Radiotherapy in the preoperative neoadjuvant treatment of locally advanced rectal cancer.

Radiotherapy and chemotherapy are effective treatments for patients with locally advanced rectal cancer (LARC) and can significantly improve the likelihood of R0 resection. Radiotherapy can be used as a local treatment to reduce the size of the tumor, improve the success rate of surgery and reduce the residual cancer cells after surgery. Early chemotherapy can also downgrade the tumor and eliminate micrometastases throughout the body, reducing the risk of recurrence and metastasis. The advent of neoadjuvant concurrent radiotherapy (nCRT) and total neoadjuvant treatment (TNT) has brought substantial clinical benefits to patients with LARC. Even so, given increasing demand for organ preservation and quality of life and the disease becoming increasingly younger in its incidence profile, there is a need to further explore new neoadjuvant treatment options to further improve tumor remission rates and provide other opportunities for patients to choose watch-and-wait (W&W) strategies that avoid surgery. Targeted drugs and immunologic agents (ICIs) have shown good efficacy in patients with advanced rectal cancer but have not been commonly used in neoadjuvant therapy for patients with LARC. In this paper, we review several aspects of neoadjuvant therapy, including radiation therapy and chemotherapy drugs, immune drugs and targeted drugs used in combination with neoadjuvant therapy, with the aim of providing direction and thoughtful perspectives for LARC clinical treatment and research trials.

Comprehensive Analysis Identifies PI3K/Akt Pathway Alternations as an Immune-Related Prognostic Biomarker in Colon Adenocarcinoma Patients Receiving Immune Checkpoint Inhibitor Treatment.

Introduction: In recent years, immune checkpoint inhibitors (ICIs) have attracted widespread attention and made breakthroughs in progress towards the treatment of various cancers. However, ICI therapy is selective, and its effects on many patients are not ideal. It is therefore critical to identify prognostic biomarkers of response to ICI therapy. The PI3K/Akt pathway plays important roles in tumor formation and metastasis. However, there are no published reports clarifying the relationship between PI3K/Akt pathway mutations and prognosis for colon adenocarcinoma (COAD) patients receiving immunotherapy. Methods: We collected data from a COAD cohort from The Cancer Genome Atlas (TCGA) database, including whole-exome sequencing (WES) data, RNA-seq data, and clinical data. We also collected data, including clinical prognosis and targeted sequencing data, from a cohort of COAD patients receiving immunotherapy. We collected 50 COAD patients (Local-COAD) from the Zhujiang Hospital of Southern Medical University and performed targeted sequencing. We analyzed the effects of PI3K/Akt pathway mutations on the patients' clinical prognosis, immunogenicity, and immune microenvironments. Gene set enrichment analysis (GSEA) was used to analyze the significantly upregulated and downregulated signaling pathways. We used these results to hypothesize potential mechanisms by which PI3K/Akt mutations could affect the prognosis of COAD patients. Results: Univariate and multivariate Cox analyses and Kaplan-Meier (KM) survival curves showed that patients with PI3K-Akt mutations had better overall survival (OS) than those without PI3K-Akt mutations. Genes with significant mutation rates in the two cohorts were screened by panoramic view. CIBERSORT was used to analyze changes in 22 types of immune cells to identify immune activated cells. Similarly, patients in the PI3K/Akt-mutated type (PI3K/Akt-MT) group had significantly increased immunogenicity, including increases in tumor mutation burden (TMB), neoantigen load (NAL), and MANTIS score. Using GSEA, we identified upregulated pathways related to immune response. Conclusion: PI3K/Akt pathway mutation status can be used as an independent predictor of response to ICI treatment in COAD patients. PI3K/Akt mutations are correlated with improved OS, higher immunogenicity, greater immune response scores, and increases in activated immune cells.

Age, sex, and specific gene mutations affect the effects of immune checkpoint inhibitors in colorectal cancer.

