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1.
Biochemistry (Mosc) ; 89(Suppl 1): S127-S147, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38621748

RESUMO

The strategies of future medicine are aimed to modernize and integrate quality approaches including early molecular-genetic profiling, identification of new therapeutic targets and adapting design for clinical trials, personalized drug screening (PDS) to help predict and individualize patient treatment regimens. In the past decade, organoid models have emerged as an innovative in vitro platform with the potential to realize the concept of patient-centered medicine. Organoids are spatially restricted three-dimensional clusters of cells ex vivo that self-organize into complex functional structures through genetically programmed determination, which is crucial for reconstructing the architecture of the primary tissue and organs. Currently, there are several strategies to create three-dimensional (3D) tumor systems using (i) surgically resected patient tissue (PDTOs, patient-derived tumor organoids) or (ii) single tumor cells circulating in the patient's blood. Successful application of 3D tumor models obtained by co-culturing autologous tumor organoids (PDTOs) and peripheral blood lymphocytes have been demonstrated in a number of studies. Such models simulate a 3D tumor architecture in vivo and contain all cell types characteristic of this tissue, including immune system cells and stem cells. Components of the tumor microenvironment, such as fibroblasts and immune system cells, affect tumor growth and its drug resistance. In this review, we analyzed the evolution of tumor models from two-dimensional (2D) cell cultures and laboratory animals to 3D tissue-specific tumor organoids, their significance in identifying mechanisms of antitumor response and drug resistance, and use of these models in drug screening and development of precision methods in cancer treatment.


Assuntos
Neoplasias , Medicina de Precisão , Animais , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Organoides , Avaliação Pré-Clínica de Medicamentos , Microambiente Tumoral
2.
BMC Complement Med Ther ; 24(1): 125, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38500118

RESUMO

BACKGROUND: Osimertinib is regarded as a promising third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for advanced non-squamous non-small cell lung cancer (NSCLC) patients who developed T790M. However the adverse effects, primarily fatigue, remain an overwhelming deficiency of Osimertinib, hindering it from achieving adequate clinical efficacy for such NSCLC. Ganoderma lucidum has been used for thousands of years in China to combat fatigue, while Ganoderma Lucidum spores powder (GLSP) is the main active ingredient. The aim of this study is to investigate whether GLSP is sufficiently effective and safe in improving fatigue and synergizing with Osimertinib in non-squamous NSCLC patients with EGFR mutant. METHOD/DESIGN: A total of 140 participants will be randomly assigned to receive either de-walled GSLP or placebo for a duration of 56 days. The primary outcome measure is the fatigue score associated with EGFR-TKI adverse reactions at week 8, evaluated by the Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Patients (QLQ-C30). Secondary outcomes include evaluation of treatment effectiveness, assessment of quality of life (QoL), and exploration of immune indicators and gut microbiota relationships. Following enrollment, visits are scheduled biweekly until week 12. TRIAL REGISTRATION: China Clinical Trial Registry ChiCTR2300072786. Registrated on June 25, 2023.


Assuntos
Acrilamidas , Compostos de Anilina , Carcinoma Pulmonar de Células não Pequenas , Indóis , Neoplasias Pulmonares , Pirimidinas , Reishi , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Qualidade de Vida , Pós/uso terapêutico , Receptores ErbB/genética , Inibidores de Proteínas Quinases/efeitos adversos , Mutação , Esporos Fúngicos , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Int J Mol Sci ; 25(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38473776

RESUMO

Glioblastoma (GB) stands out as the most prevalent and lethal form of brain cancer. Although great efforts have been made by clinicians and researchers, no significant improvement in survival has been achieved since the Stupp protocol became the standard of care (SOC) in 2005. Despite multimodality treatments, recurrence is almost universal with survival rates under 2 years after diagnosis. Here, we discuss the recent progress in our understanding of GB pathophysiology, in particular, the importance of glioma stem cells (GSCs), the tumor microenvironment conditions, and epigenetic mechanisms involved in GB growth, aggressiveness and recurrence. The discussion on therapeutic strategies first covers the SOC treatment and targeted therapies that have been shown to interfere with different signaling pathways (pRB/CDK4/RB1/P16ink4, TP53/MDM2/P14arf, PI3k/Akt-PTEN, RAS/RAF/MEK, PARP) involved in GB tumorigenesis, pathophysiology, and treatment resistance acquisition. Below, we analyze several immunotherapeutic approaches (i.e., checkpoint inhibitors, vaccines, CAR-modified NK or T cells, oncolytic virotherapy) that have been used in an attempt to enhance the immune response against GB, and thereby avoid recidivism or increase survival of GB patients. Finally, we present treatment attempts made using nanotherapies (nanometric structures having active anti-GB agents such as antibodies, chemotherapeutic/anti-angiogenic drugs or sensitizers, radionuclides, and molecules that target GB cellular receptors or open the blood-brain barrier) and non-ionizing energies (laser interstitial thermal therapy, high/low intensity focused ultrasounds, photodynamic/sonodynamic therapies and electroporation). The aim of this review is to discuss the advances and limitations of the current therapies and to present novel approaches that are under development or following clinical trials.


Assuntos
Glioblastoma , Glioma , Hipertermia Induzida , Humanos , Fosfatidilinositol 3-Quinases , Terapia Combinada , Microambiente Tumoral
4.
Mol Pharm ; 21(5): 2340-2350, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38546166

RESUMO

Uveal melanoma (UM) is the most common primary ocular malignancy in adults and has high mortality. Recurrence, metastasis, and therapeutic resistance are frequently observed in UM, but no beneficial systemic therapy is available, presenting an urgent need for developing effective therapeutic drugs. Verteporfin (VP) is a photosensitizer and a Yes-Associated Protein (YAP) inhibitor that has been used in clinical practice. However, VP's lack of tumor targetability, poor biocompatibility, and relatively low treatment efficacy hamper its application in UM management. Herein, we developed a biocompatible CD44-targeting hyaluronic acid nanoparticle (HANP) carrying VP (HANP/VP) to improve UM treatment efficacy. We found that HANP/VP showed a stronger inhibitory effect on cell proliferation than that of free VP in UM cells. Systemic delivery of HANP/VP led to targeted accumulation in the UM-tumor-bearing mouse model. Notably, HANP/VP mediated photodynamic therapy (PDT) significantly inhibited UM tumor growth after laser irradiation compared with no treatment or free VP treatment. Consistently, in HANP/VP treated tumors after laser irradiation, the tumor proliferation and YAP expression level were decreased, while the apoptotic tumor cell and CD8+ immune cell levels were elevated, contributing to effective tumor growth inhibition. Overall, the results of this preclinical study showed that HANP/VP is an effective nanomedicine for tumor treatment through PDT and inhibition of YAP in the UM tumor mouse model. Combining phototherapy and molecular-targeted therapy offers a promising approach for aggressive UM management.


Assuntos
Proliferação de Células , Ácido Hialurônico , Melanoma , Nanopartículas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Neoplasias Uveais , Verteporfina , Verteporfina/farmacologia , Verteporfina/uso terapêutico , Animais , Fotoquimioterapia/métodos , Neoplasias Uveais/tratamento farmacológico , Neoplasias Uveais/patologia , Camundongos , Melanoma/tratamento farmacológico , Melanoma/patologia , Humanos , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Linhagem Celular Tumoral , Nanopartículas/química , Proliferação de Células/efeitos dos fármacos , Ácido Hialurônico/química , Receptores de Hialuronatos/metabolismo , Apoptose/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas de Sinalização YAP , Camundongos Nus , Terapia de Alvo Molecular/métodos , Camundongos Endogâmicos BALB C , Feminino
5.
Neuro Oncol ; 26(7): 1247-1261, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38366847

