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1.
Anticancer Res ; 39(10): 5261-5284, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570422

RESUMO

Natural products (NPs) are useful sources of bioactive compounds and play important roles in the development and discovery of new drugs for diverse human diseases. Most natural products originate from terrestrial species, but diverse marine organisms are another source of new agents for cancer therapy. Natural products derived from marine organisms show diverse pharmacological activities via bioactive secondary metabolites. They regulate biological activities, such as cell proliferation, cell viability, induction of ROS production, ER stress, and apoptosis via modulation of cellular mechanisms in many cancers. Many natural products isolated from marine species require further study to elucidate the efficacy of their biological activity and anticancer effects. In this review, we summarize the biological properties and anticancer effects of diverse natural products extracted from marine organisms and their roles in tumor therapy.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Organismos Aquáticos/química , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Humanos
2.
Anticancer Res ; 39(10): 5285-5296, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570423

RESUMO

Triple-negative breast cancer (TNBC) is characterized by a lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) and unfortunately is not associated with good prognosis. Treatment of breast cancer mainly depends on chemotherapy, due to the lack of specifically approved targeted therapies for TNBC. It is of paramount importance to find new therapeutic approaches, as resistance to chemotherapy frequently occurs. Herein, we present clinical studies published within the last five years, in order to reveal possible targeted therapies against TNBC. We aimed to discuss factors against TNBC, such as tyrosine kinase inhibitors, anti-androgens, poly ADP-ribose polymerase-1 (PARP-1) inhibitors, anti-angiogenic factors, immune checkpoints and histone deacetylase inhibitors (HDACI). Furthermore, the PI3K/AKT/mTOR pathway seems to be a promising field for the development of new anti-TNBC targeted therapies. Data from 18 clinical trials with patients suffering from TNBC were summarized and presented descriptively.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Ensaios Clínicos como Assunto , Feminino , Humanos , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/metabolismo , Adulto Jovem
3.
Anticancer Res ; 39(10): 5297-5310, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570424

RESUMO

BACKGROUND/AIM: Low-molecular weight heparins (LMWHs) may possess putative antitumoral properties; however, the underlying mechanism(s) remains elusive. We evaluated the antiproliferative and antimigratory effects of enoxaparin (a LMWH) in lung adenocarcinoma A549 cells, and assessed the possible mechanism involved, and the effect on doxorubicin's efficacy. MATERIALS AND METHODS: Proliferation and migration were evaluated using BrdU and transwell assays, respectively. Immunoblotting was used to measure PAR-1, PAR-2, MMP-2, ERK1/2 and Akt proteins. Apoptosis and cell cycle studies examined the combined effect of enoxaparin and doxorubicin. RESULTS: Enoxaparin inhibited A549 cell proliferation and migration. Following PAR-1 gene knock down, enoxaparin's effect on A549 cell proliferation was diminished compared to scrambled siRNA. Our experiments verified that enoxaparin-mediated down-regulation of MAPK and PI3K, reduced MMP-2 expression and inhibited A549 cell migration. Additionally, enoxaparin increased doxorubicin's efficacy by enhancing apoptosis, while no effect on cell-cycle progression was observed. CONCLUSION: Results suggest that the anticancer activity of enoxaparin in A549 cells was mediated by the interference of two major PAR-1 downstream signaling pathways, MAPK/ERK and PI3K/Akt, which in turn inhibit proliferation and migration. Therefore, enoxaparin may be promising as an adjunct to traditional chemotherapy for lung cancer and warrants further investigation.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Enoxaparina/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Receptor PAR-1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células A549 , Adenocarcinoma de Pulmão/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Heparina de Baixo Peso Molecular/farmacologia , Humanos , Neoplasias Pulmonares/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/metabolismo
4.
Anticancer Res ; 39(10): 5329-5338, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570426

