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1.
Br J Haematol ; 202(6): 1084-1086, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37525325

RESUMO

Chemotherapy-free regimens are reshaping the treatment landscape of Philadelphia chromosome-positive acute lymphoblastic leukaemia. The report by Xie et al. suggests that the combination of dasatinib and prednisone is effective as induction and early consolidation. Survival was improved in patients who subsequently underwent allogeneic stem cell transplantation. Commentary on: Xie et al. Dasatinib plus prednisone as induction and consolidation for adults with Ph-positive acute lymphoblastic leukaemia: A single-arm, multicentre, phase 2 trial. Br J Haematol 2023;202:1119-1126.


Assuntos
Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Humanos , Dasatinibe/uso terapêutico , Prednisona/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Inibidores de Proteínas Quinases/uso terapêutico
2.
Am J Hematol ; 98(4): 645-657, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36606708

RESUMO

Advances in molecular profiling of newly diagnosed diffuse large B-cell lymphoma (DLBCL) have recently refine genetic subgroups. Genetic subgroups remain undetermined at the time of relapse or refractory (RR) disease. This study aims to decipher genetic subgroups and search for prognostic molecular biomarkers in patients with RR-DLBCL. From 2015 to 2021, targeted next-generation sequencing analyses of germline-matched tumor samples and fresh tissue from RR-DLBCL patients were performed. Unsupervised clustering of somatic mutations was performed and correlations with patient outcome were sought. A number of 120 patients with RR-DLBCL were included in LNH-EP1 study and a molecular tumor landscape was successfully analyzed in 87% of patients (104/120 tumor samples). The median age was 67.5 years (range 27.4-87.4), median number of previous treatments was 2 (range 1-9). The most frequently mutated genes were TP53 (n = 53 mutations; 42% of samples), CREBBP (n = 39; 32%), BCL2 (n = 86; 31%), KMT2D (n = 39; 28%) and PIM1 (n = 54; 22%). Unsupervised clustering separated three genetic subgroups entitled BST (enriched in BCL2, SOCS1, and TNFRSF14 mutations); TKS (enriched in TP53, KMT2D, and STAT6 mutations); and PCM (enriched in PIM1, CD79B, and MYD88 mutations). Median overall survival (OS) was 11.0 (95% confidence interval [CI]: 8.1-12.6) months. OS was not significantly different between the three genetic subgroups. GNA13 mutant was significantly associated with an increased risk of death (hazard ratio: 6.6 [95% CI: 2.1-20.6]; p = .0011) and shorter OS (p = .0340). At the time of relapse or refractory disease, three genetic subgroups of DLBCL patients were delineated, which could help advance precision molecular medicine programs.


Assuntos
Linfoma Difuso de Grandes Células B , Recidiva Local de Neoplasia , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Prognóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Mutação , Sequenciamento de Nucleotídeos em Larga Escala , Proteínas Proto-Oncogênicas c-bcl-2/genética , Biomarcadores
3.
Int J Mol Sci ; 24(11)2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37298631

RESUMO

The treatment of cancer patients has dramatically changed over the past decades with the advent of monoclonal antibodies, immune-checkpoint inhibitors, bispecific antibodies, and innovative T-cell therapy. Antibody-drug conjugates (ADCs) have also revolutionized the treatment of cancer. Several ADCs have already been approved in hematology and clinical oncology, such as trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and sacituzumab govitecan (SG) for the treatment of metastatic breast cancer, and enfortumab vedotin (EV) for the treatment of urothelial carcinoma. The efficacy of ADCs is limited by the emergence of resistance due to different mechanisms, such as antigen-related resistance, failure of internalization, impaired lysosomal function, and other mechanisms. In this review, we summarize the clinical data that contributed to the approval of T-DM1, T-DXd, SG, and EV. We also discuss the different mechanisms of resistance to ADCs, as well as the ways to overcome this resistance, such as bispecific ADCs and the combination of ADCs with immune-checkpoint inhibitors or tyrosine-kinase inhibitors.


Assuntos
Carcinoma de Células de Transição , Imunoconjugados , Neoplasias da Bexiga Urinária , Humanos , Inibidores de Checkpoint Imunológico , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Imunoconjugados/uso terapêutico , Imunoconjugados/farmacologia , Ado-Trastuzumab Emtansina/farmacologia
4.
BMC Nurs ; 21(1): 312, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36376904

