Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 38.092
Filtrar
1.
Adv Exp Med Biol ; 1148: 173-199, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31482500

RESUMO

Cancer treatment has greatly improved over the last 50 years, but it remains challenging in several cases. Useful therapeutic targets are normally unique peculiarities of cancer cells that distinguish them from normal cells and that can be tackled with appropriate drugs. It is now known that cell metabolism is rewired during tumorigenesis and metastasis as a consequence of oncogene activation and oncosuppressors inactivation, leading to a new cellular homeostasis typically directed towards anabolism. Because of these modifications, cells can become strongly or absolutely dependent on specific substrates, like sugars, lipids or amino acids. Cancer addictions are a relevant target for therapy, as removal of an essential substrate can lead to their selective cell-cycle arrest or even to cell death, leaving normal cells untouched. Enzymes can act as powerful agents in this respect, as demonstrated by asparaginase, which has been included in the treatment of Acute Lymphoblastic Leukemia for half a century. In this review, a short outline of cancer addictions will be provided, focusing on the main cancer amino acid dependencies described so far. Therapeutic enzymes which have been already experimented at the clinical level will be discussed, along with novel potential candidates that we propose as new promising molecules. The intrinsic limitations of their present molecular forms, along with molecular engineering solutions to explore, will also be presented.


Assuntos
Aminoácidos/química , Enzimas/farmacologia , Neoplasias/terapia , Asparaginase , Terapia Enzimática , Humanos , Neoplasias/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras
2.
J Appl Oral Sci ; 27: e20180596, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31508793

RESUMO

Bone development and healing processes involve a complex cascade of biological events requiring well-orchestrated synergism with bone cells, growth factors, and other trophic signaling molecules and cellular structures. Beyond health processes, MMPs play several key roles in the installation of heart and blood vessel related diseases and cancer, ranging from accelerating metastatic cells to ectopic vascular mineralization by smooth muscle cells in complementary manner. The tissue inhibitors of MMPs (TIMPs) have an important role in controlling proteolysis. Paired with the post-transcriptional efficiency of specific miRNAs, they modulate MMP performance. If druggable, these molecules are suggested to be a platform for development of "smart" medications and further clinical trials. Thus, considering the pleiotropic effect of MMPs on mammals, the purpose of this review is to update the role of those multifaceted proteases in mineralized tissues in health, such as bone, and pathophysiological disorders, such as ectopic vascular calcification and cancer.


Assuntos
Remodelação Óssea/fisiologia , Matriz Extracelular/fisiologia , Metaloproteinases da Matriz/fisiologia , Doenças Ósseas/metabolismo , Doenças Ósseas/fisiopatologia , Progressão da Doença , Humanos , Inibidores de Metaloproteinases de Matriz/uso terapêutico , Neoplasias/metabolismo , Neoplasias/fisiopatologia , Osteoblastos/fisiologia , Inibidores Teciduais de Metaloproteinases/fisiologia , Calcificação Vascular/metabolismo , Calcificação Vascular/fisiopatologia
3.
Nihon Yakurigaku Zasshi ; 154(3): 103-107, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31527358

RESUMO

Digitoxin and digoxin are plant-derived cardiac glycosides. They are Na+,K+-ATPase (sodium pump) inhibitors, and have been used clinically for treatment and prevention of heart failure and various tachycardia. On the other hand, some epidemiological studies showed that digoxin users have a lower cancer risk compared to the non-users, and that cancer patients who had been treated with digoxin face on improvement of their survival. In various in vitro studies, cardiac glycosides at sub-µM concentrations, which have no significant effect on enzymatic and ion-transporting activities of Na+,K+-ATPase, show anti-cancer effects. Na+,K+-ATPase is ubiquitously expressed, so it remains unclear why low concentrations of cardiac glycosides have cancer-specific effects. Recently, we found that the receptor-type Na+,K+-ATPase, which has no pumping activity, is associated with leucine-rich repeat-containing 8 family, member A(LRRC8A), one of the components of volume-regulated anion channel (VRAC), in the membrane microdomains of plasma membrane of cancer cells, and that this crosstalk contributes to the inhibition of the cancer cell growth by sub-µM cardiac glycosides. In this mechanism, cardiac glycosides bind to the receptor-type Na+,K+-ATPase, and then stimulate the production of reactive oxygen species (ROS) via NADPH oxidase. The ROS activate VRAC within the membrane microdomains, thus eliciting anti-proliferative effects. VRAC is ubiquitously expressed, and it is normally activated by cell swelling. However, VRAC is activated by cardiac glycoside without cell swelling. On the other hand, the cardiac glycosides-induced effects were not observed in non-cancer cells. Our findings can partly explain why cardiac glycosides elicit selective effects in cancer cells.