RESUMO

BACKGROUND/AIM: The P13K/Akt signaling pathway is a growth-regulating cellular pathway that is constitutively activated in a variety of human cancers. In previous studies, we reported that a solenopsin analog, compound B (MU-06-SC-608-7), shows inhibitory effects on Akt phosphorylation at a key activation site, as well as on proliferation of tumorigenic cells at sub-micromolar concentrations. The purpose of this study was to evaluate the effect of compound B on downstream effectors of Akt kinase, phosphorylation of Akt at a second activation site, Akt kinase activity in vitro, tumorigenic cell viability and other signaling pathways. MATERIALS AND METHODS: Western blot analyses were performed using WBras1 epithelial and H2009 human carcinoma cells and cell viability assays were performed on H2009 cells. In vitro Akt kinase assays were performed using a commercially available kit. RESULTS: Compound B decreased the phosphorylation of Akt at the Thr308 activation site and key downstream effectors of Akt kinase, but did not directly inhibit Akt kinase. Substantial decreases in cell viability were observed at concentrations above 5 µM. No effect was seen on ERK or JNK pathways. CONCLUSION: The results earmark this compound for further studies as a potential targeted cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirimidinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos
5.
Anticancer Res ; 39(10): 5353-5359, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570429

RESUMO

BACKGROUND: Identification of genetic prognostic biomarkers, such as germline variants, are urgently needed to choose optimal treatment for metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: The prognostic value of anoctamin 7 (ANO7) rs77559646 on docetaxel response was tested in a prospective PROSTY randomized trial and a retrospective Auria Biobank set. The variant rs77559646 was genotyped and its association with progression-free survival (PFS) and overall survival (OS) was tested. RESULTS: In comparison with the non-carriers, the variant carriers had longer PFS (p=0.005) and OS (p=0.003) in the PROSTY cohort. In the retrospective cohort, there was a borderline association with PFS (p=0.09), but not in OS (p=0.9). In both cohorts, Cox regression multivariate models revealed that rs77559646 was an independent prognostic factor for favourable PFS. CONCLUSION: The rs77559646 was shown to be a prognostic germline biomarker for better response to docetaxel treatments. To our knowledge, this is the first time that a non-coding germline variant has been associated with chemotherapy of mCRPC.


Assuntos
Anoctaminas/genética , Antineoplásicos/uso terapêutico , Docetaxel/uso terapêutico , Variação Genética/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Idoso , Biomarcadores Tumorais/genética , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos
6.
Anticancer Res ; 39(10): 5403-5415, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570435

RESUMO

BACKGROUND/AIM: Tubugi-1 is a more stable and accessible synthetic counterpart of natural tubulysins. This study aimed to evaluate its cytotoxic potential against anaplastic human melanoma cells. MATERIALS AND METHODS: The viability of A-375 cells was determined by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and crystal violet assay. The type of cell death and proliferative rate were investigated using flow cytometry and fluorescent microscopy, while the molecular background was evaluated by western blot. RESULTS: Tubugi-1 reduced the viability of A-375 cells, inducing massive micronucleation, followed by augmented expression of inhibitor of nuclear factor-κB and caspase-2, typical of a mitotic catastrophe. Disturbed proliferation and G2M block with prominent caspase activity, weakened the expression of B-cell lymphoma 2 and B-cell lymphoma 2-associated X transient up-regulation, coexisted with intensive autophagy. Specific inhibition of autophagy by chloroquine resulted in conversion from mitotic catastrophe to rapid apoptosis. CONCLUSION: Multilevel anticancer action of tubugi-1 is extended by co-application of an autophagy inhibitor, giving a new dimension in further preclinical advancement of this potential agent.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Citotoxinas/farmacologia , Melanoma/tratamento farmacológico , Caspase 2/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Melanoma/metabolismo , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Regulação para Cima/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo
7.
Anticancer Res ; 39(10): 5417-5425, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570436

RESUMO

BACKGROUND/AIM: Chemotherapy with docetaxel (DTX) is used for castration-resistant prostate cancer (CRPC), but it is inadequate. MATERIALS AND METHODS: We evaluated the effect of the combination treatment DTX and the mTOR inhibitor temsirolimus (TEM) in the PC3 prostate cancer cell line, by focusing on the induction of autophagy and apoptosis. RESULTS: TEM induced autophagy but not apoptosis even at a high dose, whereas DTX induced apoptosis. The combination of low-dose DTX and TEM caused a 34% suppression in cell proliferation compared to monotherapy with a higher dose of DTX. The induction of apoptosis was increased by their combination. The combination with DTX overcame the induction of autophagy by TEM. The combination treatment suppressed tumor growth 72% less than the control group after 14 days of treatment in vivo. CONCLUSION: The combination of TEM and DTX induced apoptosis by overcoming autophagy and enhanced the anticancer effect compared to monotherapy.


