ABSTRACT
On the basis of superior outcomes from electrochemogenetherapy (ECGT) compared with electrochemotherapy in mice, we determined the efficacy of ECGT applied to spontaneous canine neoplasms. Intralesional bleomycin (BLM) and feline interleukin-12 DNA injection combined with translesional electroporation resulted in complete cure of two recurrent World Health Organization stage T(2b)N(0)M(0) oral squamous cell carcinomas (SCCs) and one T(2)N(0)M(0) acanthomatous ameloblastoma. Three remaining dogs, which had no other treatment options, had partial responses to ECGT; one had mandibular T(3b)N(2b)M(1) melanoma with pulmonary and lymph node metastases; one had cubital T(3)N(0)M(1) histiocytic sarcoma with spleen metastases; and one had soft palate T(3)N(0)M(0) fibrosarcoma. The melanoma dog had decrease in the size of the primary tumor before recrudescence and euthanasia. The histiocytic sarcoma dog had resolution of the primary tumor, but was euthanized because of metastases 4 months after the only treatment. The dog with T(3)N(0)M(0) fibrosarcoma had tumor regression with recrudescence. Treatment was associated with minimal side effects and was easy to perform, was associated with repair of bone lysis in cured dogs, improved quality of life for dogs with partial responses and extended overall survival time. ECGT seems to be a safe and resulted in complete responses in SCC and acanthomatous ameloblastoma.
Subject(s)
Bleomycin/administration & dosage , Carcinoma, Squamous Cell/veterinary , Dog Diseases/therapy , Electrochemotherapy , Genetic Therapy , Interleukin-12/genetics , Neoplasms/veterinary , Animals , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Cats , Cell Line, Tumor , Combined Modality Therapy , DNA/administration & dosage , DNA/genetics , Dog Diseases/drug therapy , Dog Diseases/genetics , Dog Diseases/pathology , Dogs , Injections, Intralesional , Interleukin-12/biosynthesis , Mice , Neoplasms/drug therapy , Neoplasms/genetics , Neoplasms/pathologyABSTRACT
On the basis of superior outcomes from electrochemogene therapy (ECGT) compared with electrochemotherapy in mice, we determined the efficacy of ECGT applied to spontaneous canine neoplasms. Intralesional bleomycin and feline interleukin-12 DNA (fIL-12 DNA) injection combined with translesional electroporation resulted in complete cure of two recurrent World Health Organization stage T(2b)N(0)M(0) oral squamous cell carcinomas (SCCs) and one T(2)N(0)M(0) acanthomatous ameloblastoma. Three remaining dogs, which had no other treatment options, had partial responses to ECGT; one had mandibular T(3b)N(2b)M(1) melanoma with pulmonary and lymph node metastases; one had cubital T(3)N(0)M(1) histiocytic sarcoma with spleen metastases; and one had soft palate T(3)N(0)M(0) fibrosarcoma. The melanoma dog had decrease in size of the primary tumor before recrudescence and euthanasia. The histiocytic sarcoma dog had resolution of the primary tumor, but was euthanized because of metastases 4 months after the only treatment. The dog with T(3)N(0)M(0) fibrosarcoma had tumor regression with recrudescence. Treatment was associated with minimal side effects and was easy to perform. It was associated with repair of bone lysis in cured dogs, it improved quality of life of dogs with partial responses and extended overall survival time. ECGT seems to be a safe and resulted in complete responses in SCC and acanthomatous ameloblastoma.
Subject(s)
Bleomycin/pharmacology , Dog Diseases/therapy , Electrochemotherapy/methods , Genetic Therapy/methods , Interleukin-12/genetics , Neoplasms/veterinary , Animals , Combined Modality Therapy , Dog Diseases/drug therapy , Dog Diseases/genetics , Dogs , Humans , Interleukin-12/administration & dosage , Mice , Neoplasms/drug therapy , Neoplasms/genetics , Neoplasms/pathologyABSTRACT
Two important aspects of gene therapy are to increase the level of gene expression and track the gene delivery site and expression, and a sensitive reporter gene may be one of the options for preclinical studies and possibly for human clinical trials. We report the novel concept of increasing the activity of the gene products. With the insertion of the mini-peptide-coding sequence CWDDWLC into the plasmid DNA of a SEAP reporter gene, we observed vast increases in the enzyme activity in vitro in all murine and human cell lines used. In addition, in vivo injection of this CWDDWLC-SEAP-encoding gene resulted in the same increases in reporter gene activity, but these increases did not correspond to alterations in the level of the gene products in the serum. Minor sequence changes in this mini-peptide negate the activity increase of the reporter gene. We report the novel concept of increasing the activity of gene products as another method to improve the reporting sensitivity of reporter genes. This improved reporter gene could complement any improved vector for maximizing the reporter sensitivity. Moreover, this strategy has the potential to be used to discover peptides that improve the activity of therapeutic genes.
Subject(s)
Alkaline Phosphatase/metabolism , Genes, Reporter/genetics , Peptides/genetics , Alkaline Phosphatase/genetics , Animals , Blotting, Western , Cell Line , Electroporation , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Models, Genetic , Plasmids/geneticsABSTRACT
342 women and 225 men, undergraduate students, participated in a study to assess whether experiencing the divorce of one's parents affected narcissistic development. In a larger study on the long-term effects of divorce, these students completed the Narcissistic Personality Inventory. The analyses indicated that the scores for children from divorced families did not differ from the scores of children from intact families on any of the seven subscales.