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1.
J Environ Pathol Toxicol Oncol ; 39(3): 247-260, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865916

RESUMO

The anticancer activity of malvidin was studied in Dalton's lymphoma ascites (DLA)-induced solid and ascitic tumor mice models. Malvidin is a natural compound belonging to the family of O-methylated anthocyanidin and plays a predominant role in regulating both short- and long-term cellular activities. Animals were injected with DLA cells (1.5 × 106 cells/animal) to induce solid and ascitic tumors. The administration of malvidin (5 mg/kg bw and 10 mg/kg bw) was carried out for 10 consecutive days from the day of tumor induction for both solid and ascitic tumors. Cyclophosphamide, CTX (25 mg/kg bw), used as the standard drug, was also administered for 10 consecutive days. Treatment with malvidin showed a significant reduction in tumor volume and elevated white blood cell (WBC) count when compared to the DLA-bearing control animals. The treatment also maintained the body weight and hemoglobin level, and decreases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) were also noted. This investigation also reported the decreased levels of cellular glutathione (GSH) in ascitic tumor groups. Malvidin reduced inflammatory mediator and cytokine levels, such as tumor necrosis factor level alpha (TNF-α) and interleukin-6 (IL-6), which serve as molecular targets for cancer prevention. A decrease in the level of reactive oxygen species (ROS), like nitric oxide (NO), was observed. Histopathological examination revealed altered morphological changes in tumor tissue and the alleviation of hepatic architecture due to DLA. Immunohistochemical analysis revealed the inhibition of iNOS. This study demonstrated that malvidin exhibited significant in vivo antitumor activity and that it was reasonably imputable to its increasing endogenous mechanism. We accent the pertinence of malvidin as a potential naturally derived drug target for tumor control.


Assuntos
Antocianinas/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Ascite/tratamento farmacológico , Citocinas/sangue , Linfoma/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Antocianinas/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Ascite/metabolismo , Ascite/patologia , Biomarcadores/sangue , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Citocinas/metabolismo , Linfoma/metabolismo , Linfoma/patologia , Masculino , Camundongos , Transplante de Neoplasias , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Estresse Oxidativo/imunologia
2.
Bull Cancer ; 107(10): 1019-1023, 2020 Oct.
Artigo em Francês | MEDLINE | ID: mdl-32972763

RESUMO

In this review, we report a case of a bone's metastatic breast cancer in Malian patient treated by chemotherapy in whom SRAS-COV-2's diagnosis was made 9days after the onset gastrointestinal symptoms. Patient quickly died before any COVID-19's treatment. According to the poor outcomes of cancer patients with COVID-19, authors emphasize to an intensive attention to such patients in order to find the best therapeutic balance between the two pathologies during this pandemic.


Assuntos
Betacoronavirus , Neoplasias da Mama/complicações , Carcinoma Ductal de Mama/secundário , Infecções por Coronavirus/complicações , Diarreia/etiologia , Pandemias , Pneumonia Viral/complicações , Neoplasias da Coluna Vertebral/secundário , Vômito/etiologia , Adulto , Antineoplásicos Fitogênicos/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/complicações , Carcinoma Ductal de Mama/tratamento farmacológico , Docetaxel/uso terapêutico , Evolução Fatal , Feminino , Infecções por HIV/complicações , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/tratamento farmacológico , Tomografia Computadorizada por Raios X , Ácido Zoledrônico/uso terapêutico
3.
Anticancer Res ; 40(9): 4947-4960, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878783

RESUMO

BACKGROUND/AIM: This study aimed to investigate the anticancer effects and potential mechanisms of sclareol in a human small cell lung carcinoma (SCLC) cell line. MATERIALS AND METHODS: Cell viability was determined by the MTT assay. Cell cycle, apoptosis and caspase activity were evaluated by flow cytometry. Cell cycle and DNA damage related protein expression was determined by western blotting. In vivo evaluation of sclareol was carried out in xenografted tumor mice models. RESULTS: Sclareol significantly reduced cell viability, induced G1 phase arrest and subsequently triggered apoptosis in H1688 cells. In addition, this sclareol-induced growth arrest was associated with DNA damage as indicated by phosphorylation of H2AX, activation of ATR and Chk1. Moreover, in vivo evaluation of sclareol showed that it could inhibit tumor weight and volume in a H1688 xenograft model. CONCLUSION: Sclareol might be a novel and effective therapeutic agent for the treatment of SCLC patients.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Diterpenos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Diterpenos/uso terapêutico , Feminino , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais/efeitos dos fármacos , Carcinoma de Pequenas Células do Pulmão/patologia , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
4.
PLoS One ; 15(7): e0235848, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32735623

