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1.
J Control Release ; 370: 168-181, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38643936

ABSTRACT

The high prevalence and severity of hepatocellular carcinoma (HCC) present a significant menace to human health. Despite the significant advancements in nanotechnology-driven antineoplastic agents, there remains a conspicuous gap in the development of targeted chemotherapeutic agents specifically designed for HCC. Consequently, there is an urgent need to explore potent drug delivery systems for effective HCC treatment. Here we have exploited the interplay between HCC and adipocyte to engineer a hybrid adipocyte-derived exosome platform, serving as a versatile vehicle to specifically target HCC and exsert potent antitumor effect. A lipid-like prodrug of docetaxel (DSTG) with a reactive oxygen species (ROS)-cleavable linker, and a lipid-conjugated photosensitizer (PPLA), spontaneously co-assemble into nanoparticles, functioning as the lipid cores of the hybrid exosomes (HEMPs and NEMPs). These nanoparticles are further encapsuled within adipocyte-derived exosome membranes, enhancing their affinity towards HCC cancer cells. As such, cancer cell uptakes of hybrid exosomes are increased up to 5.73-fold compared to lipid core nanoparticles. Our in vitro and in vivo experiments have demonstrated that HEMPs not only enhance the bioactivity of the prodrug and extend its circulation in the bloodstream but also effectively inhibit tumor growth by selectively targeting hepatocellular carcinoma tumor cells. Self-facilitated synergistic drug release subsequently promoting antitumor efficacy, inducing significant inhibition of tumor growth with minimal side effects. Our findings herald a promising direction for the development of targeted HCC therapeutics.


Subject(s)
Adipocytes , Antineoplastic Agents , Carcinoma, Hepatocellular , Docetaxel , Exosomes , Liver Neoplasms , Nanoparticles , Exosomes/metabolism , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/pathology , Animals , Liver Neoplasms/drug therapy , Liver Neoplasms/therapy , Liver Neoplasms/pathology , Humans , Docetaxel/administration & dosage , Docetaxel/pharmacology , Docetaxel/therapeutic use , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Adipocytes/drug effects , Nanoparticles/chemistry , Nanoparticles/administration & dosage , Prodrugs/administration & dosage , Prodrugs/therapeutic use , Cell Line, Tumor , Photosensitizing Agents/administration & dosage , Photosensitizing Agents/therapeutic use , Photosensitizing Agents/pharmacology , Mice, Nude , Phototherapy/methods , Drug Delivery Systems , Mice , Reactive Oxygen Species/metabolism , Mice, Inbred BALB C
2.
Medicine (Baltimore) ; 103(14): e36758, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38579051

ABSTRACT

BACKGROUND: Compound Kushen injection (CKI) is a mixture of natural compounds extracted from Radix Sophorae and Smilax glabra Roxb. CKI, as an antitumor preparation, plays a vital role in the clinical treatment of lung and gastrointestinal cancers. METHODS: Electronic databases such as the China National Knowledge Infrastructure, Wanfang data, PubMed, EMBASE, and Web of Science were searched for studies. The included studies were evaluated according to the Cochrane Handbook for Systematic Reviews, and meta-analyses were performed using RevMan 5.3 software. RESULTS: Twenty-four randomized controlled trials were selected for meta-analysis. The outcomes showed that CKI adjuvant therapy significantly improved complete remission (CR) and partial response (PR) compared to patients without CKI treatment in gastrointestinal cancers (CR: odds ratio [OR] = 1.76, 95% confidence interval [CI]: [1.29, 2.41], P = .0004; PR: OR = 1.64, 95% CI: [1.29, 2.07], P =.0001), and lung cancer (CR: OR = 2.18, 95% CI: [1.36, 3.51], P = .001); PR: OR = 1.81, 95% CI: [1.31, 2.50], P = .0003). CKI adjuvant therapy had a statistically significant advantage in optimizing life and health status (quality of life [QOL] for gastrointestinal cancers: MD = 1.76, 95% CI: [6.41, 13.80], P = .001, and Karnofsky performance status [KPS] for gastrointestinal cancers: MD = 4.64, 95% CI: [2.72, 6.57], P = .001; KPS for lung cancer: MD = 6.24, 95% CI [1.78, 10.71], P = .006). CKI reduced the pain in lung cancer patients (MD = -1.76, 95% CI: [-1.94, -1.58], P < .00001), increased immunity level (MD = 2.51, 95% CI: [2.17, 2.85], P < .00001), and alleviated the adverse reactions for lung and gastrointestinal cancers (MD = 0.38, 95% CI: (0.32, 0.46); P < .00001). CONCLUSION: The combination of CKI and chemoradiotherapy for treating lung and gastrointestinal cancer has positive effects on short-term and long-term outcomes and has advantages over chemoradiotherapy alone regarding safety and efficacy.


