Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 120.109
Filtrar
1.
Intern Med ; 60(13): 2047-2053, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34193774

RESUMO

A 68-year-old man with hepatocellular carcinoma (HCC) visited his previous hospital due to abdominal pain and was diagnosed with ruptured HCC. Before visiting our hospital, he underwent HCC treatment at his previous hospital, but his tumors did not improve. Although he started treatment with sorafenib, the tumors rapidly grew. Subsequently, regorafenib was given, and the tumors shrank. After 22 months being treated with regorafenib, HCC reoccurred, with a new lung metastasis and a contrast-enhanced nodule on the peritoneal dissemination appearing. He underwent conversion surgery and survived for 4.5 years after his HCC was diagnosed.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Idoso , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Compostos de Fenilureia/uso terapêutico , Piridinas , Sorafenibe/uso terapêutico
2.
Nat Commun ; 12(1): 4193, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234122

RESUMO

Interplay between EBV infection and acquired genetic alterations during nasopharyngeal carcinoma (NPC) development remains vague. Here we report a comprehensive genomic analysis of 70 NPCs, combining whole-genome sequencing (WGS) of microdissected tumor cells with EBV oncogene expression to reveal multiple aspects of cellular-viral co-operation in tumorigenesis. Genomic aberrations along with EBV-encoded LMP1 expression underpin constitutive NF-κB activation in 90% of NPCs. A similar spectrum of somatic aberrations and viral gene expression undermine innate immunity in 79% of cases and adaptive immunity in 47% of cases; mechanisms by which NPC may evade immune surveillance despite its pro-inflammatory phenotype. Additionally, genomic changes impairing TGFBR2 promote oncogenesis and stabilize EBV infection in tumor cells. Fine-mapping of CDKN2A/CDKN2B deletion breakpoints reveals homozygous MTAP deletions in 32-34% of NPCs that confer marked sensitivity to MAT2A inhibition. Our work concludes that NPC is a homogeneously NF-κB-driven and immune-protected, yet potentially druggable, cancer.


Assuntos
Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/genética , Carcinoma Nasofaríngeo/imunologia , Neoplasias Nasofaríngeas/imunologia , Evasão Tumoral/genética , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Carcinogênese/imunologia , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/terapia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Regulação Viral da Expressão Gênica/imunologia , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/patogenicidade , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Metionina Adenosiltransferase/antagonistas & inibidores , Metionina Adenosiltransferase/metabolismo , Camundongos , NF-kappa B/metabolismo , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/virologia , Nasofaringe/imunologia , Nasofaringe/patologia , Nasofaringe/cirurgia , Nasofaringe/virologia , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Deleção de Sequência , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Evasão Tumoral/efeitos dos fármacos , Sequenciamento Completo do Genoma , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Isr Med Assoc J ; 23(7): 426-431, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34251125

RESUMO

BACKGROUND: Decisions on medication treatment in children dying from cancer are often complex and may result in polypharmacy and increased medication burden. There is no information on medication burden in pediatric cancer patients at the end of life (EOL). OBJECTIVES: To characterize medication burden during the last hospitalization in children dying from cancer. METHODS: We performed a retrospective cohort study based on medical records of 90 children who died from cancer in hospital between 01 January 2010 and 30 December 2018. Demographic and clinical information were collected for the last hospitalization. We compared medication burden (number of medication orders) at hospitalization and at time of death and examined whether changes in medication burden were associated with clinical and demographic parameters. RESULTS: Median medication burden was higher in leukemia/lymphoma patients (6 orders) compared to solid (4 orders) or CNS tumor patients (4 orders, P = 0.006). Overall, the median number of prescriptions per patient did not change until death (P = 0.42), while there was a significant reduction for some medication subgroups (chemotherapy [P = 0.035], steroids [P = 0.010]).Patients dying in the ICU (n=15) had a higher medication burden at death (6 orders) than patients dying on wards (3 orders, P = 0.001). There was a trend for a reduction in medication burden in patients with "Do not resuscitate" (DNR) orders (P = 0.055). CONCLUSIONS: Polypharmacy is ubiquitous among pediatric oncology patients at EOL. Disease type and DNR status may affect medication burden and deprescribing during the last hospitalization.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias , Cuidados Paliativos , Polimedicação , Esteroides/uso terapêutico , Assistência Terminal , Criança , Procedimentos Clínicos/estatística & dados numéricos , Demografia , Feminino , Pesquisa sobre Serviços de Saúde , Hospitalização/estatística & dados numéricos , Humanos , Israel/epidemiologia , Masculino , Estadiamento de Neoplasias , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Neoplasias/patologia , Cuidados Paliativos/métodos , Cuidados Paliativos/estatística & dados numéricos , Ordens quanto à Conduta (Ética Médica) , Assistência Terminal/métodos , Assistência Terminal/estatística & dados numéricos
5.
Biomed Pharmacother ; 139: 111584, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243623

