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1.
Int Cancer Conf J ; 13(3): 235-239, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38962051

RESUMO

Immune-checkpoint inhibitors (ICIs) are considered as the novel treatment modality in certain cancers. They may soon be used widely even as the first-line option for cancer treatment due to their remarkable efficacies and impacts on survival rates, particularly in cases of advanced metastatic cancer. Of note, these agents might unveil new autoimmune diseases as well as causing flare-ups of a pre-existing autoimmune disease. Data in this field have been accumulated during recent years. Early detection and a collaborative approach are, therefore, crucial in the management of a patient who presents with any of these conditions. Herein, we report a patient with a diagnosis of metastatic renal cell cancer presented with vasculitis involvement in the aorta during nivolumab treatment. Our aim with this case is to increase the awareness of ICI-related vasculitis involvement among rheumatologists in the light of literature.

2.
Eur J Med Chem ; 275: 116645, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38959730

RESUMO

Hypoxia-inducible factor 2α (HIF-2α) is a critical transcription factor that regulates cellular responses under hypoxic conditions. In situations of insufficient oxygen supply or patients with Von Hippel-Lindau (VHL) mutations, HIF-2α accumulates and forms a heterodimeric complex with aryl hydrocarbon receptor nuclear translocator (ARNT, or HIF-ß). This complex further binds to coactivator p300 and interacts with hypoxia response elements (HREs) on the DNA of downstream target genes, regulating the transcription of a variety of genes (e.g. VEGFA, CCND1, CXCR4, SLC2A1, etc) involved in various processes like angiogenesis, mitochondrial metabolism, cell proliferation, and metastasis. Targeting HIF-2α holds great promise for effectively addressing solid tumors associated with aberrant oxygen-sensing pathways and hypoxia mechanisms, offering broad application prospects. In this review, we provide an overview of recent advancements (2009-2024) in HIF-2α modulators such as inhibitors, agonists, and degraders for cancer therapy. Additionally, we discuss in detail the challenges and future directions regarding HIF-2α modulators.


Assuntos
Antineoplásicos , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Desenvolvimento de Medicamentos , Animais , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Fatores de Transcrição Hélice-Alça-Hélice Básicos/agonistas , Fatores de Transcrição Hélice-Alça-Hélice Básicos/antagonistas & inibidores , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Estrutura Molecular , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia
3.
Expert Opin Ther Pat ; 34(8): 593-610, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38946486

RESUMO

INTRODUCTION: Focal adhesion kinase (FAK) is a cytoplasmic non-receptor tyrosine kinase over-expressed in various malignancies which is related to various cellular functions such as adhesion, metastasis and proliferation. AREAS COVERED: There is growing evidence that FAK is a promising therapeutic target for designing inhibitors by regulating the downstream pathways of FAK. Some potential FAK inhibitors have entered clinical phase research. EXPERT OPINION: FAK could be an effective target in medicinal chemistry research and there were a variety of FAKIs have been patented recently. Here, we updated an overview of design, synthesis and structure-activity relationship of chemotherapeutic FAK inhibitors (FAKIs) from 2017 until now based on our previous work. We hope our efforts can broaden the understanding of FAKIs and provide new ideas and insights for future cancer treatment from medicinal chemistry point of view.


Assuntos
Antineoplásicos , Desenho de Fármacos , Proteína-Tirosina Quinases de Adesão Focal , Neoplasias , Patentes como Assunto , Inibidores de Proteínas Quinases , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/enzimologia , Animais , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Relação Estrutura-Atividade , Proteína-Tirosina Quinases de Adesão Focal/antagonistas & inibidores , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Desenvolvimento de Medicamentos , Química Farmacêutica , Terapia de Alvo Molecular
4.
Int J Pharm ; 661: 124420, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38971512