Subject(s)
Antineoplastic Agents , Drugs, Chinese Herbal , Gastrointestinal Neoplasms , Lung Neoplasms , Humans , Quality of Life , Systematic Reviews as Topic , Lung Neoplasms/drug therapy , Chemoradiotherapy/adverse effects , Gastrointestinal Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use , Lung
3.
Drug Saf ; 47(7): 617-641, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38607520

ABSTRACT

Enzalutamide is an oral androgen receptor signaling inhibitor utilized in the treatment of men with prostate cancer. It is a moderate inducer of the cytochrome P450 (CYP) enzymes CYP2C9 and CYP2C19, and a strong inducer of CYP3A4. It was also shown to be a mild inhibitor of the efflux transporter P-glycoprotein in patients with prostate cancer. Enzalutamide is primarily metabolized by CYP3A4 and CYP2C8. The risk of enzalutamide drug interactions arises primarily when it is coadministered with other drugs that interact with these CYPs, including CYP3A4. In this review, we begin by providing an overview of enzalutamide including its dosing, use in special populations, pharmacokinetics, changes to its prescribing information, and potential for interaction with coadministered drugs. Enzalutamide interactions with drugs from a wide range of medication classes commonly prescribed to patients with prostate cancer are described, including oral androgen deprivation therapy, agents used to treat a range of cardiovascular diseases, antidiabetic drugs, antidepressants, anti-seizure medications, common urology medications, analgesics, proton pump inhibitors, immunosuppressants, and antigout drugs. Enzalutamide interactions with common vitamins and supplements are also briefly discussed. This review provides a resource for healthcare practitioners and patients that will help provide a basis for the understanding and management of enzalutamide drug-drug interactions to inform decision making, improve patient safety, and optimize drug efficacy.


Enzalutamide is a drug that is used to treat various stages of advanced prostate cancer, a type of cancer that begins in the prostate and may spread beyond the prostate. Enzalutamide stops testosterone from stimulating prostate cancer growth. Like other drugs, enzalutamide enters the bloodstream, and then is processed and removed from the body. Sometimes, when a person takes multiple drugs, one drug can make it difficult for the body to process and remove one or more of the other drugs. This is referred to as a drug interaction. Enzalutamide drug interactions can cause the level of other drugs in the body to increase or decrease in an abnormal way. It is also possible for certain other drugs to alter the levels of enzalutamide. Drug interactions that cause the level of a drug to get too low can prevent that drug from working effectively, whereas drug interactions that cause the level of a drug to get too high can lead to side effects of that drug. People with prostate cancer are mostly aged 65 years or older and often take medications to treat a variety of diseases. Examples include medications to treat heart conditions, diabetes, high cholesterol, high blood pressure, and many other conditions. Here, we describe enzalutamide drug interactions with these types of medications. Our goal is to provide a resource to help healthcare providers and patients better understand enzalutamide drug interactions and how to manage them to improve patient safety and drug effectiveness.


Subject(s)
Benzamides , Drug Interactions , Nitriles , Phenylthiohydantoin , Humans , Phenylthiohydantoin/adverse effects , Phenylthiohydantoin/therapeutic use , Nitriles/adverse effects , Benzamides/adverse effects , Benzamides/therapeutic use , Male , Patient Safety , Prostatic Neoplasms/drug therapy , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use
5.
N Engl J Med ; 390(14): 1265-1276, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38598794

