Comorbidity profiling identifies potential subtype of elderly patients with nasopharyngeal carcinoma.

BACKGROUND: Few studies have assessed the comprehensive associations among comorbid diseases in elderly patients with nasopharyngeal carcinoma (NPC). This study sought to identify potential comorbidity patterns and explore the relationship of comorbidity patterns with the mortality risk in elderly patients with NPC. METHODS: A total of 452 elderly patients with NPC were enrolled in the study. The network analysis and latent class analysis were applied to mine comorbidity patterns. Propensity score matching was used for adjusting confounders. A restricted cubic spline model was used to analyze the nonlinear association between age and the risk of all-cause mortality. RESULTS: We identified 2 comorbidity patterns, metabolic disease-related comorbidity (MDRC) and organ disease-related comorbidity (ODRC) in elderly patients with NPC. Patients in MDRC showed a significantly higher risk of all-cause mortality (71.41% vs 87.97%, HR 1.819 [95% CI, 1.106-2.994], P = .031) and locoregional relapse (68.73% vs 80.88%, HR 1.689 [95% CI, 1.055-2.704], P = .042). Moreover, in patients with MDRC pattern, we observed an intriguing inverted S-shaped relationship between age and all-cause mortality among patients aged 68 years and older. The risk of mortality up perpetually with age increasing in ODRC group, specifically within the age range of 68-77 years (HR 4.371, 1.958-9.757). CONCLUSION: Our study shed light on the potential comorbidity patterns in elderly patients with NPC, thereby providing valuable insights into the development of comprehensive health management strategies for this specific population.

The causal impact of complement C3d receptor 2 on head and neck cancer microenvironment and its implications for immunotherapy response prediction.

This research dives into the intricate immune landscape of head and neck cancer (HNC), with a keen focus on the roles of specific immune cell subpopulations and their linked genes. We used tumour RNA-seq (in-house cohort: n = 192, TCGA-HNSC: n = 546) and Mendelian randomization to pinpoint key SNPs in immune cells that have a causal connection to HNC. Our discoveries unveil a spectrum of tumour immune phenotypes that either offer protection against or increase the risk of HNC. We underscore the therapeutic promise of Complement C3d Receptor 2 (CR2), a gene closely tied to immune cells, with its increased expression in tumour tissues linked to a more favourable prognosis. This is correlated with heightened immune pathway activity, stronger resistance to radiochemotherapy, and improved immunotherapy responses. Our research emphasises the pivotal role of CR2 in immune regulation and the significance of immune cells in tumour progression, highlighting the potential of CR2-targeted therapeutic interventions.

Machine learning-based survival prediction nomogram for postoperative parotid mucoepidermoid carcinoma.

Parotid mucoepidermoid carcinoma (P-MEC) is a significant histopathological subtype of salivary gland cancer with inherent heterogeneity and complexity. Existing clinical models inadequately offer personalized treatment options for patients. In response, we assessed the efficacy of four machine learning algorithms vis-à-vis traditional analysis in forecasting the overall survival (OS) of P-MEC patients. Using the SEER database, we analyzed data from 882 postoperative P-MEC patients (stages I-IVA). Single-factor Cox regression and four machine learning techniques (random forest, LASSO, XGBoost, best subset regression) were employed for variable selection. The optimal model was derived via stepwise backward regression, Akaike Information Criterion (AIC), and Area Under the Curve (AUC). Bootstrap resampling facilitated internal validation, while prediction accuracy was gauged through C-index, time-dependent ROC curve, and calibration curve. The model's clinical relevance was ascertained using decision curve analysis (DCA). The study found 3-, 5-, and 10-year OS rates of 0.887, 0.841, and 0.753, respectively. XGBoost, BSR, and LASSO stood out in predictive efficacy, identifying seven key prognostic factors including age, pathological grade, T stage, N stage, radiation therapy, chemotherapy, and marital status. A subsequent nomogram revealed a C-index of 0.8499 (3-year), 0.8557 (5-year), and 0.8375 (10-year) and AUC values of 0.8670, 0.8879, and 0.8767, respectively. The model also highlighted the clinical significance of postoperative radiotherapy across varying risk levels. Our prognostic model, grounded in machine learning, surpasses traditional models in prediction and offer superior visualization of variable importance.

Discovery of Anti-TNBC Agents Targeting PTP1B: Total Synthesis, Structure-Activity Relationship, In Vitro and In Vivo Investigations of Jamunones.

