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2.
Przegl Epidemiol ; 76(1): 37-50, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35860959

RESUMO

INTRODUCTION: The National Cancer Control Programme 2006-2015 (NCCP) was implemented to improve the health situation of Polish women in 2006. Its effectiveness was evaluated by analysing trends of changes in incidence rates of pre-invasive (D05) and invasive (C50) breast cancers in three age cohorts: pre-screening cohort (<50), screening cohort (50-69) and post-screening cohort (>69). MATERIAL AND METHODS: Medical data of 13,089 women with C50 and 738 women with D05 diagnosed in 2005-2014 in the Lower Silesian Voivodeship (LS) were analysed. RESULT: In 2009-2014, incidence rates of C50 (p=0.0224) and D05 (p=0.0003) were found to be higher in the LS than those recorded for Poland. During this period, there were approx. 1,400 cases of C50 and 90-100 cases of D05 per year. After the NCCP had been implemented, there was a gradual increase in the proportion of the female population included in the mammography screening, from 32% in 2007 to 45% in 2014. The age group included in the screening programme experienced a significant increase in the proportion of pre-invasive cancers - from 3% in 2005 to 7-10% in 2010-2013. In that group, cancer was statistically more frequently detected in Tis- or T1- stages (p=0.0002). Beneficial effects of screening were also observed in post-screening women. There was no similar trend in patients aged <50. CONCLUSIONS: This analysis shows positive population effects of mammography screening. The least favourable changes in the detection of early stages of breast cancer were observed in female patients aged less than 50 years. This suggests that some modifications regarding both the age range and the screening interval in the Polish population should be considered.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/prevenção & controle , Detecção Precoce de Câncer , Feminino , Humanos , Incidência , Mamografia , Programas de Rastreamento , Polônia/epidemiologia
3.
Int J Mol Sci ; 23(9)2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35563554

RESUMO

The molecular mechanisms of telomerase reverse transcriptase (TERT) upregulation in breast cancer (BC) are complex. We compared genetic variability within TERT and telomere length with the clinical data of patients with BC. Additionally, we assessed the expression of the TERT, MYC, TP53 and SP1 genes in BC patients and in BC organoids (3D cell cultures obtained from breast cancer tissues). We observed the same correlation in the blood of BC patients and in BC organoids between the expression of TERT and TP53. Only in BC patients was a correlation found between the expression of the TERT and MYC genes and between TP53 and MYC. We found associations between TERT genotypes (rs2735940 and rs10069690) and TP53 expression and telomere length. BC patients with the TT genotype rs2735940 have a shorter telomere length, but patients with A allele rs10069690 have a longer telomere length. BC patients with a short allele VNTR-MNS16A showed higher expression of the SP1 and had a longer telomere. Our results bring new insight into the regulation of TERT, MYC, TP53 and SP1 gene expression related to TERT genetic variability and telomere length. Our study also showed for the first time a similar relationship in the expression of the above genes in BC patients and in BC organoids. These findings suggest that TERT genetic variability, expression and telomere length might be useful biomarkers for BC, but their prognostic value may vary depending on the clinical parameters of BC patients and tumor aggressiveness.


Assuntos
Neoplasias da Mama , Telomerase , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Genes myc , Humanos , Polimorfismo de Nucleotídeo Único , Fator de Transcrição Sp1/genética , Telomerase/genética , Telômero/patologia , Proteína Supressora de Tumor p53/genética
4.
Cancer Immunol Immunother ; 71(12): 2901-2911, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35471603

