Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2013, vol. 22, nr 4, July-August, p. 593–602

Publication type: review article

Language: English

Caspases and Their Role in Gastric Cancer

Kaspazy i ich znaczenie w raku żołądka

Ewelina Frejlich1,A,C,D, Julia Rudno-Rudzińska1,B,E,F, Kacper Janiszewski1,B,E,F, Łukasz Salomon2,B,E,F, Krzysztof Kotulski1,C,E,F, Oskar Pelzer3,B,E,F, Zygmunt Grzebieniak1,C,E,F, Robert Tarnawa1,C,E,F, Wojciech Kielan1,C,E,F

1 2nd Department of General and Oncological Surgery, Wroclaw Medical University Hospital, Wrocław, Poland

2 Department of Gastroenterology and Hepatology, Wroclaw Medical University Hospital, Wrocław, Poland

3 Division of Surgical Oncology and General Surgery, Regional Hospital Center in Jelenia Góra, Jelenia Góra, Poland

Abstract

Caspases (Cysteine Aspartate Specific Proteases) are a group of cysteine-containing proteolytic enzymes produced by the cells of living organisms. They participate in immunological functions, proliferation, cell migration and organization. Caspases also influence the secretion of various regulative factors. Moreover, they are responsible for cellular maturation and reconstruction, and for regulating the number and quality of cells initiating the apoptosis of old cells or those that cannot play their normal role due to abnormalities. Multiple pathological processes are associated with disorders in the activity of caspases. Changes in expression of individual caspases have been observed in gastric cancer. The expression of some caspases is also correlated with particular histological traits and the frequency of metastases, which suggests their possible use as a prognostic factor. It has also been discovered that some somatic mutations in caspase coding genes might lead to inhibition of apoptosis and the progression of the disease. Gene polymorphism may be a gastric cancer risk factor, but may also play a protective function. Considering the less than satisfactory effects of conventional therapeutic methods, the search for alternative ways to activate apoptosis – through gene therapy or selective activation of individual elements of the apoptotic pathways – constitutes a promising direction for studies of new therapeutic strategies. Caspases, enzymes playing a central role in the process of programmed cellular death, may possibly be a key to the development of a more effective anti-cancer therapy.

Streszczenie

Kaspazy są grupą cysteinowych enzymów proteolitycznych wydzielanych przez komórki żywych organizmów. Pełnią funkcje immunologiczne, biorą udział w proliferacji, organizacji i migracji komórek, a także wpływają na sekrecję różnych czynników regulatorowych. Odpowiadają również za dojrzewanie i przebudowę komórkową oraz regulację liczby i jakości komórek przez uruchamianie apoptozy komórek starych, uszkodzonych lub wykazujących nieprawidłowości uniemożliwiające im spełnianie powierzonych zadań. W różnych procesach patologicznych dochodzi do zaburzeń ich działania. W nowotworach żołądka obserwowano zmiany ekspresji poszczególnych kaspaz w porównaniu z tkankami zdrowymi, jak również korelację ekspresji niektórych z nich z cechami histologicznymi i częstością przerzutów, co sugeruje możliwość ich zastosowania jako czynnika prognostycznego. Wykryto również, że niektóre mutacje somatyczne w genach kodujących kaspazy mogą doprowadzić do zahamowania apoptozy i progresji choroby. Polimorfizm genowy poszczególnych kaspaz może natomiast być czynnikiem ryzyka raka żołądka, ale również pełnić funkcje ochronne. Z powodu niesatysfakcjonujących rezultatów konwencjonalnych metod leczniczych poszukiwanie alternatywnych form aktywacji apoptozy, czy za pomocą terapii genowej, czy selektywnego pobudzania poszczególnych elementów jej szlaków, jest obiecującym kierunkiem badań nad nowymi strategiami terapeutycznymi. Kaspazy jako enzymy pełniące centralną rolę w procesie zaprogramowanej śmierci komórki wydają się kluczem do rozwoju leczenia przeciwnowotworowego.

Key words

caspases, apoptosis, gastric cancer, prognostic factor.

Słowa kluczowe

kaspazy, apoptoza, rak żołądka, czynnik prognostyczny.

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