ABSTRACT

BACKGROUND: Platinum-based chemotherapy is the recommended adjuvant treatment for patients with resectable, ALK-positive non-small-cell lung cancer (NSCLC). Data on the efficacy and safety of adjuvant alectinib as compared with chemotherapy in patients with resected ALK-positive NSCLC are lacking. METHODS: We conducted a global, phase 3, open-label, randomized trial in which patients with completely resected, ALK-positive NSCLC of stage IB (tumors ≥4 cm), II, or IIIA (as classified according to the seventh edition of the Cancer Staging Manual of the American Joint Committee on Cancer and Union for International Cancer Control) were randomly assigned in a 1:1 ratio to receive oral alectinib (600 mg twice daily) for 24 months or intravenous platinum-based chemotherapy in four 21-day cycles. The primary end point was disease-free survival, tested hierarchically among patients with stage II or IIIA disease and then in the intention-to-treat population. Other end points included central nervous system (CNS) disease-free survival, overall survival, and safety. RESULTS: In total, 257 patients were randomly assigned to receive alectinib (130 patients) or chemotherapy (127 patients). The percentage of patients alive and disease-free at 2 years was 93.8% in the alectinib group and 63.0% in the chemotherapy group among patients with stage II or IIIA disease (hazard ratio for disease recurrence or death, 0.24; 95% confidence interval [CI], 0.13 to 0.45; P<0.001) and 93.6% and 63.7%, respectively, in the intention-to-treat population (hazard ratio, 0.24; 95% CI, 0.13 to 0.43; P<0.001). Alectinib was associated with a clinically meaningful benefit with respect to CNS disease-free survival as compared with chemotherapy (hazard ratio for CNS disease recurrence or death, 0.22; 95% CI, 0.08 to 0.58). Data for overall survival were immature. No unexpected safety findings were observed. CONCLUSIONS: Among patients with resected ALK-positive NSCLC of stage IB, II, or IIIA, adjuvant alectinib significantly improved disease-free survival as compared with platinum-based chemotherapy. (Funded by F. Hoffmann-La Roche; ALINA ClinicalTrials.gov number, NCT03456076.).


Subject(s)
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Platinum Compounds , Humans , Carbazoles/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/surgery , Neoplasm Recurrence, Local/drug therapy , Piperidines/therapeutic use , Receptor Protein-Tyrosine Kinases , Treatment Outcome , Administration, Oral , Administration, Intravenous , Platinum Compounds/therapeutic use , Antineoplastic Agents/therapeutic use
6.
J Cancer Res Clin Oncol ; 150(4): 213, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38662225

ABSTRACT

Copper is a necessary micronutrient for maintaining the well-being of the human body. The biological activity of organic ligands, especially their anticancer activity, is often enhanced when they coordinate with copper(I) and (II) ions. Copper and its compounds are capable of inducing tumor cell death through various mechanisms of action, including activation of apoptosis signaling pathways by reactive oxygen species (ROS), inhibition of angiogenesis, induction of cuproptosis, and paraptosis. Some of the copper complexes are currently being evaluated in clinical trials for their ability to map tumor hypoxia in various cancers, including locally advanced rectal cancer and bulky tumors. Several studies have shown that copper nanoparticles can be used as effective agents in chemodynamic therapy, phototherapy, hyperthermia, and immunotherapy. Despite the promising anticancer activity of copper-based compounds, their use in clinical trials is subject to certain limitations. Elevated copper concentrations may promote tumor growth, angiogenesis, and metastasis by affecting cellular processes.


Subject(s)
Antineoplastic Agents , Copper , Neoplasms , Humans , Copper/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Neoplasms/drug therapy , Neoplasms/pathology , Animals , Coordination Complexes/pharmacology , Coordination Complexes/therapeutic use , Coordination Complexes/chemistry
7.
Crit Rev Oncol Hematol ; 196: 104277, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38492760

ABSTRACT

BACKGROUND: Patients with cancer can expect to receive numerous invasive vascular access procedures for intravenous therapy and clinical diagnostics. Due to the increased incidence and prevalence of cancer globally there will be significantly more people who require first-line intravenous chemotherapy over the next ten years. METHODS: Our objective was to determine the types of evidence that exist for the vascular access device (VAD) type for the delivery of systemic anti-cancer therapy (SACT) in cancer patients. We used JBI scoping review methodology to identify the types of VADs used for SACT and with a specific search strategy included articles from 2012-2022 published in the English language. We identify (i) type of VADs used for SACT delivery (ii) the type of insertion and post-insertion complications (iii) the geographical location and clinical environment (iv) and whether VAD choice impacts on quality of life (QOL). Findings were presented using the PAGER framework. MAIN FINDINGS: Our search strategy identified 10,390 titles, of these, 5318 duplicates were removed. The remaining 5072 sources were screened for eligibility, 240 articles met the inclusion criteria. The most common design include retrospective study designs (n = 91) followed by prospective study designs (n = 31). We found 28 interventional studies with 21 registered in a clinical trial registry and identified no core outcome sets papers specific to VAD for SACT. The most prevalent publications were those that featured two or more VAD types (n = 70), followed by tunnelled intravenous VADs (n = 67). Of 38 unique complications identified, the most frequent catheter related complication was catheter related thrombosis (n = 178, 74%), followed by infection (n = 170, 71%). The county where the most publications originated from was China (n = 62) with one randomized controlled multicenter study from a comprehensive cancer centre. Of the thirty three studies that included QOL we found 4 which reported on body image. No QOL measurement tools specific to the process of SACT administration via VAD are available INTERPRETATION: Our findings suggest a systematic review and meta-analysis of VAD use for intravenous SACT can be considered. However, the development of a core outcome set for SACT should be prioritised. Funding for high quality programs of research for VAD in cancer are needed. Comprehensive cancer centres should lead this research agenda.