RESUMO

BACKGROUND: Precision treatment of glioblastoma is increasingly focused on molecular subtyping, with the mesenchymal subtype particularly resistant to temozolomide. Here, we aim to develop a targeted therapy for temozolomide resensitization in the mesenchymal subtype. METHODS: We integrated kinomic profiles and kinase inhibitor screens from patient-derived proneural and mesenchymal glioma-propagating cells and public clinical datasets to identify key protein kinases implicated in temozolomide resistance. RNAseq, apoptosis assays, and comet assays were used to examine the role of p38MAPK signaling and adaptive chemoresistance in mesenchymal cells. The efficacy of dual p38MAPK and MEK/ERK inhibition using ralimetinib (selective orally active p38MAPK inhibitor; phase I/II for glioblastoma) and binimetinib (approved MEK1/2 inhibitor for melanoma; phase II for high-grade glioma) in primary and recurrent mesenchymal tumors was evaluated using an intracranial patient-derived tumor xenograft model, focusing on survival analysis. RESULTS: Our transcriptomic-kinomic integrative analysis revealed p38MAPK as the prime target whose gene signature enables patient stratification based on their molecular subtypes and provides prognostic value. Repurposed p38MAPK inhibitors synergize favorably with temozolomide to promote intracellular retention of temozolomide and exacerbate DNA damage. Mesenchymal cells exhibit adaptive chemoresistance to p38MAPK inhibition through a pH-/calcium-mediated MEK/ERK pathway. Dual p38MAPK and MEK inhibition effectively maintain temozolomide sensitivity in primary and recurrent intracranial mesenchymal glioblastoma xenografts. CONCLUSIONS: Temozolomide resistance in mesenchymal glioblastoma is associated with p38MAPK activation. Adaptive chemoresistance in p38MAPK-resistant cells is mediated by MEK/ERK signaling. Adjuvant therapy with dual p38MAPK and MEK inhibition prolongs temozolomide sensitivity, which can be developed into a precision therapy for the mesenchymal subtype.


Assuntos
Neoplasias Encefálicas , Resistencia a Medicamentos Antineoplásicos , Glioblastoma , Temozolomida , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas Quinases p38 Ativadas por Mitógeno , Temozolomida/farmacologia , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Glioblastoma/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Camundongos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Antineoplásicos Alquilantes/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Células Tumorais Cultivadas , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Prognóstico
6.
Int J Mol Sci ; 25(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38338736

RESUMO

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Liver cirrhosis, hepatitis B, hepatitis C, and non-alcoholic fatty liver disease represent major risk factors of HCC. Multiple different treatment options are available, depending on the Barcelona Clinic Liver Cancer (BCLC) algorithm. Systemic treatment is reserved for certain patients in stages B and C, who will not benefit from regional treatment methods. In the last fifteen years, the arsenal of available therapeutics has largely expanded, which improved treatment outcomes. Nevertheless, not all patients respond to these agents and novel combinations and drugs are needed. In this review, we aim to summarize the pathway of trials investigating the safety and efficacy of targeted therapeutics and immunotherapies since the introduction of sorafenib. Furthermore, we discuss the current evidence regarding resistance mechanisms and potential novel targets in the treatment of advanced HCC.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Sorafenibe/uso terapêutico , Fatores de Risco
7.
Front Immunol ; 15: 1333993, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38352872

RESUMO

Rheumatoid arthritis (RA) and postmenopausal osteoporosis (PMOP) are common bone-immune diseases. The imbalance between helper (Th17) and regulatory T cells (Tregs) produced during differentiation of CD4+ T cells plays a key regulatory role in bone remodelling disorders in RA and PMOP. However, the specific regulatory mechanism of this imbalance in bone remodelling in RA and PMOP has not been clarified. Identifying the regulatory mechanism underlying the Th17/Treg imbalance in RA and PMOP during bone remodelling represents a key factor in the research and development of new drugs for bone immune diseases. In this review, the potential roles of Th17, Treg, and Th17/Treg imbalance in regulating bone remodelling in RA and PMOP have been summarised, and the potential mechanisms by which probiotics, traditional Chinese medicine compounds, and monomers maintain bone remodelling by regulating the Th17/Treg balance are expounded. The maintenance of Th17/Treg balance could be considered as an therapeutic alternative for the treatment of RA and PMOP. This study also summarizes the advantages and disadvantages of conventional treatments and the quality of life and rehabilitation of patients with RA and PMOP. The findings presented her will provide a better understanding of the close relationship between bone immunity and bone remodelling in chronic bone diseases and new ideas for future research, prevention, and treatment of bone immune diseases.


