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1.
Chin Clin Oncol ; 13(1): 5, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38453656

RESUMO

BACKGROUND: The management of chemotherapy induced anemia (CIA) remains challenging. The potential risk and benefits in providing patient-centered care need to be balanced; the disease is multifactorial; and the major treatments including red blood cell (RBC) transfusions, erythropoiesis-stimulating agents (ESAs) and intravenous injection (i.v.)iron supplementation have a unique set of strengths and limitations. Also, most previous survey based on the patient data could not reveal the process of evaluation and decision-making for CIA treatment from a physician's perspective. As the comparison of China Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN) and European Society of Medical Oncology (ESMO) guidelines, the standard of CIA treatment in China will vary from United States and Europe, for example, the initial hemoglobin (Hb) for RBC transfusions. In order to understand the diagnosis, treatment, and unmet medical needs of CIA patients, the China Medical Education Association (CMEA), in conjunction with Cancer Hope Medium, initiated the first national survey of Chinese physicians regarding the diagnosis and treatment of CIA. METHODS: The CMEA sent an online, 12-item questionnaire (via wjx.cn) to physicians across China from September 1, 2022 to October 22, 2022. Two hundred and sixty-five samples were calculated usingsurveyplanet.com. The questionnaire evaluated the impact of anemia on chemotherapy interruption, initial treatment, the target Hb level of CIA in, and the current status of ESAs prescription in clinical practice. Respondents were asked to score their reasons for not using ESAs (including safety issues, drug access in practice or adherence) and the risk options of the current treatment including ESAs, RBC transfusion, and i.v.iron. RESULTS: A total of 331 questionnaires among 5,000 web visits were gathered, covering 247 hospitals in 29 provinces across China, of which 130 (53%) were tier IIIA hospitals, 50 (20%) were tier III B hospitals, 59 (24%) were tier IIA hospitals, and 8 (3%) were tier II B hospitals. The frequency of chemotherapy dose delay/reduction due to anemia was 24% [standard deviation (SD) 49%]. Most responding physicians rated an initial Hb level for ESAs treatment to be 80 g/L, with a favorable Hb level for chemotherapy being 100 g/L (60%), which would not limit treatment availability. The majority (67.6%, n=221) of physicians who responded indicated that they had used ESAs for anemia correction, while the others (32.4%, n=106) reported never using them. CONCLUSIONS: This is the first study in conducting a large-scale survey on the diagnosis and treatment of CIA in China from a physicians' perspective. We found that in China, nearly one-quarter of patients undergoing chemotherapy with concurrent anemia may experience interruption of chemotherapy and that the initiation of anemia treatment is not adequately timed. In treating CIA, most physicians prioritize the completion of chemotherapy via Hb level over treating the symptoms of anemia.


Assuntos
Anemia , Antineoplásicos , Hematínicos , Neoplasias , Médicos , Humanos , Estados Unidos , Antineoplásicos/uso terapêutico , Anemia/induzido quimicamente , Anemia/tratamento farmacológico , Ferro/efeitos adversos , Hematínicos/efeitos adversos , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Inquéritos e Questionários , Percepção
2.
Biomed Pharmacother ; 173: 116375, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38460372

RESUMO

Combination chemotherapy is an effective approach for triple-negative breast cancer (TNBC) therapy, especially when drugs are administered at specific optimal ratios. However, at present, strategies involving precise and controllable ratios based on effective loading and release of drugs are unavailable. Herein, we designed and synthesized a glutathione (GSH)--responsive heterotrimeric prodrug and formulated it with an amphiphilic polymer to obtain nanoparticles (DSSC2 NPs) for precise synergistic chemotherapy of TNBC. The heterotrimeric prodrug was prepared using docetaxel (DTX) and curcumin (CUR) at the optimal synergistic ratio of 1: 2. DTX and CUR were covalently conjugated by disulfide linkers. Compared with control NPs, DSSC2 NPs had quantitative/ratiometric drug loading, high drug co-loading capacity, better colloidal stability, and less premature drug leakage. After systemic administration, DSSC2 NPs selectively accumulated in tumor tissues and released the encapsulated drugs triggered by high levels of GSH in cancer cells. In vitro and in vivo experiments validated that DSSC2 NPs released DTX and CUR at the predefined ratio and had a highly synergistic therapeutic effect on tumor suppression in TNBC, which can be attributed to ratiometric drug delivery and synchronous drug activation. Altogether, the heterotrimeric prodrug delivery system developed in this study represents an effective and novel approach for combination chemotherapy.