RESUMO

BACKGROUND: Dendritic cell (DC) therapy counts to the promising strategies how to weaken and eradicate cancer disease. We aimed to develop a good manufacturing practice (GMP) protocol for monocyte-derived DC (Mo-DC) maturation using circulating tumor cells lysates with subsequent experimental T-cell priming in vitro. METHODS: DC differentiation was induced from a population of immunomagnetically enriched CD14 + monocytes out of the leukapheresis samples (n = 6). The separation was provided automatically, in a closed bag system, using CliniMACS Prodigy® separation protocols (Miltenyi Biotec). For differentiation and maturation of CD14 + cells, DendriMACs® growing medium with supplements (GM-CSF, IL-4, IL-6, IL-1B, TNFa, PGE) was used. Immature Mo-DCs were loaded with autologous circulating tumor cell (CTCs) lysates. Autologous CTCs were sorted out by size-based filtration (MetaCell®) of the leukapheresis CD14-negative fraction. A mixture of mature Mo-DCs and autologous non-target blood cells (NTBCs) was co-cultured and the activation effect of mature Mo-DCs on T-cell activation was monitored by means of multimarker gene expression profiling. RESULTS: New protocols for mMo-DC production using automatization and CTC lysates were introduced including a feasible in vitro assay for mMo-DC efficacy evaluation. Gene expression analysis revealed elevation for following genes in NTBC (T cells) subset primed by mMo-DCs: CD8A, CD4, MKI67, MIF, TNFA, CD86, and CD80 (p ≤ 0.01). CONCLUSION: Summarizing the presented data, we might conclude mMo-DCs were generated using CliniMACS Prodigy® machine and CTC lysates in a homogenous manner showing a potential to generate NTBC activation in co-cultures. Identification of the activation signals in T-cell population by simple multimarker-qPCRs could fasten the process of effective mMo-DC production.


Assuntos
Células Dendríticas , Monócitos , Células Neoplásicas Circulantes , Humanos , Células Dendríticas/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Interleucina-4/farmacologia , Interleucina-6/farmacologia , Monócitos/metabolismo , Células Neoplásicas Circulantes/metabolismo , Prostaglandinas E/farmacologia
5.
Oncol Lett ; 23(5): 159, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35399329

RESUMO

Recent breakthroughs in high-throughput technologies have enabled the development of a better understanding of the functionalities of rho-associated protein kinases (ROCKs) under various physiological and pathological conditions. Since their discovery in the late 1990s, ROCKs have attracted the attention of interdisciplinary researchers due to their ability to pleiotropically modulate a myriad of cellular mechanisms. A rapidly growing number of published studies have started to shed light on the mechanisms underlying the regulation of ROCK1 and ROCK2 via long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in different types of cancer. Detailed analyses have suggested that lncRNAs may be characteristically divided into oncogenic and tumor suppressor lncRNAs. Several exciting recent discoveries have also indicated how different lncRNAs and circRNAs modulate ROCK1/2 and mediate multistep cancer onset and progression. The present review chronicles the major advances that have been made in our understanding of the regulatory role of ROCK1/2 in different types of cancer, and how wide-ranging lncRNAs and circRNAs potentiate ROCK-driven signaling by blocking the targeting activities of tumor suppressor microRNAs.

6.
Radiother Oncol ; 160: 229-235, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34023328

RESUMO

BACKGROUND: Frequency and predictive factors for a clinical complete response (cCR) in unselected patients are unclear. MATERIAL AND METHODS: Two prospective observational studies were designed and pooled to explore predictive factors for cCR. Both studies evaluated the watch-and-wait strategy in consecutive patients; the first single-institutional study in elderly with a small tumour, the second multi-institutional study in all the patients receiving standard of care preoperative radiotherapy. RESULTS: Four hundred and ninety patients were analysed. Short-course radiotherapy alone, or with consolidation chemotherapy or chemoradiation was given to 40.6%, 40.2% and 19.2% of the patients, respectively. The median interval from the radiation start to the first tumour response assessment was 10.2 weeks for short-course radiation and 13.2 weeks for chemoradiation. Seventy-three patients had cCR and 71 underwent w&w with the median follow-up of 24 months. The regrowth rate was 26.8%. cCR rate was 39.0% for low-risk cancer (cT1-2N0), 16.8% for intermediate-risk (cT3 with unthreatened mesorectal fascia [MRF-] or cT2N+) and 5.4% for high-risk (cT4 or MRF+). In the multivariable analysis, tumour volume (or tumour length and circumferential extent) and cN status were significant predictors for cCR. In circular cancers or with a length ≥7 cm (n = 184), cCR rate was only 2.7%, sustained cCR 1.6% and the sensitivity of cCR diagnosis 23.1%. None of 27 patients with a tumour larger than 120 cm3 achieved cCR. CONCLUSIONS: Considering watch-and-wait strategy is questionable in patients with circular tumours or with tumour length ≥7 cm.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Idoso , Quimiorradioterapia , Humanos , Recidiva Local de Neoplasia , Estudos Prospectivos , Neoplasias Retais/tratamento farmacológico , Resultado do Tratamento , Conduta Expectante
7.
Oncol Lett ; 18(4): 3561-3570, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31579068

