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1.
Int J Mol Sci ; 25(6)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38542521

RESUMO

Endometrial cancer (EC) is the most common gynecological malignancy. This study aimed to evaluate the expression of E-cadherin and N-cadherin in primary endometrial lesions and the endocervix in patients with EC to identify noninvasive predictive factors. In this single-center retrospective study, data on 101 patients who underwent surgery for EC were collected. The immunohistochemical expression of E-cadherin and N-cadherin was assessed depending on the tumor grade, location, and cell differentiation. Correlations between E-cadherin and N-cadherin levels in the endocervix and the primary tumor were determined. The degree of histological tumor differentiation significantly affected E-cadherin expression (p = 0.04) but had no impact on N-cadherin levels. In type II EC, the expression of both cadherins in the tumor tissue differed from their endocervical levels. The expression of E-cadherin differed significantly between the endocervix (p < 0.001) and the tumor (p = 0.001), depending on the type of EC. The expression of E-cadherin was related to the N-cadherin level only in the endocervix in patients with type II EC (p = 0.02). E-cadherin and N-cadherin were expressed in the endocervix in patients with EC. The expression of cadherins, determined during cervical cytology, may be a valuable clinical marker of EC.


Assuntos
Colo do Útero , Neoplasias do Endométrio , Feminino , Humanos , Colo do Útero/metabolismo , Estudos Retrospectivos , Neoplasias do Endométrio/metabolismo , Caderinas/metabolismo , Endométrio/metabolismo , Biomarcadores Tumorais , Transição Epitelial-Mesenquimal
2.
J Transl Med ; 18(1): 220, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32487171

RESUMO

BACKGROUND: Previous studies have shown clinical relevance of programmed death-ligand 1 (PD-L1) and soluble PD-L1 (sPD-L1) in human cancers. However, still contradictory results exist. Our aim was evaluation of PD-L1-expressing monocytic myeloid-derived suppressor cells (M-MDSCs), monocytes/macrophages (MO/MA), tumour cells (TC) and immune/inflammatory cells (IC) as well as investigation of the sPD-L1 in ovarian cancer (OC) patients. METHODS: The group of 74 pretreatment women were enrollment to the study. The expression of PD-L1 on M-MDSCS and MO/MA was assessed by flow cytometry. The profile of sPD-L1 was examined with ELISA. The expression of PD-L1 in mononuclear cells (MCs) was analyzed using real time PCR. PD-L1 immunohistochemical analysis was prepared on TC and IC. An in silico validation of prognostic significance of PD-L1 mRNA expression was performed based microarray datasets. RESULTS: OC patients had significantly higher frequency of MO/MA versus M-MDSC in the blood, ascites and tumour (each p < 0.0001). In contrast, PD-L1 expression was higher on M-MDSCs versus MO/MA in the blood and ascites (each p < 0.0001), but not in the tumour (p > 0.05). Significantly higher accumulation of blood-circulating M-MDSC, MO/MA, PD-L1+M-MDSC, PD-L1+MO/MA and sPD-L1 was observed in patients versus control (p < 0.001, p < 0.05, p < 0.001, p < 0.001 and p < 0.0001, respectively). Accumulation of these factors was clinicopathologic-independent (p > 0.05). The expression of PD-L1 was significantly higher on IC versus TC (p < 0.0001) and was clinicopathologic-independent (p > 0.05) except higher level of PD-L1+TC in the endometrioid versus mucinous tumours. Interestingly, blood-circulating sPD-L1 positively correlated with PD-L1+M-MDSCs (p = 0.03) and PD-L1+MO/MA (p = 0.02) in the blood but not with these cells in the ascites and tumours nor with PD-L1+TC/IC (each p > 0.05). PD-L1 and sPD-L1 were not predictors of overall survival (OS; each p > 0.05). Further validation revealed no association between PD-L1 mRNA expression and OS in large independent OC patient cohort (n = 655, p > 0.05). CONCLUSIONS: Although PD-L1 may not be a prognostic factor for OC, our study demonstrated impaired immunity manifested by up-regulation of PD-L1/sPD-L1. Furthermore, there was a positive association between PD-L1+ myeloid cells and sPD-L1 in the blood, suggesting that sPD-L1 may be a noninvasive surrogate marker for PD-L1+myeloid cells immunomonitoring in OC. Overall, these data should be under consideration during future clinical studies/trials.