Assuntos
Antineoplásicos , Curcumina , Nanopartículas , Pró-Fármacos , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Docetaxel/uso terapêutico , Curcumina/farmacologia , Curcumina/uso terapêutico , Glutationa , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral
3.
Int Immunopharmacol ; 130: 111769, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38442584

RESUMO

Radiofrequency ablation (RFA) has been used as an alternative to surgical management of early-stage hepatocellular carcinoma (HCC). However, when large and irregular HCCs are subjected to RFA, a safety margin is usually difficult to obtain, thus causing a sublethal radiofrequency hyperthermia (RFH) at the ablated tumor margin. This study investigated the feasibility of using RFH to enhance the effect of OK-432 on HCC, with the aim to generate a tumor-free margin during RFA of HCC. Our results showed OK-432 could activate the cGAS-STING pathway, and RFH could further enhance the activation. Meanwhile, RFH could induce a high expression of TLR4, and TLR4 might be an upstream molecular of the cGAS-STING pathway. The combined therapy of RFH with OK-432 resulted in a better tumor response, and a prolonged survival compared to the other three treatments. In conclusion, RFH in combination with OK-432 might reduce the residual and recurrent tumor after RFA of large and irregular HCCs, and serve as a new option for other solid malignancies treated by RFA.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Hipertermia Induzida , Neoplasias Hepáticas , Proteínas de Membrana , Nucleotidiltransferases , Picibanil , Ablação por Radiofrequência , Receptor 4 Toll-Like , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Picibanil/farmacologia , Picibanil/uso terapêutico , Estudos Retrospectivos , Receptor 4 Toll-Like/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Animais , Camundongos , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Masculino
4.
Lasers Med Sci ; 39(1): 91, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38491201

RESUMO

Investigating combined treatment methodologies is crucial for addressing the complex nature of cancer. As an emerging strategy, nano-biotechnology encourages the design of unique nanocarriers possessing simultaneous therapeutic application properties. This study aims to explore the combined effects of photodynamic and anticancer treatments using a multifunctional nanocarrier system co-administering the photosensitizer IR780 and the anticancer agent curcumin (Cur) on lung cancer cells. Nanocarriers were prepared by encapsulation IR780 and Cur inside polyethylene glycol-capped mesoporous silica nanoparticles (Cur&IR780@MSN). Various concentrations of nanocarriers were evaluated on A549 cells following 5 min NIR laser light (continuous wave, 785 nm, 500 mW/cm2) irradiation. The internalization of nanocarriers was observed through the fluorescence of Cur. Changes in cell viability were determined using the MTT assay and AO/PI staining. A scratch assay analysis was also performed to examine the impact of combined treatments on cell migration. Characterization of the nanocarriers revealed adequate hydrophobic drug loading, temperature-inhibited feature, enhanced reactive oxygen species generation, a pH-dependent curcumin release profile, and high biocompatibility. Cur&IR780@MSN, which enabled the observation of synergistic treatment efficacy, successfully reduced cell viability by up to 78%. In contrast, monotherapies with curcumin-loaded nanocarriers (Cur@MSN) and IR780-loaded nanocarriers (IR780@MSN) resulted in a 38% and 56% decrease in cell viability, respectively. The constructed Cur&IR780@MSN nanocarrier has demonstrated remarkable performance in the application of combination therapies for lung cancer cells. These nanocarriers have the potential to inspire future studies in tumor treatment methods.


Assuntos
Antineoplásicos , Curcumina , Neoplasias Pulmonares , Nanopartículas , Fotoquimioterapia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Curcumina/farmacologia , Curcumina/uso terapêutico , Dióxido de Silício/química , Portadores de Fármacos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Nanopartículas/química
5.
In Vivo ; 38(2): 864-872, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38418111

