Clinical implications of micro lymph node metastasis for patients with gastric cancer.

BACKGROUND: Lymph node size is considered as a criterion for possible lymph node metastasis in imageology. Micro lymph nodes are easily overlooked by surgeons and pathologists. This study investigated the influencing factors and prognosis of micro lymph node metastasis in gastric cancer. METHODS: 191 eligible gastric cancer patients who underwent D2 lymphadenectomy from June 2016 to June 2017 in the Third Surgery Department at the Fourth Hospital of Hebei Medical University were retrospectively analyzed. Specimens were resected en bloc and the postoperative retrieval of micro lymph nodes was carried out by the operating surgeon for each lymph node station. Micro lymph nodes were submitted for pathological examination separately. According to the results of pathological results, patients were divided into the "micro-LNM (micro lymph node metastasis)" group (N = 85) and the "non micro-LNM" group (N = 106). RESULTS: The total number of lymph nodes retrieved was 10,954, of which 2998 (27.37%) were micro lymph nodes. A total of 85 (44.50%) gastric cancer patients had been proven to have micro lymph node metastasis. The mean number of micro lymph nodes retrieved was 15.7. The rate of micro lymph node metastasis was 8.1% (242/2998). Undifferentiated carcinoma (90.6% vs. 56.6%, P = 0.034) and more advanced Pathological N category (P < 0.001) were significantly related to micro lymph node metastasis. The patients with micro lymph node metastasis had a poor prognosis (HR for OS of 2.199, 95% CI = 1.335-3.622, P = 0.002). For the stage III patients, micro lymph node metastasis was associated with shorter 5-year OS (15.6% vs. 43.6%, P = 0.0004). CONCLUSIONS: Micro lymph node metastasis is an independent risk factor for poor prognosis in gastric cancer patients. Micro lymph node metastasis appears to be a supplement to N category in order to obtain more accurate pathological staging.

Biotransformation of Huperzine A by Irpex lacteus-A fungal endophyte of Huperzia serrata.

The biotransformation of huperzine A (hupA), one of the characteristic bioactive constituents of the medicinal plant Huperzia serrata, by a fungal endophyte of the host plant was studied. Two previously undescribed compounds 1-2, along with a known analog 8α,15α-epoxyhuperzine A (3), were isolated and identified. The structures of all the isolates were established by spectroscopic methods including NMR, MS, IR, and UV spectra. In particular, the absolute configurations of 1 and 2 were elucidated by CD spectra comparison and theoretic NOE strength calculation. In the LPS-induced neuro-inflammation injury assay, 1-3 exhibited moderate neuroprotective activity by increasing the viability of U251 cell lines with EC50 values of 35.3 ±â€¯0.9, 32.1 ±â€¯0.9, and 50.3 ±â€¯0.8 nM, respectively.

Biotransformation of Huperzine B by a Fungal Endophyte of Huperzia serrata.

The biotransformation of huperzine B (hupB), one of the characteristic bioactive constituents of the medicinal plant Huperzia serrata, by a fungal endophyte of the host plant was studied. One new compound, 8α,15α-epoxyhuperzine B (1), along with two known oxygenated hupB analogs, 16-hydroxyhuperzine B (2) and carinatumin B (3), was isolated and identified. The structures of all the isolates were deduced by spectroscopic methods including NMR, MS, IR, and UV spectra. The known compounds 2 and 3 were obtained from a microbial source for the first time. To the best of our knowledge, it is the first report on the microbial transformation of hupB and would facilitate further structural modification of hupB by chemo-enzymatic method. In the LPS-induced neuro-inflammation injury assay, 8α,15α-epoxyhuperzine B (1) exhibited moderate neuroprotective activity by increasing the viability of U251 cell lines with an EC50 of 40.1 nm.

Chlorella vulgaris Induces Apoptosis of Human Non-Small Cell Lung Carcinoma (NSCLC) Cells.

