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1.
Gene ; 715: 144005, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31376410

RESUMO

Members of the highly conserved pleiotropic CK1 family of serine/threonine-specific kinases are tightly regulated in the cell and play crucial regulatory roles in multiple cellular processes from protozoa to human. Since their dysregulation as well as mutations within their coding regions contribute to the development of various different pathologies, including cancer and neurodegenerative diseases, they have become interesting new drug targets within the last decade. However, to develop optimized CK1 isoform-specific therapeutics in personalized therapy concepts, a detailed knowledge of the regulation and functions of the different CK1 isoforms, their various splice variants and orthologs is mandatory. In this review we will focus on the stress-induced CK1 isoform delta (CK1δ), thereby addressing its regulation, physiological functions, the consequences of its deregulation for the development and progression of diseases, and its potential as therapeutic drug target.


Assuntos
Caseína Quinase Idelta/química , Caseína Quinase Idelta/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias/enzimologia , Transdução de Sinais , Animais , Caseína Quinase Idelta/antagonistas & inibidores , Caseína Quinase Idelta/genética , Sistemas de Liberação de Medicamentos/métodos , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/química , Isoenzimas/genética , Isoenzimas/metabolismo , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Relação Estrutura-Atividade
2.
Anticancer Res ; 39(8): 3981-3989, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366479

RESUMO

Uterine sarcomas are rare but very aggressive. Uterine myomas, on the other hand, are the most common benign tumors of the uterus. Currently there is no diagnostic technique available to distinguish them with certainty. This study aimed to summarize the published literature concerning protein-based biomarkers in the peripheral blood that can assist in this difficult differential diagnosis. In total, 48 articles, published between 1990 and 2017, were included. Most studies (n=37) concerned soft tissue sarcomas, while 11 discussed uterine sarcomas specifically. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukins (IL), cancer antigen 125 (CA 125), lactate dehydrogenase, gangliosides (LDH) and growth differentiation factor 15 (GDF-15) are the most studied proteins in soft tissue sarcomas, including uterine sarcomas. Future research on improving sarcoma diagnosis should include these proteins.


Assuntos
Leiomioma/sangue , Neoplasias/sangue , Sarcoma/sangue , Neoplasias Uterinas/sangue , Biomarcadores Tumorais/sangue , Diferenciação Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Leiomioma/patologia , Neoplasias Musculares/sangue , Neoplasias Musculares/patologia , Neoplasias/patologia , Sarcoma/patologia , Neoplasias Uterinas/patologia
3.
Anticancer Res ; 39(8): 4273-4277, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366517

RESUMO

BACKGROUND/AIM: For treatment of brain metastases, a patient's survival prognosis should be considered. Existing survival scores appear complex and require complete tumor staging. For many patients, a faster and simpler tool would be helpful. PATIENTS AND METHODS: This retrospective study investigated the prognostic value of the number of pre-treatment symptoms plus eight other factors on survival of patients irradiated for brain metastases. Other factors included whole-brain radiotherapy (WBRT) regimen, age, gender, performance score, primary tumor type, number of brain metastases, extracranial metastases, and interval between cancer diagnosis and WBRT. RESULTS: The number of symptoms (p=0.002) and all other factors were significantly associated with survival on univariate analyses. On multivariate analysis, all factors but the number of symptoms (p=0.47) and primary tumor type (p=0.48) were significant. CONCLUSION: Since the number of symptoms was not an independent predictor of survival, it cannot replace existing scoring tools and may only serve for orientation.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias/radioterapia , Prognóstico , Idoso , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Irradiação Craniana/efeitos adversos , Feminino , Humanos , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/classificação , Neoplasias/patologia
4.
Anticancer Res ; 39(8): 4385-4391, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366534

RESUMO

BACKGROUND/AIM: To identify the reason for age and gender differences in cancer risk. PATIENTS AND METHODS: Age-standardized incidence rates for 17 cancer types were compared between genders in 50 populations. For each cancer type, the female/male rate ratio was listed in fixed order of population. Correlation coefficients were calculated between these lists in all pairwise combinations. For each population, the female/male rate ratio was listed in fixed order of cancer. Correlation coefficients were calculated between lists in all pairwise combinations. RESULTS: Only four pairwise combinations for cancer type gave a correlation coefficient greater than 0.700. For each population, the lowest correlation coefficient was 0.950. CONCLUSION: The reason for the differences in risk of cancer varies with each type of cancer, but remains fixed in all populations. It is suspected that species-specific genes control stem cell telomere dynamics in a fixed strategy at rates that vary among tissues and between genders.


