ABSTRACT
The parasite, Leishmania, is the causative agent of the disease leishmaniasis and is highly endemic in 98 countries spread across the tropics, subtropics and Mediterranean Basin. It is a vector-borne disease transmitted by the bite of infected sand flies, and it appears in three clinical manifestations namely: cutaneous, mucocutaneous, and visceral leishmaniasis. It is known that at least 21 species are pathogenic to humans. To control the disease, there is no human vaccine, and the sole approach is through chemotherapy. Unfortunately, the available anti-leishmanial drugs are problematic due to their high toxicity, as well as increased parasite resistance. Therefore, making accurate diagnostic decisions for clinical treatment is highly important. Old World cutaneous leishmaniasis [CL] is mostly caused by two Leishmania species, named as L. major and L. tropica that produce skin ulcers. It is also important to note that the symptoms of CL can be confused with other skin diseases. Similar clinical symptoms such as sarcoidosis, lupus vulgaris, leprosy, and bacterial ulcer may have common clinical signs with CL ulcer. Therefore, the diagnostic confirmation of the parasite is mandatory before starting an appropriate treatment strategy
ABSTRACT
PURPOSE: Immunotherapy is one of the treatment strategies for breast cancer, the most common cancer in women worldwide. In this approach, the patient's immune system is stimulated to attack microscopic tumors and control metastasis. Here, we used interferon γ-induced protein 10 (IP-10), which induces and strengthens antitumor immunity, as an immunotherapeutic agent. We employed Leishmania tarentolae, a nonpathogenic lizard parasite that lacks the ability to persist in mammalian macrophages, was used as a live delivery system for carrying the immunotherapeutic agent. It has been already shown that arginase activity, and consequently, polyamine production, are associated with tumor progression. METHODS: A live delivery system was constructed by stable transfection of pLEXSY plasmid containing the IP-10-enhanced green fluorescent protein (IP-10-egfp) fusion gene into L. tarentolae. Then, the presence of the IP-10-egfp gene and the accurate integration location into the parasite genome were confirmed. The therapeutic efficacy of IP-10 delivered via L. tarentolae and recombinant pcDNA-(IP-10-egfp) plasmid was compared by determining the arginase activity in a mouse 4T1 breast cancer model. RESULTS: The pcDNA-(IP-10-egfp) group showed a significant reduction in tumor weight and growth. Histological evaluation also revealed that only this group demonstrated inhibition of metastasis to the lung tissue. The arginase activity in the tissue of the pcDNA-(IP-10-egfp) mice significantly decreased in comparison with that in normal mice. No significant difference was observed in arginase activity in the sera of mice receiving other therapeutic strategies. CONCLUSION: Our data indicates that IP-10 immunotherapy is a promising strategy for breast cancer treatment, as shown in the 4T1-implanted BALB/c mouse model. However, the L. tarentolae-(IP-10-EGFP) live delivery system requires dose modifications to achieve efficacy in the applied regimen (six injections in 3 weeks). Our results indicate that the arginase assay could be a good biomarker to differentiate tumoral tissues from the normal ones.