RESUMO

Classic prognostic factors, such as clinical advancement of the disease and histological grade of the tumor, continue to have a decisive role in the selection of therapeutic strategy in patients with carcinoma of the oral cavity floor and oral surface of the tongue (OCC). YAP1/Yes-associated protein 1 (YAP) and transcriptional co-activator with PDZ-binding motif, WWTR1 (TAZ) proteins, appear to be promising markers that may be used to develop personalized therapies. The aim of the present study was to analyze the associations between the levels of YAP, TAZ and tyrosine-protein phosphatase non-receptor type 14 (PTPN14) and to determine whether the increased expression of YAP and TAZ had an effect on tumor cell proliferation, as determined by minichromosome maintenance 7, DNA replication licensing factor 7 expression. Their prognostic value was also assessed. In total, 127 patients who underwent radical surgery and were subjected to adjuvant radiation therapy due to squamous cell OCC were enrolled in the present study. The results demonstrated an evident effect as YAP expression increased in cancer-associated fibroblasts, which induced unfavorable prognosis in patients. In addition, a positive association between proliferation in cancer cells and YAP expression in stromal cells was observed. A lack of YAP expression in the cytoplasm of tumor cells was a factor for poor prognosis with regard to disease-free survival and disease specific survival. No statistically significant correlations between YAP and TAZ expression and PTPN14 expression were identified, nor was a correlation between cell proliferation and the presence of YAP and TAZ in tumor cells observed. The results indicated that YAP expression levels may support the development of personalized therapies for patients.

8.
Adv Clin Exp Med ; 28(10): 1377-1383, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31638746

RESUMO

BACKGROUND: Poland is considered among the European countries with an average incidence of cervical cancer (CC; about 3,000-3,500/year) and at the same time with high mortality (5-year survival rate - 55.2%). For this reason, in 2006 Poland introduced a Population-Based Cervical Cancer Prevention and Early Detection Program addressed to women aged 25-59 years, in which a cytological test is carried out every 3 years. OBJECTIVES: The aim of the study was to assess the changes in the curability of CC patients brought by the introduction of the Screening Program in the Lower Silesian voivodeship and to identify the subpopulation of women for whom activities aimed at increasing adherence rates must be intensified. MATERIAL AND METHODS: The 5-year relative survival in 3,586 CC patients from 2000-2010 registered in the Lower Silesian Cancer Registry was analyzed. RESULTS: In the Lower Silesian voivodeship, a 55.1% 5-year survival rate was recorded in 2000-2004 and 70.5% in 2010. The highest increase in 5-year relative survival rates was found in rural communities (from 53.1% in 2000-2004 to 77.7% in 2010) and in Wroclaw (56.8% and 74.2%, respectively). In the study group, the number of patients with invasive CC (C53) detected in the local stage of the disease increased systematically from 61.5% in 2000-2004 to 74.3% in 2010. CONCLUSIONS: The introduction of the population-based screening program improved the curability rate in CC patients in the Lower Silesian voivodeship. In order to maintain the recent positive trends, further education should be continued, and activities aimed at increasing adherence to screening tests should be intensified, especially in urban-rural communities.