Assuntos
Fatores Etários , Neoplasias/epidemiologia , Fatores Sexuais , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinogênese/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/classificação , Neoplasias/genética , Neoplasias/patologia , Fatores de Risco
5.
Anticancer Res ; 39(8): 4415-4421, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366539

RESUMO

BACKGROUND/AIM: The aim of this study was to evaluate the association between the frequency of daily tooth brushing and the development of any type of malignancy. PATIENTS AND METHODS: We conducted a retrospective longitudinal study, including all adult participants who underwent health check-ups. Primary outcome was the development of any type of malignancy, compared to the frequency of daily tooth brushing, adjusting for potential confounders. RESULTS: A total of 71,449 participants were included and 5,025 participants developed a certain type of malignancy. Not brushing everyday (Odds Ratio (OR)=1.52, 95% Confidence Interval (CI)=1.03-2.25) and brushing once a day (OR=1.25, 95%CI=1.16-1.35) had significantly higher ORs for the outcome than brushing after every meal, although those who brushed once to twice a day had significantly lower OR (OR=0.78, 95%CI=0.72-0.83). CONCLUSION: As the frequency of daily tooth brushing increased, except for brushing after every meal, the development of all types of malignancies decreased.


Assuntos
Neoplasias/epidemiologia , Escovação Dentária , Feminino , Humanos , Masculino , Neoplasias/classificação , Neoplasias/patologia , Estudos Retrospectivos , Inquéritos e Questionários
6.
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
7.
J Cancer Res Clin Oncol ; 145(9): 2199-2209, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31309302

RESUMO

PURPOSE: Radiofrequency (RF) ablation therapy is of great interest in cancer therapy as it is non-ionizing radiation and can effectively penetrate into the tissue. However, the current RF ablation technique is invasive that requires RF probe insertion into the tissue and generates a non-specific heating. Recently, RF-responsive nanomaterials such as gold nanoparticles (AuNPs) and iron oxide nanoparticles (IONPs) have led to tremendous progress in this area. They have been found to be able to absorb the RF field and induce a localized heating within the target, thereby affording a non-invasive and tumor-specific RF ablation strategy. In the present study, for the first time, we used a hybrid core-shell nanostructure comprising IONPs as the core and AuNPs as the shell (IO@Au) for targeted RF ablation therapy. Due to the magnetic core, the nanohybrid can be directed toward the tumor through a magnet. Moreover, IONPs enable the nanohybrid to be used as a magnetic resonance imaging (MRI) contrast agent. RESULTS: In vitro cytotoxicity experiment showed that the combination of IO@Au and 13.56-MHz RF field significantly reduced the viability of cancer cells. Next, during an in vivo experiment, we demonstrated that magnetically targeting of IO@Au to the tumor and subsequent RF exposure dramatically suppressed the tumor growth. CONCLUSION: Therefore, the integration of targeting, imaging, and therapeutic performances into IO@Au nanohybrid could afford the promise to improve the effectiveness of RF ablation therapy.


Assuntos
Ablação por Cateter/métodos , Compostos Férricos/química , Ouro/química , Hipertermia Induzida/métodos , Nanopartículas de Magnetita/uso terapêutico , Neoplasias/cirurgia , Ablação por Radiofrequência/métodos , Animais , Compostos Férricos/uso terapêutico , Ouro/uso terapêutico , Imagem por Ressonância Magnética/métodos , Nanopartículas de Magnetita/química , Masculino , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Terapia de Alvo Molecular/métodos , Nanocompostos/química , Nanocompostos/uso terapêutico , Nanoconchas/química , Nanoconchas/uso terapêutico , Neoplasias/patologia , Células Tumorais Cultivadas
8.
J Enzyme Inhib Med Chem ; 34(1): 1321-1346, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31328585

