Tumor Treatment Research Articles

Comparison of laparoscopic hepatectomy and radiofrequency ablation for small hepatocellular carcinoma patients: a SEER population-based propensity score matching study.

This study was designed to compare the efficacy of laparoscopic hepatectomy (LH) and radiofrequency ablation (RFA) in terms of their therapeutic effect on small hepatocellular carcinoma (SHCC). The SEER database was employed to integrate SHCC patients who had received treatment with either LH (n = 1132) or RFA (n = 797). The LH group (n = 623) and the RFA group (n = 623) were matched with 1:1 propensity score matching (PSM) in order to reduce the possibility of selection bias. The Kaplan-Meier method and Cox proportional hazards regression method were employed to ascertain the prognostic factors associated with overall survival (OS) and disease-specific survival (DSS). Both before and after PSM, the 1, 3 and 5-years OS and DSS were significantly higher in the LH groups compared to the RFA group. Besides, for SHCC with tumor size ≤ 2cm (n = 418), even P values not reaching statistical significance, the survival curves were compatible with a superiority of LH over RFA for OS and DSS in overall (P = 0.054 and P = 0.077), primary SHCC (P = 0.110 and P = 0.058) and recurrent SHCC (P = 0.068 and P = 1.000) cohorts. In contrast, for SHCC with tumor size between 2 and 3 cm (n = 828), LH group always had a better OS and DSS in the all cohorts (all P < 0.05). In addition, higher AFP level, poor differentiation grade, recurrent tumor and treatment type were independent prognostic factors for OS, while poor differentiation grade, larger tumor size and treatment type were the independent prognostic factors for DSS (all P < 0.05). LH was associated with better OS and DSS than RFA in SHCC patients. Even in tumor size ≤ 2cm, LH still should be the first choice as its long-term survival benefits.

A patient-derived HCC spheroid system to model the tumor microenvironment and treatment response

Background & AimsHepatocellular carcinoma (HCC) is the third leading and fastest rising cause of cancer-related death worldwide. The discovery and preclinical development of compounds targeting HCC is hampered by the absence of authentic tractable systems recapitulating the heterogeneity of patient HCC tumors and the tumor microenvironment (TME). MethodsWe established a novel and simple patient-derived multicellular tumorspheroid model based on clinical HCC tumor tissues, processed using enzymatic and mechanical dissociation. After quality controls, 22 HCC tissues and 17 HCC serum were selected for tumorspheroid generation and perturbation studies. Cells were grown in 3D in optimized medium in presence of patient serum. Characterization of the tumorspheroid cell populations was performed by flow cytometry, immunohistochemistry and functional assays. As a proof of concept, we treated patient-derived spheroids with FDA approved anti-HCC compounds. ResultsThe model was successfully established independently from cancer etiology and grade from 22 HCC tissues. We show that the use of HCC patient serum was essential for tumorspheroid generation, the TME function and to maintain cell viability. The tumorspheroids comprised the main cell compartments including epithelial cancer cells as well as all major cell populations of the TME (cancer-associated fibroblasts, macrophages and T cells, endothelial cells). Tumorspheroids reflect HCC heterogeneity, including variability in cell type proportions and TME, and mimic the original tumor features. Moreover, we observed differential responses to FDA HCC approved drugs between donors as observed in patients. ConclusionThis patient HCC serum-tumorspheroid model provides novel opportunities for drug discovery and development as well as mechanism of action studies including compounds targeting the TME. This model will likely contribute to improve the dismal outcome of patients with HCC. Impact and implicationsHepatocellular carcinoma (HCC) is a leading and fast rising cause of cancer-related death worldwide. Despite approval of novel therapies, the outcome of advanced HCC remains unsatisfactory. By developing a novel patient-derived tumorspheroid model recapitulating tumor heterogeneity and microenvironment, we provide new opportunities for HCC drug development and analysis of mechanism of action in authentic patient tissues. The application of the patient-derived tumorspheroids combined with other HCC models will likely contribute to drug development and to improve the dismal outcome of patients with HCC.

A smart-responsive Y-shaped DNA scaffold drug conjugate achieving precise and synergetic tumor chemo-gene therapy via promoting tumor apoptosis and activating the anti-tumor immunity

Constructing precise delivery systems to enhance the antitumor efficacy of drugs represents a pressing clinical practice need. The characteristics of suitable physiological stability, flexible tunable size, and highly programmable architecture make functional DNA scaffolds an ideal solution to this requirement. Here, we designed DNA oligonucleotide probes Y1, Y2 and Y3 to construct a smart-responsive Y-shaped DNA scaffold drug conjugate (sYDD). This sYDD incorporates two AS1411 aptamers, an apurinic/apyrimidinic (AP) site, a B-cell lymphoma-2 (Bcl-2) antisense oligonucleotide (ASO) and a doxorubicin (DOX)-carrying sequence. The Bcl-2 ASO and DOX within sYDD could be responsively released in tumor cells that exhibited high expression of apurinic/apyrimidinic endonuclease 1 (APE1) and microRNA-21 (miR-21). And the in vitro and in vivo experiments demonstrated that sYDD exhibited substantial antitumor efficiency. Moreover, the flow cytometry and RNA sequencing results proved that the proposed sYDD effectively activated immune responses. This strategy provides an alternative approach for designing synergistic chemo-gene drug conjugates, which facilitates the development of precision tumor treatment modalities.