Assuntos
Antígeno B7-H1 , Células Supressoras Mieloides , Neoplasias Ovarianas , Feminino , Humanos , Macrófagos , Monócitos , Neoplasias Ovarianas/genética
4.
Int J Med Sci ; 17(18): 2987-2997, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33173419

RESUMO

Introduction: mTOR inhibitors are anticancer agents affecting mTOR/AKT/PI3K pathway that is one of the most important in human cancer cells. Hyperactivation of mTOR/AKT/PI3K and overexpression of this pathway members are frequently reported in uterine sarcoma and carcinosarcoma. Present study is aimed to assess the activity of the two mTOR inhibitors (rapamycin - RAP and sapanisertib - MLN) as a single agent and combined with gemcitabine (GEM, one of substances commonly used in systemic anticancer treatment) in uterine sarcoma and carcinosarcoma in vitro models. Material and methods: SK-UT-1 and SK-UT1-B (uterine carcinosarcoma), MES-SA (leiomyosarcoma) and ESS-1 (endometrial stromal sarcoma) cell lines were used. An MTT assay was performed to examine the cytotoxicity of RAP, MLN and mixtures: RAP+MLN, RAP+GEM, MLN+GEM against these cells. The interactions between tested compounds were assessed in isobolographic analysis. Results and conclusions: Carcinosarcoma cell lines (both SK-UT-1 and SK-UT-1B) do not respond to RAP and respond relatively weakly to MLN treatment. Additive and supraadditive effects were noted for combined treatment with GEM and MLN. Endometrial stromal sarcoma cell line (ESS-1) occured to be sensitive to both RAP and MLN, but the response was stronger for MLN. Additive effect of all tested drug combinations was observed for ESS-1. Leiomyosarcoma cell line (MES-SA) was found sensitive to both mTOR inhibitors. Additive effects in combinations of GEM, RAP and MLN were observed, what makes them promising for future preclinical and clinical trials. Additivity with slight tendency towards antagonism between GEM and MLN observed in MES-SA cell line is unexpected finding and might prompt the mechanistic research aimed to explain this phenomenon.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinossarcoma/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Leiomiossarcoma/tratamento farmacológico , Sarcoma do Estroma Endometrial/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinossarcoma/patologia , Linhagem Celular Tumoral , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Sinergismo Farmacológico , Neoplasias do Endométrio/patologia , Feminino , Humanos , Leiomiossarcoma/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Sarcoma do Estroma Endometrial/patologia , Transdução de Sinais/efeitos dos fármacos , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Gencitabina
5.
Ginekol Pol ; 89(1): 7-12, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29411340

RESUMO

OBJECTIVES: The role of angiogenesis in leiomyosarcomas still remains unclear. The aim of this study was to evaluate the NRP1 expression in the leiomyosarcoma tissues and to find the relations between its expression and the clinical features. MATERIAL AND METHODS: The study group consisted of 50 patients with diagnosis of the uterine leiomyosarcoma. Clinical and follow up data were collected. Using immunohistochemical methods the expression of NRP1 was detected. RESULTS: The lack of NRP1 expression was found in 14 cases, positive (weak or moderate) expression was noted in 36 cases. The significantly higher expression of NRP1 was observed in more severe clinical stages in comparison to lower stages of the disease. The significantly shorter survival of patients with the positive expression of NRP1 in leiomyosarcoma was observed. CONCLUSIONS: The expression of NRP1 is associated with clinical advancement and worse prognosis in uterine LMS. Neuropilin 1 can be widely used as a postoperative survival predictor for the patients suffering from uterine LMS.


