Therapy Of Malignant Tumors Research Articles

Strong Affinity between Astatine and Silver: An Available Approach to Anchoring 211At in Nanocarrier for Locoregional Oncotherapy.

Recently, 211At-related endoradiotherapy has emerged as an important oncotherapy strategy. Conjugating 211At with a nanocarrier provides a vital candidate for radionuclide therapy of various malignant tumors. In this study, we proposed utilizing the intrinsically high affinity of heavy halogens and sulfhydryl compounds for metallic silver to achieve highly efficient conjugation between 211At and Ag-based nanoparticles in a simple way. 211At@Ag-PEG-FA was obtained via a one-pot assembly of 211At, Ag, and SH-PEG-FA in extremely high radiolabeling yield (>95%) within 15 min and maintained excellent stability in simulated physiochemical media. Additionally, the prepared 211At@Ag-PEG-FA demonstrated specific binding to the breast cancer cell line (4T1), with a high endocytosis rate and low reflux, leading to significant cell growth inhibition. 211At@Ag-PEG-FA exhibits an excellent antitumor effect that completely suppressed tumor growth during the first week, effectively prolonging the median survival of mice to 44 days, relative to 18 days in the control group. All of the mice exhibited minimal side effects from 211At@Ag-PEG-FA in the experiment, indicating its acceptable biosafety. Our work shows that the strong affinity of Ag can be utilized to produce radioactivated nanomedicines with excellent stability and high efficiency, which also provides some valuable insights for the 211At radiolabeling of general compounds.

The Research Progress of Metformin Regulation of Metabolic Reprogramming in Malignant Tumors.

Metabolism reprogramming is a crucial hallmark of malignant tumors. Tumor cells demonstrateenhanced metabolic efficiency, converting nutrient inputs into glucose, amino acids, and lipids essential for theirmalignant proliferation and progression. Metformin, a commonly prescribed medication for type 2 diabetes mellitus,has garnered attention for its potential anticancer effects beyond its established hypoglycemic benefits. This review adopts a comprehensive approach to delineate the mechanisms underlying metabolite abnormalities within the primary metabolic processes of malignant tumors. This review examines the abnormal activation of G protein-coupled receptors (GPCRs) in these metabolic pathways, encompassing aerobic glycolysis with increased lactate production in glucose metabolism, heightened lipid synthesis and cholesterol accumulation in lipid metabolism, and glutamine activation alongside abnormal protein post-translational modifications in amino acid and protein metabolism. Furthermore, the intricate metabolic pathways and molecular mechanisms through which metformin exerts its anticancer effects are synthesized and analyzed, particularly its impacts on AMP-activated protein kinase activation and the mTOR pathway. The analysis reveals a multifaceted understanding of how metformin can modulate tumor metabolism, targeting key nodes in metabolic reprogramming essential for tumor growth and progression. The review compiles evidence that supports metformin's potential as an adjuvant therapy for malignant tumors, highlighting its capacity to interfere with critical metabolic pathways. In conclusion, this review offers a comprehensive overview of the plausible mechanisms mediating metformin's influence on tumor metabolism, fostering a deeper comprehension of its anticancer mechanisms. By expanding the clinical horizons of metformin and providing insight into metabolism-targeted tumor therapies, this review lays the groundwork for future research endeavors aimed at refining and advancing metabolic intervention strategies for cancer treatment.

Benign Soft Tissue Tumors of oral cavity, relevance to prosthodontics – Laconic Review.

The influence of oral soft tissue tumors on the surrounding structures and oral tissues makes them a considerable problem in prosthodontic treatment, regardless of their malignancy. Maintaining functional rehabilitation with prosthetic devices while addressing the tumor pathology is a delicate balance in the therapy of malignant tumors. Prosthodontics is relevant in this situation in a number of ways. Long-term side effects from cancer therapies, especially radiation therapy, can include mucositis, osteoradionecrosis, and xerostomia. The efficacy of prosthetic treatments may be significantly impacted by these negative effects. Patients with soft tissue tumors in the mouth cavity can greatly benefit from prosthodontic treatment, despite its difficulties. There is not much literature is available on the relevance of soft tissue tumors in various prosthodontic treatment procedures. Hence this laconic review aimed to discuss about various soft tissue tumors which are related to prosthodontic treatment and different precautions to be taken during prosthodontic procedures.

