Dendritic cells elicit cellular immune response by targeting to capture breast cancer cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the specific anti-breast cancer immune response induced by dendritic cells (DC) loaded with trastuzumab and apoptotic Her-2+ breast cancer cells.</p><p><b>METHODS</b>DCs were generated from healthy peripheral blood mononuclear cells (PBMCs) in the presence of recombinant cytokines GM-CSF, IL-4 and TNF-alpha. Mature DCs were harvested after 7 days' co-culture of PBMCs and trastuzumab-treated apoptotic SKBr3 cells. The morphologic characteristics and ultrastructure of the DC were observed under the inverted phase-contrast microscope and transmission electron microscope (TEM), respectively. Flow cytometry (FCM) was used to check the expression of several DC specific markers: CD14, CD1a, CD64, CD80, CD83, CD86, HLA-ABC and HLA-DR. DC-cytokine induced killer (DC-CIK) cells were prepared by co-culture of DCs and peripheral blood lymphocytes in the presence of anti-CD3 antibodies and human IL-2 at an appropriate concentration. The number of antigen-specific T cells was analyzed by human interferon gamma enzyme linked immunospot (ELISPOT) assay. MTT assay was employed to assess the lysis of breast cancer cell line induced by DC-CIK cells.</p><p><b>RESULTS</b>5 minutes after the adding of DCs to SKBr3 cells pretreated with trastuzumab, the apoptotic SKBr3 cells were found to be circled by DCs. 48 hours later, many membrane-wrapped organelles of the apoptotic target cells in the cytoplasm of DCs were found by TEM. The majority of the organelles were degraded. Fewer organelles from the apoptotic cells were found in DCs without Herceptin. More than 60% in every group of DCs expressed a high-affinity receptor for IgG (FcgammaRI or CD64). CD14 expression on the mature DCs were comparatively lower, and HLA-DR and HLA-ABC expressions were higher in the trastuzumab group. The expression of CD1a, CD80, CD83 and CD86 in trastuzumab group were higher than those in immature DCs group (P < 0.05). ELISPOT assay suggests that the spot number of antigen-specific T cells were higher in trastuzumab group than that in the antigen unloaded DCs group (P < 0.05). The lysis of SKBr3 cells induced by the SKBr3 antigen loaded DC-CIK cells were 1.7 times higher than that of CIK.</p><p><b>CONCLUSION</b>The lysis of SKBr3 cells induced by DC-CIK was increased after that DCs were combined with trastuzumab to capture antigen from SKBr3 cells. These findings support further investigation into the use of combination immunotherapy of the humanized monoclonal antibody, DC vaccines and immunological effector cells.</p>

Capecitabine combined with cisplatin as first-line therapy in Chinese patients with advanced gastric carcinoma-a phase II clinical study / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the effectiveness and safety of the combination chemotherapy of capecitabine (X) with fractionated administration of cisplatin (C) in Chinese patients with advanced gastric cancer (AGC).</p><p><b>METHODS</b>141 patients with AGC were enrolled between July 2002 and August 2004. All patients had measurable tumor according to the criteria of RECIST, Karnofsky performance status > or = 60, adequate bone marrow, renal and hepatic functions. Prior radiotherapy or adjuvant chemotherapy was not permitted. Patients received oral administration of capecitabine at a dose of 1000 mg/m(2) twice a day on D1-D14, and intravenous infusion of fractionated cisplatin at a dose of 20 mg/m(2)/day on D1-D5. The regimen was repeated every 3 weeks, totally for 6 cycles.</p><p><b>RESULTS</b>Of the 141 evaluable patients, there were 104 men and 37 women, with a median age of 54 years (range, 23 - 80 years). Metastases before chemotherapy were detected in lymph nodes (46.8%), liver (40.4%), lung (5.7%) and other area (10.6%). The median treatment duration was 6 cycles (range, 3 - 6 cycles). The objective response rate (RR) was 36.2% (51/141). The median follow-up period was 17.5 months. The median time to progress (TTP) was 9.0 months, and the median overall survival (OS) was 12.0 months. The most common treatment-related adverse events (grade 3/4) were: hand-foot syndrome (HFS) (2.1%), leucopenia (0.7%), abnormal alanine transaminase elevation (2.8%). There was no treatment-related death.</p><p><b>CONCLUSION</b>Capecitabine combined with fractionated cisplatin is highly effective and well tolerated as a first-line treatment for advanced gastric cancer, with comparable results to 5-Fu plus cisplatin combination therapy.</p>