The effect of age and sex on the predictive value of colorectal cancer (CRC) patients treated with immune checkpoint inhibitors (ICIs) has been controversial, and the effect of specific gene mutations on the predictive value of CRC patients treated with ICIs remains to be explored. Our study analyzed the influence of the above factors on the overall survival (OS) of CRC patients receiving ICIs and explored the influencing mechanism of various predictive biomakers. We performed survival prognostic correlation analysis and bioinformatics analysis on the clinical CRC cohort receiving ICIs in from the Memorial Sloan Kettering Cancer Center (MSKCC) and the clinical and genetic data from The Cancer Genome Atlas (TCGA)-CRC dataset, including immunogenicity analysis, tumor immune microenvironment analysis, and gene set enrichment analysis and so on. We found that mutation count >11 mutation/Mb (tumor mutation burden, TMB-high) (HR = 0.22, 95 %CI: 0.09-0.53; P < 0.001), male (HR = 0.51, 95 %CI: 0.28-0.93; P = 0.029), RNF43-mutant (MT) (HR = 0.12, 95 %CI: 0.03-0.49; P = 0.003), CREBBP-MT (HR = 0.23, 95 %CI: 0.07-0.76; P = 0.016), NOTCH3-MT (HR = 0.17, 95 %CI: 0.04-0.74; P = 0018), PTCH1-MT (HR = 0.27, 95 %CI: 0.08-0.9; P = 0.033), CIC-MT (HR = 0.23, 95 %CI: 0.05-0.93; P = 0.040), DNMT1-MT (HR = 0.12, 95 %CI: 0.02-0.93; P = 0.043) and SPEN-MT (HR = 0.31, 95 %CI: 0.09-0.99; P < 0.049) are all related to longer OS, but age≤65 years (HR = 3.01, 95 %CI: 1.18-7.65; P = 0.021), APC-MT (HR = 2.51, 95 %CI: 1.12-5.63; P = 0.026) and TP53-MT (HR = 1.94, 95 %CI: 1.03-3.65; P = 0.041) are associated with shorter OS. The reason why positive predictive markers provide survival benefits to CRC may be related to higher immunogenicity such as TMB, highly expression of mRNA related to immune response, highly infiltrating immune-active cells such as CD8 + T cells, active immune-active pathways, and DNA damage repair pathways with an increased number of mutations.

Anti-tumor efficacy of phellamurin in osteosarcoma cells: Involvement of the PI3K/AKT/mTOR pathway.

The extracts of Phellodendron amurense (P. amurense) have been shown to contain many active ingredients e.g. flavone glycosides and to exert a wide range of physiological activities including anti-tumor activity. However, the effects of phellamurin (Phe), a plant flavonone glycoside from the leaves of P. amurense, on osteosarcoma (OS) have never been reported. The effects of Phe on cell viability and apoptosis were evaluated by MTT assay and flow cytometry analysis, respectively. Western blot analysis was performed to detect the protein levels of phosphorylated phosphatidylinositol 3 kinase (PI3K) (p-PI3K), phosphorylated protein kinase B (AKT) (p-AKT), AKT, phosphorylated mammalian target of rapamycin (mTOR) (p-mTOR), and mTOR. We found that Phe suppressed the viability and promoted apoptosis in OS cells in a dose-dependent manner. Notably, Phe repressed the PI3K/AKT/mTOR pathway in OS cells. LY294002 effectively inhibited the PI3K/AKT/mTOR signaling pathway, repressed cell viability and induced apoptosis in OS cells. Activation of PI3K/AKT/mTOR pathway by 740Y-P abolished the effects of Phe on the viability and apoptosis of OS cells. We also found that Phe repressed OS tumor growth and inhibited the PI3K/AKT/mTOR pathway in vivo. In conclusion, Phe suppressed the viability and induced apoptosis in OS cells, at least, partially by inhibiting the PI3K/AKT/mTOR pathway. Our study suggested that Phe might be a new and potential chemotherapeutic agent for the treatment of OS.

