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1.
Neurol Neurochir Pol ; 58(1): 127-133, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37376975

RESUMO

AIM OF THE STUDY: To assess whether combined therapy with botulinum toxin injections (BoNT) and KinesioTaping could be helpful in managing non-motor symptoms (NMS) of cervical dystonia (CD). MATERIAL AND METHODS: Seventeen patients with CD were enrolled in this single-centre, prospective, evaluator-blinded, randomised, crossover trial. We compared three forms of treatment: BoNT treatment alone, or combined with KinesioTaping, or combined with ShamTaping. NMS were assessed using the 14-item self-reported questionnaire proposed by Klingelhoefer, the Hospital Anxiety and Depression Scale (HADS) and the Pittsburgh Sleep Quality Index (PSQI). RESULTS: There were no significant differences between the groups concerning mean results of HADS and PSQI scales, or mean total number of NMS after the procedures. The mean change from baseline HADS and PSQI scores, and total number of NMS after the procedure, also did not differ significantly between groups. ShamTaping combined with BoNT significantly increased the prevalence of pain. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study did not confirm the effectiveness of combined therapy of BoNT and KinesioTaping in the management of NMS in patients with CD. Due to a potential negative effect of improper taping on pain in CD, patients with CD should only experience KinesioTaping as an adjunctive therapy, and if it is performed by a trained, experienced physiotherapist.


Assuntos
Fita Atlética , Toxinas Botulínicas , Torcicolo , Humanos , Toxinas Botulínicas/uso terapêutico , Dor/induzido quimicamente , Dor/tratamento farmacológico , Estudos Prospectivos , Torcicolo/tratamento farmacológico , Resultado do Tratamento
2.
Neurol Neurochir Pol ; 57(4): 392-396, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37501541

RESUMO

AIM OF THE STUDY: Ophthalmological symptoms are common in patients with Parkinson's Disease (PD) and can be evaluated by the Visual Impairment in Parkinson's Disease Questionnaire (VIPD-Q). This study aimed to assess the prevalence of ophthalmological symptoms in PD depending on the type of treatment used i.e. pharmacological or subthalamic nucleus deep brain stimulation (STN-DBS). MATERIAL AND METHODS: We performed a cross-sectional study. The data was gathered from a VIPD-Q and from medical records. Patients with PD were divided into two groups based on the type of treatment - pharmacological (control group, CG) (39 patients) or STN-DBS (40 patients). RESULTS: The great majority of patients - 72 (91.1%) - experienced an ophthalmological symptom. The prevalence of three symptoms differed significantly between the groups. A burning sensation or a gritty feeling in the eyes occurred more often in patients in the STN-DBS group (40.0% vs. 15.4%; p = 0.015). On the other hand, the inability to read plain text on a coloured or grey background and problems with rapid changes of light intensity were more common in the CG group (38.5% vs. 15.0%, p = 0.018 and 28.2% vs. 10.0%, p = 0.039, respectively). CONCLUSIONS AND CLINICAL IMPLICATIONS: The prevalence of ophthalmological symptoms in PD is high. Despite significant differences in the three symptoms, the overall prevalence of ophthalmological clinical features was similar in the evaluated groups.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Doença de Parkinson/terapia , Doença de Parkinson/tratamento farmacológico , Estudos Transversais , Núcleo Subtalâmico/fisiologia , Transtornos da Visão/epidemiologia , Transtornos da Visão/etiologia , Transtornos da Visão/terapia , Resultado do Tratamento
3.
Neuroendocrinology ; 111(4): 304-319, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32335553