Twenty-three natural jamunone analogues along with a series of jamunone-based derivatives were synthesized and evaluated for their inhibitory effects against breast cancer (BC) MDA-MB-231 and MCF-7 cells. The preliminary structure-activity relationship revealed that the length of aliphatic side chain and free phenolic hydroxyl group at the scaffold played a vital role in anti-BC activities and the methyl group on chromanone affected the selectivity of molecules against MDA-MB-231 and MCF-7 cells. Among them, jamunone M (JM) was screened as the most effective anti-triple-negative breast cancer (anti-TNBC) candidate with a high selectivity against BC cells over normal human cells. Mechanistic investigations indicated that JM could induce mitochondria-mediated apoptosis and cause G0/G1 phase arrest in BC cells. Furthermore, JM significantly restrained tumor growth in MDA-MB-231 xenograft mice without apparent toxicity. Interestingly, JM could downregulate phosphatidylinositide 3-kinase (PI3K)/Akt pathway by suppressing protein-tyrosine phosphatase 1B (PTP1B) expression. These findings revealed the potential of JM as an appealing therapeutic drug candidate for TNBC.

Comparison of Volatiles in Different Jasmine Tea Grade Samples Using Electronic Nose and Automatic Thermal Desorption-Gas Chromatography-Mass Spectrometry Followed by Multivariate Statistical Analysis.

Chinese jasmine tea is a type of flower-scented tea, which is produced by mixing green tea with the Jasminum sambac flower repeatedly. Both the total amount and composition of volatiles absorbed from the Jasminum sambac flower are mostly responsible for its sensory quality grade. This study aims to compare volatile organic compound (VOC) differences in authoritative jasmine tea grade samples. Automatic thermal desorption-gas-chromatography-mass spectrometry (ATD-GC-MS) and electronic nose (E-nose), followed by multivariate data analysis is conducted. Consequently, specific VOCs with a positive or negative correlation to the grades are screened out. Partial least squares-discriminant analysis (PLS-DA) and hierarchical cluster analysis (HCA) show a satisfactory discriminant effect on rank. It is intriguing to find that the E-nose is good at distinguishing the grade difference caused by VOC concentrations but is deficient in identifying essential aromas that attribute to the unique characteristics of excellent grade jasmine tea.

MicroRNA-223 functions as an oncogene in human gastric cancer by targeting FBXW7/hCdc4.

AIMS: The aim of this study was (a) to determine the role of micro-223 (miR-223) in gastric cancer and (b) to elucidate its regulatory mechanism on the FBXW7/hCdc4 gene. MATERIALS AND METHODS: Artificial miR-223 and control oligonucleotide was transfected into gastric cancer cell line SGC7901 by using Lipofectamine2000. Apoptosis of miR-223 group and control group cells was analyzed by flow cytometry, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide and colony formation assays were performed to detect the cell viability, to survey migration of miR-223 group and control group cells; scratch wound-healing motility assays, Transwell Assay, and Western blot test were performed to measure the variance of hFBXW7. Luciferase Reporter Assay, which was done by pLUC-hFBXW7 WT-3'-UTR co-transfected with pLMP-hsa-miR-223 or pLMP plasmid (as control) into HEK293T cells, used to detect whether hFBXW7 is a direct target gene of miR-223. Gastric cancer cell line SGC7901 transfected with miR-223 or control oligonucleotide was resuspended in ECM gel and then was injected into the flank of nude mice, 4 weeks later, the nude mice were euthanized. The tumors were excised then were measured and weighted. SYBR-Green I-based real-time RT-PCR study was used to detect the level of miR-223 in 22 gastric cancer tissue and corresponding gastric mucosa tissues. Immunohistochemical method was applied to detect the protein of hFBXW7. RESULTS: Gastric cancer cell line SGC7901, transfected with miR-223, showed significant reduction in cellular apoptosis and increased proliferation and invasion in vitro. Similar results were found in tumorigenesis assays performed in nude mice. Moreover, 19 of 22 cancer tissue samples highly expressed miR-223, when compared with patient-matched normal gastric mucosa. Specifically, patients with lymph node metastasis or metastatic disease (M1) at an advanced pathological stage showed significantly higher expression of miR-223. FBXW7/hCdc4 protein (FBW7) levels in gastric cancer cases were inversely correlated with miR-223 expression. Overexpression of miR-223 in gastric cancer cell lines decreased FBW7 expression at the translational level and decreased FBXW7/hCdc4-driven luciferase-reporter activity. CONCLUSION: In summary, the data indicated that miR-223 targets FBXW7/hCdc4 expression at the post-transcriptional level and appears to regulate cellular apoptosis, proliferation, and invasion in gastric cancer. MiR-223 may serve as a novel therapeutic target in gastric cancer.