RESUMO

BACKGROUND/AIM: Recent lung cancer treatments include an immune checkpoint inhibitor (ICI) pembrolizumab, platinum-based agents, plus an additional cytotoxic anticancer agent. Nutritional indices, such as the geriatric nutritional risk index (GNRI) and the prognostic nutritional index (PNI), are known to correlate with the prognosis of cancer chemotherapy. Several previous studies have investigated the relationship between PNI and treatment response in non-small cell lung cancer patients, reporting significantly increased OS and PFS in the high PNI group before treatment. However, the relationship between the three-drug combination and GNRI/PNI is unclear. The current study aimed to investigate the association of nutritional indices with duration of treatment success and occurrence of side effects in triple therapy. PATIENTS AND METHODS: Seventy-two patients with non-small cell lung cancer, treated with combination of carboplatin, pemetrexed, and pembrolizumab from November 2019 to September 30, 2022, were classified into two groups (High and Low) for GNRI and PNI, and a retrospective study was performed. RESULTS: In terms of time-to-treatment-failure (TTF), univariate and multivariate Cox proportional hazards regression analysis showed the Low-PNI group to have significantly shorter TTF than the High-PNI group (p=0.006); multivariate analysis results also showed PNI as a factor affecting TTF (HR=2.791, 95%CI=1.362-5.721, p=0.005). On the other hand, GNRI was not shown to be a factor affecting TTF. CONCLUSION: PNI at the start of treatment was an independent prognostic factor affecting treatment success time (TTF) in non-small cell lung cancer patients receiving triple therapy. However, PNI was not shown to be a prognostic predictor of irAE development.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Idoso , Neoplasias Pulmonares/tratamento farmacológico , Avaliação Nutricional , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Estudos Retrospectivos , Prognóstico , Antineoplásicos/uso terapêutico
6.
Adv Sci (Weinh) ; 11(16): e2308316, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38380506

RESUMO

Anti-HER2 (human epidermal growth factor receptor 2) therapies significantly increase the overall survival of patients with HER2-positive breast cancer. Unfortunately, a large fraction of patients may develop primary or acquired resistance. Further, a multidrug combination used to prevent this in the clinic places a significant burden on patients. To address this issue, this work develops a nanotherapeutic platform that incorporates bimetallic gold-silver hollow nanoshells (AuAg HNSs) with exceptional near-infrared (NIR) absorption capability, the small-molecule tyrosine kinase inhibitor pyrotinib (PYR), and Herceptin (HCT). This platform realizes targeted delivery of multiple therapeutic effects, including chemo-and photothermal activities, oxidative stress, and immune response. In vitro assays reveal that the HCT-modified nanoparticles exhibit specific recognition ability and effective internalization by cells. The released PYR inhibit cell proliferation by downregulating HER2 and its associated pathways. NIR laser application induces a photothermal effect and tumor cell apoptosis, whereas an intracellular reactive oxygen species burst amplifies oxidative stress and triggers cancer cell ferroptosis. Importantly, this multimodal therapy also promotes the upregulation of genes related to TNF and NF-κB signaling pathways, enhancing immune activation and immunogenic cell death. In vivo studies confirm a significant reduction in tumor volume after treatment, substantiating the potential effectiveness of these nanocarriers.


Assuntos
Neoplasias da Mama , Ouro , Hipertermia Induzida , Receptor ErbB-2 , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/terapia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Feminino , Humanos , Camundongos , Animais , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Hipertermia Induzida/métodos , Ouro/química , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , Prata/química , Linhagem Celular Tumoral , Modelos Animais de Doenças , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Terapia Combinada/métodos , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/química , Proliferação de Células/efeitos dos fármacos
7.
Phytother Res ; 38(4): 1932-1950, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38358681

RESUMO

Morinda citrifolia L., commonly known as Noni, has a longstanding history in traditional medicine for treating various diseases. Recently, there has been an increased focus on exploring Noni extracts and phytoconstituents, particularly for their effectiveness against cancers such as lung, esophageal, liver, and breast cancer, and their potential in cancer chemoprevention. This study aims to provide a comprehensive review of in vitro and in vivo studies assessing Noni's impact on cancer, alongside an exploration of its bioactive compounds. A systematic review was conducted, encompassing a wide range of scientific databases to gather pertinent literature. This review focused on in vitro and in vivo studies, as well as clinical trials that explore the effects of Noni fruit and its phytoconstituents-including anthraquinones, flavonoids, sugar derivatives, and neolignans-on cancer. The search was meticulously structured around specific keywords and criteria to ensure a thorough analysis. The compiled studies highlight Noni's multifaceted role in cancer therapy, showcasing its various bioactive components and their modes of action. This includes mechanisms such as apoptosis induction, cell cycle arrest, antiangiogenesis, and immune system modulation, demonstrating significant anticancer and chemopreventive potential. The findings reinforce Noni's potential as a safe and effective option in cancer prevention and treatment. This review underscores the need for further research into Noni's anticancer properties, with the hope of stimulating additional studies and clinical trials to validate and expand upon these promising findings.


