Which Combination Treatment Is Better for Spinal Metastasis: Percutaneous Vertebroplasty With Radiofrequency Ablation, 125I Seed, Zoledronic Acid, or Radiotherapy?

BACKGROUND: Percutaneous vertebroplasty (PVP) can not only alleviate pain but also restore mechanical stability with injection of bone cement, whereas it exhibits a poor effect on antitumor activity. But through combinations with other therapies, it may be possible to achieve the maximum effect in clinical treatment. Thus, this study is designed to assess the clinical efficacy of PVP separately combined with 4 ways for spinal metastasis (SM) treatment. STUDY QUESTION: Which combination treatment is better for spinal metastasis, percutaneous vertebroplasty with radiofrequency ablation, I seed, zoledronic acid or radiotherapy? STUDY DESIGN: A total of 169 patients with SM were retrospectively recruited and randomly assigned to 4 groups to receive 4 different ways separately: 49 patients (group A) received PVP plus I seed, 51 (group B) received PVP plus radiofrequency ablation (RFA), 38 (group C) underwent PVP plus zoledronic acid (ZA), and 31 (group D) underwent PVP plus radiotherapy (RT). MEASURES AND OUTCOMES: All of them underwent routine examinations before operation. Visual analog scale (VAS), World Health Organization (WHO) Pain Relief, and ODI were applied to evaluate pain relief and motor function. RESULTS: PVP plus RT achieved the best efficacy in relieving pains, with the highest WHO Pain Relief (P < 0.05). The PVP plus RFA exhibited lowest ODI, suggesting the best outcome after treatment (P < 0.05). The PVP plus I showed the lowest VAS score, but it was the worst to improve the routine exercise ability and relieve pains from patients. The PVP plus ZA presented higher VAS and ODI (P < 0.05). CONCLUSIONS: PVP combined with I seed exhibited the best clinical efficacy in terms of VAS, PVP combined with RT was the best choice in terms of WHO Pain Relief, and PVP combined with RFA showed the best effect in terms of ODI for the treatment of SM.

[Influence of co-stimulatory molecules B7-H4 expression on the prognosis of patients with gastric cancer treated with cytokine-induced killer cells adoptive immunotherapy].

OBJECTIVE: To investigate the influence of co-stimulatory molecules B7-H4 expression on prognosis of gastric cancer patients treated by cytokine-induced killer cells (CIK cells) adoptive immunotherapy. METHODS: Clinical data of 156 cases of gastric cancer patients were retrospectively analyzed. Patients were divided into chemotherapy group(n=81) and chemotherapy combined with CIK cell therapy group(n=75). B7-H4 expression was detected in the surgical specimens of gastric cancer patients by immunohistochemistry assay. Disease-free survival was compared between the chemotherapy group and the CIK group at different expression levels of B7-H4. RESULTS: The difference was not statistically significant in all clinical and pathological data between the chemotherapy group and the CIK treatment group (P>0.05). The postoperative median tumor-free survival in two groups was 18.0 and 45.0 months, respectively, and the difference was statistically significant (chi(2)=11.631, P=0.001). The postoperative median survival time was 27.0 and 49.0 months, respectively, and the difference was statistically significant (chi(2)=10.907, P=0.001). In 86 patients with low B7-H4 expression, the median tumor-free survival time was 32.0 and 62.0 months, respectively, and the difference was statistically significant (chi(2)=4.663,P=0.03). In 70 patients with high B7-H4 expression, the median tumor-free survival time was 11.0 and 18.0 months, respectively, and the difference was statistically significant (chi(2)=11.971, P=0.001). CONCLUSION: The median tumor-free survival time of patients with gastric cancer may be further improved by chemotherapy combined with CIK cell therapy, regardless of the level of B7-H4 expression.

Tumor cell lysate-pulsed dendritic cells induce a T cell response against colon cancer in vitro and in vivo.

