Current noninvasive tests for colorectal cancer screening: An overview of colorectal cancer screening tests.

Colorectal cancer (CRC) has become the third most common cancer in the world. Screening has been shown to be an effective way to identify early CRC and precancerous lesions, and to reduce its morbidity and mortality. Several types of noninvasive tests have been developed for CRC screening, including the fecal occult blood test (FOBT), the fecal immunochemical test (FIT), the fecal-based DNA test and the blood-based DNA test (the SEPT9 assay). FIT has replaced FOBT and become the major screening test due to high sensitivity, specificity and low costs. The fecal DNA test exhibited higher sensitivity than FIT but its current cost is high for a screening assay. The SEPT9 assay showed good compliance while its performance in screening needs further improvements. These tests exhibited distinct sensitivity and specificity in screening for CRC and adenoma. This article will focus on the performance of the current noninvasive in vitro diagnostic tests that have been used for CRC screening. The merits and drawbacks for these screening methods will also be compared regarding the techniques, usage and costs. We hope this review can provide suggestions for both the public and clinicians in choosing the appropriate method for CRC screening.

Clinical observation of gastric bypass in treatment of type 2 diabetes.

BACKGROUND: Roux-en-Y gastric bypass (GBP) is the main surgical procedure used in type 2 diabetes. The objective of this study was to evaluate the different types of GBP in treatment of type 2 diabetes. METHODS: Patients with type 2 diabetes were randomly divided into two groups: those who underwent gastrojejunal loop anastomosis bypass and those who underwent gastrojejunal Roux-en-Y bypass. Blood glucose alterations, operation time, and operation complications were observed. RESULTS: Gastrojejunal loop anastomosis bypass and gastrojejunal Roux-en-Y bypass were both effective in the treatment of selected patients with type 2 diabetes. Compared with gastrojejunal Roux-en-Y bypass, gastrojejunal loop anastomosis bypass had the advantages of easier implementation, shorter operation time, and fewer operation complications. CONCLUSIONS: Gastrojejunal loop anastomosis is effective in treatment of type 2 diabetes. It is safe, easy to implement, and worthy of clinical popularization.

Gastrodin inhibits expression of inducible NO synthase, cyclooxygenase-2 and proinflammatory cytokines in cultured LPS-stimulated microglia via MAPK pathways.

BACKGROUND: Microglial activation plays an important role in neurodegenerative diseases by producing several proinflammatory enzymes and proinflammatory cytokines. The phenolic glucoside gastrodin, a main constituent of a Chinese herbal medicine, has been known to display anti-inflammatory properties. The current study investigates the potential mechanisms whereby gastrodin affects the expression of potentially pro-inflammatory proteins by cultured murine microglial BV-2 cells stimulated with lipopolysaccharide (LPS). METHODOLOGY/PRINCIPAL FINDINGS: BV-2 cells were pretreated with gastrodin (30, 40, and 60 µM) for 1 h and then stimulated with LPS (1 µg/ml) for another 4 h. The effects on proinflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and proinflammatory cytokines, tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß), are analysed by double-immunofluorescence labeling and RT-PCR assay. To reveal the mechanisms of action of gastrodin we investigated the involvement of mitogen-activated protein kinases (MAPKs) cascades and their downstream transcription factors, nuclear factor-κB (NF-κB) and cyclic AMP-responsive element (CRE)-binding protein (CREB). Gastrodin significantly reduced the LPS-induced protein and mRNA expression levels of iNOS, COX-2, TNF-α, IL-1ß and NF-κB. LPS (1 µg/ml, 30 min)-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) and this was inhibited by pretreatment of BV-2 cells with different concentrations of gastrodin (30, 40, and 60 µM). In addition, gastrodin blocked LPS-induced phosphorylation of inhibitor κB-α (IκB-α) (and hence the activation of NF-κB) and of CREB, respectively. CONCLUSION AND IMPLICATIONS: This study indicates that gastrodin significantly attenuate levels of neurotoxic proinflammatory mediators and proinflammatory cytokines by inhibition of the NF-κB signaling pathway and phosphorylation of MAPKs in LPS-stimulated microglial cells. Arising from the above, we suggest that gastrodin has a potential as an anti-inflammatory drug candidate in neurodegenerative diseases.

Radiotherapy of unicentric mediastinal Castleman's disease.