RESUMO

Colorectal cancer represents a worldwide spread type of cancer and it is regarded as one of the leading death causes, along with lung, breast, and prostate cancers. Since conventional surgical resection and chemotherapy proved limited efficiency, the use of alternative drug delivery systems that ensure the controlled release of cytostatic agents possess immense potential for treatment. In this regard, the present study aimed to develop and evaluate the efficiency of a series of irinotecan-loaded magnetite-silica core-shell systems. The magnetite particles were obtained through a solvothermal treatment, while the silica shell was obtained through the Stöber method directly onto the surface of magnetite particles. Subsequently, the core-shell systems were physico-chemically and morpho-structurally evaluated trough X-ray diffraction (XRD) and (high-resolution) transmission electron microscopy ((HR-)TEM) equipped with a High Annular Angular Dark Field Detector (HAADF) for elemental mapping. After the irinotecan loading, the drug delivery systems were evaluated through Fourier-transform infrared spectroscopy (FT-IR), thermogravimetry and differential scanning calorimetry (TG-DSC), and UV-Vis spectrophotometry. Additionally, the Brunauer-Emmett-Teller (BET) method was employed for determining the surface area and pore volume of the systems. The biological functionality of the core-shells was investigated through the MTT assay performed on both normal and cancer cells. The results of the study confirmed the formation of highly crystalline magnetite particles comprising the core and mesoporous silica layers of sizes varying between 2 and 7 nm as the shell. Additionally, the drug loading and release was dependent on the type of the silica synthesis procedure, since the lack of hexadecyltrimethylammonium bromide (CTAB) resulted in higher drug loading but lower cumulative release. Moreover, the nanostructured systems demonstrated a targeted efficiency towards HT-29 colorectal adenocarcinoma cells, as in the case of normal L929 fibroblast cells, the cell viability was higher than for the pristine drug. In this manner, this study provides the means and procedures for developing drug delivery systems with applicability in the treatment of cancer.

5.
BMC Cancer ; 24(1): 808, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38973010

RESUMO

BACKGROUND: Telemedicine is beneficial for improving treatment efficiency and reducing medical expenses of cancer patients. This study focuses on cancer patients participating in teleconsultations through a regional telemedicine platform in China, analyzes the consultation process, and provides references for the clinical application of telemedicine. METHODS: We collected information on teleconsultations of cancer patients conducted from 2015 to 2022 through the regional telemedicine platform. Utilizing SPSS 23.0 software, we conducted descriptive analysis to summarize the distribution of patient gender, age, region, and disease types. The ordinal logistic regression analysis was adopted to analyze the factors influencing the waiting time and consultation duration for teleconsultations. RESULTS: From 2015 to 2022, a total of 23,060 teleconsultations were conducted for cancer patients via regional telemedicine platform, with an average growth rate of 11.09%. The main types of consultations were for lung cancer, liver cancer, and breast cancer, accounting for 18.14%, 10.49%, and 9.46% respectively. 57.05% of teleconsultations had a waiting time of less than 24 h, while patient age, consultation expert level, and disease type were the main factors influencing the waiting time. 50.06% of teleconsultations had a duration of more than 20 min, and the inviting hospital level and the title of invited consultant were the main factors influencing the consultation duration. CONCLUSIONS: In China, telemedicine has been widely employed in the clinical diagnosis and treatment of cancers, covering various types of oncological diseases. However, the waiting time for teleconsultations was generally more than 12 h, indicating the need to enhance consultation scheduling and allocate more expert resources to further optimize the efficiency of teleconsultations. Additionally, further exploration is required for remote health management of outpatients with cancers outside the hospital.


Assuntos
Neoplasias , Consulta Remota , Telemedicina , Humanos , Feminino , Neoplasias/terapia , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Adulto , Idoso , China , Adulto Jovem , Adolescente , Idoso de 80 Anos ou mais , Criança
6.
Artigo em Inglês | MEDLINE | ID: mdl-38965153