RESUMO

For over half a century, the carbazole skeleton has been the key structural motif of many biologically active compounds including natural and synthetic products. Carbazoles have taken an important part in all the existing anti-cancer drugs because of their discovery from a large variety of organisms, including bacteria, fungi, plants, and animals. In this article, we specifically explored the literature from 2012 to 2018 on the anti-tumour activities reported to carbazole derivatives and we have critically collected the most significant data. The most described carbazole anti-tumour agents were classified according to their structure, starting from the tricyclic-carbazole motif to fused tetra-, penta-, hexa- and heptacyclic carbazoles. To date, three derivatives are available on the market and approved in cancer therapy.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Carbazóis/química , Carbazóis/farmacologia , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Humanos , Estrutura Molecular , Neoplasias/patologia
9.
Medicine (Baltimore) ; 98(27): e16319, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277176

RESUMO

BACKGROUND: Cognitive behavioral therapy (CBT) has been widely used in pediatric cancer patients to promote psychological adjustment (PA). Considering the diversity of region and culture in China, its effect in Chinese population is not well defined. Therefore, our study is to explore the effect of CBT on improving PA in Chinese pediatric cancer patients receiving chemotherapy. METHODS: One hundred four Chinese pediatric cancer patients receiving chemotherapy were divided into CBT group and control group randomly and equally. The resilience and negative mood were applied to evaluate the ability of psychological adjustment (PA). The Conner-Davidson Resilience Scale (CD-RISC) and depression anxiety stress scale (DASS) were employed to measure resilience and negative mood before and after intervention. The SPSS 22.0 software was used to analyze data. RESULTS: Prior to the intervention, the ability of psychological adjustment between 2 groups showed no significant difference (P > .05 for all). After intervention, the total CD-RISC score was significantly higher (56.09 ± 7.29 vs 44.75 ± 5.40), whereas the scores of depression (4.57 ± 2.94 vs 7.25 ±â€Š4.25), anxiety (5.83 ±â€Š3.07 vs 8.66 ±â€Š4.92), stress (7.51 ±â€Š4.33 vs 11.17 ±â€Š4.25) were obviously lower in CBT group than those in the control group (P < .05 for all). Moreover, the decline of negative mood score in Yolk sac tumor children was the most evident in CBT group. While the resilience changes of cancer children in stage III was most obvious. CONCLUSIONS: CBT can effectively help Chinese pediatric cancer patients modify distorted cognition to have a positive attitude towards cancer and chemotherapy. This treatment enhances resilience and relieves negative mood, which results in good psychological adjustment ability, especially in Yolk sac tumor and stage III. It has a beneficial effect on better treatment cooperation and high long-term quality of life.


Assuntos
Grupo com Ancestrais do Continente Asiático , Terapia Cognitivo-Comportamental , Ajustamento Emocional , Neoplasias/psicologia , Neoplasias/terapia , Resiliência Psicológica , Adolescente , Afeto , Antineoplásicos/uso terapêutico , Criança , China , Feminino , Humanos , Masculino , Neoplasias/patologia
10.
Medicine (Baltimore) ; 98(28): e16356, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305429

RESUMO

BACKGROUND: The prognostic significance of S100A14 for survival of cancer patients remains controversial. Therefore, we conducted this meta-analysis to explore the association between S100A14 expression and cancer prognosis. METHOD: Eligible studies were identified by searching the online databases Pubmed and EMBASE up to August 2018. Odds ratios (ORs) with 95% confidence intervals (CIs) severed as the summarized statistics for clinicopathological assessments and hazard ratios (HRs) with 95% CIs were calculated to clarify the correlation between S100A14 expression and prognosis of different cancers. RESULTS: A total of 11 studies with 1651 cancer patients were enrolled. The results indicated that S100A14 expression was not significantly associated with overall survival (OS) in total various cancers (HR = 1.54, 95% CI:0.89-2.67, P = .121). Further subgroup analysis stratified by tumor type showed that elevated S100A14 expression was associated with poor OS in breast cancer (HR = 3.66, 95% CI: 1.75-7.62, P < .001) and in ovarian cancer patients (HR = 3.78, 95%CI: 1.63-8.73, P = .002). Interestingly, high S100A14 expression was correlated with poor tumor differentiation (OR = 2.51, 95% CI: 1.52-4.13, P < .001). However, there were no significant correlations between S100A14 expression and other clinicopathologic characteristics. Begg funnel plot and Egger test showed that no publication bias was detected. CONCLUSIONS: Our meta-analysis suggests that S100A14 overexpression might be a predictive biomarker for poor prognosis in patients with breast cancer and ovarian cancer. Large-scale studies are required to confirm these results.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Biomarcadores Tumorais/metabolismo , Humanos , Prognóstico
11.
Expert Opin Ther Pat ; 29(8): 595-603, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31280615