Semi-mature MyD88-silenced bone marrow dendritic cells prolong the allograft survival in a rat model of intestinal transplantation.

BACKGROUND: Semi-mature dendritic cells (DCs) may induce tolerance rather than immunity. However, little is known about the regulatory mechanism by which these DCs induce transplant tolerance. Myeloid differentiation factor 88 (MyD88) is a key adaptor of Toll-like receptor signaling, which plays a critical role in DC maturation. Activation of MyD88-silenced immature DCs results in the generation of semi-mature DCs. We explored the possibility of using these DCs to induce intestinal transplant tolerance in rats. METHODS: MyD88 expression was silenced in bone marrow DCs (F344 rats) using small interfering RNAs for 24 hours, at which point, lipopolysaccharide (LPS) was added to the culture for another 48 hours. These cells were analyzed for their in vitro and in vivo tolerizing capacities. RESULTS: Semi-mature DCs expressing moderate levels of MHC class II and low levels of co-stimulatory molecules were found to produce interleukin (IL)-10, while IL-12 production was decreased. In vitro co-culture with completely allogeneic T cells from Wistar rats led to a significant decrease in alloreactive T-cell responses. In vivo, the transfer of semi-mature DCs (1 × 10(6) cells) followed by the transplantation of fully mismatched intestinal grafts (F344 rats) led to significantly prolonged survival compared to rats receiving immature and mature DCs. Serum from semi-mature DC-treated rats contained lower concentrations of the pro-inflammatory cytokines IL-2 and interferon-γ 5 days after transplantation. CONCLUSION: Semi-mature DCs may promote inducible allograft tolerance and this study suggests a new strategy by which to facilitate the induction of transplant tolerance.

Exosomes derived from immature bone marrow dendritic cells induce tolerogenicity of intestinal transplantation in rats.

BACKGROUND: Dendritic cells (DCs) secrete exosomes bearing major histocompatibility complex I and II (MHC I /II) and co-stimulatory molecules, and play a critical role in immune regulation. Because immature DCs can induce T-cell tolerance in vitro and in vivo, we explored the possibility of using exosomes derived from immature DCs (imDex) for the induction of intestinal transplant tolerance in rats. MATERIALS AND METHODS: ImDex were purified from F344 rat bone marrow immature DCs. The tolerizing capacities of imDex were analyzed in vitro and in vivo using a F344-to-Wistar intestinal transplantation model. RESULTS: In the context of a moderate level of MHC class II and a low co-stimulatory level expression, imDex significantly suppressed the alloreactive T-cell response with an increase in IL-10 in vitro. In vivo injection of the lower dose (20 µg) of donor (but not recipient) imDex can significantly prolong the survival of intestinal allografts. This effect was accompanied by a decrease in the anti-donor cellular response, with a significant increase in IL-10. The CD4+CD25+T cells percentage and FOXP3mRNA expression in splenic T-cells were also significantly increased in imDex treatment recipients at five days after transplantation. CONCLUSIONS: The results suggest that imDex can prolong the intestinal allograft survival and may be a potential strategy to facilitate induction of transplant tolerance.

Exosomes derived from interleukin-10-treated dendritic cells can inhibit trinitrobenzene sulfonic acid-induced rat colitis.

