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

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.


Biomedical Research , Lamiaceae , Oils, Volatile , Humans , Oils, Volatile/pharmacology , Oils, Volatile/therapeutic use , Antioxidants/pharmacology , Antioxidants/therapeutic use , Nanotechnology
2.
Genes (Basel) ; 14(6)2023 06 20.
Article En | MEDLINE | ID: mdl-37372475

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.


Antineoplastic Agents , Melanoma , Humans , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylase Inhibitors/therapeutic use , Valproic Acid/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Dacarbazine/therapeutic use , Histone Deacetylases/genetics , Histone Deacetylases/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Melanoma/drug therapy , Melanoma/genetics , Melanoma/pathology , DNA , Alkylating Agents/therapeutic use
3.
Cancers (Basel) ; 15(10)2023 May 09.
Article En | MEDLINE | ID: mdl-37345002

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.

4.
Arch Med Sci ; 19(2): 343-354, 2023.
Article En | MEDLINE | ID: mdl-37034529

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.

5.
Cancers (Basel) ; 16(1)2023 Dec 25.
Article En | MEDLINE | ID: mdl-38201542

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.

6.
Pol J Microbiol ; 71(1): 123-129, 2022 Feb 27.
Article En | MEDLINE | ID: mdl-35635161

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.


Coinfection , Epstein-Barr Virus Infections , Helicobacter Infections , Helicobacter pylori , Stomach Neoplasms , Antibodies, Bacterial , Coinfection/epidemiology , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/epidemiology , Helicobacter Infections/complications , Helicobacter Infections/epidemiology , Herpesvirus 4, Human , Humans , Pilot Projects , Poland/epidemiology , Seroepidemiologic Studies , Stomach Neoplasms/epidemiology , Stomach Neoplasms/pathology
7.
Cancers (Basel) ; 14(6)2022 Mar 11.
Article En | MEDLINE | ID: mdl-35326606

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.

9.
Sci Rep ; 11(1): 4337, 2021 02 22.
Article En | MEDLINE | ID: mdl-33619293

Non-melanoma skin cancers (NMSCs) are the most common malignancies diagnosed in Caucasian populations. Basal cell carcinoma (BCC) is the most frequent skin cancer, followed by squamous cell carcinoma (SCC). Unfortunately, most European cancer registries do not record individual types of NMSC. To evaluate the incidence of primary BCCs and SCCs regarding age, sex, tumour site and tumour subtype to determine trends in epidemiology of both cancers. Retrospective analysis of BCCs and SCCs diagnosed and treated across seven sites in Poland from 1999 to 2019. We recorded 13,913 NMSCs occurring in 10,083 patients. BCC represented 85.2% of all cases. SCC patients were older than BCC patients (77.1 ± 11.3 years vs. 70.1 ± 12.3 years, p < 0.01). The nodular subtype was the most common subtype of BCC, followed by the superficial and infiltrative subtypes. The superficial BCC subtype was more common on photoprotected areas (p < 0.01), whereas the nodular BCC subtype occurred on the face (p < 0.01). The high-risk SCC subtypes were more common on face compared to low-risk SCC subtypes (p < 0.01). BCC and SCC are common malignancies developing at various ages and anatomical sites. These data underline the need for better registration policies regarding NMSC in order to improve prevention and treatment strategies for these tumours.


Skin Neoplasms/diagnosis , Skin Neoplasms/epidemiology , Adult , Age Factors , Aged , Aged, 80 and over , Female , Humans , Incidence , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Poland/epidemiology , Public Health Surveillance , Registries , Sex Factors , Skin Neoplasms/etiology , Young Adult
10.
Sci Rep ; 10(1): 18475, 2020 10 28.
Article En | MEDLINE | ID: mdl-33116191