RESUMO

Introduction: As a key element in arguably the most important pathway MAPK signaling, the BRAF kinase gives rise to severe diseases including cancers when pathologically activated. Extensive research on BRAFi (BRAF inhibitor) has been carried out to profile the characters for optimized agents and to elaborate the therapeutic strategies for the related cancer treatment. Areas covered: This review gives an overview of recently approved BRAF agents on function mode, therapeutic efficacy, and deficiency, based on which current challenges and corresponding strategies were presented. New entities as BRAFi for medical purpose in patent literature during the period 2013-2018 were also briefly introduced. Expert opinion: With the disclosure of paradox-breaker BRAFi PLX7904 crystal in complex with BRAF, the rational design for next-generation BRAFi is becoming ever more feasible. Accompanying therapeutic strategies in BRAFi elaboration may also provide flexible choice in the future 'personal medicine'. Further digging in the greatly enriched BRAFi pool will greatly benefit the drug design processes such as FBDD- and SBDD-driven development.


Assuntos
Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Animais , Antineoplásicos/farmacologia , Desenho de Drogas , Compostos Heterocíclicos com 2 Anéis/farmacologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neoplasias/patologia , Patentes como Assunto , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/metabolismo , Sulfonamidas/farmacologia
12.
Expert Opin Ther Pat ; 29(8): 643-651, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31291131

RESUMO

Introduction: LAG-3 is checkpoint inhibitor in cancer that coordinates the downregulation of the proliferation of antigen-specific lymphocytes. There is a great need to discover and develop new therapies focused on inhibiting the action of LAG-3 and consequently improving the immune response in the various types of cancer. Areas covered: The patent literature reveals novel therapies, which provide information on cancer therapies. The authors used the patent databases of the six main patent offices of the world: United States Patent and Trademark Office, European Patent Office, World Intellectual Property Organization, Japan Patent Office, State Intellectual Property Office of China and Korean Intellectual Property Office, to generate a detailed landscape of patents and patent applications of active companies related to LAG-3 inhibitors. Specific patents have been grouped into innovative patents and adopting patents. Expert opinion: There is a continuing development of LAG-3 inhibitors, and these inhibitors are being used in combination with other cancer treatment schemes, for example, antibodies against PD-1, PD-L1, and CTLA-4. Immutep and IO Therapeutics were the leaders in generating innovator patents, followed by Gustave Roussy Institute, and Applied Research Systems ARS. Dana-Farber Cancer Institute was the leader in the generation of adopter patents, followed by Novartis .


Assuntos
Antígenos CD/efeitos dos fármacos , Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Animais , Anticorpos/administração & dosagem , Antígenos CD/imunologia , Antígenos CD/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Desenvolvimento de Medicamentos/métodos , Humanos , Neoplasias/imunologia , Neoplasias/patologia , Patentes como Assunto
13.
Expert Opin Ther Pat ; 29(8): 605-621, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31298602

RESUMO

Introduction: Retinoid X receptor (RXR) agonists have a limited role in cancer therapy with bexarotene and alitretinoin as approved drugs but their use is limited by adverse effects. Several evidence from in vitro, in vivo, and small clinical studies points to various further potential applications of RXR ligands in neurodegenerative and inflammatory diseases. Areas covered: The authors review known RXR ligand classes with their key structure-activity relationships and recent reports on pharmacological effects of RXR modulation. Based on these aspects, the authors evaluate recent patents claiming novel RXR ligands or their use. Expert opinion: While the use of RXR modulators has been claimed in several novel and promising indications, little progress has been made in the development of innovative rexinoids with improved (subtype-)selectivity. Next-generation RXR modulators that selectively target the RXR subtypes for individual indications may be required to exhaustively exploit the therapeutic potential of RXRs.