RESUMO

BACKGROUND: There is a substantial unmet clinical need for an accurate and effective blood biomarker for neuroendocrine neoplasms (NEN). We therefore evaluated, under real-world conditions in an ENETS Center of Excellence (CoE), the clinical utility of the NETest as a liquid biopsy and compared its utility with chromogranin A (CgA) measurement. METHODS: The cohorts were: gastroenteropancreatic NEN (GEP-NEN; n = 253), bronchopulmonary NEN (BPNEN; n = 64), thymic NEN (n = 1), colon cancer (n = 37), non-small-cell lung cancer (NSCLC; n = 63), benign lung disease (n = 59), and controls (n = 86). In the GEPNEN group, 164 (65%) had image-positive disease (IPD, n = 135) or were image-negative but resection-margin/biopsy-positive (n = 29), and were graded as G1 (n = 106), G2 (n = 49), G3 (n = 7), or no data (n = 2). The remainder (n = 71) had no evidence of disease (NED). In the BPNEN group, 43/64 (67%) had IPD. Histology revealed typical carcinoids (TC, n = 14), atypical carcinoids (AC, n = 14), small-cell lung cancer (SCLC, n = 11), and large-cell neuroendocrine carcinoma (LCNEC, n = 4). Disease status (stable or progressive) was evaluated according to RECIST v1.1. Blood sampling involved NETest (n = 563) and NETest/CgA analysis matched samples (n = 178). NETest was performed by PCR (on a scale of 0-100), with a score ≥20 reflecting a disease-positive status and >40 reflecting progressive disease. CgA positivity was determined by ELISA. Samples were deidentified and measurements blinded. The Kruskal-Wallis, Mann-Whitney U, and McNemar tests, and the area under the curve (AUC) of the receiver-operating characteristics (ROC) were used in the statistical analysis. RESULTS: In the GEPNEN group, NETest was significantly higher (34.4 ± 1.8, p < 0.0001) in disease-positive patients than in patients with NED (10.5 ± 1, p < 0.0001), colon cancer patients (18 ± 4, p < 0.0004), and controls (7 ± 0.5, p < 0.0001). Sensitivity for detecting disease compared to controls was 89% and specificity was 94%. NETest levels were increased in G2 vs. G1 (39 ± 3 vs. 32 ± 2, p = 0.02) and correlated with stage (localized: 26 ± 2 vs. regional/distant: 40 ± 3, p = 0.0002) and progression (55 ± 5 vs. 34 ± 2 in stable disease, p = 0.0005). In the BPNEN group, diagnostic sensitivity was 100% and levels were significantly higher in patients with bronchopulmonary carcinoids (BPC; 30 ± 1.3) who had IPD than in controls (7 ± 0.5, p < 0.0001), patients with NED (24.1 ± 1.3, p < 0.005), and NSCLC patients (17 ± 3, p = 0.0001). NETest levels were higher in patients with poorly differentiated BPNEN (LCNEC + SCLC; 59 ± 7) than in those with BPC (30 ± 1.3, p = 0.0005) or progressive disease (57.8 ± 7), compared to those with stable disease (29.4 ± 1, p < 0.0001). The AUC for differentiating disease from controls was 0.87 in the GEPNEN group and 0.99 in BPC patients (p < 0.0001). Matched CgA analysis was performed in 178 patients. In the GEPNEN group (n = 135), NETest was significantly more accurate for detecting disease (99%) than CgA positivity (53%; McNemar test χ2 = 87, p < 0.0001). In the BPNEN group (n = 43), NETest was significantly more accurate for disease detection (100%) than CgA positivity (26%; McNemar's test χ2 = 30, p < 0.0001). CONCLUSIONS: The NETest is an accurate diagnostic for GEPNEN and BPNEN. It exhibits tumor biology correlation with grading, staging, and progression. CgA as a biomarker is significantly less accurate than NETest. The NETest has substantial clinical utility that can facilitate patient management.


Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/normas , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias do Colo/diagnóstico , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Pulmonares/diagnóstico , Tumores Neuroendócrinos/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Neoplasias do Timo/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/sangue , Estudos de Coortes , Neoplasias do Colo/sangue , Feminino , Neoplasias Gastrointestinais/sangue , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/sangue , Neoplasias Pancreáticas/sangue , Sensibilidade e Especificidade , Neoplasias do Timo/sangue , Adulto Jovem
4.
Hematol Oncol ; 37(4): 383-391, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31026087

RESUMO

Richter transformation (RT) of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) to Hodgkin lymphoma (HL) is a rare and unexpected event in the course of the disease and data on this phenomenon is still limited. To better understand the clinical and histological characteristics and the outcomes of HL variant of RT (HvRS) the Polish Lymphoma Research Group performed a nationwide survey which identified 22 patients with histologically proven HvRS diagnosed between 2002 and 2016. There were 16 (73%) males. The median age at CLL/SLL and HvRS diagnosis was 59 (39-77) and 64 (40-77) years, respectively. The median interval between CLL/SLL and HvRS diagnosis was 38 months (range: 0-187). All patients had an advanced stage HL, and majority, 17 (77%), presented with B symptoms. The predominant subtypes of HL were nodular sclerosis (12; 55%) and mixed cellularity (9; 41%). Eighteen patients received non-palliative treatment, including 13 who received driamycin, bleomycin, vinblastine, and dacarbazine (ABVD) regimen first line. Objective response was: 50%, with 33% complete remissions (61% and 46% for ABVD, respectively). Median overall survival reached 13.3 months (95% CI, 3.7-NA). The only adverse prognostic factor for survival was a higher number (≤1 versus ≥2) of prior lines of treatment given for CLL/SLL with HR 3.57 (95% CI, 1.16-10.92). We conclude, HvRS harbors a poor prognosis, especially in patients heavily pretreated for CLL/SLL. Response to standard first-line anti-HL chemotherapy is unsatisfactory, and new agents should be tested to improve the outcome.


