Aleksander Wasiutyński

The possible role of factor H in colon cancer resistance to complement attack

A soluble complement inhibitor factor H (FH) and its splice variant factor H‐like protein (FHL) have been recently discovered to play a major role in malignant cell escape from complement‐mediated cytotoxicity in lung‐, ovarian‐ and glia‐derived neoplasms. The role of FH in colon cancer has not yet been examined. Here, we studied immunocytochemically FH/FHL expression in tumor samples derived from 40 patients, with both primary colon adenocarcinoma and metastatic foci in the liver. FH/FHL immunoreactivity was present in stroma of both primary and metastatic tumors, in virtually all patients. The cellular immunoreactivity was observed infrequently. Importantly, when analyzed quantitatively, FH/FHL immunoreactivity was significantly increased in liver metastases when compared with the primary sites. In addition, we have analyzed FH and FHL expression in 5 colon cancer cell lines: SW480, SW620, HCT116, HT‐29 and Lovo. FH mRNA and FH secretion were observed in SW620 and HT‐29 cells, whereas FHL was produced only by HT‐29 cell‐line. By confocal and electron microscopy, FH immunoreactivity was associated with the plasma membrane and intracellular vesicular structures. Finally, we have analyzed the role of FH in the susceptibility of SW620 colon cancer cells to complement‐mediated damage. When FH function was blocked, using specific antibody, the cells became more susceptible to lysis. Taken together, our results suggest an important role of FH/FHL in colon cancer cells defense against complement‐mediated cytotoxicity, and in metastatic process.

Spontaneous regression of renal cell carcinoma

Renal cell carcinoma (RCC) comprises 3–4% of all malignant tumours among adults in Poland. Spontaneous regression of RCC is a rare but well-known phenomenon. Its frequency is estimated to be approximately 1% and a large part of the percentage is accounted for by the regression of pulmonary metastases in the course of clear type of RCC treatment. We searched PubMed, Embase and SciVerse Scopus databases, identifying 59 case reports of spontaneous regression of RCC. Those medical histories come from reports from around the world and date back up to 40 years. This review includes their analysis as well as description of possible explanations of this phenomenon postulated by different authors, including both misdiagnosis and immunological reactions. This study indicates that reliable diagnostics and reporting of all the cases of spontaneous regression play a key role, as this is the only method which enables a better perspective in understanding this issue.

Urothelial bladder carcinoma in young patients is characterized by a relatively good prognosis

Abstract Introduction and aim. Urothelial bladder carcinoma (UBC) is a very rare condition in patients aged below 50 years. The aim of the study was to answer the question whether the characteristics of cancer in this group of patients differ from general UBC features. Material and methods. Altogether 2160 patients treated with primary transurethral resection due to a bladder tumor were included in the study. The mean age of the cohort was 69.1 years (range 11–100). Patients were divided into three subgroups depending on age: age <41 years (group 1), age 41–50 years (group 2), age >50 years (group 3). Sex ratio, tumor grade, and stage of disease were recorded. Results. Women constituted 18.5%, 19.2%, and 25.8% of the patients in groups 1, 2, and 3, respectively (P < 0.05). WHO grade 3 tumors were diagnosed in 0%, 8.5%, and 17.2%, respectively (P < 0.05). Non-invasive papillary carcinoma was found in 100.0%, 76.7%, and 62.7%, respectively (P < 0.05). The incidence of muscle-invasive bladder cancer was 0%, 11.0%, and 15.6%, respectively (P < 0.05). Conclusions. Pathological characteristics of UBC are dependent on the patients’ age. Being a very rare condition, UBC in young patients is characterized by a relatively good prognosis.