Assuntos
Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Receptores X Retinoide/efeitos dos fármacos , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/química , Desenvolvimento de Medicamentos/métodos , Humanos , Ligantes , Neoplasias/patologia , Patentes como Assunto , Receptores X Retinoide/metabolismo , Relação Estrutura-Atividade
14.
Expert Opin Ther Pat ; 29(8): 623-641, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31353978

RESUMO

Introduction: About 20 patents have been published from 2013 to 2018 for developing advanced cancer therapeutics by targeting tubulin polymerization. Currently, there are several tubulin inhibitors that are in the drug development pipeline for various cancers alone or in combination including antibody-conjugated drugs (ACDs). Areas covered: Important patents focusing on the development of tubulin inhibitors published from 2013 to 2018 are covered. This review mainly focuses on the tubulin inhibitors that are being synthesized and studied in cancer research along with their structures and their phases of development in preclinical and clinical research. Expert opinion: Regulation of microtubules is important for cell division, cell motility, intracellular transport, and cell shape maintenance. Modulating its activity proved to be very effective in various diseases including different types of cancers. Microtubules are composed of two units, namely, alpha and beta-tubulin, and modifications at these ends affect both its functions and dynamics. A number of compounds that have been designed and synthesized bearing various heterocyclic scaffolds have been proven to modulate its activity and have emerged as potent tubulin inhibitors. This encourages more to study microtubules in order to find a variety of novel, potent compounds as anticancer drugs.


Assuntos
Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Moduladores de Tubulina/farmacologia , Animais , Antineoplásicos/química , Desenho de Drogas , Desenvolvimento de Medicamentos/métodos , Humanos , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Neoplasias/patologia , Patentes como Assunto , Relação Estrutura-Atividade , Tubulina (Proteína)/efeitos dos fármacos , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/química
15.
Expert Opin Investig Drugs ; 28(8): 695-708, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31359805

RESUMO

Introduction: Immunotherapy has revolutionized the treatment of cancer. Given this growing success, at the same time, there are significant limitations and unanswered questions concerning response rates, duration of therapy, why some patients respond and others do not, and if combining different immune-agents would overcome this lack of response, increase the chance of success and postpone acquired resistance. Areas covered: The comprehension of how to properly modulate the immune pathways, the molecular and the immunological bases of the disease, will be fundamental to guide the development of therapeutic interventions and combinations that will be more suitable for treatment of cancer patients. In this review, we discuss the strategies of immunotherapy combinations in order to develop more effective immunotherapy programs, with a particular focus on melanoma and renal cancer patients, as well as the combination of immunotherapy and chemotherapy. Expert Opinion: Given the complexity of immune activation, combinatorial approaches are needed, and due to the considerable variability in tumor biology across patients and tumor types, patient selection and biomarkers need to be further explored. In summary, combined therapies have shown promising success, but additional and continuous research to identify the safety, efficacy, optimal combination, dosage and timing are still required.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Imunoterapia/métodos , Neoplasias/terapia , Animais , Antineoplásicos Imunológicos/imunologia , Antineoplásicos Imunológicos/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Humanos , Neoplasias Renais/imunologia , Neoplasias Renais/terapia , Melanoma/imunologia , Melanoma/terapia , Neoplasias/imunologia , Neoplasias/patologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia
16.
J Cancer Res Clin Oncol ; 145(8): 2141-2148, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31278473