Immunological effector cells enhance apoptosis induced by adriamycin in a multi-drug resistant human breast cancer cell line / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effects of immunologic effector cells to enhance apoptosis induced by adriamycin (ADR) in multi-drug resistant human breast cancer cell line MCF7/ADR.</p><p><b>METHODS</b>The immunologic effector cells were induced and expanded by IFN-gamma, McAb CD3, IL-1 and IL-2. The expression of P-glycoprotein (P-gp) and its relation to apoptosis in target cells were detected by TUNEL technique and immunohistochemical staining. Flow cytometry (FCM) was carried out to determine the expression level of human breast cancer related P185 antigen and the positive rate of Annexin V-FITC/PI expression. The subcellular distribution of ADR and Annexin V expression in the target cells were detected by fluorescence microscopy.</p><p><b>RESULTS</b>The immunologic effector cells down-regulated the expression of P185 and P-gp in MCF7/ADR cells. The accumulation and subcellular distribution of ADR in MCF7/ADR cells were increased after co-culture with the immunologic effector cells. After treatment with the immunologic effector cells in combination with ADR, apoptosis rate of the target cells was 10 times higher than that induced by ADR alone, and 13 times higher than that induced by the immunologic effector cells alone.</p><p><b>CONCLUSION</b>Immunologic effector cells can simultaneously down-regulate the expression of P185 and P-gp in MCF7/ADR cell line, and increase the apoptosis rate of MCF7/ADR cells in combination with ADR.</p>

Efficacy and safety of adjuvant post-surgical therapy with imatinib in gastrointestinal stromal tumor patients with high risk of recurrence: interim analysis from a multicenter prospective clinical trial / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of postoperative adjuvant chemotherapy with imatinib in gastrointestinal stromal tumor(GIST) patients who had high risk of recurrence.</p><p><b>METHODS</b>A prospective, open-label, multi-center trial conducted in sixteen teaching hospitals in China was carried out. The criteria of the enrolled patients included age more than 18 years old, CD117 positive GIST, tumor size more than 5 cm, pathological mitosis counts more than 5/50 HPF, and treatment beginning within 4 weeks after complete resection and with imatinib (400 mg, once a day) for at least 12 months. The 1, 3 year recurrence rates, disease free survival, overall survival rate and quality of life were evaluated.</p><p><b>RESULTS</b>From Aug. 16th 2004 to Sep. 13th 2005, there were totally 74 patients screened and 57 patients (34 men, 23 women) enrolled in the imatinib treatment group. The primary tumors were located in the stomach in 50.9%, the small intestine in 38.6% and the colorectum in 10.5% of the cases. All the patients received radical resection. Until the cut-off date of interim analysis, there was no evidence of tumor relapse or metastasis in all patients and no death was reported either. Among the 57 enrolled patients with intention to treat(ITT), twelve patients finished the protocol (per protocol, PP). The disease free survival was (268.3 +/-120.2) d in ITT analysis, and (396.7+/-38.2) d in the PP analysis. The incidence of adverse effect was 44.4% . The score in quality of life showed no statistically significant difference between the baseline visit and the follow-up visits.</p><p><b>CONCLUSION</b>Imatinib is a promising postoperative adjuvant chemotherapy in GISTs patients with high risk of recurrence, and the adverse effects are receivable.</p>

Cytokine-induced killer cells induce apoptosis of K562 cells expressed bcr-abl / 中国实验血液学杂志

In order to investigate whether cytokine-induced killer (CIK) cells can induce apoptosis of bcr-abl(+) K562 cells, apoptosis of K562 cells and CEM cells induced by CIK cells, etoposide or camptothecin was detected with flow cytometry DNA assay. RT-PCR showed that K562 cells expressed the bcr-abl fusion gene, K 562 cells, K562 cells/etoposide or K562 cells/camptothecin groups showed no sub-G(1) peak. K562 cells/CIK cells group showed sub-G(1) peak (38.1%). CEM cells showed no sub-G(1) peak. CEM cells/camptothecin or CEM cells/etoposide groups showed sub-G(1) peak (23.5% or 32.3% respectively). CEM cells/CIK cells group showed sub-G(1) peak (45.4%). Etoposide or camptothecin did not induce apoptosis of K562 cells. CIK cells induce apoptosis of K562 cells. Bcr-abl fusion gene prevented apoptosis induced by etoposide or camptothecin, but did not prevent apoptosis induced by CIK cells. This property may support the observed adoptive immunologic effect of allogeneic bone marrow transplantation and donor lymphocyte transfusions of CML case relapsing after allogeneic bone marrow transplantation.