Archive for the 'Immune-based Therapies' Category
April 12th, 2007. Establishment of the enzyme-linked immunosorbent assay system to detect the amino terminal secretory form of rat Erc/Mesothelin.
There are several rat model systems of mesothelioma that may be promising tools in the development of an antimesothelioma treatment. We hope our ELISA to detect the soluble form of rat Erc/Mesothelin is useful in the rat model system to exploit the antimesothelioma therapy to be used in human cases.
March 21st, 2007. Infiltration of a mesothelioma by IFN-gamma-producing cells and tumor rejection after depletion of regulatory T cells
Depletion of CD25+ cells did not appear to modulate antitumor CTL activity on a per cell basis. Our data suggests that CD25+ Treg limit the accumulation of activated T cells producing IFN-γ in the tumor tissue and, to a lesser extent, activation and/or rate of mitosis of tumor-specific T cells in lymph nodes.
March 14th, 2007. Expression of inhibitor-of-apoptosis protein family members in malignant mesothelioma
Nuclear survivin expression is reduced in effusions as compared with solid lesions concomitantly with reduced proliferation. XIAP is upregulated in mesothelioma effusions and peritoneal mesotheliomas, suggesting a prosurvival role in malignant mesothelioma cells, particularly at these anatomic sites.
January 24th, 2007. Immunotherapy and malignant mesothelioma: clinical perspectives
Thus, immunotherapy of cancer is undoubtedly a highly promising but also very challenging approach in the treatment of a disease that has slipped through the defence lines of the immune system. This article will review past and recent developments of such a clinical strategy.
January 17th, 2007. Bcl2/bcl-x(L) Inhibitor Engenders Apoptosis and Increases Chemosensitivity in Mesothelioma
Synergistic inhibition of tumor growth by the co-administration of cisplatin and 2-methoxy antimycin A3 was observed in both in vitro and in vivo experiments. Together, these findings indicate that exposure of cancer cells to small molecule Bcl-2/xl inhibitors such as 2-methoxy antimycin A3 alone, or in the combination with other chemotherapeutics, may represent a novel therapeutic strategy in treatment of cancer, especially mesothelioma.
October 17th, 2006. The biological differences between ovarian serous carcinoma and diffuse peritoneal malignant mesothelioma
The methods used were immunohistochemistry, Western blotting, and RT-PCR. DMPM specimens showed significantly higher expression of p75 (P.
July 27th, 2006. p53-Induced Apoptosis Occurs in the Absence of p14(ARF) in Malignant Pleural Mesothelioma
However, it is noteworthy that only survivin downregulation sensitized cells to CDDP-induced apoptosis. These results suggest that p53 is functional in the absence of p14(ARF) in MPM and that targeting of the downstream apoptosis inhibitor survivin can sensitize to CDDP-induced apoptosis.
June 20th, 2006. Inactivation of TGF-beta signaling in lung cancer results in increased CDK4 activity that can be rescued by ELF
Moreover, rescue of ELF in ELF-deficient cell lines decreased the expression of CDK4 and resulted in accumulation of G1/S checkpoint arrested cells. These results suggest that disruption in TGF-beta signaling mediated by loss of ELF in lung cancer leads to cell-cycle deregulation by modulating CDK4 and ELF highlights a key role of TGF-beta adaptor protein in suppressing early lung cancer.
May 12th, 2006. Foxp3 Expressing CD4+ CD25+ and CD8+CD28− T Regulatory Cells in the Peripheral Blood of Patients with Lung Cancer and Pleural Mesothelioma
However, the lack of correlation between cancer stage and the number or the function of peripheral Treg cells in LC patients refuted the hypothesis that these cells are involved in tumor spreading. A possible involvement of the peripheral Treg cell pool in cancer development and/or in inducing systemic immunosuppression in LC patients can be hypothesized.