Ribophorin II potentiates P-glycoprotein- and ABCG2-mediated multidrug resistance via activating ERK pathway in gastric cancer.

Multidrug resistance (MDR) is a critical reason of cancer chemotherapy failure. Ribophorin II (RPN2) has emerged as a vital regulator of MDR in multiple cancers including gastric cancer (GC). However, the roles and molecular mechanisms of RPN2 in MDR have not been well featured till now. The present study aimed to explore the roles and molecular mechanisms of RPN2 in MDR of drug-resistant GC cells. Results showed that the expressions of RPN2, multidrug resistance 1 (MDR1), and ATP binding cassette subfamily G member 2 (ABCG2) were upregulated in SGC7901/DDP and SGC7901/VCR cells. Knockdown of RPN2 alleviated MDR through downregulating MDR1 and ABCG2 expressions in SGC7901/DDP and SGC7901/VCR cells. RPN2 depletion inhibited the activation of MEK/ERK pathway. RPN2 overexpression enhanced MDR by upregulating P-glycoprotein (P-gp) and ABCG2 protein expressions in SGC7901/DDP or SGC7901/VCR cells, while this effect of RPN2 was abrogated by ERK knockdown or treatment with ERK inhibitor PD98059. Our findings suggested that RPN2 potentiated P-gp- and ABCG2-mediated MDR via activating MEK/ERK pathway in GC, hinting the critical values of RPN2 in ameliorating MDR and providing a promising target for GC therapy.

miR-4262, low level of which predicts poor prognosis, targets proto-oncogene CD163 to suppress cell proliferation and invasion in gastric cancer.

BACKGROUND: miR-4262 was identified as a tumor promoter in several cancers, but its exact role in gastric carcinoma is still largely unknown. METHODS: The expression of miR-4262 was detected in gastric cancer tissues. Different concentrations of miR-4262 mimic and miR-4262 antagomir were respectively transfected into primary gastric carcinoma cells. After incubation for 72 h, the overexpression efficiencies were confirmed by qPCR, cell proliferation was detected with the CCK-8 assay, cell apoptosis was detected by using the PI/Annexin V Cell Apoptosis Kit, and cell invasion was detected with the Transwell invasion assay. The molecular mechanisms underlying the action of miR-4262 in gastric carcinoma cells were also explored. RESULTS: In this study, we found that miR-4262 was significantly downregulated in gastric tissue from gastric cancer patients compared with that from the control group. Moreover, the level of miR-4262 was significantly lower in advanced gastric carcinoma. Additionally, lower level of miR-4262 was correlated with poorer prognosis and lower survival rate in gastric cancer patients. Then, different concentrations of miR-4262 mimic and miR-4262 antagomir were transfected into primary gastric carcinoma cells, respectively. The results showed that miR-4262 mimic suppressed proliferation and invasion and promoted cell apoptosis in a dose-dependent manner in gastric carcinoma cells. In contrast, miR-4262 antagomir increased proliferation and invasion and decreased cell apoptosis in a dose-dependent manner in gastric carcinoma cells. Furthermore, miR-4262 could directly target and suppress the expression of the proto-oncogene CD163. CONCLUSION: Our findings indicate that lower level of miR-4262 predicts poorer prognosis in gastric patients, and miR-4262 can target proto-oncogene CD163 to suppress gastric cancer cell proliferation and invasion.

Knockdown of long non-coding RNA XIST inhibits cell viability and invasion by regulating miR-137/PXN axis in non-small cell lung cancer.