Research Progress on Photothermal Therapy of Malignant Tumor Cells

Malignant tumors, also known as cancer, are among the diseases with the highest incidence and mortality rates in the world. Photothermal therapy (PTT) involves injecting materials with high photothermal conversion efficiency (PTA) into the human body and using the principle of photothermal conversion to kill malignant tumor cells at the lesion site with high temperatures. This paper reviews various methods of photothermal therapy for malignant tumors, summarizes the basic therapeutic logic of photothermal therapy, and forecasts the future development prospects of this treatment method.

PSMA and Sigma-1 receptor dual-targeted peptide mediates superior radionuclide imaging and therapy of prostate cancer

Radionuclide therapy, in particular peptide receptor radionuclide therapy (PRRT), has emerged as a valuable means to combat malignant tumors. The specific affinity of ACUPA peptide toward prostate-specific membrane antigen (PSMA) renders the successful development of PRRT for prostate cancer. The clinical outcome of PRRT is, however, generally challenged by moderate tumor uptake and off-target toxicity. Here, we report on a novel design of Sigma-1 receptor and PSMA dual-receptor targeted peptide (S1R/PSMA-P) for superior radionuclide imaging and therapy of prostate cancer. S1R/PSMA-P was acquired with good purity and could efficiently be labeled with 177Lu to yield 177Lu-S1R/PSMA-P with high specific activity and radiostability. Interestingly, 177Lu-S1R/PSMA-P revealed greatly enhanced affinity to LNCaP cells over single-targeted control 177Lu-PSMA-617. The single photon emission computed tomography (SPECT) imaging demonstrated exceptional uptake and retention of 177Lu-S1R/PSMA-P in LNCaP tumor, affording about 2-fold better tumor accumulation while largely reduced uptake by most normal tissues compared to 177Lu-PSMA-617. The selective uptake in LNCaP tumor was also visualized by positron emission tomography (PET) with 68Ga-S1R/PSMA-P. In accordance, a single and low dosage of 177Lu-S1R/PSMA-P at 11.1 MBq effectively suppressed tumor growth without causing apparent side effects. This dual-targeting strategy presents an appealing radionuclide therapy for malignant tumors.

Oncogenic miRNAs dependent photothermal-immunotherapy enhanced by on-demand manipulation of immunosuppressive microenvironment using engineered gold nanoparticles for effective treatment of primary and metastatic tumor

Although photothermal-immunotherapy has emerged as a promising strategy to treat malignant tumor, unexpected thermal damage, continuous tumor migration and immunosuppressive microenvironment still limit its application. To improve the therapeutic efficacy, two types of engineered gold nanoparticles (SNAs@CCM and SNA2@CCM-Man) were fabricated. The SNAs@CCM are cancer cell membrane (CCM, tumor targeting agent) coated spherical nucleic acids (SNAs, miR-21 catcher and photothermal agent). The SNAs contained two types (SNA1 and SNA2), which are gold nanoparticles grafted with the first half and second half of anti-miR-21 oligonucleotide, respectively. The SNA2@CCM-Man are CCM coated SNA2 (miR-21 catcher) in which the CCM was functionalized by mannose (Man, macrophage targeting agent). These nanoparticles were expected to not only perform miR-21 dependent photothermal-immunotherapy in tumor cells to precisely damage primary tumor and activate the anti-tumor immune response against metastatic tumor, but also restrain the miR-21 expression in tumor-associated M2-type macrophages to promote their polarization to tumor-suppressed M1-type macrophages for on-demand manipulation of immunosuppressive microenvironment avoiding immune escape. After injection, the SNAs@CCM and SNA2@CCM-Man would respectively internalize by tumor cells and M2-type macrophages via homologous targeting of cancer cell membranes and receptor-ligand interactions of mannose. Upon entry into tumor cells, the SNAs specifically hybridized with the over-expressed miR-21 in these cells, thereby silencing the oncogenic miR-21 and leading to significant intracellular aggregation of SNAs. These aggregated SNAs not only served as miR-21 catcher, but performed a strong absorption in the near-infrared region acting as in situ photothermal agents. Under NIR irradiation, these photothermal agents enable highly selective photothermal-immunotherapy, inducing the immunogenic death of primary tumors and subsequent anti-tumor immune responses via the maturation of dendritic cells (DCs) and activation of T cells. Moreover, the miR-21 plunder process also effectively inhibited the migration of tumor cells to further enhance the therapeutic efficacy. Simultaneously, the similar miR-21 capture process mediated by SNA2 in M2 macrophages continuously induced macrophage polarization towards the anti-tumor M1 type, which was able to reverse the immunosuppressive microenvironment in tumor tissue to avoid immune escape and enhance immunotherapy. Both in vivo and in vitro experiments demonstrated that our nanoparticles could inhibit the primary tumor and its metastasis through miR-21-dependent photothermal immune activation and directional polarization of macrophages, providing a promising strategy for on-demand synchronous modulation of tumor cells and immune cells in tumor tissues for better malignant tumor therapy.

