Based on superior outcomes from electrochemogene therapy (ECGT) compared to electrochemotherapy (ECT)in mice, we determined the efficacy of ECGT applied to spontaneous canine neoplasms. Intralesional bleomycin (BLM) and feline interleukin-12 DNA (fIL-12 DNA) injection combined with trans-lesional electroporation resulted in complete cure of two recurrent World Health Organization (WHO) stageT2bN0M0 oral squamous cell carcinomas (SCCs)and one T2N0M0acanthomatous ameloblastoma. Three remaining dogs, which had no other treatment options, had partial responses to ECGT; one had mandibular T3bN2bM1 melanoma with pulmonary and lymph node metastases; one had cubital T3N0M1 histiocytic sarcoma with spleen metastases; and one had soft palate T3N0M0fibrosarcoma. 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 four months after the only treatment. The dog with T 3N0M0 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 appears to be a safe and resulted in complete responses in SCC and acanthomatous ameloblastoma.
Identifying overexpressed genes in tumours is a critical step for tumour diagnosis, prognosis, and treatment. Using differential display polymerase chain reaction, sequence analysis, and gene Blast searches, we discovered that human prostaglandin F synthase (hPGFS) was upregulated in squamous cell carcinoma of the head and neck (SCCHN). Northern blot analysis indicated that up to a 16-fold increase in the level of hPGFS expression was detected in 40.5% (15 out of 37) of SCCHN primary tumours. The increased expression of hPGFS in SCCHN was primarily detected in SCC of larynx and hypopharynx (59%, Po0.05). Using the same primary tissue samples, increased levels of epidermal growth factor receptor (EGFR) expression were detected in only 32% of tumour tissues, suggesting hPGFS may have the potential to become a drug target or molecular marker for SCCHN. To determine if the increased level of hPGFS expression came from tumour cells, we determined the level of hPGFS expression in SCCHN tumour cell lines. A high level of hPGFS expression was detected in four out of five tumour SCCHN cell lines. To determine if upregulation of hPGFS is SCCHN-specific, hPGFS expression was analysed in 59 tumour cell lines derived from different types of tumours. The expression of hPGFS was increased from two-to 500-fold in a large portion of cell lines derived from lung (five out of nine), colon (five out of seven) as well as head and neck cancer (four out of five). These data link hPGFS expression to tumours located in the respiratory and digestive organs.
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