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1.
Folia Med Cracov ; 62(2): 93-107, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36256897

RESUMO

Tenosynovial Giant Cell Tumor (TGCT) is a group of typically benign lesions arising from the synovium of joints, bursae and tendon sheaths. Depending on their growth pattern and clinical course, they are divided into localized and diffuse types. It is predominantly caused by a mutation in the stromal cells of the synovial membrane leading to overexpression of the colony stimulating factor 1 that recruits CSF1R-expressing cells of the mononuclear phagocyte lineage into the tumor mass. The lesions contain mainly histiocyte-like and synovial cells accompanied by varying numbers of multinucleated giant cells, mononuclear cells, foam cells, inflammatory cells and hemosiderin deposits. The gold standard for detect- ing and monitoring the disease is MRI, where the characteristic hemosiderin accumulation can be best appreciated, but it is a histological examination that is most conclusive. The main treatment is surgical resection of all pathological tissue, but radio- and chemotherapy are also viable options for certain groups of patients.


Assuntos
Tumor de Células Gigantes de Bainha Tendinosa , Tumores de Células Gigantes , Sinovite Pigmentada Vilonodular , Humanos , Sinovite Pigmentada Vilonodular/terapia , Fator Estimulador de Colônias de Macrófagos/genética , Fator Estimulador de Colônias de Macrófagos/uso terapêutico , Tumores de Células Gigantes/tratamento farmacológico , Tumores de Células Gigantes/patologia , Tumores de Células Gigantes/cirurgia , Hemossiderina/uso terapêutico
2.
Folia Med Cracov ; 61(3): 33-42, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34882662

RESUMO

Memory trace is an effect of temporary arousal (perception, experience, action) that causes a specific change in the nervous system. Memory allows to record and recall various information, thus enabling to learn new things. It is an extremely active and dynamic process. The influence of emotions on memory is obvious, largely determined by the close cooperation of the amygdala (responsible for emotions) and the hippocampus (memory processes).


Assuntos
Nível de Alerta , Memória , Tonsila do Cerebelo , Emoções , Humanos
3.
Breast Cancer Res Treat ; 190(2): 265-275, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34476645

RESUMO

PURPOSE: CXCR1, one of the receptors for CXCL8, has been identified as a druggable target on breast cancer cancer stem cells (CSC). Reparixin (R), an investigational oral inhibitor of CXCR1, was safely administered to metastatic breast cancer patients in combination with paclitaxel (P) and appeared to reduce CSC in a window-of-opportunity trial in operable breast cancer. The fRida trial (NCT02370238) evaluated the addition of R to weekly as first-line therapy for metastatic (m) TNBC. SUBJECTS AND METHODS: Subjects with untreated mTNBC were randomized 1:1 to R or placebo days 1-21 in combination with weekly P 80 mg/m2 on days 1, 8, 15 of 28-day cycles. The primary endpoint was PFS by central review. RESULTS: 123 subjects were randomized (62 to R + P and 61 to placebo + P). PFS was not different between the 2 groups (median 5.5 and 5.6 months for R + P and placebo + P, respectively; HR 1.13, p = 0.5996). ALDH+ and CD24-/CD44+ CSC centrally evaluated by IHC were found in 16 and 34 of the 54 subjects who provided a metastatic tissue biopsy at study entry. Serious adverse events (21.3 and 20% of subjects) and grade ≥ 3 adverse reactions (ADR) (9.1 and 6.3% of all ADRs) occurred at similar frequency in both groups. CONCLUSION: fRida is the first randomized, double-blind clinical trial of a CSC-targeting agent in combination with chemotherapy in breast cancer. The primary endpoint of prolonged PFS was not met. CLINICAL TRIAL REGISTRATION/DATE OF REGISTRATION: NCT01861054/February 24, 2015.


Assuntos
Neoplasias de Mama Triplo Negativas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Paclitaxel/efeitos adversos , Sulfonamidas , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
4.
Folia Med Cracov ; 61(1): 49-56, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34185767

RESUMO

Isolated internal iliac artery aneurysms are rarely described in the available literature. The paper presents a case of a 70-year-old female with idiopathic thrombocytopenia, squamous cell cervical carcinoma, and saccular aneurysm of the left internal iliac artery, detected in magnetic resonance. The review of aneurysm of the common, external and internal iliac arteries is added.