Assuntos
Antineoplásicos , Produtos Biológicos , Neoplasias da Mama , Morinda , Humanos , Feminino , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Medicina Tradicional , Neoplasias da Mama/tratamento farmacológico , Frutas
8.
Clin Exp Pharmacol Physiol ; 51(4): e13847, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38382534

RESUMO

The use of all-trans retinoic acid and arsenic trioxide resulted in favourable therapeutic responses in standard-risk acute promyelocytic leukaemia (APL) patients. However, resistance to these agents has made treating the high-risk subgroup more problematic, and possible side effects limit their clinical dosages. Numerous studies have proven the cytotoxic properties of Gaillardin, one of the Inula oculus-christi-derived sesquiterpene lactones. Due to the adverse effects of arsenic trioxide on the high-risk subgroup of APL patients, we aimed to assess the cytotoxic effect of Gaillardin on HL-60 cells as a single or combined-form approach. The results of the trypan blue and MTT assays outlined the potent cytotoxic properties of Gaillardin. The flow cytometric analysis and the mRNA expression levels revealed that Gaillardin attenuated the proliferative capacity of HL-60 cells through cell cycle arrest and induced apoptosis via reactive oxygen species generation. Moreover, the results of synergistic experiments indicated that this sesquiterpene lactone sensitizes HL-60 cells to the cytotoxic effects of arsenic trioxide. Taken together, the findings of the present investigation highlighted the antileukemic characteristics of Gaillardin by inducing G1 cell cycle arrest and triggering apoptosis. Gaillardin acts as an antileukemic metabolite against HL-60 cells and this study provides new insight into treating APL patients, especially in the high-risk subgroup.


Assuntos
Antineoplásicos , Leucemia , Sesquiterpenos , Humanos , Trióxido de Arsênio/farmacologia , Células HL-60 , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Lactonas/farmacologia , Lactonas/uso terapêutico , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêutico , Leucemia/tratamento farmacológico , Apoptose , Óxidos/farmacologia , Óxidos/uso terapêutico
9.
Int J Mol Sci ; 25(3)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38338842

RESUMO

Hepatocellular carcinoma (HCC) is a leading global cause of cancer-related mortality. Despite the widespread adoption of sorafenib as the standard HCC treatment, its efficacy is constrained, frequently encountering resistance. To augment the effectiveness of sorafenib, this study investigated the synergy of sorafenib and vinorelbine using 22 HCC patient-derived xenograft (PDX) models. In this study, mice bearing HCC tumors were treated with the vehicle, sorafenib (15 mg/kg), vinorelbine (3 mg/kg), and sorafenib-vinorelbine combination (Sora/Vino). Rigorous monitoring of the tumor growth and side effects coupled with comprehensive histological and molecular analyses was conducted. The overall survival (OS) of mice bearing HCC orthotopic tumors was also assessed. Our data showed a notable 86.4% response rate to Sora/Vino, surpassing rates of 31.8% for sorafenib and 9.1% for vinorelbine monotherapies. Sora/Vino significantly inhibited tumor growth, prolonged OS of mice bearing HCC orthotopic tumors (p < 0.01), attenuated tumor cell proliferation and angiogenesis, and enhanced necrosis and apoptosis. The combination therapy effectively suppressed the focal adhesion kinase (FAK) pathway, which is a pivotal player in cell proliferation, tumor angiogenesis, survival, and metastasis. The noteworthy antitumor activity in 22 HCC PDX models positions Sora/Vino as a promising candidate for early-phase clinical trials, leveraging the established use of sorafenib and vinorelbine in HCC and other cancers.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Carcinoma Hepatocelular/metabolismo , Vinorelbina/farmacologia , Neoplasias Hepáticas/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Ensaios Antitumorais Modelo de Xenoenxerto , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
10.
Inflammopharmacology ; 32(2): 1593-1606, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38308794

RESUMO

BACKGROUND: Inflammation is a key biological reaction that comprises a complex network of signals that both initiate and stop the inflammation process. PURPOSE: This study targets to evaluate the anti-inflammatory potential of the leaves of the Plectranthus rugosus (P. rugosus) plant involving both in vitro and in vivo measures. The current available drugs exhibit serious side effects. Traditional medicines impart an essential role in drug development. P. rugosus is a plant used in traditional medicine of Tropical Africa, China, and Australia to treat various diseases. METHODS: Lipopolysaccharide (LPS), an endotoxin, kindles macrophages to discharge huge quantities of pro-inflammatory cytokines like TNF-α and IL-6. So, clampdown of macrophage stimulation may have a beneficial potential to treat various inflammatory disorders. The leaves of the P. rugosus are used for swelling purpose by local population; however, its use as an anti-inflammatory agent and associated disorders has no scientific evidence. RESULTS: The extracts of the plant Plectranthus rugosus ethanolic extract (PREE), Plectranthus rugosus ethyl acetate extract (PREAF), and the compound isolated (oleanolic acid) suppress the pro-inflammatory cytokines (IL-6 and TNF-α) and nitric oxide (NO), confirming its importance in traditional medicine. CONCLUSION: The pro-inflammatory cytokines are inhibited by P. rugosus extracts, as well as an isolated compound oleanolic acid without compromising cell viability.