Injectable hydrogels for Fenton-like Mn2+/Fe2+ delivery with enhanced chemodynamic therapy prevent osteosarcoma recurrence and promote wound healing after excision surgery

Local recurrence of osteosarcoma and wound healing after excision surgery are major challenges in clinical research. The present anti-tumor treatments could inhibit normal tissues, resulting in difficulties in surgical wound healing. In this study, we constructed an injectable hydrogel as a platform to co-deliver MnO2 nanoparticles and ferrocene Fc, termed as (MnO2/Fc)@PLGA for osteosarcoma treatment and wound healing after excision. By simple local injection, the hydrogel could form a protective barrier on the surgical wound after osteosarcoma excision, which could promote wound healing and steady release of MnO2/Fc nanoparticles. The released MnO2/Fc might undergo the Fenton reaction through Mn2+/Fe2+ to inhibit osteosarcoma cells with chemodynamic therapy (CDT). Furthermore, MnO2 could catalyze endogenous H2O2 to produce O2, which eliminates the adverse effects of H2O2 and remodels the hypoxic state in the local lesions. The increased O2 facilitated surgical wound healing and anti-tumor effects by regulating the hypoxia inducible factor-1 functions. In conclusion, (MnO2/Fc)@PLGA hydrogel could effectively prevent local recurrence of osteosarcoma and promote wound healing after excision surgery, thereby providing a novel strategy for tumor treatment and tissue repair.

Constrained optimal control problem of oncolytic viruses in cancer treatment

Oncolytic viruses are genetically modified viruses that selectively infect and destroy cancer cells while leaving normal and healthy cells intact. Most previous studies did not consider realistic constraints such as daily or total injection amount of oncolytic viruses; consequently, a gap exists between the research results and the real-world setting. This study aimed to investigate a constrained optimal control problem in tumor treatment utilizing oncolytic viruses, based on a mathematical model. This constraint reflects the practical scenario where the total dosage of oncolytic viruses that can be administered is limited. We introduced auxiliary state variables to address these limitations and employed the penalty function method. Furthermore, we established the existence of an optimal solution for the optimal control problem and derived the corresponding optimality system. Numerical simulations demonstrate the effectiveness of an approach that involves initiating treatment with a high dosage and gradually reducing it over time. Additionally, we confirmed that applying the optimal control strategy leads to a significant reduction in the number of cancer cells compared with uniform dosing, even when the same quantity of virus is administered.

Predictors of Durable Remission After Successful Surgery for Cushing Disease: Results From the Multicenter RAPID Registry.

Cushing disease (CD) affects mortality and quality of life along with limited long-term remission, underscoring the need to better identify recurrence risk. The identification of surgical or imaging predictors for CD remission after transsphenoidal surgery has yielded some inconsistent results and has been limited by single-center, single-surgeon, or meta-analyses studies. We sought to evaluate the multicenter Registry of Adenomas of the Pituitary and Related Disorders (RAPID) database of academic US pituitary centers to assess whether robust nonhormonal recurrence predictors could be elucidated. Patients with treated CD from 2011 to 2023 were included. The perioperative and long-term characteristics of CD patients with and without recurrence were assessed using univariable and multivariable analyses. Of 383 patients with CD from 26 surgeons achieving postoperative remission, 288 (75.2%) maintained remission at last follow-up while 95 (24.8%) showed recurrence (median time to recurrence 9.99 ± 1.34 years). Patients with recurrence required longer postoperative hospital stays (5 ± 3 vs 4 ± 2 days, P = .002), had larger average tumor volumes (1.76 ± 2.53 cm 3 vs 0.49 ± 1.17 cm 3 , P = .0001), and more often previously failed prior treatment (31.1% vs 14.9%, P = .001) mostly being prior surgery. Multivariable hazard prediction models for tumor recurrence found younger age (odds ratio [OR] = 0.95, P = .002) and Knosp grade of 0 (OR = 0.09, reference Knosp grade 4, P = .03) to be protective against recurrence. Comparison of Knosp grade 0 to 2 vs 3 to 4 showed that lower grades had reduced risk of recurrence (OR = 0.27, P = .04). Other factors such as length of stay, surgeon experience, prior tumor treatment, and Knosp grades 1, 2, or 3 failed to reach levels of statistical significance in multivariable analysis. This multicenter study centers suggests that the strongest predictors of recurrence include tumor size/invasion and age. This insight can help with patient counseling and prognostication. Long-term follow-up is necessary for patients, and early treatment of small tumors may improve outcomes.