Assuntos
Antineoplásicos/administração & dosagem , Autofagia/efeitos dos fármacos , Docetaxel/administração & dosagem , Próstata/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Sirolimo/análogos & derivados , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Terapia Combinada/métodos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células PC-3 , Inibidores de Proteínas Quinases/administração & dosagem , Sirolimo/administração & dosagem
8.
Anticancer Res ; 39(10): 5725-5731, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570474

RESUMO

BACKGROUND/AIM: In lung cancer (LC) patients, pre-existing interstitial lung disease (ILD) is a risk of chemotherapy-associated acute exacerbation of ILD (AE-ILD). AE-ILD shows a diverse clinical course varying from fatal respiratory failure to asymptomatic event, and the prognostic impact is still unclear. MATERIALS AND METHODS: We retrospectively evaluated the association between the prognosis and AE-ILD in 86 LC patients with pre-existing ILD who were treated with cytotoxic chemotherapy, especially focusing on histological types of LC. RESULTS: Thirty (34.9%) patients had AE-ILD, that was significantly associated with a poor prognosis in LC patients with ILD. When analyzed by histological types, a significant association of AE-ILD with shorter survival was observed only in the small cell LC (SCLC) group, but not in the non-small cell LC group. CONCLUSION: The development of AE-ILD by cytotoxic chemotherapy is associated with poor prognosis in LC patients with ILD, especially in patients with SCLC.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Doenças Pulmonares Intersticiais/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/patologia , Masculino , Prognóstico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/patologia
9.
Anticancer Res ; 39(10): 5773-5780, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570481

RESUMO

BACKGROUND/AIM: Serum γ-glutamyltransferase (GGT) is reportedly associated with survival and therapeutic response in various malignancies; however, as far as we are aware its impact on metastatic castration-resistant prostate cancer (mCRPC) has never been assessed. PATIENTS AND METHODS: Fifty consecutive men with mCRPC receiving enzalutamide at a single cancer center were retrospectively evaluated. The primary endpoint was overall survival (OS) and the secondary endpoints were prostate-specific antigen (PSA) response, maximal PSA change, and PSA progression-free survival (PSA-PFS). RESULTS: Multivariable analysis demonstrated that elevation of GGT (≥40 U/l) was significantly and independently associated with shorter OS (hazard ratio(HR)=3.61; p=0.004), as were lower hemoglobin (HR=6.04; p<0.001) and higher PSA (HR=4.38; p=0.009). Elevated GGT was also associated with poorer PSA response, maximal PSA change, and shorter PSA-PFS. CONCLUSION: Elevated GGT was an adverse prognostic indicator in men with mCRPC receiving enzalutamide. External validations would improve the generality of our findings.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , gama-Glutamiltransferase/sangue , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Intervalo Livre de Doença , Humanos , Masculino , Segunda Neoplasia Primária/sangue , Segunda Neoplasia Primária/tratamento farmacológico , Feniltioidantoína/uso terapêutico , Prognóstico , Antígeno Prostático Específico/sangue , Estudos Retrospectivos , Resultado do Tratamento
10.
Anticancer Res ; 39(10): 5803-5809, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570485