OBJECTIVE: Inflammatory bowel disease (IBD), which mainly refers to Crohn's disease and ulcerative colitis, is characterized by chronic inflammation of the gastrointestinal tract. Recent reports have demonstrated that exosomes derived from interleukin-10 (IL-10)-treated bone marrow-derived dendritic cells (DCs) can reduce the incidence and severity of established collagen-induced arthritis (CIA) in mice. Based on the essential role of IL-10 in the development of normal mucosal immunity, we investigated whether exosomes derived from DCs treated with IL-10 (known as IL-10-exosomes) can suppress the trinitrobenzene sulfonic acid (TNBS)-induced colitis. MATERIAL AND METHODS: We used the rat TNBS-induced colitis model to address the therapeutic potential of IL-10-exosomes in vivo. More specifically, a rectal enema of TNBS was administered to Wistar rats, and IL-10-exosomes were injected intraperitoneally on Day 3. RESULTS: In the context of a high level of major histocompatibility complex class II (MHC II) and a low level of co-stimulatory molecule and membrane-bound IL-10 expression, IL-10-exosomes treatment substantially reduced all analyzed clinical, macroscopic, and histopathologic parameters of TNBS-induced colitis. The therapeutic effects of IL-10-exosomes were associated with a down-regulation mRNA expression of IL-2, IFN-γ and TNF-α in colon tissues. Importantly, treatment with IL-10-exosomes resulted in a pronounced up-regulation of IL-10mRNA expression in colon tissues and regulatory T cells (Tregs) in Colonic lamina propria. CONCLUSIONS: The results suggest that IL-10-exosomes treatment can suppress acute TNBS-induced colitis and may offer a promising new therapeutic strategy for IBD.

Critical role of aquaporin-3 in the human epidermal growth factor-induced migration and proliferation in the human gastric adenocarcinoma cells.

BACKGROUND: Aquaporins (AQPs) are expressed in many different tumor cell types in human. New evidence for the involvement of AQPs in cell migration and proliferation adds AQPs to an expanding list of effectors in tumor biology. AIMS: The aim of this study was to investigate whether AQP3 expression in the human gastric carcinoma cell lines, AGS and SGC7901, enhances cell migration and proliferation. RESULTS: Here, we showed that AQP3 is expressed in the human gastric cancer cell lines, AGS and SGC7901. The hEGF induced AQP3 expression in a time- and dose-dependent manner and increased gastric cancer cell migration and proliferation. AQP3 knockdown by siRNA inhibited hEGF-induced AQP3 expression and thus cell migration and proliferation. Furthermore, a mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) inhibitor U0126 inhibited hEGF-induced AQP3 expression and cell migration or proliferation. METHODS: Cultured AGS or SGC7901 cells were treated with human epidermal growth factor (hEGF) and subjected to cell migration assay and cell proliferation assay. The expression or activation level of proteins was analyzed by western blot. AQP3 knockdown was obtained by small interfering (si)RNA. CONCLUSIONS: Collectively, our findings provide for the first time that AQP3 plays a critical role in hEGF-induced cancer cell migration and proliferation and that hEGF induces AQP3 expression via ERK signal transduction pathways. These finds provide evidence for a novel role of AQP3 in human gastric carcinoma as a potentially important determinant of tumor growth and spread.

Expression profile of multiple aquaporins in human gastric carcinoma and its clinical significance.

BACKGROUND: New evidence for involvement of aquaporins (AQPs) in cell migration and proliferation adds AQPs to an expanding list of effectors in tumor biology. But there is few report concerning the expression and role of AQPs in human gastric carcinogenesis so far. The aim of this current study was to investigate the expression profile of AQPs in human gastric carcinoma and its significance. METHODS: We screened the expression profile of AQP0 approximately AQP12 in gastric adenocarcinoma tissues and corresponding normal mucosa from 89 patients with gastric cancer by reverse transcriptase polymerase chain reaction (RT-PCR), Western blot analysis and immunochemical assay. The relationship between AQPs expression and clinicopathologic characteristics of patients was evaluated. RESULTS: Based on RT-PCR of 13 AQPs examined, AQP1, 3, 4, 5 and 11 were expressed in human gastric cancers or normal gastric tissues, and AQP3, 4 and 5 exhibited differential expression between human gastric carcinomas and corresponding normal tissues, which was confirmed by Western blot analyses. Immunohistochemical assay showed that AQP4 protein was expressed mainly in the membrane of parietal cell and chief cell in the normal gastric mucosa, and absent in carcinoma tissues. AQP3 and AQP5 were detected remarkably stronger in the carcinoma tissues than that in normal mucosa by immunofluorescence. AQP3 expression in cases with undifferentiated tumor was more than that in cases with well-differentiated tumor. Both AQP3 and AQP5 expression were associated with lymph node metastasis and lymphovascular invasion in patients. CONCLUSIONS: These findings of differential expressions of AQPs and their correlation with clinicopathologic characteristics implicated AQPs might play a role in human gastric carcinogenesis.