Subject(s)
Antineoplastic Agents , Neoplasms , Vascular Access Devices , Humans , Antineoplastic Agents/adverse effects , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Neoplasms/drug therapy , Quality of Life , Vascular Access Devices/adverse effects
8.
Environ Toxicol ; 39(6): 3389-3399, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38445457

ABSTRACT

Breast cancer stands as the predominant malignancy and primary cause of cancer-related mortality among females globally. Approximately 25% of breast cancers exhibit HER2 overexpression, imparting a more aggressive tumor phenotype and correlating with poor prognoses. Patients with metastatic breast cancer receiving HER2 tyrosine kinase inhibitors (HER2 TKIs), such as Lapatinib, develop acquired resistance within a year, posing a critical challenge in managing this disease. Here, we explore the potential of Artemisia argyi, a Chinese herbal medicine known for its anti-cancer properties, in mitigating HER2 TKI resistance in breast cancer. Analysis of the Cancer Genome Atlas (TCGA) revealed diminished expression of transmembrane serine protease 2 (TMPRSS2), a subfamily of membrane proteolytic enzymes, in breast cancer patients, correlating with unfavorable outcomes. Intriguingly, lapatinib-responsive patients exhibited higher TMPRSS2 expression. Our study unveiled that the compounds from Artemisia argyi, eriodictyol, and umbelliferone could inhibit the growth of lapatinib-resistant HER2-positive breast cancer cells. Mechanistically, they suppressed HER2 kinase activation by enhancing TMPRSS2 activity. Our findings propose TMPRSS2 as a critical determinant in lapatinib sensitivity, and Artemisia argyi emerges as a potential agent to overcome lapatinib via activating TMPRSS2 in HER2-positive breast cancer. This study not only unravels the molecular mechanisms driving cell death in HER2-positive breast cancer cells induced by Artemisia argyi but also lays the groundwork for developing novel inhibitors to enhance therapy outcomes.


Subject(s)
Artemisia , Breast Neoplasms , Drug Resistance, Neoplasm , Lapatinib , Plant Extracts , Receptor, ErbB-2 , Serine Endopeptidases , Lapatinib/pharmacology , Lapatinib/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Humans , Drug Resistance, Neoplasm/drug effects , Artemisia/chemistry , Female , Serine Endopeptidases/metabolism , Serine Endopeptidases/genetics , Receptor, ErbB-2/metabolism , Receptor, ErbB-2/genetics , Cell Line, Tumor , Plant Extracts/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use
9.
Nanoscale Horiz ; 9(5): 731-741, 2024 04 29.
Article in English | MEDLINE | ID: mdl-38505973

ABSTRACT

Phototherapy shows great potential for pinpoint tumour treatment. Heptamethine cyanine dyes like IR783 have high potential as agents for antitumour phototherapy due to their inherent tumour targeting ability, though their effectiveness in vivo is unsatisfactory for clinical translation. To overcome this limitation, we present an innovative strategy involving IR783-based polymeric nanoassemblies that improve the dye's performance as an antitumoural photosensitizer. In the formulation, IR783 is modified with cysteamine and used to initiate the ring-opening polymerization (ROP) of the N-carboxyanhydride of benzyl-L-aspartate (BLA), resulting in IR783-installed poly(BLA). Compared to free IR783, the IR783 dye in the polymer adopts a twisted molecular conformation and tuned electron orbital distribution, remarkably enhancing its optical properties. In aqueous environments, the polymers spontaneously assemble into nanostructures with 60 nm diameter, showcasing surface-exposed IR783 dyes that function as ligands for cancer cell and mitochondria targeting. Moreover, the nanoassemblies stabilized the dyes and enhanced the generation of reactive oxygen species (ROS) upon laser irradiation. Thus, in murine tumor models, a single injection of the nanoassemblies with laser irradiation significantly inhibits tumour growth with no detectable off-target toxicity. These findings highlight the potential for improving the performance of heptamethine cyanine dyes in antitumor phototherapy through nano-enabled strategies.