RESUMO

BACKGROUND: Second-line treatments boost overall survival in advanced gastric cancer (AGC). However, there is a paucity of information as to patterns of use and the results achieved in actual clinical practice. MATERIALS AND METHODS: The study population comprised patients with AGC in the AGAMENON registry who had received second-line. The objective was to describe the pattern of second-line therapies administered, progression-free survival following second-line (PFS-2), and post-progression survival since first-line (PPS). RESULTS: 2311 cases with 2066 progression events since first-line (89.3%) were recorded; 245 (10.6%) patients died during first-line treatment and 1326/2066 (64.1%) received a second-line. Median PFS-2 and PPS were 3.1 (95% CI, 2.9-3.3) and 5.8 months (5.5-6.3), respectively. The most widely used strategies were monoCT (56.9%), polyCT (15.0%), ramucirumab+CT (12.6%), platinum-reintroduction (8.3%), trastuzumab+CT (6.1%), and ramucirumab (1.1%). PFS-2/PPS medians gradually increased in monoCT, 2.6/5.1 months; polyCT 3.4/6.3 months; ramucirumab+CT, 4.1/6.5 months; platinum-reintroduction, 4.2/6.7 months, and for the HER2+ subgroup in particular, trastuzumab+CT, 5.2/11.7 months. Correlation between PFS since first-line and OS was moderate in the series as a whole (Kendall's τ = 0.613), lower in those subjects who received second-line (Kendall's τ = 0.539), especially with ramucirumab+CT (Kendall's τ = 0.413). CONCLUSION: This analysis reveals the diversity in second-line treatment for AGC, highlighting the effectiveness of paclitaxel-ramucirumab and, for a selected subgroup of patients, platinum reintroduction; both strategies endorsed by recent clinical guidelines.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sistema de Registros/estatística & dados numéricos , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Platina/administração & dosagem , Compostos de Platina/uso terapêutico , Neoplasias Gástricas/patologia , Análise de Sobrevida
5.
Life Sci ; 259: 118183, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32781058

RESUMO

Cancer, being a multifactorial disease has diverse presentation in different subgroups which is mainly attributed to heterogenous presentation of tumor cells. This cancer cell heterogeneity is the major reason for variable response to standard chemotherapeutic regimes owing to which high relapse rate and multi-drug resistance has increasingly been reported over the past decade. Interestingly, the research on natural compounds in combination with standard therapies have reported with interesting and promising results from the pre-clinical trials and few of which have also been tested in other phases of clinical trials. This review focusses on baicalein, an emerging anti-cancerous natural compound, its chemistry and mechanism of action. In view of promising pre-clinical this review is mainly motivated by the results observed from baicalein treatment of different cancer cell population. With the advancing scientific evidence on the anti-malignant potential of baicalein with respect to its pharmacological activities encompassing from anti-inflammatory to anti-angiogenic/anti-metastatic effects, the focus is mainly directed to understanding the precise mechanism of action of baicalein. In the process of understanding the underlying signaling cascades, the role of mitogen activated protein kinase (MAPK), mammalian target of rapamycin (mTOR), AKT serine/threonine protein kinase B (AKT), poly(ADP-ribose) polymerase (PARP), matrix metalloproteinases-2 (MMP-2), matrix metalloproteinases-9 (MMP-9) and caspase-3/-8,-9 have been highlighted as the major players for baicalein anti-malignant potential. This is also supported by the interesting pre-clinical findings which cumulatively pave the way ahead for development of baicalein as an adjunct anti-cancer treatment with chemotherapeutic agents.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Neoplasias/tratamento farmacológico , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Apoptose/efeitos dos fármacos , Humanos , Metástase Neoplásica/prevenção & controle , Neoplasias/patologia
6.
PLoS One ; 15(7): e0219632, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32706829

