Comparison of blinatumomab and CAR T-cell therapy in relapsed/refractory acute lymphoblastic leukemia: a systematic review and meta-analysis.

OBJECTIVES: This study evaluated the benefits and risks of patients with refractory or relapsed acute lymphocytic leukemia (R/R ALL) treated with anti-CD19 chimeric antigen receptor (CAR) T-cell therapy and blinatumomab. METHODS: PubMed, Web of Science, Embase, and the Cochrane Library were searched for relevant studies. RESULTS: The pooled complete remission (CR) rate and minimal residual disease (MRD) negative rate were 48%, 31% for blinatumomab, and 86% and 80% for CAR T-cell therapy. CONCLUSIONS: The CAR T-cell therapy group exhibited a higher likelihood of CR rate than the blinatumomab group in every analysis regardless of adjustment subgroups. CAR T-cell therapy was associated with a significantly prolonged overall survival (OS) and relapse-free survival (RFS) compared with blinatumomab (2-year OS 55% vs 25%; 2-year RFS 40% vs 22%). CAR T-cell therapy was more effective for achieving CR and bridging to allogeneic hematopoietic stem cell transplantation (allo-SCT) than blinatumomab (2-year OS 75% vs. 57%). An emerging role for blinatumomab is as a bridging agent pre-SCT, and for patients who achieve an MRD-negative state pre-SCT, post-SCT outcomes are expected to be the same as CAR-T. For adverse effects (AEs), blinatumomab was associated with a lower rate of grade ≥3 hematological toxicity, CRS, and neurological events.

Biodegradation of Benzo[a]pyrene by a White-Rot Fungus Phlebia acerina: Surfactant-Enhanced Degradation and Possible Genes Involved.

Polycyclic aromatic hydrocarbons (PAHs) are persistent environmental pollutants that pose a threat to human health. Among these PAHs, benzo[a]pyrene (BaP), a five-ring compound, exhibits high resistance to biodegradation. White-rot fungus Phlebia acerina S-LWZ20190614-6 has demonstrated higher BaP degradation capabilities compared with Phanerochaete chrysosporium and P. sordida YK-624, achieving a degradation rate of 57.7% after 32 days of incubation under a ligninolytic condition. To further enhance the biodegradation rate, three nonionic surfactants were used, and the addition of 1 or 2 g·L-1 of polyethylene glycol monododecyl ether (Brij 30) resulted in nearly complete BaP biodegradation by P. acerina S-LWZ20190614-6. Interestingly, Brij 30 did not significantly affect the activity of manganese peroxidase and lignin peroxidase, but it did decrease laccase activity. Furthermore, the impact of cytochrome P450 on BaP degradation by P. acerina S-LWZ20190614-6 was found to be relatively mild. Transcriptomic analysis provided insights into the degradation mechanism of BaP, revealing the involvement of genes related to energy production and the synthesis of active enzymes crucial for BaP degradation. The addition of Brij 30 significantly upregulated various transferase and binding protein genes in P. acerina S-LWZ20190614-6. Hence, the bioremediation potential of BaP by the white-rot fungus P. acerina S-LWZ20190614-6 holds promise and warrants further exploration.

Corrigendum: Identification of microtube-associated biomarkers in diffuse large B-cell lymphoma and prognosis prediction.

[This corrects the article DOI: 10.3389/fgene.2022.1092678.].

EZH2 regulates pancreatic cancer cells through E2F1, GLI1, CDK3, and Mcm4.