Assuntos
Artrite Reumatoide , Doenças Ósseas , Humanos , Feminino , Linfócitos T Reguladores , Qualidade de Vida , Artrite Reumatoide/tratamento farmacológico , Células Th17 , Doenças Ósseas/tratamento farmacológico
8.
Phytother Res ; 38(4): 1830-1837, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38353369

RESUMO

CD44+ cancer stem cells (CSCs) are believed to account for drug resistance and tumour recurrence due to their potential to self-renew and differentiate into heterogeneous lineages. Therefore, efficient treatment strategies targeting and eliminating these CSCs are required. The flavonolignan, Silibinin, has gained immense attention in targeting CD44+ CSCs as it alters functional properties like cell cycle arrest, apoptosis, inhibition of invasion and metastasis and also inhibits a range of molecular pathways. However, its limited bioavailability is a major hurdle in asserting Silibinin as a translational therapeutic agent. Combinatorial therapy of Silibinin with conventional chemotherapeutic drugs is an alternative approach in targeting CD44+ CSCs as it increases the efficacy and reduces the cytotoxicity of chemotherapeutic drugs, thus preventing drug resistance. Certain Silibinin-conjugated nano-formulations have also been successfully developed, through which there is improved absorptivity/bioavailability of Silibinin and a decrease in the concentration of therapeutic drugs leading to reduced cytotoxicity. In this review, we summarise the effectiveness of the synergistic therapeutic approach for Silibinin in targeting the molecular mechanisms of CD44+ CSCs and emphasise the potential role of Silibinin as a novel therapeutic agent.


Assuntos
Neoplasias , Humanos , Receptores de Hialuronatos/metabolismo , Receptores de Hialuronatos/uso terapêutico , Neoplasias/tratamento farmacológico , Células-Tronco Neoplásicas , Silibina/farmacologia
9.
Exp Hematol Oncol ; 13(1): 15, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336927

RESUMO

Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death globally. Although the gut microbiota's role in the antitumor efficacy of many cancers has been revealed, its involvement in the response to gefitinib therapy for LUAD remains unclear. To fill this gap, we conducted a longitudinal study that profiled gut microbiota changes in PC-9 tumor-bearing mice under different treatments, including gefitinib monotherapy and combination therapies with probiotics, antibiotics, or Traditional Chinese Medicine (TCM). Our findings demonstrated that combining probiotics or TCM with gefitinib therapy outperformed gefitinib monotherapy, as evidenced by tumor volume, body weight, and tumor marker tests. By contrast, antibiotic intervention suppressed the antitumor efficacy of gefitinib. Notably, the temporal changes in gut microbiota were strongly correlated with the different treatments, prompting us to investigate whether there is a causal relationship between gut microbiota and the antitumor efficacy of gefitinib using Mediation Analysis (MA). Finally, our research revealed that thirteen mediators (Amplicon Sequence Variants, ASVs) regulate the antitumor effect of gefitinib, regardless of treatment. Our study provides robust evidence supporting the gut microbiota's significant and potentially causal role in mediating gefitinib treatment efficacy in mice. Our findings shed light on a novel strategy for antitumor drug development by targeting the gut microbiota.

