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In recent years, the utilization of natural components has become crucial across various industries, including medicine. Particularly in biomedical contexts, hydrogel materials are of significant importance. Therefore, the objective of this research was to develop and analyze hydrogel materials infused with vitamin C. A key focus of this study was to conduct multiple syntheses with varying levels of vitamin C to explore the feasibility of creating materials with adjustable properties. The produced hydrogels underwent comprehensive physicochemical evaluation. The findings of this examination verified the correlation between the vitamin C content and the specific characteristics of the hydrogels. It was determined from these results that the samples displayed both sorptive and antioxidative capabilities, enabling their potential application in wound dressings or other biomedical uses. A notable benefit of these hydrogels is their adaptability, allowing for modifications to achieve desired attributes tailored to particular applications.
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Antioxidantes , Ácido Ascórbico , Hidrogeles , Extractos Vegetales , Ácido Ascórbico/química , Hidrogeles/química , Extractos Vegetales/química , Antioxidantes/química , Antioxidantes/farmacología , Materiales Biocompatibles/químicaRESUMEN
The use of natural ingredients in recent years has been of great importance in many industries and medicine. In biomedical applications, hydrogel materials also play a significant role. In view of this, the aim of this study was to synthesize and characterize hydrogel materials enriched with broadleaf linden hydrolate. An important aspect was to carry out a series of syntheses with varying types and amounts of crosslinking agents so as to test the possibility of synthesizing materials with controlled properties. The obtained hydrogels were subjected to detailed physicochemical analysis. The results of the tests confirmed the relationship between the selected properties and the type of crosslinking agent used. A crosslinking agent with a lower molar mass (575 g/mol) results in a material with a compact and strongly crosslinked structure, which is characterized by high surface roughness. The use of a crosslinking agent with a molecular weight of 700 g/mol resulted in a material with a looser-packed polymer network capable of absorbing larger amounts of liquids. The work also proved that regardless of the type of crosslinking agent used, the addition of linden hydrolate provides antioxidant properties, which is particularly important in view of the target biomedical application of such materials.
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The interest in the application of plant extracts as modifiers of polymers intended for biomedical purposes is constantly increasing. The therapeutical properties of the licorice root, including its anti-inflammatory and antibacterial activity, make this plant particularly promising. The same applies to silver nanoparticles showing antibacterial properties. Thus the main purpose of the research was to design hydrogel dressings containing both licorice root extract and nanosilver so as to obtain a system promoting wound regeneration processes by preventing infection and inflammation within the wound. The first step included the preparation of the plant extract via the solid-liquid extraction using the Soxhlet extractor and the synthesis of silver nanoparticles by the chemical reduction of silver ions using a sodium borohydride as a reducing agent. Subsequently, hydrogels were synthesized via photopolymerization and subjected to studies aiming at characterizing their sorption properties, surface morphology via scanning electron microscopy, and their impact on simulated physiological liquids supported by defining these liquids' influence on hydrogels' structures by FT-IR spectroscopy. Next, the tensile strength of hydrogels and their percentage elongation were determined. Performed studies also allowed for determining the hydrogels' wettability and free surface energies. Finally, the cytotoxicity of hydrogels towards L929 murine fibroblasts via the MTT reduction assay was also verified. It was demonstrated that developed materials showed stability in simulated physiological liquids. Moreover, hydrogels were characterized by high elasticity (percentage elongation within the range of 24-29%), and their surfaces were hydrophilic (wetting angles below 90°). Hydrogels containing both licorice extract and nanosilver showed smooth and homogeneous surfaces. Importantly, cytotoxic properties towards L929 murine fibroblasts were excluded; thus, developed materials seem to have great potential for application as innovative dressings.