Assuntos
Leiomiossarcoma/metabolismo , Neuropilina-1/metabolismo , Neoplasias Uterinas/metabolismo , Adulto , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Leiomiossarcoma/patologia , Pessoa de Meia-Idade , Neoplasias Uterinas/patologia
6.
Wiad Lek ; 71(5): 1089-1094, 2018.
Artigo em Polonês | MEDLINE | ID: mdl-30176647

RESUMO

Ovarian cancer is a serious diagnostic and clinical issue. It belongs to the group of cancers with the highest mortality rate, that is why new, effective methods of therapy have been sought after. In recent years, researchers have been paying attention to the use of immunothetapy in the treatment of ovarian cancer. Currently, the numer of studies with the use of PD-1/PD-L1 pathway inhibitors is increasing. It has been reported that PD-1 receptor and its ligand are expressed on tumor cells and immunology system cells in patients with ovarian cancer. Increased expression of PD-1/PD-L1 is one of the inhibition mechanisms of the anti-tumor response by induction of peripheral tolerance. That seems why blocking PD-1/PD-L1 may be so important. A significant role in activation of programmed death cell-1 is attributed to tumor microenvironment (TME). In this review we have described the meaning of PD-1/PD-L1 pathway in ovarian cancer pathogenesis and current results of clinical trials using PD-1/PD-L1 inhibitors. Numerous clinical trials are focused on the effectiveness of immunotherapies as both monotherapy and combination therapy. The promising results of initial research phases are the basis for taking action on a larger scale. Perhaps this will allow in the future to use inhibitors of the PD-1/PD-L1 pathway in the treatment of ovarian cancer.


Assuntos
Antígeno B7-H1/metabolismo , Neoplasias Ovarianas/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Transdução de Sinais , Antineoplásicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Feminino , Humanos , Imunoterapia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/etiologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores
7.
Ginekol Pol ; 88(3): 138-140, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28397202

RESUMO

OBJECTIVES: The objective of the study was to retrospectively evaluate the density of vessels exhibiting positive glycoprotein CD34 expression in the uterine leiomyosarcoma tissues and their correlation with the age of patients at the time of tumor diagnosis. MATERIAL AND METHODS: The archival paraffin blocks with the cancer tissues collected from 50 patients suffering from uterine leiomyosarcoma were used together with their clinical and demographic data. The immunohistochemical peroxidase-de-pendent methods were used to detect microvessels with positive CD34 expression. The glycoprotein CD34 expression was evaluated as a density of microvessel showing the positive immunohistochemical reaction (MVDCD34). RESULTS: The negative, statistically significant correlation between the age of patients (at the moment diagnosis) and the MVDCD34+ (R = -0.289, p = 0.042) was found. CONCLUSIONS: The study's findings may suggest that the tissues of younger people constitute a permissive environment for pro-angiogenic factors.


Assuntos
Leiomiossarcoma/patologia , Microvasos/patologia , Neoplasias Uterinas/patologia , Adulto , Fatores Etários , Idoso , Antígenos CD34/metabolismo , Feminino , Humanos , Leiomiossarcoma/irrigação sanguínea , Leiomiossarcoma/diagnóstico , Microvasos/metabolismo , Pessoa de Meia-Idade , Neoplasias Uterinas/irrigação sanguínea , Neoplasias Uterinas/diagnóstico
8.
Wiad Lek ; 70(1): 74-80, 2017.
Artigo em Polonês | MEDLINE | ID: mdl-28343198

RESUMO

Ovarian cancer is a malignancy of high mortality rates. In respect of the number of deaths caused by cancers it occupies the fourth place among women in Poland. Recent studies are focusing on the role of immune system in ovarian cancer pathogenesis. It has been reported that immune response against ovarian cancer cells may be inhibited by a number of immunosuppressive mechanisms active in cancer microenvironment. It causes difficulties in recognizing and destroying cancer cells by immune system which leads to the development of immune tolerance and is associated with a low efficacy of standard therapeutic strategies. In the presented paper we have described selected, new immunosuppressive mechanisms in ovarian cancer patients. They may be a novel, additional and relevant criterion that should be considered whilst developing new therapeutic strategies. Possibly, modulation of immunosuppressive mechanisms could contribute to modifying standard therapies and in consequence improve treatment outcome in ovarian cancer patients.