Castleman's disease is a slowly progressive and rare lymphoproliferative disorder. Here, we report a 55-year-old woman with superior mediastinal Castleman's disease being misdiagnosed for a long term. We found a 4.3 cm mass localized in the superior mediastinum accompanied with severe clinical symptoms. The patient underwent an exploratory laparotomy, but the mass failed to be totally excised. Pathologic examination revealed a mediastinal mass of Castleman's disease. After radiotherapy of 30 Gy by 15 fractions, the patient no longer presented previous symptoms. At 3 months after radiotherapy of 60 Gy by 30 fractions, Computed tomography of the chest showed significantly smaller mass, indicating partial remission. Upon a 10-month follow-up, the patient was alive and free of symptoms.

[Clinical efficacy of keloids treated by surgical ablation and immediate postoperative adjuvant radiotherapy].

OBJECTIVE: To evaluate the clinical efficacy of intralesional excision and immediate postoperative adjuvant radiotherapy in the treatment of keloids. METHODS: Eighty-one patients with a combined total of 86 keloids were treated with 6 MeV electron beam radiotherapy after surgical intralesional excision of keloids. All received a total dose of 15 - 20 Gy for 5 consecutive days beginning the day of surgery. The time interval between keloid excision and the delivery of first fraction of radiotherapy was < 6 h. The post-operative follow-up period was 12 - 31 months. RESULTS: Forty-three cases yielded excellent outcomes and there were 18 fair cases. The overall effective rate was 85.9%. There were 10 recurrent cases. Only adverse effects such as delayed wound-healing and telangiectasias (11.3%) were found. Neither severe complications nor secondary malignancies occurred. CONCLUSION: Intralesional excision of keloid and postoperative electron radiotherapy are well-tolerated and efficacious in the prevention of keloid recurrence.

Telomerase-specific oncolytic virotherapy for human hepatocellular carcinoma.

AIM: To evaluate the therapeutic efficiency of replicative adenovirus CNHK300 targeted in telomerase-positive hepatocellular carcinoma. METHODS: CNHK300, ONYX-015 (55 kDa protein deleted adenovirus) and wtAd5 (wild type adenovirus 5) were compared, and virus proliferation assay, cell viability assay, Western blot and fluorescence microscopy were used to evaluate the proliferation and cytolysis selectivity of CNHK300. RESULTS: The replicative multiples in Hep3B and HepG II after 48 h of CNHK300 proliferation were 40625 and 65326 fold, respectively, similar to that of wtAd5. However, CNHK300 exhibited attenuated replicative ability in normal fibroblast cell line BJ. CNHK300 could lyse hepatocellular carcinoma cells at a low multiplicity of infection (MOI), but could not affect growth of normal cells even at a high MOI. CONCLUSION: CNHK300 is a cancer-selective replication-competent adenovirus which can cause oncolysis of liver cancer cells as well as wtAd5 (wild type adenovirus 5), but had severely attenuated replicative and cytolytic ability in normal cells. This novel strategy of cancer treatment offers a promising treatment platform.

[Safety and efficacy of gefitinib for treatment of advanced non-small cell lung cancer].

OBJECTIVE: To evaluate the safety and efficacy of gefitinib as second-line or even third-line treatment for previously treated patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). METHODS: 156 patients with locally advanced NSCLC which were about to undergo progression after previous chemotherapy were eligible for this study. The regimen was oral intake of gefitinib 250 mg once daily in the morning or afternoon until the disease progression or toxicity has become intolerable. The drug was provided by AstroZeneca Company by its Expanded Access Program. RESULTS: 154 such patients were evaluable for response and toxicity assessment. The overall rate of objective response and disease control was 28.6% (44/154) and 89.6% (138/154). The median duration of response was 7. 5 months. The median time to disease progression (TTP) was 5. 1 months and the median overall survival time (OS) 10.0 months. The actuarial 1-year survival was 41. 0%. The response rate in adenocarcinoma was significantly higher than that in squamous carcinoma (P = 0. 026). The risk of disease progression in patients with squamous carcinoma was 1. 7 times as much as that of adenocarcinoma patients ( P = 0. 011) , and the risk of death in male was 2. 0 times as much as that in female ( P = 0. 002). At least one of these adverse events would be observed in 40.9% (63/154) of these patients, which, however was mild and reversible. Conclusion Gefitinib is effective and safe as a second-line or third-line treatment for previously treated patients with locally advanced or metastatic non-small cell lung cancer.