Assuntos
Antineoplásicos , Ácido Oleanólico , Plectranthus , Antioxidantes/uso terapêutico , Fator de Necrose Tumoral alfa , Interleucina-6 , Ácido Oleanólico/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Extratos Vegetais/uso terapêutico , Inflamação/tratamento farmacológico , Citocinas , Antineoplásicos/uso terapêutico , Óxido Nítrico , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Lipopolissacarídeos/farmacologia
11.
Eur J Med Res ; 29(1): 106, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326876

RESUMO

Scientists have been compelled to search for alternative treatments due to the increasing prevalence of chemoresistance as well as the agonising and distressing side effects of both chemotherapy and radiation. Plant extracts have been exploited to treat various medical conditions for ages. Considering this fact, the main focus of various recent studies that are being conducted to find new and potent anticancer drugs involves the identification and utilisation of potential therapeutic chemicals present in plant extracts. Koetjapic acid (KJA), which belongs to the family of triterpenes, is primarily isolated from Sandoricum koetjape. Ongoing investigations into its therapeutic applications have revealed its tendency to impede the growth and proliferation of cancer cells. Koetjapic acid activates the intrinsic apoptotic pathway and promotes the death of cancer cells. Moreover, it inhibits angiogenesis and the dissemination of tumour (metastasis) by targeting the VEGF signalling cascade. Therefore, this study aims to elucidate the underlying mechanism of anticancer activity of koetjapic acid, providing significant insight into the compound's potential as an anticancer agent.


Assuntos
Antineoplásicos , Triterpenos , Humanos , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Triterpenos/química , Apoptose , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Extratos Vegetais/farmacologia
12.
Zhongguo Zhong Yao Za Zhi ; 49(1): 175-184, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38403350

RESUMO

The occurrence and development of tumors are associated with the cell energy metabolism. Inhibiting energy metabolism of lung cancer cells is an important strategy to overcome drug resistance. Based on the cellular energy metabolism pathway, this study observed the effect of combination of shikonin(SKN) and gefitinib(GFB) on the drug resistance in non-small cell lung cancer and explored the underlying mechanism. The human non-small cell lung cancer line HCC827/GR resistant to gefitinib was used as the cell model in vitro. The CCK-8 assay and flow cytometry were employed to investigate the cell viability and apoptosis, respectively. The high performance liquid chromatography was employed to measure the intracellular accumulation of GFB. A Seahorse XFe96 Analyzer was used to detect the changes of cellular energy metabolism. Western blot was employed to determine the expression of the proteins involved in the drug resistance. The tumor-bearing nude mouse model was used to verify the efficacy of SKN+GFB in overcoming drug resistance in vivo. The results showed that SKN+GFB significantly reduced the IC_(50) of GFB on HCC827/GR cells, with the combination index of 0.628, indicating that the combination of the two drugs had a synergistic effect and promoted cell apoptosis. SKN increased the intracellular accumulation of GFB. SKN+GFB lowered the oxygen consumption rate(OCR) and glycolytic proton efflux rate(GlycoPER) in cell energy metabolism, and down-regulated the overexpression of PKM2, p-EGFR, P-gp, and HIF-1α in drug resistance. The results of reversing drug resistance test in vivo showed that GFB or SKN alone had no significant antitumor effect, while the combination at different doses induced the apoptosis of the tumor tissue and inhibited the expression of PKM2 and P-gp, demonstrating a significant antitumor effect. Moreover, the tumor inhibition rate in the high-dose combination group reached 64.01%. In summary, SKN+GFB may interfere with the energy metabolism to limit the function of HCC827/GR cells, thus reversing the GFB resistance in non-small cell lung cancer.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Naftoquinonas , Animais , Camundongos , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Gefitinibe/farmacologia , Gefitinibe/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Quinazolinas/farmacologia , Resistencia a Medicamentos Antineoplásicos , Proliferação de Células , Linhagem Celular Tumoral , Apoptose
13.
Int J Mol Sci ; 25(4)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38396953