10.
Int J Pharm ; 651: 123763, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38176478

RESUMO

Nanomaterials' application in cancer therapy has been driven by their ability to encapsulate chemotherapeutic drugs as well as to reach the tumor site. Nevertheless, nanomedicines' translation has been limited due to their lack of specificity towards cancer cells. Although the nanomaterials' surface can be coated with targeting ligands, such has been mostly achieved through non-covalent functionalization strategies that are prone to premature detachment. Notwithstanding, cancer cells often establish resistance mechanisms that impair the effect of the loaded drugs. This bottleneck may be addressed by using near-infrared (NIR)-light responsive nanomaterials. The NIR-light triggered hyperthermic effect generated by these nanomaterials can cause irreversible damage to cancer cells or sensitize them to chemotherapeutics' action. Herein, a novel covalently functionalized targeted NIR-absorbing nanomaterial for cancer chemo-photothermal therapy was developed. For such, dopamine-reduced graphene oxide nanomaterials were covalently bonded with hyaluronic acid, and then loaded with doxorubicin (DOX/HA-DOPA-rGO). The produced nanomaterials showed suitable physicochemical properties, high encapsulation efficiency, and photothermal capacity. The in vitro studies revealed that the nanomaterials are cytocompatible and that display an improved uptake by the CD44-overexpressing breast cancer cells. Importantly, the combination of DOX/HA-DOPA-rGO with NIR light reduced breast cancer cells' viability to just 23 %, showcasing their potential chemo-photothermal therapy.


Assuntos
Neoplasias da Mama , Grafite , Hipertermia Induzida , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Ácido Hialurônico/química , Terapia Fototérmica , Grafite/química , Doxorrubicina/química , Di-Hidroxifenilalanina , Fototerapia
11.
United European Gastroenterol J ; 12(2): 252-260, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38267015

RESUMO

The evolution in systemic therapies in hepatocellular carcinoma (HCC) signifies a strategy of high-cost, high-gain innovation that originated with sorafenib, despite its limited impact on tumor response. This strategic approach paved the way for the emergence of a second wave of the short-lived competitive advantage, exemplified by the incorporation of atezolizumab plus bevacizumab and tremelimumab plus durvalumab. In the context of safety concerns within the liver cancer domain, the IMBRAVE150 and HIMALAYA trials boldly incorporated bevacizumab and tremelimumab, respectively, demonstrating the continuation of the high-risk, high-reward innovation paradigm. This review delves into the strengths, weaknesses, opportunities, and threats analysis of systemic therapies in the field of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Bevacizumab/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/uso terapêutico
12.
Cancer Immunol Immunother ; 73(1): 19, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38240863

RESUMO

BACKGROUND: GD2-directed immunotherapy is highly effective in the treatment of high-risk neuroblastoma (NB), and might be an interesting target also in other high-risk tumors. METHODS: The German-Austrian Retinoblastoma Registry, Essen, was searched for patients, who were treated with anti-GD2 monoclonal antibody (mAb) dinutuximab beta (Db) in order to evaluate toxicity, response and outcome in these patients. Additionally, we evaluated anti-GD2 antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) in retinoblastoma cell lines in vitro. Furthermore, in vitro cytotoxicity assays directed against B7-H3 (CD276), a new identified potential target in RB, were performed. RESULTS: We identified four patients with relapsed stage IV retinoblastoma, who were treated with Db following autologous stem cell transplantation (ASCT). Two out of two evaluable patients with detectable tumors responded to immunotherapy. One of these and another patient who received immunotherapy without residual disease relapsed 10 and 12 months after start of Db. The other patients remained in remission until last follow-up 26 and 45 months, respectively. In vitro, significant lysis of RB cell lines by ADCC and CDC with samples from patients and healthy donors and anti-GD2 and anti-CD276-mAbs were demonstrated. CONCLUSION: Anti-GD2-directed immunotherapy represents an additional therapeutic option in high-risk metastasized RB. Moreover, CD276 is another target of interest.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Neoplasias da Retina , Retinoblastoma , Humanos , Retinoblastoma/terapia , Transplante Autólogo , Recidiva Local de Neoplasia , Imunoterapia , Gangliosídeos , Antígenos B7
13.
Annu Rev Med ; 75: 13-29, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-37729027

