Publication: Identification of the mycobacterial species that stimulate the immune system most effeciently for the theatment of bladder cancer
Abstract
MESANE KANSERİ TEDAVİSİ İÇİN BAĞIŞIKLIK SİSTEMİNİ EN ETKİLİ BİÇİMDE UYARAN MİKOBAKTERİ TÜRÜNÜN BELİRLENMESİ Günümüze değin birkaç mikobakteri türü ile yapılan çalışmalarda, mikobakterilerin hücre duvarının hem bağışıklık sistemini uyardığı hem de kanserli hücrelerin öldürülmesinde etkili olduğu kanıtlanmıştır. Bu çalışmanın konusu, bugüne dek tanımlanmış yüz kadar mikobakteri türü içerisinde, hücre duvarı en fazla bağışıklık sistemini uyaran ve en güçlü antikanser etkiyi gösteren mikobakteri türünü saptamaktır. Mesane tümörleri, yüzeyel ve derin olmak üzere kabaca iki sınıfa ayrılırlar. Olguların %70’inde, yüzeyel mesane tümörüne rastlanmaktadır. Yüzeyel mesane tümöründe progresyon, bazı risk faktörlerine dayanmaktadır. Bunlardan başlıcaları tümörün evresi, derecesi, sayısı ve boyutudur. Günümüzde intravezikal Bacillus Calmette-Guerin (BCG), yüzeyel mesane tümörlerinin tedavisinde yaygın olarak kullanılmaktadır Yüzeyel mesane tümörlerinin tedavisi ve önlenmesinde mitomisin C, doksorubisin, epirubisin, valrubisin, tiyotepa, etiglisid gibi kemoterapötik ajanlar da kullanılmasına karşın, bu ajanların intravezikal BCG uygulaması kadar etkin olmadıkları tespit edilmiştir. BCG etkin bir terapötik olmasına karşın, patojen olması ve ölüme kadar uzanan yan etkileri nedeniyle kullanımı sınırlıdır. Daha az toksik ve daha etkili ajanlar üzerinde yoğun olarak çalışılmaktadır. Bunlardan en önemlisi Mycobacterium phlei ile yapılan araştırmalardır. M.phlei’nin antitümöral etkinlik göstermesi için hücre duvar ekstresi yeterli olmaktadır. Bu bakterinin BCG’ ye benzer immünstimulan etkinliğinin yanında direkt apoptotik etkinliği olduğu da öne sürülmektedir. Ön çalışmalarımız M. phlei hücre duvarının proteinlerce zengin bileşeninin TNF-α (Tümor Nekröz Faktörü Alfa) ve IL-12 (İnterlökin 12) aktivasyonuna yol açtığını göstermiştir. Bu çalışmanın amacı bağışıklık sistemini en güçlü şekilde uyaran, nisbeten daha zararsız, öncelikle mesane tümörlerinde antitümöral etkinlik gösterebilecek hücre duvarına sahip mikobakteri türlerinin saptanmasıdır. Anahtar Sözcükler: Yüzeyel Mesane Tümörü, Mikobakteri Suşları, Hücre Zar Bileşenleri, Saflaştırma, Antitümöral Aktivite.
IDENTIFICATION OF THE MYCOBACTERIAL SPECIES THAT STIMULATE THE IMMUNE SYSTEM MOST EFFICIENTLY FOR THE TREATMENT OF BLADDER CANCER As shown by several studies with several mycobacterium species, the mycobacterium cell wall is effective in both stimulating the immune system and killing cancer cells by apoptosis. The subject of this study is to identify the most powerful and least harmful mycobacterium species among approximately one hundred species identified to date, in terms of how they stimulate the immune system and exert anticancerous activity. Bladder tumors are roughly classified into two groups: superficial and invasive. About 70% of the cases are superficial bladder carcinoma. Progression in superficial bladder carcinoma depends on several risk factors such as the stage, grade, and size of the tumor and number of tumors. Currently, intravesical (directly into bladder) application of Bacillus Calmette-Guerin (BCG) is used widely in the treatment of the superficial bladder carcinoma. Chemotherapeutic agents such as mitomycin C, doxorubicin, epirubicin, valrubicin, thiotepa, etyglycid are used also for the treatment and prevention of superficial bladder carcinoma, but it was found out that these agents are not as effective as the intravesical BCG treatment. Despite being an effective therapeutic, the pathogenicity and lethal side effects of BCG limits its usage. Intensive research has been carried out to find less toxic and more potent therapeutic agents for the treatment. Researchers often focus on Mycobacterium phlei as the primary therapeutic agent. The cell wall extract of M. phlei is sufficient for antitumoral activity. This research shows that this bacterium has direct apoptotic activity in addition to BCG-like immune-stimulating effects. Our preliminary experiments indicate that the fractions rich in cell wall proteins cause activation of TNF-α ( Tumor Necrosis Factor - Alpha) and IL-12 (Interleukin - Twelve). This research identifies the most potent and comparatively less harmful mycobacterium species that cause immunostimulation primarily in bladder tumors. Superficial Bladder Tumors, Mycobacteria Species, Cell Wall Components, Purification, Antitumoral Activity
IDENTIFICATION OF THE MYCOBACTERIAL SPECIES THAT STIMULATE THE IMMUNE SYSTEM MOST EFFICIENTLY FOR THE TREATMENT OF BLADDER CANCER As shown by several studies with several mycobacterium species, the mycobacterium cell wall is effective in both stimulating the immune system and killing cancer cells by apoptosis. The subject of this study is to identify the most powerful and least harmful mycobacterium species among approximately one hundred species identified to date, in terms of how they stimulate the immune system and exert anticancerous activity. Bladder tumors are roughly classified into two groups: superficial and invasive. About 70% of the cases are superficial bladder carcinoma. Progression in superficial bladder carcinoma depends on several risk factors such as the stage, grade, and size of the tumor and number of tumors. Currently, intravesical (directly into bladder) application of Bacillus Calmette-Guerin (BCG) is used widely in the treatment of the superficial bladder carcinoma. Chemotherapeutic agents such as mitomycin C, doxorubicin, epirubicin, valrubicin, thiotepa, etyglycid are used also for the treatment and prevention of superficial bladder carcinoma, but it was found out that these agents are not as effective as the intravesical BCG treatment. Despite being an effective therapeutic, the pathogenicity and lethal side effects of BCG limits its usage. Intensive research has been carried out to find less toxic and more potent therapeutic agents for the treatment. Researchers often focus on Mycobacterium phlei as the primary therapeutic agent. The cell wall extract of M. phlei is sufficient for antitumoral activity. This research shows that this bacterium has direct apoptotic activity in addition to BCG-like immune-stimulating effects. Our preliminary experiments indicate that the fractions rich in cell wall proteins cause activation of TNF-α ( Tumor Necrosis Factor - Alpha) and IL-12 (Interleukin - Twelve). This research identifies the most potent and comparatively less harmful mycobacterium species that cause immunostimulation primarily in bladder tumors. Superficial Bladder Tumors, Mycobacteria Species, Cell Wall Components, Purification, Antitumoral Activity