Assuntos
Glicosídeos Cardíacos/farmacologia , Neoplasias/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Canais de Ânion Dependentes de Voltagem/metabolismo , Digoxina/farmacologia , Humanos , Proteínas de Membrana/metabolismo , Espécies Reativas de Oxigênio/metabolismo
4.
Anticancer Res ; 39(9): 4597-4602, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519556

RESUMO

Our previous review of the literature assessed the existing knowledge (until 2000) about the possible link between angiotensin-converting enzyme inhibitors (ACEIs) and factors influencing the development of malignancies. We reviewed the literature for reports of statistical associations (or lack thereof) between ACEi treatment and incidence of specific cancers (e.g. breast, gastrointestinal, and skin). We concluded then that results from the epidemiological studies are conflicting, even taking the different methodology and endpoints into consideration, and thus inconclusive. Further investigation is needed beyond the observation period of most of these studies, and additional experimental studies are needed also to study the mechanisms by which agents blocking the renin-angiotensin system may obtain their inhibitory effect on tumor growth and metastasis. The present review elaborates further with more recent evidence from numerous human clinical studies from the past two decades (including large epidemiological studies, and long-term prospective and retrospective studies) on a protective association between ACEi treatment and the prognosis of patients with specific cancer types, malignancy characteristics or stage. Moreover, treatment with ACEI/angiotensin receptor blockers represents an adjuvant therapy with synergistic effects to chemotherapy and may improve patient outcomes (i.e. progression-free survival, and prolonged overall survival) in different types of cancers.


Assuntos
Neoplasias/metabolismo , Neoplasias/mortalidade , Sistema Renina-Angiotensina/efeitos dos fármacos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Clínicos como Assunto , Modelos Animais de Doenças , Progressão da Doença , Humanos , Estadiamento de Neoplasias , Neoplasias/diagnóstico , Neoplasias/etiologia , Prognóstico , Resultado do Tratamento
5.
Internist (Berl) ; 60(10): 1021-1031, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31486857

RESUMO

In pathological diagnostics, monoclonal antibodies (mAb) are mainly used for immunhistochemical analysis. After an initial histological evaluation, a precise panel of antibodies is selected in order to stain the slides by using an indirect immune method. The most frequent issues include localisation of the primary tumor in cases of metastases, determination of undifferentiated tumors, subtyping of lympho-proliferative diseases and soft tissue tumors, as well as the assessment of proliferation via Ki-67. Increasing importance in mAb-based diagnostics is attributed to the analysis of predictive biomarkers such as hormone receptors, mismatch repair proteins (MMR) and programmed death ligand 1 (PD-L1). Their evaluation is performed by using different scores, which the clinical physician needs to be aware of due to their direct therapeutic implications.