Patient reported fatigue after proton therapy for malignant brain tumours – Is there a relation between radiation dose and brain structures?

BackgroundFatigue may significantly effect everyday- and working life for radiotherapy patients. Some studies indicate a correlation between radiation dose and irradiated volume of the brain and the presence of fatigue. Our hypothesis was that patient reported outcome measures (PROMs) can improve our understanding of the patients’ symptoms following proton beam therapy (PBT) and optimize PBT for future patients. MethodsThis study included 167 adult patients (>18 years) who received PBT for malignant brain tumours. Data on dose metrics to intra-cranial structures was obtained from PBT treatment plans. To explore fatigue and health related quality of life (HRQoL); Multidimensional Fatigue Inventory (MFI-20) and EORTC QLQ-C30 was used at 6-, 12-, 24- and 36 months post PBT. The correlation between fatigue and dosimetry was explored using Spearman’s signed rank test. ResultsNo severe fatigue was recorded during the 36 months follow-up. Correlations between higher radiation dose and worsened fatigue scores were generally weak (rho < 0.3). At 12 months post PBT, higher mean dose to the brain, brainstem, hippocampi and pituitary was correlated to worsened MFI Physical Fatigue. Further, Reduced Motivation according to MFI was correlated to higher radiation dose to the brainstem and the pituitary gland. At 36 months follow-up post-PBT, both Reduced Activity and Reduced motivation according to MFI were correlated to higher radiation dose to the brain, brainstem and hippocampi. ConclusionProton beam therapy are well tolerated, with similar degree of fatigue pre- and post PBT. Achieving further reduction in mean brain dose appears beneficial.

DKN-01 Suppresses Gastric Cancer Progression Through Activating cGAS-STING Pathway to Block Macrophage M2 Polarization.

Dickkopf-1 (DKK1) is a secretory antagonist that can bind with the Wnt coreceptor to desensitize cells to canonical Wnt ligands. DKN-01 is a specific antibody targeting secreted DKK1, which has been investigated as a monotherapy or combination therapy for various malignant tumors, including gastric cancer (GC). Tumor-associated macrophages (TAMs) with high plasticity usually present M2 phenotype, which can promote tumor progression. The aim of this study was to investigate the effect of DKN-01 on macrophage polarization in GC and the underlying molecular mechanism. To ascertain the effect of DKN-01 on GC tumor growth, we established a tumor-bearing mouse model and found that DKN-01 treatment suppressed tumor growth efficiently. Through RNA-seq and pathway enrichment analysis, we identified that the differentially expressed genes after DKN-01 treatment are associated with tumor immune-related pathways. Macrophage polarization was assessed using immunohistochemistry and quantitative real-time polymerase chain reaction. DKN-01 and knockdown of DKK1 promoted M1 polarization and inhibited M2 polarization of macrophages, while DKK1 overexpression got the opposite results. Moreover, DKN-01 activated the cGAS/STING pathway, while the inactivation of cGAS-STING pathway using RU.521 reversed the inhibition of tumor growth in vivo and macrophage M2 polarization caused by DKN-01. This study reveals that DKN-01 suppresses GC tumor growth through activating cGAS-STING pathway to block macrophage M2 polarization.

Ways to improve the results of conservative therapy of malignant tumors of the head and neck organs. Part I. The current state of the issue (review)

The review analyzes the results of conservative therapy of patients with the head and neck cancer. Despite the use of modern radiation and drug technologies, the results of treatment of locally advanced forms of head and neck cancers and relapses are not satisfactory. The most effective is the simultaneous use of modified radiation and chemotherapy regimens. However, the implementation of the treatment plan with this method is limited to the development of pronounced early and late toxic effects on normal tissues and organs. The radiosensitizing effect of targeted therapy was also analyzed.