Subject(s)
Carbocyanines , Reactive Oxygen Species , Reactive Oxygen Species/metabolism , Humans , Animals , Mice , Carbocyanines/chemistry , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Phototherapy/methods , Cell Line, Tumor , Neoplasms/drug therapy , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/radiation effects , Antineoplastic Agents/therapeutic use , Polymers/chemistry , Nanostructures/chemistry , Nanostructures/therapeutic use
10.
Chemistry ; 30(31): e202304338, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38538540

ABSTRACT

Glioma, the most common primary brain tumor, is highly invasive and grows rapidly. As such, the survival of glioma patients is relatively short, highlighting the vital importance of timely diagnosis and treatment of glioma. However, the blood brain barrier (BBB) and the non-targeting delivery systems of contrast agents and drugs greatly hinder the effective glioma imaging and therapy. Fortunately, in recent years, investigators have constructed various biomimetic delivery platforms utilizing the exceptional advantages of biomimetic nanocomposites, such as immune evasion, homologous targeting ability, and BBB penetrating ability, to achieve efficient and precise delivery of substances to glioma sites for improved diagnosis and treatment. In this concept, we present the application of these biomimetic nanocomposites in fluorescence imaging (FI), magnetic resonance imaging (MRI), and multi-modal imaging, as well as in chemotherapy, phototherapy, and combined therapy for glioma. Lastly, we provide our perspective on this research field.


Subject(s)
Biomimetic Materials , Blood-Brain Barrier , Brain Neoplasms , Glioma , Magnetic Resonance Imaging , Nanocomposites , Glioma/diagnostic imaging , Glioma/therapy , Humans , Nanocomposites/chemistry , Nanocomposites/therapeutic use , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/therapy , Biomimetic Materials/chemistry , Blood-Brain Barrier/metabolism , Contrast Media/chemistry , Optical Imaging , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Animals , Drug Delivery Systems , Phototherapy , Biomimetics/methods
11.
Endocr Pract ; 30(5): 456-464, 2024 May.
Article in English | MEDLINE | ID: mdl-38447630

ABSTRACT

OBJECTIVE: We aimed to assess the early efficacy of anlotinib in patients with progressive radioactive iodine refractory differentiated thyroid cancer at the structural, biochemical, and metabolic levels. METHODS: Ten eligible patients were prospectively enrolled to receive anlotinib. Their responses were assessed at 6 weeks. Apart from the structural response according to Response Evaluation Criteria in Solid Tumors version 1.1, the biochemical response was assessed by serum thyroglobulin (Tg), and the metabolic response was assessed by 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) according to the European Organization for Research and Treatment of Cancer criteria. A safety profile was recorded. RESULTS: Structurally controlled disease (20% partial response + 80% stable disease) was observed in all patients. The median longest diameter of target lesions shrank from 20.8 mm (IQR, 14.9-27.5) to 17.0 mm (IQR, 14.1-23.7) (P < .001), and the average shrinkage rate was -15.1 ± 14.1%. Sharp serum Tg reduction by 72.8 ± 16.4% was observed in 8 measurable patients. The 18F-FDG PET/CT-mapped glucose metabolic response was not quite comparable to the structural response, with 90% of the patients having controlled disease (30% partial metabolic response + 60% stable metabolic disease), whereas 10% presented progressive metabolic disease. The most common treatment-emergent adverse events (AEs) were hypertension (100%) and proteinuria (70%). Most AEs were grade 1 or 2, whereas grade 3 AEs occurred only in hypertension. CONCLUSION: Anlotinib is generally well tolerated and can bring early disease control within the initial 6 weeks of treatment. The sharp biochemical response suggests Tg to be an early sensitive biomarker to anlotinib, whereas the heterogeneous metabolic response might play a complementary role.