RESUMO

INTRODUCTION: Surgical resection and systemic chemotherapy with temozolomide remain the mainstay for treatment of glioblastoma. However, many patients are not candidates for surgical resection given inaccessible tumor location or poor health status. Furthermore, despite being first line treatment, temozolomide has only limited efficacy. METHODS: The development of injectable hydrogel-based carrier systems allows for the delivery of a wide range of chemotherapeutics that can achieve high local concentrations, thus potentially avoiding systemic side effects and wide-spread neurotoxicity. To test this modality in a realistic environment, we developed a diblock copolypeptide hydrogel (DCH) capable of carrying and releasing paclitaxel, a compound that we found to be highly potent against primary gliomasphere cells. RESULTS: The DCH produced minimal tissue reactivity and was well tolerated in the immune-competent mouse brain. Paclitaxel-loaded hydrogel induced less tissue damage, cellular inflammation and reactive astrocytes than cremaphor-taxol (typical taxol-carrier) or hydrogel alone. In a deep subcortical xenograft model of glioblastoma in immunodeficient mice, injection of paclitaxel-loaded hydrogel led to local tumor control and improved survival. However, the tumor cells were highly migratory and were able to eventually escape the area of treatment. CONCLUSIONS: These findings suggest this technology may be ultimately applicable to patients with deep-seated inoperable tumors, but as currently formulated, complete tumor eradication would be highly unlikely. Future studies should focus on targeting the migratory potential of surviving cells.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Glioblastoma/tratamento farmacológico , Hidrogéis/química , Paclitaxel/uso terapêutico , Peptídeos/química , Animais , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Sistema Nervoso Central/patologia , Portadores de Fármacos/química , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Paclitaxel/química , Taxa de Sobrevida , Temozolomida/química , Temozolomida/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Life Sci ; 256: 117977, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32603822

RESUMO

AIMS: Silibinin is the major component of flavonolignans complex mixture (Silymarin), which is obtained from Silybum marianum (L.) Gaertn. Despite several reports about silibinin, little is known about its effects on gastric diseases. Then, the present study aims to evaluate the silibinin effect against Helicobacter pylori infection, gastric tumor cells and immunomodulation. MAIN METHODS: The anti-H. pylori effect was performed on 43504 and 43629 strains by minimum inhibitory concentration (MIC) determination, observing morphological alterations by scanning electron microscopy and in silico evaluation by molecular docking. Immunomodulatory activity (Interleukins-6 and 10, TNF-α and NO inhibition) was determined in H. pylori-stimulated macrophages and the cytotoxic activity on gastric adenocarcinoma cells prior and after metabolization by S9 fraction. KEY FINDINGS: Silibinin showed anti-H. pylori activity with MIC of 256 µg/mL, promoted important morphological changes in the bacterial cell wall, as blebs and clusters, suggesting interaction with Penicillin Binding Protein (PBP) subunits. Immunomodulatory potential was observed at 50 µg/mL with the inhibition of produced cytokines and NO by H. pylori-stimulated macrophages of 100% for TNF-ɑ, 56.83% for IL-6, and 70.29% for IL-10 and 73.33% for NO. Moreover, silibinin demonstrated significant cytotoxic activity on adenocarcinoma cells (CI50: 60.17 ± 0.95 µg/mL) with a higher selectivity index (SI: 1.52) compared to cisplatin. After metabolization silibinin showed an increase of cytotoxicity with a CI50 six-fold decrease (10.46 ± 0.25). SIGNIFICANCE: The use of silibinin may become an important alternative tool in the prevention and treatment of H. pylori infection and, consequently, in gastric cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori/efeitos dos fármacos , Simulação de Acoplamento Molecular/métodos , Silibina/farmacologia , Neoplasias Gástricas/prevenção & controle , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori/fisiologia , Camundongos , Testes de Sensibilidade Microbiana/métodos , Células RAW 264.7 , Silibina/química , Silibina/uso terapêutico , Neoplasias Gástricas/patologia
8.
PLoS One ; 15(7): e0236315, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32706791