Assuntos
Doença de Hodgkin/etiologia , Leucemia Linfocítica Crônica de Células B/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Causas de Morte , Transformação Celular Neoplásica/patologia , Progressão da Doença , Feminino , Doença de Hodgkin/sangue , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Estimativa de Kaplan-Meier , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
5.
Eur J Haematol ; 103(6): 531-541, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31449692

RESUMO

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by platelet destruction and reduced platelet production resulting in decreased platelet level and an increased risk of bleeding. Based on the immunologic mechanism of ITP, front-line standard therapy consists of corticosteroids and intravenous immunoglobulins (IVIG). If patients do not respond to the first-line treatment, or if continuous therapy is required, the disorder is called refractory ITP, and second-line therapy is indicated. This treatment may consist of rituximab, thrombopoietin receptor agonists, splenectomy, or cytotoxic drugs. Despite significant advances, many patients do not respond to any the treatments listed below, and new treatment options need to be developed for this relapsed and refractory group. Recent clinical studies have indicated promising outcomes for novel drugs, either as single agents or in combination with traditional drugs. This review discusses the latest and the most promising novel drugs for ITP in adults.


Assuntos
Corticosteroides/uso terapêutico , Citotoxinas/uso terapêutico , Hemorragia/terapia , Imunoglobulinas Intravenosas/uso terapêutico , Púrpura Trombocitopênica Idiopática/terapia , Esplenectomia , Adulto , Hemorragia/imunologia , Hemorragia/metabolismo , Hemorragia/patologia , Humanos , Púrpura Trombocitopênica Idiopática/imunologia , Púrpura Trombocitopênica Idiopática/metabolismo , Púrpura Trombocitopênica Idiopática/patologia
6.
Tumour Biol ; 39(3): 1010428317694551, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28349818

RESUMO

The SMAD proteins are responsible for transducing signals from activated transforming growth factor-beta. This is the first study assessing the expression of SMAD-1/8, SMAD-2/3, SMAD-4, and SMAD-7 in chronic lymphocytic leukemia cells with regard to their clinical significance and potential prognostic value. Overexpression of SMAD-1/8 was observed in 160 chronic lymphocytic leukemia patients compared to 42 healthy volunteers (p = 0.023) and was associated with a more progressive course of the disease (p = 0.016). Moreover, the high expression of SMAD-1/8 correlated with other, well-established prognostic factors, including clinical stage (p = 0.010) and lymphocyte doubling time (p = 0.021). The expression of SMAD-4 was lower in chronic lymphocytic leukemia patients compared with the control group (p = 0.003). Importantly, lower SMAD-4 levels correlated with longer progression-free survival (p = 0.009), progressive course of the disease (p = 0.002), advanced clinical stage (p = 0.0004), elevated beta-2-microglobulin and lactate dehydrogenase levels (p < 0.05), shorter lymphocyte doubling time (p = 0.009), and CD38 antigen expression (p = 0.039). In addition, lower SMAD-4 expression correlated with lower apoptotic index (p = 0.0007) and lower expression of receptors for vascular endothelial growth factors VEGFR-1 and VEGFR-2. A significant association was found between the low expression of inhibitory protein SMAD-7 and both zeta-chain-associated protein kinase 70-negative cells (p = 0.04) and lower apoptotic index (p = 0.004). No differences were observed in SMAD-2/3 expression. In conclusion, our results demonstrate a significant correlation between greater SMAD-1/8 and lower SMAD-4 expression in chronic lymphocytic leukemia cells, as well as more progressive outcome and poor prognosis. These data provide supporting evidence that the expression of SMAD proteins plays an important role in disease development and may be considered as a novel, biologic prognostic factor in this disease.