Long non-coding RNAs (lncRNAs) may serve as miRNA sponges to modulate the expressions of miRNA target genes. LncRNA X-inactive specific transcript (XIST) has been demonstrated to be upregulated and act as an oncogene in non-small cell lung cancer (NSCLC). However, the sponge role of XIST in NSCLC progression remains largely unknown. In this study, we demonstrated that XIST was substantially upregulated and miR-137 was aberrantly downregulated in NSCLC tissues and cells. XIST was identified to function as a competitive endogenous RNA (ceRNA) for miR-137 to promote NSCLC cell viability and invasion. Additionally, our results suggested that miR-137 targeted the 3'UTR of paxillin (PXN) to suppress NSCLC cell viability and invasion. Meanwhile, miR-137 was negatively correlated with PXN expression while XIST was positively correlated with PXN expression. More importantly, XIST positively regulated PXN levels by sponging miR-137 in vitro and in vivo. Collectively, our study provided the evidence for the cross-talk between XIST, miR-137, and PXN, shedding light on the therapy for NSCLC.

Inhibition of Notch1/Hes1 signaling pathway improves radiosensitivity of colorectal cancer cells.

Notch signaling pathway has been demonstrated to mediate radioresistance of several tumors. Our study aims to explore the function of Notch1/HES1 pathway in the radioresistance of colorectal cancer (CRC). The results demonstrated that expressions of Notch1 and Hes1 were up-regulated with the increasing irradiation dose. DAPT (N-[(3,5-difluorophenacetyl)acety1]-L-alanyl-2-phenyl]glycine-1,1-dimethylethyl ester) or si-Notch1 reduced expressions of Notch1 and Hes1, exacerbated irradiation-induced cell proliferation inhibition, and improved radiosensitivity of CRC cells. Moreover, DAPT or si-Notch1 increased radiation-induced DNA damage and attenuated radiation-triggered DNA-PK activity. Furthermore, xenograft in nude mice demonstrated that co-treated with DAPT and irradiation could inhibited tumor growth additively in vivo. Taken together, inhibition of Notch1/Hes1 signaling pathway enhances radiosensitivity of CRC cells, providing a potential therapeutic target to improve the therapeutic effect of radiotherapy for CRC patients.

Knockdown of Lncrna PVT1 Enhances Radiosensitivity in Non-Small Cell Lung Cancer by Sponging Mir-195.

BACKGROUND/AIMS: Plasmacytoma variant translocation 1 (PVT1) exerts an oncogenic role in many tumors, including lung cancer. However, the roles of PVT1 in regulating radiosensitivity of NSCLC and its underlying mechanism are still unclear. METHODS: Expression levels of PVT1 and miR-195 in NSCLC tissues and cells were examined by qRT-PCR. Effects of PVT1 and miR-195 on cell proliferation, apoptosis and colony formation abilities were assessed by MTT assay, flow cytometry and colony formation assay. Luciferase reporter assay was performed to confirm the relationship between PVT1 and miR-195. Tumor xenograft experiments were conducted to observe the effect of PVT1 on radiosensitivity of NSCLC in vivo. RESULTS: PVT1 was negatively correlated with miR-195 expression in NSCLC tissues and associated with poor prognosis of NSCLC patients. Expression of PVT1 and miR-195 varied inversely after irradiation in NSCLC cells. PVT1 knockdown or miR-195 overexpression enhanced radiosensitivity of NSCLC in vitro by inhibiting proliferation and inducing apoptosis. PVT1 directly interacted with miR-195 and regulated its expression. Moreover, PVT1 knockdown improved radiosensitivity of NSCLC cells in vitro and in vivo by sponging miR-195. CONCLUSION: Knockdown of PVT1 enhances radiosensitivity of NSCLC by sponging miR-195, providing a novel therapeutic target to improve radiotherapy efficiency in NSCLC.

