Cancer Biotherapy and Radiopharmaceuticals最新文献

Background: Nanobodies (Nbs), derived from Camelidae heavy-chain antibodies, are single-domain fragments (15 kDa) with high antigen-binding specificity, enhanced tissue penetration, and low immunogenicity. These attributes address limitations of conventional antibodies, positioning Nbs as pivotal tools for targeted molecular imaging in diagnostics and therapeutics. Methods: Nbs are screened through phage/mRNA display or single B-cell sequencing, expressed in prokaryotic or yeast systems, and humanized via CDR grafting. Functional probes are engineered by conjugating Nbs with radionuclides (⁶⁸Ga, ^99mTc) or fluorophores (IRDye 800CW) for compatibility with PET, SPECT, NIRF, and ultrasound modalities. Results: Clinical trials validated Nb efficacy: ⁶⁸Ga-HER2-Nb PET/CT achieved tumor-specific uptake in HER2+ cancers (NCT04467515), while ^99mTc-PD-L1-Nb enabled quantitative SPECT-guided immunotherapy in NSCLC. NIRF-Nb conjugates (e.g., 11A4-800CW) enhanced intraoperative tumor delineation in murine models. Dual-targeted ultrasound microbubbles demonstrated multi-biomarker imaging via acoustic pressure modulation. Conclusion: Nbs advance biological imaging through superior resolution and rapid pharmacokinetics. Challenges persist in optimizing probe stability, minimizing immunogenicity, and scaling production. Future priorities include integrating multi-modal platforms, expanding applications to neurodegenerative disorders, and refining personalized diagnostic paradigms, underscoring their transformative potential in precision medicine.

Background: Silodosin (Sild) is a selective α1A-adrenergic receptor antagonist effective in treating benign prostatic hyperplasia (BPH), a condition characterized by prostate enlargement, which leads to urinary dysfunction. Objective: This study aimed to radiolabel Sild with iodine-131 [¹³¹I]) using chloramine-T(Ch-T), optimized the process to achieve high radiochemical yields, and investigated the [¹³¹I]Sildodosin [¹³¹I]Sild) radiotracer in the prostate of murine models. Methods: Compared to a control group, biodistribution studies were conducted to evaluate the [¹³¹I]Sild radiotracer uptake in mice with BPH. Biochemical analyses were performed to assess serum prostate-specific antigen (PSA) levels, antioxidant enzyme activities catalase (CAT) and superoxide dismutase (SOD), and oxidative stress markers such as malondialdehyde (MDA) in both groups. Results: The [¹³¹I]Sild radiotracer exhibited a radiochemical yield of 93.7 ± 1.1% and maintained stability for up to 4 h in serum. Biochemical markers indicated an increase in PSA, lipid peroxidation, MDA levels, and protein content, with an increase in prostate weight in mice with BPH compared to the control group. Histopathological examination revealed disruption of tissue growth and a localized inflammatory response in BPH compared to the control. Biodistribution studies demonstrated significant uptake of the [¹³¹I]Silodosin radiotracer in BPH, with a value of 7.6 ± 0.18% ID/g at 120 min post-administration. Conclusion: The results suggest that [¹³¹I]Silodosin radiotracer holds potential as an imaging agent for chronic prostatic diseases, particularly BPH.

The fourth most common cause of cancer-related deaths in women is cervical cancer (CC) in the worldwide. Although there are differences in the accessibility of therapies across developed and developing nations, an improvement in survival rate has been observed in patients with precancerous lesions, thanks to the development of precancerous lesion identification and preventative human papillomavirus vaccination programs. Surgery can cure early-stage CC, but patients who experience a recurrence have a poor prognosis and few therapy alternatives. Recently, it has been demonstrated that the drug bevacizumab increases overall survival in this latter context when combined with chemotherapy as opposed to chemotherapy administered alone. Beyond this therapy regimen, there are no established treatments. Therefore, in this situation, new, effective treatments are desperately needed. Immunotherapy has been a revolutionary treatment.