RESUMO

PURPOSE: Timeliness of care is an important healthcare outcome measure. The objective of this study was to explore patient perspectives on the timeliness of breast cancer diagnosis and treatment at accredited breast cancer centers. METHODS: In this qualitative study, 1 hour virtual interviews were conducted with participants 18-75 years old who were diagnosed and treated for stage 0-III breast cancer at a National Accreditation Program for Breast Centers facility from 2018 to 2022. Thematic analysis was used to identify key themes of participant experiences. RESULTS: Twenty-eight participants were interviewed. Two thematic domains were identified: etiologies of expedited or delayed care and the impact of delayed or expedited care on patients. Within these domains, multiple themes emerged. For etiologies of expedited or delayed care, participants discussed (1) the effect of scheduling appointments, (2) the COVID-19 pandemic, (3) dissatisfaction with the timeline for various parts of the diagnostic workup, and (4) delays related to patient factors, including socioeconomic status. For the impact of expedited or delayed care, patients discussed (1) the emotional and mental impact of waiting, (2) the importance of communication and clear expectations, and (3) the impact of electronic health portals. Patients desired each care interval (e.g., the time from mammogram to breast biopsy) to be approximately 7 days, with longer intervals sometimes preferred prior to surgery. CONCLUSION: These patient interviews identify areas of delay and provide patient-centered, actionable items to improve the timeliness of breast cancer care.

7.
Front Oncol ; 14: 1394699, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38993645

RESUMO

Endometrial cancer (EC) is a devastating and common disease affecting women's health. The NCI Surveillance, Epidemiology, and End Results Program predicted that there would be >66,000 new cases in the United States and >13,000 deaths from EC in 2023, and EC is the sixth most common cancer among women worldwide. Regulation of mitochondrial metabolism plays a role in tumorigenesis. In proliferating cancer cells, mitochondria provide the necessary building blocks for biosynthesis of amino acids, lipids, nucleotides, and glucose. One mechanism causing altered mitochondrial activity is mitochondrial DNA (mtDNA) mutation. The polyploid human mtDNA genome is a circular double-stranded molecule essential to vertebrate life that harbors genes critical for oxidative phosphorylation plus mitochondrial-derived peptide genes. Cancer cells display aerobic glycolysis, known as the Warburg effect, which arises from the needs of fast-dividing cells and is characterized by increased glucose uptake and conversion of glucose to lactate. Solid tumors often contain at least one mtDNA substitution. Furthermore, it is common for cancer cells to harbor mixtures of wild-type and mutant mtDNA genotypes, known as heteroplasmy. Considering the increase in cancer cell energy demand, the presence of functionally relevant carcinogenesis-inducing or environment-adapting mtDNA mutations in cancer seems plausible. We review 279 EC tumor-specific mtDNA single nucleotide variants from 111 individuals from different studies. Many transition mutations indicative of error-prone DNA polymerase γ replication and C to U deamination events were present. We examine the spectrum of mutations and their heteroplasmy and discuss the potential biological impact of recurrent, non-synonymous, insertion, and deletion mutations. Lastly, we explore current EC treatments, exploiting cancer cell mitochondria for therapy and the prospect of using mtDNA variants as an EC biomarker.

8.
Front Immunol ; 15: 1401852, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38994350

RESUMO

Exosomes, as a class of small extracellular vesicles closely related to the biological behavior of various types of tumors, are currently attracting research attention in cancer diagnosis and treatment. Regarding cancer diagnosis, the stability of their membrane structure and their wide distribution in body fluids render exosomes promising biomarkers. It is expected that exosome-based liquid biopsy will become an important tool for tumor diagnosis in the future. For cancer treatment, exosomes, as the "golden communicators" between cells, can be designed to deliver different drugs, aiming to achieve low-toxicity and low-immunogenicity targeted delivery. Signaling pathways related to exosome contents can also be used for safer and more effective immunotherapy against tumors. Exosomes are derived from a wide range of sources, and exhibit different biological characteristics as well as clinical application advantages in different cancer therapies. In this review, we analyzed the main sources of exosomes that have great potential and broad prospects in cancer diagnosis and therapy. Moreover, we compared their therapeutic advantages, providing new ideas for the clinical application of exosomes.