Pancreatic cancer (PC) is one of the most common malignant tumors in digestive tract. To explore the role of epigenetic factor EZH2 in the malignant proliferation of PC, so as to provide effective medical help in PC. Sixty paraffin sections of PC were collected and the expression of EZH2 in PC tissues was detected by immunohistochemical assay. Three normal pancreas tissue samples were used as controls. The regulation of EZH2 gene on proliferation and migration of normal pancreatic cell and PC cell were determined by MTS, colony forming, Ki-67 antibody, scratch and Transwell assays. Through differential gene annotation and differential gene signaling pathway analysis, differentially expressed genes related to cell proliferation were selected and verified by RT-qPCR. EZH2 is mainly expressed in the nuclei of pancreatic tumor cells, but not in normal pancreatic cells. The results of cell function experiments showed that EZH2 overexpression could enhance the proliferation and migration ability of PC cell BXPC-3. Cell proliferation ability increased by 38% compared to the control group. EZH2 knockdown resulted in reduced proliferation and migration ability of cells. Compared with control, proliferation ability of cells reduced by 16%-40%. The results of bioinformatics analysis of transcriptome data and RT-qPCR demonstrated that EZH2 could regulate the expression of E2F1, GLI1, CDK3 and Mcm4 in normal and PC cells. The results revealed that EZH2 might regulate the proliferation of normal pancreatic cell and PC cell through E2F1, GLI1, CDK3 and Mcm4.

Identification of microtubule-associated biomarkers in diffuse large B-cell lymphoma and prognosis prediction.

Background: Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease with a complicated prognosis. Even though various prognostic evaluations have been applied currently, they usually only use the clinical factors that overlook the molecular underlying DLBCL progression. Therefore, more accurate prognostic assessment needs further exploration. In the present study, we constructed a novel prognostic model based on microtubule associated genes (MAGs). Methods: A total of 33 normal controls and 1360 DLBCL samples containing gene-expression from the Gene Expression Omnibus (GEO) database were included. Subsequently, the univariate Cox, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were used to select the best prognosis related genes into the MAGs model. To validate the model, Kaplan-Meier curve, and nomogram were analyzed. Results: A risk score model based on fourteen candidate MAGs (CCDC78, CD300LG, CTAG2, DYNLL2, MAPKAPK2, MREG, NME8, PGK2, RALBP1, SIGLEC1, SLC1A1, SLC39A12, TMEM63A, and WRAP73) was established. The K-M curve presented that the high-risk patients had a significantly inferior overall survival (OS) time compared to low-risk patients in training and validation datasets. Furthermore, knocking-out TMEM63A, a key gene belonging to the MAGs model, inhibited cell proliferation noticeably. Conclusion: The novel MAGs prognostic model has a well predictive capability, which may as a supplement for the current assessments. Furthermore, candidate TMEM63A gene has therapeutic target potentially in DLBCL.

Identification of Potential Biomarkers for Liver Cancer Through Gene Mutation and Clinical Characteristics.

Liver cancer is a common malignant tumor worldwide, which is a serious threat to the health of people. We try to investigate some mutations and clinical indicators as candidate markers for the development of liver cancer through targeted region capture technology combined with next-generation sequencing. We collected peripheral blood and liver cancer tissue samples from 32 liver patients concurrently. The SeqCap EZ Prime Choice Probe was used to perform the targeted enrichment; this probe captures 1,000 known cancer-associated genes. We calculated the tumor mutation burden (TMB) for each patient. The high-frequency mutations and these relative genes were identified. Eventually, survival analysis was performed based on the mutations and clinical indicators. In 32 liver patients, a total of 29 high-frequency mutations were investigated. They were located in 25 genes, which were enriched in 9 cellular components (CCs), 6 molecular functions (MFs), and 21 biological processes (BPs). Among them, EZH2 c.1544A>G and CCND1 c.839A>T had the highest mutation frequency (5/32). In the protein-protein interaction (PPI) network, EZH2-DNMT3A, NOTCH1-CCND1, and ABL1-CCND1 were the top three pairs. The survival analysis showed that there were significant differences in progression-free survival (PFS) and overall survival (OS) between the Karnofsky performance score (KPS) groups. The PFS and OS in the TMB high group were higher than those in the TMB low group. OS and tumor stage had a remarkable relationship. In conclusion, EZH2 c.1544A>G and CCND1 c.839A>T might be potential biomarkers of liver cancer. TMB might be used as a prognosis and survival indicator of liver cancer.

Intraperitoneal Chemotherapy Using Fluorouracil Implants Combined With Radical Resection and Postoperative Adjuvant Chemotherapy for Stage III Gastric Cancer: A Multi-Center, Randomized, Open-Label, Controlled Clinical Study.