RESUMO

BACKGROUND: Cancer is one of the most dreaded diseases characterized by uncontrolled proliferation of abnormal cells that occurs due to impairment of cell division and apoptosis process. Cancer is categorized into several types on the basis of affected organs and breast cancer (BC) is the most predominant cause of mortality among women. Although, several synthetic and semi-synthetic therapies have been developed for the treatment of BC but they exhibit numerous serious adverse effects therefore; pharmacological agents with fewer/no side effects need to be explored. Plants and phytoconstituents perhaps fulfill the aforementioned requirement and could serve as a potential and alternative therapy for BC treatment. The ongoing biomedical research, clinical trials and number of patents granted have further boosted the acceptance of the plants and plant-derived constituents in the effective treatment of BC. PURPOSE OF STUDY: Various treatment strategies such as checkpoint inhibitors, targeting micro RNA, apoptotic pathway, BRCA-1 gene, P53 protein, P13K/Akt/mTOR pathway, notch signaling pathway, hedgehog/gli-1 signaling pathway, poly-ADP ribose polymerase inhibitors, mitogen-activated protein kinase inhibitors etc. are available for BC. In addition to these synthetic and semi-synthetic drug therapies, several natural constituents such as alkaloids, sesquiterpenes, polyphenols, flavonoids and diterpenoids from medicinal plants, vegetables and fruits are reported to possess promising anti-cancer activity. The purpose of the present review is to highlight the various signaling pathways through which plants/herbs show the anti-cancer potential especially against the BC. STUDY DESIGN: The literature for the present study was collected from various databases such as Pubmed, Scopus, Chemical Abstracts, Medicinal and aromatic plant abstracts, Web of Science etc. The different patent databases were also reviewed for the anti-cancer (BC) potential of the particular herbs/plants and their formulations. RESULT AND CONCLUSION: In this review, we have discussed the number of plants along with their patents of different herbal formulations which are being used for the treatment of BC and other types of cancers. We have also delineated the different signaling mechanisms through which they inhibit the growth of BC cells. In nutshell, we can conclude that large numbers of herbs or their extracts are reported for the treatment of BC. But still, there is further need for research in-depth to translate the use of natural products clinically BC treatment.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Preparações de Plantas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Feminino , Humanos , Fitoterapia , Plantas Medicinais/química
6.
Int J Nanomedicine ; 16: 4597-4614, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34267515

RESUMO

Malignant gliomas (MGs) are the most common and devastating primary brain tumor. At present, surgical interventions, radiotherapy, and chemotherapy are only marginally effective in prolonging the life expectancy of patients with MGs. Inherent heterogeneity, aggressive invasion and infiltration, intact physical barriers, and the numerous mechanisms underlying chemotherapy and radiotherapy resistance contribute to the poor prognosis for patients with MGs. Various studies have investigated methods to overcome these obstacles in MG treatment. In this review, we address difficulties in MG treatment and focus on promising polymeric local drug delivery systems. In contrast to most local delivery systems, which are directly implanted into the residual cavity after intratumoral injection or the surgical removal of a tumor, some rapidly developing and promising nanotechnological methods-including surface-decorated nanoparticles, magnetic nanoparticles, and focused ultrasound assist transport-are administered through (systemic) intravascular injection. We also discuss further synergistic and multimodal strategies for heightening therapeutic efficacy. Finally, we outline the challenges and therapeutic potential of these polymeric drug delivery systems.