Assuntos
Leucemia Linfocítica Crônica de Células B/genética , Proteína Smad1/biossíntese , Proteína Smad2/biossíntese , Proteína Smad4/biossíntese , Proteína Smad7/biossíntese , Idoso , Idoso de 80 Anos ou mais , Apoptose/genética , Intervalo Livre de Doença , Regulação Leucêmica da Expressão Gênica , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteína Smad1/genética , Proteína Smad2/genética , Proteína Smad4/genética , Proteína Smad7/genética , Fator de Crescimento Transformador beta/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/biossíntese , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/biossíntese , Proteína-Tirosina Quinase ZAP-70/biossíntese
7.
Molecules ; 21(8)2016 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-27483232

RESUMO

Honokiol and triphenylmethanes are small molecules with anti-tumor properties. Recently, we synthesized new honokiol analogues (HAs) that possess common features of both groups. We assessed the anti-tumor effectiveness of HAs in B-cell leukemia/lymphoma cells, namely in chronic lymphocytic leukemia (CLL) cells ex vivo and in pre-B-cell acute lymphoblastic leukemia (Nalm-6), Burkitt lymphoma (BL; Raji), diffuse large B-cell lymphoma (DLBCL; Toledo) and multiple myeloma (MM; RPMI 8226) cell lines. Four of these compounds appeared to be significantly active against the majority of cells examined, with no significant impact on healthy lymphocytes. These active HAs induced caspase-dependent apoptosis, causing significant deregulation of several apoptosis-regulating proteins. Overall, these compounds downregulated Bcl-2 and XIAP and upregulated Bax, Bak and survivin proteins. In conclusion, some of the HAs are potent tumor-selective inducers of apoptosis in ex vivo CLL and in BL, DLBCL and MM cells in vitro. Further preclinical studies of these agents are recommended.


Assuntos
Antineoplásicos/farmacologia , Compostos de Bifenilo/farmacologia , Leucemia/metabolismo , Lignanas/farmacologia , Linfoma/metabolismo , Mieloma Múltiplo/metabolismo , Compostos de Tritil/farmacologia , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Leucemia/tratamento farmacológico , Linfoma/tratamento farmacológico , Mieloma Múltiplo/tratamento farmacológico
8.
Postepy Hig Med Dosw (Online) ; 70: 43-55, 2016 Feb 08.
Artigo em Polonês | MEDLINE | ID: mdl-26864063

RESUMO

The use of non-vitamin K antagonist oral anticoagulants (NOACs) has become a breakthrough in anticoagulant treatment and it is expected to rise significantly in upcoming years. The use of conventional anticoagulants have several limitations: subcutaneous administration of heparin, or close monitoring of INR during application of vitamin K antagonists. In the last decade, target-specific oral anticoagulants (TSOAC) including dabigatran, rivaroxaban, apixaban, edoxaban have been marketed for prophylaxis and treatment. Therefore, it is crucial to understand the potential uses, side effects, and management of these agents in routine practice. NOACs have major pharmacologic advantages, including a rapid onset and offset of action, fewer drug interactions than conventional anticoagulants, and predictable pharmacokinetics. These agents are gaining popularity among both physicians and patients because of their easiness of administration and the eliminating the requirement for regular coagulation monitoring. In this review, we focus on discussing practical recommendations for the use of NOACs and the risks and benefits of incorporating them into routine practice.


Assuntos
Anticoagulantes/uso terapêutico , Administração Oral , Dabigatrana/uso terapêutico , Humanos , Padrões de Prática Médica , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , Tiazóis/uso terapêutico
9.
Molecules ; 19(9): 14304-15, 2014 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-25215588

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is one of the most common non-Hodgkin lymphomas in adults. The disease is very heterogeneous in its presentation, that is DLBCL patients may differ from each other not only in regard to histology of tissue infiltration, clinical course or response to treatment, but also in respect to diversity in gene expression profiling. A growing body of knowledge on the biology of DLBCL, including abnormalities in intracellular signaling, has allowed the development of new treatment strategies, specifically directed against lymphoma cells. The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway plays an important role in controlling proliferation and survival of tumor cells in various types of malignancies, including DLBCL, and therefore it may be a promising target for therapeutic intervention. Currently, novel anticancer drugs are undergoing assessment in different phases of clinical trials in aggressive lymphomas, with promising outcomes. In this review we present a state of art review on various classes of small molecule inhibitors selectively involving PI3K/Akt/mTOR pathway and their clinical potential in this disease.