BACKGROUND: Reducing peritoneal recurrence after radical surgery is an important choice to improve the prognosis of patients with advanced gastric cancer. Intraoperative intraperitoneal chemotherapy has the potential to be a promising treatment strategy. In the present study, we conducted a multi-center, randomized, controlled clinical study to evaluate the efficacy and safety of intraoperative intraperitoneal chemotherapy using sustained-release fluorouracil implants plus radical gastrectomy and adjuvant chemotherapy for cTNM stage III gastric cancer. METHODS: The patients were randomized into intraperitoneal chemotherapy group (sustained-release fluorouracil implants administration after standard D2 radical gastrectomy, and followed by XELOX adjuvant chemotherapy) and control group (standard D2 radical gastrectomy, and followed by XELOX adjuvant chemotherapy). A total of 122 patients from three centers were enrolled from September 2015 to February 2017. RESULTS: One hundred and two eligible patients completed the treatment course. The median follow-up time was 41.7 months (36.1-52.9 months). The 3-year progression-free survival rate and overall survival of patients in the intraperitoneal chemotherapy group were 43.9% and 49.1%, respectively, which were significantly better than those of the control group, 31.0% and 38.4%. In the intraperitoneal chemotherapy group, the number of cases with peritoneal recurrence was significantly less than that of the control group, 9 cases (17.3%) vs. 19 cases (44.2%). There were neither significant differences between the groups in the incidence of hematogenous metastasis, lymph node metastasis, nor local metastasis. CONCLUSION: For cTNM stage III gastric cancer, intraoperative sustained-release fluorouracil implants after radical resection combined with postoperative adjuvant chemotherapy, could significantly reduce the risk of peritoneal recurrence and prolong PFS.Clinical Trial Registration: https://clinicaltrials.gov/, identifier (NCT02269904).

A Preliminary Study on the Establishment of the PDTX Model.

OBJECTIVE: The current study aims to explore the establishment of the patient-derived tumor xenograft (PDTX) model. MATERIALS AND METHODS: Twenty patients with gastric cancer, 10 males and 10 females, were enrolled in the current study. Firstly, the volume, invasion and metastasis of the xenografts were observed. Subsequently, the correlation between tumor tissues of the PDTX mouse model and the patients' primary tumor tissues was evaluated by pathological H&E staining and immunohistochemistry. RESULTS: The results showed that the PDTX models corresponding to 15 of the 20 patients were successfully established, and the success rate of PDTX model establishment was 75%. Furthermore, the PDTX models maintained the differentiation degree, morphological characteristics and structural characteristics of tumor cells. CONCLUSION: A PDTX model can be used as a substitute for cancer patients in clinical practice and may be suitable for clinical pharmacodynamic screening and new drug development.

Piperlongumine inhibits gastric cancer cells via suppression of the JAK1,2/STAT3 signaling pathway.

Piperlongumine (PL), a major active component of long peppers, has been reported to possess anti­cancer properties; however, its effect on gastric cancer (GC) has remained to be demonstrated. The present study assessed the effects of PL on the MKN45 and AGS GC cell lines and explored the underlying mechanisms. An MTT assay revealed that PL suppressed the proliferation of GC cells, while flow cytometric analysis showed that PL inhibited cell cycle progression. Furthermore, Transwell assays revealed the inhibitory effects of PL on the invasion and migration of GC cells. In addition, PL reduced the phosphorylation of Janus kinase (JAK)1, JAK2 and signal transducer and activator of transcription (STAT)3 in a concentration­dependent manner, as indicated by western blot analysis, and decreased the expression of STAT3­dependent tumor­associated genes in GC cells, as revealed by PCR analysis. In conclusion, the present study was the first, to the best of our knowledge, to reveal the efficacy of PL against GC. The consumption of long peppers is therefore recommended for the prevention and treatment of GC, and PL may be a promising candidate drug for treating GC.

Knockdown of CUL4B inhibits proliferation and promotes apoptosis of colorectal cancer cells through suppressing the Wnt/ß-catenin signaling pathway.

