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1.
Int J Mol Sci ; 24(20)2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37894959

RESUMO

The Lamiaceae is one of the most important families in the production of essential oils known to have a wide spectrum of biological activity. Recent research has highlighted the dermatological capabilities of various Lamiaceae essential oils, which appear to offer potential in free radical scavenging and anti-inflammatory activity. Some have also been extensively studied for their tissue remodeling and wound-healing, anti-aging, anti-melanogenic, and anti-cancer properties. Certain Lamiaceae essential oils are promising as novel therapeutic alternatives for skin disorders. This potential has seen substantial efforts dedicated to the development of modern formulations based on nanotechnology, enabling the topical application of various Lamiaceae essential oils. This review provides a comprehensive summary of the utilization of various essential oils from the Lamiaceae family over the past decade. It offers an overview of the current state of knowledge concerning the use of these oils as antioxidants, anti-inflammatory agents, wound-healers, anti-aging agents, anti-melanogenic agents, and anticancer agents, both alone and in combination with nanoparticles. Additionally, the review explores their potential applicability in patents regarding skin diseases.


Assuntos
Pesquisa Biomédica , Lamiaceae , Óleos Voláteis , Humanos , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Nanotecnologia
2.
Pol J Pathol ; 69(1): 33-41, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29895124

RESUMO

Preoperative systemic therapy including neoadjuvant chemotherapy (NCT) is standard treatment in locally advanced breast cancer (LABC), the aim of which is to enable a radical surgery and to reduce the risk of local and distant recurrence. It has been established that NCT in LABC may effectively induce apoptosis. The study objective was to assess the role of a proapoptotic second mitochondria-derived activator of apoptosis (SMAC) in LABC. The study group comprised 56 patients with advanced non-metastatic breast cancer (stage IIB -node positive and III), who received NCT followed by surgery and adjuvant treatment. Expression of SMAC protein was analysed using the immunohistochemistry technique in core biopsies sampled from the patients' breasts before NCT and in surgical specimens collected after completion of NCT. Expression of SMAC was significantly higher in the breast cancer specimens after NCT (p < 0.01). High expression of SMAC in the core biopsy before NCT correlated with a pathological complete remission (pCR, p < 0.01). The patients with a high expression of SMAC in the surgical specimens after NCT had longer DFS. Our study proves a potential role of SMAC expression in LABC as a novel favourable prognostic factor in LABC for pCR and disease-free survival (DFS).


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/química , Peptídeos e Proteínas de Sinalização Intracelular/análise , Proteínas Mitocondriais/análise , Adulto , Idoso , Proteínas Reguladoras de Apoptose , Biópsia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Mastectomia , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
3.
Ginekol Pol ; 89(8): 415-420, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30215459

RESUMO

INTRODUCTION: Breast cancer can be classified into five subtypes based on variations in the status of three hormonal receptors that are responsible for the cancer's heterogeneity: estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). These classifications influence the choice of therapies (either neoadjuvant or adjuvant), and the range of prognoses, from good (luminal A subtype) to poor (triple-negative cancers). OBJECTIVE: The aim of the study was to compare the serum concentration of selected miRNAs (miRNA-21, miRNA-10b, and miRNA-200c) between in two groups of breast cancer patients with differing ER, PR, and HER2 statuses. MATERIALS AND METHODS: The study was performed on two groups of patients. One group (TNBC) consisted of patients with triple-negative cancer, and the other group (ER(+)/PR(+)) was comprised of patients with positive ER and PR receptors. RESULTS: The mean level of miRNA-200c was significantly higher in the ER(+)/PR(+) group than in the TNBC group (p < 0.05). No statistically significant difference was found between the two groups with regard to the mean levels of miRNA-21 or miRNA-10b. CONCLUSION: The level of miRNA-200c was lower in triple-negative patients when compared with the levels in the study's ER/PR positive group.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , MicroRNA Circulante/sangue , MicroRNAs/sangue , Neoplasias de Mama Triplo Negativas/sangue , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias da Mama/química , Neoplasias da Mama/genética , MicroRNA Circulante/genética , Feminino , Humanos , MicroRNAs/genética , Pessoa de Meia-Idade , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Neoplasias de Mama Triplo Negativas/química , Neoplasias de Mama Triplo Negativas/genética
4.
Postepy Hig Med Dosw (Online) ; 69: 586-97, 2015 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-25983297