Clinical Outcomes of Carbon Ion Radiation Therapy for Malignant Peripheral Nerve Sheath Tumors

Purposeto investigate outcome and toxicity of patients affected by malignant peripheral nerve sheath tumors (MPNSTs) treated with high-dose carbon ion radiotherapy (CIRT). Patients and methodswe retrospectively analyzed the outcome of 23 patients with MPNST treated between July 2013 and December 2020. Out of these, 13 patients (56.5%) had incompletely resected tumors, 8 patients (34.7%) experienced recurrence after surgery, and 2 patients (8.7%) had unresectable tumors. Before CIRT treatment, 4 patients underwent a second surgery after the first local recurrence (LR), and 1 patient underwent a third surgery for the second local relapse of disease. Six (26%) of patients received neoadjuvant chemotherapy. The most frequent tumor site was brachial plexus (N=9; 39.1%). In five patients (21.7%) neurofibromatosis type 1 (NF1) disorder was found, while 4 patients (17, 4%) had radiation-induced MPNST. The median CIRT prescribed total dose was 69.8 Gy [RBE] (range, 54-76.8) delivered in a median of 16 fractions (range, 15-22). Eleven patients (47.82%) were treated according to a sequential boost protocol with a median prescribed dose to CTV-LR of 45 Gy[RBE] (range, 41.4 – 54). ResultsAfter a median follow-up time of 23 months (range 3-100 months), the OS rates at 1-year and 2-year were respectively: 82.38%, 61.51%. The 1-year and 2-year LRFS rates were respectively: 65.07%, 48.80%; the 1-year and 2-year PFS rates were respectively: 56.37%, 40.99%. No patients showed acute or late Grade 4 toxicity or any treatment-related deaths. Ten patients (43.48%) reported acute toxicities of Grade ≥2: dermatitis in 6 patients, mucositis in 2 patients, peripheral neuropathy in 4 patients. Eight patients (34.78%) reported late toxicities of Grade ≥2, mainly due to loco-regional neuropathy. Conclusionshigh dose CIRT shows favorable local effect with acceptable toxicities in patients with gross residual and LR after surgery, or unresectable malignant peripheral nerve sheath tumors. Advanced treatment modalities such as particle therapy should be considered for MPNSTs.

Preparation and characterization of mesoporous HA coating with paclitaxel loaded lignin nanospheres on titanium surface

BackgroundPrimary malignant bone tumor is a disease that can lead to death. The usually applied clinical treatment strategy is surgical resection of the primary tumor. However, tumor cells are difficult to clean up, easy to make the tumor recurrence, and the bone defect caused by surgical resection also hindered the postoperative recovery. Materials and methodsHerein, in this work, mesoporous hydroxyapatite (HA) coating with petal-structure was prepared on titanium (Ti) implant surfaces by micro-arc oxidation (MAO) to accelerate the bone growth, and then paclitaxel (PTX) loaded lignin nanospheres were deposited into the HA coatings to get a sustained release for killing residual tumor cells. ResultsThe results showed that many gaps and holes of micro-scale were formed in the petal-structured HA coatings, they worked as traps for the PTX loaded nanospheres to enhance the deposited amount and immobilization stability, playing good role of drug loading platform. The encapsulation of PTX by lignin ensured a lower release rate and a higher sustaining release time when compared with the PTX without encapsulation. In addition, the HA coating with PTX loaded lignin nanospheres showed higher killing effect to tumor cells than to osteoblast. ConclusionThe mesoporous HA coating with paclitaxel loaded lignin nanospheres endowed the titanium surface with good biological property and tumor cell-killing effect, so the obtained Ti-based material had a highly hopeful application as the localized implant for therapy of primary malignant bone tumor.

An Integrated Nanoplatform via Dual Channel Excitation for Both Precise Fluorescence Imaging and Photodynamic Therapy of Orthotopic Breast Tumor in NIR-II Region.

