected cells, and the expression of PTEN was detected after transfection. Results The cells transfected with pcDNA3.1-mTOR showed a increased growth rate than those transfected with the non-loaded plasmid and those without transfection. The expression of the protein PTEN decreased obviously in the cells after mTOR trasnfection. Conclusion mTOR can regulate the expression of PTEN via PI3K/AKT/PTEN pathways through a negative feedback mechanism. Increased mTOR expression promotes MCF-7 cell growth, suggesting the potential value of mTOR specific inhibitor in the treatment of breast cancer.

Objective:This study aimed to establish a mouse model of breast cancer by inoculating human breast cancer cells into mice with normal immune function. Methods:Forty female BALB/C mice were randomized into four groups, with 10 mice in each group. The four groups were established according to the dosage of cyclophosphamide and prednisone, namely, the control group, low dose group, medium dose group, and high dose group. The mouse models of breast cancer were established by injecting human breast cancer cells into the fat pad of the right second breast of mice in the groups. Mice in the four groups were observed based on the time of tumorigenesis, rate of tumor formation, tumor imaging and pathological features, and metastasis of vital internal organs. Results:In the high dose group, the time of tumor formation was lower than that of the other groups, but the rate of tumor formation was high. Some visceral metastases occurred in the mice. By contrast, the medium dose group revealed completely opposite results. No death and tumor formation in both the control and low dose groups were reported. Conclusion:A human breast carcinoma model in mice was successfully established. Using this model, the onset and development of breast cancer could be much better imitated in the normal immune system of mice.

Objective To investigate the clinical efficacy of the curettage and aspiration technique in laparoscopic radical gastrectomy for the treatment of gastric cancer.Methods The clinical data of 55 patients who received laparoscopic radical gastrectomy by curettage and aspiration technique with Peng's multifunctional operative dissector at the Shaoxing People's Hospital from June 2008 to February 2011 were retrospectively analyzed.Tumors located at the upper stomach in 10 patients,at the middle stomach in 15 patients and at the lower stomach in 30 patients.The numbers of patients had tumor in TNM stage Ⅰ,Ⅱ,Ⅲ A were 16,35 and 4.Patients were followed up via phone call and out-patient examination till October 2013.Results Laparoscopic radical gastrectomy was successfully carried out on all the 55 patients.Of the 55 patients,39 received laparoscopic distal subtotal gastrectomy and 16 received laparoscopic total gastrectomy.The operation time,volume of intraoperative blood loss,number of lymph nodes dissected,distances of proximal and distal resection margins to the tumors,time to flatus,time to fluid diet and duration of postoperative hospital stay and incidence of postoperative complications were (241 ± 42)minutes,(273±115)mL,32 ±9,(5.8±1.4)cm,(5.1 ±l.7)cm,(78 ±24)hours,(95 ±17)hours,(12 ±4)days and 7.3％ (4/55),respectively.Two patients were complicated with pulmonary infection,1 with anastomotic fistula,1 with incisional infection,and all of them were cured by symptomatic treatment.No patients died perioperatively.All the 55 patients were followed up for 12.0-55.0 months,and the mean time of follow-up was 35.9 months.The cumulative 48-month survival rate was 54.8％.The postoperative recurrence and metastasis rate was 10.9％ (6/55).Peritoneal metastasis was detected in 2 patients,liver metastasis in 1 patient,para-aortic nodes metastasis in 1 patient,residual gastric metastasis in 1 patient,and bone metastasis in 1 patient.Conclusion Laparoscopic radical gastrectomy by curettage and aspiration technique is safe and feasible,with the advantages of minimal trauma,low morbidity and quick recovery.

Axillary interventions, represented by axillary lymph node dissection (ALND), has been a key component in radical surgeries for breast cancer since the proposal of radical mastectomy. ALND substantially affects the quality of life of the patients. In recent years, many studies suggested that axillary interventions may not be necessary for all breast cancer patients, and for early early-stage patients, it brings more harm than benefit. Sentinel lymph node biopsy (SLNB) has provided good guidance to indicate the necessity of ALND, but several studies revealed that not all patients with positive SLNB results benefited from ALND. In this review, the authors summarize the recent progress of researches of these two hot issues.
Axilla ; Breast Neoplasms ; surgery ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes ; Quality of Life ; Sentinel Lymph Node Biopsy