RESUMO

BACKGROUND: HER2 overexpression is an unfavorable prognostic factor in patients with breast cancer, but it is also a target for the monoclonal antibody trastuzumab, which is effective in adjuvant and palliative settings. HER2 positivity is an inclusion criterion for immunotherapy, but it is not a positive predictive factor, and only half of patients benefit from the treatment. AIM: The aim of this study was to evaluate the prognostic and predictive value of HER3, PTEN and phosphorylated HER2 (p-HER2) expression in primary breast tumors of patients treated with trastuzumab in an adjuvant or palliative regimen. MATERIAL/METHODS: Immunohistochemical (IHC) analysis with 3 antibodies specific to the proteins was performed in tumor specimens obtained from 81 HER2-positive patients treated with trastuzumab. RESULTS: HER3 overexpression was present in 55.6% of the examined tumors, and PTEN or pHER2 positivity was present in 32.0% and 34.6% of them, respectively. HER3 overexpression and PTEN positivity correlated with larger tumor size (p=0.016 and p=0.008, respectively). p-HER2 positivity correlated with more advanced clinical stage of the disease (p=0.032). There was no correlation between the proteins' expression and survival for 31 patients treated with trastuzumab in the palliative regimen. DISCUSSION: HER3 overexpression, PTEN positivity and p-HER2 positivity in tumor cells of HER2-positive patients correlate with more advanced clinical stage of breast cancer. Expression of these proteins does not predict outcome of trastuzumab treatment.


Assuntos
Neoplasias da Mama/metabolismo , PTEN Fosfo-Hidrolase/genética , Receptor ErbB-2/metabolismo , Receptor ErbB-3/genética , Trastuzumab/uso terapêutico , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Fosforilação , Prognóstico , Receptor ErbB-2/efeitos dos fármacos , Receptor ErbB-2/genética , Resultado do Tratamento
5.
Mol Cell Biochem ; 372(1-2): 47-55, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22949034

RESUMO

Different low-molecular-weight thiols, including glutathione, cysteine, and cysteinylglycine are physiological free radical scavengers. On the other hand, homocysteine may play a role as an oxidant. The aim of our present study was to establish in vitro the effects of the commercial extract of Aronia melanocarpa (Aronox(®)) on the amount of selected low-molecular-weight thiols and the activity of antioxidative enzymes (superoxide dismutase, glutathione peroxidase, and glutathione reductase) in plasma obtained from patients with invasive breast cancer during different phases of treatment [before or after the surgery and patients after different phases of chemotherapy (doxorubicin and cyclophosphamide)] and from healthy subjects. Patients were hospitalized in Department of Oncological Surgery and Department of Chemotherapy, Medical University of Lodz, Poland. The level of low-molecular-weight thiols was determined by high-performance liquid chromatography. We observed that in the presence of the Aronia extract changes in amount of thiols in plasma from breast cancer patients (at all tested groups) were significantly reduced. Our results showed that tested commercial extract reduced modifications of antioxidative enzymes activity in plasma from patients during different phases of treatment, but this effect was not statistical significant. Our results suggest that the Aronia extract supplementation in breast cancer patients has a beneficial effect on thiols concentration in plasma. Plasma, as reported in this work, could be used as an experimental model to evaluate the beneficial action of plant supplements, including phenolic extracts on thiols or other molecules during different phases of treatment.


Assuntos
Antioxidantes/administração & dosagem , Neoplasias da Mama/sangue , Carcinoma Ductal de Mama/sangue , Cisteína/sangue , Dipeptídeos/sangue , Glutationa/sangue , Extratos Vegetais/administração & dosagem , Adulto , Idoso , Antibióticos Antineoplásicos/uso terapêutico , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias da Mama/enzimologia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/enzimologia , Carcinoma Ductal de Mama/terapia , Estudos de Casos e Controles , Terapia Combinada , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Glutationa Peroxidase/sangue , Glutationa Redutase/sangue , Humanos , Pessoa de Meia-Idade , Photinia , Superóxido Dismutase/sangue
6.
Platelets ; 24(6): 462-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22871094