Subject(s)
Indoles , Iodine Radioisotopes , Positron Emission Tomography Computed Tomography , Quinolines , Thyroid Neoplasms , Humans , Female , Male , Middle Aged , Quinolines/therapeutic use , Quinolines/administration & dosage , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/radiotherapy , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/pathology , Indoles/therapeutic use , Indoles/administration & dosage , Adult , Iodine Radioisotopes/therapeutic use , Aged , Fluorodeoxyglucose F18 , Prospective Studies , Thyroglobulin/blood , Antineoplastic Agents/therapeutic use , Treatment Outcome
12.
Pharmacol Res ; 203: 107150, 2024 May.
Article in English | MEDLINE | ID: mdl-38521285

ABSTRACT

Cancer, with its diversity, heterogeneity, and complexity, is a significant contributor to global morbidity, disability, and mortality, highlighting the necessity for transformative treatment approaches. Photodynamic therapy (PDT) has aroused continuous interest as a viable alternative to conventional cancer treatments that encounter drug resistance. Nanotechnology has brought new advances in medicine and has shown great potential in drug delivery and cancer treatment. For precise and efficient therapeutic utilization of such a tumor therapeutic approach with high spatiotemporal selectivity and minimal invasiveness, the carrier-free noncovalent nanoparticles (NPs) based on chemo-photodynamic combination therapy is essential. Utilizing natural products as the foundation for nanodrug development offers unparalleled advantages, including exceptional pharmacological activity, easy functionalization/modification, and well biocompatibility. The natural-product-based, carrier-free, noncovalent NPs revealed excellent synergistic anticancer activity in comparison with free photosensitizers and free bioactive natural products, representing an alternative and favorable combination therapeutic avenue to improve therapeutic efficacy. Herein, a comprehensive summary of current strategies and representative application examples of carrier-free noncovalent NPs in the past decade based on natural products (such as paclitaxel, 10-hydroxycamptothecin, doxorubicin, etoposide, combretastatin A4, epigallocatechin gallate, and curcumin) for tumor chemo-photodynamic combination therapy. We highlight the insightful design and synthesis of the smart carrier-free NPs that aim to enhance PDT efficacy. Meanwhile, we discuss the future challenges and potential opportunities associated with these NPs to provide new enlightenment, spur innovative ideas, and facilitate PDT-mediated clinical transformation.


Subject(s)
Biological Products , Nanoparticles , Neoplasms , Photochemotherapy , Humans , Animals , Neoplasms/drug therapy , Nanoparticles/chemistry , Biological Products/chemistry , Biological Products/therapeutic use , Biological Products/pharmacology , Biological Products/administration & dosage , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Photosensitizing Agents/therapeutic use , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Photosensitizing Agents/administration & dosage
13.
Article in English | MEDLINE | ID: mdl-38503502

ABSTRACT

Acute promyelocytic leukemia (APL) is driven by the promyelocytic leukemia (PML)/retinoic acid receptor α (RARA) fusion oncoprotein. Over the years, it has emerged as a model system to understand how this simple (and sometimes sole) genetic alteration can transform hematopoietic progenitors through the acquisition of dominant-negative properties toward both transcriptional control by nuclear receptors and PML-mediated senescence. The fortuitous identification of two drugs, arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA), that respectively bind PML and RARA to initiate PML/RARA degradation, has allowed an unprecedented dissection of the cellular and molecular mechanisms involved in patients' cure by the ATO/ATRA combination. This analysis has unraveled the dual and complementary roles of RARA and PML in both APL initiation and cure by the ATRA/ATO combination. We discuss how some of the features unraveled by APL studies may be more broadly applicable to some other forms of leukemia. In particular, the functional synergy between drugs that promote differentiation and those that initiate apoptosis/senescence to impede self-renewal could pave the way to novel curative combinations.