Assuntos
Sistema Imunitário , Tolerância Imunológica , Neoplasias Ovarianas/imunologia , Feminino , Humanos , Imunoterapia , Neoplasias Ovarianas/etiologia , Neoplasias Ovarianas/terapia
9.
Wiad Lek ; 69(6): 799-803, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28214818

RESUMO

The low incidence of uterine sarcomas requires many issues associated with its biology and clinical course to be followed with more research. Unsatisfactory surgical outcomes and a high risk of cancer dissemination make it worthwhile to consider the feasibility of supplementary systemic treatment. The currently employed chemo- and hormonal therapy is characterised by low efficacy. There is some hope in reports on targeted treatment. However, a comprehensive assessment of the efficacy of this kind of therapy is restricted by a small number of patients using it. Moreover, clinical studies using targeted therapies involve patients with a highly advanced disease, and the therapeutic results are assessed mainly via analysis of progression-free survival but not the clinical response.


Assuntos
Gerenciamento Clínico , Leiomiossarcoma/tratamento farmacológico , Neoplasias Uterinas/tratamento farmacológico , Antineoplásicos/uso terapêutico , Feminino , Humanos , Leiomiossarcoma/radioterapia , Leiomiossarcoma/cirurgia , Guias de Prática Clínica como Assunto , Neoplasias Uterinas/radioterapia , Neoplasias Uterinas/cirurgia
10.
Ginekol Pol ; 86(6): 414-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26255447

RESUMO

OBJECTIVES: Most investigators agree that endometriosis is associated with a state of subclinical, non-infectious peritoneal inflammation. The objective of the study was to assess concentrations of two markers of the acute inflammatory phase proteins, haptoglobin and ceruloplasmin, in peritoneal fluid of endometriotic women. MATERIAL AND METHODS: 229 women who underwent diagnostic or therapeutic laparoscopy were included in the study Minimal, mild, moderate and severe endometriosis according to ASRM was confirmed in 119 women (study groups), whereas 110 patients suffered from simple serous or dermoid ovarian cysts (reference groups). Haptoglobin and ceruloplasmin concentrations in the peritoneal fluid samples aspirated during laparoscopy were measured using commercially available radial immunodiffusion kits. RESULTS: The concentration of haptoglobin in the peritoneal fluid of women with endometriosis was significantly higher as compared to patients with serous and dermoid ovarian cysts. Significantly higher haptoglobin level was observed in patients with severe and moderate endometriosis as compared to women from both reference groups. No significant difference in the peritoneal fluid ceruloplasmin levels was found between patients with endometriosis and women from reference groups. However, it was noted that ceruloplasmin levels are higher in the subgroup of patients with severe endometriosis as compared to both reference groups and women with mild disease. CONCLUSIONS: Our results support the hypothesis that endometriosis is associated with subclinical inflammation within the peritoneal cavity It may be speculated that pro-inflammatory stimuli strong enough to cause an increase in acute inflammatory phase proteins peritoneal fluid concentrations are observed only in the advanced stages of the disease.


Assuntos
Ceruloplasmina/análise , Endometriose/metabolismo , Haptoglobinas/análise , Peritônio/química , Adulto , Biomarcadores/análise , Endometriose/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cistos Ovarianos/metabolismo , Cistos Ovarianos/patologia , Peritônio/metabolismo
11.
Prz Menopauzalny ; 14(2): 152-4, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26327905

RESUMO

Presence of fibrothecoma is not usually accompanied by elevated levels of tumor markers. In recent years, however, there have been isolated reports of fibrothecoma and Meigs' syndrome, accompanied by an increase in tumor markers. We present a case of fibrothecoma with Meigs' syndrome and elevated levels of both CA-125 (cancer antigen 125) and HE-4 (human epididymis protein 4). In this paper, we present a case of Meigs' syndrome associated with an increased CA-125 and HE-4 level due to ovarian fibrothecoma.