Assuntos
Carcinoma , Aneurisma Ilíaco , Idoso , Aorta Abdominal , Feminino , Humanos , Aneurisma Ilíaco/complicações , Aneurisma Ilíaco/diagnóstico por imagem , Artéria Ilíaca/diagnóstico por imagem , Resultado do Tratamento
5.
J Neurol Surg A Cent Eur Neurosurg ; 82(5): 463-467, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33822351

RESUMO

BACKGROUND: A perineural (Tarlov) cyst is a fluid-filled lesion occurring between the perineurium and the endoneurium of spinal nerve roots. The aim of the study was to evaluate the prevalence and morphology of perineural cysts, detected incidentally in patients with symptomatic degenerative disk disease. MATERIALS/METHODS: The study was based on the retrospective data gathered during magnetic resonance imaging (MRI) examinations. RESULTS AND CONCLUSIONS: Out of 3,128 spinal MRI examinations, perineural cysts were detected in 286 patients (9%). The cysts were most commonly observed in the sacral region, followed by thoracic, cervical, and lumbar regions. Cysts were more common in women than in men and the average age of patients was 54.8 years. In the majority, a single cyst was found. The average longest dimension of the lesion was 11.72 mm.


Assuntos
Cistos de Tarlov , Feminino , Humanos , Região Lombossacral , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Raízes Nervosas Espinhais , Cistos de Tarlov/diagnóstico por imagem , Cistos de Tarlov/epidemiologia
6.
Front Oncol ; 10: 563613, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33628725

RESUMO

INTRODUCTION: Expression of PD-L1 protein on tumor cells, which is so far the only validated predictive factor for immunotherapy, is regulated by epigenetic and genetic factors. Among the most important ones that regulate gene expression are microRNAs. MATERIALS AND METHODS: The study included 60 patients with NSCLC who underwent first or second line immunotherapy with pembrolizumab or nivolumab. FFPE materials were collected before the start of immunotherapy. We examined relative expression of microRNAs (miR-141, miR-200a, miR-200b, miR-200c, miR-429, miR-508-3p, miR-1184, miR-1255a) and PD-L1 mRNA expression. Copy number variation (CNV) of PD-L1 gene by qPCR and FISH methods were assessed. Two single nucleotide polymorphisms (SNPs) in promoter region of PD-L1 gene (rs822335 and rs822336) were examined. Expression of PD-L1 protein on tumor cells was assessed by immunohistochemistry (IHC). The response rate to immunotherapy and progression free survival (PFS) measured in weeks and overall survival (OS) measured in months from the start of immunotherapy were evaluated. RESULTS: Response to immunotherapy was observed in nine patients (15%, including one complete response), disease stabilization in 22 patients (36.7%), and progression in 29 patients (48.3%). Significantly higher (p=0.015) expression of miR-200b and significantly lower (p=0.043) expression of miR-429 were observed in responders compared to patients who did not respond to immunotherapy. The median PFS in the whole group of patients was 16 weeks, and the median OS was 10.5 month. In univariate analysis, the median PFS was significantly higher in patients with high miR-200b expression (HR=0.4253, 95%CI: 0.1737-1.0417, p=0.05) and high miR-508 expression (HR=0.4401, 95%CI: 0.1903-1.0178, p=0.05) and with low expression of miR-429 (HR=0.1288, 95%CI: 0.01727-0.9606, p=0.0456) compared to patients with low and high expression of these molecules, respectively. The median OS was higher in patients with low expression of miR-429 (HR=0,6288, 95%CI: 0,3053-1,2949, p=0.06) compared with patients with high expression of this microRNA. In multivariate analysis, we found that patients with PD-L1 expression on ≥1% of tumor cells compared to patients without PD-L1 expression on cancer cells had a significantly lower risk of progression (HR=0.3857, 95%CI: 0.1612-0.9226, p=0.0323) and death (HR=0.377, 95%CI: 0.1636-0.8688, p=0.022). CONCLUSION: The miR-200b and miR-429 molecules in tumor cells seem to have greatest impact on the effectiveness of immunotherapy in NSCLC patients.