Although research on photodynamic therapy (PDT) of malignant tumor has made considerable progress in recent years, it is a remaining challenge to extend PDT to the second near-infrared window (NIR-II) along with real-time and accurate NIR-II fluorescence imaging to determine drug enrichment status and achieve high treatment efficacy. In this work, lanthanide nanoparticles (Ln NPs)-based nanoplatform (LCR) equipped with photosensitizerChlorin e6 (Ce6) and targeting molecular NH2-PEG1000-cRGDfK aredeveloped, which can achieve NIR-II photodynamic therapy (PDT) and NIR-II fluorescence imaging by dual channel excitation. Under 808nm excitation, Nd3+ in the outer layer can absorb the energy and transfer inward to emit strong NIR-II emissions (1064 and 1525nm). Due to the low background noise of NIR-II light and the targeting effect of NH2-PEG1000-cRGDfK, LCR can recognize tiny tumor tissue (≈3mm) and monitor drug distribution in vivo. Under 1530nm excitation, internal Er3+ can be self-sensitized, generating intense upconversion emission (662nm) that can effectively activate Ce6 for in vivo PDT due to the deep tissue penetration of NIR-II light. This study provides a paradigm of theranostic nanoplatform for both real-time fluorescence imaging and PDT of orthotopic breast tumor in NIR-II window.

Effectiveness of palliative photodynamic therapy for unresectable biliary cancer. Systematic review and meta-analysis

A systematic review and meta-analysis was aimed to assess the effectiveness of palliative photodynamic therapy for unresectable malignant tumors of the biliary system in order to justify the feasibility of including photodynamic therapy (PDT) in the complex treatment of this category of patients. Publications in the databases PubMed Central, the bibliographic database of scientifi citations of the RSCI, and the Cochrane library were considered. Heterogeneity was assessed graphically using forest plots and statistically using tau2 and I2 statistics. A meta-analysis of 5-year survival revealed a statistically signifiantly longer pooled estimate of the survival period in groups where PDT was used – 339±161 days (95% CI 25-710; p &lt; 0.001) compared to groups where PDT was not used – 83±16 days (95% CI 33-100; p &lt; 0.001). Heterogeneity among studies was found to be statistically insignifiant (I2 = 29%, p = 0.23). A meta-analysis of the risk difference for adverse events revealed a statistically signifiantly lower risk (-0.2306; 95% CI -0.3917-0.0696; p = 0.005) of adverse events after PDT compared with the comparison group. Heterogeneity among studies was found to be statistically insignifiant (I2 = 0%, p = 0.35). There were no signifiant publication biases in either meta-analysis. The presented meta-analysis demonstrated that PDT may be the method of choice in the palliative complex treatment of patients with unresectable cholangicarcinomas, increasing the ˝ve-year survival of patients along with the absence of increased risks of postoperative complications in comparison with other methods of palliative surgical treatment.

Retrospective clinical study analysis of skin adverse reactions related to epidermal growth factor receptor inhibitors.

Epidermal growth factor receptor inhibitors (EGFRIs) represent a cornerstone in the targeted therapy of malignant tumors. While effective, dermatological adverse events (dAEs) associated with EGFRIs pose a significant challenge, often necessitating treatment discontinuation due to their severity and potential to impede the continuity of cancer therapy. Despite extensive research, the specific mechanisms and predictors of these adverse events remain poorly understood, particularly in diverse populations. This gap in knowledge underscores the need for targeted studies to better predict and manage these events, enhancing patient outcomes and adherence to life-saving therapies. This observational study was conducted at The First Affiliated Hospital of Guangxi Medical University, covering cancer patients treated with EGFRIs from 2020 to 2022. We analyzed clinical data including patient demographics, treatment specifics, and the development and timing of dAEs. The study employed SPSS 26.0 software for data analysis, focusing on the incidence of dAEs and factors influencing their occurrence. We used Kaplan-Meier and Cox regression methods to establish a predictive model for dAEs, tracking their onset and impact on treatment continuity. In our study of 120 patients treated with EGFR inhibitors at The First Affiliated Hospital of Guangxi Medical University, we found a high prevalence of dAEs, with 84.2% of patients experiencing such effects. The most common manifestations were papulopustular rashes, observed as pustules in 52.5% and papules in 57.4% of cases, followed by nail lesions in 62.4% of patients, oral or other mucosal ulcers in 34.7%, and hair changes in 26.7%. The median incubation time (MIT) for dAEs was 5 weeks. We identified drug type, ethnicity, and occupation as statistically significant risk factors (P<0.05 for all) that influenced the MIT, which the Cox regression model further identified as protective factors. Nomograms were developed to assess the risk of dAEs, although it is important to note that these models have only been internally validated, lacking external validation data at this stage. The study highlights the high incidence of EGFRIs-associated dAEs, with specific dermatological manifestations posing significant challenges in cancer therapy. The identification of drug type, ethnicity, and occupation as influential factors on the MIT for dAEs informs clinical decisions. Our prediction model serves as a practical tool for evaluating the risk of developing dAEs over time, aiming to optimize patient management and mitigate treatment interruptions.