Objective: This study explored the effective components and molecular targets of Danggui Buxue decoction (DBD) combined with borneol (DBD&Bor) in alleviating myelosuppression. Methods: A network pharmacology strategy was used to identify the active components and key targets of DBD&Bor in the context of myelosuppression. In vivo, the effects of the DBD&Bor and its effective components on cyclophosphamide (CTX)-induced myelosuppression in rats were evaluated through immunohematological analysis, histopathological analysis, and organ index analysis. In vitro, the impact of the effective components of DBD&Bor on CTX-stimulated apoptosis and cell cycle of K562 cells was analyzed using flow cytometry. Finally, the recovery experiment was used to verify further the relationship between the effective ingredient and the target. Results: Network pharmacology and ultrahigh-performance liquid chromatography-tandem mass spectrometry analysis revealed that the principal components, catechin, isorhamnetin, and erythrodiol, in DBD&Bor may function as a prospective antimyelosuppression compound. Animal experiments demonstrated that in DBD&Bor, catechin and isorhamnetin could reverse the reduction in hematopoietic stem cell number, the production of stem cell marker (C-kit), and blood cell counts induced by CTX in rats. In addition, CD3, CD4, and CD8α are significantly increased in peripheral blood mononuclear cells, and thymic and splenic pathological damage is significantly attenuated. Also, the improvement effect of catechin was more noticeable. Therefore, the authors chose catechin for further study. Nevertheless, in vivo, overexpression of CDK2 negated the beneficial effects of catechin on myelosuppression. In vitro experiments demonstrated that catechin reduced CTX-induced apoptosis and cell cycle arrest in K562 cells by inhibiting CDK2. Conclusion: The primary component catechin in DBD&Bor inhibits the expression of CDK2, improving CTX-induced myelosuppression in rats and inhibiting apoptosis and cell cycle arrest in K562 cells.

Aim: This review examined multiple deep learning (DL) methods, including artificial neural networks (ANNs), convolutional neural networks (CNNs), k-nearest neighbors (KNNs), as well as generative adversarial networks (GANs), relying on their abilities to differentially extract key features for the identification and classification of skin lesions. Background: Skin cancer is among the most prevalent cancer types in humans and is associated with tremendous socioeconomic and psychological burdens for patients and caregivers alike. Incidences of skin cancers have progressively increased during the last decades. Early diagnoses of skin cancers may aid in the implementation of more effective treatment and therapeutic regimens. Indeed, several recent studies have focused on early detection strategies for skin cancer. Among the lesion features that can aid the recognition and characterization of skin cancers are symmetry, color, size, and shape. Results: Our assessment indicates that CNNs delivered maximum accuracy in visual lesion recognition, yet GANs have surfaced as a strong tool for training augmentation through simulated image creation. However, there were significant limitations associated with existing datasets, such as provision of insufficient skin tone variability, demanding computational needs, and unequal lesion representations, which may hamper efficiency, inclusivity, and generalizability of DL models. Researchers must combine diverse high-resolution datasets within a structural framework to develop efficient computational models with unsupervised learning methods to enhance noninvasive and precise skin cancer detection. Conclusion: The breakthroughs in image-based computational skin cancer detection may be crucial in reducing the requirement of invasive diagnostic tests and expanding the scope of skin cancer screening toward broad demographics, thereby aiding early cancer detection in a time- and cost-efficient manner.

Background: Nab-paclitaxel effectively inhibits tumor proliferation and modulates macrophage polarization to improve the tumor microenvironment. However, its potential to achieve radiosensitization in cholangiocarcinoma remains to be elucidated. Materials and Methods: The proliferation inhibition and radiosensitizing effects of nab-paclitaxel were assessed using cell counting kit-8 and colony formation assays in NOZ and TFK1 cell lines. Cell apoptosis, cell cycle progression, DNA damage, and macrophage polarization status were analyzed via flow cytometry immunofluorescence, enzyme-linked immunosorbent assay, and qRT-PCR. A tumor-bearing mouse model was established to validate radiosensitization in vivo. Potentially related genes and proteins involved in nab-paclitaxel-induced radiosensitization were identified through RNA transcriptome sequencing and Western blotting. Results: Nab-paclitaxel exhibited significant radiosensitizing effects on cholangiocarcinoma cells. Combined with radiotherapy, nab-paclitaxel increased DNA damage, promoted apoptosis, and effectively inhibited M2 polarization of macrophages in vivo and in vitro. The radiosensitizing effect is involved in the activation of the AMP-dependent protein kinase (AMPK) signaling pathway. Nab-paclitaxel significantly upregulated phosphorylated AMPKα, apoptotic proteins as zinc finger matrin-type 3, and nuclear factor kappa-B levels following radiation exposure. Conclusions: Our study confirmed the radiosensitizing effect of nab-paclitaxel on cholangiocarcinoma cells through a dual effect of antitumor proliferation and inhibition of M2 macrophage polarization, and the underlying mechanism involved activation of the AMPK signaling pathway.