RESUMO

BACKGROUND/AIM: Cabazitaxel (CBZ) is approved for docetaxel-resistant castration-resistant prostate cancer (CRPC). This retrospective study aimed at assessing the efficacy and prognostic markers of cabazitaxel treatment in Japanese CRPC patients. PATIENTS AND METHODS: The medical records of 44 consecutive Japanese patients with CRPC who started cabazitaxel at our Institution between January 2011 and February 2019 were reviewed and statistically analysed. RESULTS: The median follow-up period after cabazitaxel initiation was 13.2 [interquartile range (IQR)=6.9-21.5] months. The objective response rate, median progression-free survival period, and median overall survival period (OS) were 45.5%, 4.3 months, and 20.7 months, respectively. On multivariate analysis, higher prostate-specific antigen (PSA; >100 ng/ml), lower haemoglobin (<10 g/dl), and lower number of prior docetaxel therapy cycles (<10) were predictors for shorter OS. CONCLUSION: Patients with anemia, high PSA, and lower number of docetaxel therapy cycles might have shorter survival period from introduction of cabazitaxel therapy. In addition, PSA decline might still be a useful indicator as a predictor of prognosis of the metastatic CRPC patients treated with cabazitaxel.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Taxoides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Docetaxel/uso terapêutico , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/metabolismo , Segunda Neoplasia Primária/mortalidade , Antígeno Prostático Específico/metabolismo , Neoplasias de Próstata Resistentes à Castração/metabolismo , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
11.
Medicine (Baltimore) ; 98(38): e16988, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567935

RESUMO

RATIONALE: Peripherally inserted central catheters (PICC), normally located at the lower 1/3rd of the superior vena cava (SVC) and cavo-atrial junction, are commonly used in cancer patients. Persistent left superior vena cava (PLSVC) is a vascular anomaly, in patients with which seldom research was reported about PICC implanted. After obtaining written informed consent, we present a case where two successful insertions of PICC were performed in a 50-year-old female patient with PLSVC and right SVC. PATIENTS CONCERNS: The patient had ovarian cancer and was admitted for chemotherapy using PICC. DIAGNOSES: Ovarian cancer and PLSVC. INTERVENTIONS AND OUTCOMES: Following insertion of PICC in PLSVC, thrombosis developed. PICC was removed after routine anticoagulation therapy. Owing to tumor recurrence, a second PICC was inserted in the right SVC without any complications. LESSONS: PICC insertion in PLSVC for chemotherapy may be associated with an increased risk of deep venous thrombosis of the upper extremity. A right catheter insertion in patient with PLSVC was preferred.


Assuntos
Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Malformações Vasculares/complicações , Veia Cava Superior/anormalidades , Trombose Venosa/diagnóstico , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Braço , Cateterismo Periférico/efeitos adversos , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/complicações , Neoplasias Ovarianas/complicações , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologia
12.
Anticancer Res ; 39(10): 5483-5494, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570442

RESUMO

BACKGROUND/AIM: Canine mammary gland tumors (CMGTs) are the most common tumors in female dogs. Rivoceranib (also known as apatinib) is a novel anti-angiogenic tyrosine kinase inhibitor that selectively binds to vascular endothelial growth factor receptor-2 (VEGFR2). The aim of this study was to disclose the antitumor effects of rivoceranib on CMGT cell lines. MATERIALS AND METHODS: The direct effects of rivoceranib on CMGT cells in vitro were analyzed by cell proliferation and migration assays. Cell-cycle distribution and apoptotic ratio were analyzed by flow cytometry. Expression levels of phosphorylated VEGFR2 were evaluated by western blot analysis. RESULTS: Rivoceranib treatment significantly reduced the proliferation and migration of CMGT cells in a dose-dependent manner. Flow cytometry results revealed significant increases in G0/G1 phase arrest and apoptosis proportional to the drug concentration used. Rivoceranib reduced the level of phosphorylated VEGFR2. CONCLUSION: We confirm that rivoceranib exerts antitumor effects on CMGT cells by inhibiting biological functions.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Mamárias Animais/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cães , Feminino , Fase G1/efeitos dos fármacos , Neoplasias Mamárias Animais/metabolismo , Fosforilação/efeitos dos fármacos , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo
13.
Anticancer Res ; 39(10): 5559-5564, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570450

