Cancer Biotherapy and Radiopharmaceuticals最新文献

Background: Glioma is a malignant brain tumor with poor prognosis. Sevoflurane has been shown to have antitumor effects in various cancers. However, the underlying role and mechanism of sevoflurane in glioma is still unclear. Materials and Methods: Glioma cell lines were exposed different concentrations of sevoflurane (sev). The cell proliferation and migration were examined by Cell Counting Kit-8 (CCK-8) and Transwell assays, respectively. All protein levels were measured by Western blot. The levels of noncoding RNA in the INK4 locus (ANRIL) and let-7b-5p were detected by quantitative real-time polymerase chain reaction. The binding sites between ANRIL and let-7b-5p were predicted by StarBase v.3.0 and confirmed using dual-luciferase reporter assay. Results: Sevoflurane treatment suppressed proliferation and migration of glioma cells. The expression of ANRIL was downregulated in glioma cells after treatment with sevoflurane in a dose-dependent manner, and overexpression of ANRIL reversed sevoflurane-induced inhibition of proliferation and migration of glioma cells. Furthermore, let-7b-5p was targeted by ANRIL, and ANRIL knockdown recovered the promoting effects of silencing let-7b-5p on proliferation, migration, and JAK2/STAT3 pathway in sevoflurane-treated glioma cells. Conclusions: Sevoflurane hindered proliferation and migration through JAK2/STAT3 pathway mediated by ANRIL and let-7b-5p in glioma cells, indicating a new reference for the application of anesthetics like sevoflurane in glioma.

Background: Selective internal radiation therapy (SIRT) using a suitable β^--emitting radionuclide is a promising treatment modality for unresectable liver carcinoma. Yttrium-90 (⁹⁰Y) [T_1/2 = 64.2 h, E_β(max) = 2.28 MeV, no detectable γ-photon] is the most preferred radioisotope for SIRT owing to its favorable decay characteristics. Objective: The present study describes indigenous development and evaluation of intrinsically radiolabeled [⁹⁰Y]yttria alumino silicate ([⁹⁰Y]YAS) glass microsphere, a formulation biosimilar to "TheraSphere" (commercially available, U.S. FDA-approved formulation), for SIRT of unresectable liver carcinoma in human patients. Methods: YAS glass microspheres of composition 40Y₂O₃-20Al₂O₃-40SiO₂ (w/w) and diameter ranging between 20 and 36 μm were synthesized with almost 100% conversion efficiency and >99% sphericity. Intrinsically labeled [⁹⁰Y]YAS glass microspheres were produced by thermal neutron irradiation of cold YAS glass microspheres in a research reactor. Subsequent to in vitro evaluations and in vivo studies in healthy Wistar rats, customized doses of [⁹⁰Y]YAS glass microspheres were administered in human patients. Results: [⁹⁰Y]YAS glass microspheres were produced with 137.7 ± 8.6 MBq/mg YAS glass (∼6800 Bq per microsphere) specific activity and 99.94% ± 0.02% radionuclidic purity at the end of irradiation. The formulation exhibited excellent in vitro stability in human serum and showed >97% retention in the liver up to 7 d post-administration when biodistribution studies were carried out in healthy Wistar rats. Yttrium-90 positron emission tomography scans recorded at different time points post-administration of customized dose of [⁹⁰Y]YAS glass microspheres in human patients showed near-quantitative retention of the formulation in the injected lobe. Conclusions: The study confirmed the suitability of indigenously prepared [⁹⁰Y]YAS glass microspheres for clinical use in the treatment of unresectable hepatocellular carcinoma.

With the development of the social economy and the deepening understanding of cancer, cancer has become a significant cause of death, threatening human health. Although researchers have made rapid progress in cancer treatment strategies in recent years, the overall survival of cancer patients is still not optimistic. Therefore, it is essential to reveal the spatial pattern of gene expression, spatial heterogeneity of cell populations, microenvironment interactions, and other aspects of cancer. Spatiotemporal transcriptomics can help analyze the mechanism of cancer occurrence and development, greatly help precise cancer treatment, and improve clinical prognosis. Here, we review the integration strategies of single-cell RNA sequencing and spatial transcriptomics data, summarize the recent advances in spatiotemporal transcriptomics in cancer studies, and discuss the combined application of spatial multiomics, which provides new directions and strategies for the precise treatment and clinical prognosis of cancer.