To investigate whether tumor cell lysate-pulsed (TP) dendritic cells (DCs) induce cytotoxic T lymphocyte (CTL) activity against colon cancer in vitro and in vivo. Hematopoietic progenitor cells were magnetically isolated from BALB/c mice bone marrow cells. These cells were cultured with cytokines GM-CSF, IL-4, and TNFalpha to induce their maturation. They were analyzed by morphological observation and phenotype analysis. DCs were pulsed with tumor cell lysate obtained by rapid freezing and thawing at a 1:3 DC:tumor cell ratio. CTL activity and interferon gamma (IFNgamma) secretion was evaluated ex vivo. In order to determine whether or not vaccination with CT26 TP DCs induce the therapeutic potential in the established colon tumor model, CT26 colon tumor cells were implanted subcutaneously (s.c.) in the midflank of naïve BALB/c mice. Tumor-bearing mice were injected with vaccination with CT26 TP DCs on days 3 and 10. Tumor growth was assessed every 2-3 days. Finally, CTL activity and IFNgamma secretion were evaluated in immunized mice. Hematopoietic progenitor cells from mice bone marrow cells cultured with cytokines for 8 days showed the character of typical mature DCs. Morphologically, these cells were large with oval or irregularly shaped nuclei and with many small dendrites. Phenotypically, FACS analysis showed that they expressed high levels of MHC II, CD11b, CD80, and CD86 antigen, and were negative for CD8alpha. However, immature DCs cultured with cytokines for 5 days did not have typical DCs phenotypic markers. Ex vivo primed T cells with CT26 TP DCs were able to induce effective CTL activity against CT26 tumor cells, but not B16 tumor cells (E:T = 100:1, 60.36 +/- 7.11% specific lysis in CT26 group vs. 17.36 +/- 4.10% specific lysis in B16 group), and produced higher levels of IFNgamma when stimulated with CT26 tumor cells but not when stimulated with B16 tumor cells (1210.33 +/- 72.15 pg/ml in CT26 group vs. 182.25 +/- 25.51 pg/ml in B16 group, P < 0.01). Vaccination with CT26 TP DCs could induce anti-tumor immunity against CT26 colon tumor in murine therapeutic models (tumor volume on day 19: CT26 TP DCs 342 +/- 55 mm(3) vs. the other control groups, P < 0.05). In addition, all splenic CD3(+) T cells obtained from mice vaccinated with CT26 TP DCs produced high levels of IFNgamma and shown specific cytotoxic activity against CT26 tumor cells, but no cytotoxic activity when stimulated with B16 tumor cells. Tumor cell lysate-pulsed DCs can induce tumor-specific CTL activity against colon cancer in vitro and in vivo.

Bone marrow-derived dendritic cells pulsed with tumor lysates induce anti-tumor immunity against gastric cancer ex vivo.

AIM: To investigate whether bone marrow-derived denritic cells pulsed with tumor lysates induce immunity against gastric cancer ex vivo. METHODS: c-kit(+) hematopoietic progenitor cells were magnetically isolated with a MiniMACS separator from BALB/c mice bone marrow cells. These cells were cultured with cytokines GM-CSF, IL-4, and TNFalpha to induce their maturation. They were analysed by morphological observation, phenotype analysis, and mixed lymphocyte reaction (MLR). Bone marrow-derived DCs (BM-DCs) were pulsed with tumor cell lysate obtained by rapid freezing and thawing at a 1:3 DC:tumor cell ratio. Finally, cytotoxic T lymphocyte (CTL) activity and interferon gamma (IFNgamma) secretion was evaluated ex vivo. RESULTS: c-kit(+) hematopoietic progenitor cells from mice bone marrow cells cultured with cytokines for 8 d showed the character of typical mature DCs. Morphologically, observed by light microscope, these cells were large with oval or irregularly shaped nuclei and with many small dendrites. Phenotypically, FACS analysis showed that they expressed high levels of Ia, DEC-205, CD11b, CD80 and CD86 antigen, moderate levels of CD40, and negative for F4/80. Functionally, these cells gained the capacity to stimulate allogeneic T cells in MLR assay. However, immature DCs cultured with cytokines for 5 d did not have typical DCs phenotypic markers and could not stimulate allogeneic T cells. Ex vivo primed T cells with SGC-7901 tumor cell lysate-pulsed (TP) DCs were able to induce effective CTL activity against SGC-7901 tumor cells (E:T = 100:1, 69.55% +/- 6.05% specific lysis), but not B16 tumor cells, and produced higher levels of IFNgamma when stimulated with SGC-7901 tumor cells but not when stimulated with B16 tumor cells (1575.31 +/- 60.25 pg/mL in SGC-7901 group vs 164.11 +/- 18.52 pg/mL in B16 group, P < 0.01). CONCLUSION: BM-derived DCs pulsed with tumor lysates can induce anti-tumor immunity specific to gastric cancer ex vivo.