12.
Ginekol Pol ; 85(8): 600-4, 2014 Aug.
Artigo em Polonês | MEDLINE | ID: mdl-25219140

RESUMO

UNLABELLED: Uterine sarcomas are heterogeneous malignancies, both clinically and histologically. The process of oncogenesis depends on gene mutations and uncontrolled mitotic cell division that is promoted by blocking pathways of apoptosis. Caspase 9 and p53 protein play an important role in the process of cell apoptosis. OBJECTIVES: The aim of the study was to assess the expression of selected apoptosis proteins (caspase 9 and p53) using immunohistochemistry. MATERIAL AND METHODS: A total of 28 tissue samples diagnosed in postoperative histopathological examination as leiomyosarcoma were tested. Twenty eight samples of leiomyomas were used as the control group. Colorful reactions with appropriate antibodies were performed to assess the expression of caspase 9 and p53. From every section 5 fields on view were chosen, in each one 100 cells were assessed using 400x magnification. T-Student parametric test and U Mann-Whitney test were used for statistical analysis. RESULTS: Expression of caspase 9 was significantly lower (p < 0.05) in leiomyosarcoma tissues (33.2%) as compared to leiomyomas (60.4%). Expression of p53 protein was significantly lower in leiomyosarcoma tissues than in leiomyomas (30.1% vs. 51.3%, p < 0.001). CONCLUSIONS: Significantly lower expression of caspase 9 and p53 in leiomyosarcoma tissue samples suggests that impaired deregulation of apoptosis mechanisms plays a role in the development of these tumors.


Assuntos
Biomarcadores Tumorais/metabolismo , Caspase 9/metabolismo , Leiomioma/metabolismo , Leiomiossarcoma/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Feminino , Humanos , Imuno-Histoquímica
13.
Mediators Inflamm ; 2013: 624540, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23861560

RESUMO

The etiopathogenesis of endometriosis still remains unknown. Recent data provide new valuable information concerning the role of oxidative stress in the pathophysiology of the disease. It has been proved that levels of different lipid peroxidation end products are increased in both peritoneal fluid (PF) and serum of endometriotic patients. We assessed the concentration of oxidized low-density lipoproteins (oxLDL) in PF of 110 women with different stages of endometriosis and 119 women with serous (n = 78) or dermoid (n = 41) ovarian cysts, as the reference groups. PF oxLDL levels were evaluated by ELISA. We found that concentrations of oxLDL in PF of endometriotic women were significantly higher compared to women with serous but not dermoid ovarian cysts. Interestingly, by analyzing concentrations of oxLDL in women with different stages of the disease, it was noted that they are significantly higher only in the subgroup of patients with stage IV endometriosis as compared to women with ovarian serous cysts. In case of minimal, mild, and moderate disease, PF oxLDL levels were similar to those noted in reference groups. Our results indicate that disrupted oxidative status in the peritoneal cavity of women with endometriosis may play a role in the pathogenesis of advanced stages of the disease.


Assuntos
Endometriose/metabolismo , Peroxidação de Lipídeos , Lipoproteínas LDL/metabolismo , Cistos Ovarianos/metabolismo , Estresse Oxidativo , Adolescente , Adulto , Líquido Ascítico/metabolismo , Progressão da Doença , Endometriose/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Laparoscopia , Pessoa de Meia-Idade , Cistos Ovarianos/patologia , Oxigênio/química , Adulto Jovem
14.
Wiad Lek ; 66(2 Pt 2): 192-4, 2013.
Artigo em Polonês | MEDLINE | ID: mdl-25775816

RESUMO

The majority of adult women with endometriosis report that their symptoms started in adolescence. Early diagnosis and optimal treatment prevent disease progression and mitigate long-term morbidities, such as infertility and chronic pelvic pain.


Assuntos
Endometriose/diagnóstico , Endometriose/terapia , Infertilidade Feminina/prevenção & controle , Saúde da Mulher , Adolescente , Serviços de Saúde do Adolescente/organização & administração , Diagnóstico Precoce , Feminino , Ginecologia/organização & administração , Humanos
15.
Ginekol Pol ; 83(10): 737-43, 2012 Oct.
Artigo em Polonês | MEDLINE | ID: mdl-23383558