Assuntos
Portadores de Fármacos , Glioma/tratamento farmacológico , Polímeros , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Terapia Combinada , Portadores de Fármacos/química , Humanos , Polímeros/química
7.
Int J Mol Sci ; 22(13)2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206957

RESUMO

In recent decades, the conduct of uniform prospective clinical trials has led to improved remission rates and survival for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia. However, high-risk patients continue to have inferior outcomes, where chemoresistance and relapse are common due to the survival mechanisms utilised by leukaemic cells. One such mechanism is through hijacking of the bone marrow microenvironment, where healthy haematopoietic machinery is transformed or remodelled into a hiding ground or "sanctuary" where leukaemic cells can escape chemotherapy-induced cytotoxicity. The bone marrow microenvironment, which consists of endosteal and vascular niches, can support leukaemogenesis through intercellular "crosstalk" with niche cells, including mesenchymal stem cells, endothelial cells, osteoblasts, and osteoclasts. Here, we summarise the regulatory mechanisms associated with leukaemia-bone marrow niche interaction and provide a comprehensive review of the key therapeutics that target CXCL12/CXCR4, Notch, Wnt/b-catenin, and hypoxia-related signalling pathways within the leukaemic niches and agents involved in remodelling of niche bone and vasculature. From a therapeutic perspective, targeting these cellular interactions is an exciting novel strategy for enhancing treatment efficacy, and further clinical application has significant potential to improve the outcome of patients with leukaemia.


Assuntos
Leucemia/tratamento farmacológico , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Humanos , Leucemia/patologia , Transdução de Sinais
8.
Molecules ; 26(12)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201298

RESUMO

The tumor microenvironment (TME) is a heterogenous assemblage of malignant and non-malignant cells, including infiltrating immune cells and other stromal cells, together with extracellular matrix and a variety of soluble factors. This complex and dynamic milieu strongly affects tumor differentiation, progression, immune evasion, and response to therapy, thus being an important therapeutic target. The phenotypic and functional features of the various cell types present in the TME are largely dependent on their ability to adopt different metabolic programs. Hence, modulating the metabolism of the cells in the TME, and their metabolic crosstalk, has emerged as a promising strategy in the context of anticancer therapies. Natural compounds offer an attractive tool in this respect as their multiple biological activities can potentially be harnessed to '(re)-educate' TME cells towards antitumoral roles. The present review discusses how natural compounds shape the metabolism of stromal cells in the TME and how this may impact tumor development and progression.


Assuntos
Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Neoplasias/tratamento farmacológico , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Progressão da Doença , Humanos , Neoplasias/metabolismo , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo
9.
Int J Mol Sci ; 22(11)2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34204103

RESUMO

Research on the neurobiology of cancer, which lies at the border of neuroscience and oncology, has elucidated the mechanisms and pathways that enable the nervous system to modulate processes associated with cancer initiation and progression. This research has also shown that several drugs which modulate interactions between the nervous system and the tumor micro- and macroenvironments significantly reduced the progression of cancer in animal models. Encouraging results were also provided by prospective clinical trials investigating the effect of drugs that reduce adrenergic signaling on the course of cancer in oncological patients. Moreover, it has been shown that reducing adrenergic signaling might also reduce the incidence of cancer in animal models, as well as in humans. However, even if many experimental and clinical findings have confirmed the preventive and therapeutic potential of drugs that reduce the stimulatory effect of the nervous system on processes related to cancer initiation and progression, several questions remain unanswered. Therefore, the aim of this review is to critically evaluate the efficiency of these drugs and to discuss questions that need to be answered before their introduction into conventional cancer treatment and prevention.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , Animais , Antineoplásicos/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Progressão da Doença , Humanos , Microbiota/efeitos dos fármacos , Neoplasias/patologia , Transdução de Sinais/efeitos dos fármacos
10.
Molecules ; 26(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209495