OBJECTIVE: Chlorella vulgaris (C. vulgaris), a unicellular green microalga, has been widely used as a food supplement and reported to have antioxidant and anticancer properties. The current study was designed to assess the cytotoxic, apoptotic, and DNA-damaging effects of C. vulgaris growth factor (CGF), hot water C. vulgaris extracts, inlung tumor A549 and NCI-H460 cell lines. METHODS: A549 cells, NCI-H460 cells, and normal human fibroblasts were treated with CGF at various concentrations (0-300 µg/ml) for 24 hr. The comet assay and γH2AX assay showed DNA damage in A549 and NCI-H460 cells upon CGF exposure. Evaluation of apoptosis by the TUNEL assay and DNA fragmentation analysis by agarose gel electrophoresis showed that CGF induced apoptosis in A549 and NCI-H460 cells. RESULTS: Chlorella vulgaris hot water extract induced apoptosis and DNA damage in human lung carcinoma cells. CONCLUSION: CGF can thus be considered a potential cytotoxic or genotoxic drug for treatment of lung carcinoma.

[Effects of XELOX regimen as neoadjuvant chemotherapy on radical resection rate and prognosis in patients with advanced gastric cancer].

OBJECTIVE: The purpose of this study was to investigate the efficacy and mechanism of oxaliplatin in combination with capecitabine (XELOX) regimen as neoadjuvant chemotherapy in the treatment of patients with advanced gastric cancer. METHODS: Eighty-five patients with advanced gastric cancer (stage IIB and IIIC) were randomly divided into two groups: neoadjuvant chemotherapy group (40 cases) and surgery alone group (45 cases). In the neoadjuvant chemotherapy group, patients received oral administration of Xeloda 1000 mg/m(2) twice a day on days 1-14 and intravenous infusion of oxaliplatin 130 mg/m(2) on day 1 (XELOX regimen). The regimen was repeated every 21 days. In the surgery alone group, patients directly received radical resection of gastric cancer. The R0 resection rate, overall survival and disease free survival (DFS) were observed in all cases. The cycles and apoptosis rate of the gastric cancer cells were detected by flow cytometry. The expression of proliferating cell nuclear antigen (PCNA), p21, p53 and survivin was detected by Western blot. RESULTS: In the neoadjuvant chemotherapy group, the total effective rate was 32.5% (13/40), and the tumor control rate was 90% (36/40), with few side effects. Compared with the surgery alone group, R0 resection rate was significantly higher in the neoadjuvant chemotherapy group (P < 0.05). The survival analysis indicated that both the overall survival and DFS were longer in the neoadjuvant chemotherapy group in comparison with those in the surgery alone group, but no significant differences were found (P > 0.05). In the neoadjuvant chemotherapy group, both the apoptosis rate and the ratio of cells in stage G0 and G1 were significantly higher than those in the surgery alone group (P < 0.05). The expression of PCNA and survivin was lower in the neoadjuvant chemotherapy group, while the expression of p21 and p53 was higher. CONCLUSIONS: XELOX regimen as neoadjuvant chemotherapy in the treatment of patients with advanced gastric cancer can effectively improve the R0 resection rate and prolong the survival time of the patients. Its mechanism is probably that the neoadjuvant chemotherapy can markedly enhance apoptosis in gastric cancer cells and inhibit their proliferation.

Synergistic effects of tetrandrine on the antifungal activity of topical ketoconazole cream in the treatment of dermatophytoses: a clinical trial.

OBJECTIVE: To evaluate the synergistic effects of tetrandrine (TET) on the antifungal activity of topical ketoconazole (KCZ) in the treatment of dermatophytoses. METHODS: The minimum inhibitory concentrations (MICs) for KCZ and combined KCZ and TET were compared in vitro. A randomized, double-blind trial was conducted among 97 patients with dermatophytoses who were assigned to 3 groups and received: treatment with combination of 2% KZC and 2% TET cream (KCZ + TET group), or only 2% KZC cream (KCZ group), or 2% TET cream (TET group). Patients with tinea corporis and/or tinea cruris were treated for 2 weeks, separately. The patients with tinea pedis and/or tinea manuum were treated for 4 weeks. RESULTS: Compared with KZC alone, combined use of KZC and TET showed lower MICs against clinical isolates of dermatophytes (P<0.05 for all). In the patients with tinea corporis and/or tinea cruris, the rates of overall cure (clinical cure plus mycologic clearance) were 81.25% vs. 33.33% for combined treatment and KZC monotherapy, respectively, after 4 weeks. All clinical indices were significantly different between the combination therapy and only KCZ therapy groups (P<0.05). Among the patients with tinea pedis and/or tinea manuum after 4 weeks treatment, the overall cure rates in the KCZ + TET group and KCZ group were 75.00% vs. 40.00%, respectively. In the KCZ + TET group, all the clinical indices were significantly better than those in the KCZ group and TET group (P<0.05). The rates of overall efficacy in the TET group were all zero. No local skin redness or itching was observed during TET treatment. No clinically significant changes were found in post-treatment routine blood, urine, or stool tests, ECG, or tests for liver and kidney function; no serious adverse events occurred. CONCLUSION: TET synergistically enhanced the clinical efficacy of topical KZC cream in the treatment of dermatophytoses.