Assuntos
Biomarcadores Tumorais , Exossomos , Neoplasias , Humanos , Exossomos/metabolismo , Exossomos/imunologia , Neoplasias/terapia , Neoplasias/imunologia , Animais , Imunoterapia/métodos , Biópsia Líquida/métodos
9.
Support Care Cancer ; 32(8): 509, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38992238

RESUMO

PURPOSE: Exercise and physical activity (PA) during oncological treatment have many benefits. However, PA levels and adherence are often low. This systematic review of qualitative literature aims to explore the experience and the perceived barriers and facilitators to exercise and physical activity during treatment. METHODS: A systematic search of the published literature was carried out in the Embase and Medline databases; full details for the protocol can be found in the Prospero database (CRD42022371206). Studies eligible for inclusion were qualitative and included participants that were either currently undergoing oncological treatment or had finished treatment within the last 6 months. The findings from each study were tabulated and synthesised into analytical themes. RESULTS: Eighteen full texts from 309 studies met inclusion criteria with a total of 420 participants including both curative and palliative treatment intents. Four overarching themes were generated: (1) Facilitators; (2) Barriers; (3) Experience of PA/exercise and (4) Transforming attitudes. Sub-themes that showed perceptions of PA or exercise during treatment were positive, and seeing personal positive change was highly motivating, especially in a group class setting. Barriers included lack of support or guidance from healthcare professionals (HCPs), environmental challenges and disease burden/fear or worsening symptoms. CONCLUSIONS: Despite having positive perceptions of exercise and PA during oncological treatment, there are significant barriers impacting participation. Lack of support from HCPs and fear of worsening symptoms were significant barriers. Future research should focus on impacting these barriers to ultimately improve PA and exercise levels in those undergoing oncological treatment.


Assuntos
Exercício Físico , Neoplasias , Pesquisa Qualitativa , Humanos , Neoplasias/psicologia , Neoplasias/terapia , Exercício Físico/psicologia , Atitude Frente a Saúde , Terapia por Exercício/métodos , Terapia por Exercício/psicologia , Motivação
10.
Oncol Res ; 32(7): 1163-1172, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948019

RESUMO

Background: Osteosarcoma is the most common malignant primary bone tumor. The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy. Moreover, current treatment regimens bear a significant risk of serious side effects. Thus, there is an unmet clinical need for effective therapies with improved safety profiles. Taurolidine is an antibacterial agent that has been shown to induce cell death in different types of cancer cell lines. Methods: In this study, we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma. K7M2 murine osteosarcoma cells were injected, both intramuscular and intraperitoneal, into 60 BALB/c mice on day zero. Animals were then randomized to receive treatment with taurolidine 2% (800 mg/kg), taurolidine 1% (400 mg/kg), or NaCl 0.9% control for seven days by intravenous or intraperitoneal administration. Results: After 35 days, mice were euthanized, and the tumors were harvested for analysis. Eighteen mice were excluded from the analysis due to complications. Body weight was significantly lower in the 2% taurolidine intraperitoneal treatment group from day 9 to 21, consistent with elevated mortality in this group. Intraperitoneal tumor weight was significantly lower in the 1% (p = 0.003) and 2% (p = 0.006) intraperitoneal taurolidine treatment groups compared to the control. No antineoplastic effects were observed on intramuscular tumors or for intravenous administration of taurolidine. There were no significant differences in microvessel density or mitotic rate between treatment groups. Reduced body weight and elevated mortality in the 2% taurolidine intraperitoneal group suggest that the lower 1% dose is preferable. Conclusions: In conclusion, there is no evidence of antiangiogenic activity, and the antitumor effects of taurolidine on osteosarcoma observed in this study are limited. Moreover, its toxic profile grants further evaluation. Given these observations, further research is necessary to refine the use of taurolidine in osteosarcoma treatment.