Assuntos
Linfoma Difuso de Grandes Células B/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Bibliotecas de Moléculas Pequenas/administração & dosagem , Serina-Treonina Quinases TOR/metabolismo , Antineoplásicos , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Fosfatidilinositol 3-Quinases/genética , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/genética
10.
Postepy Hig Med Dosw (Online) ; 68: 301-9, 2014 Mar 20.
Artigo em Polonês | MEDLINE | ID: mdl-24662798

RESUMO

Transforming growth factor beta (TGF-ß) plays a crucial role and takes part in many processes in the human body both in physiology and pathology. This cytokine is involved in angiogenesis, regulates apoptosis and stimulates divisions of cells, such as hepatocytes, lymphocytes or hematopoietic cells. SMAD proteins family is a unique group of particles responsible for transducting the signal induced by TGF-ß into the nucleus. This molecules, after receiving a signal from activated TGF-ß, act on transcription factors in the nucleus, leading directly to the expression of the corresponding genes. According to current knowledge, disturbances in the functioning of SMAD proteins are present in a number of diseases. The reduced expression was observed, for example in cardiovascular diseases such as primary pulmonary hypertension or myocardial infarction, autoimmune diseases for instance systemic lupus erythematosus and multiple sclerosis, Alzheimer's disease or osteoporosis. The latest clinical data showed the presence of mutations in SMAD proteins in cancerogenesis. Mutation of SMAD-4 protein can be detected in half of the patients with pancreatic cancer, 20% of patients with colorectal cancer and 10% of patients with lung cancer. However, mutation in SMAD-2 protein was observed in 7% of both patients with colorectal cancer and lung cancer. On the basis of numerous works, SMAD protein expression would be valuable prognostic factor in some of neoplastic diseases.


Assuntos
Mutação , Neoplasias/genética , Neoplasias/metabolismo , Proteínas Smad/genética , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Apoptose/genética , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neovascularização Patológica/genética , Neoplasias Pancreáticas/genética , Transdução de Sinais/fisiologia
11.
Expert Opin Drug Metab Toxicol ; 20(4): 207-224, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38516702

RESUMO

INTRODUCTION: Bruton tyrosine kinase inhibitors (BTKi) have been used for the management of human diseases since the approval of the first-in class agent, ibrutinib, by the Food and Drug Administration in 2013 for the treatment of patients with mantle cell lymphoma (MCL). Ibrutinib is a covalent inhibitor along with second-class BTKis: acalabrutinib and zanubrutinib. These well-tolerated agents have transformed the treatment landscape of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). A new class of these inhibitors, non-covalent, might become an answer to the emerging resistance by avoiding the sustained contact with the kinase binding domain. AREAS COVERED: This article examines the chemical composition, mechanism of action, metabolic characteristics, and potential toxicity of inhibitors targeting Bruton tyrosine kinase. A comprehensive search was conducted across English-language articles in PubMed, Web of Science, and Google Scholar. EXPERT OPINION: Bruton tyrosine kinase inhibitors have greatly enhanced the armamentarium against lymphoid malignancies including CLL/SLL. Their future lies in the choice of appropriate patients who will benefit from the treatment without significant adverse reaction. Combination chemotherapy-free fixed-duration regimens with targeted molecules will allow for MRD-driven approach in patients with CLL/SLL in the near future.


Assuntos
Adenina , Tirosina Quinase da Agamaglobulinemia , Antineoplásicos , Leucemia Linfocítica Crônica de Células B , Animais , Humanos , Adenina/efeitos adversos , Adenina/análogos & derivados , Adenina/uso terapêutico , Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Piperidinas/efeitos adversos , Piperidinas/uso terapêutico , /uso terapêutico
12.
Mediators Inflamm ; 2013: 523170, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23606792

RESUMO

Nowadays, it is believed that the main role in the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma plays Helicobacter pylori infection. This world-wide distributed bacteria is in charge of most cases of not only upper gastrointestinal tract disorders but also some of extragastric problems. Constant stimulation of the immune system causes a B-lymphocytes proliferation, which is considered to be responsible for the neoplastic transformation. On the other hand, there are 10%-20% of patients who do not respond to Helicobacter pylori eradication treatment. This group has often a chromosome translocation, which suggests that there is another unknown, so far, pathogenetic mechanism of MALT lymphoma. Majority of genetic abnormalities are connected with nuclear factor-κB (NF-κB) pathway, which activates the uncontrolled proliferation of neoplastic cells. Translocations already described in studies are t(11;18)(q21;q21), which is the most common, t(14;18)(q32;q21), t(14;18)(q32;q21), and t(3;14)(p14.1;q32). This non-Hodgkin's lymphoma is an indolent type originated outside lymph nodes. In more than 50% of cases, it occurs in the stomach. Occasionally, it can be found in salivary and thyroid gland, lung, breast, bladder, skin, or any other place in the human body. This paper is a review of the current knowledge on etiology, pathogenesis, treatment, and follow-up of gastric MALT lymphoma.