Basosquamous carcinoma (BSC) is a rare non-melanoma skin cancer that shares the characteristic features of both basal and squamous cell carcinomas (BCC, SCC). Our research enables better characterization of BSC in comparison to high-risk subtypes of BCC and SCC. Paper includes a retrospective analysis of BSC cases regarding sex, age, number of tumors and anatomical distribution in comparison to BCC and SCC evaluating the differences and defining the implications. Histologically confirmed carcinomas recorded between 1999 and 2019 were studied. 181 diagnosed BSC cases were identified, making this study the largest cohorts of BSC patients reported worldwide. Most cases were reported on head and neck. Analysis of facial anatomic distribution shows that most commonly affected sites were the nose (43%) and the cheek (25%). The age at excision of metatypical BCC was higher than those of low-risk BCC (P < 0.05), however similar to high-risk BCC (P = 0.20). We revisited that the concept of BSC is the most similar to high-risk subtypes of BCC. Patients with diagnosed BSC have higher risk of second nonmelanoma skin cancer. Therefore, the frequency of follow-up examination should be adjusted to the individual risk of another skin cancer.


Carcinoma, Basal Cell/epidemiology , Carcinoma, Basosquamous/epidemiology , Carcinoma, Squamous Cell/epidemiology , Skin Neoplasms/epidemiology , Aged , Carcinoma, Basal Cell/pathology , Carcinoma, Basosquamous/pathology , Carcinoma, Squamous Cell/pathology , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local , Retrospective Studies , Risk , Skin Neoplasms/pathology
11.
Ginekol Pol ; 89(8): 415-420, 2018.
Article En | MEDLINE | ID: mdl-30215459

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.


Biomarkers, Tumor/blood , Breast Neoplasms/blood , Circulating MicroRNA/blood , MicroRNAs/blood , Triple Negative Breast Neoplasms/blood , Adult , Aged , Biomarkers, Tumor/genetics , Breast Neoplasms/chemistry , Breast Neoplasms/genetics , Circulating MicroRNA/genetics , Female , Humans , MicroRNAs/genetics , Middle Aged , Receptor, ErbB-2/analysis , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Triple Negative Breast Neoplasms/chemistry , Triple Negative Breast Neoplasms/genetics
12.
Pol J Pathol ; 69(1): 33-41, 2018.
Article En | MEDLINE | ID: mdl-29895124

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).


Biomarkers, Tumor/analysis , Breast Neoplasms/chemistry , Intracellular Signaling Peptides and Proteins/analysis , Mitochondrial Proteins/analysis , Adult , Aged , Apoptosis Regulatory Proteins , Biopsy , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Chemotherapy, Adjuvant , Disease-Free Survival , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Mastectomy , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Risk Factors , Time Factors , Treatment Outcome
13.
Postepy Hig Med Dosw (Online) ; 69: 586-97, 2015 May 05.
Article En | MEDLINE | ID: mdl-25983297

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.


Breast Neoplasms/metabolism , PTEN Phosphohydrolase/genetics , Receptor, ErbB-2/metabolism , Receptor, ErbB-3/genetics , Trastuzumab/therapeutic use , Breast Neoplasms/diagnosis , Breast Neoplasms/drug therapy , Female , Gene Expression , Humans , Immunohistochemistry , Middle Aged , Phosphorylation , Prognosis , Receptor, ErbB-2/drug effects , Receptor, ErbB-2/genetics , Treatment Outcome
14.
Adv Clin Exp Med ; 23(4): 567-73, 2014.
Article En | MEDLINE | ID: mdl-25166441