RESUMO

BACKGROUND/AIM: Tyrosine kinase inhibitors are important in the treatment of metastatic renal cell cancer (mRCC). The aim of the study was to evaluate the costs and effects of sunitinib in mRCC. PATIENTS AND METHODS: A total of 81 mRCC patients who received first-line sunitinib therapy between 2010 and 2014 were recruited. Drug doses, laboratory and imaging studies, outpatient visits and inpatient stays were recorded. Health-related quality of life (HRQoL) was measured (15D- and EQ-5D - 3L questionnaires). RESULTS: The cost of sunitinib (mean 22,268 €/patient range 274 € to 105,121 €) covered 73% of the total costs during the treatment period. The total treatment cost was 30,530 €/patient (range=1,661-111,516 €). The median overall survival was 17.9 months. HRQoL decreased during treatment. CONCLUSION: The main cost during sunitinib treatment of mRCC was the drug itself (73% of the total costs). Drug costs and HRQoL should be considered when choosing treatment for mRCC.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/economia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/economia , Sunitinibe/economia , Sunitinibe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/economia , Antineoplásicos/uso terapêutico , Análise Custo-Benefício/métodos , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida
14.
Anticancer Res ; 39(10): 5611-5615, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570457

RESUMO

BACKGROUND/AIM: Chemotherapy is the mainstay treatment of osteosarcoma. The purpose of this study was to elucidate the factors that affect the rate of chemotherapy treatment of osteosarcoma patients. MATERIALS AND METHODS: We queried the National Cancer Database for bone cancer patients. We included patients diagnosed with osteosarcoma of the upper extremities regardless of age and sex. With bivariate and multivariate models, we analyzed the demographic, facility, and tumor-specific characteristics, comparing the group that received chemotherapy with those that did not. RESULTS: Female patients (OR=0.567; 95%CI=0.337-0.955), non-White patients (OR=0.485; 95%CI=0.25-0.939), and patients with government insurance (OR=0.506; 95%CI=0.285-0.9) had lower odds of receiving chemotherapy treatment than male, white, and privately insured patients. Patients with stages II (OR=4.817; 95%CI=2.594-8.946) and IV disease (OR=0.457; 95%CI=1.931-10.286) had higher odds of receiving chemotherapy than those with stage I disease. CONCLUSION: Age, sex, race and insurance affected the rate of chemotherapy treatment in patients with upper limb osteosarcoma.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Extremidade Superior/patologia , Adulto , Quimioterapia Adjuvante/métodos , Terapia Combinada/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
Medicine (Baltimore) ; 98(39): e17364, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574883

RESUMO

OBJECTIVE: We performed a meta-analyisis to evaluate the efficacy of maintenance dexamethasone against acute or delayed chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately or highly emetic risk chemotherapy regimen. METHODS: PubMed, Embase, and Cochrane Library were searched for eligible studies. Data comparing maintenance dexamethasone with single-dose dexamethasone during the acute, delayed, and overall phase of CINV were extracted. Overall risk ratio (RR) was used to estimate the efficacy and adverse effects. RESULTS: Nine studies were included. In delayed phase, maintenance dexamethasone has similar efficacy to single-dose dexamethasone for no emetic episodes (RR, 1.06; 95% confidence interval [CI], 1.00-1.14), complete response (RR, 1.04; 95% CI, 0.98-1.11), complete control (RR, 1.07; 95% CI, 0.98-1.16), and total control (RR, 1.06; 95% CI, 0.91-1.23). In overall phase, maintenance dexamethasone has similar efficacy to single-dose dexamethasone for no emetic episodes (RR, 1.02; 95% CI, 0.94-1.11), complete response (RR, 1.02; 95% CI, 0.95 -1.09), complete control (RR, 1.03; 95% CI, 0.94-1.13), total control (RR, 1.05; 95% CI, 0.90-1.23), and no rescue medication (RR, 1.07; 95% CI, 0.97-1.19). Maintenance dexamethasone was only superior to single-dose dexamethasone for no rescue medication during delayed phase (RR, 1.10; 95% CI, 1.01-1.21, P = .034). The incidence of hiccup was observed higher in maintenance dexamethasone group (RR = 3.16, 95% CI, 1.12-8.92). CONCLUSION: The single-dose dexamethasone regimen offers high and similar overall control of symptoms as the maintenance dexamethasone regimen in this population. Multiple-day dexamethasone was suitable for patients who used rescue medication during the delayed phase.