EGFR-TKIs - induced cardiotoxicity in NSCLC: incidence, evaluation, and monitoring.

The advent of targeted drug therapy has greatly changed the treatment landscape of advanced non-small cell lung cancer(NSCLC), but the cardioxic side effects of targeted drug anti-cancer therapy seriously affect the prognosis of NSCLC, and it has become the second leading cause of death in cancer patients. Therefore, early identification of the cardiotoxic side effects of targeted drugs is crucial for the prevention and treatment of cardiovascular diseases. The cardiotoxic side effects that may be caused by novel targeted drugs epidermal growth factor receptor inhibitors, including thromboembolic events, heart failure, cardiomyopathy, arrhythmia and hypertension, are discussed, and the mechanisms of their respective adverse cardiovascular reactions are summarized, to provide useful recommendations for cardiac management of patients with advanced lung cancer to maximize treatment outcomes for lung cancer survivors. Clinicians need to balance the risk-benefit ratio between targeted therapy for malignant tumors and drug-induced cardiotoxicity, and evaluate and monitor TKIs-induced cardiotoxicity through electrocardiogram, cardiac imaging, biomarkers, etc., so as to remove the susceptibility risk factors as soon as possible and provide a reference for the clinical use of such drugs in the treatment of malignant tumors.

Antitumor Therapy through Photothermal Performance Synergized with Catalytic Activity Based on the Boron Cluster Supramolecular Frameworks.

Chemodynamic therapy (CDT) has received widespread attention as a tumor optical treatment strategy in the field of malignant tumor therapy. Nonmetallic multifunctional nanomaterials as CDT agents, due to their low toxicity, long-lasting effects, and safety characteristics, have promising applications in the integrated diagnosis and treatment of cancer. Here, we modified the supramolecular framework of boron clusters, coupled with a variety of dyes to develop a series of metal-free agent compounds, and demonstrated that these nonmetallic compounds have excellent CDT activities through experiments. Subsequently, the best performing Methylene Blue/[closo-B12H12]2- (MB@B12H12) was used as an example. Through theoretical calculations, electron paramagnetic resonance spectroscopy, and 808 nm light irradiation, we confirmed that MB@B12H12 exhibited photothermal performance and CDT activity further. More importantly, we applied MB@B12H12 to melanoma cells and subcutaneous tumor, demonstrating its effective suppression of melanoma growth in vitro and in vivo through the synergistic effects of photothermal performance and CDT activity. This study emphasizes the generalizability of the coupling of dyes to [closo-B12H12]2- with important clinical translational potential for CDT reagents. Among them, MB@B12H12 may have a brighter future, paving the way for the rapid development of metal-free CDT reagents.

Synthesis and Characterization of a Novel PET Tracer for Noninvasive Evaluation of FGL1 Status in Tumors.

Fibrinogen-like protein 1 (FGL1) is a potential novel immune checkpoint target for malignant tumor diagnosis and therapy. Accurate detection of FGL1 levels in tumors via noninvasive PET imaging might be beneficial for managing the disease. To achieve this, multiple FGL1-targeting peptides (FGLP) were designed, and a promising candidate, 68Ga-NOTA-FGLP2, was identified through a high-throughput screening approach using microPET imaging of 68Ga-labeled peptides. Subsequent in vitro cell experiments showed that uptake values of 68Ga-NOTA-FGLP2 in FGL1 positive Huh7 tumor cells were significantly higher than those in FGL1 negative U87 MG tumor cells. Further microPET imaging showed that the Huh7 xenografts were clearly visualized with a favorable contrast. ROI analysis showed that the uptake values of the tracer in Huh7 xenografts were 2.63 ± 0.07% ID/g at 30 min p.i.. After treatment with an excess of unlabeled FGLP2, the tumor uptake significantly decreased to 0.54 ± 0.05% ID/g at 30 min p.i.. Moreover, the uptake in U87 MG xenografts was 0.44 ± 0.06% ID/g at the same time point. The tracer was excreted mainly through the renal system. 18F-FDG PET imaging was also performed in mice bearing Huh7 and U87 MG xenografts, respectively. However, there was no significant difference in the uptake between the tumors with different FGL1 expressions. Preclinical data indicated that 68Ga-NOTA-FGLP2 might be a suitable radiotracer for in vivo noninvasive visualization of tumors with abundant expression of FGL1. Further investigation of 68Ga-NOTA-FGLP2 for tumor diagnosis and therapy is undergoing.