RESUMO

Biosynthetic gold nanoparticles (bAuNPs) present a promising avenue for enhancing bio-compatibility and offering an economically and environmentally responsible alternative to traditional production methods, achieved through a reduction in the use of hazardous chemicals. While the potential of bAuNPs as anticancer agents has been explored, there is a limited body of research focusing on the crucial physicochemical conditions influencing bAuNP production. In this study, we aim to identify the optimal growth phase of Pseudomonas aeruginosa cultures that maximizes the redox potential and coordinates the formation of bAuNPs with increased efficiency. The investigation employs 2,6-dichlorophenolindophenol (DCIP) as a redox indicator. Simultaneously, we explore the impact of temperature, pH, and incubation duration on the biosynthesis of bAuNPs, with a specific emphasis on their potential application as antitumor agents. Characterization of the resulting bAuNPs is conducted using ATR-FT-IR, TEM, and UV-Vis spectroscopy. To gain insights into the anticancer potential of bAuNPs, an experimental model is employed, utilizing both non-neoplastic (HPEpiC) and neoplastic (PC3) epithelial cell lines. Notably, P. aeruginosa cultures at 9 h/OD600 = 1, combined with biosynthesis at pH 9.0 for 24 h at 58 °C, produce bAuNPs that exhibit smaller, more spherical, and less aggregated characteristics. Crucially, these nanoparticles demonstrate negligible effects on HPEpiC cells while significantly impacting PC3 cells, resulting in reduced viability, migration, and lower IL-6 levels. This research lays the groundwork for the development of more specialized, economical, and ecologically friendly treatment modalities.


Assuntos
Antineoplásicos , Nanopartículas Metálicas , Neoplasias da Próstata , Humanos , Masculino , Antibacterianos/química , Ouro/química , Espectroscopia de Infravermelho com Transformada de Fourier , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Química Verde/métodos , Extratos Vegetais/química
14.
Medicina (Kaunas) ; 60(2)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38399496

RESUMO

Background and Objectives: Nowadays, the development of enabled pharmaceutical nanoparticles of solid lipid type is continuously growing, because they have the potential to be used for targeted drug release leading to an increased effect of chemotherapy, being used in lung cancer nano-diagnosis and nano-therapy. The current study reports the preliminary results obtained regarding the biological effect of a new nano-enabled pharmaceutical formulation in terms of its cytotoxic and biosafety profile. Materials and Methods: The pharmaceutical formulations consist of solid lipid nanoparticles (SLN) obtained via the emulsification-diffusion method by loading green iron oxide nanoparticles (green-IONPs) with a pentacyclic triterpene (oleanolic acid-OA). Further, a complex biological assessment was performed, employing three-dimensional (3D) bronchial microtissues (EpiAirwayTM) to determine the biosafety profile of the SLN samples. The cytotoxic potential of the samples was evaluated on human lung carcinoma, using an in vitro model (A549 human lung carcinoma monolayer). Results: The data revealed that the A549 cell line was strongly affected after treatment with SLN samples, especially those that contained OA-loaded green-IONPs obtained with Ocimum basilicum extract (under 30% viability rates). The biosafety profile investigation of the 3D normal in vitro bronchial model showed that all the SLN samples negatively affected the viability of the bronchial microtissues (below 50%). As regards the morphological changes, all the samples induce major changes such as loss of the surface epithelium integrity, loss of epithelial junctions, loss of cilia, hyperkeratosis, and cell death caused by apoptosis. Conclusions: In summary, the culprit for the negative impact on viability and morphology of 3D normal bronchial microtissues could be the too-high dose (500 µg/mL) of the SLN sample used. Nevertheless, further adjustments in the SLN synthesis process and another complex in vitro evaluation will be considered for future research.


Assuntos
Antineoplásicos , Carcinoma , Neoplasias Pulmonares , Nanopartículas , Humanos , Composição de Medicamentos/métodos , Neoplasias Pulmonares/patologia , Antineoplásicos/uso terapêutico , Pulmão/patologia , Portadores de Fármacos/uso terapêutico , Tamanho da Partícula
15.
J Nat Med ; 78(2): 342-354, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38324123