Assuntos
Programas de Rastreamento/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Cooperação do Paciente/estatística & dados numéricos , Neoplasias do Colo do Útero/diagnóstico , Adulto , Detecção Precoce de Câncer , Feminino , Humanos , Incidência , Masculino , Programas de Rastreamento/organização & administração , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Cooperação do Paciente/psicologia , Polônia/epidemiologia , Vigilância da População , Avaliação de Programas e Projetos de Saúde , Taxa de Sobrevida/tendências , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
9.
Folia Histochem Cytobiol ; 52(3): 171-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25308732

RESUMO

The presence of circulating tumor cells (CTCs) in patients with metastatic carcinoma is generally associated with poor clinical outcome. There have been many investigations showing a possible use of CTCs as minimally invasive predictive and prognostic biomarker in cancer medicine. In this report a size-based method (MetaCell®) for quick and easy enrichment and cultivation of CTCs is presented to enable possible CTCs use in esophageal cancer (EC) management. In total, 43 patients with diagnosed EC, 20 with adenocarcinoma (AdenoCa) and 23 with squamous cell carcinoma (SCC), were enrolled into the adaptive prospective-like study .All the patients were candidates for surgery. The CTCs were detected in 27 patients (62.8%), with a higher rate in adenocarcinoma (75%) than SCC (52%). Finally, there were 26 patients with resectable tumors exhibiting CTCs-positivity in 69.2% and 17 patients with non-resectable tumors with 41.7% CTCs-positivity. Interestingly, in the patients undergoing neoadjuvant therapy, the CTCs were detected at time of surgery in 55.5% (10/18). The overall size-based filtration approach enabled to isolate viable CTCs and evaluate to their cytomorphological features by means of vital fluorescent staining. The CTCs were cultured in vitro for further downstream applications including immunohistochemical analysis. This is the first report of the successful culturing of esophageal cancer CTCs. The detection of CTCs presence could help in the future to guide timing of surgical treatment in EC patients.


Assuntos
Adenocarcinoma/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/diagnóstico , Células Neoplásicas Circulantes , Adenocarcinoma/patologia , Carcinoma de Células Escamosas/patologia , Contagem de Células , Neoplasias Esofágicas/sangue , Filtração , Humanos , Estudos Prospectivos , Coloração e Rotulagem
10.
J Cancer Educ ; 29(3): 428-33, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24627083

RESUMO

Cancer patient treatment in Poland remains unsatisfactory when compared to that in other countries. In 2005, this alarming situation prompted the Polish government to launch the "National Program for Combating Neoplastic Diseases" (NPCND). One part of this project was to improve the quality of oncology instruction at the undergraduate level over the years 2006 and 2007 (subsequently extended until 2010 thanks to promising results and the relatively small financial outlay). The program's main aims were to improve existing oncology therapy and to ameliorate the quality of undergraduate oncology education. To evaluate the changes in the quality of undergraduate education as a result of the NPCND program, medical universities were asked to fill out a questionnaire. Responses indicate that the program had a major positive impact on the quality of cancer education mainly as a result of the introduction of a uniform program of training and an increase in the number of classes devoted to oncology. The main unresolved problem is that university hospitals seldom have integrated units catering in-house for surgery, radiotherapy, chemotherapy, etc., and most such "hands-on" teaching still has to be done externally.


Assuntos
Educação de Graduação em Medicina , Educação em Saúde , Oncologia/educação , Programas Nacionais de Saúde , Neoplasias/prevenção & controle , Estudantes de Medicina/psicologia , Currículo , Humanos , Polônia , Inquéritos e Questionários , Fatores de Tempo , Universidades
11.
J Histochem Cytochem ; 61(5): 330-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23392733