RESUMO

Blood platelets from patients with cancer (before or after the surgery) exhibit a variety of qualitative abnormalities. Different anti-cancer drugs may also induce the oxidative/nitrative stress in blood platelets and change their hemostatic properties. The aim of our study was to explain the effect of superoxide anion radicals ([Formula: see text]) production on hemostatic properties of blood platelets (activated by a strong physiological agonist - thrombin) from breast cancer patients before the surgery, after the surgery, and after various phases (I-IV) of chemotherapy (doxorubicin and cyclophosphamide). Patients were hospitalized in the Department of Oncological Surgery and at the Department of Chemotherapy, Medical University of Lodz, Poland. We measured the platelet aggregation as the marker of hemostatic activity of blood platelets. We observed an increase of [Formula: see text] in thrombin-activated blood platelets from patients with breast cancer (before or after the surgery and after various phases of the chemotherapy) compared to the healthy group. Our other experiments demonstrated that aggregation (induced by thrombin) of blood platelets from patients with breast cancer before the surgery, after the surgery, and after various phases of the chemotherapy differs from aggregation of platelets obtained from healthy volunteers. Moreover, our results showed the correlation between the [Formula: see text] generation and changes of platelet aggregation in breast cancer patients before the surgery, after the surgery, and after the chemotherapy (I and IV phases). Considering the data presented in this study, we suggest that the production of [Formula: see text] in blood platelets (activated by thrombin) obtained from breast cancer patients may induce the changes of platelet aggregation, which may contribute in thrombosis in these patients.


Assuntos
Plaquetas/fisiologia , Neoplasias da Mama/sangue , Ativação Plaquetária/fisiologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Período Perioperatório , Agregação Plaquetária , Testes de Função Plaquetária
7.
Arch Gynecol Obstet ; 288(4): 889-99, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23584885

RESUMO

PURPOSE: To evaluate the membrane expression of DR4, DR5, DcR1 and DcR2 in the normal endometrium (NE), atypical endometrial hyperplasia (AEH) and endometrioid adenocarcinoma (EAC). METHODS: The study comprised 197 patients: 20 NE, 18 AEH and 159 EAC. Tissue microarrays were constructed. Membrane expression of DR4, DR5, DcR1 and DcR2 was examined and presented as total score (TS). RESULTS: In EAC, the membrane expression of DR4, DR5 and DcR2 was less common compared to NE (p < 0.001; p < 0.001; p = 0.018) and AEH (p < 0.001; p < 0.001; p = 0.004). In EAC the membrane expression of DcR1 did not differ when compared to NE (p = 0.055) and AEH (p = 0.173). A strong correlation was found between the type of endometrial tissue (NE/AEH/EAC) and the TS of DR4 (p < 0.001), DR5 (p < 0.001), DcR1 (p = 0.033) and DcR2 (p < 0.001). In EAC, the TS of DR4, DR5, DcR1 and DcR2 was not related to grading and staging. In EAC, the membrane expression of DR5, but not DR4, DcR1 and DcR2, was related to better disease-free survival (DFS). The overall survival (OS) was not related to membrane TRAIL receptors expression. CONCLUSIONS: The membrane expression of the receptors for TRAIL DR4, DR5, DcR1 and DcR2 is greater in NE than EAC. The level of membrane staining of the receptors in EAC is not dependent on grading and staging. In EAC patients, membrane expression of DR4, DR5, DcR1 and DcR2 are not independent predictors of survival.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Endometrioide/metabolismo , Hiperplasia Endometrial/metabolismo , Neoplasias do Endométrio/metabolismo , Endométrio/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Receptores Chamariz do Fator de Necrose Tumoral/metabolismo , Biomarcadores/metabolismo , Carcinoma Endometrioide/mortalidade , Membrana Celular/metabolismo , Neoplasias do Endométrio/mortalidade , Feminino , Proteínas Ligadas por GPI/metabolismo , Humanos , Imuno-Histoquímica , Membro 10c de Receptores do Fator de Necrose Tumoral , Análise de Sobrevida , Análise Serial de Tecidos
8.
Ginekol Pol ; 84(6): 444-9, 2013 Jun.
Artigo em Polonês | MEDLINE | ID: mdl-24032262