RESUMO

PURPOSE: Many cancer patients (PTS) suffer from somatic or non-somatic symptoms. Studies have shown positive effects of music intervention (MI) on aspects of quality of life or symptom management. METHODS: Since there are poor data available about patient's needs regarding the use of MI as an adjunct to cancer treatment, n = 548 tumor PTS were polled anonymously at the outpatient department of the University Hospital Mannheim Tumor Center using a self-designed questionnaire. Univariate and multivariate analyses were performed. RESULTS: 486 data sets were eligible for analysis. 240 of the PTS were male and median age was 63 years. 38% had metastatic disease. 81% (n = 386) were currently receiving anti-tumor treatment. The majority of the PTS stated to have somatic symptoms. However, some of the PTS reported non-somatic symptoms like anxiety, loneliness, and depression. N = 187 (40%) of the PTS reported interest in complementary MI. In the univariate and multivariate analyses, especially PTS with non-somatic complaints and PTS, actively playing or making music showed significantly more interest in complementary MI, hoping for a relaxing therapeutic effect. PTS who play instruments would prefer more active forms of MI. CONCLUSION: 40% of PTS reported interest in additional MI during cancer treatment. PTS with non-somatic symptoms as well as patients affine to music might benefit from the use of MI potentially reducing their symptom burden. The inconsistent and heterogeneous data from randomized trials underline the importance of systematic research approaches with more relevant and standardized endpoints.


Assuntos
Terapias Complementares/métodos , Musicoterapia , Música , Neoplasias/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/complicações , Ansiedade/epidemiologia , Ansiedade/psicologia , Ansiedade/terapia , Terapias Complementares/psicologia , Terapias Complementares/estatística & dados numéricos , Depressão/complicações , Depressão/epidemiologia , Depressão/psicologia , Depressão/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Música/psicologia , Neoplasias/epidemiologia , Neoplasias/patologia , Neoplasias/psicologia , Qualidade de Vida , Estresse Psicológico/epidemiologia , Estresse Psicológico/etiologia , Estresse Psicológico/terapia , Inquéritos e Questionários , Adulto Jovem
17.
Expert Opin Ther Pat ; 29(7): 481-485, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31216214

RESUMO

Introduction: OX40 is checkpoint inhibitor in cancer that coordinates the downregulation of the proliferation of antigen-specific lymphocytes. There is a great need to discover and develop new therapies focused on inhibiting the action of OX40 and consequently improving the immune response in the various types of cancer. Authors of patent US2018256711A1 propose a method to eradicate cancer that utilizes anti-OX40 agonist antibody in combination with anti-PD-L1 antagonist antibody. Areas covered: Patent US2018256711A1 describes a method of cancer combinatorial treatment consisting of the utilization of a pharmaceutical cocktail containing anti-OX40 and an anti-PD-L1 antibody. Expert opinion: The results of the clinical trials only support trials regarding the tolerability of combinatorial therapy, even when the objectives of determining the safety and pharmacokinetics of the treatment are proposed.


Assuntos
Antígeno B7-H1/antagonistas & inibidores , Neoplasias/terapia , Receptores OX40/agonistas , Animais , Anticorpos/administração & dosagem , Anticorpos/imunologia , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Neoplasias/imunologia , Neoplasias/patologia , Patentes como Assunto , Resultado do Tratamento
18.
Nat Immunol ; 20(7): 835-851, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31160797

RESUMO

How tumor cells genetically lose antigenicity and evade immune checkpoints remains largely elusive. We report that tissue-specific expression of the human long noncoding RNA LINK-A in mouse mammary glands initiates metastatic mammary gland tumors, which phenotypically resemble human triple-negative breast cancer (TNBC). LINK-A expression facilitated crosstalk between phosphatidylinositol-(3,4,5)-trisphosphate and inhibitory G-protein-coupled receptor (GPCR) pathways, attenuating protein kinase A-mediated phosphorylation of the E3 ubiquitin ligase TRIM71. Consequently, LINK-A expression enhanced K48-polyubiquitination-mediated degradation of the antigen peptide-loading complex (PLC) and intrinsic tumor suppressors Rb and p53. Treatment with LINK-A locked nucleic acids or GPCR antagonists stabilized the PLC components, Rb and p53, and sensitized mammary gland tumors to immune checkpoint blockers. Patients with programmed ccll death protein-1(PD-1) blockade-resistant TNBC exhibited elevated LINK-A levels and downregulated PLC components. Hence we demonstrate lncRNA-dependent downregulation of antigenicity and intrinsic tumor suppression, which provides the basis for developing combinational immunotherapy treatment regimens and early TNBC prevention.