Assuntos
Anticorpos Monoclonais , Antineoplásicos Imunológicos , Biomarcadores Tumorais/metabolismo , Reparo de Erro de Pareamento de DNA , Imuno-Histoquímica/métodos , Neoplasias/patologia , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Neoplasias/genética , Neoplasias/metabolismo
6.
J Cancer Res Clin Oncol ; 145(10): 2413-2422, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31492983

RESUMO

PURPOSE: Polo-like kinase 4 (PLK4) is a serine/threonine protein kinase that regulates centriole duplication. PLK4 deregulation causes centrosome number abnormalities, mitotic defects, chromosomal instability and, consequently, tumorigenesis. Therefore, PLK4 has emerged as a therapeutic target for the treatment of multiple cancers. In this review, we summarize the critical role of centrosome amplification and PLK4 in cancer. We also highlight recent advances in the development of PLK4 inhibitors and discuss potential combination therapies for cancer. METHODS: The relevant literature from PubMed is reviewed in this article. The ClinicalTrials.gov database was searched for clinical trials related to the specific topic. RESULTS: PLK4 is aberrantly expressed in multiple cancers and has prognostic value. Targeting PLK4 with inhibitors suppresses tumor growth in vitro and in vivo. CONCLUSIONS: PLK4 plays an important role in centrosome amplification and tumor progression. PLK4 inhibitors used alone or in combination with other drugs have shown significant anticancer efficacy, suggesting a potential therapeutic strategy for cancer. The results of relevant clinical trials await evaluation.


Assuntos
Biomarcadores Tumorais , Neoplasias/etiologia , Neoplasias/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Centrossomo/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Terapia de Alvo Molecular , Metástase Neoplásica , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Especificidade de Órgãos/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/genética , Relação Estrutura-Atividade , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
7.
J Cancer Res Clin Oncol ; 145(10): 2625-2631, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31492984

RESUMO

PURPOSE: Immune checkpoint inhibitors (ICIs) are effective against a wide variety of cancers. However, they also induce a plethora of unique immune-related adverse events (irAEs). Since for many organ systems symptoms can be unspecific, differential diagnosis with progression of disease or infection may be difficult. C-reactive protein (CRP) has been suggested as a marker for infection. The purpose of this study was to evaluate the diagnostic value of CRP in differentiating infectious causes from autoimmune side effects induced by ICIs. METHODS: In order to investigate the role of CRP in irAEs, we screened our patient data base. Only events with full infectious workup were included. In total 88 events of irAEs in 37 melanoma patients were analyzed. CRP levels before and during irAEs were evaluated. Statistical analyses were conducted using the Chi-square test for categorical variables. RESULTS: At the onset of irAE, CRP rose in 93% of cases to a mean of 52.7 mg/L (CI 35.1-70.3) from 8.4 mg/L at baseline (normal < 5 mg/L) (P < 0.0001). Other causes of CRP elevation including infectious diseases were excluded, and procalcitonin (PCT) levels were normal in 92% of events. Importantly, in 42% of cases CRP elevations preceded clinical symptoms. CONCLUSION: CRP elevation can predict the onset of irAEs in patients treated with ICIs in the absence of infectious disease.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Biomarcadores , Proteína C-Reativa , Imunomodulação , Adulto , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais , Feminino , Humanos , Imunomodulação/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/metabolismo , Adulto Jovem
8.
Gene ; 716: 144025, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31394177