RESUMO

The natural product nobiletin is a small molecule, widely studied with regard to its therapeutic effects, including in cancer cell lines and tumors. Recently, nobiletin has also been shown to affect circadian rhythms via their enhancement, resulting in protection against metabolic syndrome. We hypothesized that nobiletin's anti-oncogenic effects, such as prevention of cell migration and formation of anchorage independent colonies, are correspondingly accompanied by modulation of circadian rhythms. Concurrently, we wished to determine whether the circadian and anti-oncogenic effects of nobiletin differed across cancer cell lines. In this study, we assessed nobiletin's circadian and therapeutic characteristics to ascertain whether these effects depend on cell line, which here also varied in terms of baseline circadian rhythmicity. Three cell culture models where nobiletin's effects on cell proliferation and migration have been studied previously were evaluated: U2OS (bone osteosarcoma), which possesses robust circadian rhythms; MCF7 (breast adenocarcinoma), which has weak circadian rhythms; and MDA-MB-231 (breast adenocarcinoma), which is arrhythmic. We found that circadian, migration, and proliferative effects following nobiletin treatment were subtle in the U2OS and MCF7 cells. On the other hand, changes were clear in MDA-MB-231s, where nobiletin rescued rhythmicity and substantially reduced oncogenic features, specifically two-dimensional cell motility and anchorage-independent growth. Based on these results and those previously described, we posit that the effects of nobiletin are indeed cell-type dependent, and that a positive correlation may exist between nobiletin's circadian and therapeutic effects.


Assuntos
Antineoplásicos Fitogênicos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ritmo Circadiano/efeitos dos fármacos , Flavonas , Adenocarcinoma/tratamento farmacológico , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Flavonas/farmacologia , Flavonas/uso terapêutico , Humanos , Osteossarcoma/tratamento farmacológico
9.
Medicine (Baltimore) ; 99(25): e20734, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569214

RESUMO

BACKGROUD: Paclitaxel (PTX) has become a widely used second-line therapy for advanced gastric cancer. There exists controversy whether targeted therapy combined with PTX can provide additional benefit over PTX alone. Therefore, a meta-analysis was carried out to evaluate the efficacy and safety of the two therapy regimes. METHODS: We searched systematically for studies from the databases of PubMed, Embase, Web of Science and the Cochrane Library published between January 2000 and August 2019. Only randomized controlled trials were eligible. Statistical analysis was performed by meta-analysis. The primary end points were progression-free survival and overall survival, objective response rate and adverse events were the secondary end points. RESULTS: A total of 4 randomized controlled trials with 1574 patients (PTX + targeted therapy, n = 786; PTX, n = 788) were included for the final analysis. As compared with PTX monotherapy, PTX + targeted therapy significantly improved progression-free survival (hazard ratio  = 0.88, 95% confidence interval [CI] 0.84-0.92, P < .001), overall survival (hazard ratio  = 0.90, 95% CI: 0.86-0.95, P < .001) and was associated with a better objective response rate (RR = 1.80; 95% CI: 1.45-2.24; P < .001). PTX+targeted therapy group significantly increased incidences of grade 3 to 5 neutropenia, fatigue and neuropathy (P < .05). No statistically significant differences were observed in the incidences of grade 3 to 5 anemia, decreased appetite, nausea, diarrhea and abdominal pain between the two treatments (P >.05). CONCLUSIONS: Second-line PTX+targeted therapy is a more effective treatment option with tolerable safety profile for advanced gastric cancer as a result of improved survival, though with additional toxicity.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Paclitaxel/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Neoplasias Gástricas/patologia
10.
Anticancer Res ; 40(5): 2955-2960, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366448

RESUMO

BACKGROUND/AIM: Currently, there is no recommendation for the treatment of breast cancer (BC) with bone-marrow cell infiltration (BMI). We evaluated the efficacy and safety of weekly-paclitaxel in this population. PATIENTS AND METHODS: This retrospective study included all BC patients with BMI receiving weekly-paclitaxel between January 2014 and May 2018. Overall-survival (OS) was the primary endpoint. Secondary endpoints were progression-free-survival (PFS) and safety. RESULTS: BMI was diagnosed in 26 patients. This infiltration was suggested by peripheral blood smear in 73% of cases. All patients had anemia, and 77% had thrombocytopenia. OS and PFS were 7.2 months [95% confidence interval (CI)=2.6-20.7] and 3.3 months (95%CI=1.6-7.2), respectively. Good performance-status, absence of thrombocytopenia and presence of less than 5% of circulating erythroblasts at BMI diagnosis, were associated with better survival. One patient presented grade 5 febrile neutropenia but no episodes of bleeding were reported. CONCLUSION: Weekly-paclitaxel is an effective therapeutic option with limited toxicity for BC with BMI.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Paclitaxel/uso terapêutico , Adulto , Idoso , Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Paclitaxel/farmacologia , Análise de Sobrevida
11.
Phytomedicine ; 70: 153215, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32388040