RESUMO

BUBR1 (budding uninhibited by benzimidazole-related 1) represents the component of a controlling complex in mitosis. Defects in mitotic control complex result in chromosomal instability and, as a result, disturb the mitotic process. This study was aimed at examining the prognostic value linked to the expression of BUBR1 in a group of patients with breast cancer. We analyzed the expression of BUBR1 in 98 stage II breast cancer patients with a median follow-up of 15 years. Immunohistochemical reactions were performed using monoclonal antibodies against BUBR1. We also studied the prognostic value of BUBR1 mRNA expression using the Kaplan-Meier (KM) plotter, which assessed the effect of 22,277 genes on survival in 2422 breast cancer patients. A background database was established using gene expression data and survival information on 2422 patients downloaded from the Gene Expression Omnibus (GEO; Affymetrix HGU133A and HGU133+2 microarrays). The median relapse-free survival was 6.43 years. Univariate and multivariate analyses showed that higher expression of BUBR1 was typical for cases of shorter overall survival, disease-free time, and disease-specific survival. KM plotter analysis showed that elevated BUBR1 mRNA expression had a negative impact on patients' relapse-free, distant metastases-free, and overall survival. Elevated BUBR1 expression was associated with poor survival in early stage breast cancer patients.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Regulação Neoplásica da Expressão Gênica , Proteínas Serina-Treonina Quinases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sobrevida
12.
Anticancer Res ; 32(12): 5291-7, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23225429

RESUMO

AIM: The study aimed at the evaluation of the effects of radiotherapy on expression of metallothionein (MT) isoforms, both in the form of quantitative alterations in mRNA, and differences in expression of MTI/II proteins in rectal tumours. MATERIALS AND METHODS: Material for the study originated from 21 patients with rectal cancer at stage II or III. Material for immunohistochemical studies [MTI/II, Minichromosome Maintenance Protein 3 (MCM3), Ki-67] and real-time polymerase chain reaction (PCR) (mRNA of MT1F, MT1X and MT2A) was sampled twice: during rectoscopic examination before the start of the preoperative radiotherapy (samples A) and from the post operative specimen, following radiotherapy (samples B). RESULTS: The level of mRNA expression for each of the studied MT isoforms was higher in cancer cells subjected to irradiation. The most extensive differences were observed for the MT2A isoforms (p=0.09). No differences were disclosed between samples A and B in expression of MT I/II protein. The material sampled after radiotherapy manifested a tendency for reduced proliferative activity of the tumour cells: the decrease of MCM3 expression was significant (p=0.022), while in the case of Ki-67, the difference approached statistical significance (p=0.096). CONCLUSION: Application of radiotherapy to rectal adenocarcinoma cells is followed by an increase in MT mRNA expression level, affecting first of all the MT2A isoform. However, we failed to note an increased expression of MTI/II protein coded by the gene. Moreover, application of radiotherapy was followed by a decrease in expression of MCM3 protein. Our results cannot clearly confirm induction of MT after irradiation of human adenocarcinoma cells. The role of MT in radioprotection remains ambiguous.


Assuntos
Adenocarcinoma/radioterapia , Proteínas de Ciclo Celular/biossíntese , Proteínas de Ligação a DNA/biossíntese , Antígeno Ki-67/biossíntese , Metalotioneína/biossíntese , Proteínas Nucleares/biossíntese , RNA Mensageiro/biossíntese , Neoplasias Retais/radioterapia , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Proteínas de Ciclo Celular/genética , Proteínas de Ligação a DNA/genética , Feminino , Expressão Gênica/efeitos da radiação , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Antígeno Ki-67/genética , Masculino , Metalotioneína/genética , Pessoa de Meia-Idade , Componente 3 do Complexo de Manutenção de Minicromossomo , Proteínas Nucleares/genética , Isoformas de Proteínas/biossíntese , Isoformas de Proteínas/efeitos da radiação , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Retais/genética , Neoplasias Retais/metabolismo , Neoplasias Retais/patologia
13.
Anticancer Res ; 32(8): 3177-84, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22843890

RESUMO

BACKGROUND: Y-Box-Binding (YB1) protein represents a multifunctional protein, which plays a significant role in processes of proliferation, apoptosis and control of tumour cell response to toxic agents, including chemotherapy. The present study aimed at evaluating the prognostic significance of YB1 expression in breast cancer. MATERIALS AND METHODS: We analyzed nuclear and cytoplasmic expression of YB1 in 101 patients with stage II breast cancer, with 17 years of follow-up. Immunohistochemical reactions were performed on paraffin sections of primary tumours, using monoclonal antibodies against YB1. Results were tested for their correlation with clinical and pathological data. RESULTS: Patients with a pronounced expression of the nuclear form the YB1 protein demonstrated a highly significant shortening of disease-free survival, disease-specific survival and overall survival. The prognostic value of YB1 was also corroborated by multivariate analysis. CONCLUSION: We demonstrated that high nuclear expression of YB1 is associated with poor survival of patients with early-stage breast cancer.


