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1

Ocena ekspresji Foxp3 i RORgamma t w jednojądrzastych komórkach krwi obwodowej u chorych z rakiem krtani jako wskaźników zaawansowania zmian nowotworowych — badania wstępne

100%

Papież P., Bryś M., Lewy-Trenda I., Stasikowska O., Woś J., Papierz W.

Otolaryngologia Polska

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2011

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vol. 65(5)

109-116

EN

The degree of activation of cells involved in cellular immune re-sponse against tumor antigens (cytotoxic lymphocytes Te) as well as efficiency of the mechanisms which promote immunosuppression (Treg — regulatory cells CD4±CD25±Foxp3±) may determine the course of the neoplastic disease. The aim of this study was to assess the function of autologous peripheral blood mononuclear cells (PBMCs) involved in the immunological processes on the basis of expression of Foxp3 and RORgamma t molecules as well as analysis of the relationships with clinical and morphological features of the tumor (pT and pN stage, G feature, degree of invasiveness according to the TFG classification) in laryngeal carcinoma. Materia! and methods: The analysis included a group of 59 patients with verified squamous celt carcinoma of the larynx. In the pathologic evaluation pTNM classification criteria, depth of invasion and degree of histological dif-ferentiation were used. Expression levels of mRNA for Foxp3 and RORgamma t in peripheral blood mononuclear cells by quantitative analysis of the amplified product in real time (real-time RT2-PCR) were evaluated. The level of Foxp3 and RORgamma t protein expression by Western blot analysis was determined. Results: In squamous celt carcinomas of the larynx, with the highest tumor aggressiveness the significantly highest level of mRNA and protein expres-sion for Foxp3 molecule were observed. The severity of Foxp3 expression at both gene and protein level were positively linearly correlated with the degree of local extent of the tumor (pT3-4), depth of invasion (invasion of cartilage) and the degree of histological differentiation (low-differentiated tumors G3). In the study group of laryngeal cancers significantly lower level of RORgamma t expression in carcinomas with less invasive changes (pT1-2, high-differentiated tumors G1, carcinomas with microinvasion without evi-dence of invasion beyond the lamina propria) was also noted. Conclusions: The study results indicate the important role of immune celt activity as indicators of advancement of clinical and morphological changes in squamous celt carcinoma of the larynx

2

SILDENAFIL UPREGULATES TUMOR NECROSIS FACTOR α PRODUCTION IN PERIPHERAL BLOOD MONONUCLEAR CELLS OF HEALTHY MEN - PRELIMINARY REPORT

100%

Kaleta B., Boguska A., Borysowski J., Górski A.

Acta Poloniae Pharmaceutica - Drug Research

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2019

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vol. 76

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issue 1

123-128

EN

Sildenafil is a selective type 5 phosphodiesterase (PDE5) inhibitor, commonly used in the treatment of erectile dysfunction (ED) and pulmonary arterial hypertension (PAH). The results of recent studies suggest that this drug modulates function of the immune system. However, only few studies were performed in humans. Therefore, the aim of this study was to investigate the ability of sildenafil to regulate the production of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β and IL-6 in peripheral blood mononuclear cells (PBMCs) from healthy men. Phorbol myristate acetate (PMA) - stimulated and unstimulated PBMCs from 16 participants were cultured in the absence or presence of sildenafil (400 ng/ml and 4 µg/ml). TNF-α, IL-1β and IL-6 concentrations in culture supernatants were measured by enzyme-linked immunosorbent assay (ELISA). Cell viability was assessed by trypan blue staining. Sildenafil at a concentration of 400 ng/ml significantly increased TNF-α production in stimulated PBMCs (p<0.05) but had no effects on IL-1β and IL-6. The drug did not affect PBMCs viability. This is the first report describing such effects of sildenafil in humans.

3

Ocena ekspresji Foxp3 i RORgamma t w jednojądrzastych komórkach krwi obwodowej u chorych z rakiem krtani jako wskaźników zaawansowania zmian nowotworowych - badania wstępne

100%

Papież P., Bryś M., Lewy-Trenda I., Stasikowska O., Woś J., Papierz W., Starska K.