RESUMO

BACKGROUND: Existing meta-analysis have shown that the miR-200 family can be taken as a prognostic biomarker for many tumors. However, great heterogeneity was shown in predicting overall survival (OS) and progression-free survival (PFS). Emerging studies indicate that the expression levels of members of the miR-200 family are tissue-specific among various tumor tissues, which may be the main reason of the heterogeneity in predicting survival prognosis of tumor patients with the miR-200 family as biomarkers. By further analysis of heterogeneity of the miR-200 family as a biomarker for predicting survival prognosis of patients with different tumors, we expected to provide an accurate basis for the clinical application of the miR-200 family to predict the prognosis of patients with different tumors. METHODS: Eligible published studies were identified by searching the databases of PubMed, Embase and Web of Science. The clinical data of patients in the studies were pooled, and pooled hazard ratios (HR) with 95% confidence intervals (95% CI) were used to calculate the strength of this association. The expressions of miRNAs were extracted from The Cancer Genome Atlas (TCGA). We presented the expressions of each member in miR-200 family in 15 types of cancer by boxplot, and analyzed the correlation among the members of miR-200 family by Spearman method. Different subgroup analyses were then performed based on the correlation among the members of miR-200 family, and the publication bias was assessed using the funnel plot of the Egger bias indicator test. RESULTS: Of 36 articles, including 15 tumor types and 4644 patients were included to perform meta-analysis. It was found that miR-200 family members can be used as independent protective factors in patients with various tumors but the miR-200 family has a higher heterogeneity in predicting prognosis: OS (HR = 0.82, 95% CI: 0.66-1.03, I2 = 85%, P < 0.01) and PFS (HR = 0.81, 95% CI: 0.57-1.16, I2 = 97%, P < 0.01). The data from TCGA database were used to analyze the expression levels of the miR-200 family and the results showed that the expression of miR-429 in different cancers is very different, and there are significant differences in expression levels compared with other miR-200 family members; the expression levels of miR-200a and miR-200b in various tumor tissues were similar to each other, respectively; miR-200c and miR-141 showed similar expression levels in each of most types of cancer tissues except ovarian cancer (OC). The expression levels of members of the miR-200 family in breast cancer (BRCA), cervical cancer (CESC), colon cancer (COAD), esophageal cancer (ESCA), head and neck cancer (HNSC), lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) are relatively stable, but great variations can be found in the expression levels of miR-200 family members in ovarian cancer (OC), liver cancer (LIHC), renal clear cell carcinoma (KIRC) and renal papillary cell carcinoma (KIRP). Cluster analysis of expression of target genes of miR-200 family in different cancers yielded similar results to the expression level of the miR-200 family. Subgroup analysis of OC, LIHC, GC and LUAD based on expression levels and clustering results reduced or even eliminated the heterogeneity of miR-200 family members in predicting patient outcomes. CONCLUSIONS: Our results convincingly demonstrated that the miR-200 family could serve as a prognostic biomarker for cancers mentioned above and has potential value in clinical practice. MiR-200 family as prognostic biomarkers needs to be performed according to different tumor tissues and correlation between members in miR-200 family.


Assuntos
MicroRNAs/metabolismo , Neoplasias/mortalidade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Mineração de Dados , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Prognóstico , Análise de Sobrevida
9.
Results Probl Cell Differ ; 67: 487-529, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31435808

RESUMO

The role of the Golgi apparatus in carcinogenesis still remains unclear. A number of structural and functional cis-, medial-, and trans-Golgi proteins as well as a complexity of metabolic pathways which they mediate may indicate a central role of the Golgi apparatus in the development and progression of cancer. Pleiotropy of cellular function of the Golgi apparatus makes it a "metabolic heart" or a relay station of a cell, which combines multiple signaling pathways involved in carcinogenesis. Therefore, any damage to or structural abnormality of the Golgi apparatus, causing its fragmentation and/or biochemical dysregulation, results in an up- or downregulation of signaling pathways and may in turn promote tumor progression, as well as local nodal and distant metastases. Three alternative or parallel models of spatial and functional Golgi organization within tumor cells were proposed: (1) compacted Golgi structure, (2) normal Golgi structure with its increased activity, and (3) the Golgi fragmentation with ministacks formation. Regardless of the assumed model, the increased activity of oncogenesis initiators and promoters with inhibition of suppressor proteins results in an increased cell motility and migration, increased angiogenesis, significantly activated trafficking kinetics, proliferation, EMT induction, decreased susceptibility to apoptosis-inducing factors, and modulating immune response to tumor cell antigens. Eventually, this will lead to the increased metastatic potential of cancer cells and an increased risk of lymph node and distant metastases. This chapter provided an overview of the current state of knowledge of selected Golgi proteins, their role in cytophysiology as well as potential involvement in tumorigenesis.