Short hairpin RNA targeting beta-catenin suppresses cell proliferation and induces apoptosis in human gastric carcinoma cells.

OBJECTIVE: Aberrant activation of Wnt/beta-catenin signaling is involved in various cancers, including human gastric cancer. Here we investigate the role of Wnt/beta-catenin signaling in regulating gastric cancer cell apoptosis. MATERIAL AND METHODS: Expression of beta-catenin was investigated after transfection with beta-catenin short hairpin RNA (shRNA) in gastric cancer cells by Western blotting and immunofluorescence analysis. beta-catenin/T-cell factor transcriptional activity was also investigated by using a luciferase reporter assay. Next, the effects of beta-catenin shRNA on cell proliferation and apoptosis were evaluated by the 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide assay and flow cytometric analysis. To investigate the precise mechanism of these effects, a comprehensive analysis was performed using a cDNA microarray. RESULTS: shRNA targeting beta-catenin resulted in a significant decrease in beta-catenin expression, and its nuclear localization and cell proliferation. Meanwhile, increased cell apoptosis was confirmed. The comprehensive analysis showed that shRNA targeting beta-catenin upregulated 26 apoptosis-related genes (including PERP, TRAF3, PDCD2, TNFRSF25, AKT2 and YWHAZ) and downregulated 48 apoptosis-related genes (including MALT1, IRAK1, TNFAIP3, PPP1R13L, TRIP and YWHAB) in gastric cancer cells. Pathway analysis suggested that the nuclear factor-kappaB pathway was involved in beta-catenin knockdown-induced apoptosis. CONCLUSIONS: Attenuation of beta-catenin by shRNA resulted in suppressed cell proliferation and apparent apoptosis, suggesting that beta-catenin may be a target for therapy of gastric cancer.

Clinicopathological features associated with lymph node metastasis in early gastric cancer: analysis of a single-institution experience in China.

BACKGROUND: An accurate assessment of potential lymph node metastasis is an important issue for the appropriate treatment of early gastric cancer. Minimizing the number of invasive procedures used in cancer therapy is critical for improving the patient's quality of life. OBJECTIVE: To evaluate the clinicopathological features associated with lymph node metastasis of early gastric cancer in patients from a single institution in China. METHODS: A retrospective review of data from 410 patients surgically treated for early gastric cancer at the First Affiliated Hospital (Nanjing, China) between 1998 and 2007, was conducted. The clinicopathological variables associated with lymph node metastasis were evaluated. RESULTS: Lymph node metastasis was observed in 12.20% of patients. The macroscopic type, tumour size, location in the stomach, depth of gastric carcinoma infiltration, and presence of vascular or lymphatic invasion showed a positive correlation with the incidence of lymph node metastasis by univariate analysis. Multivariate analyses revealed histological classification, macroscopic type, tumour size, depth of gastric carcinoma infiltration, and the presence of vascular or lymphatic invasion to be significantly and independently related to lymph node metastasis. The depth of gastric carcinoma infiltration was the strongest predictive factor for lymph node metastasis. For intramucosal cancer, tumour size was the unique risk factor for lymph node metastasis. For submucosal cancer, histological classification and tumour size were independent risk factors for lymph node metastasis. CONCLUSIONS: Histological classification, macroscopic type, tumour size, depth of gastric carcinoma infiltration, and the presence of vascular or lymphatic invasion are independent risk factors for lymph node metastasis in patients with early gastric cancer in China. Minimal invasive treatment, such as endoscopic mucosal resection, may be possible for highly selected cancers.

Inducing effects of hepatocyte growth factor on the expression of vascular endothelial growth factor in human colorectal carcinoma cells through MEK and PI3K signaling pathways.

BACKGROUND: Vascular endothelial growth factor plays a key role in human colorectal carcinoma invasion and metastasis. However, the regulation mechanism remains unknown. Recent studies have shown that several cytokines can regulate the expression of vascular endothelial growth factor in tumor cells. In this study, we investigated whether hepatocyte growth factor can regulate the expression of vascular endothelial growth factor in colorectal carcinoma cells. METHODS: Hepatocyte growth factor and vascular endothelial growth factor in human serum were measured by ELISA. The mRNA level of vascular endothelial growth factor was analyzed by reverse transcription-PCR. Western blot assay was performed to evaluate levels of c-Met and several other proteins involved in the MAPK and PI3K signaling pathways in colorectal carcinoma cells. RESULTS: Serum hepatocyte growth factor and vascular endothelial growth factor were significantly increased in colorectal carcinoma subjects. In vitro extraneous hepatocyte growth factor markedly increased protein and mRNA levels of vascular endothelial growth factor in colorectal carcinoma cells. Hepatocyte growth factor induced phosphorylation of c-Met, ERK1/2 and AKT in a dose-dependent manner. Specific inhibitors on MEK and PI3K inhibited the hepatocyte growth factor-induced expression of vascular endothelial growth factor in colorectal carcinoma cells. CONCLUSION: This present study indicates that hepatocyte growth factor upregulates the expression of vascular endothelial growth factor in colorectal carcinoma cells via the MEK/ERK and PI3K/AKT signaling pathways.