RESUMO

OBJECTIVES: To assess the prognostic significance of Ki-67 expression in the tissue microarray method (TMA) for disease free survival (DFS) and overall survival (OS) in endometrioid endometrial cancer (EEC). MATERIAL AND METHODS: The study examined 159 consecutive patients aged 37-86 (62.82 +/- 9.95) with EEC stages I-III according to FIGO, treated surgically at the Pirogow Memorial Hospital of Lodz between 2000 and 2007. Afterwards they were subsequently treated and examined at the Regional Cancer Center Copernicus Memorial Hospital of Lodz. Tissue cores 2 mm in size, in duplicate, were taken from the formalin-fixed and paraffin-embedded tissue donor blocks from surgery and constructed into the TMA recipient blocks. Using TMA method, the relationship between Ki-67 expression, DFS and OS was examined. DFS was defined as a period from primary surgery until relapse. OS was defined as a period from primary surgery until the end of the follow-up (60 months) or until the death of the patient. The study was approved by the Ethics Committee of the Medical University of Lodz (RNN/82/11/KE; KE/1673/12). RESULTS: The follow-up time varied between 3-60 months (51.42 +/- 15.87). In 31 patients (19.50%) the relapse of was diagnosed 1-59 months (24.97 +/- 16.08) after commencement of the treatment. During follow-up 32 patients (20.12%) died. DFS and OS were 80.50% and 79.88%, respectively The lack of Ki-67 expression was found in 37 cases (23.27%) while in 122 patients (76.73%) the expression was present (p < 0.001). The expression of Ki-67 in 1-10%, 11-20% and > 20% was present in 76 cases, 26 cases and 20 cases, respectively Positive correlation between the expression of Ki-67 and staging was present (r = 0.353; p < 0.001). In EEC patients with no relapse diagnosed during follow-up the expression of Ki-67 was present in 7.63 +/- 7.57% of EEC cells, when compared to 23.06 +/- 22.93% in EEC patients in relapsed disease (p < 0.001). The relationship between increased Ki-67 expression and increased grading was not statistically significant (r = 0.149; p = 0.061). The expression of Ki-67 did not depend on patient age (r = 0.040; p = 0.617). In univariate analysis negative correlation was found between the expression of Ki-67 and DFS (p < 0.001) and OS (p = 0.01). In multivariate analysis worse DFS was related to higher staging of EEC (p < 0.0 01) and increased expression of Ki-67 (p < 0.001). Worse OS was related to higher staging in multivariate analysis (p < 0.001). Ki-67 expression was not related to OS in multivariate analysis. Age of patients and grading of the EEC were not related to DFS and OS. CONCLUSIONS: The expression of the Ki-67 can significantly affect therapeutic decisions in selected EEC patients. The high Ki-67 expression in EEC patients is related to increased risk of relapse. The TMA technique is a good method for the assessment of the Ki-67 in studies conducted in EEC patients and makes it easier to carry out immunohistochemistry in large populations of patients.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/metabolismo , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/metabolismo , Antígeno Ki-67/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/patologia , Intervalo Livre de Doença , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Polônia , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Análise Serial de Tecidos/métodos
9.
Ginekol Pol ; 84(2): 95-101, 2013 Feb.
Artigo em Polonês | MEDLINE | ID: mdl-23668054

RESUMO

OBJECTIVES: To assess prognostic significance of progesterone receptors (PR) and estrogen receptors (ER) expression in the tissue microarray (TMA) technique for disease free survival (DFS) and overall survival (OS) in endometrioid endometrial cancer (EEC). MATERIAL AND METHODS: The study included 151 consecutive patients, aged 37-86 years (62.80 +/- 9.99), with the EEC in stages I-III (FIGO), treated surgically at the Pirogow Memorial Hospital of Lodz between 2000 and 2007. Afterwards, they were subsequently treated and examined at the Regional Cancer Center, Copernicus Memorial Hospital of Lodz. Tissue cores 2 mm in size, in duplicate, were taken from the formalin-fixed and paraffin-embedded tissue donor blocks from surgery and constructed into the TMA recipient blocks. Using TMAs, the expression of PR and ER was examined and presented as Total Score (TS). The TS was determined by adding the intensity and marker distribution scores in a given case. The relationship between PR and ER expression, DFS and OS was examined. DFS was defined as the period from primary surgery until relapse. OS was defined as the period from primary surgery until the end of the follow-up (60 months) or until the death of the patient. The study was approved by the Ethics Committee of the Medical University of Lodz (RNN/82/11/KE). RESULTS: Lack of the PR and ER expression was found in 46 cases (30.46%) and 67 cases (44.37%), respectively. The expression of the PR and ER was weak in 24 cases (15.89%) and 22 cases (14.57%), respectively. Strong PR and ER expression was found in 81 patients (53.65%) and 62 patients (41.06%), respectively. Follow-up after surgery varied from 3 to 60 months (50.95 +/- 16.36). In 30 patients (19.87%) relapse was diagnosed 1-54 months (22.17 +/- 15.59) after surgery. During follow-ups, 29 patients (19.21%) died. In univariate analysis better DFS was related to the presence of PR (p = 0.010), higher TS of PR (HR = 0.81; 95% CI 0.71-0.94), the presence of ER (p = 0.001) and higher TS of ER (HR = 0.88; 95% CI 0.78-0.99). DFS differed significantly between the groups: without PR and ER expression (A), with presence of the PR but not ER expression (B), with the ER but not PR expression (C) and with the PR and ER expression (D) (p = 0.004). In univariate analysis OS was not related to PR expression (p = 0.110), TS of PR (HR = 0.89; 95% CI 0.80-1.02) and ER expression (p = 0.070). TS of ER was connected to better OS (HR = 0.83; 95% CI 0.72-0.96). The OS differed between groups A, B, C and D (p = 0.006). In multivariate analysis variants of PR/ER expression influenced the DFS (p = 0.039) and OS (p = 0.016). CONCLUSIONS: The expression of the PR and ER can significantly affect therapeutic decisions in selected patients with EEC. In EEC, common assessment of PR and ER expression is of higher prognostic value, than compared to single evaluation of PR and ER receptors.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Endometrioide/metabolismo , Neoplasias do Endométrio/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Idoso , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/patologia , Intervalo Livre de Doença , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polônia , Prognóstico , Análise Serial de Tecidos/métodos , Células Tumorais Cultivadas
10.
Arch Med Sci ; 19(2): 343-354, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37034529