RESUMO

Evodiamine, a novel alkaloid, was isolated from the fruit of tetradium. It exerts a diversity of pharmacological effects and has been used to treat gastropathy, hypertension, and eczema. Several studies reported that evodiamine has various biological effects, including anti-nociceptive, anti-bacterial, anti-obesity, and anti-cancer activities. However, there is no research regarding its effects on drug-resistant cancer. This study aimed to investigate the effect of evodiamine on human vemurafenib-resistant melanoma cells (A375/R cells) proliferation ability and its mechanism. Cell activity was assessed using the cell counting kit-8 (CCK-8) method. Flow cytometry assay was used to assess cell apoptosis and cell cycle. A xenograft model was used to analyze the inhibitory effects of evodiamine on tumor growth. Bioinformatics analyses, network pharmacology, and molecular docking were used to explore the potential mechanism of evodiamine in vemurafenib-resistant melanoma. RT-qPCR and Western blotting were performed to reveal the molecular mechanism. The alkaloid extract of the fruit of tetradium, evodiamine showed the strongest tumor inhibitory effect on vemurafenib-resistant melanoma cells compared to treatment with vemurafenib alone. Evodiamine inhibited vemurafenib-resistant melanoma cell growth, proliferation, and induced apoptosis, conforming to a dose-effect relationship and time-effect relationship. Results from network pharmacology and molecular docking suggested that evodiamine might interact with IRS4 to suppress growth of human vemurafenib-resistant melanoma cells. Interestingly, evodiamine suppressed IRS4 expression and then inhibited PI3K/AKT signaling pathway, and thus had the therapeutic action on vemurafenib-resistant melanoma.


Assuntos
Alcaloides , Antineoplásicos , Melanoma , Quinazolinas , Humanos , Vemurafenib/farmacologia , Vemurafenib/uso terapêutico , Melanoma/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Simulação de Acoplamento Molecular , Transdução de Sinais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Proliferação de Células , Alcaloides/farmacologia , Linhagem Celular Tumoral , Proteínas Substratos do Receptor de Insulina/metabolismo
16.
Sci Rep ; 14(1): 4349, 2024 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-38388674

RESUMO

Chemotherapy-induced alopecia (CIA) is a common and debilitating condition in children, with limited research on its characteristics and treatment. Therefore, this study aims to describe the characteristics of pediatric patients with CIA and the treatment outcomes of topical minoxidil and L-cystine, medicinal yeast, and pantothenic acid complex-based dietary supplements (CYP). This retrospective cohort study analyzed data from patients who underwent high-dose conditioning chemotherapy followed by hematopoietic stem cell transplantation and were treated with either topical minoxidil or CYP for CIA between January 2011 and January 2022. Among the 70 patients evaluated, 61 (87.1%) experienced clinical improvement. Patients in the groups with superior treatment outcomes received a greater cumulative amount of minoxidil and underwent treatment for a more extended duration (P < 0.05) than those in the other groups. All 70 (100%) patients received topical minoxidil, and 42 (60%) were administered CYP. Hair thickness was significantly higher in the combination therapy group than in the minoxidil monotherapy group (21.4% vs. 9.3%, P = 0.02). However, only 3 (4.3%) patients reported mild and self-limiting adverse events. In conclusion, our study shows that minoxidil and CYP administration represent viable treatment options for pediatric CIA.


Assuntos
Antineoplásicos , Minoxidil , Humanos , Criança , Minoxidil/efeitos adversos , Estudos Retrospectivos , Alopecia/induzido quimicamente , Alopecia/tratamento farmacológico , Resultado do Tratamento , Suplementos Nutricionais , Antineoplásicos/uso terapêutico , Administração Tópica
17.
Chemistry ; 30(13): e202400007, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38258423

RESUMO

Modern nanodrug delivery technologies offer new approaches in the fight against cancer. However, due to the heterogeneity of tumors and side effects of anticancer drugs, monotherapies are less effective. Herein, we report a novel pH and light dual-responsive nanodrug delivery platform. The platform was formed by sulfonate-modified gold nanoparticles loaded with the anticancer drugs doxorubicin (DOX) and glucose oxidase (GOx) and then covered by water-soluble pillar[5]arene as a nanovalve. The nanovalve formed by the host-guest interaction between pillar[5]arene and the sulfonic acid group grafted onto the gold nanoparticle increased the drug loading capacity of the nanoplatform and enabled sustained release of the drug in a simulated weakly acidic tumor environment. The released GOx can consume intracellular glucose, namely, starvation therapy, while the generated hydrogen peroxide can further kill tumor cells, complementing DOX chemotherapy. Gold nanoparticles have good photothermal conversion ability and can enhance the drugs release rate under specific wavelengths of light irradiation. The results of in vitro and in vivo experiments showed that this novel nanodrug delivery platform has good biocompatibility and better therapeutic efficacy relative to monotherapy. This study successfully developed a combined chemo/starvation therapy strategy with good tumor suppression, providing a new approach for cancer treatment.


