Advances of Angiopoietin-Tie axis in vascular and lymphatic system-related diseases / 生物工程学报

Endothelial cells that form the inner layers of both blood and lymphatic vessels are important components of the vascular system and are involved in the pathogenesis of vascular and lymphatic diseases. Angiopoietin (Ang)-Tie axis in endothelial cells is the second endothelium-specific ligand-receptor signaling system necessary for embryonic cardiovascular and lymphatic development in addition to the vascular endothelial growth factor receptor pathway. The Ang-Tie axis also maintains vascular homeostasis by regulating postnatal angiogenesis, vessel remodeling, vascular permeability, and inflammation. Therefore, the dysfunction of this system leads to many vascular and lymphatic diseases. In light of the recent advances on the role of the Ang-Tie axis in vascular and lymphatic system-related diseases, this review summarizes the functions of the Ang-Tie axis in inflammation-induced vascular permeability, vascular remodeling, ocular angiogenesis, shear stress response, atherosclerosis, tumor angiogenesis, and metastasis. Moreover, this review summarizes the relevant therapeutic antibodies, recombinant proteins, and small molecular drugs associated with the Ang-Tie axis.

Tripodalsporormielones A-C, unprecedented cage-like polyketides with complex polyvdent bridged and fused ring systems

A chemical investigation on

Recommendations from Experts in the Management of Adverse Reactions to ALK Inhibitors (2021 Version) / 中国肺癌杂志

Anaplastic lymphoma kinase (ALK) fusion gene, as a tumor driver gene, was crucial for the occurrence and development of non-small cell lung cancer (NSCLC). Recently, targeted ALK fusion gene has become the main treatment method for ALK-positive NSCLC. The first and second generation ALK inhibitors (ALKi), such as crizotinib, ceritinib, alectinib and ensartinib have been approved in China. However, there was no guidance for the management of ALKi adverse reactions. Therefore, this "Recommendations from experts in the management of adverse reactions to ALK inhibitors (2021 version)" has been summarized, led by Lung Cancer Professional Committee of Sichuan Cancer Society and Sichuan Medical Quality Control Center for Tumor Diseases, to provide practical and feasible strategies for clinical ALKi management specification of adverse reactions.
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Safety and Preliminary Efficacy of Ceritinib 450 mg with Food in Chinese ALK-positive Non-small Cell Lung Cancer / 中国肺癌杂志

BACKGROUND@#Anaplastic lymphoma kinase (ALK) rearrangement is a common driver gene of non-small cell lung cancer (NSCLC). Ceritinib is a second-generation ALK inhibitor, which can bring survival benefits to ALK-positive metastatic NSCLC. However, few studies focus on the safety and efficacy of ceritinib in China. Therefore, this study intends to investigate the safety and preliminary efficacy of ceritinib 450 mg with meals in Chinese patients with ALK-positive NSCLC through a real world study.@*METHODS@#From October 2018 to December 2019, patients with ALK-positive NSCLC from 8 medical centers in Sichuan province were recruited in this study. All of these participants received ceritinib 450 mg/d with food. The basic characteristics, adverse effects (AEs) and responses were collected and analyzed in order to evaluate the safety and efficacy of ceritinib.@*RESULTS@#A total of 109 patients were included in this study. Data cutoff was January 23, 2020. The median duration of treatment exposure was 5.87 mon (range: 0.4 mon-15.7 mon). Total AEs were reported in 98 (89.9%) of 109 patients and grade 3 or 4 AEs were reported in 22.9% of patients. Most common AEs (mainly grade 1 or 2) were diarrhea (60.6%), elevated alanine aminotransferase (ALT)(38.5%) and aspartate aminotransferase (AST)(37.6%). As of data cutoff, 45 patients discontinued ceritinib. The overall response rate (ORR) was 37.6% (95%CI: 28.5%-47.4%) and disease control rate (DCR) was 86.2% (95%CI: 78.3%-92.1%).@*CONCLUSIONS@#The treatment of ceritinib 450 mg with food for Chinese ALK-positive NSCLC patients had a good safety profile and favorable DCR in real-world setting. However, this conclusion needs to be further verified by large sample, prospective trials.

