Most cited article - PubMed ID 2474913
Experimental devascularization (devitalization) of the rectum and sigmoideum
National cancer databases document that melanoma is the most aggressive and deadly cutaneous malignancy with worldwide increasing incidence in the Caucasian population. Around 10% of melanomas occur in families. Several germline mutations were identified that might help to indicate individuals at risk for preventive interventions and early disease detection. More than 50% of sporadic melanomas carry mutations in Ras/Raf/mitogen-activated protein kinase (MAPK/MEK) pathway, which may represent aims of novel targeted therapies. Despite advances in targeted therapies and immunotherapies, the outcomes in metastatic tumor are still unsatisfactory. Here, we review animal models that help our understanding of melanoma development and treatment, including non-vertebrate, mouse, swine, and other mammal models, with an emphasis on those with spontaneously developing melanoma. Special attention is paid to the melanoma-bearing Libechov minipig (MeLiM). This original swine model of hereditary metastatic melanoma enables studying biological processes underlying melanoma progression, as well as spontaneous regression. Current histological, immunohistochemical, biochemical, genetic, hematological, immunological, and skin microbiome findings in the MeLiM model are summarized, together with development of new therapeutic approaches based on tumor devitalization. The ongoing study of molecular and immunological base of spontaneous regression in MeLiM model has potential to bring new knowledge of clinical importance.
- Keywords
- MeLiM, animal model, devitalization, genetics, melanoma, mutation, progression, spontaneous regression, swine,
- MeSH
- Melanoma, Cutaneous Malignant MeSH
- Melanoma genetics MeSH
- Swine, Miniature genetics MeSH
- Disease Models, Animal MeSH
- Skin Neoplasms genetics MeSH
- Swine genetics MeSH
- Disease Progression MeSH
- Neoplasms, Second Primary genetics MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Colorectal cancer is the third most common cancer. Approximately 20% of patients have at the time of presentation metastasized colorectal cancer, which is incurable in ~80% of cases. The present case report describes a typical case diagnosed with an advanced invasive colorectal adenocarcinoma, with two suspect hypodense lesions in the liver, as revealed by sonography. Judged inoperable for a curative outcome by radical resection, the patient was treated with a novel surgical technique based on stimulating the immune system, termed 'autologous tumor immunizing devascularization' (ATID). The tumor was isolated from its surroundings by ligature of arteries and veins, and subsequently the completely devascularized tumor was left in situ. The distal part of the rectum was closed, and a stoma was made from the proximal part of the colon. Following ATID, the stressing pathophysiological condition of the completely isolated tumor provoked a generalized cellular immune response, which led to the elimination of the devascularized tumor and distant lesions without causing sepsis. The patient did not experience any serious side-effects following the operation, and refused any adjuvant chemo- and/or radiotherapy. To date, the patient has no complaints and remains in good health after the ATID intervention, already more than 14 years. The present case study provides a typical demonstration of the clinical safety of ATID, and also indicates both the immunizing and the curative potential of the method.
- Keywords
- antigen, colon and rectum, colorectal neoplasms, immunotherapy, ligation, neoplasm, surgery specialty,
- Publication type
- Journal Article MeSH