Assuntos
Antineoplásicos , Nanopartículas Metálicas , Nanopartículas , Neoplasias , Humanos , Ouro , Fototerapia , Sistemas de Liberação de Medicamentos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Neoplasias/tratamento farmacológico , Liberação Controlada de Fármacos , Linhagem Celular Tumoral
18.
Eur J Med Res ; 29(1): 90, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291541

RESUMO

Cancer is a disease that can cause abnormal cell growth and can spread throughout the body. It is among the most significant causes of death worldwide, resulting in approx. 10 million deaths annually. Many synthetic anticancer drugs are available, but they often come with side effects and can interact negatively with other medications. Additionally, many chemotherapy drugs used for cancer treatment can develop resistance and harm normal cells, leading to dose-limiting side effects. As a result, finding effective cancer treatments and developing new drugs remains a significant challenge. However, plants are a potent source of natural products with the potential for cancer treatment. These biologically active compounds may be the basis for enhanced or less toxic derivatives. Herbal medicines/phytomedicines, or plant-based drugs, are becoming more popular in treating complicated diseases like cancer due to their effectiveness and are a particularly attractive option due to their affordability, availability, and lack of serious side effects. They have broad applicability and therapeutic efficacy, which has spurred scientific research into their potential as anticancer agents. This review focuses on Paclitaxel (PTX), a plant-based drug derived from Taxus sp., and its ability to treat specific tumors. PTX and its derivatives are effective against various cancer cell lines. Researchers can use this detailed information to develop effective and affordable treatments for cancer.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Paclitaxel/farmacologia , Paclitaxel/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Plantas
19.
ACS Nano ; 18(5): 4398-4413, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38275273

RESUMO

Arsenic trioxide (As2O3) has achieved groundbreaking success in the treatment of acute promyelocytic leukemia (APL). However, its toxic side effects seriously limit its therapeutic application in the treatment of solid tumors. To detoxify the severe side effects of arsenic, herein we synthesized innovative 2D ultrathin As2Se3 nanosheets (As2Se3 NSs) with synergistic photothermal-triggered immunotherapy effects. As2Se3 NSs are biocompatible and biodegradable under physiological conditions and can release As(III) and Se(0). Furthermore, selenium increases the immunomodulatory efficacy of arsenic treatments, facilitating reprogramming of the tumor microenvironment by As2Se3 NSs by enhancing the infiltration of natural killer cells and effector tumor-specific CD8+ T cells. The synergistic combination of photothermal therapy and immunotherapy driven by As2Se3 NSs via a simple but effective all-in-one strategy achieved efficient anticancer effects, addressing the key limitations of As2O3 for solid tumor treatment. This work demonstrates not only the great potential of selenium for detoxifying arsenic but also the application of 2D As2Se3 nanosheets for cancer therapy.


Assuntos
Antineoplásicos , Arsênio , Arsenicais , Neoplasias , Selênio , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linfócitos T CD8-Positivos , Imunoterapia , Neoplasias/tratamento farmacológico , Óxidos/farmacologia , Selênio/farmacologia , Selênio/uso terapêutico , Microambiente Tumoral , Trióxido de Arsênio
20.
Phytother Res ; 38(2): 1104-1158, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38176694

RESUMO

Natural products have played a significant role throughout history in the prevention and treatment of numerous diseases, particularly cancers. As a natural product primarily derived from various medicinal plants in the Withania genus, withanolides have been shown in several studies to exhibit potential activities in cancer treatment. Consequently, understanding the molecular mechanism of withanolides could herald the discovery of new anticancer agents. Withanolides have been studied widely, especially in the last 20 years, and attracted the attention of numerous researchers. Currently, over 1200 withanolides have been classified, with approximately a quarter of them having been reported in the literature to be able to modulate the survival and death of cancer cells through multiple avenues. To what extent, though, has the anticancer effects of these compounds been studied? How far are they from being developed into clinical drugs? What are their potential, characteristic features, and challenges? In this review, we elaborate on the current knowledge of natural compounds belonging to this class and provide an overview of their natural sources, anticancer activity, mechanism of action, molecular targets, and implications for anticancer drug research. In addition, direct targets and clinical research to guide the design and implementation of future preclinical and clinical studies to accelerate the application of withanolides have been highlighted.


Assuntos
Antineoplásicos , Neoplasias , Plantas Medicinais , Withania , Vitanolídeos , Humanos , Vitanolídeos/farmacologia , Vitanolídeos/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico
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