It is now well understood that many signaling pathways are vital in carrying out and controlling essential pro-survival and pro-growth cellular functions. The NOTCH signaling pathway, a highly conserved evolutionary signaling pathway, has been thoroughly studied since the discovery of NOTCH phenotypes about 100 years ago in Drosophila melanogaster. Abnormal NOTCH signaling has been linked to the pathophysiology of several diseases, notably cancer. In tumorigenesis, NOTCH plays the role of a "double-edged sword," that is, it may act as an oncogene or as a tumor suppressor gene depending on the nature of the context. However, its involvement in several cancers and inhibition of the same provides targeted therapy for the management of cancer. The use of gamma (γ)-secretase inhibitors and monoclonal antibodies for cancer treatment involved NOTCH receptors inhibition, leading to the possibility of a targeted approach for cancer treatment. Likewise, several natural compounds, including curcumin, resveratrol, diallyl sulfide, and genistein, also play a dynamic role in the management of cancer by inhibition of NOTCH receptors. This review outlines the functions and structure of NOTCH receptors and their associated ligands with the mechanism of the signaling pathway. In addition, it also emphasizes the role of NOTCH-targeted nanomedicine in various cancer treatment strategies.

Objective: The objective of this study was to investigate the feasibility of 1-d ⁶⁸Ga-DOTA-FAPI-04 and ¹⁸F-FDG (2-deoxy-2[¹⁸F]fluoro-d-glucose) positron emission tomography/computed tomography (PET/CT) for detecting ovarian cancer recurrence and metastasis. Materials and Methods: Fifty-two patients who underwent ¹⁸F-FDG and ⁶⁸Ga-DOTA-FAPI-04 PET/CT were divided into 1- and 2-d groups. Image acquisition, injection time, and total waiting time were compared. For the ⁶⁸Ga-DOTA-FAPI-04 PET/CT scans, low-dose CT scans and low injection dosages were employed, and total radiation dose was assessed for both protocols. The comparative analysis included assessment of patient-based detection rates and lesion-based diagnostic efficacy. Results: The total waiting time was significantly shorter in the 1-d group than in the 2-d group (p = 0.000). The radiation doses stemming from internal radiation and external radiation between the groups showed no differences (p = 0.151 vs. 0.716). In the patient-based analysis, the detection rates for local recurrence, peritoneal, lymph node, and other metastases were not significantly different in both protocols (p ∈ [0.351, 1.000]). For the lesion-based analysis, no differences were noted in terms of sensitivity, specificity, positive predictive value, negative predictive value, and accuracy (p ∈ [0.371, 1.000]). Conclusions: The 1-d PET/CT protocol reduced waiting time and exhibited equivalent detectability compared with the 2-d protocol, suggesting its clinical value.

Background: Real-time quantification of radioligand binding to cells under in vivo-like conditions improves evaluation of clinical potential. Materials and Methods: SKOV-3 tumor cells were grown in a monolayer on a thin glass plate placed in a sealable shallow chamber with a continuous flow of ¹²⁵I-trastuzumab solution. The time-dependent cell binding was measured using a NaI detector, and the binding parameters were derived by computational analysis. Results: The detection efficiency of ¹²⁵I was 65 cps/kBq for radioligand bound to the cells. Experiments were analyzed to find the values of k_on and k_off. The resulting k_on was 3.2-7.9 × 10⁴ M^-1 s^-1 and k_off was 0.11-4.2 × 10^-5 s^-1. Conclusions: Radioligands can be rapidly evaluated by binding to living cells for selection and optimization of radioconjugates for diagnostic and therapeutic purposes.

Background: Early detection of skeletal metastasis is of great interest to determine the prognosis of cancer. Positron emission tomography-computed tomography (PET-CT) imaging provides a better temporal and spectral resolution than single photon emission computed tomography-computed tomography (SPECT-CT) imaging, and hence is more suitable to detect small metastatic lesions. Although [¹⁸F]NaF has been approved by U.S. FDA for a similar purpose, requirement of a medical cyclotron for its regular formulation restricts its extensive utilization. Efforts have been made to find suitable alternative molecules that can be labeled with ⁶⁸Ga and used in PET-CT imaging. Objective: The main objective of this study is to synthesize and evaluate a new [⁶⁸Ga]Ga-labeled NOTA-conjugated geminal bisphosphonate for its potential use in early detection of skeletal metastases using PET-CT. Methods: The authors performed a multistep synthesis of a new NOTA-conjugated bisphosphonic acid using thiourea linker and radiolabeled the molecule with ⁶⁸Ga. The radiolabeled formulation was evaluated for its in vitro stability, affinity for hydroxyapatite (HA) particles, preclinical biodistribution in animal models, and PET-CT imaging in patients. Results: The bifunctional chelator (NOTA)-conjugated bisphosphonate was synthesized with 97.8% purity and radiolabeled with ⁶⁸Ga in high yield (>98%). The radiolabeled formulation was found to retain its stability in vitro to the extent of >95% up to 4 h in physiological saline and human serum. The formulation also showed high affinity for HA particles in vitro with K_d = 907 ± 14 mL/g. Preclinical biodistribution studies in normal Wistar rats demonstrated rapid and almost exclusive skeletal accumulation of the complex. PET-CT imaging in a patient confirmed its ability to detect small metastatic skeletal lesions. Conclusions: The newly synthesized [⁶⁸Ga]Ga-labeled NOTA-conjugated bisphosphonate is a promising radiotracer for PET-CT imaging for skeletal metastases.