[Safety and effectiveness of oxaliplatin combined with capecitabine or oxaliplatin combined with S-1 neoadjuvant chemotherapy in the treatment of advanced gastric cancer].

Objective: To explore the safety and efficacy of oxaliplatin plus capecitabine (CapeOX) or oxaliplatin plus S-1 (SOX) regimen neoadjuvant chemotherapy in the treatment of advanced gastric cancer. Methods: A retrospective cohort study was performed. Clinical data of patients diagnosed as advanced gastric cancer undergoing CapeOX/SOX neoadjuvant chemotherapy and standard laparoscopic radical operation for gastric cancer in Ruijin Hospital of Shanghai Jiaotong University School of Medicine from April 2016 to April 2019 were retrospectively collected. Inclusion criteria were as follows: (1) age≥18 years; (2) gastric adenocarcinoma was confirmed by histopathology and the clinical stage was T3-4aN+M0; (3) tumor could be resectable; (4) preoperative neoadjuvant chemotherapy was CapeOX or SOX regimen without radiotherapy or other regimen chemotherapy; (5) no other concurrent malignant tumor; (6) the Eastern Cooperative Oncology Group (ECOG) score ≤ 1; (7) no bone marrow suppression; (8) normal liver and kidney function. Exclusion criteria were as follows: (1) patients with recurrent gastric cancer; (2) patients receiving emergency surgery due to tumor perforation, bleeding, obstruction, etc.; (3) allergy to oxaliplatin, S-1, capecitabine or any drug excipients; (4) diagnosed with coronary heart disease, cardiomyopathy, or the New York Heart Association class III or IV; (5) pregnant or lactating women. A total of 118 patients were enrolled as the neoadjuvant chemotherapy group, and 379 patients with locally advanced gastric cancer who received surgery combined with postoperative adjuvant chemotherapy over the same period simultaneously were included as the adjuvant chemotherapy group. After propensity score matching was performed including gender, age, ECOG score, tumor site, clinical stage, chemotherapy regimen and other factors by 1:1 ratio, there were 40 cases in each group. The differences between the two groups in general conditions, efficacy of neoadjuvant chemotherapy, intraoperative conditions, postoperative conditions, histopathological results, chemotherapy-related adverse events, and survival status were compared and analyzed. Results: Comparison of baseline demographics between the two groups showed no statistically significant difference (all P>0.05). In the neoadjuvant chemotherapy group, 5.0% (2/40) of patients achieved clinical complete response, 57.5% (23/40) achieved partial response, 32.5% (13/40) remained stable disease, and 5.0% (2/40) had disease progression before surgery. Objective response rate was 62.5% (25/40), and disease control rate was 95.0% (38/40). There were no statistically significant differences between neoadjuvant chemotherapy group and adjuvant chemotherapy group in terms of operation time, intraoperative blood loss, number of lymph node harvested, length of postoperative hospital stay, and postoperative mortality and morbidity (all P>0.05). Postoperative complications were well managed with conservative treatment. No Clavien-Dindo IV or V complications were observed in both groups. Pathological results showed that the proportion of patients with pathological stage T1 in the neoadjuvant chemotherapy group was significantly higher than that in the adjuvant chemotherapy group [27.5% (11/40) vs. 5.0% (2/40)], while the proportion of patients with pathological stage T3 was significantly lower than that in the adjuvant chemotherapy group [20.0% (8/40) vs. 45.0% (18/40)], with statistically significant difference (χ(2)=15.432, P=0.001). In the neoadjuvant chemotherapy group, there were 4 cases of tumor regression grade 0, 8 cases of grade 1, 16 cases of grade 2, and 12 cases of grade 3. The pathological complete response rate was 10% (4/40), the overall pathological response rate was 70.0% (28/40). There was no statistically significant difference in the incidence of chemotherapy-related adverse events between neoadjuvant chemotherapy group and adjuvant chemotherapy group [40% (16/40) vs. 37.5% (15/40), P>0.05). There were no statistically significant differences in OS (43 months vs. 40 months) and 3-year OS rate (66.1% vs. 59.8%) between neoadjuvant chemotherapy group and adjuvant chemotherapy group (P=0.428). The disease-free survival (DFS) and 3-year DFS rates of the neoadjuvant chemotherapy group were significantly superior to those of the adjuvant chemotherapy group (36 months vs. 28 months, 51.4% vs. 35.8%, P=0.048). Conclusion: CapeOX or SOX regimen neoadjuvant chemotherapy is a safe, effective and feasible treatment mode for advanced gastric cancer without increasing surgical risk and can improve the DFS of patients.