Down-regulation of LncRNA TUG1 enhances radiosensitivity in bladder cancer via suppressing HMGB1 expression.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been reported to regulate the sensitivity of different cancer cells to chemoradiotherapy. Aberrant expression of lncRNA Taurine-upregulated gene 1 (TUG1) has been found to be involved in the development of bladder cancer, however, its function and underlying mechanism in the radioresistance of bladder cancer remains unclear. METHODS: Quantitative real-time PCR (qRT-PCR) was conducted to measure the expression of TUG1 and HMGB1 mRNA in bladder cancer tissues and cell lines. HMGB1 protein levels were tested by western blot assays. Different doses of X-ray were used for radiation treatment of bladder cancer cells. Colony survival and cell viability were detected by clonogenic assay and CCK-8 Kit, respectively. Cell apoptosis was determined by flow cytometry. A xenograft mouse model was constructed to observe the effect of TUG1 on tumor growth in vivo. RESULTS: The levels of TUG1 and HMGB1 were remarkably increased in bladder cancer tissues and cell lines. Radiation treatment markedly elevated the expression of TUG1 and HMGB1. TUG1 knockdown inhibited cell proliferation, promoted cell apoptosis and decreased colony survival in SW780 and BIU87 cells under radiation. Moreover, TUG1 depletion suppressed the HMGB1 mRNA and protein levels. Furthermore, overexpression of HMGB1 reversed TUG1 knockdown-induced effect in bladder cancer cells. Radiation treatment dramatically reduced the tumor volume and weight in xenograft model, and this effect was more obvious when combined with TUG1 silencing. CONCLUSION: LncRNA TUG1 knockdown enhances radiosensitivity of bladder cancer by suppressing HMGB1 expression. TUG1 acts as a potential regulator of radioresistance of bladder cancer, and it may represent a promising therapeutic target for bladder cancer patients.

Downregulation of lncRNA ANRIL inhibits proliferation, induces apoptosis, and enhances radiosensitivity in nasopharyngeal carcinoma cells through regulating miR-125a.

Increasing evidence demonstrated that long non-coding RNA ANRIL serves as a fatal oncogene in many cancers, including nasopharyngeal carcinoma (NPC). However, little is known whether ANRIL regulated NPC cell radioresistance. Quantitative real-time PCR (qRT-PCR) was performed to examine the expression of lncRNA ANRIL and miR-125a in NPC tissues and cell lines. MTT assay was conducted to measure the cell viability of CNE2 and HONE1 cells. The apoptotic rate of CNE2 and HONE1 cells was determined by flow cytometry analysis. Colony survival was determined by clonogenic assay. Luciferase reporter assay was performed to verity the direct target of miR-125a. LncRNA ANRIL was evidently elevated in NPC tissues and cell lines. ANRIL inhibition suppressed proliferation, induced apoptosis, and enhanced radiosensitivity in NPC. Moreover, ANRIL could negatively modulate miR-125a expression. Furethermore, ANRIL upregulation reserved the inhibited proliferation, induced apoptosis, and enhanced radiosensitivity triggered by miR-125a overexpression. The expression of lncRNA ANRIL was upregulated in NPC tissues and cells. Moreover, knockdown of ANRIL repressed proliferation, promoted apoptosis, and improved radiosensitivity in NPC via functioning as a miR-125a sponge.

A meta-analysis of Shenqi Fuzheng combined with radiation in the treatment of nonsmall cell lung cancer.

OBJECTIVE: The objective of this study is to evaluate the efficacy and toxicity reduction of Shenqi Fuzheng injection in the treatment of nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: Through searching the PubMed, WANFANG and CNKI, we recruited clinical trials related to Shenqi Fuzheng combined with radiation in the treatment of NSCLC. We extracted the treatment effective data and radiation related toxicities data. The clinical efficacy and radiation toxicity was pooled by meta-analysis. The statistical heterogeneity was evaluated by I 2 tests. RESULTS: By searching the related databases, we finally included 7 studies in this meta-analysis. The pooled results indicated that Shenqi Fuzheng injection can improve the clinical efficacy (relative risk [RR] =1.27, 95% confidence interval [CI]: 1.13-1.43), and decrease the radiation pneumonia (RR = 0.41, 95% CI: 0.26-0.46), radiation esophagitis (RR = 0.46, 95% CI: 0.37-0.59) and bone marrow suppression (RR = 0.44, 95% CI: 0.36-0.53). CONCLUSION: Shenqi Fuzheng injection can improve the clinical efficacy and decrease the radiation toxicities in the NSCLC patients treated with radiation.