RESUMO

Introduction: Neoadjuvant treatment in locally advanced breast cancer (LABC) is intended to decrease the cancer mass, increase the likelihood of radical resection and improve survival. Resistance to chemotherapy may depend on cellular expression of anti-apoptotic proteins. XIAP and survivin are the most potent inhibitors of apoptosis (IAP), but their role in drug-induced cancer cell apoptosis remains unclear. This study was designed to evaluate the impact of pre-treatment expression of XIAP and survivin on pathological complete response and survival in LABC patients. Material and methods: The study included 60 LABC patients treated with anthracycline-based chemotherapy. XIAP and survivin expression was assessed immunohistochemically in pre-treatment core biopsy specimens. Results: Pathological complete response was achieved in 33% of the LABC patients. Low/intermediate expression of both XIAP and survivin was significantly associated with pathological complete response (p ≤ 0.04 and p < 0.001, respectively) and positively correlated with disease-free survival (p = 0.017 and p < 0.001) and overall survival (p = 0.052 and p < 0.001). The area under receiver operating characteristics curves (AUC) revealed predictive value of survivin expression for relapse and death in breast cancer patients (AUC = 0.63, p = 0.001 and AUC = 0.8, p < 0.001, respectively). Conclusions: Our findings suggest that downregulation of XIAP and survivin in LABC patients might predict better treatment outcomes after anthracycline-based chemotherapy. This, in turn, may indicate XIAP and survivin proteins as potential targets for innovative anticancer therapies.

11.
Cancers (Basel) ; 16(1)2023 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-38201542

RESUMO

The number of cancer cases will reach 24 million in 2040, according to the International Agency for Research on Cancer. Current treatments for cancer are not effective and selective for most patients; for this reason, new anticancer drugs need to be developed and researched enough. There are potentially useful drugs for cancer isolated from plants that are being used in the clinic. Available information about phytochemistry, traditional uses, in vitro and in vivo experiments with plants, and pure compounds isolated from the Euphorbiaceae family indicates that this family of plants has the potential to develop anticancer drugs. This review examines selected species from the Euphorbiaceae family and their bioactive compounds that could have potential against different types of cancer cells. It reviews the activity of crude extracts, isolated compounds, and nanoparticles and the potential underlying mechanisms of action.

12.
Genes (Basel) ; 14(6)2023 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-37372475

RESUMO

The inhibition of histone deacetylases (HDACs) holds promise as a potential anti-cancer therapy as histone and non-histone protein acetylation is frequently disrupted in cancer, leading to cancer initiation and progression. Additionally, the use of a histone deacetylase inhibitor (HDACi) such as the class I HDAC inhibitor-valproic acid (VPA) has been shown to enhance the effectiveness of DNA-damaging factors, such as cisplatin or radiation. In this study, we found that the use of VPA in combination with talazoparib (BMN-673-PARP1 inhibitor-PARPi) and/or Dacarbazine (DTIC-alkylating agent) resulted in an increased rate of DNA double strand breaks (DSBs) and reduced survival (while not affecting primary melanocytes) and the proliferation of melanoma cells. Furthermore, the pharmacological inhibition of class I HDACs sensitizes melanoma cells to apoptosis following exposure to DTIC and BMN-673. In addition, the inhibition of HDACs causes the sensitization of melanoma cells to DTIV and BMN-673 in melanoma xenografts in vivo. At the mRNA and protein level, the histone deacetylase inhibitor downregulated RAD51 and FANCD2. This study aims to demonstrate that combining an HDACi, alkylating agent and PARPi could potentially enhance the treatment of melanoma, which is commonly recognized as being among the most aggressive malignant tumors. The findings presented here point to a scenario in which HDACs, via enhancing the HR-dependent repair of DSBs created during the processing of DNA lesions, are essential nodes in the resistance of malignant melanoma cells to methylating agent-based therapies.