Assuntos
Infecções por Helicobacter/complicações , Linfoma de Zona Marginal Tipo Células B/etiologia , Linfoma de Zona Marginal Tipo Células B/metabolismo , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/metabolismo , Humanos , Linfoma de Zona Marginal Tipo Células B/imunologia , Linfoma de Zona Marginal Tipo Células B/patologia , NF-kappa B/metabolismo , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia
13.
Postepy Hig Med Dosw (Online) ; 67: 1166-72, 2013 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-24379257

RESUMO

Ranpirnase (onconase; ONC) is an endoribonuclease obtained from the frog Rana pipiens. This enzyme exhibits anticancer properties mediated by degradation of cellular RNA and induction of apoptosis. In this study we assessed cytotoxicity of ONC in combination with currently used anticancer drugs on a human diffuse large B-cell lymphoma (DLBCL)-derived cell line (Toledo). Cytotoxic activity was measured by the exclusion of propidium iodide assay while apoptosis was assessed using the annexin-V binding method. Additionally, flow cytometry was used to assess the decline of mitochondrial potential and to determine activation of caspases 3, 8 and 9. It was observed that in vitro treatment with ONC in combination with rituximab, mafosfamide, vincristine, doxorubicin, and dexamethasone (drugs corresponding with elements of R-CHOP regimen) resulted in increased cytotoxicity. As a result ONC showed marked cytotoxicity against Toledo cells. Importantly, in combination of ONC with drugs imitating the R-CHOP regimen, this effect was significantly intensified. The main mechanism responsible for this event was induction of apoptosis along a mitochondrial dependent pathway. In conclusion, these data indicate that further preclinical and eventually clinical studies assessing activity of ONC+R-CHOP treatment are warranted.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Ribonucleases/administração & dosagem , Anticorpos Monoclonais Murinos/administração & dosagem , Apoptose/efeitos dos fármacos , Linhagem Celular , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Humanos , Prednisona/administração & dosagem , Rituximab , Resultado do Tratamento , Vincristina/administração & dosagem
14.
J Clin Med ; 12(14)2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37510802

RESUMO

We investigated the diagnostic capacity of selected circulating biomarkers (CBMs) for the early detection of bone metastasis (BMets) in patients with pancreatic neuroendocrine neoplasms (PanNENs). A total of 115 patients with PanNENs and 40 controls were enrolled. We measured the serum levels of ferritin, cytokeratin 18 (CY18), CA19-9, CA125, AFP, CEA, and beta-2 microglobulin (B2M). A total of eight PanNEN patients developed BMets, and one hundred seven remained BMets-free. We observed a significantly higher level of CA125 and CY18 in BMets patients vs. non-BMets patients (p = 0.01 and p = 0.04, respectively). CA125, CY18, and B2M area under receiver operator characteristic (AUROC) analyses differentiated both patients groups; CA125 area under the curve (AUC) 0.77, p < 0.01; CY18 AUC data were 0.72, p = 0.03, and B2M AUC 0.67, p = 0.02. On the basis of CBM metrics in both subgroups, we reached a sensitivity/specificity for CA125 of 75/76%; for CY18 of 75/69%, for B2M of 100/50%, for CA125, and the CY18 combination of 93/90%, respectively. According to current results, CA125 and CY18 seem to have the potential capacity as fair biomarkers for BMets detection, despite the small number of cases. Further studies are warranted in the larger PanNEN patient group.