Assuntos
Carcinogênese , Complexo de Golgi/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Movimento Celular , Humanos , Transdução de Sinais
10.
Adv Exp Med Biol ; 1152: 173-215, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456184

RESUMO

Cancer is the result of a cell's acquisition of a variety of biological capabilities or 'hallmarks' as outlined by Hanahan and Weinberg. These include sustained proliferative signalling, the ability to evade growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and the ability to invade other tissue and metastasize. More recently, the ability to escape immune destruction has been recognized as another important hallmark of tumours. It is suggested that genome instability and inflammation accelerates the acquisition of a variety of the above hallmarks. Inflammation, is a product of the body's response to tissue damage or pathogen invasion. It is required for tissue repair and host defense, but prolonged inflammation can often be the cause for disease. In a cancer patient, it is often unclear whether inflammation plays a protective or deleterious role in disease progression. Chemotherapy drugs can suppress tumour growth but also induce pathways in tumour cells that have been shown experimentally to support tumour progression or, in other cases, encourage an anti-tumour immune response. Thus, with the goal of better understanding the context under which each of these possible outcomes occurs, recent progress exploring chemotherapy-induced inflammatory cytokine production and the effects of cytokines on drug efficacy in the tumour microenvironment will be reviewed. The implications of chemotherapy on host and tumour cytokine pathways and their effect on the treatment of cancer patients will also be discussed.


Assuntos
Citocinas/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Microambiente Tumoral , Humanos , Neovascularização Patológica , Transdução de Sinais
12.
Life Sci ; 234: 116781, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31430455

RESUMO

Cancer stem cells (CSCs) are a population of self-renewal cells with high tumorigenic potency. CSCs can adopt easily with changes in the nearby milieu, and are more resistant to conventional therapies than other cells within a tumor. CSC resistance can be induced secondary to radio- and chemotherapy, or even after chemotherapy secession. A combination of both intrinsic and extrinsic factors is contributed to CSC-mediated therapy resistance. CSCs represent protective autophagy and efficient cell cycling, along with highly qualified epithelial-mesenchymal transition (EMT) regulators, reactive oxygen species (ROS) scavengers, drug transporters, and anti-apoptotic and DNA repairing systems. In addition, CSCs develop cross-talking and share some characteristics with other cells within the tumor microenvironment (TME) being more intense in higher stage tumors, and thereby sophisticating tumor-targeted therapies. TME, in fact, is a nest for aggravating resistance mechanisms in CSCs. TME is exposed constantly to the nutritional, metabolic and oxygen deprivation; these conditions promote CSC adaptation. This review is aimed to discuss main (intrinsic and extrinsic) mechanisms of CSC resistance and suggest some strategies to revoke this important promoter of therapy failure.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Células-Tronco Neoplásicas/patologia , Animais , Antineoplásicos/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos da radiação , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/efeitos da radiação , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/efeitos da radiação
13.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 36(4): 691-695, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31441273

RESUMO

Tumor cells have unique energy metabolism phenomena, namely high glucose absorption, aerobic glycolysis and high lactic acid production, which are characterized by down-regulation of related proteins involved in oxidative metabolism in tumor cells, and up-regulation of glucose transporters and monocarboxylate transporters. Studies have shown that drugs that target tumor cell glucose metabolism have the ability to selectively kill tumor cells, bringing new hope for tumor treatment. Tumor stem cells are considered to be the root cause of tumor recurrence, metastasis and poor prognosis, and their energy metabolism characteristics have not yet been agreed. Studies have shown that reversing the energy metabolism of tumor stem cells can increase their chemosensitivity. This article reviews recent studies on tumor and tumor stem cell glucose metabolism and the opportunities and challenges of tumor treatment through targeting glucose metabolism, which might provide new ideas and opportunities for clinical tumor therapy.