Loss of the Orphan Nuclear Receptor SHP Is More Pronounced in Fibrolamellar Carcinoma than in Typical Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) remains a major problem in oncology. The molecular mechanisms which underlie its pathogenesis are poorly understood. Recently the Small Heterodimer Partner (SHP), an orphan nuclear receptor, was suggested to be involved as a tumor suppressor in hepatocellular carcinoma development. To date, there are no such studies regarding fibrolamellar carcinoma, a less common variant of HCC, which usually affects young people and displays distinct morphological features. The aim of our project was to evaluate the SHP levels in typical and fibrolamellar hepatocellular carcinoma with respect to the levels of one of the cell cycle regulators, cyclin D1. We assessed the immunoreactivity levels of SHP and cyclin D1 in 48 typical hepatocellular carcinomas, 9 tumors representing the fibrolamellar variant, 29 non malignant liver tissues and 7 macroregenerative nodules. We detected significantly lower SHP immunoreactivity in hepatocellular carcinoma when compared to non malignant liver tissue. Moreover, we found that SHP immunoreactivity is reduced in fibrolamellar carcinoma when compared to typical hepatocellular carcinoma. We also found that SHP is more commonly lost in HCC which arises in the liver with steatosis. The comparison between the cyclin D1 and SHP expression revealed the negative correlation between these proteins in the high grade HCC. Our results indicate that the impact of loss of SHP protein may be even more pronounced in fibrolamellar carcinoma than in a typical form of HCC. Further investigation of mechanisms through which the loss of SHP function may influence HCC formation may provide important information in order to design more effective HCC therapy.

Study of the Effect of 3-Undecanone and 3-Undecanol on Cellular and Humoral Immunity in Mice

Abstract The in vivo effects of 3-undecanone and 3-undecanol on the cellular and humoral immunity were studied in inbred Balb/c mice. Mice were subjected to the inhalation of both compounds for three days. An increase of antibody production and increase of the lysozyme level in sera of mice which inhaled 10% 3-undecanol were observed. Mice that inhaled 3-undecanol presented a higher activation of respiratory burst (RBA test) and phagocytic activity of blood granulocytes (PKA test) than the corresponding controls. In the group that inhaled 3-undecanol the proliferative response of lymphocytes isolated from blood and the spleen to mitogens ConA and LPS was significantly higher than in the controls. The mice that inhaled 3-undecanone no immunostimulatory effects were observed

The study of the protein complement in myocardial infarction.

BACKGROUND Activation of the complement system during myocardial ischemia and reperfusion results in its injury by multiple processes. The aim of this study was to evaluate contribution of innate, humoral mechanisms of nonspecific immune response in the myocardium subjected to infarction. Complement components and inhibitors were analyzed. MATERIALS AND METHODS Myocardial specimens from the archives of Chair and Department of Pathology, Medical University of Warsaw from 2010 to 2013, were used in the study. The examined proteins were evaluated using immunohistochemistry and immunofluorescence techniques. Tissues from 36 men and 14 women, mean age 65.02 ± 14.65, were used in the study. The control group comprised healthy myocardial tissue collected from 10 subjects. RESULTS Statistical analysis of IHC reaction for proteins and inhibitors of the complement system and membrane attack complex demonstrated markedly higher immunoreactivity level in the myocardium with ischemic necrosis versus healthy myocardial tissue. A correlation analysis demonstrated statistically significant positive correlation between the examined proteins and inhibitors of the complement system and protectin and membrane attack complex. A significant correlation was not found between immunoreactivity of the examined proteins and clinical and morphological parameters of the analyzed cases. CONCLUSIONS Studies have shown that of the complement proteins presence on the surface of the myocardium subjected to ischemic destruction exacerbate.

Possible role of complement factors and their inhibitors in the myocardial infarction: an immunohistochemical study.

Ongoing development of our civilization is accompanied by a marked increase of incidence of cardiovascular diseases and cardiovascular mortality. Ischemic heart disease with its extreme form – myocardial infarction – is one of the main problems of modern medicine. Despite much research devoted to this disease entity, its pathomechanism remains incompletely understood. Basing on research reports, more and more emphasis is put on immune reactions in the myocardium. Available literature lacks detailed studies examining the role of complement system and its inhibitors in the development and pathogenesis of myocardial infarction. Cells of ischemic myocardium were proven to become foreign antigens for the immune system of the patients body. This results in complement activation of formation of so called membrane attacking complex that injures myocardial cells. By binding to its surface, it extends the myocardial destruction caused by the infarction itself. Results of immunochemistry studies presented in this paper have demonstrated the existence colocalization of complement components (C4d, C9) and membrane inhibitors (CD55, CD59) as well as soluble inhibitors (factor H) of the complement in the examined muscle tissue that underwent ischemic necrosis. Positive immunohistochemical reaction was found in the myocardial cells, intercellular matrix and blood vessels.