15.
Expert Opin Drug Metab Toxicol ; 19(9): 617-633, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37714711

RESUMO

INTRODUCTION: Phosphoinositide 3-kinase delta (PI3Kδ) inhibitors are a class of novel agents that are mainly used to treat B-cell malignancies. They function by inhibiting one or more enzymes which are part of the PI3K/AKT/mTOR pathway. Idelalisib is a first-in-class PI3Kδ inhibitor effective in patients with B-cell lymphoid malignancies. AREAS COVERED: This article reviews the chemical structure, mechanism of action, and metabolic and toxicological properties of PI3Kδ inhibitors and discusses their clinical applications in monotherapy and in combination with other agents for the treatment of chronic lymphocytic leukemia (CLL). A search was conducted of PubMed, Web of Science, and Google Scholar for articles in English. RESULTS/CONCLUSION: PI3Kδ inhibitors hold potential for the treatment of B-cell malignancies, including CLL. However, their use is also associated with severe toxicities, including pneumonia, cytopenias, hepatitis, and rash. Newer drugs are in development to reduce toxicity with novel schedules and/or combinations. EXPERT OPINION: The development of novel PI3Kδ inhibitors might help to reduce toxicity and improve efficacy in patients with CLL and other B-cell lymphoid malignancies.


Assuntos
Antineoplásicos , Leucemia Linfocítica Crônica de Células B , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/patologia , Inibidores de Fosfoinositídeo-3 Quinase , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/uso terapêutico , Antineoplásicos/efeitos adversos , Fosfatidilinositol 3-Quinase/uso terapêutico
16.
J Pers Med ; 13(9)2023 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-37763082

RESUMO

Melatonin (MLT), a pineal gland hormone, not only regulates circadian and seasonal rhythms, but also plays an important role in many aspects of human physiology and pathophysiology. MLT is of great interest as a natural substance with anti-cancer activities. The aim of this study was to assess the cytotoxicity and apoptosis of MLT, used alone or in combination with one of the most active anti-cancer drugs, doxorubicin (DOX), and a well-known anti-inflammatory drug, dexamethasone (DEX), on a diffuse large B-cell lymphoma (DLBCL)-derived cell line. The cytotoxicity and cell cycle distribution were measured using propidium iodide staining, while apoptosis was assessed using the annexin-V binding method. Additionally, to elucidate the mechanisms of action, caspase-3, -8, and -9 and a decline in the mitochondrial potential were determined using flow cytometry. MLT inhibited cell viability as well as induced apoptosis and cell cycle arrest at the G0/G1 phase. The pro-apoptotic effect was exerted through both the mitochondrial and caspase-dependent pathways. Furthermore, we observed increased cytotoxic and pro-apoptotic activity as well as the modulation of the cell cycle after the combination of MLT with DOX, DEX, or a combination of DOX + DEX, compared with both drugs or MLT used alone. Our findings confirm that MLT is a promising in vitro anti-tumour agent that requires further evaluation when used with other drugs active against DLBCL.

17.
Adv Clin Exp Med ; 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38014929

RESUMO

BACKGROUND: Autoimmune cytopenias (ACs), including immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA) and autoimmune granulocytopenia, are rare complications observed in lymphoma patients. They may appear before, during or after lymphoma diagnosis, whether the patients had disease progression or not. OBJECTIVES: This study aims to correlate ACs with lymphoma type, disease course and prognosis. We performed a multicenter retrospective analysis of adult patients with malignant lymphoma and ACs coexistence diagnosed and treated in centers aligned with the Polish Lymphoma Research Group (PLRG). MATERIAL AND METHODS: The analysis covers the years 2016-2022 and included 51 patients comprised of 23 women and 28 men. Of these, 35 patients were diagnosed with AIHA, 15 patients with ITP and 1 patient with both AIHA and ITP. RESULTS: The most common type of lymphoma was Hodgkin lymphoma (HL) (12 patients) and diffuse large B-cell lymphoma (DLBCL) (14 patients). At the time of diagnosis, 31 (61%) of patients had stage 4 of HL or DLBCL, according to Ann Arbor classification. In total, the response to treatment was evaluated in 50 patients, with 25 being in complete remission and 6 in partial remission. We observed that B cell symptoms (p = 0.036), bone marrow involvement (p = 0.073), splenomegaly (p = 0.025), and more than 2 lines of treatment were more common in AIHA compared to ITP patients. Conversely, eucopenia (p = 0.056) and ACs without lymphoma progression (p = 0.002) were more often diagnosed in ITP patients. CONCLUSIONS: In the study group, relapsed and refractory disease was observed more often, and shorter overall survival (OS) was noted in patients with DLBCL. We found that AC is associated with a worse prognosis in comparison to the general population of lymphoma patients. There were no differences in response to AC therapy. To have more accurate data, a larger group, as part of a multicenter study, should be evaluated.