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Glycyrrhiza , Nanopartículas del Metal , Ratones , Animales , Hidrogeles/química , Plata/química , Nanopartículas del Metal/química , Espectroscopía Infrarroja por Transformada de Fourier , Antibacterianos/farmacología , Antibacterianos/química , Extractos Vegetales/farmacología , Antioxidantes , VendajesRESUMEN
Hydrogels belong to the group of polymers with a three-dimensional crosslinked structure, and their crosslinking density strongly affects their physicochemical properties. Here, we verified the impact of both the average molecular weight of crosslinking agents used during the photopolymerization of hydrogels and that of their content on selected properties of these materials. First, PVP-based hydrogels modified with Aloe vera juice and L-ascorbic acid were prepared using UV radiation. Next, their surface morphology was characterized via optical scanning electron microscopy, whereas their chemical structure was investigated by FT-IR spectroscopy. Moreover, we verified the tendency of the hydrogels to degrade in selected physiological liquids, as well as their tensile strength, percentage of elongation, and swelling capability. We found that the more crosslinking agent in the hydrogel matrix, the higher its tensile strength and the less elongation. The hydrogels showed the highest stability during incubation in SBF and 2% hemoglobin solution. A sharp decrease in the pH of distilled water observed during the incubation of the hydrogels was probably due to the release of Aloe vera juice from the hydrogel matrices. This was additionally confirmed by the decrease in the intensity of the absorption band derived from the polysaccharides included in this additive and by the decrease in the swelling ratio after 48 h. Importantly, all hydrogels demonstrated swelling properties, and it was proven that the higher content of the crosslinking agent in hydrogels, the lower their swelling ability.
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Aloe , Hidrogeles , Aloe/química , Ácido Ascórbico , Vendajes , Hemoglobinas , Hidrogeles/química , Peso Molecular , Polímeros/química , Polisacáridos , Espectroscopía Infrarroja por Transformada de Fourier , AguaRESUMEN
CAR-T (chimeric antigen receptor T) cells have emerged as a milestone in the treatment of patients with refractory B-cell neoplasms. However, despite having unprecedented efficacy against hematological malignancies, the treatment is far from flawless. Its greatest drawbacks arise from a challenging and expensive production process, strict patient eligibility criteria and serious toxicity profile. One possible solution, supported by robust research, is the replacement of T lymphocytes with NK cells for CAR expression. NK cells seem to be an attractive vehicle for CAR expression as they can be derived from multiple sources and safely infused regardless of donor-patient matching, which greatly reduces the cost of the treatment. CAR-NK cells are known to be effective against hematological malignancies, and a growing number of preclinical findings indicate that they have activity against non-hematological neoplasms. Here, we present a thorough overview of the current state of knowledge regarding the use of CAR-NK cells in treating various solid tumors.
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Inmunoterapia Adoptiva , Células Asesinas Naturales/inmunología , Neoplasias/terapia , Receptores de Antígenos de Linfocitos T/inmunología , Animales , Antígenos de Neoplasias/inmunología , Técnicas de Cultivo de Célula , Ensayos Clínicos como Asunto , Terapia Combinada/métodos , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Ingeniería Genética , Humanos , Células Asesinas Naturales/metabolismo , Neoplasias/diagnóstico , Neoplasias/etiología , Neoplasias/metabolismo , Receptores de Antígenos de Linfocitos T/genética , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/inmunología , Resultado del TratamientoRESUMEN
Many investigations are currently being performed to develop the effective synthesis methodology of magnetic nanoparticles with appropriately functionalized surfaces. Here, the novelty of the presented work involves the preparation of nano-sized PEGylated Fe3O4@Ag particles, i.e., the main purpose was the synthesis of magnetic nanoparticles with a functionalized surface. Firstly, Fe3O4 particles were prepared via the Massart process. Next, Ag+ reduction was conducted in the presence of Fe3O4 particles to form a nanosilver coating. The reaction was performed with arabic gum as a stabilizing agent. Sound energy-using sonication was applied to disintegrate the particles' agglomerates. Next, the PEGylation process aimed at the formation of a coating on the particles' surface using PEG (poly(ethylene glycol)) has been performed. It was proved that the arabic gum limited the agglomeration of nanoparticles, which was probably caused by the steric effect caused by the branched compounds from the stabilizer that adsorbed on the surface of nanoparticles. This effect was also enhanced by the electrostatic repulsions. The process of sonication caused the disintegration of aggregates. Formation of iron (II, III) oxide with a cubic structure was proved by diffraction peaks. Formation of a nanosilver coating on the Fe3O4 nanoparticles was confirmed by diffraction peaks with 2θ values 38.15° and 44.35°. PEG coating on the particles' surface was proven via FT-IR (Fourier Transform Infrared Spectroscopy) analysis. Obtained PEG-nanosilver-coated Fe3O4 nanoparticles may find applications as carriers for targeted drug delivery using an external magnetic field.