[Efficacy of antitumour colon cancer cell vaccine modified by Escherichia coli cytosine deaminase gene].

OBJECTIVES: To evaluate the efficacy of antitumour colon cancer cell vaccine modified by escherichia coli cytosine deaminase (EC-CD). METHODS: Mouse colon cancer cell vaccine CT26/CD was established by gene modification using retrovirus plasmid pLCDSN. Its tumorigenicity and effect on liver metastasis model established with wild-type colon cancer were evaluated. RESULTS: CT26/CD was established successfully and proliferated in medium containing 0.6 g/L G418 stably. EC-CD gene expression on these mutant cells was confirmed by RT-PCR. These mutant cells were more sensitive to 5-fluorocytosine (5-FC) compared with the wild-type ones (P=0.000), and presented excellent bystander effect. CT26/CD had the same tumorigenicity as its parental cells (P=0.892). CT26/CD, combined with the prodrug 5-FC, could inhibit tumor progress and live metastasis, and prolonged the survival of the liver metastasis model animals (P=0.000). CONCLUSION: The colon cancer cell vaccine modified by EC-CD presented anti-tumor effect in vivo, when treated with the prodrug.

Tamoxifen can reverse multidrug resistance of colorectal carcinoma in vivo.

AIM: To investigate the effect of tamoxifen (TAM) on multidrug resistance (MDR) of colorectal carcinoma in vivo and its relationship with estrogen receptor (ER). METHODS: Multidrug resistance was determined by means of semi-quantitative retro-transcription polymerase chain reaction (RT-PCR) to test mdr1 gene mRNA and ER expression was studied by immunohistochemistry. Tumor tissues from three cases of human colon carcinoma, which had mdr1(+)/ER(+), mdr1(+)/ER(-), mdr1(-) expressions, were planted subcutaneously in the neck of nude mice to establish three xenograft models. These models were subdivided into four subgroups randomly: Doxorubicin (DOX)-treated group, TAM-treated group, DOX and TAM group and control group. The dimensions of these xenografts were measured after each course of treatment and the xenografts were removed at the end of the experiments for measurements of weight and the variation of mdr1 mRNA level with RT-PCR. In each course, TAM (15 mg/(kg/d)) was administrated orally per day in the first seven days and DOX (3.6 mg/kg) was injected peritoneally on the first day. Data was evaluated by q and t tests. RESULTS: In the animal models with mdr1(-) tumor, the weights and volumes of the planted tumor in DOX group ((39.1+/-2.29) mg, (31.44+/-1.61) mm(3)) and TAM and DOX group ((38.72+/-2.56) mg, (31.31+/-1.74) mm(3)), which were lesser than that of control group ((45.48+/-3.92) mg, (36.42+/-2.77)mm(3), P = 0.037, P = 0.016 respectively) significantly. In the animal models with mdr1(+)/ER(+) tumor, the weights and volumes of planted tumor were not affected by DOX or TAM treatment; however, in TAM and DOX group ((425.5+/-28.58) mg, (340.35+/-22.28) mm(3)), they were significantly less than that of control group ((634.23+/-119.41) mg, (507.45+/-93.34) mm(3), P = 0.022, P = 0.045 respectively), which are similar to that in the models with mdr1(+)/ER(-) tumor. No significant changes were found in the expressive level of mdr1 mRNA following these treatments. CONCLUSION: The expression of mdr1 gene corresponds to the sensitivity of colon cancer to anti-tumor drugs in vivo. TAM can reverse the MDR of colorectal carcinoma in nude mice, which is independent of the expression of ER; however, no change was observed in the expressive level of mdr1 mRNA.