RESUMO

Multiple myeloma is a cancer of bone marrow plasma cells that represents approximately 10% of hematologic malignancies. Though it is typically incurable, a remarkable suite of new therapies developed over the last 25 years has enabled durable disease control in most patients. This article briefly introduces the clinical features of multiple myeloma and aspects of multiple myeloma biology that modern therapies exploit. Key current and emerging treatment modalities are then reviewed, including cereblon-modulating agents, proteasome inhibitors, monoclonal antibodies, other molecularly targeted therapies (selinexor, venetoclax), chimeric antigen receptor T cells, T cell-engaging bispecific antibodies, and antibody-drug conjugates. For each modality, mechanism of action and clinical considerations are discussed. These therapies are combined and sequenced in modern treatment pathways, discussed at the conclusion of the article, which have led to substantial improvements in outcomes for multiple myeloma patients in recent years.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Imunoterapia , Inibidores de Proteassoma/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Terapia Biológica
14.
Adv Healthc Mater ; 13(4): e2302395, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37947303

RESUMO

Ferrofluidic robots with excellent deformability and controllability have been intensively studied recently. However, most of these studies are in vitro and the use of ferrofluids for in vivo medicinal applications remains a big challenge. The application of ferrofluidic robots to the body requires the solution of many key problems. In this study, biocompatibility, controllability, and tumor-killing efficacy are considered when creating a ferrofluid-based millirobot for in vivo tumor-targeted therapy. For biocompatibility problems, corn oil is used specifically for the ferrofluid robot. In addition, a control system is built that enables a 3D magnetic drive to be implemented in complex biological media. Using the photothermal conversion property of 1064 nm, the ferrofluid robot can kill tumor cells in vitro; inhibit tumor volume, destroy the tumor interstitium, increase tumor cell apoptosis, and inhibit tumor cell proliferation in vivo. This study provides a reference for ferrofluid-based millirobots to achieve targeted therapies in vivo.


Assuntos
Hipertermia Induzida , Neoplasias , Humanos , Terapia Fototérmica , Neoplasias/terapia , Neoplasias/patologia , Fototerapia
15.
Artigo em Chinês | WPRIM | ID: wpr-1030015

RESUMO

Vitiligo is a dermatological condition of autoimmune origin, characterized by the acquired loss of pigmentation in the skin and mucous membranes. Inflammatory cytokines, including interferon (IFN)-γ, interleukin (IL)-17, tumor necrosis factor (TNF)-α, IL-6, IL-8, IL-21, IL-33, phosphodiester enzyme (PDE)-4, and transforming growth factor (TGF)-β, play a crucial role in the progression of vitiligo. Among these, the IFN-γ/chemokine ligand (CXCL) 10 axis is particularly significant. In recent times, the advent of targeted therapeutic approaches, focusing on modulating cytokines and their corresponding receptors implicated in the pathogenesis of vitiligo, has assumed paramount significance. JAK inhibitors and their combination therapy with phototherapy have been clinically proven to have promising therapeutic prospects. This review undertakes a comprehensive appraisal of the therapeutic efficacy and tailored drug selection pertaining to diverse biological agents employed in the management of vitiligo, aiming to provide valuable insights for clinical therapeutic decisions.

16.
Curr Neuropharmacol ; 22(1): 53-64, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37550909

RESUMO

A majority of older patients suffer from neuropathic pain (NP) that significantly alters their daily activities and imposes a significant burden on health care. Multiple comorbidities and the risk of polypharmacy in the elderly make it challenging to determine the appropriate drug, dosage, and maintenance of therapy. Age-dependent processes play a contributing role in neuropathy given that diabetic neuropathy (DN) is the most common form of neuropathy. This narrative review is mainly focused on the drug treatment approach for neuropathy-associated pain in aged people including both drugs and dietary supplements, considering the latter as add-on mechanism-based treatments to increase the effectiveness of usual treatments by implementing their activity or activating other analgesic pathways. On one hand, the limited clinical studies assessing the effectiveness and the adverse effects of existing pain management options in this age segment of the population (> 65), on the other hand, the expanding global demographics of the elderly contribute to building up an unresolved pain management problem that needs the attention of healthcare providers, researchers, and health authorities as well as the expansion of the current therapeutic options.


Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Neuralgia , Idoso , Humanos , Neuropatias Diabéticas/complicações , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/induzido quimicamente , Neuralgia/tratamento farmacológico , Analgésicos/uso terapêutico , Analgésicos/efeitos adversos , Manejo da Dor , Suplementos Nutricionais , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/tratamento farmacológico
17.
Int J Mol Sci ; 24(23)2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38068888

RESUMO

Polydopamine (PDA)-based nanostructures are used for biomedical purposes. A hybrid drug nanocarrier based on a PDA decorated with polyamidoamine (PAMAM) dendrimers G 3.0 (DG3) followed by a connection with glycol (PEG) moieties, folic acid (FA), and drug doxorubicin (DOX) was used for combined chemo- and photothermal therapy (CT-PTT) of liver cancer. Oxidative stress plays a crucial role in the development of cancer, and PDA seems to have the ability to both donate and accept electrons. We investigated oxidative stress in organs by evaluating oxidative stress markers in vivo. In the liver, the level of reduced glutathione (GSH) was lower and the level of Trolox equivalent antioxidant capacity (TEAC) was higher in the group receiving doxorubicin encapsulated in PDA nanoparticles with phototherapy (PDA@DG3@PEG@FA@DOX + PTT) compared to the control group. The concentration of thiobarbituric acid reactive substances (TBARS) in livers, was higher in the group receiving PDA coated with PAMAM dendrimers and functionalized with PEG and FA (PDA@DG3@PEG@FA) than in other groups. Markers in the brain also showed lower levels of GSH in the PDA@DG3@PEG@FA group than in the control group. Markers of oxidative stress indicated changes in the organs of animals receiving PDA nanoparticles with PAMAM dendrimers functionalized with FA in CT-PTT of liver cancer under in vivo conditions. Our work will provide insights into oxidative stress, which can be an indicator of the toxic potential of PDA nanoparticles and provide new strategies to improve existing therapies.


Assuntos
Dendrímeros , Neoplasias Hepáticas , Nanopartículas , Humanos , Camundongos , Animais , Dendrímeros/química , Terapia Fototérmica , Xenoenxertos , Doxorrubicina/química , Nanopartículas/química , Fototerapia , Neoplasias Hepáticas/tratamento farmacológico , Estresse Oxidativo , Linhagem Celular Tumoral
18.
Biomed Pharmacother ; 169: 115846, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37944443

RESUMO

Breast cancer is characterized by insidious onset, rapid progression, easy recurrence, and metastasis. Conventional monotherapies are usually ineffective due to insufficient drug delivery. Therefore, the combination of multimodal therapy with tumor microenvironment (TME)-responsive nanoplatforms is increasingly being considered for the targeted treatment of breast cancer. We synthesized bioactive hybrid nanoparticles for synergistic chemotherapy and photothermal therapy. Briefly, doxorubicin (DOX) and indocyanine green (ICG)-loaded nanoparticles (DI) of average particle size 113.58 ± 2.14 nm were synthesized, and their surface were modified with polydopamine (PDA) and attached to the anaerobic probiotic Bifidobacterium infantis (Bif). The bioactive Bif@DIP hybrid showed good photothermal conversion efficiency of about 38.04%. In addition, the self-driving ability of Bif allowed targeted delivery of the PDA-coated DI nanoparticles (DIP) to the hypoxic regions of the tumor. The low pH and high GSH levels in the TME stimulated the controlled release of DOX and ICG from the Bif@DIP hybrid, which then triggered apoptosis of tumor cells and induced immunogenic cell death (ICD), resulting in effective and sustained anti-tumor effect with minimum systemic toxicity. Thus, the self-driven Bif@DIP hybrid is a promising nanodrug for the targeted chemotherapy and photothermal therapy against solid cancers.