Qualitative Analyses of Protein Phosphorylation in Bovine Pluripotent Stem Cells Generated from Embryonic Fibroblasts.

Pluripotent stem cells (PSCs) generated from somatic cells via ectopic expression of specific transcription factors provide an unlimited cell resource for regenerative medicine and transgenic breeding. Here, we describe the successful generation of bovine induced PSCs (biPSCs) from foetal fibroblasts by lentivirus-mediated delivery of bovine pluripotency reprogramming factors (PRFs) OCT3/4, SOX2, KLF4, c-MYC, NANOG and LIN28. The generated biPSCs resembled embryonic stem cells (ESCs) in their gene expression profiles, self-renewal capabilities and proliferation, as well as maintenance of a normal karyotype and differentiation into diverse cell types of all three germ layers both in vitro and in vivo. Qualitative phosphoproteomics of biPSCs revealed a large number of phosphorylated proteins, which might be related to the control of biPSCs status. The successful generation of biPSCs and the analysis of their phosphoproteome would further our understanding of the epigenetic mechanisms underlying iPSC pluripotency, thus promoting their application in bovine transgenic breeding and marking avenues for future research.

Vascular endothelial growth factors C and D represent novel prognostic markers in colorectal carcinoma using quantitative image analysis.

BACKGROUND/AIMS: Vascular endothelial growth factor C (VEGF-C) and vascular endothelial growth factor D (VEGF-D) are potent lymphangiogenic and angiogenetic mediators in many kinds of tumors. However, the exact impacts of VEGF-C and VEGF-D on the prognosis of colorectal cancer (CRC) remain elusive. The aims of this study were to demonstrate the expression of VEGF-C and VEGF-D and to correlate their expression levels with clinicopathological factors and long-term survival in patients with CRC. PATIENTS AND METHODS: Between January 1996 and January 1998, 69 patients with pathologically confirmed CRC who received routine follow-up at the Ruijin Hospital were included in this study. VEGF-C and VEGF-D protein expression and microvessel density of 69 surgical specimens were assessed by immunohistochemistry, with 20 samples of normal colorectal tissues as controls. All patients were followed up for 108 months or until death. The Immunohistochemical stains were quantified and analyzed by means of a Zeiss Axioplan 2 imaging analysis system. RESULTS: The protein expression of VEGF-C and VEGF-D in tumor tissues was much higher than that in normal colorectal tissues (p < 0.01). The VEGF-C expression significantly correlated with lymph node metastasis (p = 0.011) and clinical stages of CRC (p < 0.01). The VEGF-D expression correlated with patient ages (p = 0.013), depth of tumor invasion (p = 0.013), and lymph node metastasis (p = 0.028). The expression of VEGF-C and VEGF-D was significantly correlated with the microvessel density. Both overall survival and disease-free survival at 108 months were significantly lower in the CRC patients with a high VEGF-C and/or a high VEGF-D expression, and the patients with a high expression of both VEGF-C and VEGF-D had the shortest overall survival and disease-free survival when compared with other patients. CONCLUSION: The VEGF-C or VEGF-D expression was significantly correlated with lymph node metastasis and long-term prognosis and could be applied as prognostic markers in CRC.

Neuroprotective effect of retro-inverso Prosaptide D5 on focal cerebral ischemia in rat.

Prosaposin (the precursor of saposins A-D) has been identified as a neurotrophic factor in vitro and in vivo. In this study, a novel 11-mer retro-inverso peptidomimetic, Prosaptide D5, was injected i.m. to assess its effectiveness in a rat ischemic model produced by reversible total occlusion of the left middle cerebral artery (MCA). Prosaptide (300 microg/kg, i.m.) injected 3 h after reversible occlusion reduced brain infarct area by 56% compared with a saline group (p < 0.01) at 21 h of reperfusion. A similar injection of D5 6h after occlusion produced a 32% decrease.

Inhibitory effects of nimodipine on platelet aggregation and thrombosis.