Lymph node metastasis (LNM) plays a critical role in the prognosis of head and neck squamous cell carcinoma (HNSCC). To enhance prognostic predictions and investigate the molecular interplay between LNM and HNSCC, we developed an LNM-associated gene signature. Data was sourced from The Cancer Genome Atlas (TCGA), encompassing RNA-sequencing and clinical profiles. We stratified patients based on LNM status and identified differentially expressed genes (DEGs) between lymph node-negative (N0) and lymph node-positive (N1-3) groups. A prognostic model was then constructed while employing Least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses. Patients were randomly allocated into training (70%) and internal validation (30%) cohorts, with an additional external dataset used for validation. The predictive model's performance was assessed through receiver operating characteristic curves and survival analyses. We identified 79 LNM-related prognostic DEGs that formed the basis of our LNM-related risk score (LNMRS). This score stratified patients into low- and high-risk categories, with those having lower LNMRS exhibiting improved survival outcomes, increased immune cell infiltration, and enhanced responses to immunotherapy (PD-1/CTLA4 inhibitors) and chemotherapy. In contrast, patients with high LNMRS showed poorer prognosis and reduced immune responsiveness. Our LNM-related model provides insights into the molecular mechanisms linking LNM and HNSCC and offers a promising tool for personalized treatment strategies. This approach underscores the potential of integrating LNM status with gene expression profiles to refine prognosis and optimize therapeutic interventions in HNSCC.

Background: This retrospective multicenter study investigated the biodistribution of fluorodeoxyglucose (¹⁸F-FDG) in the positron emission tomography (PET)/computed tomography (CT) in digital PET/CT (dPET) compared to analog PET/CT (aPET), focusing differences in physiological uptake in reference and small structures across various scanner models. Materials and Methods: One hundred thirty patients with similar preimaging conditions underwent both dPET and aPET imaging within 6 months. Visual evaluations and paired comparative analyses of semiquantitative parameters were performed for small and reference structures. Results: ¹⁸F-FDG uptake was higher in both reference and small structures for dPET compared to three different aPET scanners. The Siemens mCT20-4R (mCT20) demonstrated comparable results to dPET. Notably, mCT20 had higher standardized uptake value (SUV_max) for the conus medullaris (CM) (3.20 vs. 2.76). CM was most highly visible with dPET on visual evaluation by physicians. Conclusions: Digital PET/CT provides higher SUV values in both small and reference structures. This leads to improved visualization of ¹⁸F-FDG physiological biodistribution. Given the growing adoption of dPET technology, these advancements should be carefully considered in image interpretation and clinical research.

Background: The abnormal expression of kinase family member 4A (KIF4A) is linked to breast cancer progression, with numerous miRNAs exhibiting abnormal expression. Thus, there is an urgent need to investigate the mechanisms of action of miRNAs and their target genes for the diagnosis and treatment of breast cancer. Materials and Methods: A bioinformatics analysis was conducted to screen for KIF4A, a key gene involved in oxidative stress in breast cancer cells. Using CCK8, EdU, cell healing, and Transwell assays, the knockdown of KIF4A was found to effectively inhibit the proliferation, migration, and invasion of breast cancer cells. Dual-luciferase assay and Western blotting confirmed that miR-223-3p targets and regulates KIF4A expression. The impact of miR-223-3p and KIF4A on oxidative stress in breast cancer cells was assessed through reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) measurements. Flow cytometry was used to evaluate tumor cell apoptosis. Results: Our results suggest that KIF4A is a downstream target of miR-223-3p. miR-223-3p inhibits the proliferation and invasion of breast cancer cells by directly targeting and downregulating KIF4A. Importantly, we found that miR-223-3p and KIF4A play important roles in regulating oxidative stress and apoptosis in breast cancer cells. Specifically, miR-223-3p promoted apoptosis by inhibiting the expression of KIF4A, increasing the accumulation level of ROS and MDA, and inhibiting the activity of SOD while KIF4A was overexpressed.