Phase II trial of sequential gefitinib after minor response or partial response to chemotherapy in Chinese patients with advanced non-small-cell lung cancer.

BACKGROUND: Basic research of gefitinib (Iressa, ZD1839) has demonstrated the combination effects of gefitinib and chemotherapy were sequence-dependent. To evaluate the efficacy of sequential administration of gefitinib following a minor response or partial response to two to three cycles of chemotherapy, a phase II clinical trial was done in Chinese patients with advanced non-small-cell lung cancer (NSCLC). METHODS: Thirty-three consecutive patients with advanced NSCLC that had been pretreated with at least one chemotherapeutic regimen and were responding to chemotherapy following 2 to 3 cycles of treatment, entered the trial from May 2004 to February 2006. Patients received gefitinib at an oral dose of 250 mg once daily for 4 weeks. RESULTS: Thirty-three patients were evaluable for response and toxicity. The objective response rate was 24.2% (8 of 33) (95% CI, 11% to 42%). The symptom improvement rate was 54.5% (18 of 33) (95% CI, 41% to 69%). The median duration of response was 7 months (95%CI, 4.0 to 13.2 months). The median time to disease progression (TTP) was 6.5 months (95%CI, 0.7 to 16.6 months). The median overall survival time (OS) was 9.8 months (range, 2.1 to 18.0 months), and the actuarial 1-year survival was 36.4%. Toxicity was relatively mild and included only one patient (3.0%) with grade 4 diarrhea, 1 (3.0%) with grade 3 rash, 1 (3.0%) with grade 3 nausea, and 1 with grade 3 vomiting (3.0%). CONCLUSION: Preliminary results suggest that sequential administration of gefitinib following a response to chemotherapy may be beneficial for Chinese patients with advanced NSCLC. Further randomized clinical trials are needed.

[Experimental study of effect of epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 in combination with irinotecan].

OBJECTIVE: To assess the optimal regimen and its mechanism of ZD1839 in combination with SN38, the active metabolite of irinotecan (CPT-11), in the colon cancer cell lines HT-29 and LoVo. METHODS: Chou and Talalay method was used to analyze the combination effects of sequencing of ZD1839 and SN38. Western blotting and immunoprecipitation were used to determine the effects of ZD1839 and/or SN38 on their targeted enzymes and downstream markers. Apoptosis was assayed by analyzing histone-associated DNA fragment. RESULTS: Sequential SN38 followed by ZD1839 produced a synergistic effect. In contrast, SN38 following ZD1839 exhibited an antagonist effect. SN38 markedly inhibited topoisomerase I (Topo-I) activity. ZD1839 did not alter epidermal growth factor receptor (EGFR) expression, but resulted in a complete inhibition of EGFR phosphorylation. Sequential ZD1839 followed by SN38 did not show any enhanced inhibition effect on Topo-I activity, phosphorylation of EGFR and one of its downstream markers MAPK. However, simultaneous SN38 plus ZD1839, and sequential SN38 followed by ZD1839 administrations showed modest inhibition effect on EGFR's another downstream marker AKT. The combination schedules also showed prominent influence on cell cycle distribution. ZD1839 maintained SN38-induced DNA damage and apoptosis. CONCLUSION: Sequential SN38 followed by ZD1839 may be a favorable combination schedule.

[hTERT promoter regulated replication-selective adenovirus CNHK300 in treatment of hepatocellular carcinoma].

