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Biomacromolecules Aug 2023Melanoma is resistant to conventional chemotherapy and radiotherapy. Therefore, it is essential to develop a targeted, low-toxic, and minimally invasive treatment. Here,...
Melanoma is resistant to conventional chemotherapy and radiotherapy. Therefore, it is essential to develop a targeted, low-toxic, and minimally invasive treatment. Here, DTIC/ICG-FeO@TpBD BSP/HA microneedles (MNs) were designed and fabricated, which can enhance targeting to melanoma and perform photothermal therapy (PTT) and chemotherapy simultaneously to synergistically exert anticancer effects. The system consisted of magnetic nanoparticles (DTIC/ICG-FeO@TpBD), dissoluble matrix (Bletilla polysaccharide (BSP)/hyaluronic acid (HA)), and a polyvinyl alcohol backing layer. Due to the good magnetic responsiveness of FeO@TpBD, dacarbazine (DTIC) and indocyanine green (ICG) can be better targeted to the tumor tissue and improve the therapeutic effect. BSP and HA have good biocompatibility and transdermal ability, so that the MNs can completely penetrate the tumor tissue, be dissolved by the interstitial fluid, and release DTIC and ICG. Under near-infrared (NIR) light irradiation, ICG converts light energy into thermal energy and induces ablation of B16-OVA melanoma cells. In vivo results showed that DTIC/ICG-FeO@TpBD BSP/HA MNs combined with chemotherapy and PTT could effectively inhibit the growth of melanoma without tumor recurrence or significant weight loss in mice. Therefore, DTIC/ICG-FeO@TpBD BSP/HA MNs are expected to provide new ideas and therapeutic approaches for the clinical treatment of melanoma.
Topics: Animals; Mice; Metal-Organic Frameworks; Hyperthermia, Induced; Melanoma; Phototherapy; Indocyanine Green; Dacarbazine; Cell Line, Tumor; Nanoparticles
PubMed: 37475132
DOI: 10.1021/acs.biomac.3c00488 -
Clinical Lymphoma, Myeloma & Leukemia Nov 2022Chemotherapy for classic Hodgkin lymphoma (cHL) patients on hemodialysis (HD) is an extremely challenging situation because pharmacokinetic and pharmacodynamic studies... (Review)
Review
Chemotherapy for classic Hodgkin lymphoma (cHL) patients on hemodialysis (HD) is an extremely challenging situation because pharmacokinetic and pharmacodynamic studies of most chemotherapeutics are lacking for the HD patient, and the small amount of evidence available comes mostly from case reports and small case series. In this review, we provide recommendations based on treatment experience of cHL patients on HD in the literature. HD patients undergoing chemotherapy are at risk of overdose and toxicities because many drugs are significantly eliminated by the kidneys, and at the same time, are at risk of undertreatment because many drugs are removed by HD. Therefore, dose modifications and timing of drug administration in relation to HD sessions must be carefully planned according to the distinct traits of each chemotherapeutic. We carried out an exhaustive literature review of reports of actual administrations of chemotherapeutics to cHL on HD, and also extrapolated data from reports of the same chemotherapeutics that were administered to HD patients with malignancies other than cHL. We summarized the information found in the literature, and provide practical and balanced recommendations concerning dose modifications and optimal timing of drug administration in relation to HD sessions for each chemotherapeutic. Chemotherapy regimens and individual chemotherapeutics studied in this review include ABVD (doxorubicin + bleomycin + vinblastine + dacarbazine), BEACOPP (bleomycin + etoposide + doxorubicin + cyclophosphamide + vincristine + procarbazine + prednisolone), MOPP (mechlorethamine + vincristine + procarbazine + prednisolone), gemcitabine, vinorelbine, brentuximab vedotin, and PD-1 inhibitors (nivolumab and pembrolizumab).
Topics: Humans; Hodgkin Disease; Vinblastine; Vincristine; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Brentuximab Vedotin; Mechlorethamine; Procarbazine; Vinorelbine; Nivolumab; Immune Checkpoint Inhibitors; Bleomycin; Dacarbazine; Doxorubicin; Cyclophosphamide; Prednisolone; Renal Dialysis
PubMed: 35948477
DOI: 10.1016/j.clml.2022.07.008 -
Developmental Neuroscience 2023Glioblastoma (GBM), the most common and lethal primary brain tumor in adults, requires multi-treatment intervention which unfortunately barely shifts the needle in... (Review)
Review
Glioblastoma (GBM), the most common and lethal primary brain tumor in adults, requires multi-treatment intervention which unfortunately barely shifts the needle in overall survival. The treatment options after diagnosis and surgical resection (if possible) include irradiation, temozolomide (TMZ) chemotherapy, and now tumor treating fields (TTFields). TTFields are electric fields delivered locoregionally to the head/tumor via a wearable medical device (Optune®). Overall, the concomitant treatment of TTFields and TMZ target tumor cells but spare normal cell types in the brain. Here, we examine whether primary cilia, microtubule-based "antennas" found on both normal brain cells and GBM cells, play specific roles in sensitizing tumor cells to treatment. We discuss evidence supporting GBM cilia being exploited by tumor cells to promote their growth and treatment resistance. We review how primary cilia on normal brain and GBM cells are affected by GBM treatments as monotherapy or concomitant modalities. We also focus on latest findings indicating a differential regulation of GBM ciliogenesis by TTFields and TMZ. Future studies await arrival of intracranial TTFields models to determine if GBM cilia carry a prognostic capacity.
Topics: Adult; Humans; Cilia; Brain; Temozolomide
PubMed: 38630257
DOI: 10.1159/000529193 -
Clinical Immunology (Orlando, Fla.) Nov 2023In our previous study, we found for the first time that temozolomide (TMZ), the first-line chemotherapeutic agent for glioblastoma (GBM), can generate a large amount of...
BACKGROUND
In our previous study, we found for the first time that temozolomide (TMZ), the first-line chemotherapeutic agent for glioblastoma (GBM), can generate a large amount of reactive oxygen species (ROS) under ultrasound irradiation. Sonodynamic therapy (SDT) using TMZ as the sonosensitizer produced more potent antitumor effects than TMZ alone. Here, we further evaluate the effects of TMZ-based SDT on subcellular structures and investigate the immunogenic cell death (ICD)-inducing capability of TMZ-based SDT.
METHODS
The sonotoxic effects of TMZ were explored in LN229 and GL261 glioma cells. The morphology of endoplasmic reticulum and mitochondria was observed by transmission electron microscopy. The nuclear DNA damage was represented by γ-H2AX staining. Bone marrow-derived dendritic cells (BMDCs) were employed to assess ICD-inducing capability of TMZ-based SDT. A cyclic arginine-glycine-aspartic (c(RGDyC))-modified nanoliposome drug delivery platform was used to improve the tumor targeting of SDT.
RESULTS
TMZ-based SDT had a greater inhibitory effect on glioma cells than TMZ alone. Transmission electron microscopy revealed that TMZ-based SDT caused endoplasmic reticulum dilation and mitochondrial swelling. In addition, endoplasmic reticulum stress response (ERSR), nuclear DNA damage and mitochondrial permeability transition pore (mPTP) opening were promoted in TMZ-based SDT group. Most importantly, we found that TMZ-based SDT could promote the "danger signals" produced by glioma cells and induce the maturation and activation of BMDCs, which was associated with the mitochondrial DNA released into the cytoplasm in glioma cells. In vivo experiments showed that TMZ-based SDT could remodel glioma immune microenvironment and provoke durable and powerful anti-tumor immune responses. What's more, the engineered nanoliposome vector of TMZ conferred SDT tumor targeting, providing an option for safer clinical application of TMZ in combination with SDT in the future.