Assuntos
Apresentação do Antígeno/imunologia , Regulação Neoplásica da Expressão Gênica , Neoplasias/genética , Neoplasias/imunologia , Oncogenes , RNA Longo não Codificante/genética , Evasão Tumoral/genética , Evasão Tumoral/imunologia , Adenoma/genética , Adenoma/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Humanos , Camundongos , Neoplasias/metabolismo , Neoplasias/patologia , Fosforilação , Receptores Acoplados a Proteínas-G/antagonistas & inibidores , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Proteína Supressora de Tumor p53/metabolismo , Ubiquitinação , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Nat Commun ; 10(1): 2416, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31186412

RESUMO

Cancer response to immunotherapy depends on the infiltration of CD8+ T cells and the presence of tumor-associated macrophages within tumors. Still, little is known about the determinants of these factors. We show that LIF assumes a crucial role in the regulation of CD8+ T cell tumor infiltration, while promoting the presence of protumoral tumor-associated macrophages. We observe that the blockade of LIF in tumors expressing high levels of LIF decreases CD206, CD163 and CCL2 and induces CXCL9 expression in tumor-associated macrophages. The blockade of LIF releases the epigenetic silencing of CXCL9 triggering CD8+ T cell tumor infiltration. The combination of LIF neutralizing antibodies with the inhibition of the PD1 immune checkpoint promotes tumor regression, immunological memory and an increase in overall survival.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Quimiocina CXCL9/metabolismo , Fator Inibidor de Leucemia/imunologia , Macrófagos/imunologia , Neoplasias/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Animais , Anticorpos Neutralizantes/farmacologia , Linfócitos T CD8-Positivos/metabolismo , Quimiocina CCL2/metabolismo , Epigênese Genética , Humanos , Memória Imunológica , Fator Inibidor de Leucemia/antagonistas & inibidores , Fator Inibidor de Leucemia/metabolismo , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos SCID , Transplante de Neoplasias , Neoplasias/imunologia , Neoplasias/patologia , Receptor de Morte Celular Programada 1/imunologia , Microambiente Tumoral/imunologia
20.
Cancer Immunol Immunother ; 68(7): 1039-1058, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31165204

RESUMO

The emergence of immunotherapy has revolutionized medical oncology with unprecedented advances in cancer treatment over the past two decades. However, a major obstacle in cancer immunotherapy is identifying appropriate tumor-specific antigens to make targeted therapy achievable with fewer normal cells being impaired. The similarity between placentation and tumor development and growth has inspired many investigators to discover antigens for effective immunotherapy of cancers. Placenta-specific 1 (PLAC1) is one of the recently discovered placental antigens with limited normal tissue expression and fundamental roles in placental function and development. There is a growing body of evidence showing that PLAC1 is frequently activated in a wide variety of cancer types and promotes cancer progression. Based on the restricted expression of PLAC1 in testis, placenta and a wide variety of cancers, we have designated this molecule with new terminology, cancer-testis-placenta (CTP) antigen, a feature that PLAC1 shares with many other cancer testis antigens. Recent reports from our lab provide compelling evidence on the preferential expression of PLAC1 in prostate cancer and its potential utility in prostate cancer immunotherapy. PLAC1 may be regarded as a potential CTP antigen for targeted cancer immunotherapy based on the available data on its promoting function in cancer development and also its expression in cancers of different histological origin. In this review, we will summarize current data on PLAC1 with emphasis on its association with cancer development and immunotherapy.


Assuntos
Antígenos de Neoplasias/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Neoplasias/terapia , Proteínas da Gravidez/antagonistas & inibidores , Antígenos de Neoplasias/metabolismo , Antineoplásicos Imunológicos/farmacologia , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Progressão da Doença , Feminino , Humanos , Imunoterapia/métodos , Masculino , Terapia de Alvo Molecular/métodos , Neoplasias/imunologia , Neoplasias/patologia , Placenta/patologia , Gravidez , Proteínas da Gravidez/imunologia , Proteínas da Gravidez/metabolismo , Testículo/patologia
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