Tumor M2 pyruvate kinase in diagnosis of nonsmall cell lung cancer: A meta-analysis based on Chinese population.

OBJECTIVE: The purpose of this study was to evaluate the value of tumor M2 pyruvate kinase (tumor M2-PK) in the diagnosis of nonsmall cell lung cancer. METHODS: The diagnosis clinical studies of tumor M2-PK in the diagnosis of nonsmall cell lung cancer were electronic researched in the Medline, EMBASE, WANFANG, and CNIK databases. The data of true positive, false positive, false negative, and true negative were extracted from each of the individual studies. We use  Stata11.0 (http://www.stata.com; Stata Corporation, College Station, TX) and MetaDiSc 1.4 software to pool the diagnostic sensitivity, specificity, and diagnostic area under the receiver operating characteristic (ROC). RESULTS: Eleven diagnostic clinical studies with 1294 subjects were included in this diagnostic meta-analysis. The combined sensitivity, specificity, positive likely hood ratio, negative likely hood ratio were 0.69 (0.65-0.72), 0.92 (0.89-0.94), 7.84 (5.92-10.38), 0.36 (0.32-0.40). And the area under the ROC curve was 0.92 (0.90-0.94). CONCLUSION: Serum tumor M2-PK can be a potential biomarker for diagnosis of nonsmall cell lung cancer.

Aidi injection combined with radiation in the treatment of non-small cell lung cancer: A meta-analysis evaluation the efficacy and side effects.

OBJECTIVE: The purpose of this meta-analysis was to assess the clinical efficacy and side effects of Aidi injection combined with radiation in the treatment of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: By searching PubMed, the Cochrane central register of controlled trials, EMBSE and CNKI databases, the efficacy and side effect data of Aidi injection combined with radiation in the treatment of NSCLC from the published clinical studies were collected. The data were pooled using Stata version 11.0 software (http://www.stata.com; Stata Corporation, College Station, TX). RESULTS: Ten clinical studies with 1084 subjects were included in this meta-analysis. The combined data showed the clinical efficacy in experiment group was higher than that of control group (risk ratio [RR] = 1.72, 95% confidence interval [CI]: 1.52-1.96, P = 0.00); four articles reported the life quality improvement. The pooled data showed that the use of Aidi can significantly improve the quality of life in the procedure of radiation (RR = 2.29, 95% CI: 1.76-2.98, P = 0.00); six studies reported the radiation toxicities. The pooled data showed that Aidi injection can significant decrease the radiation pneumonia (OR = 0.46, 95% CI: 0. 34-0.63), radiation esophagitis (OR = 0.53, 95% CI: 0.40-0.71), and marrow suppression (OR = 0.50, 95% CI: 0.42-0.59). CONCLUSION: Aidi injection can improve the clinical efficacy, quality of life, and decrease the radiation-related toxicities in NSCLC patients who received radiation.

Prognostic significance of CYFRA21-1, CEA and hemoglobin in patients with esophageal squamous cancer undergoing concurrent chemoradiotherapy.