RESUMO

INTRODUCTION: The process of T cells activation is necessary for the performance of the defense functions. Successful activation depends on direct lymphocyte - antigen-presenting cell contact and signal transmission to the lymphocyte. Activated T cells exhibit surface expression of molecules such as CD69, CD25 and HLA-DR. The effect of cell activation is a cascade of molecular events leading to proliferation and clonal expansion of antigen-specific T cells. OBJECTIVES: The aim of this study was to evaluate the phenotype and T cell activation markers: CD69, CD25 and HLA - DR in the peripheral blood and tumor tissue of ovarian cancer patients. MATERIAL AND METHODS: The study group consisted of 26 patients operated due to ovarian cancer (FIGO Ilb - IV). Mononuclear immune cells were isolated from peripheral blood and ovarian cancer tissue. To obtain peripheral blood lymphocytes, blood was collected into heparinized tubes and diluted 1:1 with PBS, then layered on Gradisol L and centrifuged 20 minutes at 2800 rpm. Mononuclear cells were washed twice with PBS and labeled with monoclonal antibodies. A small piece of tumor tissue (about 1cm3) was fragmented with a surgical blade. Minced tissue was suspended in PBS and layered on Gradisol L for mononuclear cells isolation. To assess the phenotype and activation status of peripheral blood and tumor infiltrating lymphocytes, we used FACS Canto cytometer and monoclonal antibodies conjugated with fluorochromes: anti-CD3-FITC, anti-CD4-PE-Cy5, anti-CD8-APC, anti-CD25-PE, anti-CD69-PE-Cy7, anti-HLA-DR-PE-Cy7. Statistical analysis was performed using the Statistica 5.0 and Wilcoxon test. RESULTS: In all cases we detected T helper CD3+CD4+ and cytotoxic CD3+CD8+. T lymphocytes in both blood samples and tumor tissues. We observed no statistically significant difference in the percentage of CD3+ CD4+ cells among the mononuclear cells present in peripheral blood and tumor tissue. The percentage of CD3+CD8+ cytotoxic T lymphocytes was higher among mononuclear cells isolated from the tumor tissue. The percentage of CD3+ lymphocytes expressing the very early activation marker CD69 was significantly higher among tumor infiltrating lymphocytes compared with peripheral blood lymphocytes. Similarly the percentages of CD3+CD4+CD69+ T helper lymphocytes and CD3+CD8+CD69+ cytotoxic T lymphocytes were significantly higher on lymphocytes isolated from tumor tissue when compared to blood. The expression of an early activation marker - CD25 was significantly higher on the CD3+ and CD3+CD8+ peripheral blood lymphocytes compared to CD3+ and CD3+CD8+ tumor infiltrating lymphocytes. There were no statistically important differences between the percentages of, isolated from blood and tissue, CD3+CD4+ T helper lymphocytes. The expression of the late activation marker - HLA-DR was significantly higher on CD3+ lymphocytes isolated from tumor tissue compared with peripheral blood. Similarly the percentages of CD3+CD4+ lymphocytes and CD3+CD8+ cytotoxic T cells expressing HLA-DR were significantly higher among tumor infiltrating lymphocytes when compared to peripheral blood ones. CONCLUSIONS: T cells obtained from ovarian cancer tissues are activated cells. The state of T cell activation may be the result of direct contact of these cells with tumor antigens. The low expression of CD25 may suggest abnormal clonal expansion of antigen-specific lymphocytes.


Assuntos
Biomarcadores Tumorais/metabolismo , Citocinas/sangue , Ativação Linfocitária , Linfócitos do Interstício Tumoral/metabolismo , Neoplasias Ovarianas/imunologia , Linfócitos T Reguladores/metabolismo , Adulto , Idoso , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Citocinas/imunologia , Feminino , Antígenos HLA-DR/sangue , Humanos , Imunofenotipagem , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia
16.
Ginekol Pol ; 83(6): 424-8, 2012 Jun.
Artigo em Polonês | MEDLINE | ID: mdl-22880461