OBJECTIVE: To evaluate the therapeutic efficiency of replicative adenovirus CNHK300 targeted at telomerase-positive hepatocellular carcinoma. METHODS: Human liver cancer cell line HepGII and Hep3B, human embryonic kidney cell line 293, and normal human fibroblasts of the line BJ were cultured and added with adenoviruses CNHK300, ONYX-015 (55 000 protein deleted adenovirus), or wtAd5 (wild type 5) with different multiplicity of infection (MOI) for 7 days. 293 cells were used to measure the titer of the filial generation virus from different cells. The cell survival rate was calculated by MTT method 2, 4, 6, and 8 days after. Different cells were added with CNHK300 virus and then the E1A protein in the cytoplasm was measured by western blotting. Fluorescence microscopy was used to observe the CNHK300-EGFP proliferation after the cells were cultured and added with the virus for 1.5 hours. RESULTS: The replicative viruses CNHK300 and wtAd5 proliferated rapidly in HepGII and Hep3B cells since 24 hours after inoculation and proliferated 40625 and 65326 times respectively with a proliferation potential similar to that of the wild-type adenovirus and much higher than that of the ONYX-015 virus. CNHK300 of the MOI of 0.0002 killed half of the cancer cells, especially those of the line Hep3B, within 5 approximately 6 days, and CNHK300 virus of the MOI of 0.5 pfu/cell killed almost all the HepGII cells in the 8th day, with a killing power lower than that of the wild-type virus and higher than that of the ONYX-015 cells. The IC(50) was as low as MOI of 0.002 pfu/cell for the Hep3B cell and was as high as MOI of 100 pfu/cell for the BJ cell. CNHK300 was a less powerful killer of fibroblasts than wild-type virus. E1A expression was shown by western blotting in 293 cells and CNHK300-infected liver cancer cells, but not in the CNHK300-infected normal human fibroblasts. Fluorescence microscopy showed only isolated fluorescence-positive fibroblasts till the 10th day of infection, but obvious proliferation of CNHK300-EGFP virus since the 3rd day and fluorescence-positive cells in sheets by the 7th day, however, the fluorescent intensity was weakened since the 10th day. CONCLUSION: Tumor-selective adenovirus CNHK300 replicates in telomerase-positive liver cancer cells efficiently as well as wtAd5 and causes oncolysis, but has severely attenuated proliferation and cytolysis in normal cells.

[Gene therapy for ovarian cancers by adenovirus-mediated complete antibody gene].

OBJECTIVE: To study the feasibility of adenoviral transduction of Herceptin complete antibody gene and its effect on Her2 over-expressing cancer. METHODS: The genes of VH and VL from the monoclonal antibody Herceptin were cloned into the genome of replication-defective adenovirus by viral recombination technology to produce the recombinant adenovirus Ad-SG-Her. Normal human liver cells of the line L-02 were transfected with Ad-SG-Her and ELISA was used to detect the expression of Herceptin antibody 3 and 7 days after. Forty BALB/c nude mice were inoculated with Her2 high-expressing oophoroma cells of SK-OV-3 line and were randomized into 4 equal groups: group A injected with Ad-SG-Her at the dosage of: 2 x 10(9) plaque forming unit (pfu) through the caudal vein, group B injected with Ad-SG-Her at the dosage of 1 x 10(9) pfu, group C injected with Ad-SG-Her at the dosage of 5 x 10(8) pfu, and control group. On the days 3, 7, 10, 14, 21, 28, and 35 after the injection of virus, the antibody expression in the serum was measured by ELISA and the size of tumor was measured vernier caliper. Western blot and IFA was used to detect the specificity for Her2-overexpressing ovarian cancer cell lines SK-OV-3 and the integrity of complete antibody. Anti-tumor effects were also observed in nude mice bearing SK-OV-3 tumors. RESULTS: The constructed recombinant adenovirus Ad-SG-Her could express Herceptin efficiently both in vitro and in vivo. The biological activity of the expressed antibody was similar to that of the commercial Herceptin as shown by Western blotting, IFA, and ELISA. Herceptin expression of Ad-SG-Her was detected since day 3 after treatment in the groups A, B, and C and reached the peak on days 7 - 10. The expression lasted for four weeks or so. The expression level was significantly different between group A and the groups B and C (all P < 0.05), however, without a significant difference between the group B and group C. The antibody expression of group A might increase to 103.5 micro g/ml, high enough to inhibit tumor growth and induce tumor cell apoptosis. The antibody expression of the group B was below 40 micro g/ml, and that of the group C was below 30 micro g/ml. Furthermore the expressed antibody doses were statistically significantly different at different time points. Almost no tumor growth was seen in the group A during the observation period in comparison with the groups B and C and the control group (all P < 0.05). The tumor growth was almost not influenced in the group B and C and the control group. CONCLUSION: Ad-SG-Her efficiently expresses humanized complete Herceptin with effective bioactivity and induces long-term stable expression both in vitro and in vivo. The system may serve as a new antitumoral gene therapy strategy in antibody field.