PURPOSE: To evaluate the prognostic value of serum CYFRA21-1, CEA and hemoglobin levels regarding long-term survival of patients with esophageal squamous cell carcinoma (ESCC) treated with concurrent chemoradiotherapy (CRT). METHODS: Age, gender, Karnofsky Performance Status (KPS), tumor location, tumor length, T stage, N stage and serum hemoglobin, and CYFRA21-1 and CEA levels before concurrent CRT were retrospectively investigated and related to outcome in 113 patients receiving 5-fluorouracil and cisplatin combined with radiotherapy for ESCC. The Kaplan-Meier method was used to analyze prognosis, the log-rank to compare groups, the Cox proportional hazards model for multivariate analysis, and ROC curve analysis for assessment of predictive performance of biologic markers. RESULTS: The median survival time was 20.1 months and the 1-, 2-, 3-, 5- year overall survival rates were 66.4%, 43.4%, 31.9% and 15.0%, respectively. Univariate analysis showed that factors associated with prognosis were KPS, tumor length, T-stage, N-stage, hemoglobin, CYFRA21-1 and CEA level. Multivariate analysis showed T-stage, N-stage, hemoglobin, CYFRA21-1 and CEA level were independent predictors of prognosis. By ROC curve, CYFRA21-1 and hemoglobin showed better predictive performance for OS than CEA (AUC= 0.791, 0.704, 0.545; P=0.000, 0.000, 0.409). CONCLUSIONS: Of all clinicopathological and molecular factors, T stage, N stage, hemoglobin, CYFRA21-1 and CEA level were independent predictors of prognosis for patients with ESCC treated with concurrent CRT. Among biomarkers, CYFRA21-1 and hemoglobin may have a better predictive potential than CEA for long-term outcomes.

[Endostatin in different administration routes combined with adriamycin chemotherapy in the treatment of liver cancer xenograft in mice].

OBJECTIVE: To study the antiangiogenetic and tumor inhibitory effects of endostatin (Es) by intratumoral versus intravenous administration combined with adriamycin (Adm) for treatment of transplanted tumor in mice. METHODS: Forty mice were subjected to subcutaneous implantation of H22 cells and randomly divided into 4 groups by the body weight when the tumor diameter reached 1 cm, namely the control group (with intratumoral and intravenous injection of normal saline), Es intratumoral group (with intratumoral injection Es and intraperitoneal Adm injection), Es vein group (with intravenous Es injection and intraperitoneal Adm injection), and Adm group (with intratumoral saline injection and intraperitoneal Adm injection). The tumor volumes and tumor inhibition rates were calculated, and the expression of vascular endothelial growth factor (VEGF) and the microvessel density (MVD) of the tumors were examined, with the survival time of the mice also observed. RESULTS: The tumor volume was smaller in Es intratumoral group than in the other groups (P<0.05). The expression of VEGF and M VD in Es intratumoral group was significantly decreased as compared with that in the other groups (P<0.05). The survival time was significantly longer in Es intratumoral group and Es vein group than in the other groups (P<0.05), but showed no significant difference between Es intratumoral group and Es vein group (P>0.05). CONCLUSION: In combination with Adm regimen, Es given intratumoral injection produces better effect than intravenous Es injection against angiogenesis and tumor growth, no significant difference can be found in the survival time between them.

[Effect of sequential intratumoral injection of xenogeneic antigens for immunotherapy in immunized mice bearing S180 tumor].

OBJECTIVE: To investigate the therapeutic effect of sequential intratumoral injection of xenogeneic antigens in immunized tumor-bearing mice. METHODS: Sequential intratumoral injection of the xenoantigens was performed in immunized mice bearing S180 tumor. The tumor size changes were observed, and the tumor-infiltrating lymphocytes (TIL) including CD3+CD4+T, CD3+CD8+T, and CD3+CD4+CD25+T lymphocytes were counted with flow cytometry. The concentrations of IL-2 and TNF-alpha in the tumor was measured using ELISA. RESULTS: No significant difference was found in the number of CD3+T lymphocytes in the TILs between different groups. After the immunotherapy, the percentages of CD3+CD4+T, CD3+CD8+T and CD3+CD4+CD25+T lymphocytes were 54%, 22% and 2.91%, respectively, with the CD4+/CD8+ ratio of 2.49, significantly different from that in the control group (P<0.05). The concentrations of IL-2 and TNF-alpha were 100.61 pg/ml and 54.114 pg/ml, respectively, significantly different from those in the control group (P<0.05). CONCLUSION: Sequential intratumoral injection of heteragenetic antigena can significantly increase the amount of effector cells and cytokines in the micro-environment of the tumor, and decrease the expression of T regulatory.