BACKGROUND: The preoperative radiological diagnosis of GIST is complicated by its varied macroscopic morphology. Moreover, the precision of preoperative histopathological diagnostics is reduced by the submucosal localization of the lesion. OBJECTIVES: The goal of the study was to perform a retrospective analysis of the clinical and histopathological factors seen in patients operated on for a stomach GIST tumor with unclear diagnosis. MATERIAL AND METHODS: Two groups of GIST patients treated in our department were compared with regard to their histopathological and clinical data. The first group (9 patients, group 1) comprised patients with a histopathological diagnosis for stomach GIST confirmed before the surgical procedure, while the second group (10 patients, group 2) comprised patients with no solid histopathological diagnosis before surgery. The following clinical and histopathological variables were analyzed in the study: age, gender, presence or absence of metastases, anatomical location of metastases, symptoms, tumor size, surgical mortality, tumor recurrence, treatment with imatinib, patient survival in months, histological subtype, mitotic index, cellular atypia, necrosis, tumor ulceration and Ki-67. The results were analyzed statistically. RESULTS: The mean survival time differed significantly between the two study groups: group 1 being 12 months and group 2 being 8 months. The lower survival time in group 2 was connected with the higher stage of the disease at the moment of diagnosis. CONCLUSIONS: Our findings suggest that GIST tumors with an unclear diagnosis are recognized at a late stage of the disease. The more advanced stage of the tumor probably results from faster tumor growth caused by higher proliferation activity. These GIST tumors are characterized by a lower survival rate due to the later stage of the disease at the time of diagnosis.


Gastrointestinal Stromal Tumors/pathology , Stomach Neoplasms/pathology , Aged , Female , Gastrointestinal Stromal Tumors/mortality , Gastrointestinal Stromal Tumors/surgery , Humans , Immunohistochemistry , Ki-67 Antigen/analysis , Male , Middle Aged , Retrospective Studies , Stomach Neoplasms/mortality , Stomach Neoplasms/surgery , Survival Rate
15.
Arch Med Sci ; 10(1): 84-90, 2014 Feb 24.
Article En | MEDLINE | ID: mdl-24701219

INTRODUCTION: The value of argyrophilic nucleolar organizer regions (AgNORs) to predict survival in patients with ovarian cancer has not been clearly explained yet. The aim of study was to assess the value of analysis of the mean number of AgNORs per nucleus (mAgNOR) and mean percentage of nuclei with five or more AgNORs per nucleus (pAgNOR) in the prediction of disease-free survival (DFS) and overall survival (OS) in patients with serous ovarian cancer. MATERIAL AND METHODS: The study examined 52 patients treated for serous ovarian cancer with a follow-up period of 2-143 months. After silver staining paraffin specimens from primary surgery, mAgNOR and pAgNOR in cancer cells were counted and analyzed. Age, grading, radicality of surgery and FIGO staging were analyzed as covariates. RESULTS: Mean mAgNOR equaled 4.4 ±0.9 and pAgNOR equaled 42.2 ±20.8%. Both mAgNOR and pAgNOR were the lowest in G1 tumors. The mAgNOR and pAgNOR were lower in stage I than stage IV cancers. The DFS and OS rates were respectively 15.4% and 21.2%. In univariate analysis FIGO staging, grading, and pAgNOR were associated with worse prognosis, while radicality of surgery remained a significant protective factor in terms of DFS. Higher FIGO staging and older age worsened OS. In multivariate analysis FIGO staging remained significantly associated with both DFS (HR 1.98; 95% CI 1.05-3.71) and OS (HR 1.76; 95% CI 1.00-3.10), while age affected OS rates (HR 1.78; 95% CI 1.04-2.95). CONCLUSIONS: mAgNOR and pAgNOR are useful markers of cellular kinetics. Prospective studies in larger populations are needed to confirm these results in terms of AgNORs' effects on survival.

16.
Ginekol Pol ; 84(6): 444-9, 2013 Jun.
Article Pl | MEDLINE | ID: mdl-24032262

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.


Biomarkers, Tumor/metabolism , Carcinoma, Endometrioid/diagnosis , Carcinoma, Endometrioid/metabolism , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/metabolism , Ki-67 Antigen/metabolism , Adult , Aged , Aged, 80 and over , Carcinoma, Endometrioid/mortality , Carcinoma, Endometrioid/pathology , Disease-Free Survival , Endometrial Neoplasms/mortality , Endometrial Neoplasms/pathology , Female , Follow-Up Studies , Humans , Middle Aged , Poland , Predictive Value of Tests , Prognosis , Risk Assessment , Tissue Array Analysis/methods
17.
Ginekol Pol ; 84(2): 95-101, 2013 Feb.
Article Pl | MEDLINE | ID: mdl-23668054

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.