Assuntos
Neoplasias Ósseas , Modelos Animais de Doenças , Osteossarcoma , Taurina , Tiadiazinas , Carga Tumoral , Animais , Taurina/análogos & derivados , Taurina/farmacologia , Taurina/uso terapêutico , Tiadiazinas/farmacologia , Tiadiazinas/uso terapêutico , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Osteossarcoma/irrigação sanguínea , Camundongos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Carga Tumoral/efeitos dos fármacos , Densidade Microvascular/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Humanos , Neovascularização Patológica/tratamento farmacológico
11.
Theranostics ; 14(9): 3693-3707, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948062

RESUMO

Background: Immune checkpoint inhibitors (ICI) are routinely used in advanced clear cell renal cell carcinoma (ccRCC). However, a substantial group of patients does not respond to ICI therapy. Radiation is a promising approach to increase ICI response rates since it can generate anti-tumor immunity. Targeted radionuclide therapy (TRT) is a systemic radiation treatment, ideally suited for precision irradiation of metastasized cancer. Therefore, the aim of this study is to explore the potential of combined TRT, targeting carbonic anhydrase IX (CAIX) which is overexpressed in ccRCC, using [177Lu]Lu-DOTA-hG250, and ICI for the treatment of ccRCC. Methods: In this study, we evaluated the therapeutic and immunological action of [177Lu]Lu-DOTA-hG250 combined with aPD-1/a-CTLA-4 ICI. First, the biodistribution of [177Lu]Lu-DOTA-hG250 was investigated in BALB/cAnNRj mice bearing Renca-CAIX or CT26-CAIX tumors. Renca-CAIX and CT26-CAIX tumors are characterized by poor versus extensive T-cell infiltration and homogeneous versus heterogeneous PD-L1 expression, respectively. Tumor-absorbed radiation doses were estimated through dosimetry. Subsequently, [177Lu]Lu-DOTA-hG250 TRT efficacy with and without ICI was evaluated by monitoring tumor growth and survival. Therapy-induced changes in the tumor microenvironment were studied by collection of tumor tissue before and 5 or 8 days after treatment and analyzed by immunohistochemistry, flow cytometry, and RNA profiling. Results: Biodistribution studies showed high tumor uptake of [177Lu]Lu-DOTA-hG250 in both tumor models. Dose escalation therapy studies in Renca-CAIX tumor-bearing mice demonstrated dose-dependent anti-tumor efficacy of [177Lu]Lu-DOTA-hG250 and remarkable therapeutic synergy including complete remissions when a presumed subtherapeutic TRT dose (4 MBq, which had no significant efficacy as monotherapy) was combined with aPD-1+aCTLA-4. Similar results were obtained in the CT26-CAIX model for 4 MBq [177Lu]Lu-DOTA-hG250 + a-PD1. Ex vivo analyses of treated tumors revealed DNA damage, T-cell infiltration, and modulated immune signaling pathways in the TME after combination treatment. Conclusions: Subtherapeutic [177Lu]Lu-DOTA-hG250 combined with ICI showed superior therapeutic outcome and significantly altered the TME. Our results underline the importance of investigating this combination treatment for patients with advanced ccRCC in a clinical setting. Further investigations should focus on how the combination therapy should be optimally applied in the future.


Assuntos
Anidrase Carbônica IX , Carcinoma de Células Renais , Inibidores de Checkpoint Imunológico , Neoplasias Renais , Animais , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/terapia , Carcinoma de Células Renais/patologia , Camundongos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Neoplasias Renais/radioterapia , Anidrase Carbônica IX/metabolismo , Anidrase Carbônica IX/antagonistas & inibidores , Humanos , Linhagem Celular Tumoral , Radioisótopos/uso terapêutico , Radioisótopos/farmacologia , Radioisótopos/administração & dosagem , Lutécio/uso terapêutico , Feminino , Antígenos de Neoplasias/metabolismo , Distribuição Tecidual , Microambiente Tumoral/efeitos dos fármacos , Proteína Tumoral 1 Controlada por Tradução , Ensaios Antitumorais Modelo de Xenoenxerto , Terapia Combinada/métodos , Camundongos Endogâmicos BALB C , Anticorpos Monoclonais
12.
Front Genet ; 15: 1401544, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948360