AIM: To study the inhibitory effects of nimodipine (Nim) on rat platelet aggregation and arterial thrombosis in vivo. METHODS: The aggregation rate of platelets induced by ADP and inhibition rate of Nim were measured by the change of light transmission. Effect of Nim on arterial occlusion time was measured by electric stimulation. Effect of Nim on the contents of 6-keto-PGF1 alpha and TXB2 in serum was measured by radioimmunoassay. RESULTS: Nim 4.5, 9, 18, and 36 mg.kg-1.d-1 ig for 4 d restrained the platelet aggregation. The IC50 (95% confidence limits) was 26 (9-44) mg.kg-1. Nim 4.5, 9, and 18 mg.kg-1.d-1 ig for 4 d markedly prolonged the time of thrombotic occlusion in carotid artery induced by electric stimulation. Nim 9 and 18 mg.kg-1.d-1 improved the imbalance of 6-keto-PGF1 alpha/TXB2 in serum after thrombosis. CONCLUSION: Nim was a potent inhibitor of platelet aggregation, which was partially concerned with the improved balance of 6-keto-PGF1 alpha/TXB2.

[Effects of doxepin on isolated basilar and saphenous artery rings of rabbits].

AIM: To study the effects of doxepin (Dox) on cerebral artery. METHODS: The effects of Dox were observed using the isolated basilar and saphenous artery rings of rabbits. RESULTS: Dox inhibited the constriction of the basilar and saphenous artery rings evoked by KCl with IC50 5.75 mumol.L-1 (95% confidence limits were 2.3-14 mumol.L-1, n = 8) and 34.6 mumol.L-1 (95% confidence limits were 3.8-316 mumol.L-1, n = 8), respectively. Dox also inhibited the constriction of the basilar and saphenous artery rings of the rabbits stimulated by 5-hydroxytryptamine (5-HT), IC50 were 6.3 mumol.L-1 (95% confidence limits were 1.7-23.3 mumol.L-1, n = 7) and 8.0 mumol.L-1 (95% confidence limits were 6.3-10.3 mumol.L-1, n = 6), respectively. In both samples (basilar and saphenous artery rings) CaCl2 evoked, the pD2 of Dox was 5.28 +/- 0.40 and 4.76 +/- 0.14, respectively (n = 6, P < 0.01). Dox 5.8 mumol.L-1 inhibited the constriction of the saphenous artery evoked by norepinephrine (NE) in Ca(2+)-free medium. Dox 30 mumol.L-1 inhibited the constriction of the saphenous artery evoked both by NE and by readmission of CaCl2 (1.25 mmol.L-1). CONCLUSION: As compared with its effect on the saphenous artery, Dox selectively inhibited the basilar artery.

[Effects of tetramethylpyrazine on rabbit basilar artery ring and canine vertebroarterial circulation].

Tetramethylpyrazine (TMP) inhibited the contraction of rabbit basilar artery and mesenteric arteries caused by KCl with an IC50 of 1.3 mmol.L-1 and 7.5 mmol.L-1 (P < 0.01). The contraction of the rabbit basilar and mesenteric artery ring evoked by KCl, CaCl2 and norepinephrine was inhibited noncompetitively by TMP with the pD2' values of 2.18 +/- 0.16 and 1.83 +/- 0.18 (P < 0.01), 2.13 +/- 0.12 and 2.08 +/- 0.12 (P > 0.05), 3.08 +/- 0.16 and 2.57 +/- 0.08 (P < 0.01), respectively. The contraction of rabbit basilar artery and saphenous veins evoked by 5-HT was also inhibited by TMP with an IC50 of 0.22 mmol.L-1 and 2.2 mmol.L-1 (P < 0.01), respectively. TMP antagonized the myogenic activity of rat portal vein strips. TMP increased canine vertebroarterial blood flow and had no effect on femoral artery blood pressure. The results suggested that TMP may block the calcium channel, inhibit the contraction of rabbit basilar artery, and improve the canine vertebroarterial circulation selectively.

[Inhibited effects of amitriptyline on rabbit basilar and mesenteric artery rings].

The effects of amitriptyline (Ami) on isolated rabbit basilar and mesenteric artery rings were studied and compared with verapamil (Ver). Ami inhibited the contraction of the rabbit basilar and mesenteric artery rings evoked by KCl, CaCl2 and norepinephrine, noncompetitively. The pD'2 values for Ami to antagonize effects of KCl, CaCl2, NE on both arteries were 5.79 +/- 0.10 and 4.97 +/- 0.12 (P less than 0.01), 4.50 +/- 0.30 and 4.58 +/- 0.12 (P greater than 0.05), 5.80 +/- 0.13 and 5.56 +/- 0.12 (P less than 0.01), respectively. The characteristics of such effects of Ami were the same as Ver. The results suggest that Ami may block calcium channels and inhibit rabbit basilar artery selectively.