Assuntos
Antineoplásicos , Melanoma , Humanos , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Ácido Valproico/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Dacarbazina/uso terapêutico , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/patologia , DNA , Alquilantes/uso terapêutico
13.
Cancers (Basel) ; 15(10)2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37345002

RESUMO

BACKGROUND: In melanoma treatment, an approach following positive sentinel lymph node biopsy (SLNB) has been recently deescalated from completion lymph node dissection (CLND) to active surveillance based on phase III trials data. In this study, we aim to evaluate treatment strategies in SLNB-positive melanoma patients in real-world practice. METHODS: Five-hundred-fifty-seven melanoma SLNB-positive patients from seven comprehensive cancer centers treated between 2017 and 2021 were included. Kaplan-Meier methods and the Cox Proportional-Hazards Model were used for analysis. RESULTS: The median follow-up was 25 months. Between 2017 and 2021, the percentage of patients undergoing CLND decreased (88-41%), while the use of adjuvant treatment increased (11-51%). The 3-year OS and RFS rates were 77.9% and 59.6%, respectively. Adjuvant therapy prolonged RFS (HR:0.69, p = 0.036)), but CLND did not (HR:1.22, p = 0.272). There were no statistically significant differences in OS for either adjuvant systemic treatment or CLND. Lower progression risk was also found, and time-dependent hazard ratios estimation in patients treated with systemic adjuvant therapy was confirmed (HR:0.20, p = 0.002 for BRAF inhibitors and HR:0.50, p = 0.015 for anti-PD-1 inhibitors). CONCLUSIONS: Treatment of SLNB-positive melanoma patients is constantly evolving, and the role of surgery is currently rather limited. Whether CLND has been performed or not, in a group of SLNB-positive patients, adjuvant systemic treatment should be offered to all eligible patients.

14.
Arch Gynecol Obstet ; 286(4): 995-1000, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22627994

RESUMO

PURPOSE: Since 2009 the new FIGO Staging System of endometrial cancer, which changed the previous FIGO 1988 Staging System, has been in use. The aim of the study was to compare prognosis in patients with endometrioid endometrial cancer at stage IB of the 2009 FIGO Staging System and of the 1988 FIGO Staging System. METHODS: We analyzed 173 patients: 108 patients (group A) at stage IB in FIGO 1988 Staging System, and 68 patients (group B) at stage IB in FIGO 2009 Staging System from 262 consecutive endometrioid endometrial cancer patients. The disease-free survival (DFS) and overall survival (OS) were compared between these groups. RESULTS: The DFS rate was 96.3 % in group A and it was 87.7 % in group B (p = 0.029). Relapses were observed in 12 patients (6.4 %) from 6 to 57 months (mean 28.1; SD = 14.6) after initial surgery, and occurred in four patients from group A (3.7 %) and eight patients from group B (12.3 %) (p = 0.032). The OS rate was 94.4 % in group A and it was 83.1 % in group B (p = 0.018). During follow-up, 17 patients (9.8 %) died: six patients from group A (5.6 %), and 11 patients from group B (16.9 %). CONCLUSIONS: Stage IB in FIGO 2009 Staging System is associated with worse prognosis compared to stage IB according to FIGO 1988 classification. There seems to be a need to use exclusively the new FIGO 2009 classification worldwide to avoid therapeutic mistakes, which can be caused by diverse nomenclature.