RESUMO

Introduction: Synergistic medication, a crucial therapeutic strategy in cancer treatment, involves combining multiple drugs to enhance therapeutic effectiveness and mitigate side effects. Current research predominantly employs deep learning models for extracting features from cell line and cancer drug structure data. However, these methods often overlook the intricate nonlinear relationships within the data, neglecting the distribution characteristics and weighted probability densities of gene expression data in multi-dimensional space. It also fails to fully exploit the structural information of cancer drugs and the potential interactions between drug molecules. Methods: To overcome these challenges, we introduce an innovative end-to-end learning model specifically tailored for cancer drugs, named Dual Kernel Density and Positional Encoding (DKPE) for Graph Synergy Representation Network (DKPEGraphSYN). This model is engineered to refine the prediction of drug combination synergy effects in cancer. DKPE-GraphSYN utilizes Dual Kernel Density Estimation and Positional Encoding techniques to effectively capture the weighted probability density and spatial distribution information of gene expression, while exploring the interactions and potential relationships between cancer drug molecules via a graph neural network. Results: Experimental results show that our prediction model achieves significant performance enhancements in forecasting drug synergy effects on a comprehensive cancer drug and cell line synergy dataset, achieving an AUPR of 0.969 and an AUC of 0.976. Discussion: These results confirm our model's superior accuracy in predicting cancer drug combinations, providing a supportive method for clinical medication strategy in cancer.

13.
Oncol Nurs Forum ; 51(4): 294-296, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38950098

RESUMO

The position statement on fertility preservation was produced through collaborative efforts among the Association of Pediatric Hematology/Oncology Nurses, Canadian Association of Nurses in Oncology/Association canadienne des.


Assuntos
Preservação da Fertilidade , Neoplasias , Enfermagem Oncológica , Humanos , Preservação da Fertilidade/métodos , Neoplasias/complicações , Feminino , Masculino , Canadá , Enfermagem Oncológica/métodos , Adulto , Sobreviventes de Câncer/psicologia , Criança , Guias de Prática Clínica como Assunto , Adolescente
14.
Explor Target Antitumor Ther ; 5(3): 714-741, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966169

RESUMO

Antibody-drug conjugates (ADCs) have emerged as a promising class of anticancer agents. Currently, the Food and Drug Administration has granted approval to 12 compounds, with 2 later undergoing withdrawal. Moreover, several other compounds are currently under clinical development at different stages. Despite substantial antitumoral activity observed among different tumor types, adverse events and the development of resistance represent significant challenges in their use. Over the last years, an increasing number of clinical trials have been testing these drugs in different combinations with other anticancer agents, such as traditional chemotherapy, immune checkpoint inhibitors, monoclonal antibodies, and small targeted agents, reporting promising results based on possible synergistic effects and a potential for improved treatment outcomes among different tumor types. Here we will review combinations of ADCs with other antitumor agents aiming at describing the current state of the art and future directions.

15.
Biomed Pharmacother ; : 117002, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38960836

RESUMO

This review provides an in-depth examination of the role that tumor-associated macrophages (TAMs) play in the progression of prostate cancer (PCa), with a particular focus on the factors influencing the polarization of M1 and M2 macrophages and the implications of targeting these cells for cancer progression. The development and prognosis of PCa are significantly influenced by the behavior of macrophages within the tumor microenvironment. M1 macrophages typically exhibit anti-tumor properties by secreting pro-inflammatory cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), thereby enhancing the immune response. Conversely, M2 macrophages contribute to tumor cell migration and invasion through the production of factors like arginase-1 (Arg1) and interleukin-10 (IL-10). This review not only explores the diverse factors that affect macrophage polarization but also delves into the potential therapeutic strategies targeting macrophage polarization, including the critical roles of non-coding RNA and exosomes in regulating this process. The polarization state of macrophages is highlighted as a key determinant in PCa progression, offering a novel perspective for clinical treatment. Future research should concentrate on gaining a deeper understanding of the molecular mechanisms underlying macrophage polarization and on developing effective targeted therapeutic strategies. The exploration of the potential of combination therapies to improve treatment efficacy is also emphasized. By emphasizing the importance of macrophages as a therapeutic target in PCa, this review aims to provide valuable insights and research directions for clinicians and researchers.