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Materiales Biocompatibles Revestidos , Nanopartículas de Magnetita/química , Polietilenglicoles/química , Plata/química , Materiales Biocompatibles Revestidos/síntesis química , Materiales Biocompatibles Revestidos/químicaRESUMEN
Expression of the tetraspanin CD151 is frequently upregulated in epithelial malignancies and correlates with poor prognosis. Here, we report that CD151 is involved in regulation of the expression of fibroblast growth factor receptor 2 (FGFR2). Depletion of CD151 in breast cancer cells resulted in an increased level of FGFR2. Accordingly, an inverse correlation between CD151 and FGFR2 was observed in breast cancer tissues. CD151-dependent regulation of the FGFR2 expression relies on post-transcriptional mechanisms involving HuR (also known as ELAVL1), a multifunctional RNA-binding protein, and the assembly of processing bodies (P-bodies). Depletion of CD151 correlated with inhibition of PKC, a well-established downstream target of CD151. Accordingly, the levels of dialcylglycerol species were decreased in CD151-negative cells, and inhibition of PKC resulted in the increased expression of FGFR2. Whereas expression of FGFR2 itself did not correlate with any of the clinicopathological data, we found that FGFR2-/CD151+ patients were more likely to have developed lymph node metastasis. Conversely, FGFR2-/CD151- patients demonstrated better overall survival. These results illustrate functional interdependency between CD151 complexes and FGFR2, and suggest a previously unsuspected role of CD151 in breast tumorigenesis.
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Neoplasias de la Mama/metabolismo , Proteína Quinasa C/metabolismo , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/biosíntesis , Tetraspanina 24/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Carcinogénesis , Línea Celular Tumoral , Femenino , Humanos , Células MCF-7 , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Transducción de Señal , Tetraspanina 24/biosíntesis , Tetraspanina 24/genética , Transcripción GenéticaRESUMEN
BACKGROUND This study aimed to undertake an analysis of ten years of real-world evidence (RWE) on overall survival (OS) following treatment of advanced gastrointestinal stromal tumor (GIST) with imatinib, sunitinib, and sorafenib using data from the Polish National Health Fund. MATERIAL AND METHODS Data from the Polish National Health Fund, the sole Polish public payer, identified 1,641 patients with advanced GIST who were treated with imatinib (n=1047), sunitinib (n=457), and sorafenib (n=137). The differences in overall survival (OS) were analyzed. RESULTS For patients with advanced GIST, the median follow-up time for patients treated with imatinib was 71 months (95% CI, 64.8-79.2), the median OS was 56.9 months (95% CI, 50.4-61.2), with survival at 12 months (89.5%), 24 months (77.9%), 36 months (66.9%), and 60 months (48.4%). The median follow-up time for patients treated with sunitinib was 41.4 months (95% CI, 34.6-49.3), the median OS was 22.8 months (95% CI, 19.2-26.8), with survival at 12 months (68.2%), 24 months (47.1%), and 36 months (31%). The median follow-up time for patients treated with sorafenib was 17.4 months (95% CI, 14.6-22.9), the median OS was 16.9 months (95% CI, 13.7-24.3), with survival at 12 months (61.9%), at 24 months (36.2%), and at 36 months (16.8%). CONCLUSIONS Real-world data collected in a ten-year period confirmed the effectiveness of the use of imatinib, sunitinib, or sorafenib for the treatment of advanced GIST and was comparable with the findings from clinical trials.