Subject(s)
Antineoplastic Agents , Arsenic Trioxide , Arsenicals , Leukemia, Promyelocytic, Acute , Oncogene Proteins, Fusion , Oxides , Tretinoin , Leukemia, Promyelocytic, Acute/drug therapy , Leukemia, Promyelocytic, Acute/genetics , Humans , Tretinoin/therapeutic use , Tretinoin/pharmacology , Arsenic Trioxide/pharmacology , Arsenic Trioxide/therapeutic use , Oxides/pharmacology , Oxides/therapeutic use , Arsenicals/pharmacology , Arsenicals/therapeutic use , Oncogene Proteins, Fusion/genetics , Oncogene Proteins, Fusion/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Receptors, Retinoic Acid/metabolism , Receptors, Retinoic Acid/genetics , Retinoic Acid Receptor alpha/metabolism , Retinoic Acid Receptor alpha/genetics , Promyelocytic Leukemia Protein/metabolism , Promyelocytic Leukemia Protein/genetics , Transcription Factors/metabolism , Transcription Factors/genetics
14.
Naunyn Schmiedebergs Arch Pharmacol ; 397(9): 6745-6761, 2024 09.
Article in English | MEDLINE | ID: mdl-38507104

ABSTRACT

Cantharidin, a terpenoid produced by blister beetles, has been used in traditional Chinese medicine to treat various ailments and cancers. However, its biological activity, impact, and anticancer mechanisms remain unclear. The Cantharidin chemical gene connections were identified using various databases. The GSE21815 dataset was used to collect the gene expression information. Differential gene analysis and gene ontology analyses were performed. Gene set enrichment analysis was used to assess the activation of disease pathways. Weighted gene co-expression network analysis and differential analysis were used to identify illness-associated genes, examine differential genes, and discover therapeutic targets via protein-protein interactions. MCODE analysis of major subgroup networks was used to identify critical genes influenced by Cantharidin, examine variations in the expression of key clustered genes in colorectal cancer vs. control samples, and describe the subject operators. Single-cell GSE188711 dataset was preprocessed to investigate Cantharidin's therapeutic targets and signaling pathways in colorectal cancer. Single-cell RNA sequencing was utilized to identify 22 cell clusters and marker genes for two different cell types in each cluster. The effects of different Cantharidin concentrations on colorectal cancer cells were studied in vitro. One hundred and ninety-seven Cantharidin-associated target genes and 480 critical genes implicated in the development of the illness were identified. Cantharidin significantly inhibited the proliferation and migration of HCT116 cells and promoted apoptosis at certain concentrations. Patients on current therapy develop inherent and acquired resistance. Our study suggests that Cantharidin may play an anti-CRC role by modulating immune function.


Subject(s)
Antineoplastic Agents , Cantharidin , Colorectal Neoplasms , Computational Biology , Network Pharmacology , Cantharidin/pharmacology , Humans , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Gene Regulatory Networks , Gene Expression Regulation, Neoplastic/drug effects , Databases, Genetic , Cell Proliferation/drug effects , Protein Interaction Maps , HCT116 Cells , Signal Transduction/drug effects , Cell Line, Tumor
15.
Molecules ; 29(6)2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38542956

ABSTRACT

Natural products, particularly medicinal plants, are crucial in combating cancer and aiding in the discovery and development of new therapeutic agents owing to their biologically active compounds. They offer a promising avenue for developing effective anticancer medications because of their low toxicity, diverse chemical structures, and ability to target various cancers. Allicin is one of the main ingredients in garlic (Allium sativum L.). It is a bioactive sulfur compound maintained in various plant sections in a precursor state. Numerous studies have documented the positive health benefits of this natural compound on many chronic conditions, including gastric, hepatic, breast, lung, cervical, prostate, and colon cancer. Moreover, allicin may target several cancer hallmarks or fundamental biological traits and functions that influence cancer development and spread. Cancer hallmarks include sustained proliferation, evasion of growth suppressors, metastasis, replicative immortality, angiogenesis, resistance to cell death, altered cellular energetics, and immune evasion. The findings of this review should provide researchers and medical professionals with a solid basis to support fundamental and clinical investigations of allicin as a prospective anticancer drug. This review outlines the anticancer role of allicin in each hallmark of cancer.


Subject(s)
Antineoplastic Agents , Colonic Neoplasms , Garlic , Plants, Medicinal , Male , Humans , Plant Extracts/chemistry , Prospective Studies , Sulfinic Acids/chemistry , Disulfides , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Colonic Neoplasms/drug therapy , Garlic/chemistry
16.
J Cancer Res Ther ; 20(1): 181-188, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38554318