16.
Angew Chem Int Ed Engl ; : e202408769, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38960984

RESUMO

The clinical application of photodynamic therapy (PDT) is limited by oxygen-dependence and side effects caused by photosensitizer residues. Photoinitiators based on the H-abstraction reaction can address these challenges because they can generate alkyl radical-killing cells independently of oxygen and undergo rapid bleaching following H-abstraction. Nonetheless, the development of photoinitiators for PDT has been impeded by the absence of effective design strategies. Herein, we have developed aryl-ketone substituted cyanine (ACy-R), the first red-light triggered H-abstraction photoinitiators for hypoxic cancer therapy. These ACy-R molecules inherited the near-infrared absorption of cyanine dye, and aryl-ketone modification imparted H-abstraction capability. Experimental and quantum calculations revealed that modifying the electron-withdrawing groups of the aryl (e.g., ACy-5F) improved the contribution of the O atom to the photon excitation process promoting intersystem crossing and H-abstraction ability. Particularly, ACy-5F rapidly penetrated cells and enriched in the endoplasmic reticulum. Even under severe hypoxia, ACy-5F initiated red-light induced H-abstraction with intracellular biomolecules, inducing necroptosis and ferroptosis. Moreover, ACy-5F was degraded after H-abstraction, thus avoiding the side effects of long-term phototoxicity after therapy. This study not only provides a crucial molecular tool for hypoxic tumors therapy, but also presents a promising strategy for the development of multifunctional photosensitizers and photoinitiators.

17.
Cancer Treat Rev ; 129: 102792, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38972135

RESUMO

INTRODUCTION: Bone metastases negatively affect prognosis in patients with advanced renal cell carcinoma (aRCC). We conducted a systematic literature review to identify clinical trial publications including patients with aRCC with and without bone metastases. METHODS: The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta­Analyses (PRISMA) guidelines and registered with PROSPERO (CRD42022355436). MEDLINE and Embase databases were searched (September 2, 2022) to identify publications reporting efficacy and safety outcomes for patients with/without bone metastasis from clinical trials of systemic RCC therapies. Risk of bias was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Of 526 publications screened, 19 were eligible: seven (from five studies) reported phase 3 trials, six reported phase 2 trials, one reported phase 1b/2 trials, and five were pooled analyses. Five publications reported moderate-quality evidence, while 14 were graded as low- or very low-quality evidence, suggesting a high potential for uncertainty. Five studies reported benefits of investigational therapies versus comparators in patients with and without bone metastases; these studies included cabozantinib, nivolumab, cabozantinib plus nivolumab, and lenvatinib plus pembrolizumab treatment arms. Data were also available for nivolumab plus ipilimumab. Bone metastases were consistently associated with poor prognosis in patients with aRCC. Preliminary data support the hypothesis that therapies targeting pathways implicated in the development of bone metastases may be beneficial, and warrant further investigation. However, data to support treatment decision-making are lacking. CONCLUSION: Our findings highlight the need for clinical data to assist in defining the optimal treatment for patients with aRCC and bone metastasis.

18.
Colloids Surf B Biointerfaces ; 242: 114074, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38972257

RESUMO

As the field of cancer therapeutics evolves, integrating two-dimensional (2D) nanomaterials with photo-immunotherapy has emerged as a promising approach with significant potential to augment cancer treatment efficacy. These 2D nanomaterials include graphene-based 2D nanomaterials, 2D MXenes, 2D layered double hydroxides, black phosphorus nanosheets, 2D metal-organic frameworks, and 2D transition metal dichalcogenides. They exhibit high load capacities, multiple functionalization pathways, optimal biocompatibility, and physiological stability. Predominantly, they function as anti-tumor delivery systems, amalgamating diverse therapeutic modalities, most notably phototherapy and immunotherapy, and the former is a recognized non-invasive treatment modality, and the latter represents the most promising anti-cancer strategy presently accessible. Thus, integrating phototherapy and immunotherapy founded on 2D nanomaterials unveils a novel paradigm in the war against cancer. This review delineates the latest developments in 2D nanomaterials as delivery systems for synergistic photo-immunotherapy in cancer treatment. We elaborate on the burgeoning realm of photo-immunotherapy, exploring the interplay between phototherapy and enhanced immune cells, immune response modulation, or immunosuppressive tumor microenvironments. Notably, the strategies to augment photo-immunotherapy have also been discussed. Finally, we discuss the challenges and future perspectives of these 2D nanomaterials in photo-immunotherapy.

