Miljenko Bura

The possibility that the stomach, affected by general stress, might initiate a counter-response has not until recently been considered in theories of stress. We suggest that the stomach, as the most sensitive part of the gastrointestinal tract and the largest neuroendocrine organ in the body, is crucial for the initiation of a full stress response against all noxious stress pathology. The end result would be a strong protection of all organs invaded by 'stress'. Consistent with this assumption, this coping response is best explained in terms of 'organoprotection'. Endogenous organoprotectors (eg prostaglandins, somatostatin, dopamine) are proposed as mediators. Such an endogenous counteraction could even be afforded by their suitable application. A new gastric juice peptide, M(r) 40,000, named BPC, was recently isolated. Herein, a 15 amino acid fragment (BPC 157), thought to be essential for its activity, has been fully characterized and investigated. As has been demonstrated for many organoprotective agents using different models of various tissue lesions, despite the poorly understood final mechanism, practically all organ systems appear to benefit from BPC activity. These effects have been achieved in many species using very low dosages (mostly microgram and ng/kg range) after ip, ig, and intramucosal (local) application. The effect was apparent already after one application. Long lasting activity was also demonstrated. BPC was highly effective when applied simultaneously with noxious agents or in already pathological, as well as chronical, conditions. Therefore, it seems that BPC treatment does not share any of the so far known limitations for 'conventional organoprotectors'. No influence on different basal parameters and no toxicity were observed. These findings provide a breakthrough in stress theory. BPC, as a possible endogenous free radical scavenger and organoprotection mediator, could be a useful prototype of a new class of drugs, organoprotective agents.

Cathepsin D, a protease with the capability of degrading matrix proteins, is implicated in the process of breast and colorectal cancer invasion and metastasis. Biochemical studies in laryngeal cancer have shown a potential prognostic significance of cathepsin D content determination. We studied immunohistochemical positivity of cathepsin D in tumor epithelium and stroma of 61 surgical specimens of squamous cell laryngeal cancer. Immunohistochemical reaction was quantitatively assessed using a PC-based image analysis system SFORM-VAMS. The results were correlated to clinical and morphological parameters and survival. Immunohistochemical positivity was noted in neoplastic cells and tumor stroma. Significant prognostic value for cathepsin D was established separately for epithelial tumor component and tumor stroma using log-rank test, the Cox proportional hazards regression model, and C4.5 machine learning system. In all groups, patients above the median cathepsin D staining showed significantly shorter survival time. C4.5 machine learning system extracted cutoff values for the decision tree that defines the probabilities of patients survival and death with high sensitivity (92.8% alive, 73.6% dead), 100% specificity, and 86.9% accuracy. This makes immunohistochemical cathepsin D estimation an independent prognostic parameter in laryngeal carcinomas within a 5-year period from the time of tumor surgery.