Colorectal cancer is one of the leading causes of cancer related deaths worldwide. Cullin 4B (CUL4B) is over-expressed in diverse cancer types. However, the function and precise molecular mechanism of CUL4B in colorectal cancer remains largely unknown. Therefore, in this study, we examined the expression of CUL4B in colorectal cancer cell lines and its effects on cellular proliferation and apoptosis, and the underlying mechanism was also explored. Our results showed that CUL4B was significantly overexpressed in colorectal cancer cell lines. Silencing CUL4B obviously inhibited proliferation and tumorigenicity of colorectal cancer cells both in vitro and in vivo, and it also promoted the apoptosis of colorectal cancer cells. Moreover, knockdown of CUL4B inhibited the expression of ß-catenin, cyclin D1 and c-Myc in colorectal cancer cells. Taken together, these results showed that knockdown of CUL4B inhibit proliferation and promotes apoptosis of colorectal cancer cells through suppressing the Wnt/ß-catenin signaling pathway. Therefore, CUL4B may represent a novel therapeutic target for colorectal cancer treatment.

[Effect of perioperative blood transfusion on the prognosis of gastric cancer].

OBJECTIVE: To explore the association of perioperative blood transfusion (PBT) with survival of gastric cancer after surgery. METHODS: We retrospectively reviewed the medical records of 1 000 gastric cancer patients, including 738 non-transfused (73.8%) and 262 transfused (26.2%) cases. A one to one match was created using propensity score analysis, except preoperative hemoglobin level and operative blood loss. The survival was analyzed by Kaplan-Meier survival model. RESULTS: The 5-year survival rate of the 1 000 cases of gastric cancer patients was 39.9%. Before matching, there was a significant difference between transfused group (33.6%) and non-transfused group (49.1%, P<0.005). Univariate analysis showed that age, tumor size, hemoglobin level, albumin level, depth of invasion, lymph node metastasis, lymph node dissection, surgery mode, adjuvant chemotherapy, blood loss and blood transfusion during perioperative period were associated with prognosis in the gastric cancer patients (all P<0.05). Multivariate analysis showed that tumor invasion, lymph node metastasis, lymph node dissection, chemotherapy and perioperative blood transfusion were independent prognostic factors in gastric cancer (all P<0.05). After matching, the 5-year survival rate of the 262 non-transfused patients was 37.7%, while that of the 262 transfused patients was 33.6% (P>0.05). CONCLUSIONS: Perioperative blood transfusion has no significant effect on the prognosis of gastric cancer patients.

[Interim report of prospective clinical study of two different digestive tract reconstruction after total gastrectomy].

OBJECTIVE: To compare post-operative long-term complications and quality of life of two digestive reconstruction procedures after total gastrectomy. METHODS: A total of 109 gastric cancer patients in Tianjin Medical University Cancer Hospital from March 2012 to February 2013 were prospectively enrolled and randomly divided into functional jejunal interposition (FJI) group (52 cases) and Roux-en-Y (R-Y) group (57 cases). The post-operative complications, nutritional status, and the quality of life were compared between two groups. RESULTS: One, 3 and 6 months after operation, the incidence of R-S syndrome in FJI group was lower as compared to R-Y group[13% (6/45) vs. 37% (18/49), 3% (1/30) vs. 42% (14/33), 5% (1/21) vs. 48% (11/23), all P<0.01], while 3 months after operation, the incidence of reflux and heartburn in FJI group was higher[53% (16/30) vs. 21% (7/33), P<0.01; 37% (11/30) vs. 12% (4/33), P<0.05]. There were no significant differences in quality of life questionnaire QLQ-C30 between R-Y and FJI groups. QLQ-STO22 stomach module revealed in FJI group, the eating score was better, but reflux score was worse as compared to R-Y group 3 months after operation (all P<0.01). CONCLUSIONS: Functional jejunal interposition keeps intestinal continuity preserving and food duodenal passing, which is a reasonable digestive reconstruction procedure.

Expression of Rac1, HIF-1α, and VEGF in gastric carcinoma: correlation with angiogenesis and prognosis.