RESUMO

Since cancer is a multifactorial disease with a high mortality rate, the study of new therapeutic strategies is one of the main objectives in modern research. Numerous chemotherapeutic agents, although widely used, have the disadvantage of being not very soluble in water or selective towards cancerous cells, with consequent side effects. Therefore, in recent years, a greater interest has emerged in innovative drug delivery systems (DDSs) such as calixarene, a third-generation supramolecular compound. Calixarene and its water-soluble derivatives show good biocompatibility and have low cytotoxicity. Thanks to their chemical-physical characteristics, calixarenes can be easily functionalized, and by itself can encapsulate host molecules forming nanostructures capable of releasing drugs in a controlled way. The encapsulation of anticancer drugs in a calixarene derivate improves their bioavailability and efficacy. Thus, the use of calixarenes as carriers of anticancer drugs could reduce their side effects and increase their affinity towards the target. This review summarizes the numerous research advances regarding the development of calixarene nanoparticles capable of encapsulating various anticancer drugs.


Assuntos
Antineoplásicos , Calixarenos , Portadores de Fármacos , Nanopartículas , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Calixarenos/química , Calixarenos/uso terapêutico , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico
11.
Int J Nanomedicine ; 16: 4495-4513, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239301

RESUMO

Purpose: Hepatocellular carcinoma (HCC) is a common malignant tumor that seriously threatens human life and health. Currently, the majority of antitumor drugs are administered in an injectable manner, which can cause pain and side effects to patients. Objective of this study is to establish an effective oral drug delivery system for anti hepatoma drugs. Methods: In this study, intestinal targeting cell penetrating peptide (R6LRVG) was obtained by binding cell penetrating peptide (R6) with the polypeptide of LRVG (targeting intestinal epithelial cells). Next, R6LRVG-modified tyroserleutide-poly(lactic-co-glycolic acid) (PLGA) nanoparticles (YSL-PLGA/R6LRVG NPs) were prepared. After that, the nanoparticles were characterized and their stability was evaluated. The cellular uptake, in vitro bioactivity and in vivo antitumor activity of the nanoparticles were investigated. In addition, the mechanism, including the endocytic pathway and respiratory rate detection of mitochondria, was further investigated. Results: YSL-PLGA/R6LRVG NPs were successfully prepared. Characterization revealed YSL-PLGA/R6LRVG NPs to be globular particles with smooth surfaces and an average diameter of 222.6 nm. The entrapment efficiency and drug loading of tyroserleutide were 70.27% and 19.69%, respectively. Furthermore, the YSL-PLGA/R6LRVG NPs group exhibited the largest amount of YSL uptake. We also found that cell uptake of YSL-PLGA/R6LRVG NPs could be related to the endocytosis pathways mediated by reticulin and caveolae/lipid rafts. Additionally, the YSL-PLGA/R6LRVG NPs could interfere with mitochondrial function. In vivo experiments revealed that orally administered YSL-PLGA/R6LRVG NPs exerted excellent anticancer effects in tumor-bearing mice. Hematoxylin-eosin staining did not show any histological changes in the major organs. Conclusion: To summarize, YSL-PLGA/R6LRVG NPs could be a useful oral delivery system of YSL and may provide a new platform for the oral delivery of anticancer drugs.