Assuntos
Neoplasias da Mama/mortalidade , Núcleo Celular/metabolismo , Análise de Sobrevida , Proteína 1 de Ligação a Y-Box/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Prognóstico
14.
Ginekol Pol ; 83(9): 681-7, 2012 Sep.
Artigo em Polonês | MEDLINE | ID: mdl-23342897

RESUMO

UNLABELLED: Breast cancer resistance protein (BCRP, ABCG2) is a xenobiotic half-transporter protein. It is a member of the ATP-binding cassette protein family and functions as an energy-dependent efflux pump. BCRP is involved in multidrug resistance. The study aimed at examining BCRP expression in breast cancers and at defining a relationship between activity of this protein and clinical course of the cancer. MATERIALS AND METHODS: We analyzed the expression of BCRP in 101 stage II breast cancer patients. All the patients were diagnosed and treated at the Lower Silesia Oncology Centre (LSOC) between January 1993 and June 1994. After the treatment the patients remained under constant control at LSOC. Mean duration of the observation was 14.2 years (ranging between 9.1 and 16.5 years). Data related to relapse of the disease and deaths were obtained from medical documentation stored in LSOC. The immunohistochemical reactions were performed on paraffin sections of primary tumours, using monoclonal antibodies against BCRP. The intensity of immunohistochemical reactions with BCRP antibody was evaluated using the semi-quantitative IRS (ImmunoReactive Score) scale, which took into account the intensity of the colour reaction and percentage of positive cells. Results of the immunohistochemical reactions, pathological and of clinical observations were subjected to statistical analysis. Correlations between these factors and BCRP were analyzed using Spearman and Chi2 tests. In order to estimate the survival rate, we used Kaplan Meier statistics, log-rank tests and Cox proportional hazard regression. RESULTS: In our analysis we observed a positive correlation between the expression of the BCRP protein and grade of tumour advancement (r = 0.2 p = 0.03). We found also a negative correlation between the expression of BCRP and the estrogen (r = 0.24 p = 0.02) and progesteron (r = 0.28 p = 0.02) receptors. In a univariate analysis a significantly shorter disease free survival (DFS) and disease specific survival (DSS) was noted in patients with metastases to the lymph nodes (p = 0.003 and p = 0.0006), over the age of 50 years old ((p = 0.02 and p = 0.04) and clearly statistically significant in patients with a high expression of BCRP (p = 0.00044 and p = 0.00005). Overall survival (OS) was shorter in patients over the age of 50 (p = 0.01), with higher stage of the disease - IIB (p = 0.025), with metastases to the lymph nodes (p = 0.003) and also clearly statistically significant in patients with a high expression of BCRP (p = 0.00004). A multivariate analysis allowed to reveal that only higher expression of BCRP and metastases to lymph nodes were typical for cases of DFS (p = 0.,028 and p = 0.00015), DSS (p = 0.00052 and 0.000017) and OS (p = 0.0018 and p = 0.000007) time. CONCLUSIONS: We demonstrated that high BCRP expression level is associated with poor survival in early stage breast cancer patients.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Neoplasias da Mama/metabolismo , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Proteínas de Neoplasias/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Adulto , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Polônia , Recidiva , Análise de Sobrevida
15.
Appl Immunohistochem Mol Morphol ; 19(6): 540-6, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21617523