March 22nd, 2006. Recombinant GM-CSF plus autologous tumor cells as a vaccine for patients with mesothelioma
Conclusion: Vaccination with autologous MM tumor cell lysate with GM-CSF induced tumor specific immunity in 32% of patients, was safe and was associated with stable disease but no major tumour regressions.
March 16th, 2006. Expression of HLA-G in malignant mesothelioma and clinically aggressive breast carcinoma
In conclusion, HLA-G is focally expressed in MM and breast carcinoma, while HLA-ABC expression is conserved. However, the up-regulated expression of HLA-G in MM effusions and its possible association with shorter disease-free survival in advanced stage of breast carcinoma suggest a possible role in immune response evasion in some tumors.
March 15th, 2006. Mesothelioma environment comprises cytokines and Treg cells that suppress immune responses
Mesothelioma is infiltrated by immune effector cells, but also contains cytokines and regulatory T cells that suppress an efficient immune response. Immunotherapy of mesothelioma might be more effective when combined with drugs that eliminate or control regulatory T cells.
March 15th, 2006. Intra-tumoural regulatory T cells: A potential new target in cancer immunotherapy
We showed that the depletion of intra-tumoural T(reg) cells with anti-CD25 mAb injected directly into the tumours can cause significantly reduced tumour growth. Localised, intra-tumoural depletion of T(reg) cells is a new, clinically relevant treatment option for established tumours.
February 28th, 2006. alpha-Tocopheryl succinate induces DR4 and DR5 expression by a p53-dependent route: Implication for sensitisation of resistant cancer cells to TRAIL apoptosis
Treatment with sub-lethal doses of α-TOS restored expression of DR4 and DR5. The ability of α-TOS to modulate expression of pro-apoptotic genes may play a role in sensitisation of tumour cells to immunological stimuli.
December 17th, 2005. Activation of Tumor-Associated Macrophages by the Vascular Disrupting Agent 5,6-Dimethylxanthenone-4-Acetic Acid Induces an Effective CD8+ T-Cell�Mediated Antitumor Immune Response in Murine Models of Lung Cancer and Mesothel
These data show that activation of tumor-associated macrophages by DMXAA is an efficient way to generate a CD8+ T-cell–dependent antitumor immune response even in animals with relatively nonimmunogenic tumors. Given these properties, DMXAA might also be useful in boosting other forms of immunotherapy.
December 2nd, 2005. Interleukin-2 for the treatment of solid tumors other than melanoma and renal cell carcinoma
The activity of IL-2 in monotherapy or in association with immunotherapy is clinically relevant in hepatocarcinoma, mesothelioma and in malignant overflows as palliative treatment. Randomized trials would be required in order to be able to draw conclusions about its indication in other tumors.
November 25th, 2005. Inhibition of the Met Receptor in Mesothelioma
Conclusions: Taken together, these findings suggest that inhibition of the Met receptor may be an effective therapeutic strategy for patients with MPM and provides a mechanism, the presence of a HGF/Met autocrine loop, by which to select patients for PHA-665752 treatment.
October 15th, 2005. Long-term Follow-up of Patients with Malignant Pleural Mesothelioma Receiving High-Dose Adenovirus Herpes Simplex Thymidine Kinase/Ganciclovir Suicide Gene Therapy
Conclusions: Intrapleural Ad.HSVtk/ganciclovir is safe and well tolerated in mesothelioma patients and resulted in long-term durable responses in two patients. Given the limited amount of gene transfer observed, we postulate that Ad.HSVtk may have been effective due to induction of antitumor immune responses. We hypothesize that approaches aiming to augment the immune effects of Ad gene transfer (i.e., with the use of cytokines) may lead to increased numbers of therapeutic responses in otherwise untreatable pleural malignancies.
May 15th, 2005. Humoral immune response to mesothelin in mesothelioma and ovarian cancer patients
Conclusions: Our findings indicate that mesothelin is a new tumor antigen in patients with mesothelioma and ovarian cancer and the immunogenicity of mesothelin is associated with its high expression on the tumor cells. Mesothelin represents an excellent target for immune-based therapies.
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