BACKGROUND: The aim of this study was to investigate the relationship between the expression of hypoxia-inducible factor-1α (HIF-1α), Ras-related C3 botulinum toxin substrate 1 (Rac1), and vascular endothelial growth factor (VEGF), as well as their correlation with angiogenesis and prognosis in gastric carcinoma. MATERIAL AND METHODS: The expression of Rac1, HIF-1α, VEGF, and CD34 (described in terms of microvessel density, MVD) was determined by immunohistochemical staining of tissues from 60 radically resected gastric cancer specimens. RESULTS: The proportion of specimens expressing Rac1, HIF-1α, and VEGF was 37/60 (61.7%), 35/60 (58.3%), and 40/60 (66.7%), respectively. The levels of Rac1, HIF-1α, and VEGF expression were significantly correlated with Lauren's classification, lymph node metastasis, and pathologic staging (p < 0.05). There were positive correlations between MVD and the expression of Rac1, HIF-1α, and VEGF. The mean survival time and 5-year survival rate in cases with positive Rac1, HIF-1α, and VEGF expression and MVD ≥ 26.3 were significantly shorter than those with negative Rac1, HIF-1α, and VEGF expression and MVD < 26.3. CONCLUSION: Rac1, HIF-1α, and VEGF play an important role in tumor invasion and metastasis, especially in tumor angiogenesis. Thus, testing the expression of Rac1, HIF-1α, and VEGF may be a useful index for treatment and prognosis.

Prognosis of gastric cancer patients with node-negative metastasis following curative resection: outcomes of the survival and recurrence.

BACKGROUND: The purpose of the present study was to provide valuable prognostic information on lymph node-negative gastric cancer patients following curative resection. METHODS: Data from 112 lymph node-negative gastric cancer patients who underwent curative resection were reviewed to identify the independent factors of overall survival and recurrence. RESULTS: The five-year survival rate of lymph node-negative gastric cancer patients was 85.7%, and recurrence was identified in 25 patients after curative surgery. The five-year survival rate of lymph node-negative gastric cancer patients was higher than that of lymph node-positive gastric cancer patients (P<0.001). Recurrence in lymph node-negative gastric cancer patients was less than that of lymph node-positive gastric cancer patients (P=0.001). The median survival after recurrence of lymph node-negative gastric cancer patients was longer than that of lymph node-positive gastric cancer patients (P=0.021). Using multivariate analyses, the following results were determined for lymph node-negative gastric cancer patients: sex, operative type and the presence of serosal involvement were independent factors of overall survival; and lymphadenectomy, number of dissected nodes and the presence of serosal involvement were independent factors of recurrence. CONCLUSIONS: The prognosis of lymph node-negative gastric cancer patients was better than that of lymph node-positive gastric cancer patients. Male sex, subtotal gastrectomy and nonserosal involvement should be considered to be the favourable predictors of postoperative long-term survival of lymph node-negative gastric cancer patients. Conversely, limited lymphadenectomy, few dissected nodes and serosal involvement should be considered to be risk factors of postoperative recurrence of lymph node-negative gastric cancer patients.

The most appropriate category of metastatic lymph nodes to evaluate overall survival of gastric cancer following curative resection.

AIMS: The purpose of this study was to provide a nodal grouping category based on metastatic lymph nodes to evaluate overall survival in gastric cancer patients following curative resection (R0). PATIENTS AND METHODS: We reviewed data of 308 gastric cancer patients following curative resection to evaluate significantly survival differences in different categories of the number of metastatic lymph nodes. RESULTS: In 308 evaluable patients, 5-year survival rate (YSR) was 52.9% (median follow-up, 84 months; range, 6-144 months). A total of 6309 lymph nodes were harvested and examined from all 308 patients, and the average number of lymph nodes harvested for per patient was 20.5 (range, 15-49). The average number of metastatic lymph nodes was 5.4 (range, 0-37) per patient. The initial metastatic node cutoffs were designed as 0, 1-4, 5-8, 9-11, 12-16, and >or=17. According to this new category of the number of metastatic lymph nodes, the 5-YSR of various patient groups were 85.7%, 62.8%, 34.3%, 0%, 0%, and 3.4%, respectively. However, we found that there were not significant prognostic differences between patients with 9 metastatic lymph nodes and patients with more than 9 metastatic lymph nodes (P > 0.05). So we redesigned the later cutoffs of number of metastatic lymph nodes. They were as follows: 0, 1-4, 5-8, and >or=9 of metastatic lymph nodes. We demonstrated this new category of the number of metastatic lymph nodes was more appropriate to evaluate overall survival of gastric cancer patients following curative resection than anyone of the current metastatic lymph nodal stagings (such as N stag in UICC, location of metastatic lymph nodes in JCGC, or ratio of metastatic lymph nodes) by using the case-control matched fashion. CONCLUSIONS: Our new category of the number of metastatic lymph nodes was an important prognostic factor of gastric cancer patients following curative resection. There were significant overall survival differences in gastric cancer patient groups with various numbers of metastatic lymph nodes following curative resection.