RESUMO

The membrane cofactor protein, CD46 represents a complement inhibitor, which protects autologous cells from complement-mediated cytotoxicity. On tumor cells, CD46 may exhibit the potential to protect them from immune responses of the host. The present study aimed at evaluation of prognostic significance of CD46 expression in breast cancers. The analyses were performed on 70 samples of breast cancer. Immunohistochemical reactions were performed on paraffin sections of studied tumors using monoclonal antibodies directed against CD46. Results of the immunohistochemical reactions and of clinical observations were subjected to statistical analysis. Multivariate analysis showed that expression of CD46 and involvement of lymph nodes represent independent risk factors for disease-free survival and overall survival. Kaplan-Meier analysis showed that patients with tumors negative for CD46 have an increased progression-free time and overall survival time as compared with patients with the CD46-positive tumors. The study demonstrates that breast cancers manifest CD46 expression and that it is linked to a less favorable prognosis.


Assuntos
Antígenos de Neoplasias/metabolismo , Neoplasias da Mama/diagnóstico , Carcinoma/diagnóstico , Proteína Cofatora de Membrana/metabolismo , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/imunologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Carcinoma/imunologia , Carcinoma/patologia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Evasão da Resposta Imune , Imuno-Histoquímica , Proteína Cofatora de Membrana/genética , Proteína Cofatora de Membrana/imunologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Regulação para Cima
16.
Rep Pract Oncol Radiother ; 16(5): 173-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-24376976

RESUMO

BACKGROUND: Hepatocyte growth factor plays an important role in tumor growth, metastasis and angiogenesis. C-met is HGF's high affinity receptor. AIM: The aim of the study was to assess the correlations between c-met expression and clinic-pathological factors in breast cancer tissues. Furthermore, the purpose of the study was to evaluate the prognostic value of the hepatocyte growth factor receptor (HGFR, c-met) expressions in homogenous group of breast cancer patients. MATERIALS AND METHODS: Tumor samples were collected from 302 patients with breast carcinoma treated with primary surgery. We have assessed the percentage of tumor cells with c-met expression, the intensity of reaction and the ratio of these two factors-immunoreactivity according to the Remmele score. RESULTS: We have observed no correlations between HGFR immunoreactivities and clinical parameters (tumor size, grade, axillary lymph node status, age). In 5-year observation we have found prognostic value of assessing c-met immunoreactivity in primary tumor. CONCLUSION: Our study has revealed prognostic value of c-met. Unlike in other authors' studies, our patients' group is very homogenous which might contribute to obtained results.

17.
Pol Merkur Lekarski ; 28(168): 505-8, 2010 Jun.
Artigo em Polonês | MEDLINE | ID: mdl-20642115

RESUMO

YKL-40 is detected in the early nineties not only a glycoprotein secreted by cancer cells, but also of neutrophils, chondrocytes and endothelial cells. Biological function of YKL-40 are not exactly known, it is suggested that this protein participates in many physiological and pathological processes such as proliferation, angiogenesis, mitogenesis and remodelling. It is also a factor antyapoptotic and growth factor for some cells. Increased levels of YKL-40 in serum have been described in many diseases running with inflammation such as rheumatoid arthritis, systemic lupus erythematosus and Crohn's disease, and also in the group of cardiovascular diseases. Determination of the concentration of serum YKL-40 was also used in oncology. The tumors at various sites were found elevated levels of this marker in serum, as well as overexpression in tumor tissue. It was observed that higher titers YKL-40 levels are associated with shorter overall survival and disease-free period. It is suggested that measuring the concentration of YKL-40 in serum and its expression in tumor tissues may serve as a valuable and independent prognostic factor.


Assuntos
Biomarcadores Tumorais/sangue , Glicoproteínas/sangue , Lectinas/sangue , Neoplasias/metabolismo , Adipocinas , Proteína 1 Semelhante à Quitinase-3 , Intervalo Livre de Doença , Humanos , Neoplasias/diagnóstico , Neoplasias/mortalidade , Prognóstico , Taxa de Sobrevida
18.
Folia Histochem Cytobiol ; 48(1): 78-83, 2010 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-20529820