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Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/patología , Adulto , Anciano , Antineoplásicos/uso terapéutico , Benzamidas/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Tumores del Estroma Gastrointestinal/inmunología , Humanos , Mesilato de Imatinib/uso terapéutico , Indoles/uso terapéutico , Masculino , Persona de Mediana Edad , Polonia , Inhibidores de Proteínas Quinasas/uso terapéutico , Práctica de Salud Pública , Pirroles/uso terapéutico , Sorafenib/uso terapéutico , Sunitinib/uso terapéutico , Resultado del TratamientoRESUMEN
INTRODUCTION: In Poland, it is uniquely possible to assess real effects of the introduction of new oncological therapies on the overall survival in patients as such therapies are funded by one payer only - the National Health Fund (NHF). Data collected by the NHF make it possible to analyse the survival of all patients who were diagnosed with melanoma. AIM: The paper presents findings of a retrospective analysis of the efficacy of systemic treatment in patients with malignant melanoma of the skin in Poland with regard to the overall survival. MATERIAL AND METHODS: The analysis of the overall survival was performed with the Kaplan-Meier method in the population receiving systemic treatment. Three groups of patients were analysed. Group 1 included all patients who had started systemic treatment between 1 March 2011 and 1 March 2015: 1,258 patients. The median overall survival was 8.4 months. Group 2 included 444 patients who had started systemic treatment between 1 March 2011 and 28 February 2013. The median overall survival was 6.6 months in this group. Group 3 included 814 patients who had started systemic treatment between 1 March 2013 and 1 March 2015 and included 546 patients who were also treated in drug programmes with ipilimumab and vemurafenib (approx. 67%). The median overall survival was 9.4 months. RESULTS: A difference in the overall survival between group 3 and 2 was statistically significant (p < 0.05). CONCLUSIONS: The introduction of vemurafenib and ipilimumab into systemic treatment in Poland using public funds had a significant effect on the prolongation of the overall survival in patients with malignant melanoma of the skin.
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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).
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Biomarcadores de Tumor/análisis , Neoplasias de la Mama/química , Péptidos y Proteínas de Señalización Intracelular/análisis , Proteínas Mitocondriales/análisis , Adulto , Anciano , Proteínas Reguladoras de la Apoptosis , Biopsia , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Mastectomía , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
Cigarette smoking is the leading risk factor of lung cancer. Data from several clinical studies suggest that continuation of smoking during therapy of tobacco-related cancers is associated with lower response rates to chemotherapy and/or radiotherapy, and even with decreased survival. Although nicotine--an addictive component of tobacco--is not a carcinogen, it may influence cancer development and progression or effectiveness of anti-cancer therapy. Several in vitro and in vivo trials have evaluated the influence of nicotine on lung cancer cells. The best known mechanisms by which nicotine impacts cancer biology involve suppression of apoptosis induced by certain drugs or radiation, promotion of proliferation, angiogenesis, invasion and migration of cancer cells. This effect is mainly mediated by membranous nicotinic acetylcholine receptors whose stimulation leads to sustained activation of such intracellular pathways as PI3K/Akt/mTOR, RAS/RAF/MEK/ERK and JAK/STAT, induction of NF-κB activity, enhanced transcription of mitogenic promoters, inhibition of the mitochondrial death pathway or stimulation of pro-angiogenic factors. We herein summarize the mechanisms underlying nicotine's influence on biology of lung cancer cells and the effectiveness of anti-cancer therapy.
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Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Resistencia a Antineoplásicos/fisiología , Neoplasias Pulmonares/metabolismo , Nicotina/farmacología , Fumar/efectos adversos , Apoptosis/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/fisiopatología , Neoplasias Pulmonares/radioterapia , Invasividad Neoplásica/fisiopatología , Procesos Neoplásicos , Neovascularización Patológica/metabolismo , Receptores Nicotínicos/metabolismo , Transducción de Señal/fisiologíaRESUMEN
AIM OF THE STUDY: To was to determine the impact of chronic obstructive pulmonary disease (COPD) and active smoking on the efficacy of chemotherapy and complete blood count (CBC) in patients with non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: The retrospective evaluation included 50 patients with stage IIIB-IV NSCLC, who started cisplatin-based chemotherapy. Peripheral blood CBC values were collected for testing before chemotherapy and after the first and third cycles. RESULTS: COPD was diagnosed in 49% of patients, while 42% of those enrolled were current smokers. Current smoking (p = 0.92) and COPD (p = 0.91) status did not affect the response to treatment. The non-COPD population presented a significantly higher pretreatment absolute lymphocyte count (ALC) than the COPD population (2.31 vs. 1.81 × 109/l; p = 0.0374). Also, only the non-COPD group demonstrated an elevated absolute monocyte count (AMC) following the first and third cycles of chemotherapy (p = 0.004). In current smokers, pretreatment values for white blood cells (WBC), absolute neutrophil count (ANC), and platelets (PLT) were higher than in the ex-smoker population (WBC 9.94 vs. 8.7 (× 109/l); p = 0.01; ANC 6.47 vs. 5.61 (× 109/l); p = 0.037; PLT 316 vs. 266 (× 109/l); p = 0.049). Ex-smokers demonstrated AMC level elevation after the first cycle of chemotherapy and PLT level elevation after the third cycle, while current smokers also demonstrated an early decrease in LMR. CONCLUSIONS: COPD and smoking induce chronic systemic inflammation and oxidative stress, which influence the results of standard laboratory tests, but do not change the response rate of lung cancer on chemotherapy.
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The goal of preoperative pharmacotherapy in patients with breast cancer is to enable breast conserving surgery in stage T3N0-1M0 or radical mastectomy in patients with primary inoperative tumors (T1-4N0-3M0). The choice of optimal treatment should be based not only on risk factors resulting from the stage but also on predicted cancer responsiveness to the treatment. The breast cancer subtypes defined by immunohistochemical profile (expression of ER, PR, HER2 and Ki67) are characterized by different responsiveness to therapy. Complete response confirmed by histopathological evaluation after neoadjuvant chemotherapy is a positive prognostic factor in some breast cancer subtypes. This marker is not of value in postmenopausal patients with ER/PR+ HER2- tumors, who are candidates for neoadjuvant hormone therapy. These patients have a good prognosis if in a histopathological report after surgery there are features such as pT1, pN0, Ki67 < 3%, and ER Allred score ≥ 3. The goal of the paper is to present current knowledge about preoperative pharmacotherapy of breast cancer.
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BACKGROUND: The proposed involvement of CD151 in breast cancer (BCa) progression is based on findings from studies in invasive ductal carcinoma (IDC). The IDC and invasive lobular carcinoma (ILC) represent distinct disease entities. Here we evaluated clinical significance of CD151 alone and in association with integrin α3ß1 in patients with ILC in context of the data of our recent IDC study. METHODS: Expression of CD151 and/or integrin α3ß1 was evaluated in ILC samples (N=117) using immunohistochemistry. The findings were analysed in relation to our results from an IDC cohort (N=182) demonstrating a prognostic value of an expression of CD151/integrin α3ß1 complex in patients with HER2-negative tumours. RESULTS: Unlike in the IDCs, neither CD151 nor CD151/α3ß1 complex showed any correlation with any of the ILC characteristics. Lack of both CD151 and α3ß1 was significantly correlated with poor survival (P=0.034) in lymph node-negative ILC N(-) cases. The CD151(-)/α3ß1(-) patients had 3.12-fold higher risk of death from BCa in comparison with the rest of the ILC N(-) patients. CONCLUSIONS: Biological role of CD151/α3ß1 varies between ILC and IDC. Assessment of CD151/α3ß1 might help to identify ILC N(-) patients with increased risk of distant metastases.
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Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/metabolismo , Integrina alfa3beta1/metabolismo , Ganglios Linfáticos/patología , Tetraspanina 24/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/patología , Femenino , Humanos , Inmunohistoquímica/métodos , Persona de Mediana Edad , Pronóstico , Receptor ErbB-2/metabolismoRESUMEN
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.
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Neoplasias de la Mama/metabolismo , Fosfohidrolasa PTEN/genética , Receptor ErbB-2/metabolismo , Receptor ErbB-3/genética , Trastuzumab/uso terapéutico , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Fosforilación , Pronóstico , Receptor ErbB-2/efectos de los fármacos , Receptor ErbB-2/genética , Resultado del TratamientoRESUMEN
Lapatinib is approved in combination with capecitabine for treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) who have progressed on prior trastuzumab in the metastatic setting. Vinorelbine is an important chemotherapy option for MBC. We evaluated efficacy and safety of lapatinib plus vinorelbine, compared with lapatinib plus capecitabine, in women with HER2-positive MBC. In this open-label, multicenter, phase II study, eligible patients (N = 112) were randomized 2:1 to lapatinib plus vinorelbine [(N = 75) 1,250 mg orally once daily (QD) continuously plus 20 mg/m(2)/day intravenously] or lapatinib plus capecitabine [(N = 37) 1,250 mg orally QD continuously plus 2,000 mg/m(2)/day orally, 2 doses]. The primary endpoint was progression-free survival (PFS). Other endpoints included overall survival (OS) and safety. Patients progressing within the study were given the option of crossover to the other treatment arm; time to second progression was an exploratory endpoint. Patient demographics, stratification, and prognostic factors were well balanced between treatments. Median PFS in both arms was 6.2 months [95 % confidence interval (CI) 4.2, 8.8 (lapatinib plus vinorelbine); 4.4, 8.3 (lapatinib plus capecitabine)]. Median OS on lapatinib plus vinorelbine was 24.3 months (95 % CI 16.4, NE) and 19.4 months (95 % CI 16.4, 27.2) on lapatinib plus capecitabine. In total, 42 patients opted to cross over; median PFS was 3.2 months (95 % CI 1.7, 5.1) on lapatinib plus vinorelbine and 4.0 months (95 % CI 2.1, 5.8) on lapatinib plus capecitabine. Lapatinib plus vinorelbine offers an effective treatment option for patients with HER2-overexpressing MBC, having displayed comparable efficacy and tolerability rates to lapatinib plus capecitabine.
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Neoplasias de la Mama/tratamiento farmacológico , Quinazolinas/administración & dosificación , Receptor ErbB-2/biosíntesis , Vinblastina/análogos & derivados , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Capecitabina , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Lapatinib , Persona de Mediana Edad , Metástasis de la Neoplasia , Receptor ErbB-2/genética , Vinblastina/administración & dosificación , VinorelbinaRESUMEN
BACKGROUND: Acanthosis nigricans is characterized by hyperpigmentation and hyperkeratosis of the skin or mucous membranes. Its malignant form is associated with internal neoplasms, especially gastric adenocarcinoma (55-61%). Coexistence with prostate cancer is uncommon. In the paraneoplastic type of this dermatosis, the skin and mucous lesions are characteristically of more sudden onset and more severe than those in the benign form. The efficacy of various treatment strategies remains disappointing. CASE PRESENTATION: We here report a case of 66-year-old Caucasian patient with metastatic prostate cancer and a mild form of acanthosis nigricans that preceded the diagnosis of malignancy and resolved with chemotherapy in parallel with the prostate cancer. The dermatosis recurred when the prostate cancer progressed. CONCLUSION: Concurrent acanthosis nigricans and prostate cancer is rare, and few such cases have been reported. Anti-tumor therapy occasionally results in regression of this dermatosis. Underlying malignant disease should be suspected in individuals with elderly-onset of acanthosis nigricans.
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Acantosis Nigricans/complicaciones , Neoplasias de la Próstata/complicaciones , Anciano , Antineoplásicos/uso terapéutico , Neoplasias Óseas/secundario , Progresión de la Enfermedad , Humanos , Masculino , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , RecurrenciaRESUMEN
Tamoxifen is a selective estrogen receptor modulator used for the treatment of oestrogen/progesterone receptor positive breast cancer. It has antagonistic or agonistic activity depending on the tissue location. Generally it causes mild and reversible side effects, however more serious ones including cardiovascular and thromboembolic adverse events, uterine cancer or acute pancreatitis can also occur. Tamoxifen, like oestrogens, increases the plasma level of TG and liver secretion of VLDL. Moreover, it inhibits the key enzymes of triglyceride metabolism. In this report we present a case of a 55-year-old woman with a history of a poorly controlled hypertriglyceridaemia diagnosed with breast cancer. She was treated with surgery and adjuvant chemotherapy, radiotherapy and hormonotherapy with tamoxifen. About three months after hormonal treatment, her triglyceride level increased. Five months later she developed an acute necrotic pancreatitis that required hospitalization. Her serum samples on admission were highly lipemic. An abdominal ultrasound showed no evidence of gallstones or dilation of the bile ducts. There was no history of alcohol abuse or abdominal trauma. Tamoxifen was suspected as a trigger factor for pancreatitis. After the drug withdrawal and administration of the conservative management the patient's medical condition improved. Due to a postmenopausal status of the patient and no harmful effect on serum lipids, an adjuvant hormonotherapy with aromatase inhibitor was started.