[Expression change of apoptosis-associated genes after hyperthermia, chemotherapy and radiotherapy in human colon cancer-transplanted nude mice].

OBJECTIVE: To investigate the expression change of apoptosis-associated genes in human colon cancer cells transplanted into nude mice after hyperthermia, chemotherapy and radiotherapy. METHODS: Human colon cancer cell line HT29 was transplanted into the hind limbs of nude mice. Under the laboratory-simulated condition of hyperthermia(43 degree centigrade, 60 min), actual radiation doses and MMC doses were calculated in reference to the clinical practice. The mice were divided into 6 groups according to the treatment approaches: hyperthermia (group A), chemotherapy (group B), radiotherapy (group D), thermochemotherapy (group C), thermoradiotherapy (group E) and thermochemoradiotherapy (group F). The mice were sacrificed at different time points and the tumor tissues were taken for further procedures. The morphologic changes of P53, Bcl-2 and Bax expression in membrane, cytoplasm and nucleus of tumor cell after treatment were observed by immunohistochemistry stain (SP method). RESULTS: All of the six approaches of treatment could down-regulate the expression of P53 and Bcl-2, and up-regulate the expression of Bax in different levels. There was no significant difference in the amount of reduction of P53 expression among group A, C and E. The extent of reduction in the above mentioned groups was significantly different as compared to group B and D. By comparing to group D, the extent of reduction of P53 expression was greater in group B. Down-regulation of Bcl-2 could be enhanced when hyperthermia was combined with chemotherapy (group C) or radiation (group E), but more obvious down-regulation was found in group E as compared to group C. Hyperthermia itself could not obviously up-regulate Bax expression, and it occurred at last. Bax expression increased more by chemotherapy treatment (group B) than that by radiation (group D). By comparing to group C, the greater increase occurred in group E. CONCLUSIONS: Hyperthermia enhances the effects of radiosensitivity and chemosensitivity on tumors by changing the expression of apoptosis-associated genes P53, Bcl-2 and Bax. Hyperthermia combined with chemotherapy and/or radiation has a greater effect on down-regulation of P53 and Bcl-2 expression and up-regulation of Bax expression than any single therapy.

Analysis of risk factors for the interval time, number and pattern of hepatic metastases from gastric cancer after radical gastrectomy.

AIM: To analyze the risk factors for interval time, number and pattern of hepatic metastases from gastric cancer after radical gastrectomy, and provide evidence for predicting and preventing hepatic metastasis from gastric cancer after radical gastrectomy. METHODS: A retrospective study of 87 patients with hepatic metastasis who underwent radical gastrectomy for gastric cancer from 1996 to 2001. The data was analyzed to evaluate significant risk factors for interval time, number and pattern of hepatic metastases originating from gastric cancer after radical gastrectomy. RESULTS: The size of gastric cancer and lymph node metastases were independently correlated with the interval time of hepatic metastases; the depth of invasion was independently correlated with the number of hepatic metastases; while the depth of invasion and Lauren classification were independently correlated with the pattern of hepatic metastases. CONCLUSION: We evaluated the interval time of hepatic metastases with the size of gastric cancer and lymph node metastases. The depth of invasion could be used to evaluate the number of hepatic metastases, while the depth of invasion and the Lauren classification could be used to evaluate the pattern of hepatic metastases in patients who underwent radical gastrectomy.

[Prognostic analysis of liver metastasis in gastric cancer patients with radical gastrectomy].

