ABSTRACT
Hemolin proteins are cell adhesion molecules from lepidopterans involved in a wide range of cell interactions concerning their adhesion properties. However, hemolins roles in cell proliferation and wound healing are not fully elucidated. It has been recently reported that rLosac, a recombinant hemolin from the caterpillar Lonomia obliqua, presents antiapoptotic activity and is capable of improving in vitro wound healing. Therefore, this study aimed to explore rLosacs in vivo effects using a skin wound healing model in rats. Methods Circular full-thickness wounds in the rat dorsum skin were treated either with rLosac, or with saline (control), allowing healing by keeping the wounds occluded and moist. During the wound healing, the following tissue regeneration parameters were evaluated: wound closure and collagen content. Furthermore, tissue sections were subjected to histological and immunohistochemical analyses. Results The rLosac treatment has demonstrated its capacity to improve wound healing, as reflected in findings of a larger number of activated fibroblasts, proliferation of epithelial cells, increase of collagen type 1, and decrease of inflammatory infiltrate. Conclusion The findings have indicated the rLosac protein as a very promising molecule for the development of new wound-healing formulations.
Subject(s)
Wound Healing , Apoptosis Regulatory Proteins/analysis , Apoptosis Regulatory Proteins/adverse effects , Lepidoptera/chemistryABSTRACT
The lack of a cancer cure results in the increasing number of drugs in development to treat cancer. Progress toward highly targeted drugs will increase significantly in the next years, as there are more drugs that apply new science and target difficult-to-treat forms of cancer. There is a strong need that the new cancer treatments continue to improve, to become more targeted and less toxic medicines. From and understanding of the core components of the apoptosis machinery at the molecular and structural levels, many potential new therapies for leukemia and lymphoma are emerging. Livin, a member of the inhibitor of apoptosis proteins [IAPs], has been considered to be a poor prognostic marker in malignancies, however, little is known about the clinical relevance of Livin expression in acute lymphoblastic leukemia [ALL]. In this study, the expression of Livin was analyzed in 10 normal healthy controls and 37 patients with de novo acute lymphoblastic leukemia [ALL]; 23 males and 14 females; 13 children and 24 adults; 19 B-lineage, 15 T-lineage, and 3 undifferentiated; 28 with TLC below 50.000/ul and 9 with TLC exceeding 50.000/ul; 30 with BM blast infiltration exceeding 90% and 7 below total infiltration. Diagnosis of ALL was based on morphological, cytochemical and immunophenotyping criteria, and Livin expression was analyzed using a Real-Time Quantitative Reverse-Transcriptase Polymerase Chain Reaction [RTO-PCR] to investigate a possible association or correlation with the clinical features at diagnosis, such as sex, age, lineage, HB, TLC, platelets and BM infiltration. Living was higherly expressed in all the 37 ALL studied patients, i.e., [100%]. Both Living expression rates and expression levels were statistically significantly higher in All patients than in controls [p<0.001], with no statistically significant differences, associations or correlations between Livin expression rates and expression levels and any of the above clinical data [P>0.05]. The death mechanism by which mammalian cells maintain homeostasis is apoptosis. Defects in the apoptotic pathway lead to expansion of cancer and affect the ability to respond to therapy. The inhibitor of apoptosis proteins [IAPs] family has become increasingly prominent in the field of cancer and aberrant expression or function of IAPs have been implied to be involved in the pathogenesis and progression of human cancer. Pathological over-expression of IAPs has been documented in cancer and leukemia, and the functional importance of IAPs for apoptosis supression in cancers has been documented by antisense experiments. Livin is an IAP family member, which is expressed at high levels preferentially in human carcinomas. Livin-specific antisense oligonucleotides were developed for modulation of Livin expression and for treatment of diseases associated with aberrant expression of Livin. Many studies suggest that Livin expression is a novel prognostic marker in ALL and thus needs to be incorporated into the patient stratification and treatment protocols. In addition, a quarter of ALL patients fail therapy and novel treatments that are focused on undermining specifically the leukemic process are needed urgently