CONCLUSIONS
TMZ-based SDT was capable of triggering ICD in glioma. The discovery of TMZ as a sonosensitizer have shown great promise in the treatment of GBM.
Topics: Humans; Temozolomide; Immunogenic Cell Death; Apoptosis; Glioma; Glioblastoma; Cell Line, Tumor; Brain Neoplasms; Tumor Microenvironment
PubMed: 37716612
DOI: 10.1016/j.clim.2023.109772 -
Cells Dec 2022Glioblastoma, a grade IV astrocytoma, is regarded as the most aggressive primary brain tumour with an overall median survival of 16.0 months following the standard... (Review)
Review
Glioblastoma, a grade IV astrocytoma, is regarded as the most aggressive primary brain tumour with an overall median survival of 16.0 months following the standard treatment regimen of surgical resection, followed by radiotherapy and chemotherapy with temozolomide. Despite such intensive treatment, the tumour almost invariably recurs. This poor prognosis has most commonly been attributed to the initiation, propagation, and differentiation of cancer stem cells. Despite the unprecedented advances in biomedical research over the last decade, the current in vitro models are limited at preserving the inter- and intra-tumoural heterogeneity of primary tumours. The ability to understand and manipulate complex cancers such as glioblastoma requires disease models to be clinically and translationally relevant and encompass the cellular heterogeneity of such cancers. Therefore, brain cancer research models need to aim to recapitulate glioblastoma stem cell function, whilst remaining amenable for analysis. Fortunately, the recent development of 3D cultures has overcome some of these challenges, and cerebral organoids are emerging as cutting-edge tools in glioblastoma research. The opportunity to generate cerebral organoids via induced pluripotent stem cells, and to perform co-cultures with patient-derived cancer stem cells (GLICO model), has enabled the analysis of cancer development in a context that better mimics brain tissue architecture. In this article, we review the recent literature on the use of patient-derived glioblastoma organoid models and their applicability for drug screening, as well as provide a potential workflow for screening using the GLICO model. The proposed workflow is practical for use in most laboratories with accessible materials and equipment, a good first pass, and no animal work required. This workflow is also amenable for analysis, with separate measures of invasion, growth, and viability.
Topics: Humans; Glioblastoma; Neoplasm Recurrence, Local; Temozolomide; Brain Neoplasms; Organoids
PubMed: 36611949
DOI: 10.3390/cells12010153 -
CMAJ : Canadian Medical Association... Oct 2023
Topics: Humans; Suicide, Assisted; Palliative Care; Dacarbazine; Doxorubicin; Canada
PubMed: 37844931
DOI: 10.1503/cmaj.230259 -
La Tunisie Medicale Jul 2023Langerhans cell sarcoma (LCS) is a very rare malignant tumor of Langerhans cells that may metastasize to many organs. The diagnosis of this tumor is difficult and its...
INTRODUCTION
Langerhans cell sarcoma (LCS) is a very rare malignant tumor of Langerhans cells that may metastasize to many organs. The diagnosis of this tumor is difficult and its prognosis is poor.
AIM
To report the difficulty to diagnose LCS, and discuss therapeutic management of this rare entity.
CASE PRESENTATION
We report a case of LCS in a 52-year-old man who presented with an axillar lymphadenopathy. The diagnosis of nodular sclerosis type Hodgkin's disease was established after histologic examination. The patient was treated with chemotherapy (ABVD regimen: Doxorubicin, Bleomycin, Vinblastine, Dacarbazine) and radiotherapy with a partial response. However, disease recurrence was observed and histological analysis confirmed the diagnosis of Langerhans cell sarcoma. A revision of the initial histological examination concluded to the diagnosis of sarcoma from the beginning. We chose the ESHAP (Etoposide, Methylprednisolone, Aracytine, Cisplatin) regimen and clinical improvement of LCS was obtained after 2 cycles but the patient had a fatal outcome and died by disease progression.
