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Renal cell cancer (RCC) is one of the most important urogenital tumors because of it's high mortality and increasing incidence. RCC, which accounts about 3% of all malignant tumors in the adults, is the most lethal urogenital cancer. The high mortality rate stimulate investigator groups to study RCC pathogenesis including immunological part. It is interesting that immunotherapy was firstly started in patients with metastatic RCC using IL-2 and interferon gamma. The first results were promising but the exact mechanism of acting was not found. In the RCC, as in the others tumors, immune cells (T lymphocytes, NK and NKT cells) are responsible for main antitumor effect. Their effect was caused by cytotoxic activity on the tumor cells. In the investigation investigators will determine patterns of aggregation of tumor infiltrating immune cells in the blood, healthy kidney and carcinomatous tissue. But, presence of this cells not implicated that this cells are active. Their activity will be determined by proofing cytotoxicity of different subgroup of immune cells. In that way investigators will present different patterns of aggregation of tumor infiltrating immune cells and their cytotoxicity which will direct that this cells are active with antitumor effect. Correlation of collected data with classical prognostic factors in the patients with RCC as tumor staging, tumor grading (Fuhrman) and histological subtype will help to determine some immunological factors as possible new prognostic factors. For conclusion, the results of this study will allow better understanding of RCC pathogenesis, specially their immunological part and become a foundation for the future investigations.
Cellular immunity will be investigated in the two group of patients: operated patients with RCC and healthy volunteers.
In the study investigators will determine patterns of aggregation of tumor infiltrating immune cells in the blood (RCC patients and volunteers), healthy kidney and carcinomatous tissue as their cytotoxicity (only RCC patients).
Investigators will determine:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| RCC patients | RCC patients (30 pts) will include patients with kidney cancer (renal cell cancer). Investigators will collect and analyze:
| ||
| Healthy patients | In this group (30 patients) will be recruiting healthy patients (volunteer). Investigators will collect and analyze:
|
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| Measure | Description | Time Frame |
|---|---|---|
| Distribution of immune cells between two groups measured in the blood samples | Determination of distribution of immune cells between two groups in their blood samples with their comparison. | 7 months |
| Distribution of immune cells between different tissue samples (RCC vs. healthy tissue vs. borderline tissue) | Determination of distribution of immune cells between different tissue samples with their comparison | 7 months |
| Determination of NK cytotoxicity | Determination of NK cytotoxicity | 7 months |
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Inclusion Criteria:
Exclusion Criteria:
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Two groups of the patients:
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| Name | Affiliation | Role |
|---|---|---|
| Dean Markić, MD, PhD | Clinical Hospital Center Rijeka | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Hospital Center Rijeka | Rijeka | 51 000 | Croatia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22105113 | Background | Sotosek S, Sotosek Tokmadzic V, Mrakovcic-Sutic I, Tomas MI, Dominovic M, Tulic V, Sutic I, Maricic A, Sokolic J, Sustic A. Comparative study of frequency of different lymphocytes subpopulation in peripheral blood of patients with prostate cancer and benign prostatic hyperplasia. Wien Klin Wochenschr. 2011 Dec;123(23-24):718-25. doi: 10.1007/s00508-011-0096-7. Epub 2011 Nov 23. | |
| 20537642 |
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All included patients will signed informed consent. Individual participant data will not be shared with other researchers.
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| ID | Term |
|---|---|
| D007680 | Kidney Neoplasms |
| D002292 | Carcinoma, Renal Cell |
| ID | Term |
|---|---|
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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Investigators will collect:
patients with kidney cancer:
healthy control:
| Background |
| Sotosek Tokmadzic V, Laskarin G, Mahmutefendic H, Lucin P, Mrakovcic-Sutic I, Zupan Z, Sustic A. Expression of cytolytic protein-perforin in peripheral blood lymphocytes in severe traumatic brain injured patients. Injury. 2012 May;43(5):624-31. doi: 10.1016/j.injury.2010.05.009. Epub 2010 May 26. |
| 22220404 | Background | Mrakovcic-Sutic I, Bacic D, Golubovic S, Bacic R, Marinovic M. Cross-talk between NKT and regulatory T cells (Tregs) in modulation of immune response in patients with colorectal cancer following different pain management techniques. Coll Antropol. 2011 Sep;35 Suppl 2:57-60. |
| 28384121 | Background | Xia Y, Zhang Q, Zhen Q, Zhao Y, Liu N, Li T, Hao Y, Zhang Y, Luo C, Wu X. Negative regulation of tumor-infiltrating NK cell in clear cell renal cell carcinoma patients through the exosomal pathway. Oncotarget. 2017 Jun 6;8(23):37783-37795. doi: 10.18632/oncotarget.16354. |
| 15887015 | Background | Cozar JM, Canton J, Tallada M, Concha A, Cabrera T, Garrido F, Ruiz-Cabello Osuna F. Analysis of NK cells and chemokine receptors in tumor infiltrating CD4 T lymphocytes in human renal carcinomas. Cancer Immunol Immunother. 2005 Sep;54(9):858-66. doi: 10.1007/s00262-004-0646-1. Epub 2005 May 11. |
| 12394762 | Background | Shabtai M, Ye H, Frischer Z, Martin J, Waltzer WC, Malinowski K. Increased expression of activation markers in renal cell carcinoma infiltrating lymphocytes. J Urol. 2002 Nov;168(5):2216-9. doi: 10.1016/S0022-5347(05)64358-3. |
| 25637538 | Background | Zhang Q, Jia Q, Deng T, Song B, Li L. Heterogeneous expansion of CD4+ tumor-infiltrating T-lymphocytes in clear cell renal cell carcinomas. Biochem Biophys Res Commun. 2015 Feb 27;458(1):70-6. doi: 10.1016/j.bbrc.2015.01.069. Epub 2015 Jan 28. |
| 22079021 | Background | Oldham KA, Parsonage G, Bhatt RI, Wallace DM, Deshmukh N, Chaudhri S, Adams DH, Lee SP. T lymphocyte recruitment into renal cell carcinoma tissue: a role for chemokine receptors CXCR3, CXCR6, CCR5, and CCR6. Eur Urol. 2012 Feb;61(2):385-94. doi: 10.1016/j.eururo.2011.10.035. Epub 2011 Nov 4. |
| 2972244 | Background | Finke JH, Tubbs R, Connelly B, Pontes E, Montie J. Tumor-infiltrating lymphocytes in patients with renal-cell carcinoma. Ann N Y Acad Sci. 1988;532:387-94. doi: 10.1111/j.1749-6632.1988.tb36356.x. No abstract available. |
| D052776 |
| Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |