melitten has been researched along with Testicular-Neoplasms* in 4 studies
2 review(s) available for melitten and Testicular-Neoplasms
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Use of hecate-chorionic gonadotropin beta conjugate in therapy of lutenizing hormone receptor expressing gonadal somatic cell tumors.
Improvement of cancer treatment is a major challenge of medical research. Despite the immense efforts made in the improvement of diagnosis and treatment, cancer remains a major concern and cause of morbidity and mortality. Most of the modern anti-neoplastic therapies have severe side effects, and tumor cells often develop drug resistance. There is promise in the new generation of treatments (gene therapy, immunotherapy, vaccines, etc.) that are under development, but the efficacies and side effects of such therapies have so far been disappointing. Receptor-based therapies are not new, but many normal cells also present the same receptors reducing the specificity of such approaches. Several lytic peptides have been investigated because of they appear to kill cancer cells due to changes of their membrane potential. Thus, linking receptor-specific ligands to lytic peptides is expected to augment the specificity of targeting and decrease the toxicity of lytic peptides on normal cells. One such polypeptide is hecate (an analogue to the bee venom main component, melittin) that preferentially kills cancer cells at low doses. When this peptide is fused with the 81-95 amino acid fragment of chorionic gonadotropin-beta (CGbeta) subunit (hecate-CGbeta), it targets cells expressing luteinizing hormone receptor (LHR), even at very low doses, or when LHR is expressed at low level. Our recent data showed that this peptide conjugate is efficient in destroying LHR-positive cells in xenografts and more importantly in transgenic mouse models developing LHR-positive somatic cell tumors in gonads. The mechanism of action of hecate-CGbeta after binding to LHR is destruction of cell membranes resulting in rapid cell death by necrosis with minimal side effects. This review summarizes our findings on the action of this novel peptide and considers the future potential of this family of targeting peptides in the treatment of neoplasias. Topics: Animals; Chorionic Gonadotropin, beta Subunit, Human; Drug Delivery Systems; Female; Genetic Therapy; Humans; Male; Melitten; Models, Biological; Ovarian Neoplasms; Receptors, LH; Testicular Neoplasms | 2007 |
Targeting breast and prostate cancers through their hormone receptors.
A targeted treatment that effectively destroys human breast, prostate, ovarian, and testicular cancer cells that express luteinizing hormone/chorionic gonadotropin (LH/CG) receptors has been developed. The treatment consists of a conjugate of a membrane-disrupting lytic peptide (Hecate, Phor14, or Phor21) and a 15-amino acid segment of the beta chain of CG. Because these conjugates act primarily by destroying cell membranes, their effects are independent of cell proliferation. The conjugates are relatively small molecules, are rapidly metabolized, and are not antigenic. In a series of independent experiments conducted in three different laboratories, the validity of the concept has been established, and it has been shown that the LH/CG receptor capacity of the cancer cells is directly related to the sensitivity of the lytic peptide conjugates. Sensitivity to the drugs can be increased by pretreating prostate or breast cancer cells with FSH or estradiol to up-regulate LH/CG receptors. A series of 23 in vivo experiments involving a total of 1630 nude mice bearing xenografts of human prostate or breast cancer cells showed convincingly that all three lytic peptide-betaCG compounds were highly effective in destroying tumors and reducing tumor burden. Hecate-betaCG was less effective in mice bearing ovarian epithelial cancer cell xenografts, but was highly effective in treating granulosa cell tumors in transgenic mice. In addition, Hecate-betaCG and Phor14-betaCG were highly effective in targeting and destroying prostate and breast cancer cell metastases in the presence or absence of the primary tumors. Although effective in vitro, neither Hecate nor Phor14 alone were effective in reducing primary tumor volume or burden in nude mice bearing prostate or breast cancer xenografts. Topics: Animals; Antineoplastic Agents; Breast Neoplasms; Cell Membrane; Chorionic Gonadotropin, beta Subunit, Human; Drug Screening Assays, Antitumor; Female; Humans; Male; Melitten; Peptides; Prostatic Neoplasms; Receptors, LH; Testicular Neoplasms | 2005 |
2 other study(ies) available for melitten and Testicular-Neoplasms
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A novel targeted therapy of Leydig and granulosa cell tumors through the luteinizing hormone receptor using a hecate-chorionic gonadotropin beta conjugate in transgenic mice.