7.
Pol Merkur Lekarski ; 46(275): 195-204, 2019 May 27.
Artigo em Polonês | MEDLINE | ID: mdl-31152530

RESUMO

Breast cancer is the most common cancer in women. Family history of breast cancer, age at menarche, number of pregnancies and births, history of breast biopsies, use of hormone replacement therapy and time from the last menstrual period are the key events to note. In addition, a high percentage of cases has been demonstrated in women with a genetically conditioned cancer, i.e. mutations in genes BRCA1, BRCA2, syndromes of Li-Fraumeni, Cowden and Peutz-Jeghers. Over 90% of cases are local or regional when detected. The diagnostics approach consists of self-control, breast palpation by the doctor, breast imaging usually with ultrasound, mammography and magnetic resonance. To confirm the diagnosis, a fine-, core-needle or mammotome biopsy is performed. The final diagnosis is based on a wide panel of immunohistochemical and cytogenetic tests. Histological examination provides accurate assessment of the tumor type, grade, estrogen and progesterone hormone receptor status, HER2 overexpression and Ki67 proliferation index. The data makes possible to qualify to one of four groups of breast cancer biological subtypes, which allows individualized treatment of the patient.


Assuntos
Neoplasias da Mama , Biópsia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Feminino , Humanos , Mamografia , Mutação
8.
BMC Infect Dis ; 18(1): 190, 2018 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-29678144

RESUMO

BACKGROUND: Chronic active Epstein-Barr virus (EBV) disease (CAEBV) is defined as a severe, progressive lymphoproliferative disorder associated with active EBV infection persisting longer than 6 months and developing in patients without recognised immunodeficiency. Rarely, interstitial pneumonitis (IP) occurs as a serious complication in CAEBV patients. The standard therapeutic regimen for IP in CAEBV has not yet been defined. Although interferon alpha (IFN-alpha) is known to suppress viral DNA replication by affecting its basal promoter activation process, it is rarely used in CAEBV patients. CASE PRESENTATION: A 22-year-old Caucasian woman, diagnosed with CAEBV 1.5 years earlier, was admitted to the Immunology Clinic due to a 4-week history of productive cough, fever and general weakness. Cultures of blood, urine and sputum were negative, but EBV DNA copies were found in the sputum, whole blood, isolated peripheral blood lymphocytes as well as in the blood plasma. Cytokine assessment in peripheral blood revealed the lack of IFN-alpha synthesis. Disseminated maculate infiltrative areas in both lungs were observed on a computed tomography (CT) chest scan. The patient was not qualified for the allogeneic hematopoietic stem cell transplantation (allo-HSCT) due to the risk of immunosuppression-related complications of infectious IP. Inhaled (1.5 million units 3 times a day) and subcutaneous (6 million units 3 times a week) IFN-alpha was implemented. To the best of our knowledge, this was the first documented use of inhaled IFN-alpha in a patient with CAEBV and concomitant IP. Patient's status has improved, and she was eventually qualified to allo-HSCT with reduced conditioning. Currently, the patient feels well, no EBV was detected and further regression of pulmonary changes was documented. CONCLUSIONS: CAEBV should be considered in patients who present with interstitial lung infiltration and involvement of other organs. Although more promising results have been obtained with allo-HSCT, inhaled IFN-alpha may also be a therapeutic option in patients with CAEBV and a concomitant IP.


Assuntos
Antivirais/uso terapêutico , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Interferon-alfa/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doença Crônica , Feminino , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 4/patogenicidade , Humanos , Doenças Pulmonares Intersticiais/virologia , Adulto Jovem
9.
Ann Agric Environ Med ; 24(3): 527-531, 2017 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-28954503

RESUMO

INTRODUCTION AND OBJECTIVE: Cervical squamous cell carcinoma is one of the most common malignancies of women. Its incidence and morphology was analyzed based on the magnetic resonance (MR) data among rural and urban residents. MATERIAL AND METHODS: The study involved 61 Caucasian women (58.26±9.63 years) preliminary diagnosed with a cervical cancer without any previous treatment. Standard MR examination, including diffusion weighted imagining, apparent diffusion coefficient (ADC) value measurement and dynamic contrast enhancement, was performed. RESULTS: The rural residents (n=22) were insignificantly older. Their first and last menstruation were observed later and number of pregnancy was higher than in urban women (n=39). However, the incidence of miscarriage was insignificantly rarer. All the tumour linear diameters as well as its volume were insignificantly higher in rural women. The ADC value of the cervical tumor was insignificantly lower, while ADC of lymphatic nodules was higher in rural women. Insignificant changes in tumour grade between both examined groups were found in histological, clinical and radiological examinations. Place of residence did not influence any clinical symptoms nor tumour volume and its ADC. Colporrhoea and colpodynia were insignificantly more often observed in urban women, while parametrium, urinary bladder and rectal infiltrations were more commonly seen in rural residents. Higher risk of lymphatic spread to the internal iliac and parametral lymphatic nodes was reporte[b]d in the rural community. CONCLUSIONS: Cervical cancer had similar morphology and growth pattern, regardless of the place of residence. However, a insignificantly larger tumour size among rural residents may suggest a higher incidence of lymphatic spread, probably as a result of less aaccess to modern health care.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Neoplasias do Colo do Útero/diagnóstico por imagem , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Características de Residência , População Rural , Carga Tumoral , População Urbana , Neoplasias do Colo do Útero/patologia
10.
Lancet Oncol ; 17(6): 791-800, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27179402