ABSTRACT

INTRODUCTION: Rotheca serrata (Lamiaceae), a highly medicinal plant is used as an antidote for snakebite and the plant possesses medicinal properties like hepatoprotective, antitussive, antioxidant, anticancer, neuro-protective, used in rheumatoid arthritis and is also a α-glucoside inhibitor. AIM OF THE STUDY: This work aimed to study the anticancerous effect of Rotheca serrata (root and leaf) on cancer cell lines MCF-7 (breast cancer cell line) and Neuroblastoma SH-SY5Y. MATERIALS AND METHODS: This investigation was a preliminary one which supported the retrospective and safe use of plants as described in Ayurveda. Dulbecco's Modified Eagle Medium with High Glucose (DMEM-HG) for culturing MCF-7- Human Breast cancer cell line and Minimum essential Medium (MEM)+F12 medium for culturing SH-SY5Y- Homo sapiens bone marrow neuroblast were used. MTT assay measured the cell proliferation rate and conversely, when metabolic events lead to apoptosis or necrosis, the reduction in cell viability. RESULTS: The results indicated that the Methanolic extract of Rotheca serrata (root and leaf) showed high anticancer activity. Different concentrations of plant extracts (25, 50, 100, 200, 400 µg/ml) were used to study the anticancerous activity, amongst which the significant results were obtained for 400 µg/ml concentration (both root & leaf). Effective anticancer activity against MCF - 7 breast cancer cells was shown in methanoilc extracts and were expressed as IC 50 values; in root (IC 50 value = 61.8259 ± 7.428 µg/ml) and in leaf (IC 50 value = 78.1497 ± 6.316 µg/ml). The MTT assay in case of neuroblastoma (SH-SY5Y) cell lines revealed that 400 µg/ml concentration of leaf methanolic extract showed effective inhibition of cancer cells with IC 50 value 37.8462 ± 2.957 µg/ml as compared to IC 50 value of root methanolic extract which was 57.0895 ± 2.351 µg/ml. CONCLUSION: R. serrata possess anticancer activity against breast cancer cell line (MCF-7) and neuroblastoma (SH-SY 5Y) cell lines. This study may to design plant-based drugs without side effects. Dosage compensation for specific type of cancer needs to be monitored in patients with 1st stage.


Subject(s)
Antineoplastic Agents , Breast Neoplasms , Lamiaceae , Neuroblastoma , Humans , Female , Neuroblastoma/drug therapy , MCF-7 Cells , Retrospective Studies , Cell Line, Tumor , Antineoplastic Agents/therapeutic use , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Breast Neoplasms/drug therapy , Cell Survival
17.
Lasers Med Sci ; 39(1): 91, 2024 Mar 16.
Article in English | MEDLINE | ID: mdl-38491201

ABSTRACT

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.


Subject(s)
Antineoplastic Agents , Curcumin , Lung Neoplasms , Nanoparticles , Photochemotherapy , Humans , Lung Neoplasms/drug therapy , Curcumin/pharmacology , Curcumin/therapeutic use , Silicon Dioxide/chemistry , Drug Carriers/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Nanoparticles/chemistry
18.
Int Immunopharmacol ; 130: 111769, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38442584

ABSTRACT

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.


Subject(s)
Antineoplastic Agents , Carcinoma, Hepatocellular , Hyperthermia, Induced , Liver Neoplasms , Membrane Proteins , Nucleotidyltransferases , Picibanil , Radiofrequency Ablation , Toll-Like Receptor 4 , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Neoplasm Recurrence, Local/pathology , Picibanil/pharmacology , Picibanil/therapeutic use , Retrospective Studies , Toll-Like Receptor 4/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Animals , Mice , Cell Line, Tumor , Mice, Inbred C57BL , Male
19.
Biomed Pharmacother ; 173: 116375, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38460372

ABSTRACT

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.


Subject(s)
Antineoplastic Agents , Curcumin , Nanoparticles , Prodrugs , Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/drug therapy , Drug Carriers , Drug Delivery Systems , Docetaxel/therapeutic use , Curcumin/pharmacology , Curcumin/therapeutic use , Glutathione , Antineoplastic Agents/therapeutic use , Cell Line, Tumor
20.
Chin Clin Oncol ; 13(1): 5, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38453656

ABSTRACT

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.


Subject(s)
Anemia , Antineoplastic Agents , Hematinics , Neoplasms , Physicians , Humans , United States , Antineoplastic Agents/therapeutic use , Anemia/chemically induced , Anemia/drug therapy , Iron/adverse effects , Hematinics/adverse effects , Neoplasms/drug therapy , Neoplasms/complications , Surveys and Questionnaires , Perception
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