Assuntos
Antineoplásicos/química , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/química , Oligopeptídeos/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Administração Oral , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Humanos , Camundongos
12.
Molecules ; 26(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204564

RESUMO

Based on phenotypic screening, the major advantages of phosphorus dendrimers and dendrons as drugs allowed the discovery of new therapeutic applications, for instance, as anti-cancer and anti-tuberculosis agents. These biological activities depend on the nature of the chemical groups (neutral or cationic) on their surface as well as their generation. As lessons to learn, in the oncology domain, the increase in the generation of metallo-dendrimers is in the same direction as the anti-proliferative activities, in contrast to the development of polycationic dendrimers, where the most potent anti-tuberculosis phosphorus dendrimer was observed to have the lowest generation (G0). The examples presented in this original analysis of phosphorus dendrimers and dendrons provide support for the lessons learned and for the development of new nanoparticles in nanomedicine.


Assuntos
Dendrímeros/farmacologia , Nanomedicina/tendências , Fósforo/farmacologia , Animais , Antineoplásicos/uso terapêutico , Antituberculosos/uso terapêutico , Dendrímeros/química , Humanos , Estrutura Molecular , Nanomedicina/métodos , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Fósforo/química , Tuberculose/tratamento farmacológico
13.
Medicina (Kaunas) ; 57(6)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205407

RESUMO

Tumor chemosensitivity assays (TCAs), also known as drug response assays or individualized tumor response tests, have been gaining attention over the past few decades. Although there have been strong positive correlations between the results of these assays and clinical outcomes, they are still not considered routine tests in the care of cancer patients. The correlations between the assays' results (drug sensitivity or resistance) and the clinical evaluations (e.g., response to treatment, progression-free survival) are highly promising. However, there is still a need to design randomized controlled prospective studies to secure the place of these assays in routine use. One of the best ideas to increase the value of these assays could be the combination of the assay results with the omics technologies (e.g., pharmacogenetics that gives an idea of the possible side effects of the drugs). In the near future, the importance of personalized chemotherapy is expected to dictate the use of these omics technologies. The omics relies on the macromolecules (Deoxyribonucleic acid -DNA-, ribonucleic acid -RNA-) and proteins (meaning the structure) while TCAs operate on living cell populations (meaning the function). Therefore, wise combinations of TCAs and omics could be a highly promising novel landscape in the modern care of cancer patients.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/uso terapêutico , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Farmacogenética , Estudos Prospectivos
14.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207315

RESUMO

Pevonedistat is a neddylation inhibitor that blocks proteasomal degradation of cullin-RING ligase (CRL) proteins involved in the degradation of short-lived regulatory proteins, including those involved with cell-cycle regulation. We determined the sensitivity and mechanism of action of pevonedistat cytotoxicity in neuroblastoma. Pevonedistat cytotoxicity was assessed using cell viability assays and apoptosis. We examined mechanisms of action using flow cytometry, bromodeoxyuridine (BrDU) and immunoblots. Orthotopic mouse xenografts of human neuroblastoma were generated to assess in vivo anti-tumor activity. Neuroblastoma cell lines were very sensitive to pevonedistat (IC50 136-400 nM). The mechanism of pevonedistat cytotoxicity depended on p53 status. Neuroblastoma cells with mutant (p53MUT) or reduced levels of wild-type p53 (p53si-p53) underwent G2-M cell-cycle arrest with rereplication, whereas p53 wild-type (p53WT) cell lines underwent G0-G1 cell-cycle arrest and apoptosis. In orthotopic neuroblastoma models, pevonedistat decreased tumor weight independent of p53 status. Control mice had an average tumor weight of 1.6 mg + 0.8 mg versus 0.5 mg + 0.4 mg (p < 0.05) in mice treated with pevonedistat. The mechanism of action of pevonedistat in neuroblastoma cell lines in vitro appears p53 dependent. However, in vivo studies using mouse neuroblastoma orthotopic models showed a significant decrease in tumor weight following pevonedistat treatment independent of the p53 status. Novel chemotherapy agents, such as the NEDD8-activating enzyme (NAE) inhibitor pevonedistat, deserve further study in the treatment of neuroblastoma.