Biomarkers, Tumor/metabolism , Carcinoma, Endometrioid/metabolism , Endometrial Neoplasms/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Adult , Aged , Carcinoma, Endometrioid/mortality , Carcinoma, Endometrioid/pathology , Disease-Free Survival , Endometrial Neoplasms/mortality , Endometrial Neoplasms/pathology , Female , Humans , Middle Aged , Neoplasm Staging , Poland , Prognosis , Tissue Array Analysis/methods , Tumor Cells, Cultured
18.
Arch Gynecol Obstet ; 288(4): 889-99, 2013 Oct.
Article En | MEDLINE | ID: mdl-23584885

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.


Biomarkers, Tumor/metabolism , Carcinoma, Endometrioid/metabolism , Endometrial Hyperplasia/metabolism , Endometrial Neoplasms/metabolism , Endometrium/metabolism , Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism , Tumor Necrosis Factor Decoy Receptors/metabolism , Biomarkers/metabolism , Carcinoma, Endometrioid/mortality , Cell Membrane/metabolism , Endometrial Neoplasms/mortality , Female , GPI-Linked Proteins/metabolism , Humans , Immunohistochemistry , Receptors, Tumor Necrosis Factor, Member 10c , Survival Analysis , Tissue Array Analysis
19.
Arch Med Sci ; 9(1): 79-85, 2013 Feb 21.
Article En | MEDLINE | ID: mdl-23515230

INTRODUCTION: There is a need to assess the value of the novel potentially useful biomarkers in ovarian tumors. The aim of study was to assess the value of sAgNOR analysis in ovarian serous epithelial tumors. MATERIAL AND METHODS: The analysis was performed in ovaries from 113 patients treated operatively due to serous ovarian tumors (30 adenomas, 14 borderline tumors and 69 cancers). After silver staining of paraffin specimens from surgery, sAgNOR in tumor cells was analyzed. Additionally, the value of the argyrophilic nucleolar organizer region area/nucleus ratio (sAgNOR) in the prediction of disease-free survival (DFS) and overall survival (OS) in 52 patients with serous ovarian cancer with complete follow-ups in November 2009 was evaluated. Age, grading, radicality of surgery and FIGO staging were analyzed as additional factors. RESULTS: SAGNOR IN ADENOMAS, BORDERLINE TUMORS AND CANCERS WAS IN THE FOLLOWING RANGES: (0.73 ±0.23) × 10(6), (0.81 ±0.18) × 10(6) and (0.96 ±0.33) × 10(6) [AgNOR/cm(2)] respectively. In cancers from G1 to G3 sAgNOR was (1.02 ±0.32) × 10(6) (G1), (0.98 ±0.37) × 10(6) (G2) and (0.82 ±0.24) × 10(6) (G3) [AgNOR/cm(2)] respectively. In univariate analysis, but not in multivariate analysis, staging negatively correlated with better DFS and OS. sAgNOR, age of patients, grading and radicality of surgery were not associated with DFS or OS in either univariate or multivariate analysis. CONCLUSIONS: sAgNOR analysis is not sufficient to precisely characterize cellular kinetics in serous ovarian tumors, and the analysis of sAgNOR, mAgNOR and pAgNOR should be performed commonly. The prognostic significance of sAgNOR in patients with serous ovarian cancer was not proven.

20.
Platelets ; 24(6): 462-8, 2013.
Article En | MEDLINE | ID: mdl-22871094

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.


Blood Platelets/physiology , Breast Neoplasms/blood , Platelet Activation/physiology , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , Case-Control Studies , Female , Humans , Middle Aged , Perioperative Period , Platelet Aggregation , Platelet Function Tests
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