Quantity of Treg cells and Th17 cells in spleen of primary immune thrombocytopenic purpura patients / 中华血液学杂志

Objective@#To observe the quantity of Treg cells and Th17 cells in spleen of adult primary immune thrombocytopenic purpura (ITP) patients.@*Methods@#43 ITP cases with splenectomy treatment were enrolled from December 2008 to June 2016 at Union Hospital of Fujian Medical University, including 20 males and 23 females with a median age of 36 (18-76) years. The controls were thirty patients who underwent splenectomy because of pancreatic diseases or splenic impairment, including 21 males and 9 females with a median age of 47 (21-69) years. The quantity and ratio of Treg cells and Th17 cells were examined by immunohistochemistry between ITP patients and controls.@*Results@#①The quantity of Treg cells in ITP were less than controls[ (11.3±4.7) /mm2 vs (59.0±15.0) /mm2, t=-22.894, P<0.001], but Th17 cells were more than controls[ (235.2±69.4) /mm2 vs (181.1±23.7) /mm2, t=13.768, P<0.001]. So the ratio of Treg/Th17 in ITP was lower than controls (0.048±0.027 vs 0.328±0.086, t=19.522, P<0.001) . ② The quantity of Treg cells in cases without response after splenectomy were less than cases with response[ (9.5±5.0) /mm2 vs (11.6±4.7) /mm2, t=2.723, P=0.010], and there is no statistical differences between the two groups about the quantity of Th17 cells and the ratio of Treg/Th17 cells[ (232.3±80.8) /mm2 vs (239.6±66.9) /mm2, t=1.108, P=0.277; 0.040±0.024 vs 0.053±0.027, t=0.540, P=0.592].@*Conclusions@#There is a significant difference about the quantity of Treg cells and Th17 cells in spleen between ITP patients and healthy controls, and they are relevant to the response after splenectomy.

Summary of the Literatures on Coagulation Disorders Associated with Tigecyclin / 中国药师

Tigecycline is a new broad-spectrum antibiotic,which is the first glycyclines antibiotic used in clinic. Tigecycline is ac-tive against Gram-positive/negative bacteria and anaerobicbacteria, especially multidrug-resistant (MDR) pathogens. In this review, the literatures associated with tigecycline-induced coagulopathy published after 2005 were searched in Pubmed and the clinical charac-teristics as well as the research progress were summarized. The mechanism of tigecycline-induced coagulopathy was also explored. Cli-nicians should observe coagulation markers of patients during the treatment with tigecycline. If coagulation disorders or active bleeding occurs,tigecycline treatment should be stopped and symptomatic and supportive treatment should be given immediately.

Inhibition Function of Dominant-negative Mutant Gene Survivin-D53A to SPC-A1 Lung Adenocarcinoma Xenograft in Nude Mice Models / 生物医学工程学杂志

Survivin-D53A (SVV-D53A) is a dominant-negative mutant survivin, which represents a potential promising target for cancer gene therapy. The present study was designed to determine whether SVV-D53A plasmid encapsuled by DOTAP: Chol liposome would have the anti-tumor activity against SPC-A1 lung adenocarcinoma, and to detect the possible mechanisms. In our experiment, SPC-A1 cells were transfected in vitro with SVV-D53A plasmid and examined for protein expression by Western blot, then flow cytometric analysis was used to detect apoptosis. SPC-A1 lung adenocarcinoma xenografts were established in vivo in the nude mice, which received the i. v. administrations of SVV-D53A plasmid/liposome complexes. After mice were sacrificed, the paraffin-embedded tumor tissue sections were used for proliferating cell nuclear antigen (PCNA) expression and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Compared with the control group, the mice treated with SVV-D53A plasmid had an obviously reduced tumor volume, with high level of apoptosis and decreased cell proliferation in tumor tissue. The research results proved that the administration of SVV-D53A plasmid resulted in significant inhibition of SPC-A1 cells both in vitro and in vivo. The functional mechanism is that the anti-tumor response causes and induces tumor cell apoptosis.

