To evaluate the effectiveness and safety of autologous cytokine-induced killer (CIK) cells in elderly patients with diffuse large B-cell lymphoma. Peripheral blood mononuclear cells (PBMC) were isolated from nine elderly patients with diffuse large B-cell lymphoma. PBMCs were augmented by priming with interferon gamma (IFN-γ) followed by IL-2 and monoclonal antibody (mAb) against CD3. Autologous CIK cells (range 5 × 10(9)-1 × 10(10)) were then infused back to individual patients; infusion was repeated every 4 weeks for 32 weeks (eight cycles). Patients were assessed for changes in lymphocyte subgroup, tumor-related biological parameters, imaging characteristics, the condition of remission, quality of life (QOL), and survival. Prior to CIK infusion, two patients were in complete remission and seven patients were in partial remission. After autologous CIK cell transfusions, the proportion of CD3+, CD3+CD8+, and CD3+CD56+ cells were significantly increased compared with baseline (P < 0.05); whereas serum levels of β2-microglobulin and LDH were significantly decreased (P < 0.05). The lymphoma symptoms were reduced and QOL was improved (P < 0.05) in all patients. All patients achieved complete remission at study endpoint. No adverse reactions were reported. Autologous CIK cell immunotherapy is safe and efficacious for the treatment of elderly patients with diffuse large B-cell lymphoma.

Aim: To evaluate the in vivo antitumor effects of Cantide and the combined effect with 5‐fluorouracil. Methods: An in situ human hepatocellular carcinoma model was established in mice livers orthotopically. Drugs were administered intravenously and tumor sizes were monitored with calipers. Plasma alpha‐fetoprotein (AFP) were detected by radiation immunoassay. Morphology of tumors was evaluated by hematoxylin‐eosin (H&E) staining of histological sections. Human telomerase reverse transcriptase (hTERT) protein levels were detected by Western blotting. Results: Cantide significantly inhibit in situ human hepatocellular carcinoma growth in mice with a 75 and 50 mg·kg‐1·d‐1 administration of Cantide compared to the saline group in a dose‐dependent manner, which included injecting Cantide 25 mg·kg‐1·d‐1‐VS mg·kg‐1·d‐1 by iv for 20 d after surgically removing the tumor in liver. Cantide was also found to prevent tumor recurrence in the liver and metastasis in the lung, showing a dose‐dependent response. When Cantide was administered by iv combined with 5‐fluorouracil, it resulted in a significant reduction in tumor growth compared to either agent alone treatment group. After the treatment with Cantide alone or combined with 5‐fluorouracil, plasma AFP concentration decreased in a dose‐dependent manner. Conclusion: These results demonstrated that Cantide was an effective antitumor antisense oligonucleotide in vivo and has the potential to be developed into a clinical anti‐cancer drug.

These data suggest that IGF-IR AS[S]ODN can effectively and specifically inhibit HCC growth in vitro and in vivo. Blockage of IGF-IR expression could be a promising therapeutic approach for the management of patients with HCC.

BackgroundHuman xenograft models, resulting from orthotopic transplantation (implantation into the anatomically correct site) of histologically intact tissue into animals, are important for investigating local tumor growth, vascular and lymphatic invasion at the primary tumor site and metastasis.Methodology/Principal FindingsWe used surgical orthotopic transplantation to establish a nude mouse model of primary hepatic lymphoma (PHL), HLBL-0102. We performed orthotopic transfer of the HLBL-0102 tumor for 42 generations and characterized the tumor cells. The maintenance of PHL characteristics were supported by immunohistochemical and cytogenetic analysis. We also report the antitumor effect of Cantide, an antisense phosphorothioate oligonucleotide against hTERT, on the growth of HLBL-0102 tumors. We showed a significant, dose-dependent inhibition of tumor weight and serum LDH activity in the orthotopically transplanted animals by Cantide. Importantly, survival was prolonged in Cantide-treated HLBL-0102 tumor-bearing mice when compared to mock-treated mice.Conclusions/SignificanceOur study provided the basis for the development of a clinical trial protocol to treat PHL.

AIM:To establish a liver metastasis model of human colorectal carcinoma in nude mice.METHODS:Orthotopic transplantation of histologically intact colorectal tissues from patients into colorectal mucosa of nude mice. Tumorgenicity, invasion, metastasis and morphological characteristics of the transplanted tumors were studied by light microscopy, electron microscopy and immunohistochemistry.RESULTS:Liver metastasis models of human colon carcinoma (HCA-HMN-1) and human rectal carcinoma (HRA-HMN-2) were established after sceening from 34 colorectal carcinomas.They had been passaged in vivo for 18 and 21 generations respectively. There were lymphatic, hemotogenous and implanting metastasesis.CEA secretion was maintained after transplantation. The primary and liver metastatic tumors were similar to the original human carcinoma in histopathological and ultrastructural features, DNA content and chromosomal karyotype.CONCLUSION:The liver metastasis models provide useful tools for the study of mechanism of metastasis and its treatment of human colorectal cancer.