Assuntos
Carcinoma Endometrioide/diagnóstico , Neoplasias do Endométrio/diagnóstico , Carcinoma Endometrioide/classificação , Carcinoma Endometrioide/mortalidade , Intervalo Livre de Doença , Neoplasias do Endométrio/classificação , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Estadiamento de Neoplasias , Polônia/epidemiologia , Gravidez , Prognóstico
15.
Ginekol Pol ; 83(5): 342-6, 2012 May.
Artigo em Polonês | MEDLINE | ID: mdl-22708330

RESUMO

OBJECTIVES: To assess the effectiveness of the donor-block biopsies with a 2 mm-size needle in endometrioid endometrial cancer (EEC) in the tissue microarray (TMA) technique and the application of the TMA for estrogen receptors (ER) and progesterone receptors (PR) expression in EEC. MATERIAL AND METHODS: The study examined EEC tissues from 60 patients. Tissue cores, 2 mm in size, in duplicate, were taken from the formalin-fixed and paraffin-embedded tissue donor blocks and constructed into the TMA recipient block. The presence of EEC tissue in the TMAs was analyzed, and the ER and PR expressions were examined. RESULTS: EEC tissue in TMAs was confirmed in 56 cases (93.33%). In 49 of them (81.67%), both cores presented with cancer tissues. In 4 cases (6.67%) EEC tissue was absent. All cases with ECC present on the TMA slides were appropriate for the ER and PR analysis. In 29 EEC cases (51.98%) both ER and PR were expressed. In 3 cases (5.36%) only ER was expressed, in 8 cases (14.29%) only PR was expressed, and in 16 cases (28.57%) ER and PR were assessed as negative. CONCLUSIONS: Two 2 mm-sized tissue cores from donor-block biopsies constructed into the TMA recipient block were sufficient to diagnose EEC and enabled the assessment of ER and PR expression in 93.3% of the cases. The use of the described TMA technique makes the immunohistochemical study of EEC easier and more time-efficient.


Assuntos
Carcinoma Endometrioide/metabolismo , Neoplasias do Endométrio/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Biomarcadores Tumorais/metabolismo , Biópsia , Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Análise Serial de Tecidos/métodos
16.
Pol J Microbiol ; 71(1): 123-129, 2022 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-35635161

RESUMO

The infectious agents may be the etiological factor of up to 15-20% of cancers. In stomach cancer, attention is paid to Helicobacter pylori and Epstein-Barr virus, both of which cause gastritis and can lead to tumor development. In co-infection, the inflammatory process is much more intense. We assessed the seroprevalence towards H. pylori and EBV in 32 patients with diagnosed gastric cancer. H. pylori antibodies were found in 69% patients, and anti-EBV - in all of them. The study confirmed that co-infection of H. pylori and EBV seems to be important in etiopathology of gastric cancer.


Assuntos
Coinfecção , Infecções por Vírus Epstein-Barr , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Anticorpos Antibacterianos , Coinfecção/epidemiologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Herpesvirus Humano 4 , Humanos , Projetos Piloto , Polônia/epidemiologia , Estudos Soroepidemiológicos , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia
17.
Cancers (Basel) ; 14(6)2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35326606

RESUMO

Many of the anticancer agents that are currently in use demonstrate severe side effects and encounter increasing resistance from the target cancer cells. Thus, despite significant advances in cancer therapy in recent decades, there is still a need to discover and develop new, alternative anticancer agents. The plant kingdom contains a range of phytochemicals that play important roles in the prevention and treatment of many diseases. The Solanaceae family is widely used in the treatment of various diseases, including cancer, due to its bioactive ingredient content. The purpose of this literature review is to highlight the antitumour activity of Solanaceae extracts-single isolated compounds and nanoparticles with extracts-and their synergistic effect with chemotherapeutic agents in various in vitro and in vivo cancer models. In addition, the biological properties of many plants of the Solanaceae family have not yet been investigated, which represents a challenge and an opportunity for future anticancer therapy.

18.
Mol Cell Biochem ; 355(1-2): 193-9, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21533764

RESUMO

The aim of our study was to explain the effect of elevated homocysteine (measured by HPLC) on haemostatic activity of plasma from breast cancer patients (fibrin polymerization and lysis; the thrombin and prothrombin time), because homocysteine (Hcys) induces changes in haemostasis, as well blood clotting as fibrinolysis. Patients were hospitalized in Department of Oncological Surgery, Medical University of Lodz, Poland. All patients have not had preadjuvant therapy, and samples from patients were taken before surgery. We observed that changes of selected parameters of haemostatic properties of plasma, e.g., the prothrombin time and thrombin time were prolonged in plasma from invasive breast cancer when compared with the control group (healthy subjects) and patients with benign breast diseases. Our results showed also that the correlation between the increased amount of Hcys and changes of selected parameters of haemostasis in invasive breast cancer patients exists. Considering the data presented in this study, we suggest that the elevated Hcys in invasive breast cancer patients may induce the changes of haemostatic properties of plasma isolated from these patients.