18.
Arch Med Sci ; 19(5): 1243-1251, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37732037

RESUMO

Introduction: Although breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is infrequent, with less than 1000 noted cases worldwide, patients consenting for breast implant surgery should be aware of its risk. We describe the first Polish multicenter case-series data on BIA-ALCL patients and present diagnostic and treatment recommendation for breast surgeons. Material and methods: In cooperation with the Polish Society of Surgical Oncology and Polish Lymphoma Research Group, we collected BIA-ALCL cases in Poland. Results: We retrospectively reviewed clinical data of seven BIA-ALCL patients, diagnosed between July 2013 and November 2019. The median time from implant placement to the first BIA-ALCL symptoms was 65 months (range: 33-96 months). All the patients were exposed to textured implants at presentation. Capsulectomy with implant removal was performed in all the patients with immediate reimplantation in 2 cases. In a median follow-up of 19 months (range 5-81 months), there was no recurrence and all the patients stayed alive. Between 2013 and 2019, the incidence of BIA-ALCL in Polish female population age 30 and above ranged from 0 to 0.021/100 000/year. Conclusions: BIA-ALCL is scarce in the Polish population. In a short-term follow-up, patients' prognosis remains excellent. Due to the withdrawal of roughly textured implants from the market and the exclusion of likely the most potent etiologic factor, it might be expected that the incidence of BIA-ALCL will become even rarer.

19.
Brain Behav ; 12(4): e2541, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35238494

RESUMO

INTRODUCTION: Studies explored physiotherapeutic approaches in cervical dystonia (CD) patients with or without botulinum toxin (BoNT) injections, however the results are varying. There are no clinical trials investigating the effects of kinesiology taping in CD patients. The objective of this study is to investigate the efficacy of kinesiology taping as an adjunct to the BoNT injections in patients with CD. METHODS: Twenty-five patients were enrolled to the study. Patients were randomly assigned to the experimental 1 (BoNT + KinesioTaping), experimental 2 (BoNT + ShamTaping) or control (BoNT) treatment. After 12 weeks they were moved to the next experimental group and finally every patient received all 3 proposed treatment options. The severity of CD was quantified with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) including Torticollis severity, Disability, and Pain scales. Quality of life was evaluated using Craniocervical dystonia questionnaire (CDQ4). RESULTS: In all treatment groups, there was a significant improvement in dystonia symptoms measured with TWSTRS (total score) after BoNT injection regardless of the allocation to the experimental treatment (p < .05). ANOVA analysis revealed no differences in any of the TWSTRS variables after the intervention. Quality of life was significantly improved after application of taping (p < .05, p = .03). CONCLUSIONS: Application of KinesioTaping after BoNT injection provided no additional effect on the severity of dystonia, although the quality of life was improved in patients with CD. Further research investigating the effect of KinesioTaping prior to BoNT injection is required.


Assuntos
Fita Atlética , Toxinas Botulínicas Tipo A , Distúrbios Distônicos , Torcicolo , Adulto , Toxinas Botulínicas Tipo A/uso terapêutico , Distúrbios Distônicos/tratamento farmacológico , Humanos , Medição da Dor , Qualidade de Vida , Torcicolo/tratamento farmacológico , Resultado do Tratamento
20.
J Clin Med ; 11(15)2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35956064

RESUMO

Bing-Neel syndrome (BNS) is a rare presentation of Waldenström macroglobulinemia (WM). BNS is a consequence of the central nervous system (CNS) involvement by lymphoplasmacytic lymphoma (LPL) and, rarely, the peripheral nervous system. The data on BNS are extremely scarce. Therefore, we performed a multicenter retrospective analysis of BNS patients diagnosed and treated in centers aligned with the Polish Lymphoma Research Group. The analysis covers the years 2014-2021. Eleven patients were included, 55% females and the median age at BNS diagnosis was 61 years. The median time from WM to BNS was 3.5 years; 27% of patients did have a diagnosis of WM and BNS made simultaneously or within 30 days from each other. Isolated parenchymal involvement was the least frequent (20%). Patients were treated with different regimens, mostly able to cross the blood-brain barrier, including 18% treated with ibrutinib first line. The cumulative objective response to treatment was 73%. With the median follow-up of 20 months (95% CI, 2-32), the 36-month estimates were: overall survival (OS) 47%, progression-free survival (PFS) 33%, and cumulative incidence of BNS-associated death 41%. The performance status according to ECOG was significant for PFS (HR = 7.79) and the hemoglobin concentration below 11 g/dL was correlated with PFS. To conclude, BNS is a very rare manifestation of WM. It is associated with a poor outcome with most patients succumbing to BNS.

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