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Effect of a novel somatostatin analogue combined with cytotoxic drugs on human tumour xenografts and metastasis of B16 melanoma.

ABSTRACT: A novel somatostatin analogue, TT-232 (which inhibits the proliferation of various cell cultures and transplantable mouse tumours), was examined regarding its effect on human melanoma and lymphoma xenografts as a single treatment or in combination with DTIC (dacarbazine) and etoposide. TT-232 inhibited the growth of HT-18 melanoma xenografts, a dose of 5 mg kg(-1) being the most effective. Combination of 1 mg kg(-1) TT-232 with 30 or 60 mg kg(-1) DTIC (administered daily) resulted in a stronger inhibitory effect compared to TT-232 or DTIC as a single modality. Antimetastatic effect of TT-232 treatment combined with DTIC was studied using the B16 mouse melanoma muscle - lung metastasis model. The number of lung metastases of B16 melanoma could be decreased by the daily administration of 1 mg kg(-1) TT-232 or 60 mg kg(-1), but not of 30 mg kg(-1) DTIC. TT-232, combined with 30 or 60 mg kg(-1) DTIC decreased the lung metastasis number significantly lower than the control. Nearly 50% growth inhibition of HT-58 lymphoma was achieved by daily treatment with 1 mg kg(-1) TT-232. 5 mg kg(-1) etoposide, administered daily, resulted in a similar effect. The combination of 1 mg kg(-1) TT-232 and 5 mg kg(-1) etoposide was significantly more effective than TT-232 or etoposide as a single treatment. The very strong tumour growth inhibitory effect of 10 mg kg(-1) etoposide could even be increased by combination with TT-232. These experimental data suggest that TT-232 may be an effective new tool in the combination chemotherapy of malignant tumours like melanoma and lymphoma.

SUBMITTER: Szende B

PROVIDER: S-EPMC2376778 | biostudies-other | 2003 Jan

REPOSITORIES: biostudies-other

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The somatostatin analogue octreotide inhibits growth of small intestine neuroendocrine tumour cells.

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| S-EPMC3485222 | biostudies-literature

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| S-EPMC6756137 | biostudies-literature

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Quantification of B16 melanoma cells in lungs using triplex Q-PCR--a new approach to evaluate melanoma cell metastasis and tumor control.

Project description:Skin cancer is the most common type of all cancers. However, it comprises several different types of cancers, one of which is malignant melanoma. Even though melanomas only make up about 5% of skin cancers, they are responsible for the majority of skin cancer deaths due to the poor chance of survival once the tumor has metastasized. In the present study, we have developed a new assay for quantitative analysis of B16 melanoma metastasis in the lungs. We have used a triplex Q-PCR to determine the expression of the melanoma genes GP100/Pmel and tyrosinase-related protein 2 (TRP-2), and found that B16.F10gp cells were detectable in the lungs as early as 2 hours after intravenous challenge with ? 10(4) tumor cells. When investigating the gene expression as a function of time, we observed a gradual decrease from 2-24 hours post tumor challenge followed by an increase of approximately 2 log10 on day 11. The early decrease was accelerated in the presence of activated NK cells. To further evaluate our assay, we also investigated the level of metastasis in the context of vaccination with replication defective adenoviral vectors, Ad-Ii-GP and Ad-GP, previously found to significantly delay the outgrowth of subcutaneous melanomas. Results obtained using Q-PCR were compared to conventional counting of metastatic foci under a dissection microscope. A marked reduction in gene expression was observed in the lungs after vaccination with both vectors; however, Ad-Ii-GP showed the highest protection, and matching results were obtained by enumeration of visible tumor nodules on the lung surfaces. Finally, we could show that inhibition of tumor metastasis required antigen-specific CD8 T cells and IFN?, but not perforin. In conclusion, the presented results validate triplex Q-PCR as a fast, objective, and quantitative method for analysis of melanoma metastasis in the lungs.

| S-EPMC3909236 | biostudies-literature

TRPM5 mediates acidic extracellular pH signaling and TRPM5 inhibition reduces spontaneous metastasis in mouse B16-BL6 melanoma cells.

Project description:Extracellular acidity is a hallmark of solid tumors and is associated with metastasis in the tumor microenvironment. Acidic extracellular pH (pH e ) has been found to increase intracellular Ca2+ and matrix metalloproteinase-9 (MMP-9) expression by activating NF-?B in the mouse B16 melanoma model. The present study assessed whether TRPM5, an intracellular Ca2+-dependent monovalent cation channel, is associated with acidic pH e signaling and induction of MMP-9 expression in this mouse melanoma model. Treatment of B16 cells with Trpm5 siRNA reduced acidic pH e -induced MMP-9 expression. Enforced expression of Trpm5 increased the rate of acidic pH e -induced MMP-9 expression, as well as increasing experimental lung metastasis. This genetic manipulation did not alter the pH e critical for MMP-9 induction but simply amplified the percentage of inducible MMP-9 at each pH e . Treatment of tumor bearing mice with triphenylphosphine oxide (TPPO), an inhibitor of TRPM5, significantly reduced spontaneous lung metastasis. In silico analysis of clinical samples showed that high TRPM5 mRNA expression correlated with poor overall survival rate in patients with melanoma and gastric cancer but not in patients with cancers of the ovary, lung, breast, and rectum. These results showed that TRPM5 amplifies acidic pH e signaling and may be a promising target for preventing metastasis of some types of tumor.

| S-EPMC5667964 | biostudies-literature

Growth and metastasis of B16-F10 melanoma cells is not critically dependent on host CD73 expression in mice.

Project description:BackgroundRecent studies have suggested that adenosine generated by ecto-5'-nucleotidase (CD73) in the tumor microenvironment plays a major role in promoting tumor growth by suppressing the immune response and stimulating angiogenesis via A2A and A2B receptors. However, adenosine has also been reported to inhibit tumor growth acting via A1 and A3 receptors. Therefore the aim of this study was to clarify the role of host CD73, which catalyzes the extracellular hydrolysis of AMP to adenosine, on tumor growth and metastasis of B16-F10 melanoma cells.MethodsCD73 and alkaline phosphatase (AP) activity of B16-F10 melanoma cells were measured by HPLC. Tumor cells were injected either subcutaneously or intradermally in WT and CD73-/- mice and tumor growth was monitored by MRI at 9.4 T. Immune cell subpopulations within tumors were assessed by FACS after enzymatic digestion. An endothelium specific CD73-/- was created using Tie2-Cre+ mice and CD73flox/flox (loxP) mice. Chimeric mice lacking CD73-/- on hematopoietic cells was generated by bone marrow transplantation. Lung metastatic spread was measured after intravenous B16-F10 application.ResultsB16-F10 cells showed very little CD73 and negligible AP activity. Neither complete loss of host CD73 nor specific knockout of CD73 on endothelial cells or hematopoietic cells affected tumor growth after subcutaneous or intradermal tumor cell application. Only peritumoral edema formation was significantly attenuated in global CD73-/- mice in the intradermal model. Immune cell composition revealed no differences in the different transgenic mice models. Also lung metastasis after intravenous B16-F10 injection was not altered in CD73-/- mice.ConclusionsCD73 expression on host cells, particularly on endothelial and hematopoietic cells, does not modulate tumor growth and metastatic spread of B16-F10 melanoma cells most likely because of insufficient adenosine formation by the tumor itself.

| S-EPMC4265456 | biostudies-literature

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