Assuntos
Antieméticos/administração & dosagem , Antineoplásicos/efeitos adversos , Dexametasona/administração & dosagem , Náusea/prevenção & controle , Vômito/prevenção & controle , Protocolos Clínicos , Humanos , Náusea/induzido quimicamente , Vômito/induzido quimicamente
16.
Gan To Kagaku Ryoho ; 46(8): 1319-1321, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31501379

RESUMO

A66 -year-old man was diagnosed with chronic myeloid leukemia(CML). Imatinib treatment had been initiated, and a major molecular response(MMR)was achieved. The patient had anemia and was diagnosed with descending colon cancer. The patient was surgically treated, and then received postoperative adjuvant chemotherapy with UFT/LV. However, imatinib was not administered during that period. The patient could undergo postoperative adjuvant chemotherapy for 6 months without acute exacerbation of the CML.


Assuntos
Neoplasias do Colo , Leucemia Mielogênica Crônica BCR-ABL Positiva , Idoso , Antineoplásicos , Quimioterapia Adjuvante , Colo Descendente , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Masculino , Resultado do Tratamento
17.
Adv Exp Med Biol ; 1167: 237-248, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31520359

RESUMO

In recent years, there has been growing interest in using Drosophila for drug discovery as it provides a unique opportunity to screen small molecules against complex disease phenotypes in a whole animal setting. Furthermore, gene-compound interaction experiments that combine compound feeding with complex genetic manipulations enable exploration of compound mechanisms of response and resistance to an extent that is difficult to achieve in other experimental models. Here, I discuss how compound screening and testing approaches reported in Drosophila fit into the current cancer drug discovery pipeline. I then propose a framework for a Drosophila-based cancer drug discovery strategy which would allow the Drosophila research community to effectively leverage the power of Drosophila to identify candidate therapeutics and push our discoveries into the clinic.


Assuntos
Antineoplásicos/farmacologia , Drosophila , Descoberta de Drogas , Neoplasias/tratamento farmacológico , Animais , Modelos Animais de Doenças , Técnicas Genéticas , Fenótipo
18.
Bol. latinoam. Caribe plantas med. aromát ; 18(5): 480-491, sept. 2019. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-1008273

RESUMO

In the present study, we investigated the antiproliferative activity of essential oil from leaves of Melissa officinalis L. grown in Southern Bosnia and Herzegovina. In vitro evaluation of antiproliferative activity of the M. officinalis essential oil was carried out on three human tumor cell lines: MCF-7, NCI-H460 and MOLT-4 by MTT assay. M. officinalis essential oil was characterized by high percentage of monoterpenes (77,5%), followed by the sesquiterpene fraction (14,5%) and aliphatic compounds (2,2%). The main constituents of the essential oil of M. officinalis are citral (47,2%), caryophyllene oxide (10,2%), citronellal (5,4%), geraniol (6,6%), geranyl acetate (4,1%) and ß- caryophyllene (3,8%). The essential oil showed significant antiproliferative activity against three cancer cell lines, MOLT-4, MCF-7, and NCI-H460 cells, with GI50 values of <5, 6±2 and 31±17 µg/mL, respectively. The results revealed that M. officinalis L. essential oil has a potential as anticancer therapeutic agent.


En el presente estudio, investigamos la actividad antiproliferativa del aceite esencial de las hojas de Melissa officinalis L. cultivadas en el sur de Bosnia y Herzegovina. La evaluación in vitro de la actividad antiproliferativa del aceite esencial de M. officinalis se llevó a cabo en tres líneas celulares de tumores humanos: MCF-7, NCI-H460 y MOLT-4 utilizando el ensayo de MTT. El aceite esencial de M. officinalis se caracterizó por un alto porcentaje de monoterpenos (77,5%), seguido de la fracción sesquiterpénica (14,5%) y compuestos alifáticos (2,2%). Los principales constituyentes del aceite esencial de M. officinalis fueron citral (47,2%), óxido de cariofileno (10,2%), citronelal (5,4%), geraniol (6,6%), acetato de geranilo (4, 1%), y ß-cariofileno (3,8%). El aceite esencial mostró una actividad antiproliferativa significativa contra las líneas celulares de cáncer MOLT-4, MCF-7 y NCI-H460, con valores GI50 de <5, 6±2 y 31±17 µg/mL, respectivamente. Los resultados revelaron que el aceite esencial de M. officinalis L. tiene potencial como agente terapéutico contra el cáncer.