RESUMO

BACKGROUND: Endotracheal suctioning (ETS) is one of the most common invasive procedures performed by critical care nurses (CCNs) to remove accumulated pulmonary secretions, ensure airway patency for adequate ventilation and oxygenation as well as prevent atelectasis in intubated patients. OBJECTIVES: To assess the practice of CCNs in intensive care units (ICUs) before, during, and after performing the ETS procedure and identify factors affecting their practice. METHODS: A cross-sectional and non-participant observational design was conducted in the ICUs of four hospitals in Hodeida city, Yemen. The data were collected using a 25-item observational checklist in the period from May to August 2019. RESULTS: More than half (55%) of CCNs scored undesirable (< 50%) regarding their adherence to ETS practice guidelines while the rest scored moderate (50-75%), with none of showing desirable adherence (> 70%) to the guidelines. There was no significant association between gender, age, education level, or length of experience of CCNs in the ICUs and their practice during performance ETS procedures. However, training (p = 0.010) and receiving information about ETS (p = 0.028) significantly improved the CCNs' practice. CONCLUSION: Most CCNs at the ICUs of Hodeida hospitals do not adhere to evidence-based practice guidelines when performing ETS procedures, possibly resulting in numerous adverse effects and complications for patients. CCNs receiving information and training show better ETS practice than do their counterparts. Therefore, it is necessary to provide the nursing staff with clear guidelines, continuous education and monitoring to improve their practices.

5.
Biol Chem ; 402(4): 513-524, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33938181

RESUMO

Increasing antibiotic resistance in Gram-negative bacteria has mandated the development of both novel antibiotics and alternative therapeutic strategies. Evidence of interplay between several gastrointestinal peptides and the gut microbiota led us to investigate potential and broad-spectrum roles for the incretin hormone, human glucose-dependent insulinotropic polypeptide (GIP) against the Enterobacteriaceae bacteria, Escherichia coli and Erwinia amylovora. GIP had a potent disruptive action on drug efflux pumps of the multidrug resistant bacteria E. coli TG1 and E. amylovora 1189 strains. The effect was comparable to bacterial mutants lacking the inner and outer membrane efflux pump factor proteins AcrB and TolC. While GIP was devoid of direct antimicrobial activity, it has a potent membrane depolarizing effect, and at low concentrations, it significantly potentiated the activity of eight antibiotics and bile salt by reducing MICs by 4-8-fold in E. coli TG1 and 4-20-fold in E. amylovora 1189. GIP can thus be regarded as an antimicrobial adjuvant with potential for augmenting the available antibiotic arsenal.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Enterobacteriaceae/efeitos dos fármacos , Erwinia amylovora/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Peptídeos Semelhantes ao Glucagon/farmacologia , Antibacterianos/química , Peptídeos Semelhantes ao Glucagon/química , Humanos , Testes de Sensibilidade Microbiana
6.
Curr Oncol Rep ; 22(4): 33, 2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-32144513

RESUMO

PURPOSE OF REVIEW: Burkitt's lymphoma and its leukemic form (Burkitt cell acute lymphoblastic leukemia) are a highly aggressive disease. We review the classification, clinical presentation, histology, cytogenetics, and the treatment of the disease. RECENT FINDINGS: Burkitt's lymphoma might be associated with tumor lysis syndrome which is a potentially fatal complication that occurs spontaneously or upon initiation of chemotherapy. Major improvements were made in the treatment of pediatric and adults population using short-course dose-intensive chemotherapy regimens, usually 1 week after a prephase induction. Addition of Rituximab to chemotherapy has become a standard of care. Relapsed/refractory disease has a very poor prognosis and the benefit from autologous/allogeneic hematopoietic stem cell transplant remains uncertain. Rituximab-based short-course dose-intensive chemotherapy is the standard of care of Burkitt's lymphoma even in the immunodeficiency-related form.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Rituximab/administração & dosagem , Antígenos CD20/metabolismo , Linfoma de Burkitt/genética , Linfoma de Burkitt/metabolismo , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 8/genética , Humanos , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Translocação Genética
7.
Future Oncol ; 16(14): 961-972, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32297538

RESUMO

Acute myeloid leukemia (AML) is a heterogeneous neoplasm characterized by the monoclonal proliferation of immature progenitors. It is the most common acute leukemia in adults and its incidence increases with age. The standard traditional treatment in fit patients was the '3 + 7' regimen and cytarabine consolidation followed or not with allogeneic stem cell transplantation. Recently, several targeted therapies such as gemtuzumab ozogamicin targeting the CD33+ AML, midostaurin, gilteritinib and crenolanib inhibiting FLT3-positive AML and ivosidenib and enasidenib blocking IDH-mutated AML have been approved. These new drugs led to the change of the landscape of the treatment of AML and transforming this disease to a targetable one. We aimed in this paper to review the implications of each new target, the mechanisms of action of these new drugs and we discuss all the studies leading to the approval of these new drugs in their indications according to each target.