RESUMO

UNLABELLED: Knowledge of the role of interleukin 17 (IL-17) has led to the identification of new subpopulation of T helper lymphocytes--Th17 and T cytotoxic lymphocytes secreting IL-17 (Tc17). An increasing amount of attention is paid to their role in anti-tumor immunity. AIM: The aim of this study was to evaluate the percentage of peripheral blood, peritoneal fluid and cancer tissue CD4+ and CD8+ T lymphocytes producing IL-17 in patients with ovarian cancer MATERIAL AND METHODS: Forty patients operated due to advanced ovarian carcinoma and twenty-four patients with functional follicle ovarian cysts were recruited. Peripheral blood, peritoneal fluid and cancer tissue mononuclear cells from ovarian cancer patients were stimulated for 4 hours ex vivo with phorbol myristate acetate (PMA) (50 ng/ ml) and ionomycin (1 microg/ml). The percentage of CD4+ and CD8+ T cells producing IL-17 was measured using flow cytometry. RESULTS: CD4+ and CD8+ T lymphocytes producing IL-17 were detected in the peripheral blood, peritoneal fluid and cancer tissue of ovarian cancer patients. The percentage of CD4+ T cells producing IL-17 was higher in the peripheral blood, peritoneal fluid and cancer tissue when compared to CD8+/IL 17+ T cells. The percentage of CD4+/ IL-17+ was significantly higher in cancer tissue compared to T cells derived form peripheral blood. There was no difference in the percentage of CD4+/IL-17 + T cells between peripheral blood and peritoneal fluid and peritoneal fluid and cancer tissue of ovarian cancer patients. There was no difference in the percentage of CD8+/IL-17 + T lymphocytes in the peripheral blood, peritoneal fluid and cancer tissue in patients suffering from ovarian cancer. CONCLUSIONS: Increased percentage of CD4+/IL-17+ and CD8+/IL-17+ T cells in cancer tissue indicates that these cells are accumulated in ovarian cancer microenvironment.


Assuntos
Líquido Ascítico/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Interleucina-17/metabolismo , Neoplasias Ovarianas/imunologia , Feminino , Citometria de Fluxo , Humanos , Estadiamento de Neoplasias , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/patologia , Polônia , Linfócitos T/metabolismo
17.
Ginekol Pol ; 93(4): 321-328, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35156700

RESUMO

Comprehensive endometrial cancer staging requires mandatory lymph node status assessment. However, some randomized clinical studies show that full lymphadenectomy may have no therapeutic benefit in patients presented with early-stage disease. Sentinel lymph node mapping can be considered in patients at low to intermediate risk for nodal metastases and is an acceptable alternative to systemic lymphadenectomy for lymph node staging in FIGO stage I/II patients. Similarly, patients with serious comorbidities who might not tolerate a standard systemic lymphadenectomy may benefit from the procedure. Sentinel lymph node detection rates depend on cancer stage, histology, and technique used. The procedure is most performed with the use of radioactive technetium colloid (99mTc) combined with a blue dye or indocyanine green. Recently, more interest is also paid to new nanoparticles including carbon, superparamagnetic iron oxide, and mannose tracer agents. Growing interest in sentinel lymph node mapping technique has led to design increasing number of research projects regarding various mapping approaches in different endometrial cancer populations. Much attention has been paid to a non-invasive sentinel lymph node mapping technique e.g., radiomics. This article reviews the latest research on sentinel lymph node mapping perspectives in endometrial cancer patients.


Assuntos
Neoplasias do Endométrio , Linfonodo Sentinela , Feminino , Humanos , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela/métodos , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Consenso , Linfonodos/patologia , Excisão de Linfonodo , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/cirurgia , Neoplasias do Endométrio/patologia , Estadiamento de Neoplasias
18.
Nutrients ; 14(16)2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-36014877

RESUMO

One of the many factors involved in the development of uterine fibroids is vitamin D deficiency. One aspect of this deficiency is decreased serum concentration of calcidiol-25(OH)D, a metabolite of D3 vitamin. The active form of vitamin D3, which arises after numerous enzymatic reactions, is calcitriol-1,25(OH)2D3; this compound is transported to various body tissues. Vitamin D possesses extra-genomic effects due to its influence on various signaling pathways, i.e., through activating tyrosine kinases and by genomic effects via binding to a specific nuclear receptor, vitamin D receptor (VDR). The vitamin D/VDR complex regulates the expression of genes and is involved in the pathogenesis of fibroids. Numerous studies have shown that vitamin D supplementation reduces fibroid size. It has also been shown that the expression of VDR in myoma tissue is significantly lower than in the uterine muscle tissue at the tumor periphery. However, the expression of VDR in non-myoma uterine muscle has not previously been investigated. Our VDR expression studies were performed immunohistochemically with tissue microarrays (TMA) in three tissue groups: 98 uterine myoma tissues, 98 uterine tissues (tumor margin), and 12 tissues of normal uterine muscle (i.e., without fibroids). A statistical analysis showed significantly lower VDR expression in uterine muscle at the periphery of the fibroid than in healthy uterine muscle. Lower expression of VDR at the periphery of the myoma compared to that in normal uterine muscle may indicate potential for new myomas. This observation and the described reduction in the size of fibroids after vitamin D supplementation supports the hypothesis of causal development of uterine fibroids and may be useful for the prevention of re-development in the event of their excision from the uterus.