The clinical and endoscopic efficacy of step-up and top-down infliximab therapy in Crohn's disease / 中华内科杂志

ObjectiveTo compare the efficacy of step-up and top-down infliximab therapy on patients with Crohn's disease (CD).MethodsA prospective and open-label study was performed by the First Affiliated Hospital of SUN Yat-sen University during September 2007 to December 2010.Active CD patients who were refractory to steroid/immunomodulator or who were steroid-dependent were enrolled into step-up group.Active CD patients who had no steroid or immunomodulator therapy before were enrolled into top-down group. All patients were intravenously infused with infliximab of 5 mg/kg body weight in an induction regimen of 3 doses at week 0,2 and 6,followed by maintenance dosing every 8 weeks beginning at week 14.The clinical and endoscopic follow up lasted 30 weeks.Clinical symptoms and mucosal healing status under endoscopy were evaluated by follow-up at week 10 and 30.Results Forty-one CD patients were enrolled,with 24 in step-up group and 17 in top-down group. There were significant differences in disease duration (P =0.006),combination therapy (P ＜ 0.001 ) and severity of disease ( P =0.011 ) in baseline between step-up and top-down groups.At week 10 and 30 during treatment,the clinical remission rates in step-up group were 45.8％ (11/24) and 58.3％ (14/24) respectively; the mucosal healing rates in step-up group were 33.3％ (8/24) and 54.2％ (13/24) respectively; the clinical remission rates in topdown group were 70.6％ ( 12/17)and 82.4％ (14/17) respectively; and the mucosal healing rates in topdown group were 35.3％ (6/17) and 52.9％ (9/17) respectively.No significant differences in clinical remission and mucosal healing rates at both week 10 and 30 were observed between the two groups.The prevalences of adverse events in step-up and top-down group were 41.7％ (10/24) and 29.4％ (5/17)respectively ( P =0.422).ConclusionBoth step-up and top-down infliximab therapy can induce remission in more than half of CD patients,while top-down therapy might be more benefitiary to symptom and endoscopic remission.

Clinical observation on the efficacy of Endostar combined with platin-based chemotherapy for 55 cases of advanced non-small cell lung cancer / 肿瘤

Objective:To observe the efficacy, median progression-free survival (PFS) and adverse reaction induced by rh-endostatin injection (Endostar) plus platin-based chemotherapy for advanced non-small cell lung cancer (NSCLC).Methods:Fifty five histologically or cytologically confirmed advanced NSCLC patients received Endostar combined with platin-based chemotherapy for more than 2 cycles. The evaluated parameters included PFS, response rate (RR), clinical benefit rate (CBR) and adverse reaction. Results:Of the 51 patients who can be evaluated for response, 15 (29.4%) achieved partial response (PR), 27 (52.9%) had stable disease (SD), 9 (17.6%) had progressive disease(PD), no patient had complete response(CR). The overall RR was 29.4% (15/51) and CBR was 82.4% (42/51). The median PFS was 6.3 months. There were no significant differences in the short-term efficacy and PFS between the patients who had different pathological features (P=0.037), those had naive or relapsed diseases (P=0.101), or those received different chemotherapeutic regimens (P=0.232). The total white cells and platelets decreased by 72.7% and 54.5%, respectively. The frequency of grade Ⅲ or Ⅳ neutropenia and thrombocytopenia were 36.4% (20 caces) and 21.8% (12 cases), respectively. Four patients stopped the therapy for adverse reaction. One died of gastrointestinal hemorrhage; one had uncontrolled grade Ⅲ hypertension; one had superventricular arrhythmia; one had grade Ⅳ hepatic dysfunction. Conclusion:The combination of Endostar and platin-based chemotherapy increased the CBR and prolonged the PFS of the patients with advanced NSCLC. The toxicities were tolerable.

Use of a novel biologics-infliximab in the treatment of ten patients with Crohn's disease / 中华消化杂志

Objective To investigate the efficacy and safety of a novel biologies-infliximab in the treatment of patients with Crohn's disease (CD). Methods A prospective study was conducted in 10 patients with CD(8 with active refractory CD and 2 with severe lower gastrointestinal bleeding caused by CD). All patients were intravenously infused with infliximab of 5 mg/kg body weight in an induction regimen of 3 doses at week 0, 2 and 6, followed by maintenance dosing every 8 weeks beginning at week 14. The clinical and endoscopic efficacy of infliximab were evaluated by follow-up of 30 weeks. Results ① Five out of 8 patients with active CD had initial clinical response at week 2. Clinical remission was found in 4 patients at week 30, (3 of them in symptomatic remission without corticosteroids). ② Two patients with severe lower gastrointestinal bleeding caused by CD were in control of bleeding and absence of further recurrence by 30 weeks follow-up. ③ Endoscopy was performed in 6 patients at week 30 to evaluate the healing of mucosal ulceration. Four patients were evaluated for complete or almost mucosal healing. ④ Adverse events were seen in 7 out of 10 patients with infliximab treatment, among whom 2 cases had severe side effect including pneumonia in one and delayed hypersensitirity reaction in the other. Conclusion Infliximab has efficacy for the induction and maintenance of remission in part of patients with active CD. Some patients achieved mucosal healing with infliximab therapy and low incidence of serious adverse events.

Effect of threat stress on expression of GnRH receptor in stomach of Sprague-Dawley (SD) rats / 临床检验杂志

Objective To study the localizations and the quantity of GnRH receptor in stomach of Sprague-Dawley (SD) rats under stress.Methods The model of stress SD rats was established by fear. Then, stomachs were taken from the rats in acute stress group (2h-12h), chronic stress group (1d-4w) and the control group respectively.The localizations and the quantity of GnRH receptor in stomachs were detected using immunohistochemistry and Western blotting.Results The results of immunohistochemistry showed that immunoreactivity of GnRH receptor was displayed in the gastric parietal cells and the epithelial cells of the gastric pits in stomachs of rats in all groups. The immunoreactive materials were distributed in membrane and cytoplasm of all positive cells, but not in nuclei. Meanwhile, the results of Western blotting showed that the number of GnRH receptor decreased significantly when SD rats were in stress from 2h to 2w (P

Effects of TGF-?_1 and TNF-? antisense PS-ODNS on e x vivo expansion of hematopoietic stem/progenitor cells(HSPC) / 中国病理生理杂志

AIM: To study the effect of TGF-? 1 and TN F-? antisense PS-ODNS on ex vivo expansion of hematopoietic stem/progenitor cell s (HSPC). METHODS: CD 34 + cells were purified from fres h umbilical cord blood by immunomagnetic beads, and mononuclear cells were purifi ed from bone marrow by Ficoll-hypaque . The effects of TGF-? 1 and /or TNF-? an tisense PS-ODNS on ex vivo expansion of CD 34 + cells、CFU-GEMM、CFU-G M、CFU-E and BFU-E were detected by using liquid and semi-solid culture systems . RESULTS: TGF-? 1 antisense PS-ODNS cooperated with cytokines increased the number of CD 34 + cells,CFU-GEMM,CFU-GM,CFU-E and BFU-E , which was as 4,2.6,2.7,1.8,2.1 times as that of the control (the cytokine s combination), respectively. TNF-? antisense PS-ODNS cooperated with cytokines respectively increased the number of CD 34 + cells, CFU-GEMM, CFU-GM, CF U-E and BFU-E by 4, 2 9, 2 6, 1 7, 1 8 times as that of the control. The ab ove two antisense PS-ODNS cooperated with cytokines could respectively increased the number of CD 34 + cells, CFU-GEMM, CFU-GM, CFU-E and BFU-E by 5 3,2 1, 2 7, 1 9, 1 8 times as that of the control. CONCLUSION: I nhibition of endogenous TGF-? 1 and TNF-? by antisense PS-ODNS will be one of the effective methods to expand HSPC ex vivo.