Assuntos
Óleos Voláteis/farmacologia , Melissa , Antineoplásicos/farmacologia , Sesquiterpenos/análise , Técnicas In Vitro , Óleos Voláteis/química , Células Tumorais Cultivadas , Folhas de Planta , Monoterpenos/análise , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Antineoplásicos/química
19.
Bratisl Lek Listy ; 120(9): 636-640, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31475545

RESUMO

Cancer-related mortality have been declining in the last decades. Approximately half of adults and more than two thirds of children oncological patients live longer than 5 years after diagnosis. However, this optimistic scenario has been counterbalanced by an increasing cardiovascular risk in cancer patients. Atherosclerotic damage has been underestimated in oncology practice for a long time, but recently a significant number of cancer patients with cardiovascular risk factors and serious artery disease during and after anticancer therapy has been reported. Complexity of atherosclerosis in cancer patients is challenging. Herein, we describe cardiovascular risk factors and pathophysiological mechanisms of atherosclerosis induced by selected classic chemotherapeutics, targeted cancer therapies, hormonal agents and radiotherapy and new clinical data regarding atherosclerosis, which received a particular attention in recent years (Tab. 1, Ref. 26). Keywords: cardiovascular disease, atherosclerosis, cardiotoxicity, risk factors, hypertension, hyperlipidemia.


Assuntos
Antineoplásicos/efeitos adversos , Aterosclerose/complicações , Neoplasias/complicações , Humanos , Fatores de Risco
20.
Bratisl Lek Listy ; 120(9): 646-649, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31475547

RESUMO

BACKGROUND: It has been demonstrated that proteasome inhibitors might be potential anticancer drugs. The copper complexes can be used as specific proteasome inhibitors in tumor cells able to induce apoptosis by the ubiquitin-proteasome pathway. The goal of our study was to test the cytotoxic and proteasome inhibitory effects of five Schiff base Cu(II) complexes - [Cu2(sal-D,L-glu)2(isoquinoline)2] . 2C2H5OH (1), [Cu(sal-5-met-L-glu)(H2O)].H2O (2), [Cu(ethanol)2(imidazole)4][Cu2(sal-D,L-glu)2(imidazole)2] (3), [Cu(sal-D,L-glu)(2-methylimidazole)] (4) on human lung carcinoma cells A549, cervix carcinoma cells HeLa and glioblastoma cells U-118MG. MATERIAL AND METHODS: For the cytotoxic analysis we used MTT test and for monitoring the proteasome inhibition western blot analysis. RESULTS: We have observed different cytotoxic effects of tested complexes on human cancer cells depending on the ligand present in their structure. Cu(II) complexes 4 and 5 were the most effective against A549 cells; all complexes were cytotoxic against HeLa cells and the complex 4 was the most effective against U-118MG. Moreover, we have detected the inhibition of the proteasome activity in human cancer cells A549 by Cu(II) complexes 1, 2 and 4 at IC50 concentration. CONCLUSION: Results of our study suggest that isoquinoline- and imidazole-based copper complexes could be used as inhibitors of the proteasome system in cancer cells A549 (Tab. 1, Fig. 1, Ref. 26).


Assuntos
Cobre/farmacologia , Inibidores de Proteassoma/farmacologia , Bases de Schiff/farmacologia , Células A549 , Antineoplásicos/farmacologia , Apoptose , Complexos de Coordenação/farmacologia , Células HeLa , Humanos , Complexo de Endopeptidases do Proteassoma
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