CONCLUSION
Because of its rarity, diagnosis is difficult and an optimal treatment strategy for this disease has not yet been identified. Polychemotherapy can be an effective modality for the treatment of LCS.
Topics: Male; Humans; Middle Aged; Langerhans Cell Sarcoma; Antineoplastic Combined Chemotherapy Protocols; Hodgkin Disease; Bleomycin; Dacarbazine; Doxorubicin; Vinblastine; Neoplasm Recurrence, Local
PubMed: 38445429
DOI: No ID Found -
International Journal of Molecular... Dec 2022Therapeutic options for treating advanced melanoma have progressed rapidly in recent decades. Until 6 years ago, the regimen for treating advanced melanoma consisted... (Review)
Review
Therapeutic options for treating advanced melanoma have progressed rapidly in recent decades. Until 6 years ago, the regimen for treating advanced melanoma consisted mainly of cytotoxic agents such as dacarbazine and type I interferons. Since 2014, anti-programmed cell death 1 (PD1) antibodies have been recognized as anchor drugs for treating advanced melanoma, with or without additional combination drugs such as ipilimumab, but the efficacies of these immunotherapies are not fully satisfactory. In this review, we describe the development of the currently available anti-PD1 Abs-based immunotherapies for advanced melanoma, focusing on their efficacy and immune-related adverse events (AEs), as well as clinical trials still ongoing for the future treatment of advanced melanoma.
Topics: Humans; Immune Checkpoint Inhibitors; Melanoma; Ipilimumab; Immunotherapy; Dacarbazine; CTLA-4 Antigen
PubMed: 36555362
DOI: 10.3390/ijms232415720 -
Neuro-oncology Nov 2021
Topics: Antineoplastic Agents, Alkylating; Dacarbazine; Glioblastoma; Humans; Temozolomide
PubMed: 34347098
DOI: 10.1093/neuonc/noab186 -
Frontiers in Bioscience (Landmark... Sep 2023O6-methylguanine-DNA-methyltransferase (MGMT) is a DNA repair enzyme, which reverses the alkylation of guanine O6 through directtransfer of the methyl group, maintains... (Review)
Review
O6-methylguanine-DNA-methyltransferase (MGMT) is a DNA repair enzyme, which reverses the alkylation of guanine O6 through directtransfer of the methyl group, maintains the gene stability and avoids tumor occurrence. Studies have shown that gene methylation, polymorphism and protein expression are involved in the process of various tumor development, such as colon cancer, gastric carcinoma, etc. gene promotes methylation, protein expression and enzyme activity from various tissues, which resultsin different effects on the prognosis of patients. MGMT promoter methylation is a positive factor for the prognosis of Glioblastoma (GBM), which can prolong overall survival and progression-free survival, reduce the resistance of tumor cells to temozolomide treatment, and improve the prognosis. The treatment of tumors based on MGMT focuses on three aspects: targeting MGMT to increase the sensitivity of alkylated drug therapy in tumors, immunotherapy combined with alkylated agents on tumor treatment, and treatment for patients with MGMT promoter non-methylation. Similarly, a number of studies have targeted MGMT to reduce alkylated agent resistance in other systems. Although numerous studies on MGMT in tumors have been reported, there are problems that need to be solved, such as selection and consensus of MGMT promoter methylation detection methods (CpG detection sites, cut-off value) and the treatment of MGMT non-methylated GBM patients, especially elderly patients. In this review, we describe the regulation of MGMT expression and its role inchemotherapy, especially in gliomas. Further studies exploring new methods targeting MGMT with better curative effect and less toxicity are advocated. We anticipate that these developments will be progressive and sufficiently used for clinical application.
Topics: Humans; Antineoplastic Agents, Alkylating; Brain Neoplasms; Dacarbazine; DNA; DNA Methylation; DNA Repair Enzymes; Glioblastoma; O(6)-Methylguanine-DNA Methyltransferase
PubMed: 37796680
DOI: 10.31083/j.fbl2809197