Assuntos
Metabolismo Energético , Glicólise , Neoplasias/metabolismo , Células-Tronco Neoplásicas/metabolismo , Glucose/metabolismo , Humanos , Ácido Láctico/metabolismo
14.
Anticancer Res ; 39(7): 3341-3345, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262854

RESUMO

In early 2000, the term 'targeted therapy' became popular and was used to indicate all types of tyrosine kinase inhibitors (TKI). However, the term targeted therapy had been used much earlier. Targeting tumor metabolism was already considered as targeted therapy, with methotrexate and 5-fluorouracil as the most successful examples. Hormone therapy is another successful type of targeted therapy. Imatinib was the first TKI for the fusion protein BCR-ABL and represented a breakthrough in the treatment of chronic myeloid leukemia. Many other TKIs have been introduced into the clinic, but most were less specific and had multiple targets, and therefore, by definition, not targeted. However, with the introduction of TKIs developed specifically against mutations in the active site of a TK, more truly targeted TKI have been approved, such as new anaplastic lymphoma kinase - echinoderm microtubule-associated protein-like 4 (ALK-EML4) inhibitors and the epidermal growth factor-T790M-targeted osimertinib. This article summarizes the content of the Burger-Kelland award lecture given by the Author in February 2019 during the 40th EORTC-PAMM Group meeting in Verona, Italy and reviews the development of various targeted agents.


Assuntos
Antineoplásicos/uso terapêutico , Terapia de Alvo Molecular , Neoplasias/terapia , Humanos , Neoplasias/metabolismo , Proteínas Tirosina Quinases/metabolismo
15.
Anticancer Res ; 39(7): 3347-3351, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262855

RESUMO

BS69 is encoded by a gene located on chromosome 10, in a region frequently deleted in human cancers and BS69 expression is often down-regulated in human cancers. In addition, BS69 acts as a transcriptional repressor via interaction with transcriptional factors associated with tumorigenesis, such as cellular homolog of the avian myeloblastosis viral oncoprotein, v-ets erythroblastosis virus E26 oncogene homolog 2 oncoprotein, MYC-associated protein X gene-associated protein. Overexpression of BS69 can suppress proliferation of osteosarcoma, breast cancer and glioma cells in vitro; and inhibits tumor growth in xenograft models. Therefore, BS69 may act as a tumor suppressor, and may be a new target for cancer therapy. However, BS69 down-regulation has been found to be involved in cellular senescence and is associated with the reversion of the malignant phenotype of breast cancer cells. Therefore, additional studies are necessary to clarify the role of BS69 in tumor development.


Assuntos
Proteínas de Transporte/metabolismo , Neoplasias/metabolismo , Animais , Senescência Celular , Humanos , Proteínas Supressoras de Tumor/metabolismo
16.
Anticancer Res ; 39(7): 3353-3363, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262856

RESUMO

Vitamin D, or more precisely its active metabolite calcitriol (1,25-(OH)2D3), plays a fundamental role in bone metabolism and differentiation as well as in intestinal absorption of calcium and regulation of calcium-phosphate metabolism. Recent decades have brought about the discovery of the role of calcitriol in processes regulating cell differentiation, proliferation, angiogenesis and apoptosis. This creates the potential for numerous therapeutic applications of vitamin D in diseases associated with autoaggressive immune responses or in cancer. This study presents selected issues regarding current knowledge of the anti-cancer mechanisms of vitamin D.


Assuntos
Neoplasias , Vitamina D/fisiologia , Vitaminas/fisiologia , Animais , Apoptose , Ciclo Celular , Proteínas Hedgehog/metabolismo , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Neovascularização Patológica , Receptores de Calcitriol/fisiologia , Proteína Supressora de Tumor p53/metabolismo , Raios Ultravioleta/efeitos adversos
17.
Anticancer Res ; 39(7): 3379-3384, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262859

RESUMO

BACKGROUND/AIM: PTP1B tyrosine phosphatase is involved in the development of many types of cancers, such as breast cancer or lung cancer. Therefore, PTP1B is a promising target for anticancer therapy. The purpose of this review was to present the studies on selected PTP1B inhibitors as a possible treatment and describe the latest trends of current research in this field. MATERIALS AND METHODS: This literature review was performed using the PubMed database and the analysis of previous research studies of our Department. RESULTS: Recent studies have shown that PTP1B, due to its implication in oncogenic transformation, represents a promising drug target. CONCLUSION: The selected compounds that are effective PTP1B inhibitors can be considered a promising anticancer treatment, both as monotherapy and in combination with other anticancer drugs.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Antineoplásicos/farmacologia , Humanos , Neoplasias/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Quinases da Família src/metabolismo
18.
Anticancer Res ; 39(7): 3385-3394, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262860