We investigated the antitumoral efficacy, endocrine consequences, and molecular mechanisms underlying cell death induced by the Hecate-chorionic gonadotropin (CG)beta conjugate, a fusion protein of a 23-amino acid lytic peptide Hecate with a 15-amino acid (81-95) fragment of the human CGbeta chain. Transgenic (TG) mice expressing the inhibin alpha-subunit promoter (inhalpha)/Simian Virus 40 T-antigen (Tag) transgene, developing luteinizing hormone (LH) receptor (R) expressing Leydig and granulosa cell tumors, and wild-type control littermates were treated either with vehicle, Hecate, or Hecate-CGbeta conjugate for 3 weeks. Hecate-CGbeta conjugate treatment reduced the testicular and ovarian tumor burden (P < .05), whereas a concomitant increase (testis; P < .05) or no change (ovary) in tumor volumes occured with Hectate treatment. A drop in serum progesterone, produced by the tumors, and an increase in LH levels occured in Hecate-CGbeta treated mice, in comparison with vehicle and Hecate groups, providing further support for the positive treatment response. Hecate-CGbeta conjugate induced a rapid and cell-specific membrane permeabilization of LHR-expressing cells in vitro, suggesting a necrotic mode of cell death without activation of apoptosis. These results prove the principle that the Hecate-CGbeta conjugate provides a novel specific lead into gonadal somatic cell cancer therapy by targeted destruction of LHR-expressing tumor cells. Topics: Amino Acid Chloromethyl Ketones; Animals; Apoptosis; Blotting, Northern; Caspase 3; Caspases; Cell Death; Cell Line, Tumor; Cell Separation; Chorionic Gonadotropin, beta Subunit, Human; Disease Models, Animal; Enzyme Activation; Female; Flow Cytometry; Granulosa Cell Tumor; Humans; Leydig Cell Tumor; Male; Melitten; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Fluorescence; Necrosis; Ovarian Neoplasms; Progesterone; Promoter Regions, Genetic; Protein Structure, Tertiary; Receptors, LH; Recombinant Fusion Proteins; Testicular Neoplasms; Time Factors | 2005 |
A novel approach of targeted ablation of mammary carcinoma cells through luteinizing hormone receptors using Hecate-CGbeta conjugate.
Recent studies have shown that human and animal mammary gland carcinoma cell line express luteinizing hormone receptors (LHRs). We have examined the cytotoxic effect of Hecate-CGbeta conjugate, that is, fusion of a lytic peptide (Hecate) and a 15-amino acid fragment of the CGbeta-chain in vitro. To test the hypothesis that the Hecate-CGbeta conjugate selectively abolishes cells possessing LHR, estrogen dependent and independent human breast cancer cell lines (MCF-7; MDA-MB-231) and a mouse Leydig tumor cell line (BLT-1) were treated in vitro with Hecate-CGbeta conjugate and Hecate alone. Cytotoxic effects of the Hecate-CGbeta conjugate and the Hecate alone was measured by lactate dehydrogenase (LDH) release immediately after treatment. We observed that the Hecate-CGbeta conjugate selectively, in dose-dependent manner destroys cells possessing LHR in lower concentrations of preparate comparing to the Hecate alone and that the cytotoxic effect is strongly correlated with the number of LHR. Using Western blot analysis we characterized the LHR on membranes of MDA-MB-231, MCF-7 and BLT-1 tumor cell lines. In addition, we showed the evaluation of inhibition potential of the Hecate-CGbeta conjugate to LHR. At a concentration of 33 microM the conjugate inhibited (50%; IC50) the binding of CG to LHR. We suggest further development of this novel approach for the treatment of breast cancer by the Hecate-CGbeta for in vivo trials. Topics: Animals; Antineoplastic Agents; Binding, Competitive; Breast Neoplasms; Carcinoma; Chorionic Gonadotropin, beta Subunit, Human; Dose-Response Relationship, Drug; Drug Delivery Systems; Humans; L-Lactate Dehydrogenase; Leydig Cell Tumor; Male; Melitten; Mice; Peptide Fragments; Receptors, LH; Recombinant Fusion Proteins; Testicular Neoplasms; Tumor Cells, Cultured | 2003 |