[Effect of local application of allicinvia gastroscopy on cell proliferation and apoptosis of progressive gastric carcinoma].

OBJECTIVE: To study the effects of local application of allicin via gastroscopy on progressive gastric carcinoma, and to investigate its possible mechanisms. METHODS: Eighty patients with progressive gastric adenocarcinoma, whose diagnosis was confirmed by gastroscopy and pathological examination, were assigned to 2 groups, 40 in each group. Forty-eight hours before operation, allicin was infused via gastroscopy to the lesion region of patients in the allicin group, and normal saline was infused instead to those in the control group. The gastric carcinoma tissue gotten from gastrectomy was taken to determine the percentage of cells in various cell cycle phases ( G0/ G1, S and G2/M), the cell apoptosis rate, proliferation index value and apoptosis related gene protein such as Fas, Bax and Bcl-2 by flow cytometry. RESULTS: In the allicin group, the cell apoptosis rate was 9.60 +/- 1.52%, the percentage of cell in G0/G1 phase was 72.12 +/- 8.35%, in G2/M phase 9.54 +/- 3.20%, and PI 27.80 +/- 8.35, while in the control group, the corresponding data was 2.20 +/- 0.58%, 69.56 +/- 5.15%, 13.20 +/- 3.05%, and 30.40 +/- 5.15, respectively, and significant difference in all the 4 indexes could be found between the two groups (P < 0.05, P < 0.01). Moreover, allicin showed effects in up-regulating the protein expressions of apoptosis promoting gene Bax and apoptosis initiating gene Fas (P < 0.05, P < 0.01), and down-regulating that of anti-apoptosis gene Bcl-2 (P < 0.05). CONCLUSION: Local application of allicin via gastroscopy can inhibit the cell growth and proliferation of progressive gastric carcinoma, and can also promote gastric carcinoma cell apoptosis.

[Drug distribution in gastric cancer and adjacent tissues by preoperative intraperitoneal chemotherapy with Co-fluorouracil liposome].

OBJECTIVE: To examine the distribution of fluorouracil in gastric cancer (CA), lymph node (LN), normal gastric mucosa (NG), peritoneum (PE), greater omentum (GO) and lesser omentum (LO) by preoperative intraperitoneal chemotherapy with Co-fluorouracil liposome (Co 5-Fu), and offer an experimental basis for clinic practice. METHODS: Ninety-six gastric cancer patients were divided into four groups: Co 5-Fu i.v. injection group (Co 5-Fu i.v.), Co 5-Fu intraperitoneal perfusion group (Co 5-Fu i.p.), 5-Fu i.v. injection group (5-Fu i.v.) and intraperitoneal perfusion group (5-Fu i.p.) given on day-2, day-1 and 60 minutes before operation. Fluorouracil concentration in all tissues collected during operation were examined by high performance liquid chromatography (HPLC). RESULTS: The fluorouracil concentration in the tissues in Co 5-Fu i.p. group was significantly higher than that in Co 5-Fu i.v. or 5-Fu i.p. group (P < 0.05 or P < 0.01), and that in 5-Fu i.p. group was greatly higher than that at 5-Fu i.v. group (P < 0.01). In Co 5-Fu i.p. group, the concentration of drug in LN, CA, PE, NG, GO and LO decreased gradually with the former 3 tissues significantly higher than the latter 3 tissues (P < 0.01), and adjacent lymph node was the highest. In Co 5-Fu i.v. group, the ranking was LN, CA, NG, PE, GO and LO with the former 3 tissues significantly higher than the latter 3 tissues (P < 0.01) and showing tumor tissues higher than the other tissues (P < 0.01). In 5-Fu i.p. group, the ranking was PE, LN, CA, NG, GO and LO with the former 2 tissues significantly higher than the latter tissues (P < 0.01). CONCLUSION: Co 5-Fu possesses drug targeting, slow release and long effect in gastric cancer tissues and adjacent lymph nodes. Preoperative chemotherapy with Co 5-Fu i.p. is more advantageous than 5-Fu given i.v. or 5-Fu i.p.