Assuntos
Antineoplásicos/uso terapêutico , Ciclopentanos/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Neuroblastoma/tratamento farmacológico , Pirimidinas/uso terapêutico , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Ciclopentanos/farmacologia , Inibidores Enzimáticos/farmacologia , Humanos , Camundongos , Proteína NEDD8/antagonistas & inibidores , Proteína NEDD8/metabolismo , Pirimidinas/farmacologia , Proteína Supressora de Tumor p53/metabolismo
15.
Urol Clin North Am ; 48(3): 349-363, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34210490

RESUMO

Recent studies show that the prevalence of germline pathogenic and likely pathogenic variants (also known as mutations) in DNA repair genes in metastatic prostate cancer is higher than previously recognized and higher than in unaffected men. Specific gene dysfunction is important in prostate cancer initiation and/or evolution to metastases. This article reviews key literature on individual genes, recognizing BRCA2 as the gene most commonly altered in the metastatic setting. This article discusses the importance of representative and diverse inclusion, and efforts to advance management for at-risk carrier populations to maximize clinical benefit.


Assuntos
Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Antineoplásicos/uso terapêutico , Dano ao DNA , Predisposição Genética para Doença , Testes Genéticos , Mutação em Linhagem Germinativa , Humanos , Indóis/uso terapêutico , Masculino , Metástase Neoplásica/tratamento farmacológico , Ftalazinas/uso terapêutico , Piperazinas/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico
16.
Urol Clin North Am ; 48(3): 365-371, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34210491

RESUMO

Germline testing should be performed to support treatment selection for patients with metastatic prostate cancer, and should be identified in patients with high-risk localized disease. Patients with germline BRCA1/2 mutations should be educated regarding additional personal cancer risk, and risk for family members. Guidelines recommend that all men with metastatic prostate cancer should also undergo somatic tissue and germline testing for priority genes BRCA1/2, PALB2, ATM, and MSH2/6. The advent of high throughput sequencing enables patients to be tested for a more comprehensive panel of germline and somatic mutations.


Assuntos
Predisposição Genética para Doença , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Dano ao DNA , Reparo do DNA , Genes BRCA1 , Genes BRCA2 , Testes Genéticos , Mutação em Linhagem Germinativa , Humanos , Indóis/uso terapêutico , Masculino , Metástase Neoplásica/tratamento farmacológico , Ftalazinas/uso terapêutico , Piperazinas/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico
17.
Anticancer Res ; 41(7): 3213-3232, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230116

RESUMO

BACKGROUND/AIM: Bromelain, papain and chymotrypsin are proteolytic enzymes. They can be found in fruits such as pineapple or papaya, but also in the human body, namely in the pancreas. Besides their enzymatic function, they are said to reduce side-effects and even to improve the outcome of cancer therapies. We, therefore, aimed to critically examine and systematically review existing evidence on the role that these enzymes might play in cancer treatment. MATERIALS AND METHODS: In May 2019, a systematic literature search was conducted by using five electronic databases (Embase, Cochrane, PsychInfo, CINAHL and Medline) to find studies concerning the use, effectiveness and potential harm of enzyme therapy on cancer patients. RESULTS: Out of 13,046 search results, 15 studies with 3,008 patients were included in this systematic review. Patients treated with enzymes were diagnosed with various entities of gastrointestinal, gynecologic, head and neck and lung cancer as well as hematological malignancies. The therapy concepts included mainly oral intake of enzymes in addition to conventional therapies. Investigated outcomes were side-effects of anticancer therapy, quality of life, as well as anticancer effects and survival rates. In summary, due to conflicting results and moderate quality of the included studies, the evidence is insufficient to attribute positive effects to enzymes in terms of better tolerability of the various antineoplastic therapies or even improvement in treatment efficacy. In most cases, enzyme therapy was well tolerated; side-effects were mainly gastrointestinal complaints such as diarrhea or meteorism. CONCLUSION: On the basis of existing evidence, there is no clear therapeutic benefit of enzymes neither as supportive therapy nor as part of antineoplastic therapy.


