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98 Biotechnology | Progress Report
accreditation. teases are also key players in a wide range of
biological processes; for example, in regulat-
Cancer cellular and ing the cell cycle, cell growth and differentia-
molecular biology tion, affect the haemostatic system, antigen
processing and angiogenesis. In addition, it is
The renal cell carcinoma (RCC) accounts for becoming apparent that the aberrant function-
approximately 2-3% of human malignancies ing of certain proteases may be involved in sev-
and, among urologic tumors, it is the most ag- eral disease states, including Alzheimer’s dis-
gressive. Clear cell RCC (ccRCC) is the most fre- ease, in cancer metastasis and in inflammation
quent RCC histological subtype, which is char- (over-reactive inflammatory reactions in CNS
acterized by frequent inactivation of the VHL often cause irreversible neuronal damage).Oth-
gene. This mutation confers chemoresistance er fields of investigation include the isolation
and radioresistance, making ccRCC one of the and characterization of snake venom peptides
most difficult metastatic cancers to treat. Our with antimicrobial activity, structurally relat-
group has been investigating molecular ther- ed to beta-defensins. In the field of antiven-
apeutic targets, biomarkers and also, mecha- oms, a novel anti-coral snake venom formu-
nisms of radioresistance of ccRCC. lation, based on Australian venoms produced
very promising results, with the new formula-
Biological screening of tion being much more effective than the cur-
snake venoms and toxins rently available antivenom produced in Brazil.
Snake venoms are an extremely rich source Biological evaluation of
of biologically active substances modulating new products for health
several aspects of the regulation of homeosta-
sis. The investigation of potential new drugs This activity is mainly based on the biological
in biological samples has been a major field evaluation of substances and biomaterials per-
of research in many laboratories. This activi- forming in vitro and in vivo tests. These tests
ty has focused part of its efforts in screening are carried out in compliance with the rules
and isolating toxins with potential therapeu- of ISO-10.993 and some other internation-
tic uses. Amongst those, toxins from the Bra- al directives. Such tests include: cytotoxicity,
zilian rattlesnake which seem to be involved genotoxicity, hemocompatibility etc. and some
in the down regulation of the sodium/potassi- others tests of systemic toxicity and implants.
um pump have been investigated. Such mole- Synthesis of polymeric biomaterials was also
cules have a potential for further understand- done, resulting in three patents submitted to
ing the fine physiology of many cell types and INPI in 2007. A biomaterial can be defined as
for guiding the rationale design of cellular me- a substance (with the exception of drugs) or
tabolism modulators. Also, toxins with mod- a combination of substances (either synthet-
ulatory activity on the blood clotting system ic or natural), employed in the treatment, im-
(Snake Venom Serine Protease - SVSP) are under provement or substitution of organism tissues,
investigation. Such toxins might be employed organs or function. Since interaction with the
for the treatment of coagulation disorders and biological system is involved, biocompatibility
as auxiliary drugs in major surgeries where un- implies the capability of the material to exhib-
expected activation of the blood clotting cas- it in the host the appropriate functional and
cade could put the patient at risk. These pro- “biomimetic” qualifications. In recent years, in-
Instituto de Pesquisas Energéticas e Nucleares