Assuntos
Neoplasias da Mama , Hipertermia Induzida , Nanopartículas , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Verde de Indocianina , Terapia Fototérmica , Fototerapia/métodos , Doxorrubicina , Nanopartículas/química , Linhagem Celular Tumoral , Microambiente Tumoral
19.
Mol Biol Rep ; 50(11): 9663-9676, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37828275

RESUMO

As far as health issues are concerned, cancer causes one out of every six deaths around the globe. As potent therapeutics are still awaited for the successful treatment of cancer, some unconventional treatments like radiotherapy, surgery, and chemotherapy and some advanced technologies like gene therapy, stem cell therapy, natural antioxidants, targeted therapy, photodynamic therapy, nanoparticles, and precision medicine are available to diagnose and treat cancer. In the present scenario, the prime focus is on developing efficient nanomedicines to treat cancer. Although stem cell therapy has the capability to target primary as well as metastatic cancer foci, it also has the ability to repair and regenerate injured tissues. However, nanoparticles are designed to have such novel therapeutic capabilities. Targeted therapy is also now available to arrest the growth and development of cancer cells without damaging healthy tissues. Another alternative approach in this direction is photodynamic therapy (PDT), which has more potential to treat cancer as it does minimal damage and does not limit other technologies, as in the case of chemotherapy and radiotherapy. The best possible way to treat cancer is by developing novel therapeutics through translational research. In the present scenario, an important event in modern oncology therapy is the shift from an organ-centric paradigm guiding therapy to complete molecular investigations. The lacunae in anticancer therapy may be addressed through the creation of contemporary and pertinent cancer therapeutic techniques. In the meantime, the growth of nanotechnology, material sciences, and biomedical sciences has revealed a wide range of contemporary therapies with intelligent features, adaptable functions, and modification potential. The development of numerous therapeutic techniques for the treatment of cancer is summarized in this article. Additionally, it can serve as a resource for oncology and immunology researchers.


Assuntos
Nanopartículas , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Nanopartículas/uso terapêutico , Transplante de Células-Tronco , Medicina de Precisão
20.
Phytomedicine ; 121: 155087, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37832267

RESUMO

BACKGROUND: About 30% of pulmonary stage IV adenocarcinomas die within 3 months of diagnosis. Western medical treatments with Platinum-Based Chemotherapy=PBC and tyrosine-kinase inhibitors Targeted Therapy=TT can improve prognosis. In China, Traditional Chinese Medicine herbal treatments (TCM) are often used in addition to PBC and TT. A considerable number of patients refuse Western medical treatments and use TCM alone. However, the survival impact of the latter is unknown. HYPOTHESES TESTED: Treatment with TCM alone is prognostically superior to PBC alone. Addition of PBC or TT or both TT to TCM improves survival. METHODS: In this prospective observational, non-interventional study of 1017 consecutive first-onset stage IV NSCLC patients with up to 10 years follow-up, 261 who Died of Disease (DOD) within 3 months were omitted, as they never got the optimal Western medical therapies. All 218 non-adenocarcinomas were also omitted, leaving 538 stage IV adenocarcinomas treated by TCM alone (n = 29), PBC alone (N = 19) and TCM and other Western medical combinations (299 TCM and PBC, 50 TCM and TT, 141 TCM and PBC and TT) with 3 - 120 months follow-up. Survivals were compared using Alive with Disease (AWD) and DOD as endpoints. RESULTS: The patients treated only with TCM had 7 months better median survival than those that received PBC alone (17 and 10 months). The patients that received TCM and PBC had a better median survival (24 months) than TCM alone and much better than PBC alone. None of the patients that received TCM alone survived > 54 months, whereas 18% of TCM and PBC patients survived much longer. Over the observation period of 3 - 120 months, survivals of TCM and TT, TCM and PBC and TT, and TCM and PBC were not different and therefore grouped as TCM and Western medicines. Median survival times of PBC alone and TCM alone were lower than that of TCM and Western medical treatments (p < 0.0001, 10, 17 and 27 months). CONCLUSIONS: Pulmonary stage IV adenocarcinoma patients with at least 3 months survival, treated with TCM alone have a significantly better survival than those treated with PBC alone. Adding Western PBC, TT or both to TCM further improves prognosis.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Medicamentos de Ervas Chinesas , Neoplasias Pulmonares , Humanos , Medicina Tradicional Chinesa/métodos , Medicamentos de Ervas Chinesas/uso terapêutico , Platina/uso terapêutico , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia
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