RESUMO

BACKGROUND: Recalcitrant cancers appear as a major obstacle to chemotherapy, prompting scientists to intensify the search for novel drugs to tackle the cell lines expressing multi-drug resistant (MDR) phenotypes. PURPOSE: The purpose of this study was to evaluate the antiproliferative potential of a ferrulic acid derivative, 8,8-bis-(dihydroconiferyl)-diferulate (DHCF2) on a panel of 18 cancer cell lines, including various sensitive and drug-resistant phenotypes, belonging to human and animals. The mode of induction of cell death by this compound was further studied. METHODS: The antiproliferative activity, autophagy, ferroptotic and necroptotic cell death were evaluated by the resazurin reduction assay (RRA). CCRF-CEM leukemia cells were used for all mechanistic studies. A caspase-Glo assay was applied to evaluate the activity of caspases. Cell cycle analysis (PI staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP) (JC-1) and reactive oxygen species (ROS) (H2DCFH-DA) were assessed by flow cytometry. RESULTS: DHCF2 demonstrated impressive cytotoxic effects towards the 18 cancer cell lines tested, with IC50 values all below 6.5 µM. The obtained IC50 values were in the range of 1.17 µM (towards CCRF-CEM leukemia cells) to 6.34 µM (towards drug-resistant HCT116 p53-/- human colon adenocarcinoma cells) for DHCF2 and from 0.02 µM (against CCRF-CEM cells) to 122.96 µM (against multidrug-resistant CEM/ADR5000 leukemia cells) for the reference drug, doxorubicin. DHCF2 had IC50 values lower than those of doxorubicin, against CEM/ADR5000 cells and on some melanoma cell lines, such as MaMel-80a cells, Mel-2a cells, MV3 cells and SKMel-505 cells. DHCF2 induced autophagy as well as apoptosis in CCRF-CEM cells though caspases activation, MMP alteration and increase of ROS production. CONCLUSION: The studied diferulic acid, DHCF2, is a promising antiproliferative compound. It deserves further indepth investigations with the ultimate aim to develop a novel drug to fight cancer drug resistance.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Leucemia/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Doxorrubicina/uso terapêutico , Doxorrubicina/toxicidade , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Humanos , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade
12.
AAPS PharmSciTech ; 21(5): 151, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32440910

RESUMO

Triple-negative breast (TNBC) cancer that is upregulated with epidermal growth factor receptor (EGFR), and devoid of both the hormonal receptors and epidermal growth factor receptor 2 (HER 2), has led to a concept of treating TNBC with EGFR-targeted therapeutics. The combination of paclitaxel (PTX) and piperine (PIP) may improve the bioavailability of paclitaxel for cancer therapy. TPGS (vit E-PEG 1000-succinate)-coated liposomes were prepared with PTX alone or in combination with PIP, and either with (targeted) or without (non-targeted) cetuximab (CTX) conjugation. The Bradford assay indicated that 75% of CTX has been conjugated on the liposomes. The size and percent encapsulation of PTX&PIP co-loaded liposomes were found to be in the range of 204 to 218 nm and 31-73%, respectively. The drug release rate was found to be higher at pH 5.5 in comparison with release at pH 6.4 and pH 7.4. Cellular uptake and toxicity studies on MDA-MB-231 cells showed that PTX&PIP co-loaded targeted liposomes have demonstrated superior uptake and cytotoxicity than their non-targeted counterparts. The IC50 values of both of the liposomal formulations were found to be significantly higher than PTX control. Indeed, combining PIP with PTX control has improved the cytotoxicity of PTX control, which proved the synergistic anticancer effect of PIP. Lyophilized liposomes showed an excellent stability profile with the size range between 189 and 210 nm. Plasma stability study revealed a slight increase in the particle size due to the adsorption of plasma proteins on the surface of liposomes. The long-term stability study also indicated that liposomes were stable at 4°C.


Assuntos
Alcaloides/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Benzodioxóis/uso terapêutico , Paclitaxel/uso terapêutico , Piperidinas/uso terapêutico , Alcamidas Poli-Insaturadas/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Alcaloides/farmacologia , Antineoplásicos Fitogênicos/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica , Benzodioxóis/farmacologia , Linhagem Celular Tumoral , Composição de Medicamentos , Estabilidade de Medicamentos , Sinergismo Farmacológico , Receptores ErbB/efeitos dos fármacos , Feminino , Liofilização , Humanos , Lipossomos , Paclitaxel/metabolismo , Paclitaxel/farmacologia , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Receptor ErbB-2
13.
Environ Toxicol ; 35(10): 1125-1136, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32449848