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Synchronous cancers account for 0.7-1.8% of all gynecologic cancers. Among them, synchronous ovarian and endometrial cancers are predominant (40-53%). Patients with synchronous cancers have better prognosis than those with single disseminated cancer. We present 10 patients with synchronous ovarian and endometrial cancers who were treated at the Chemotherapy Department of the Medical University of Lodz in 2009-2013. The most often reported symptom of the disease was abnormal vaginal bleeding (6 patients). The range of the patients' age was 48-62 and the median age was 56. Five patients had stage I of ovarian cancer, single patients had stage IIA, IIB and IIIB, 2 patients had stage IIIC. Three patients had I, 5 - II, and 2 - III stage of endometrial cancer. All patients had endometrioid type of endometrial cancer, 7 of them had also the same histological type of ovarian cancer. All patients had adjuvant chemotherapy because of ovarian cancer, none of them had adjuvant radiotherapy. One patient was lost to follow up. For other patients a median follow up was 13 months (range: 3-53 months). One patient experienced relapse, all patients are alive. Synchronous ovarian and endometrial cancers are usually diagnosed at an earlier stage, have lower histological grade and better prognosis than single cancers. The most common histological type of both endometrial and ovarian cancers is endometrioid carcinoma. The first symptoms reported by our patients and the course of the disease were concordant with data from the literature.
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BACKGROUND: In the preplanned interim analysis of the TOPAZ-1 study, durvalumab plus gemcitabine-cisplatin significantly improved overall survival versus placebo plus gemcitabine-cisplatin in participants with advanced biliary tract cancer. We aimed to report updated overall survival and safety data from TOPAZ-1 with additional follow-up and data maturity beyond the interim analysis. METHODS: TOPAZ-1 was a phase 3, randomised, double-masked, placebo-controlled, global study done at 105 sites in 17 countries. Participants aged 18 years or older with unresectable, locally advanced, or metastatic biliary tract cancer were randomly assigned (1:1) to durvalumab plus gemcitabine-cisplatin or placebo plus gemcitabine-cisplatin using a computer-generated randomisation scheme, stratified by disease status and primary tumour location. Participants received durvalumab (1500 mg) or placebo on day 1 of each cycle every 3 weeks for up to eight cycles, plus gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2) intravenously on days 1 and 8 of each cycle every 3 weeks for up to eight cycles, followed by durvalumab (1500 mg) or placebo monotherapy every 4 weeks until disease progression or other discontinuation criteria were met. Investigators and participants were masked to study treatment. The primary endpoint was overall survival. TOPAZ-1 met its primary endpoint at the preplanned interim analysis, and the study is active but no longer recruiting participants. Updated overall survival and safety data from TOPAZ-1, with additional follow-up (data cutoff Feb 25, 2022) and data maturity beyond the interim analysis, are reported here. Efficacy was assessed in the full analysis set (all randomly assigned participants). Safety was assessed in the safety analysis set (all participants who received at least one dose of study treatment). The TOPAZ-1 study is registered with ClinicalTrials.gov, NCT03875235. FINDINGS: From April 16, 2019, to Dec 11, 2020, 914 participants were enrolled, 685 of whom were randomly assigned (341 to the durvalumab plus gemcitabine-cisplatin group and 344 to the placebo plus gemcitabine-cisplatin group). 345 (50%) participants were male and 340 (50%) were female. Median follow-up at the updated data cutoff was 23·4 months (95% CI 20·6-25·2) in the durvalumab plus gemcitabine-cisplatin group and 22·4 months (21·4-23·8) in the placebo plus gemcitabine-cisplatin group. At the updated data cutoff, 248 (73%) participants in the durvalumab plus gemcitabine-cisplatin group and 279 (81%) participants in the placebo plus gemcitabine-cisplatin group had died (median overall survival 12·9 months [95% CI 11·6-14·1] vs 11·3 months [10·1-12·5]; hazard ratio 0·76 [95% CI 0·64-0·91]). Kaplan-Meier-estimated 24-month overall survival rates were 23·6% (95% CI 18·7-28·9) in the durvalumab plus gemcitabine-cisplatin group and 11·5% (7·6-16·2) in the placebo plus gemcitabine-cisplatin group. Maximum grade 3 or 4 adverse events occurred in 250 (74%) of 338 participants in the durvalumab plus gemcitabine-cisplatin group and 257 (75%) of 342 in the placebo plus gemcitabine-cisplatin group. The most common maximum grade 3 or 4 treatment-related adverse events were decreased neutrophil count (70 [21%] vs 86 [25%]), anaemia (64 [19%] vs 64 [19%]), and neutropenia (63 [19%] vs 68 [20%]). INTERPRETATION: Durvalumab plus gemcitabine-cisplatin showed robust and sustained overall survival benefit with no new safety signals. Findings continue to support the regimen as a standard of care for people with untreated, advanced biliary tract cancer. FUNDING: AstraZeneca.