Assuntos
Leucemia Mieloide Aguda/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos como Assunto , Gerenciamento Clínico , Suscetibilidade a Doenças , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/etiologia , Resultado do Tratamento
12.
Future Oncol ; 13(22): 1999-2006, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28829195

RESUMO

The adjuvant chemotherapy (FOLFOX) represents the standard of care in stage III colon cancer with some exceptions in old patients. Adjuvant treatment must also be discussed in high-risk stage II colon cancer. However, 40-50% of patients develop disease recurrence after curative R0 surgical resection. The liver was the most common site of recurrence followed by peritoneum. Although adjuvant chemotherapy improved disease-free survival and overall survival, 5-year overall survival remains less than 55% in stage III colon cancer. Different strategies could be adopted to escalate the standard adjuvant chemotherapy in these patients going from aggressive intravenous chemotherapy, hepatic arterial infusion chemotherapy, hyperthermic intraperitoneal chemotherapy to adding targeted therapies or immunotherapies. We reported in this review the published and ongoing trials evaluating these treatment modalities in colon cancer.

18.
Cancer Treat Rev ; 124: 102697, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38401478

RESUMO

Salivary Gland carcinomas (SGCs) are rare tumors accounting for less than 1% of all cancers with 21 histologically diverse subtypes. The rarity of the disease presents a challenge for clinicians to conduct large size randomized controlled trials. Surgery and radiotherapy remain the only curative treatment for localized disease, whereas treatments for recurrent and metastatic disease remain more challenging with very disappointing results for chemotherapy. The different histological subtypes harbor various genetic alterations, some pathognomonic with a diagnostic impact for pathologists in confirming a difficult diagnosis and others with therapeutic implications regardless of the histologic subtype. Current international guidelines urge pathologists to identify androgen receptor status, HER-2 expression that could be determined by immunohistochemistry, and TRK status in patients with non-adenoid cystic salivary gland carcinoma that are eligible to initiate a systemic treatment, in order to offer them available targeted therapies or refer them to clinical trials based on their mutational profile. A more advanced molecular profiling by next generation sequencing would offer a larger panel of molecular alterations with possible therapeutic implications such as NOTCH, PI3K, BRAF, MYB, and EGFR. In the following review, we present the most common genetic alterations in SGCs as well as actionable mutations with the latest available data on therapeutic options and upcoming clinical trials.


Assuntos
Carcinoma , Neoplasias das Glândulas Salivares , Humanos , Oncogenes , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/terapia , Neoplasias das Glândulas Salivares/metabolismo , Mutação , Glândulas Salivares/metabolismo , Glândulas Salivares/patologia
19.
Cancer Drug Resist ; 7: 22, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39050884

RESUMO

Human epidermal growth factor 2 (HER2)-positive breast cancer (BC) represents nearly 20% of all breast tumors. Historically, these patients had a high rate of relapse and dismal prognosis. The advent of HER2-targeting monoclonal antibodies such as trastuzumab followed by pertuzumab had improved the prognosis of HER2-positive metastatic BC. More recently, antibody-drug conjugates (ADCs) are now reshaping the treatment paradigm of solid tumors, especially breast cancer. Tratsuzumab emtansine (T-DM1) was one of the first ADC developed in oncology and was approved for the management of HER2-positive metastatic BC. In a head-to-head comparison, trastuzumab deruxtecan (T-DXd) defeated T-DM1 as a second-line treatment. The efficacy of ADCs is counterbalanced by the appearance of acquired resistance to these agents. In this paper, we summarize the mechanisms of action and resistance of T-DM1 and T-DXd, as well as their clinical efficacy. Additionally, we also discuss potential strategies for addressing resistance to ADC.

20.
J Pers Med ; 14(7)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-39063920

RESUMO

The advent of targeted therapies such as monoclonal antibodies, adoptive T-cell therapies, and antibody-drug conjugates (ADCs) dramatically changed the treatment landscape of diffuse large B-cell lymphoma (DLBCL) over the last two decades. Rituximab was the first one approved. Chimeric antigen receptor T-cells are currently approved as second-line treatment in patients with DLBCL refractory to first-line chemo-immunotherapy. Polatuzumab, a CD79b-targeting ADC, is approved as first-line treatment in high-risk patients in combination with chemo-immunotherapy. Bispecific antibodies (BsAbs) are a novel category of drugs that are also changing the treatment paradigm of patients with DLBCL. They are engineered to bind to two different targets at the same time. To date, two BsAbs (glofitamab and epcoritamab) are approved as monotherapy in third-line treatment in DLBCL. Combination strategies with chemotherapy, immunotherapy, and ADCs are currently under investigation with encouraging results in first-line or subsequent lines of treatment. In the following review, we focus on the structure of BsAbs, the mechanism of action, clinical efficacy, and the mechanisms of resistance to BsAbs.

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