[Synthesis and characterization of folic acid-conjugated chitosan nanoparticles as a tumor-targeted drug carrier].

OBJECTIVE: To synthesize and characterize paclitaxel (PTX)-loaded folate-conjugated chitosan (FA-CTS/PTX) nanoparticles and evaluate its cytotoxicity in vitro. METHODS: CTS/PTX and FA-CTS/PTX nanoparticles were prepared using reductive amidation and ionic gelation of chitosan with tripolyphosphate anions (TPP). The particle size was determined by laser scattering and the morphology observed using transmission electron microscopy, and the PTX content in the nanoparticles was determined using ultraviolet spectrophotometer at 227 nm. The in vitro cytotoxicity of the nanoparticles against HeLa cells was evaluated by MTT assay. Fluorescence microscopy was used to observe the HeLa cells incubated with FA-chitosan nanoparticles in the presence or absence of folic acid in the culture medium. RESULTS: PTX loading did not cause adhesion of the FA-CTS nanoparticles, which presented with uniform spherical morphology with an average diameter of 282.8 nm. The loading and encapsulation efficiencies of FA-CTS/PTX were 9.0% and 75.4%, respectively. The FA-CTS nanoparticles showed a greater extent of intracellular uptake in the absence of folic acid, indicating that the cellular uptake of the nanoparticles occurred through endocytosis mediated by the folate receptors. The PTX-loaded FA-CTS nanoparticles exhibited potent cytotoxicity against HeLa cells, an effect 2- to 3-fold stronger than that of PTX-loaded CTS nanoparticles. CONCLUSION: FA-CTS can be a promising drug carrier with high efficiency in condensing drug, good tumor-targeting ability and low cytotoxicity.

[Expression of DNA transcription- and repair-related genes in cisplatin-resistant human ovarian carcinoma cell line COC1/DDP].

OBJECTIVE: To study the molecular mechanism underlying cisplatin resistance in ovarian carcinoma by detecting the expressions of DNA transcription- and repair-related genes in cisplatin-resistant human ovarian carcinoma COC1 cell line. METHODS: The differential expression of DNA transcription- and repair-related genes between the parental COC1 and cisplatin-resistant COC1/DDP cell line was determined using cDNA microarray. RESULTS AND CONCLUSION: Compared with COC1 cells, 143 genes in COC1/DDP cells showed significant differential expression, among which 20 were DNA transcription- and repair-related genes including 13 significantly up-regulated genes and 7 down-regulated ones. Abnormality of DNA transcription and repair might be involved in the development of cisplatin resistance in COC1/DDP cells.

Synthesis of targeted drug delivery system for fluorouracil using sulfadiazine as the carrier.

OBJECTIVE: To synthesize a targeted drug delivery system for 5-fluorouracil (5Fu) using sulfadiazine (SF) as a carrier with reduced side-effects and strong antitumor activity. METHODS: SF-poly (ethylene glycol) (PEG) conjugate was initially synthesized. 5Fu was subjected to reaction with trichloromethyl chloroformate to prepare chloroformyl 5Fu, which was linked to a spacer hydroxyl group of PEG that served as a macromolecular linking arm between SF and 5Fu. The content of 5Fu in the conjugate was determined by ultraviolet spectrophotometry. Spectrum of ultraviolet and infrared along with differential scanning calorimetry were employed to identify the structure of the conjugate of SFPEG-end capped 5Fu. RESULTS: The drug loading content of the conjugate was 3.2 %, and structural analysis confirmed the linkage between 5Fu and SF via PEG. CONCLUSION: Targeted drug delivery system for 5Fu using SF as a carrier has been successfully synthesized by this means.