Laparoscopic versus conventional open resection of rectal carcinoma: A clinical comparative study.

AIM: To evaluate the feasibility of laparoscopic resection of rectal carcinoma and to compare the short-term outcome of laparoscopic procedure with conventional open surgery for rectal cancer. METHODS: Thirty-eight patients with rectal cancer were included in a prospective non-randomized study. The patients were assigned to laparoscopic (n=18) or open (n=18) colorectal resection. Case selection, surgical technique, and clinical and pathological results were reviewed. RESULTS: The operative time was longer in laparoscopic resection group (LAP) than in open resection group (189+/-18 min vs 146+/-22 min, P<0.05). Intraoperative blood loss and postoperative complications were less in LAP resection group than in open resection group. An earlier return of bowel motility was observed after laparoscopic surgery. The overall postoperative morbidity was 5.6% in the LAP resection group and 27.8% in open resection group (P<0.05). No anastomotic leakage was found in both groups. The pathologic examination showed that the length of the resected specimen, the mean number of harvested lymph nodes in laparoscopic resection group were comparable to those in open resection group. CONCLUSION: Laparoscopic total mesorectal excision (TME) for rectal cancer is a feasible but technically demanding procedure. The present study demonstrates the safety of the procedure, while oncologic results are comparable to the open surgery, with a favorable short-term outcome.

Specific CEA-producing colorectal carcinoma cell killing with recombinant adenoviral vector containing cytosine deaminase gene.

AIM: To kill CEA positive colorectal carcinoma cells specifically using the E coli cytosine deaminase (CD) suicide gene, a new replication-deficient recombinant adenoviral vector was constructed in which CD gene was controlled under CEA promoter and its in vitro cytotoxic effects were evaluated. METHODS: Shuttle plasmid containing CD gene and regulatory sequence of the CEA gene was constructed and recombined with the right arm of adenovirus genome DNA in 293 cell strain. Dot blotting and PCR were used to identify positive plaques. The purification of adenovirus was performed with ultra-concentration in CsCl step gradients and the titration was measured with plaque formation assay. Cytotoxic effects were assayed with MTT method, The fifty percent inhibition concentration (IC(50)) of 5-FC was calculated using a curve-fitting parameter. The human colorectal carcinoma cell line, which was CEA-producing, and the CEA-nonproducing Hela cell line were applied in cytological tests. An established recombinant adenovirus vector AdCMVCD, in which the CD gene was controlled under CMV promoter, was used as virus control. Quantitative results were expressed as the mean +/- SD of the mean. Statistical analysis was performed using ANOVA test. RESULTS: The desired recombinant adenovirus vector was named AdCEACD. The results of dot blotting and PCR showed that the recombinant adenovirus contained CEA promoter and CD gene. Virus titer was about 5.0 X 10(14)pfu/L(-1) after purification. The CEA-producing Lovo cells were sensitive to 5-FC and had the same cytotoxic effect after infection with AdCEACD and AdCMVCD (The IC(50) values of 5-FC in parent Lovo cells, Lovo cells infected with 100 M.O.I AdCEACD and Lovo cells infected with 10 M.O.I AdCMVCD were >15000, 216.5+/-38.1 and 128.8+/-25.4 micromol.L(-1), P<0.001, respectively), and the cytotoxicity of 5-FC increased accordingly when the m.o.i of adenoviruses were enhanced (The value of IC(50) of 5-FC was reduced to 27.9+/-4.2 micromol.L(-1) in 1000 M.O.I AdCEACD infected Lovo cells and 24.8+/-7.1 micromol.L(-1) in 100 M.O.I AdCMVCD infected Lovo cells, P<0.05, P<0.01, respectively). The CEA-nonproducing Hela cells had no effect after infection with AdCEACD, but Hela cells had the cytotoxic sensitivity to 5-FC after infection with AdCMVCD (The IC(50) of 5-FC in parent Hele cells and Hela cells infected with AdCMVCD at 10 M.O.I was >15000 and 214.5+/-31.3 micromol.L(-1), P<0.001). AdCEACD/5-FC system also had bystander effect, and the viability was about 30 percent when the proportion of transfected cells was only 10 percent. CONCLUSION: The recombinant adenovirus vector AdCEACD has the character of cell type-specific gene delivery. The AdCEACD/5-FC system may become a new, potent and specific approach for the gene therapy of CEA-positive neoplasms, especially colon carcinoma.