Plasmacytic hyperplasia—the early form of posttransplant lymphoproliferative disorder—with atypical morphology and clinical course in patient after liver transplantation: a case report

This case report describes an early lesion of posttransplant lymphoproliferative disorder (PLTD)--plasmacytic hyperplasia with atypical morphology. The 54-year-old patient was 4 months after liver transplantation due to alcoholic cirrhosis. The postoperative course had been uneventful without graft rejection episodes. Primary immunosuppressive therapy included tacrolimus and prednisone. On admission to the hospital the patient showed rapidly increasing jaundice, hepatomegaly, anemia, thrombocytopenia, and significant leukocytosis. A biopsy suggested generalized infection. Acute Epstein-Barr virus (EBV) infection was confirmed using serological methods. Despite treatment the patient died. On autopsy we found features of generalized infection. Histological examination of the enlarged lymph nodes showed plasmacytic hyperplasia despite lymph node atrophy. Plasmacytic hyperplasia, an early lesion of PTLD despite usually a good prognosis with multifactor therapy may display a rapid course that leads to death through intensified immunosuppression. In accordance with other reports we confirmed reactivation of EBV infection as the probable cause of plasmacytic hyperplasia. The lymph node morphology of plasmacytic hyperplasia may be atypical with atrophy of lymphoid components accompanying plasma cell proliferation.

Morphometric abnormalities in spleen and kidney of the progeny of mice fed American cranberry extract (Vaccinium macrocarpon) during pregnancy and lactation.

Cranberries and cranberry-derived diet supplements are often recommended for the treatment of urinary tract infections, also during pregnancy. These products contain strongly anti-angiogenic chemical compounds which could not be indifferent to the developing fetus. In the present work we evaluated the effect of feeding pregnant and lactating mice American cranberry extract (daily dose 0.88 mg) on the morphology and some parameters of spleen and kidney function of their adult progeny. Six weeks after delivery the morphometry of spleen and kidney, cytometric analysis of spleen lymphocytes, evaluation of humoral response to SRBC (Sheep Red Blood Cells), and examination of serum creatinine/urea concentration, were performed in the offspring. Spleens of progeny from experimental (E) group differed from the spleens of progeny of control mice in the lower number of lymphatic nodules and their larger diameter. Cytometry of spleen cells from progeny of E mothers revealed more CD19+ and CD8+ lymphocytes than in the control group. No difference was seen in the response to immunization by red blood cells of sheep (SRBC) between control and E offspring. An increase in the diameter of glomeruli was observed in the kidneys of the experimental group in comparison with the control group. No abnormalities in creatinine and urea serum level were observed. A higher concentration of VEGF and bFGF in E offspring sera in comparison to the controls was seen. CONCLUSION Although the observed differences between the control and experimental group were not large, caution is recommended in using cranberries and their extracts during pregnancy until more research will be done on this topic.

Do all well-differentiated thyroid cancers constitute a definite contraindication to obtaining organs for transplantation? A case report.

In this case a thyroid gland tumor was diagnosed with fine needle aspiration (FNA) in a 34-year-old female donor of a liver fragment for living related liver transplantation. This diagnosis disqualified her as a donor. The increased incidence of thyroid cancer in Poland presents the possibility of their occurrence in potential donors. Well-differentiated thyroid papillary carcinomas larger than 1 cm in diameter, as well as follicular and medullary carcinomas (regardless their size and or clinical staging), present absolute contraindication to donation. Papillary microcarcinoma restricted to the thyroid gland (with no metastases in local lymph nodes) because of its specific behavior and almost always benign course, requires an individualized approach. It seemed that when a recipient is in a life-threatening condition, we should consider taking organs from a donor suffering of papillary microcarcinoma restricted to the thyroid gland.