RESUMO

BACKGROUND: In the primary analysis of the NeoSphere trial, patients given neoadjuvant pertuzumab, trastuzumab, and docetaxel showed a significantly improved pathological complete response compared with those given trastuzumab and docetaxel after surgery. Here, we report 5-year progression-free survival, disease-free survival, and safety. METHODS: In this multicentre, open-label, phase 2 randomised trial in hospitals and medical clinics, treatment-naive adults with locally advanced, inflammatory, or early-stage HER2-positive breast cancer were randomly assigned (1:1:1:1) to receive four neoadjuvant cycles of trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) plus docetaxel (75 mg/m(2) every 3 weeks, increasing to 100 mg/m(2) from cycle 2 if tolerated; group A), pertuzumab (840 mg loading dose, followed by 420 mg every 3 weeks) and trastuzumab plus docetaxel (group B), pertuzumab and trastuzumab (group C), or pertuzumab and docetaxel (group D). After surgery, patients received three cycles of FEC (fluorouracil 600 mg/m(2), epirubicin 90 mg/m(2), and cyclophosphamide 600 mg/m(2)) every 3 weeks (patients in group C received four cycles of docetaxel prior to FEC), and trastuzumab 6 mg/kg every 3 weeks to complete 1 year's treatment (17 cycles in total). Randomisation was done by a central centre using dynamic allocation, stratified by operable, locally advanced, and inflammatory breast cancer, and by oestrogen and/or progesterone receptor positivity. Safety analyses were done according to treatment received. The primary endpoint (pathological complete response) was previously reported; secondary endpoints reported here are 5-year progression-free survival (analysed in the intention-to-treat population) and disease-free survival (analysed in patients who had surgery). Secondary and exploratory analyses were not powered for formal statistical hypothesis testing, and therefore results are for descriptive purposes only. The study ended on Sept 22, 2014 (last patient, last visit). This study is registered with ClinicalTrials.gov, number NCT00545688. FINDINGS: Between Dec 17, 2007, and Dec 22, 2009, 417 eligible patients were randomly assigned to group A (107 patients), group B (107 patients), group C (107 patients), or group D (96 patients). One patient in group A withdrew before treatment. One patient assigned to group D received group A treatment, one patient assigned to group D received group B treatment, and one patient assigned to group B received group C treatment. At clinical cutoff, 87 patients had progressed or died. 5-year progression-free survival rates were 81% (95% CI 71-87) for group A, 86% (77-91) for group B, 73% (64-81) for group C, and 73% (63-81) for group D (hazard ratios 0·69 [95% CI 0·34-1·40] group B vs group A, 1·25 [0·68-2·30] group C vs group A, and 2·05 [1·07-3·93] group D vs group B). Disease-free survival results were consistent with progression-free survival results and were 81% (95% CI 72-88) for group A, 84% (72-91) for group B, 80% (70-86) for group C, and 75% (64-83) for group D. Patients who achieved total pathological complete response (all groups combined) had longer progression-free survival compared with patients who did not (85% [76-91] in patients who achieved total pathological response vs 76% [71-81] in patients who did not achieve total pathological response; hazard ratio 0·54 [95% CI 0·29-1·00]). There were no new or long-term safety concerns and tolerability was similar across groups (neoadjuvant and adjuvant treatment periods combined). The most common grade 3 or worse adverse events were neutropenia (group A: 71 [66%] of 107 patients; group B: 59 [55%] of 107; group C: 40 [37%] of 108; group D: 60 [64%] of 94), febrile neutropenia (group A: 10 [9%]; group B: 12 [11%]; group C: 5 [5%]; group D: 15 [16%]), and leucopenia (group A: 13 [12%]; group B: 6 [6%]; group C: 4 [4%]; group D: 8 [9%]). The number of patients with one or more serious adverse event was similar across groups (19-22 serious adverse events per group in 18-22% of patients). INTERPRETATION: Progression-free survival and disease-free survival at 5-year follow-up show large and overlapping CIs, but support the primary endpoint (pathological complete response) and suggest that neoadjuvant pertuzumab is beneficial when combined with trastuzumab and docetaxel. Additionally, they suggest that total pathological complete response could be an early indicator of long-term outcome in early-stage HER2-positive breast cancer. FUNDING: F Hoffmann-La Roche.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Inflamatórias Mamárias/tratamento farmacológico , Terapia Neoadjuvante , Recidiva Local de Neoplasia/tratamento farmacológico , Receptor ErbB-2/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Quimioterapia Adjuvante , Feminino , Seguimentos , Humanos , Neoplasias Inflamatórias Mamárias/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Fatores de Tempo , Trastuzumab/administração & dosagem , Adulto Jovem
11.
Pol Merkur Lekarski ; 40(238): 211-5, 2016 Apr.
Artigo em Polonês | MEDLINE | ID: mdl-27137819

