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Determination of the Activity of CD134 (OX-40) and CD137 (4-1BB) Adhesive Nolecules by Means of Flow Cytometry in Patients with Colorectal Cancer Metastases to the Liver

100%

Cepowicz D., Zaręba K., Gryko M., Stasiak-Bermuta A., Kędra B.

Polish Journal of Surgery

2011

vol. 83

issue 8

424-429

Colorectal carcinoma (CRC) is one of the most common reasons of mortality in patients diagnosed with neoplasms. In nearly 20% of patients with colorectal carcinoma metastatic lesions are diagnosed. In general, survival of patients with metastatic lesions to the liver and other organs is poor. Conventional therapy of colorectal carcinoma is based on the surgical excision of the tumor, chemotherapy, and radiotherapy.The aim of the study was to determine the expression of CD134 and CD137 molecules inside the tumor, at the border of the tumor, in the healthy tissue, and peripheral blood, considering patients with colorectal carcinoma metastases to the liver.Material and methods. The study group comprised 39 patients subject to surgical treatment at the Department of General and Gastroenterological Surgery, due to colorectal carcinoma with liver metastases. CD134 and CD137 adhesive molecule levels were determined inside the tumor, at the border of the tumor, and in the healthy margins of the surgical incision. Additionally, the authors evaluated the peripheral blood level of the above-mentioned molecules on the day of the surgical procedure, and 10 days, thereafter.Results. The mean CD134 levels were the highest inside the tumor, significantly decreasing towards the direction of healthy tissues. The average peripheral blood molecule levels were four-fold higher on the day of the surgical procedure, as compared to values obtained on the tenth postoperative day. This dependency also concerned the remaining statistical measures.The mean CD137 levels showed no significant difference, regardless their location. The authors observed significant, peripheral blood, CD137 level differences, considering the day of the surgical procedure and tenth postoperative period. The mean CD137 peripheral blood level was several times higher on the day of the surgical procedure, as compared to the postoperative period.Conclusions. The determination of the activity of CD134 and CD137 molecules might create opportunities to plan treatment and predict prognosis in case of colorectal carcinoma. Proper immuno-therapeutic management which is based on the expression of the above-mentioned molecules might help determine the risk of metastases, preventing from their development. In advanced cases treatment of liver metastases might be possible.

Natalizumab: nowa droga w terapii stwardnienia rozsianego

84%

Jałosiński M., Jatczak I., Głąbiński A.

Aktualności Neurologiczne

2007

vol. 7

issue 3

195-201

Natalizumab (Tysabri®) is the first approved for therapy, commertially available selective antagonist of integrins. Integrins are glycoproteins belonging to adhesion molecules family, which play an important role in the process of cell adhesion. Natalizumab binds to α4 chain of integrins α4β1 and α4β7 present on the surface of almost all subpopulations of leukocytes. Blockade of interaction between integrin and its ligand prevents leukocyte transmigration through endothelium to the tissue site of inflammation. The clinical efficacy of natalizumab in remitting-relapsing MS was analyzed in two multicenter, randomized and placebo controlled third phase clinical trials: AFFIRM (Natalizumab Safety and Efficacy in RR-MS) and SENTINEL [Safety and Efficacy of Natalizumab in Combination with Avonex (IFN-β-1α) in Patients with MS). In AFFIRM trial natalizumab was evaluated in monotherapy, in SENTINEL study as add on therapy to IFN-β-1α. Both trials confirmed that natalizumab is beneficial in all analyzed endpoints. There was statistically significant decrease of relapse number and the risk of the disease progression. There was also beneficial influence of natalizumab therapy on the central nervous system (CNS) MRI parameters. After two years of therapy the number of gadolinium-enhanced MS plaques, as well as the number of the new and enlarging hyperintensive T2 plaques, was decreased. Because of the rare but serious side effect (progressive multifocal leukoencephalopathy, PML) the registration of natalizumab was suspended in June 2004. Detailed analysis of the results of both third phase clinical trials led to reapproval of natalizumab to therapy in June 2006. The strict criteria of patients’ inclusion to natalizumab therapy were established to minimize the risk of the serious side effects.

Natalizumab (Tysabri®) jest pierwszym dostępnym komercyjnie lekiem będącym selektywnym antagonistą integryn. Integryny są glikoproteinami należącymi do grupy molekuł adhezyjnych i odgrywającymi istotną rolę w procesie adhezji komórkowej. Natalizumab wiąże się z podjednostką α4 integryn α4β1 i α4β7 obecnych na powierzchni prawie wszystkich leukocytów. Zablokowanie oddziaływania pomiędzy integryną i jej ligandem zapobiega transmigracji leukocytów przez śródbłonek do miejsca rozwoju reakcji zapalnej. Skuteczność leczenia stwardnienia rozsianego (SM) natalizumabem była oceniana w dwóch wieloośrodkowych, randomizowanych i kontrolowanych placebo badaniach klinicznych trzeciej fazy. Były to badania AFFIRM (Natalizumab Safety and Efficacy in RR-MS) oraz SENTINEL [Safety and Efficacy of Natalizumab in Combination with Avonex (IFN-β-Ια) in Patients with MS]. W pierwszym badaniu analizowano skuteczność natalizumabu w monoterapii SM, w drugim oceniano jego skuteczność w połączeniu z leczeniem IFN-β-Ια. Wykazano, iż terapia natalizumabem wpływała korzystnie na wszystkie analizowane parametry końcowe obu badań. Zaobserwowano istotny statystycznie spadek ilości rzutów SM oraz spadek ryzyka progresji tej choroby. Udowodniono również korzystny wpływ leczenia natalizumabem na obraz NMR ośrodkowego układu nerwowego. Po 2 latach terapii zaobserwowano spadek ilości plak Gd+, zmniejszenie liczby nowych plak oraz powiększających się plak hiperintensywnych w obrazach T2-zależnych. Ze względu na wystąpienie groźnego powikłania pod postacią postępującej wieloogniskowej leukoencefalopatii (PML) rejestracja natalizumabu została zawieszona w czerwcu 2004 r. Dokładna analiza wyników badań trzeciej fazy spowodowała przywrócenie rejestracji natalizumabu w czerwcu 2006 r. Ustalone zostały szczegółowe kryteria włączenia pacjentów do tego leczenia w celu zminimalizowania ryzyka wystąpienia poważnych efektów ubocznych.

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1 Jałosiński M.

1 Kędra B.

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1 Zaręba K.

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Determination of the Activity of CD134 (OX-40) and CD137 (4-1BB) Adhesive Nolecules by Means of Flow Cytometry in Patients with Colorectal Cancer Metastases to the Liver

Natalizumab: nowa droga w terapii stwardnienia rozsianego