RESUMO

This study aimed to evaluate the in vivo anticancer effects of daucosterol which was earlier reported to possess in vitro anticancer effects. Breast tumor was induced in 30 rats using the environmental carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) while 6 control rats received olive oil (NOR). Animals with palpable tumors were randomized into five groups (n = 6) each as follows: negative control group treated with the vehicle (DMBA); positive control group treated with 5 mg/kg BW doxorubicin (DOXO + DMBA); three groups treated with daucosterol at doses of 2.5, 5, and 10 mg/kg BW (DAU + DMBA). Treatment lasted 28 days afterward, tumor (mass, volume, cancer antigen [CA] 15-3 level and histoarchitecture), hematological and toxicological parameters were examined. The tumor volume gradually increased in the DMBA group during the 28 days, with a tumor volume gain of ∼390 cm3 . Daucosterol at all doses reduced tumor volume (∼133.7 cm3 at 10 mg/kg) as well as protein, malondialdehyde (MDA), and CA 15-3 levels compared to DMBA rats. Tumor sections in daucosterol-treated rats showed a lower proliferation of mammary ducts with mild (5 and 10 mg/kg) to moderate (2.5 mg/kg) inflammatory responses. Moreover, it exhibited an antioxidant effect, evidenced by a significant and dose-dependent decreased in MDA levels, as well as an increase in catalase activity compared to the DMBA group. Daucosterol showed for the first time in vivo antitumor effects that corroborate its previous in vitro effects.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Capparaceae/química , Neoplasias Mamárias Experimentais/tratamento farmacológico , Sitosteroides/farmacologia , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/uso terapêutico , Antioxidantes/metabolismo , Carcinógenos/toxicidade , Relação Dose-Resposta a Droga , Feminino , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Estrutura Molecular , Casca de Planta/química , Ratos , Ratos Wistar , Sitosteroides/isolamento & purificação , Sitosteroides/uso terapêutico
14.
Med Sci Monit ; 26: e921162, 2020 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-32246704

RESUMO

BACKGROUND This study used network pharmacology method and cell model to assess the effects of Radix Astragali (RA) on cholangiocarcinoma (CCA) and to predict core targets and molecular mechanisms. MATERIAL AND METHODS We performed an in vitro study to assess the effect of RA on CCA using CCK8 assay, the Live-Cell Analysis System, and trypan blue staining. The components and targets of RA were analyzed using the Traditional Chinese Medicine Systems Pharmacology database, and genes associated with CCA were retrieved from the GeneCards and OMIM platforms. Protein-protein interactions were analyzed with the STRING platform. The components-targets-disease network was built by Cytoscape. The TIMER database revealed the expression of core targets with diverse immune infiltration levels. GO and KEGG analyses were performed to identify molecular-biology processes and signaling pathways. The predictions were verified by Western blotting. RESULTS Concentration-dependent antitumor activity was confirmed in the cholangiocarcinoma QBC939 cell line treated with RA. RA contained 16 active compounds, with quercetin and kaempferol as the core compounds. The most important biotargets for RA in CCA were caspase 3, MAPK8, MYC, EGFR, and PARP. The TIMER database revealed that the expression of caspase3 and MYC was related with diverse immune infiltration levels of CCA. The results of Western blotting showed RA significantly influenced the expression of the 5 targets that network pharmacology predicted. CONCLUSIONS RA is an active medicinal material that can be developed into a safe and effective multi-targeted anticancer treatment for CCA.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Medicina Tradicional Chinesa/métodos , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
15.
Zhonghua Zhong Liu Za Zhi ; 42(3): 161-169, 2020 Mar 23.
Artigo em Chinês | MEDLINE | ID: mdl-32252194

RESUMO

Breast cancer is the most common malignant tumor among women. Taxanes are one of the most frequently used chemotherapy regimens for breast cancer. In order to guide clinicians rational use of taxanes and further standardize the diagnosis and treatment of breast cancer, the expert group proposed this "Expert consensus on the clinical practice of taxanes for the treatment of breast cancer" based on substantial evidence and thorough discussion.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Guias de Prática Clínica como Assunto , Taxoides/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/patologia , Neoplasias da Mama/psicologia , Quimioterapia Adjuvante , Consenso , Feminino , Humanos , Qualidade de Vida
16.
Zhongguo Zhong Yao Za Zhi ; 45(2): 444-450, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32237330