RESUMO

Overexpression of acyl-coenzyme A:cholesterol acyltransferase (ACAT) results in increased cholesteryl ester levels and has been involved in a variety of cancer types. As a consequence, cholesterol metabolism has raised interest as a potential target for cancer treatment. Inhibition of ACAT results in suppression of proliferation in a range of cancer cell types both in vitro and in vivo. The exact mechanism of this phenomenon is being investigated, and the most important findings are presented in this review.


Assuntos
Neoplasias/tratamento farmacológico , Esterol O-Aciltransferase/antagonistas & inibidores , Animais , Humanos , Neoplasias/metabolismo , Esterol O-Aciltransferase/metabolismo
19.
Anticancer Res ; 39(7): 3419-3422, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262864

RESUMO

As part of the Pharmacology & Molecular Mechanisms (PAMM) Group, European Organization for Research and Treatment on Cancer (EORTC) 2019 winter Meeting Educational sessions, special focus has been placed on strategies to be undertaken to reduce the attrition rate when developing immune-oncology drugs. Immune checkpoint inhibitors have been game-changing drugs in several settings over the past decade such as melanoma and lung cancer. However, during the last years a rising number of studies failing to further improve clinical outcome in patients with cancer was recorded. Extensive pharmacometrics such as pharmacokinetics/pharmacodynamics modeling support should help to overcome the current glass ceiling that has apparently been reached with immuno-oncology drugs (IOD). In particular, it should help in the issue of setting up combinatorial regimen (i.e. combining immune checkpoint inhibitors with cytotoxics, anti-angiogenesis or targeted therapies) that can no longer be addressed when following standard trial-and-error approaches, but rather by using mathematical-derived algorithms as decision-making tools by investigators for rational design. In routine clinical setting, developing therapeutic drug monitoring of immune checkpoint inhibitors with adaptive dosing strategies has been a long-neglected strategy. Still, substantial improvements might be achieved using dedicated tools for precision medicine and personalized medicine in immunotherapy.


Assuntos
Antineoplásicos Imunológicos/farmacocinética , Animais , Antineoplásicos Imunológicos/uso terapêutico , Humanos , Imunoterapia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Farmacologia Clínica/métodos
20.
Anticancer Res ; 39(7): 3443-3451, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262868

RESUMO

BACKGROUND/AIM: This study aimed to investigate aclarubicin (ACR)-induced oxidative DNA damage and apoptosis. MATERIALS AND METHODS: ACR-induced apoptosis was analyzed using HL-60 leukemia cells and HP100 cells, hydrogen peroxide (H2O2)-resistant cells derived from HL-60 cells. ACR-induced DNA damage was analyzed using plasmid DNA. RESULTS: HL-60 cells were more sensitive to ACR than HP100 cells. In HP100 cells, DNA ladder formation and caspase-3/7 activity induced by ACR were suppressed or delayed in comparison to those in HL-60 cells. ACR-induced DNA damage occurred in the presence of Cu(II), and scavenger experiments showed that the reactive species causing DNA damage appeared to be generated from H2O2 and Cu(I). Moreover, we detected intracellular Cu(I) induced by ACR in HL-60 cells, using CopperGREEN™, a fluorescent probe for detection of Cu(I) ion specifically. CONCLUSION: ACR-induced DNA damage and apoptosis can be accounted for by the involvement of H2O2 and Cu(I).


Assuntos
Aclarubicina/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Apoptose/efeitos dos fármacos , Cobre/farmacologia , Dano ao DNA , Peróxido de Hidrogênio/metabolismo , Linhagem Celular Tumoral , Humanos , Neoplasias/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA