Xiaotan Sanjie decoction attenuates tumor angiogenesis by manipulating Notch-1-regulated proliferation of gastric cancer stem-like cells

AIM: To determine the underlying mechanisms of action and influence of Xiaotan Sanjie (XTSJ) decoction on gastric cancer stem-like cells (GCSCs).

Xiaotan Tongfu granules contribute to the prevention of stress ulcers

AIM:To investigate the efficacy and potential mechanism of Xiaotan Tongfu granules(XTTF)in stress ulcers.METHODS:One hundred sixty rats were randomly divided into 4 groups(n=10)as follows:the model group(MP group),the control group(CP group),the ranitidine group(RP group)and the XTTF granule group(XP group).Rats in the MP group received no drugs,rats in the CP group received 0.2 mL of a 0.9%sodium chloride solution via oral gavage,and rats in the RP and XP groups received the same volume of ranitidine(50 mg/kg)or XTTF granule(4.9 g/kg).The cold-restraint stress model was applied to induce stress ulcers after 7 consecutive days of drug administration.Afterwards,rats were sacrificed at 0,3,6 and24 h.Gastric pH was measured by a precise pH meter;gastric emptying rate(GER)was measured by using a methylcellulose test meal;myeloperoxidase activity(MPO),macrophage migration inhibitory factor(MIF),proliferating cell nuclear antigen(PCNA),and heat shock protein 70(HSP70)were measured by immunohistochemical staining;and mucosal cell apoptosis was measured by transferase dUTP nick end labeling.RESULTS:In the cold-restraint stress model,the development of stress ulcers peaked at 3 h and basically regressed after 24 h.Gastric lesions were significantly different in the RP and XP groups at each time point.Interestingly,although this index was much lower in the RP group than in the XP group immediately following stress induction(7.00±1.10 vs 10.00±1.79,P<0.05.Concerning gastric pH,between the RP and XP groups,we detected a statistically significant difference immediately after stress induction(0 h:4.56±0.47 vs 3.34±0.28,P<0.05)but not at any of the subsequent time points.For GER,compared to the RP group,GER was remarkably elevated in the XP group because a statistically significant difference was detected(3 h:46.84±2.70 vs 61.16±5.12,P<0.05;6 h:60.96±6.71 vs 73.41±6.16,P<0.05;24 h:77.47±3.17 vs 91.31±4.34,P<0.05).With respect to MPO and MIF,comparisons between the RP and XP groups revealed statistically significant differences at 3 h(MPO:18.94±1.20 vs 13.51±0.89,P<0.05;MIF:150.67±9.85 vs 122.17±5.67,P<0.05)and 6 h(MPO:13.22±1.54 vs 8.83±0.65,P<0.05;MIF:135.50±9.46 vs 109.83±6.40,P<0.05).With regard to HSP70,HSP70 expression was significantly increased in the RP and XP groups at 3 and 6 h compared to the MP and CP groups.In addition,comparing the RP and XP groups also showed statistically significant differences at 3 and 6 h.The expression of PCNA was higher in the RP and XP groups 3 h after stress induction.Between these two groups,small but statistically significant differences were observed at all of the time points(3 h:69.50±21.52 vs 79.33±15.68,P<0.05;6 h:107.83±4.40 vs 121.33±5.71,P<0.05;24 h:125.33±5.65 vs 128.50±14.49,P<0.05)except 0 h.With regard to apoptosis,the apoptotic activity in the RP and XP groups was significantly different from that in the MP and CP groups.The XP group exhibited a higher inhibition of cell apoptosis than the RP group at3 h(232.58±24.51 vs 174.46±10.35,P<0.05)and6 h(164.74±18.31 vs 117.71±12.08,P<0.05).CONCLUSION:The Xiaotan Tongfu granule was demonstrated to be similar to ranitidine in preventing stress ulcers.It exhibited multiple underlying mechanisms and deserves further study.

Network pharmacology-based approach to investigate the mechanisms of Yiyi Fuzi Baijiang Powder in the treatment of malignant tumors

Objective:To systematically investigate the main active components,targets,target-related diseases and action mechanism of Yiyi Fuzi Baijiang powder(YFBP)of Zhang Zhongjing,a Chinese physician of Eastern Han Dynasty of China(3 century A.D.)using the method of network pharmacology.Methods:The active components of YFBP were identified from several databases(TCMSP,TCM Database@Taiwan and TCMID).The potential active compounds were screened based on oral bioavailability and drug-like index in the TCMSP database.DrugBank,TCMSP,and TCMID database searches were performed to predict target-related diseases.Biological functions and KEGG pathway outcomes of all potential targets were analyzed using the DAVID database.Results:A total of 24 active compounds of YFBP,133 related targets,and 305 potential related diseases were obtained.These results showed that YFBP may treat inflammation,pain,and cancer.The functional enrichment analysis indicated that YFBP probably exerts its therapeutic effects by regulating neuroactive ligand-receptor interactions,the TNF signaling pathway,and the PI3K-Akt signaling pathway.Conclusion:This study provides preliminary confirmation that YFBP has the great potentials to treat inflammation,pain,and tumors,which supports Zhang Zhongjing’s original intention to treat intestinal carbuncle with ancient prescription YFBP,but also provides a scientific basis for its treatment in the malignant tumors.

Secondary acute promyelocytic leukemia following chemotherapy for gastric cancer: A case report

Therapy-related acute myeloid leukemia(t-AML) refers to a heterogeneous group of myeloid neoplasms that develop in patients following extensive exposure to either cytotoxic agents or radiation.The development of t-AML has been reported following treatment of cancers ranging from hematological malignancies to solid tumors; however, to our knowledge, t-AML has never been reported following treatment of gastric cancer.In this study, we report the development of t-acute promyelocytic leukemia in a cT 4N1M0 gastric cancer patient after an approximate 44 mo latency period following treatment with 4 cycles of oxaliplatin(OXP)(85 mg/m2 on day 1) plus capecitabine(1250 mg/m2 orally twice daily on days 1-14) in combination with recombinant human granulocyte-colony stimulating factor treatment.Karyotype analysis of the patient revealed 46,XY,t(15;17)(q22;q21)[15]/46,idem,-9,+add(9)(p22)[2]/46,XY[3], which, according to previous studies, includes some "favorable" genetic abnormalities.The patient was then treated with all-trans retinoic acid(ATRA, 25 mg/m2/d) plus arsenic trioxide(ATO, 10 mg/d) and attained complete remission.Our case illuminated the role of certain cytotoxic agents in the induction of t-AML following gastric cancer treatment.We recommend instituting a mandatory additional evaluation for patients undergoing these therapies in the future.

Traditional Chinese medicine integrated with chemotherapy for stage Ⅳ non-surgical gastric cancer: a retrospective clinical analysis

OBJECTIVE： Traditional Chinese medicine （TCM） is regarded as an important treatment for gastric cancer patients, especially for those in advanced stage. To evaluate the effects of TCM treatment on gastric cancer patients, the authors performed a retrospective study to report the result of the integrated treatment of TCM with chemotherapy for stage IV non-surgical gastric cancer. METHODS： In this study, 182 patients with stage IV and non-surgical gastric cancer were retrospectively analyzed to evaluate the effects of TCM integrated with chemotherapy. Among the 182 cases, 88 cases received integrated therapy consisting of TCM and chemotherapy, while 94 cases received chemotherapy alone. The overall survival and Karnofsky performance status （KPS） score were measured as the main outcome. RESULTS： The median overall survival of the integrated therapy group and chemotherapy group were 16.9 and 10.5 months, respectively. The 1-, 3- and 5-year survival rates of integrated therapy group vs. chemotherapy group were 70% vs. 32%, 18% vs. 4%, and 11% vs. 0%, respectively. There was a significant difference between the two groups （x2 = 42.244, P 〈 0.001 ）. After six-month treatment, KPS scores of the integrated therapy group and the chemotherapy group were 75.00 ± 14.78 and 60.64 ± 21.39, respectively （P 〈 0.001）. The Cox regression analysis showed that TCM treatment is a protective factor for patients＇ overall survival. CONCLUSION： This study demonstrated that TCM integrated with chemotherapy may prolong overal survival and improve survival rate and life quality of patients with stage IV non-surgical gastric cancer

Ziyin Huatan Recipe, a Chinese herbal compound, inhibits migration and invasion of gastric cancer by upregulating RUNX3 expression

Objectives: Ziyin Huatan Recipe(ZYHT), a traditional Chinese medicine comprised of Lilii Bulbus, Pinelliae Rhizoma, and Hedyotis Diffusa, has shown promise in treating gastric cancer(GC). However, its potential mechanism has not yet been clearly addressed. This study aimed to predict targets and molecular mechanisms of ZYHT in treating GC by network pharmacology analysis and to explore the role of ZYHT in GC both in vitro and in vivo.Methods: Targets and molecular mechanisms of ZYHT were predicted via network pharmacology analysis. The effects of ZYHT on the expression of metastasis-associated targets were further validated by Western blot and quantitative real-time polymerase chain reaction. To explore the specific molecular mechanisms of the effects of ZYHT on migration and invasion, the runt-related transcription factor 3(RUNX3) gene was knocked out by clustered regularly interspaced short palindromic repeats/Cas9, and lentiviral vectors were transfected into SGC-7901 cells. Then lung metastasis model of GC in nude mice was established to explore the anti-metastasis effect of ZYHT. Western blot and immunohistochemistry were used to explore the impact of ZYHT on the expression of metastasis-related proteins with or without RUNX3 gene.Results: The network pharmacology analysis showed that ZYHT might inhibit focal adhesion, migration,invasion and metastasis of GC. ZYHT inhibited the proliferation, migration and invasion of GC cells in vitro via regulating the expression of metastasis-associated targets. Knocking out RUNX3 almost completely reversed the cell phenotypes(migration and invasion) and protein expression levels elicited by ZYHT.In vivo studies showed that ZYHT inhibited the metastasis of GC cells to the lung and prolonged the survival time of the nude mice. Knocking out RUNX3 partly reversed the metastasis of GC cells to the lung and the protein expression levels elicited by ZYHT.Conclusion: ZYHT can effectively inhibit the invasion and migration of GC in vitro and in vivo, and its molecular mechanism may relate to the upregulation of RUNX3 expression.