OBJECTIVE: To elucidate the prognostic factors of liver metastasis in gastric cancer patients with radical gastrectomy. METHODS: Clinicopathological data of 87 liver metastasis patients, undergone radical gastrectomy for gastric cancer from 1996 to 2001, were retrospectively analyzed. RESULTS: Of these 87 patients, the 1-, 3- and 5-year survival rates were 28.8%, 3.6% and 0 respectively and the average survival time after gastrectomy was (11.3+/-1.1) months. By univariate analysis, tumor location, tumor size, histologic differentiation, invasive depth, Lauren classification, metastasis of lymph nodes from lymphadenectomy, vascular invasion, nervous invasion, peritoneal metastasis, number of liver metastasis, liver metastatic distribution and resection of liver metastasis were found to be significant factors associated with the prognosis of liver metastatic patients after radical gastrectomy. By multivariate analysis, location, the Lauren classification, liver metastatic distribution and resection of liver metastasis were found to be independent factors associated with hepatic metastasis after radical gastrectomy. CONCLUSION: Location of gastric cancer, Lauren classification, liver metastatic distribution and resection of liver metastasis are important factors to evaluate the prognosis of liver metastasis in gastric cancer patients with radical gastrectomy.

Change in expression of apoptosis genes after hyperthermia, chemotherapy and radiotherapy in human colon cancer transplanted into nude mice.

AIM: To investigate the change in expression of p53, Bcl-2, and Bax genes in human colon cancer cells transplanted into nude mice after hyperthermia, chemotherapy, radiotherapy, thermochemotherapy, thermoradiotherapy and thermochemoradiotherapy. METHODS: Human colon cancer cell line (HT29) was transplanted into the hind limbs of nude mice. Under laboratory simulated conditions of hyperthermia (43 centigrade, 60 min), the actual radiation doses and doses of mitomycin C (MMC) were calculated in reference to the clinical radiotherapy for human rectal cancer and chemotherapy prescription for colon cancer. The mice were divided into 6 groups according to the treatment approaches: hyperthermia, chemotherapy, radiotherapy, thermochemotherapy, thermoradiotherapy, and thermochemoradiotherapy. The mice were sacrificed at different time points and the tumor tissue was taken for further procedures. The morphologic changes in membrane, cytoplasm and nuclei of tumor cells of p53, Bcl-2, and Bax after treatment, were observed by immunohistochemistry staining. RESULTS: All of the six treatment modalities down-regulated the expression of p53, Bcl-2 and up-regulated the expression of Bax at different levels. The combined therapy of hyperthermia, with chemotherapy, and/or irradiation showed a greater effect on down-regulating the expression of p53 (0.208 +/- 0.009 vs 0.155 +/- 0.0115, P < 0.01) and Bcl-2 (0.086 +/- 0.010 vs 0.026 +/- 0.0170, P < 0.01) and up-regulating Bax expression (0.091 +/- 0.0013 vs 0.207 +/- 0.027, P < 0.01) compared with any single therapy. CONCLUSION: Hyperthermia enhances the effect of radio- and chemotherapy on tumors by changing the expression of apoptosis genes, such as p53, Bcl-2 and Bax.

Non-taxane compounds from the bark of Taxus yunnanensis.

From the bark of Taxus yunnanensis, 15 non-taxane compounds were isolated. Through spectroscopic methods such as ID and 2D NMR and MS experiments, one of them was determined as a new abietane-type diterpenoid named taxayunnin (1). The other 14 known compounds were identified as taxamairin C (2), taxamairin A (3), 3beta-hydroxy-sandaracopimaric acid (4), (+)-3-hydroxy-isodrimenin (5), rubrosterone (6), ponasterone A (7), ecdysterone (8), 20-hydroxy-echysone-20,22-monoacetonide (9), 7-oxositosterol (10), stigmast-4-en-6beta-ol-3-one (11), 5alpha,6beta-dihydroxy-daucosterol (12), beta-sitosterol (13), daucosterol (14), 1-O-beta-D-glucopyranosyl-(2S, 3R, 4E, 8Z)-2-N-(2'-hydroxypalmitoy])-octadeca-sphinga-4,8-dienine (15), respectively. Compounds 4-6, 9-12 and 15 were isolated from Taxus plants for the first time.