Assuntos
Leiomioma , Receptores de Calcitriol , Colecalciferol , Feminino , Humanos , Imuno-Histoquímica , Leiomioma/genética , Leiomioma/metabolismo , Receptores de Calcitriol/biossíntese , Receptores de Calcitriol/genética , Vitamina D , Deficiência de Vitamina D/genética , Deficiência de Vitamina D/metabolismo
19.
Ginekol Pol ; 82(5): 350-3, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21851033

RESUMO

INTRODUCTION: Podoplanin is a transmembrane glycoprotein expressed in endothelial lymphatic cells. It was proven to be a predictive marker in a variety of cancers e.g. mesothelioma and head and neck squamous-cell carcinoma. Ovarian clear cell carcinoma (OCCC) is a rare and unique histopathologic subtype of epithelial ovarian cancer (EOC). The molecular basis of that phenomenon remains unknown. OBJECTIVES: The aim of our study was to assess podoplanin expression on the protein level in OCCC. MATERIAL AND METHODS: Immunohistochemistry was performed on paraffin-embedded tissues from 19 patients with diagnosed OCCC. RESULTS: Podoplanin expression was present (moderate or strong) in 52% of OCCC cases (10/19). Nine of eleven (81.2%) postmenopausal and one of eight (12.5%) premenopausal women were podoplanin positive. No differences in podoplanin expression were found in relation to clinical features of the tumor CONCLUSION: The incidence of podoplanin expression is higher in ovarian clear cell adenocarcinoma in postmenopausal patients.


Assuntos
Adenocarcinoma de Células Claras/metabolismo , Biomarcadores Tumorais/análise , Glicoproteínas de Membrana/análise , Neoplasias Ovarianas/metabolismo , Adenocarcinoma de Células Claras/patologia , Adulto , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia
20.
Adv Clin Exp Med ; 30(10): 1057-1064, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34510841

RESUMO

BACKGROUND: Endometrial cancers (EC) are a heterogeneous group of malignant neoplasms differing in etiology, clinical-pathological features and prognosis. OBJECTIVES: To determine the differences between the expression of selected molecular factors and find connections between them in order to isolate possible biomarkers influencing treatment options. MATERIAL AND METHODS: The investigated data involved archival histological preparations obtained from uterine EC samples taken from 137 patients, treated surgically between 2007 and 2014. The immunohistochemical Dako EnVisionTM Flex+ method was applied. RESULTS: The expression of ERß, MLH1 and BRCA1 was lower in ECI than in ECII patients. The ERα expression was higher in early Fédération internationale de gynécologie et d'obstétrique (FIGO) (IA) stages than in advanced (IB-IV) stages, while ERß expression was significantly higher in advanced stages compared to stage IA and increased with grading. The BRCA1 expression also increased with grading. In both type I and type II EC patients, ERα expression correlated with MYH9 and BRCA1, while ERß expression correlated with BAP expression. High expression of BRCA1 correlated with several proteins: BAP, MYH9 and FAK. High BAP expression also correlated with high MYH9 expression. A correlation in the expression of these proteins was also demonstrated in the group consisting only of patients with ECI. A significant correlation was found between BAP expression and MYH9 among patients diagnosed with ECI. In the ECII group, no correlation was found between the tested proteins. CONCLUSIONS: The ECI and ECII patients differed in the studied molecular factors, mainly in terms of ER and BRCA1 expression. Changes in BRCA1 expression were linked to alterations in BAP expression, but were also associated with the proteins MYH9 and FAK.


Assuntos
Neoplasias do Endométrio , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Feminino , Humanos , Estadiamento de Neoplasias , Prognóstico
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