Polish Journal of Otolaryngology

|

2011

|

vol. 65

|

issue 5

109-116

EN

The degree of activation of cells involved in cellular immune re-sponse against tumor antigens (cytotoxic lymphocytes Te) as well as efficiency of the mechanisms which promote immunosuppression (Treg - regulatory cells CD4±CD25±Foxp3±) may determine the course of the neoplastic disease. The aim of this study was to assess the function of autologous peripheral blood mononuclear cells (PBMCs) involved in the immunological processes on the basis of expression of Foxp3 and RORgamma t molecules as well as analysis of the relationships with clinical and morphological features of the tumor (pT and pN stage, G feature, degree of invasiveness according to the TFG classification) in laryngeal carcinoma. Materia! and methods: The analysis included a group of 59 patients with verified squamous celt carcinoma of the larynx. In the pathologic evaluation pTNM classification criteria, depth of invasion and degree of histological dif-ferentiation were used. Expression levels of mRNA for Foxp3 and RORgamma t in peripheral blood mononuclear cells by quantitative analysis of the amplified product in real time (real-time RT2-PCR) were evaluated. The level of Foxp3 and RORgamma t protein expression by Western blot analysis was determined. Results: In squamous celt carcinomas of the larynx, with the highest tumor aggressiveness the significantly highest level of mRNA and protein expres-sion for Foxp3 molecule were observed. The severity of Foxp3 expression at both gene and protein level were positively linearly correlated with the degree of local extent of the tumor (pT3-4), depth of invasion (invasion of cartilage) and the degree of histological differentiation (low-differentiated tumors G3). In the study group of laryngeal cancers significantly lower level of RORgamma t expression in carcinomas with less invasive changes (pT1-2, high-differentiated tumors G1, carcinomas with microinvasion without evi-dence of invasion beyond the lamina propria) was also noted. Conclusions: The study results indicate the important role of immune celt activity as indicators of advancement of clinical and morphological changes in squamous celt carcinoma of the larynx.

4

INCREASED LEVELS OF INTERLEUKIN-10 EXPRESSION COMPARED TO INTERLEUKIN-6 IN LEUKOCYTES OF HEALTHY SUBJECTS. COULD IT BE USEFUL IN THE FUTURE OF THE DEPRESSION DIAGNOSIS?

88%

Grzybkowska A., Anczykowska K., Pyczek J. M., Żychowska M.

Acta Neuropsychologica

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2018

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vol. 16(3)

243-248

EN

It is a well known, that the physical activity promotes mental health. Physically active people relatively rarely suffer from psychosomatic and depressive disorders. It is possible that the differences in gene activity in peripheral blood leukocytes may be associated with depression, especially genes participating in inflammatory response. Thus, the aim of our study was to investigate the levels of IL6 and IL10 mRNA and IL10/IL6 ratio in peripheral blood leukocytes in healthy, physically active individuals. One hundred healthy young men (20-23 years old) participated in this study. All of them declared regular physical activity. Participants were non-smokers, and consumed alcohol occasionally. To access genes expression, 2 ml of venous blood was collected. RNA isolation was performed and then the relative expression of IL6 and IL10 was calculated using quantitative real-time polymerase chain reaction (Q-RT-PCR). Pro and anti-inflammatory balance was calculated as 2^relative of IL10/ 2^relative expression of IL6. Low expression of tested genes was found in healthy young men. Mean expression for IL6 was 2^0.051 (n=90) and for IL10 2^0.08 (n=98). Mean ratio IL10/IL6 was 2^1.58. Higher expression of IL10 compared to IL6 may be essential not only for the physical performance but also for the mental health. Diverse reports in the literature may be associated with choosing various control groups, i.e. sedentary or older individuals. It is possible, that measuring the expression of IL6 and IL10 (especially the ratio IL10/IL6) in peripheral blood leukocytes may be useful in the assessment of depressive disorders. Thus, molecular study of active young men can confirm the need for physical activity among people suffering from depression, but further studies are needed, particularly among people with psychosomatic disorders.

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1 Acta Neuropsychologica

1 Acta Poloniae Pharmaceutica - Drug Research

1 Otolaryngologia Polska

1 Polish Journal of Otolaryngology

1 2019

1 2018

2 2011

2 Bryś M.

2 Lewy-Trenda I.

2 Papierz W.

2 Papież P.

2 Stasikowska O.

2 Woś J.

1 Anczykowska K.

1 Boguska A.

1 Borysowski J.

1 Grzybkowska A.

1 Górski A.

1 Kaleta B.

1 Pyczek J. M.

1 Starska K.

1 Żychowska M.

Ocena ekspresji Foxp3 i RORgamma t w jednojądrzastych komórkach krwi obwodowej u chorych z rakiem krtani jako wskaźników zaawansowania zmian nowotworowych — badania wstępne

SILDENAFIL UPREGULATES TUMOR NECROSIS FACTOR α PRODUCTION IN PERIPHERAL BLOOD MONONUCLEAR CELLS OF HEALTHY MEN - PRELIMINARY REPORT

Ocena ekspresji Foxp3 i RORgamma t w jednojądrzastych komórkach krwi obwodowej u chorych z rakiem krtani jako wskaźników zaawansowania zmian nowotworowych - badania wstępne

INCREASED LEVELS OF INTERLEUKIN-10 EXPRESSION COMPARED TO INTERLEUKIN-6 IN LEUKOCYTES OF HEALTHY SUBJECTS. COULD IT BE USEFUL IN THE FUTURE OF THE DEPRESSION DIAGNOSIS?