19.
ESC Heart Fail ; 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38970349

RESUMO

AIMS: Individuals with congenital heart disease (CHD) are at an increased risk for cancer. As cancer survival rates improve, the prevalence of late side effects, such as heart failure (HF), is becoming more evident. This study aims to evaluate the risk of developing HF following a cancer diagnosis in patients with CHD, compared with those without CHD and with CHD patients who do not have cancer. METHODS: CHD patients (n = 69 799) and randomly selected non-CHD controls (n = 650 406), born in Sweden between 1952 and 2017, were identified from the Swedish National Health Registers and Total Population Register (excluding those with syndromes and transplant recipients). CHD patients who developed cancer (n = 1309) were propensity score-matched with non-CHD patients who developed cancer (n = 9425), resulting in a cohort of 1232 CHD patients with cancer and 2602 non-CHD controls with cancer (after exclusion of individuals with HF prior to cancer diagnosis). In a separate analysis, CHD patients with cancer were propensity score-matched with CHD patients without cancer (n = 68 490). A total of 1233 CHD patients with cancer and 2257 CHD patients without cancer were included in the study. RESULTS: Among CHD patients with cancer, 73 (5.9%) developed HF during a mean follow-up time of 8.5 ± 8.7. Comparatively, in the propensity-matched control population, 29 (1.1%) non-CHD cancer patients (mean follow-up time of 7.3 ± 7.5) and 101 (4.5%) CHD patients without cancer (mean follow-up time of 9.9 ± 9.2) developed HF. CHD patients exhibited a significantly higher risk of HF post-cancer diagnosis compared with the non-CHD control group [hazard ratio (HR) 4.39, 95% confidence interval (CI) 2.83-6.81], after adjusting for age at cancer diagnosis and comorbidities. In the analysis between CHD patients with cancer and those without cancer, the results indicated a significantly higher risk of developing HF in CHD patients with cancer (HR 1.53, 95% CI 1.13-2.07). CONCLUSIONS: CHD patients face a more than four-fold increased risk of developing HF after a cancer diagnosis compared with cancer patients without CHD. Among CHD patients, the risk of HF is only modestly higher for those with cancer than for those without cancer. This suggests that the increased HF risk in CHD patients with cancer, relative to non-CHD cancer patients, may be more attributable to CHD itself than to cancer treatment-related side effects.

20.
Front Artif Intell ; 7: 1402719, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38887603

RESUMO

Introduction: Breast cancer is an extremely common and potentially fatal illness that impacts millions of women worldwide. Multiple criteria and inclinations must be taken into account when selecting the optimal treatment option for each patient. Methods: The selection of breast cancer treatments can be modeled as a multi-attribute group decision-making (MAGDM) problem, in which a group of experts evaluate and rank alternative treatments based on multiple attributes. MAGDM methods can aid in enhancing the quality and efficacy of breast cancer treatment selection decisions. For this purpose, we introduce the concept of a 2-tuple linguistic interval-valued q-rung orthopair fuzzy set (2TLIVq-ROFS), a new development in fuzzy set theory that incorporates the characteristics of interval-valued q-rung orthopair fuzzy set (IVq-ROFS) and 2-tuple linguistic terms. It can express the quantitative and qualitative aspects of uncertain information, as well as the decision-makers' level of satisfaction and dissatisfaction. Results: Then, the 2TLIVq-ROF weighted average (2TLIVq-ROFWA) operator and the 2TLIVq-ROF weighted geometric (2TLIVq-ROFWJ) operator are introduced as two new aggregation operators. In addition, the multi-attribute border approximation area comparison (MABAC) method is extended to solve the MAGDM problem with 2TLIVq-ROF information. Discussion: To demonstrate the efficacy and applicability of the suggested model, a case study of selecting the optimal breast cancer treatment is presented. The results of the computations show that the suggested MAGDM model is able to handle imprecision and subjectivity in complicated decision-making scenarios and opens new research scenarios for scholars.

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