Assuntos
Neoplasias da Mama/sangue , Carcinoma Ductal de Mama/sangue , Hemostasia , Homocisteína/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Fibrina/metabolismo , Fibrinólise , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Estatísticas não Paramétricas , Tempo de Trombina
19.
Int J Gynecol Pathol ; 30(4): 328-34, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21623209

RESUMO

Incidences of endometrial carcinoma (EC) among women of Western countries is increasing, reaching a level of 18/100,000. In 2009, the International Federation of Gynecology and Obstetrics (FIGO) proposed a new staging system in EC. The purpose of this study included the evaluation of distribution of EC in categories of age, histologic grade, and surgical staging according to the 1989 and the 2009 FIGO guidelines. The original staging assessments have been updated to reflect the current staging system in 123 consecutive patients. Statistical analysis was carried out. The median age of patients was 61 years. A comparison of old and new staging systems shows that a significant number of patients moved to stage I: 78.05%, versus 56.91% based on the 1989 classification (P=0.044). The number of patients in stage II changed as well: 9.76% according to new staging system and 30.89% by definitions of FIGO 1989 (P=0.001). Of patients in stage II, 21.1% had G1 tumors according to the old versus 8.3% by the new classification (P=0.001). We have not identified any associations between the histologic status of a cervix and EC. The most common type of EC is the endometrioid subtype, found in 87.8% of patients. We have noted a significant association between the tumor grade and cervical stromal infiltration. The new classification system for EC seems to be an improved staging instrument. Having up to 80% of patients with endometrial cancer in stage I and following them, might elucidate the impact of current staging on survival and life quality.


Assuntos
Colo do Útero/patologia , Neoplasias do Endométrio/patologia , Estadiamento de Neoplasias , Guias de Prática Clínica como Assunto , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/classificação , Feminino , Ginecologia , Humanos , Cooperação Internacional , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias/normas , Obstetrícia , Guias de Prática Clínica como Assunto/normas , Prognóstico , Estudos Retrospectivos
20.
Ginekol Pol ; 82(10): 743-8, 2011 Oct.
Artigo em Polonês | MEDLINE | ID: mdl-22379937

RESUMO

OBJECTIVES: To assess the relationship between selected clinical and pathological factors and disease free survival (DFS) and overall survival (OS) in endometrioid endometrial cancer patients. MATERIAL AND METHODS: A retrospective review of 262 patients aged 37-86 (6.0 +/- 9.0) was performed. Selected clinical and pathological data were correlated with DFS and OS. RESULTS: Follow-up was 8-123 months (64.9 +/- 27.1). In 4 patients (1.5%) clinical progression was diagnosed during the treatment. In 43 patients (16.4%) relapse was diagnosed 2-61 months (23.9 +/- 15.7) after commencing treatment. DFS and OS were 82.1% and 81.3% respectively. In univariate analysis worse DFS was related to older patients (p = 0.007) and non-radical surgery (p < 0.001). In multivariate analysis worse DFS was related to older patients (HR = 1.058; 95% CI = 1.024-1.093; p < 0.001), younger at menopause (HR = 0.910; 95% CI = 0.851-0.973; p = 0.006), with higher staging (HR = 2.639; 95% CI = 1.968-3.539; p < 0.001) operated non-radically (HR = 0.220; 95% CI = 0.096-0.504; p < 0.001). In univariate analysis worse OS was connected with older patients (p = 0.018), diabetes type II (p = 0.019) and non-radical surgery (p < 0.001). In multivariate analysis worse OS was related to younger age at menopause (HR = 0.932; 95% CI = 0.873-0.996; p = 0.039), diabetes type II (HR = 2.372; 95% CI = 1.260-4.466; p = 0.008), higher staging (HR = 2.053; 95% CI = 1.482-2.845; p < 0.001), and non-radical surgery (HR = 0.240; 95% CI = 0.091-0.636; p = 0.004). CONCLUSIONS: Relapsed endometrial cancer developed in 90.7% during four years after commencing treatment. In 79.1% of these patients distant metastases were present. Most significant prognostic factors were radicality of surgery age of patients and staging. The presence of diabetes type II and early menopause were connected with worse prognosis.


Assuntos
Carcinoma Endometrioide/epidemiologia , Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/patologia , Saúde da Mulher , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/terapia , Intervalos de Confiança , Intervalo Livre de Doença , Neoplasias do Endométrio/terapia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Estadiamento de Neoplasias , Razão de Chances , Polônia , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Taxa de Sobrevida
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