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.
Animals ; Arginase ; Breast Neoplasms ; Chemokine CXCL10 ; Female ; Genetic Therapy* ; Genome ; Humans ; Immune System ; Immunotherapy ; Interferons ; Leishmania ; Lizards ; Lung ; Macrophages ; Mice ; Neoplasm Metastasis ; Parasites ; Plasmids ; Transfection ; Tumor Burden

Dexmedetomidine is a selective α-2 adrenoceptor agonist with anxiolytic, sedative, and analgesic properties that prolongs analgesia and decreases opioid-related side effects when used in neuraxial and perineural areas as a local anesthetics adjuvant. The current study was designed to evaluate the effects of a single perineural administration of dexmedetomidine without local anesthetics on narcotic consumption and pain intensity in patients with femoral shaft fractures undergoing surgery. This prospective randomized single-blind clinical trial was conducted in patients undergoing femoral fracture shaft surgery. Based on block permuted randomization, the patients were randomly divided into intervention and control groups. The intervention group received 100µg dexmedetomidine, for a femoral nerve block without any local anesthetics. Total intraoperative opioid consumption, postoperative opioid consumption, visual analogue score (VAS) for pain, and hemodynamic parameters were recorded and compared. Finally the data from 60 patients with a mean age of 30.4±12.3 were analyzed (90% male). There were no significant differences between the baseline characteristics of the two groups (p>0.05). The mean total consumption of narcotics was reduced during induction and maintenance of anesthesia in the intervention group (p<0.05). The amount of postoperative narcotics required showed a significant difference in the intervention group compared with the control group (p<0.05). It is likely that perineural administration of dexmedetomidine significantly not only reduced intra and postoperative narcotic requirement but also decreased postoperative pain intensity in patients undergoing femoral shaft surgery. Femoral blockade by dexmedetomidine can provide excellent analgesia while minimizing the side-effects of opioids.
Analgesia ; Analgesics, Opioid ; Anesthesia ; Anesthetics, Local ; Dexmedetomidine ; Femoral Fractures ; Femoral Nerve ; Hemodynamics ; Humans ; Narcotics ; Nerve Block ; Pain Management ; Pain, Postoperative ; Propofol ; Prospective Studies ; Random Allocation

PURPOSE: Adenosis lesions of the breast, including sclerosing adenosis and adenosis tumors, are a group of benign proliferative disorders that may mimic the features of malignancy on imaging. In this study, we aim to describe the features of breast adenosis lesions with suspicious or borderline findings on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). METHODS: In our database, we identified 49 pathologically proven breast adenosis lesions for which the final assessment of the breast MRI report was classified as either category 4 (n=45) or category 5 (n=4), according to the Breast Imaging Reporting and Data System (BI-RADS) published by the American College of Radiology (ACR). The lesions had a final diagnosis of either pure adenosis (n=33, 67.3%) or mixed adenosis associated with other benign pathologies (n=16, 32.7%). RESULTS: Of the 49 adenosis lesions detected on DCE-MRI, 32 (65.3%) appeared as enhancing masses, 16 (32.7%) as nonmass enhancements, and one (2.1%) as a tiny enhancing focus. Analysis of the enhancing masses based on the ACR BI-RADS lexicon revealed that among the mass descriptors, the most common features were irregular shape in 12 (37.5%), noncircumscribed margin in 20 (62.5%), heterogeneous internal pattern in 16 (50.0%), rapid initial enhancement in 32 (100.0%), and wash-out delayed en-hancement pattern in 21 (65.6%). Of the 16 nonmass enhancing lesions, the most common descriptors included focal distribution in seven (43.8%), segmental distribution in six (37.5%), clumped internal pattern in nine (56.3%), rapid initial enhancement in 16 (100.0%), and wash-out delayed enhancement pattern in eight (50.0%). CONCLUSION: Adenosis lesions of the breast may appear suspicious on breast MRI. Awareness of these suspi-cious-appearing features would be helpful in obviating unnecessary breast biopsies.
Biopsy ; Breast* ; Diagnosis ; Fibrocystic Breast Disease ; Information Systems ; Magnetic Resonance Imaging* ; Pathology ; Subject Headings

No abstract available.
Breast* ; Magnetic Resonance Imaging*

This investigation aimed to evaluate the differential expression of HoxB7 and notch genes in different developmental stages of Echinococcus granulosus sensu stricto. The expression of HoxB7 gene was observed at all developmental stages. Nevertheless, significant fold differences in the expression level was documented in the juvenile worm with 3 or more proglottids, the germinal layer from infected sheep, and the adult worm from an experimentally infected dog. The notch gene was expressed at all developmental stages of E. granulosus; however, the fold difference was significantly increased at the microcysts in monophasic culture medium and the germinal layer of infected sheep in comparison with other stages. The findings demonstrated that the 2 aforementioned genes evaluated in the present study were differentially expressed at different developmental stages of the parasite and may contribute to some important biological processes of E. granulosus.
Adult* ; Animals ; Biological Processes ; Dogs ; Echinococcus granulosus* ; Echinococcus* ; Humans ; Parasites ; Real-Time Polymerase Chain Reaction ; Sheep