Dihydroartemisinin-driven selective anti-lung cancer proliferation by binding to EGFR and inhibition of NRAS signaling pathway-induced DNA damage.

Chemotherapeutic agents can inhibit the proliferation of malignant cells due to their cytotoxicity, which is limited by collateral damage. Dihydroartemisinin (DHA), has a selective anti-cancer effect, whose target and mechanism remain uncovered. The present work aims to examine the selective inhibitory effect of DHA as well as the mechanisms involved. The findings revealed that the Lewis cell line (LLC) and A549 cell line (A549) had an extremely rapid proliferation rate compared with the 16HBE cell line (16HBE). LLC and A549 showed an increased expression of NRAS compared with 16HBE. Interestingly, DHA was found to inhibit the proliferation and facilitate the apoptosis of LLC and A549 with significant anti-cancer efficacy and down-regulation of NRAS. Results from molecular docking and cellular thermal shift assay revealed that DHA could bind to epidermal growth factor receptor (EGFR) molecules, attenuating the EGF binding and thus driving the suppressive effect. LLC and A549 also exhibited obvious DNA damage in response to DHA. Further results demonstrated that over-expression of NRAS abated DHA-induced blockage of NRAS. Moreover, not only the DNA damage was impaired, but the proliferation of lung cancer cells was also revitalized while NRAS was over-expression. Taken together, DHA could induce selective anti-lung cancer efficacy through binding to EGFR and thereby abolishing the NRAS signaling pathway, thus leading to DNA damage, which provides a novel theoretical basis for phytomedicine molecular therapy of malignant tumors.

Can magnetic nanoparticles enhance adoptive cell therapy via driving migration of lymphocytes into tumors?

Therapy of malignant tumors still represents a huge problem for healthcare, since these diseases lead to a high rate of disability and premature death of the population. The main problems of adoptive cell therapy for malignant tumors are a low rate of migration of effector lymphocytes into tumors, as well as their low activity in tumors due to suppressive tumor microenvironment. In addition, it should be noted that systemic intravenous administration of a large number of activated lymphocytes may be accompanied by a pronounced cytokine release syndrome, which leads to significant negative side effects, including high temperature, blood clotting disorders, aggression of immune cells against their own tissues, even neurotoxicity. Functional nanomaterials, such as magnetic nanoparticles with various surface modifications (PEG, PEI, DMSA, citrate, etc.) are highly promising agents for targeted delivery of different anti-tumor substances. Magnet-driven enrichment of effector anti-tumor lymphocytes in tumors would highly increase the effectiveness and enhance safety of adoptive lymphocyte therapy. However, different research groups obtained opposing data about the feasibility and efficiency of such approach. Thus, this review is focused on experimental details of the contradicting studies and aims to elucidate the possible reasons of these controversies and the best practices to efficiently target lymphocytes into tumors.

Current progress in chimeric antigen receptor T‐cell therapy for malignant tumors

AbstractIn the realm of malignant tumor treatment, particularly regarding hematologic malignancies, chimeric antigen receptor T‐cell (CAR‐T) immunotherapy has witnessed remarkable advancements in recent years. This approach involves genetically modifying and engineering a patient's T‐cells ex vivo to express a specific CAR, known as CAR‐T cells. When these modified cells are reintroduced into the patient, they can specifically recognize target antigens and exhibit highly efficient cytotoxicity against cells expressing these antigens, making them suitable for the treatment of malignant tumors. CD19, which is expressed on the surface of B lymphocytes at different stages of differentiation, has been identified as a suitable target for the treatment of most B‐cell lymphomas. CAR‐T cells targeting CD19 have demonstrated excellent specificity, cytotoxicity, and persistence in both in vitro and clinical trials, showing tremendous potential for application. However, identifying appropriate targets for CAR‐T therapy in solid tumors remains a challenge, leading to limited advancements in this area. This review discusses the mechanisms, applications, limitations, and prospects of CAR‐T therapy in hematologic malignancies and solid tumors, aiming to provide directions for future research in this field.