RESUMO

The traditional Chinese medicine(TCM) decoction pieces for treating tumors in China-Japan Friendship Hospital in both outpatient and inpatient departments from January 1 to December 31, 2018 were analyzed in this paper, and the statistical analysis on the frequency and proportion of TCM decoction pieces, as well as the average dosage and dosage range were conducted. Such data were then compared with Chinese Pharmacopoeia. At the same time, data mining association rules were used to study the compatibility of TCM in oncology, and finally, the drug use in TCM was discussed. The top 20(use frequency) TCM decoction pieces for tumors were mainly based on tonic medicines; the use frequency of toxic TCM decoction pieces was low, mainly of small poisonous pieces, with dosage exceeding pharmacopoeia. The drug combinations with higher frequency included Fried Atractylodis Macrocephalae Rhizoma-Poria Cocos(16.11%), and Astragali Radix-Poria Cocos(15.10%). Drug pairs with strong associations included Achyranthes Bidentata→Parasitic Loranthus, Coix Seed→Achyranthes Bidentata, Achyranthes Bidentata→Hairyvein Agrimony, Cuscutae Semen→Achyranthes Bidentata and so on. According to the use of drugs, the drug monitoring can be emphasized from the aspects of usage and dosage, selection of processed TCM, compatibility, decoction methods, and patient education. Pharmacists can analyze the characteristics and regularity of the use of TCM for tumors through data mining methods, and this can be a cutting point for drug monitoring.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Mineração de Dados , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias/tratamento farmacológico , China , Humanos , Japão , Medicina Tradicional Chinesa
17.
Environ Toxicol ; 35(9): 971-981, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32302048

RESUMO

Hepatocellular carcinoma (HCC) ranks the sixth position among various cancers worldwide. Recent research shows that natural and dietary compounds possess many therapeutic effects. Citral is a monoterpene aldehyde that contains geranial and neral. The present study was considered to study the role of citral against N-nitrosodiethylamine (NDEA)-induced HCC via modulation of antioxidants and xenobiotic-metabolizing enzymes in vivo. NDEA-alone-administered group II animals profoundly showed increased tumor incidence, reactive oxygen species, liver marker enzyme levels, serum bilirubin levels, tumor markers of carcinoembryonic antigen, α-fetoprotein, proliferative markers of argyrophilic nucleolar organizing regions, proliferating cell nuclear antigen (PCNA) expressions, phase I xenobiotic-metabolic enzymes and simultaneously decreased antioxidants, and phase II enzymes levels. Citral (100 mg/kg b.w.) treatment significantly reverted the levels in group III cancer-bearing animals when compared to group II cancer-bearing animals. In group IV animals, citral-alone administration did not produce any adverse effect during the experimental condition. Based on the results, citral significantly inhibits the hepatocellular carcinogenesis through restoring the antioxidants and phase II xenobiotic-enzyme levels; thereby, it strongly proves as an antiproliferative agent against rat HCC.


Assuntos
Monoterpenos Acíclicos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Antioxidantes/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Animais , Antígeno Carcinoembrionário/análise , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Dietilnitrosamina , Humanos , Testes de Função Hepática , Neoplasias Hepáticas Experimentais/enzimologia , Neoplasias Hepáticas Experimentais/patologia , Masculino , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Wistar , alfa-Fetoproteínas/análise
18.
Phytother Res ; 34(9): 2203-2213, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32239572

RESUMO

Ailanthone (AIT) is a quassinoid natural product isolated from the worldwide-distributed plant Ailanthus altissima. The drug displays multiple pharmacological properties, in particular significant antitumor effects against a variety of cancer cell lines in vitro. Potent in vivo activities have been evidenced in mice bearing hepatocellular carcinoma, nonsmall cell lung cancer and castration-resistant prostate cancer. This review focusses on the mechanism of action of AIT, notably to highlight the capacity of the drug to activate DNA damage responses, to inhibit the Hsp90 co-chaperone p23 and to modulate the expression of several microRNA. The interconnexion between these effects is discussed. The unique capacity of AIT to downregulate oncogenic miR-21 and to upregulate the tumor suppressor miRNAs miR-126, miR-148a, miR-195, and miR-449a is presented. AIT exploits several microRNAs to exert its anticancer effects in distinct tumor types. AIT is one of the rare antitumor natural products that binds to and strongly inhibits cochaperone p23, opening interesting perspectives to treat cancers. However, the toxicity profile of the molecule may limit its development as an anticancer drug, unless it can be properly formulated to prevent AIT-induced gastro-intestinal damages in particular. The antitumor properties of AIT and analogs are underlined, with the aim to encourage further pharmacological studies with this underexplored natural product and related quassinoids. HIGHLIGHTS: Ailanthone (AIT) is an anticancer quassinoid isolated from Ailanthus altissima It inhibits proliferation and induces cell death of many cancer cell types The drug activates DNA damage response and targets p23 cochaperone Up or downregulation of several microRNA by AIT contributes to the anticancer activity Analogs or specific formulations must be developed to prevent the toxicity of AIT.