Assuntos
Neoplasias/tratamento farmacológico , Peptídeo Hidrolases/farmacologia , Peptídeo Hidrolases/uso terapêutico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Humanos , Oncologia/métodos , Qualidade de Vida , Taxa de Sobrevida
18.
Anticancer Res ; 41(7): 3583-3588, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230154

RESUMO

BACKGROUND/AIM: This study aimed to evaluate the prognostic significance of PLA2G2A expression in patients with locally advanced gastric cancer (GC). PATIENTS AND METHODS: PLA2G2A expression levels in cancerous tissue specimens and adjacent normal mucosa obtained from 134 patients with stage II/III GC who received adjuvant chemotherapy with S-1 after curative resection were measured using real-time quantitative polymerase chain reaction. Subsequently, the associations of PLA2G2A expression with clinicopathological features and survival were evaluated. RESULTS: No association was observed between clinicopathological features and PLA2G2A expression levels. Overall survival was significantly longer in patients with high PLA2G2A expression levels (p=0.022). Multivariate analysis revealed that PLA2G2A expression was a significant, independent prognostic factor (hazard ratio=0.136; 95% confidence interval=0.0185-0.992; p=0.049). CONCLUSION: PLA2G2A mRNA expression may serve as a useful prognostic marker in patients with locally advanced GC who receive curative surgery and adjuvant chemotherapy with S-1.


Assuntos
Fosfolipases A2 do Grupo II/metabolismo , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Tegafur/uso terapêutico , Idoso , Antineoplásicos/uso terapêutico , Quimioterapia Adjuvante/métodos , Combinação de Medicamentos , Feminino , Gastrectomia/métodos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Humanos , Masculino , Estadiamento de Neoplasias/métodos , Prognóstico , RNA Mensageiro/metabolismo , Estômago/efeitos dos fármacos , Estômago/patologia , Estômago/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
19.
Anticancer Res ; 41(7): 3615-3624, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230158

RESUMO

BACKGROUND/AIM: The aim of this study was to investigate the efficacy and safety of adjuvant chemotherapy in elderly patients with stage III colorectal cancer in a real-world setting. PATIENTS AND METHODS: A total of 165 patients of ≥70 years of age with stage III colorectal cancer who underwent a curative operation between 2008 and 2020 were enrolled in this study. RESULTS: Among septuagenarians, the relapse-free and overall survival rates in the single-agent therapy group and the combination therapy group were significantly better than those in the group treated by surgery alone. However, no significant differences were observed in the relapse-free and overall survival rates of the single-agent therapy group and the combination therapy group. Among octogenarians in whom all regimens were single-agent therapy, adjuvant chemotherapy tended to improve the relapse-free and overall survival rates but not the time to recurrence or cancer-specific survival. CONCLUSION: Single-agent adjuvant chemotherapy may be a useful treatment option for septuagenarians with stage III colorectal cancer. However, the efficacy of adjuvant chemotherapy in octogenarians was not shown in this study.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante/métodos , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias/métodos , Taxa de Sobrevida
20.
Gan To Kagaku Ryoho ; 48(7): 939-943, 2021 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-34267032

RESUMO

In recent years, attention has been focused on environmental exposure of anticancer drugs, and guidelines for occupational exposure measures in cancer drug therapy have been created in Japan. Exposure measures related to the preparation and administration of anticancer drugs are being standardized. Although exposure measures have been implemented for the preparation and administration of the infusion pump(IP)used for continuous fluorouracil administration for 46-hour in FOLFOX and FOLFIRI therapies, which are standard chemotherapies for colorectal cancer, needle-removal procedures after the end of administration have not been investigated. Therefore, in this study, we investigated anticancer drug exposure at the time of IP needle removal to establish a safe needle-removal procedure from the viewpoint of anticancer drug exposure countermeasures. The results suggest that the IP's clamp lock position and the pulsing flush of the Huber needle may reduce antineoplastic exposure. In the future, we would like to consider this an educational method for needle-removal techniques.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/uso terapêutico , Humanos , Bombas de Infusão , Japão , Leucovorina/uso terapêutico , Compostos Organoplatínicos/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...