RESUMO

The aim of the study was to evaluate the prognostic value of the vascular endothelial growth factor A (VEGF-A) and hepatocyte growth factor receptor (HGFR, c-met) expressions in homogenous group of breast cancer patients. Tumor samples were collected from 98 patients with invasive ductal breast carcinoma stage II treated with primary surgery. We have observed a strong correlation between VEGF-A and c-met. No correlations were found between VEGF-A or HGFR expressions and clinical parameters (tumor size, grade, axillary lymph node status, age), 5- and 10-years DFS or OS. Our study did not reveal any prognostic value of c-met or VEGF. In addition they are not useful to separate a patients' subgroup with poor prognosis. Unlike in other authors' studies, our patients' group is very homogenous which might tribute to obtained results.


Assuntos
Neoplasias da Mama/enzimologia , Proteínas Proto-Oncogênicas c-met/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/enzimologia , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Prognóstico
19.
Pathol Oncol Res ; 16(3): 337-44, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19821158

RESUMO

Available evidence suggests that vascular endothelial growth factor (VEGF) a potent regulator of vasculogenesis and tumor angiogenesis may be a predictor of recurrence in breast cancer patients. We sought to determine whether VEGF serum levels (VEGF-A, VEGF-C and VEGF-D) in 377 patients with malignant and benign breast tumors differ and whether there is association between vascular growth factors, clinicopathologic features and prognosis. There was no significant difference in investigated circulating angiogenic markers between patients with malignant and non malignant lesions. We found strong correlation between VEGF-A and VEGF-D and between VEGF- C and VEGF-D. Besides serum VEGF-D levels and estrogen receptor (ER) expressions no other correlations between VEGF and clinicopathologic variables were observed. However, elevated VEGF-A and VEGF-C concentrations were associated with increased number of erythrocytes, leukocytes and platelets. In Cox model values of angiogenic serum markers and recognized prognostic markers in breast cancer, VEGF-C turned out as independent prognostic factor. Our study is the first analysis showing correlation between serum concentrations of three angiogenic factors: VEGF-A, VEGF-C, VEGF-D. Associations between angiogenic cytokines and number of blood cells may be due to release of VEGF from platelets and leucocytes. Prognostic role of VEGF is still uncertain, though VEGF-C has a potential to serve as a prognostic marker.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Fator C de Crescimento do Endotélio Vascular/sangue , Fator D de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neovascularização Patológica/sangue , Neovascularização Patológica/mortalidade , Neovascularização Patológica/patologia , Prognóstico
20.
Int J Gynecol Cancer ; 19(8): 1454-8, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20009906

RESUMO

OBJECTIVE: To evaluate the access to axilla, postoperative complications, and cosmetic results of the modified radical mastectomy with a Y-shaped approach especially designed for women with obesity. METHODS: One hundred seventeen consecutive women with obesity with infiltrating breast cancer were studied. All of them were not eligible for breast-conserving therapy and underwent modified radical mastectomy. Operation was performed using a surgical technique designed to improve the axillary clearance and to eliminate the lateral dog ear deformity. Two oblique incisions were added to the traditional transverse Stewart incision at the lateral part forming the Y-shaped approach. After lateral flap retraction, the axillary dissection was done. Before closing the wound, the triangular flap was advanced medially, whereas superior and inferior areas of redundant skin overlying the latissimus dorsi muscle were excised. RESULTS: No intraoperative complications were observed. In each case, the axillary dissection (with level 3 node clearance when needed) was performed with ease. The wound was healed by primary adhesion, giving an excellent cosmetic result without lateral dog ear deformity. Skin flap necrosis was found in 2 elderly patients. Wound hematoma and surgical site infection developed in 1 patient each. Necrosis of the apex of axillary triangle occurred in one woman with diabetes. These rare complications were managed successfully in all the cases. CONCLUSIONS: The Y-shaped approach for modified radical mastectomy is a simple and safe technique. It facilitates the wide access to axilla and improves cosmesis in women with obesity by eliminating lateral dog ear deformity.


Assuntos
Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Mastectomia Radical Modificada , Obesidade/complicações , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Axila , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/patologia , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Resultado do Tratamento
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