Assuntos
Ailanthus/química , Antineoplásicos Fitogênicos/farmacologia , Quassinas/farmacologia , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos , MicroRNAs/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Quassinas/isolamento & purificação , Quassinas/uso terapêutico
19.
Artigo em Alemão | MEDLINE | ID: mdl-32211937

RESUMO

Mistletoe (Viscum album L.) continues to be the medical herb prescribed most frequently for cancer patients in German-speaking countries. Demand for this therapy often comes from patients themselves and requires careful consideration by the attending physician during consultation.In German-speaking countries, mistletoe extracts are available as approved drugs (based on monographs of the commissions C and E of the German Federal Institute for Drugs and Medical Devices). In Switzerland, treatment costs are generally covered by statutory health insurance. In Germany, coverage is limited to palliative care. In adjuvant cases, treating physicians can request coverage by the health insurance if patients suffer from side effects due to the antitumoral treatment.The spectrum of Viscum album extract includes mistletoe lectin I; II, and III, viscotoxins, flavonoids, amino acids, polysaccharides, and membrane lipids. Preclinical studies have demonstrated cytotoxic, apoptosis-inducing, and immunomodulatory effects.Many clinical studies indicate a supportive efficacy of mistletoe extracts in tumor patients, even though methodological quality is discussed controversially in many cases. Clinical data regarding effects on survival of patients is inconsistent; effects concerning quality of life as well as the tolerability of antitumoral treatments are evaluated more positively.In view of the high demand on the patient side and increasing scientific evidence, the general conditions for prescriptions should continue as well as the ongoing scientific evaluation.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Erva-de-Passarinho/química , Neoplasias/tratamento farmacológico , Fitoterapia/métodos , Viscum album , Antineoplásicos Fitogênicos/efeitos adversos , Alemanha , Humanos , Imunomodulação , Erva-de-Passarinho/metabolismo , Neoplasias/patologia , Neoplasias/psicologia , Extratos Vegetais/uso terapêutico , Qualidade de Vida , Suíça
20.
Phytother Res ; 34(8): 2053-2066, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32185829

RESUMO

Gemcitabine (GEM) resistance in pancreatic adenocarcinoma mediated by the receptor for advanced glycation end products (RAGE) has been demonstrated. Therefore, investigating the safety and the potential of new auxiliary methods for pancreatic cancer treatment is urgent. Ursolic acid (UA), a natural pentacyclic triterpenoid found in apple peels, rosemary, and thyme, has been reported to have anticancer capacity. This study aimed to reveal the underlying mechanisms of UA in cell death and drug enhancement, especially in GEM-resistant pancreatic cancer cells. First, GEM-resistant cells (MIA Paca-2GEMR cells) were established by incrementally increasing GEM culture concentrations. UA treatment reduced cell viability through cell cycle arrest and endoplasmic reticulum (ER) stress, resulting in apoptosis and autophagy in a dose-dependent manner in MIA Paca-2 and MIA Paca-2GEMR cells. High RAGE expression in MIA Paca-2GEMR cells was suppressed by UA treatment. Interestingly, knocking down RAGE expression showed similar UA-induced effects in both cell lines. Remarkably, UA had a drug-enhancing effect by decreasing cell viability and increasing cell cytotoxicity when combined with GEM treatment. In conclusions, UA triggered ER stress, subsequently regulating apoptosis- and autophagy-related pathways and increasing GEM chemosensitivity in pancreatic cancer cells by inhibiting the expression of RAGE.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Triterpenos/uso terapêutico , Antineoplásicos Fitogênicos/farmacologia , Apoptose , Autofagia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Neoplasias Pancreáticas/mortalidade , Taxa de Sobrevida , Triterpenos/farmacologia
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