RESUMO

Testicular tumours are rare neoplasms, which most commonly affects men aged 25 to 35 years. Among young adult males it is the most common cause of testicular swelling. In recent decades, the number of cases of testicular tumours has greatly increased. The most significant predisposing factors are cryptorchidism and some endocrine disorders, especially increased levels of gonadotropins and female sex hormones. Testicular trauma, inguinal hernia, extreme values of body mass index (BMI), high-calorie diet rich in dairy products as well as high social status are also regarded as risk factors. Furthermore, some chromosomal abnormalities like increased number of chromosomes 7, 8. 12, 21 and X, loss of chromosomes 4, 5, 11, 13, 18, or Y, mutation in the gene Xq27; as well as multiplied copy of the gene i(12p) are associated with tumor development. It has been proven that high testosterone levels and regular physical activity may prevent testicular tumours. Since one of the first sign the lesion is often a lump or swelling of the testis and the appearance of abnormal structure in the scrotum routine testicular self-examination seems to be important in early detection. In all suspected cases an immediate ultrasound examination of both testicles is highly recommended. It is also advised to conduct a computerized tomography (CT) and a positron emission tomography (PET) scan for staging of the tumor to select the best mode of treatment.


Assuntos
Neoplasias Testiculares/epidemiologia , Adulto , Humanos , Masculino , Tomografia por Emissão de Pósitrons , Fatores de Risco , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/genética , Tomografia Computadorizada por Raios X
12.
Eur J Cancer ; 62: 62-75, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27208905

RESUMO

BACKGROUND: In the phase III, open-label, randomised HannaH study, fixed-dose neoadjuvant-adjuvant subcutaneous trastuzumab for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer was non-inferior to standard weight-based intravenous infusion in terms of serum trough concentration and pathological complete response (pCR). Evidence suggests that pCR, particularly total pCR (tpCR), is likely to predict clinical benefit. We report associations between tpCR and event-free survival (EFS) from HannaH (the largest population from a single study of patients presenting with newly diagnosed HER2-positive breast cancer treated with neoadjuvant-adjuvant trastuzumab to date) plus long-term efficacy and safety. METHODS: Eligible patients received four cycles of neoadjuvant docetaxel followed by four cycles of fluorouracil/epirubicin/cyclophosphamide administered concurrently with 3-weekly subcutaneous (600 mg fixed dose) or intravenous trastuzumab (8 mg/kg loading, 6 mg/kg maintenance doses). Post-surgery, patients received adjuvant trastuzumab as randomised to complete 1 year of standard treatment. In exploratory analyses, we used Cox regression to assess associations between tpCR and EFS. EFS rates per subgroup were estimated using the Kaplan-Meier method. FINDINGS: Three-year EFS rates were 76% for subcutaneous and 73% for intravenous trastuzumab (unstratified hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.69-1.30; intention-to-treat population). Three-year overall survival rates were 92% for subcutaneous and 90% for intravenous trastuzumab (unstratified HR 0.76, 95% CI 0.44-1.32). tpCR was associated with a reduced risk of an EFS event: subcutaneous arm HR 0.38 (95% CI 0.22-0.65); intravenous arm HR 0.32 (95% CI 0.18-0.60). Results were similar for subgroups, including oestrogen receptor status. The few additional adverse events occurring during treatment-free follow-up were balanced between arms. INTERPRETATION: Long-term efficacy supports the established non-inferiority of subcutaneous trastuzumab, and its safety profile remains consistent with the known intravenous profile. In each of HannaH's treatment arms, tpCR was associated with improved EFS, adding to evidence that tpCR is associated with clinical benefit in HER2-positive early breast cancer.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Trastuzumab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Injeções Subcutâneas , Pessoa de Meia-Idade , Terapia Neoadjuvante , Adulto Jovem
13.
Cancer Res ; 76(11): 3156-65, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27197152

RESUMO

Myeloid-derived suppressor cells (MDSC) contribute to immune suppression in cancer, but the mechanisms through which they drive metastatic progression are not fully understood. In this study, we show how MDSC convey stem-like qualities to breast cancer cells that coordinately help enable immune suppression and escape. We found that MDSC promoted tumor formation by enhancing breast cancer cell stem-like properties as well as by suppressing T-cell activation. Mechanistic investigations indicated that these effects relied upon cross-talk between the STAT3 and NOTCH pathways in cancer cells, with MDSC inducing IL6-dependent phosphorylation of STAT3 and activating NOTCH through nitric oxide leading to prolonged STAT3 activation. In clinical specimens of breast cancer, the presence of MDSC correlated with the presence of cancer stem-like cells (CSC) and independently predicted poor survival outcomes. Collectively, our work revealed an immune-associated mechanism that extrinsically confers cancer cell stemness properties and affects patient outcome. We suggest that targeting STAT3-NOTCH cross-talk between MDSC and CSC could offer a unique locus to improve cancer treatment, by coordinately targeting a coupled mechanism that enables cancer stemness and immune escape. Cancer Res; 76(11); 3156-65. ©2016 AACR.


Assuntos
Neoplasias da Mama/patologia , Interleucina-6/metabolismo , Células Supressoras Mieloides/patologia , Células-Tronco Neoplásicas/patologia , Óxido Nítrico/metabolismo , Receptores Notch/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Apoptose , Western Blotting , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Proliferação de Células , Estudos de Coortes , Feminino , Citometria de Fluxo , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Interleucina-6/genética , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células Supressoras Mieloides/metabolismo , Estadiamento de Neoplasias , Células-Tronco Neoplásicas/metabolismo , Fosforilação , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptor Cross-Talk , Receptores Notch/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição STAT3/genética , Transdução de Sinais , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Ann Agric Environ Med ; 22(4): 724-30, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26706986

RESUMO

INTRODUCTION: Breast cancer is the most frequent malignant neoplasm in women. The evaluation of the quality of life has become a treatment parameter as important as survival. OBJECTIVE: The aim of the study was evaluation of the quality of life among women treated for breast cancer who underwent surgical procedures using two alternative methods: mastectomy or breast conserving therapy (BCT). MATERIALS AND METHOD: 85 patients treated with BCT and 94 patients who underwent mastectomy were evaluated. Standard questionnaires for the evaluation of the quality of life of cancer patients were used - QLQ-C30 (Quality of life questionnaire - core 30) with QLQ-BR23 (Breast Cancer Module). The Hospital Anxiety and Depression Scale was also applied. RESULTS: Social and demographic factors (age, education, marital status) influenced the evaluation of the life quality among both groups. Obtained data was also dependent on the type of surgical procedure and chemical treatment. The level of anxiety and depression also influenced the general quality of life and was higher in women who underwent mastectomy. CONCLUSIONS: Quality of life plays an important role in the treatment process. Women after BCT declared a higher quality of life compared to patients after mastectomy. The process of making the decision concerning the planned surgical procedure should take into consideration the influence of the intervention on the quality of patients' future life.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/psicologia , Mastectomia , Qualidade de Vida/psicologia , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Polônia , Inquéritos e Questionários
15.
Prz Menopauzalny ; 14(3): 196-202, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26528110

RESUMO

Breast cancer is the most frequently diagnosed neoplastic disease in women around menopause often leading to a significant reduction of these women's ability to function normally in everyday life. The increased breast cancer incidence observed in epidemiological studies in a group of women actively participating in social and professional life implicates the necessity of conducting multidirectional studies in order to identify risk factors associated with the occurrence of this type of neoplasm. Taking the possibility of influencing the neoplastic transformation process in individuals as a criterion, all the risk factors initiating the process can be divided into two groups. The first group would include inherent factors such as age, sex, race, genetic makeup promoting familial occurrence of the neoplastic disease or the occurrence of benign proliferative lesions of the mammary gland. They all constitute independent parameters and do not undergo simple modification in the course of an individual's life. The second group would include extrinsic factors conditioned by lifestyle, diet or long-term medical intervention such as using oral hormonal contraceptives or hormonal replacement therapy and their influence on the neoplastic process may be modified to a certain degree. Identification of modifiable factors may contribute to development of prevention strategies decreasing breast cancer incidence.

16.
PLoS One ; 10(10): e0140178, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26460692

RESUMO

Epstein-Barr virus (EBV) is a ubiquitous γ-herpesvirus that infects more than 90% of the world population. The potential involvement of EBV in the clinical course of chronic lymphocytic leukemia (CLL) remains unexplained. The aim of this study was to determine whether EBV-DNA load in the peripheral blood mononuclear cells (PBMCs) of CLL patients may influence heterogeneity in the course of the disease. The study included peripheral blood samples from 115 previously untreated patients with CLL (54 women and 61 men) and 40 healthy controls (16 women and 24 men). We analyzed the association between the EBV-DNA load in PBMCs and the stage of the disease, adverse prognostic factors, and clinical outcome. Detectable numbers of EBV-DNA copies in PBMCs were found in 62 out of 115 CLL patients (53.91%). The EBV-DNA copy number/µg DNA was significantly higher in patients who required early implementation of treatment, presented with lymphocyte count doubling time <12 months, displayed CD38-positive or ZAP-70-positive phenotype, and with the del(11q22.3) cytogenetic abnormality. Furthermore, the EBV-DNA copy number/µg DNA showed significant positive correlation with the concentrations of lactate dehydrogenase (LDH) and beta-2-microglobulin. We have shown that in CLL patients, higher EBV-DNA copy number predicted shorter survival and shorter time to disease progression, and it was associated with other established unfavorable prognostic factors. This suggests that EBV may negatively affect the outcome of CLL.


Assuntos
DNA Viral/sangue , Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfocítica Crônica de Células B/virologia , Carga Viral , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Linfócitos B/imunologia , Estudos de Casos e Controles , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/imunologia , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Probabilidade , Prognóstico , Modelos de Riscos Proporcionais
17.
Breast ; 24(6): 769-73, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26384789

RESUMO

Lapatinib plus capecitabine (lap+cap) is approved as treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC), who have progressed on prior trastuzumab in the metastatic setting. We previously reported progression-free survival (PFS), overall survival (OS) and safety results from this open-label, multicentre, phase II study (VITAL; NCT01013740) conducted in women with HER2 positive MBC, to evaluate the efficacy and safety of lap plus vinorelbine (lap+vin), an important chemotherapy option for MBC, compared with lap+cap. In total, 112 patients were randomised 2:1 to treatment with lap+vin (N = 75) or lap+cap (N = 37). Results showed that the median PFS (primary endpoint) and OS (secondary endpoint) post-randomisation were comparable between treatment arms, with no new safety signals detected. Here, we assessed the final OS in this study at 40 months post-randomisation. At the time of final analyses, 24 (32%) patients were ongoing in the lap+vin arm, compared with 14 (38%) patients in the lap+cap arm (92% in both arms had discontinued treatment). Median OS in the lap+vin arm was 23.3 months (95% confidence intervals [CI]: 18.5, 31.1), compared with 20.3 months (95% CI: 16.4, 31.8) in the lap+cap arm. The median follow-up in the lap+vin arm was 18.86 months (95% CI: 10.68, 26.02), compared with 19.38 (95% CI: 25.56) months in the lap+cap arm. Similar rates of death (56-57%) were observed in both arms. The final OS was consistent with the previously reported data and suggest that lap+vin offers an effective treatment option for women with HER2-positive MBC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/mortalidade , Quinazolinas/administração & dosagem , Receptor ErbB-2/análise , Vimblastina/análogos & derivados , Adulto , Idoso , Neoplasias da Mama/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lapatinib , Metástase Linfática , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vinorelbina
18.
Pol Merkur Lekarski ; 38(227): 280-2, 2015 May.
Artigo em Polonês | MEDLINE | ID: mdl-26039024

RESUMO

Mantle cell lymphoma is a rare aggressive lymphoma derived from B cells, characterized by rapid progression and subsequent recurrence. It is considered to be an incurable disease, with exception of a certain group of patients treated with an autogenic stem cell transplantation. The mean survival time is three years, after applying the conventional regimen based on COP (cyclophosphamide, vincristine, prednisone) or CHOP chemotherapy (COP + doxorubicin). An addition of rituximab to CHOP regimen significantly prolongs progression-free survival. The present case reports ten years progression-free survival in a female patient with mantle cell lymphoma with baseline clinical stage IVB (MIPI 5), treated with nine courses of CHOP chemotherapy. Rituximab was added from 3 to 8 course. The complete clinical, radiological and histopathological response has been obtained.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/terapia , Adulto , Anticorpos Monoclonais Murinos/administração & dosagem , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma de Célula do Manto/patologia , Prednisolona , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Rituximab , Transplante de Células-Tronco , Vincristina/uso terapêutico
19.
Ann Agric Environ Med ; 22(1): 185-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25780852

RESUMO

OBJECTIVE: Evaluation of the presence of symptoms of anxiety and depression in women treated for breast cancer who underwent surgical procedure using one of two alternative methods, either radical mastectomy or breast conserving treatment (BCT). METHODS: A questionnaire survey involved 85 patients treated in a conservative way and 94 patients after breast amputation. Hospital Anxiety and Depression Scale (HADS), Beck Depression Inventory (BDI) and depression degree evaluation questionnaire were used in the study. The patients' esponses were statistically analyzed. RESULTS: Based on the HADS questionnaire, the total anxiety level in the group of women treated with BCT was 6.96 points, while in the group of patients who had undergone mastectomy the value was 7.8 points. The observed results were statistically significant. In the case of depression, the following values were found: patients after amputation had 8.04 scale value points, and those after BCT had 6.8 scale value points. The observed differences were statistically significant. Negative correlation was found between the level of anxiety and depression. The total level of depression evaluated using the Beck scale was 16.3 points in the BCT group, which means that they suffered from mild depression, while in the mastectomy group the level was 19.6 points, which corresponds to moderate depression. CONCLUSIONS: The level of anxiety and depression among women with breast cancer was influenced by the type of the applied surgical procedure and adjuvant chemotherapy. Demographic variables did not influence the level of anxiety and depression.


Assuntos
Ansiedade/epidemiologia , Neoplasias da Mama/terapia , Quimioterapia Adjuvante/efeitos adversos , Depressão/epidemiologia , Mastectomia Radical/efeitos adversos , Mastectomia Segmentar/efeitos adversos , Adulto , Idoso , Ansiedade/etiologia , Neoplasias da Mama/cirurgia , Depressão/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Polônia/epidemiologia , Inquéritos e Questionários
20.
Pol Merkur Lekarski ; 38(223): 55-60, 2015 Jan.
Artigo em Polonês | MEDLINE | ID: mdl-25763591

RESUMO

Benign ovarian focal lesions - such cystic, inflammatory, vascular and metaplastic changes - may occur at any age but they are most commonly observed in girls at puberty and in young women. The most important preliminary procedures in case of suspected adnexal pathologies are interview, physical examination and classical female bimanual pelvic examination which together with imaging techniques allow correct diagnosis. The commonly available and inexpensive method of female reproductive organs imaging is an ultrasonography (USG). Magnetic resonance (MR), computed tomography (CT) and in case of malignant lesions also positron emission tomography (PET) may also be performed. In doubtful cases, when the evaluation of lesions using USG method is difficult MR is recommended. Due to high resolution, it facilitates precise evaluation of the type and size of lesions, allows distinguishing simple and complex fluid collections while fat saturation sequences make it possible to distinguish cysts containing blood and fat. Moreover, the patient is not exposed to ionizing radiation, which is especially important in women in reproductive age and in children. Computed tomography is recommended for preoperative staging and monitoring of treatment of malignant adnexal neoplasms as well as localization of small peritoneal metastases.


Assuntos
Diagnóstico por Imagem/métodos , Doenças Ovarianas/diagnóstico , Diagnóstico Diferencial , Feminino , Fluordesoxiglucose F18 , Humanos , Imageamento por Ressonância Magnética , Neoplasias Ovarianas/diagnóstico , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/secundário , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X
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