Multi-functional nanosonosensitizer-engineered bacteria to overcome tumor hypoxia for enhanced sonodynamic therapy

BackgroundUltrasound-triggered sonodynamic therapy (SDT), with high safety and acceptance, has become a promising tumor treatment. However, the dense stroma, hypoxic microenvironment of tumor, and the unpredictable treatment timing limit the effectiveness of sonosensitizers and the antitumor therapeutic effect. Thus, it is crucial to develop an imaging-guided sensitization strategy for hypoxic tumor sonosensitization to improve the efficacy of SDT. MethodsIn this study, we developed a biohybrid system CB@HPP, which genetically engineered bacteria to express catalase (CB) and modified nanosonosensitizers (HPP) to the surface of these bacteria. Tumor hypoxia relief, tumor targeting, biocompatibility, and antitumor efficacy were evaluated through in vitro and in vivo experiments. In addition, the photoacoustic (PA), ultrasound (US), and fluorescence (FL) imaging effects of CB@HPP were evaluated in vivo and in vitro. ResultsAfter intravenous injection, CB@HPP was able to target tumor tissue. CB@HPP possessed efficient catalase activity and successfully degraded hydrogen peroxide to produce oxygen. Increased oxygen levels relief intratumoral hypoxia, thereby enhancing CB@HPP-mediated. In addition, CB@HPP showed FL/PA/US multimodal imaging capabilities, which reflects the aggregation effect of CB@HPP in the tumor and suggest the timing of treatment. ConclusionThe biohybrid system CB@HPP significantly alleviates tumor hypoxia, and multimodal imaging-mediated oxygen-producing SDT effectively suppresses tumors. This integrated imaging and therapeutic biohybrid system provides a more efficient and attractive cancer treatment strategy for SDT. Statement of significanceThis study developed a sensitizing SDT strategy for imaging-guided drug-targeted delivery and in situ oxygen production. We designed a biohybrid system CB@HPP, which was hybridized by the engineered bacteria with catalytic oxygen production and nanosonosensitizer with multimodal imaging capability. CB@HPP significantly alleviates tumor hypoxia, and multimodal imaging-mediated oxygen-producing SDT effectively suppresses tumors. This integrated imaging and therapeutic biohybrid system provides a more efficient and attractive cancer treatment strategy for SDT.

Repurposing of Antidiarrheal Loperamide for Treating Melanoma by Inducing Cell Apoptosis and Cell Metastasis Suppression In vitro and In vivo.

Melanoma is the most common skin tumor worldwide and still lacks effective therapeutic agents in clinical practice. Repurposing of existing drugs for clinical tumor treatment is an attractive and effective strategy. Loperamide is a commonly used anti-diarrheal drug with excellent safety profiles. However, the affection and mechanism of loperamide in melanoma remain unknown. Herein, the potential anti-melanoma effects and mechanism of loperamide were investigated in vitro and in vivo. In the present study, we demonstrated that loperamide possessed a strong inhibition in cell viability and proliferation in melanoma using MTT, colony formation and EUD incorporation assays. Meanwhile, xenograft tumor models were established to investigate the anti-melanoma activity of loperamide in vivo. Moreover, the effects of loperamide on apoptosis in melanoma cells and potential mechanisms were explored by Annexin V-FITC apoptosis detection, cell cycle, mitochondrial membrane potential assay, reactive oxygen species level detection, and apoptosis-correlation proteins analysis. Furthermore, loperamide-suppressed melanoma metastasis was studied by migration and invasion assays. What's more, immunohistochemical and immunofluorescence staining assays were applied to demonstrate the mechanism of loperamide against melanoma in vivo. Finally, we performed the analysis of routine blood and blood biochemical, as well as hematoxylin- eosin (H&E) staining, in order to investigate the safety properties of loperamide. Loperamide could observably inhibit melanoma cell proliferation in vitro and in vivo. Meanwhile, loperamide induced melanoma cell apoptosis by accumulation of the sub-G1 cells population, enhancement of reactive oxygen species level, depletion of mitochondrial membrane potential, and apoptosis-related protein activation in vitro. Of note, apoptosis-inducing effects were also observed in vivo. Subsequently, loperamide markedly restrained melanoma cell migration and invasion in vitro and in vivo. Ultimately, loperamide was witnessed to have an amicable safety profile. These findings suggested that repurposing of loperamide might have great potential as a novel and safe alternative strategy to cure melanoma via inhibiting proliferation, inducing apoptosis and cell cycle arrest, and suppressing migration and invasion.

Clinical Efficacy of Microwave Ablation Combined with Percutaneous Osteoplasty in the Treatment of Flat Bone Metastases.

Evaluating the clinical efficacy and safety of microwave ablation combined with percutaneous osteoplasty (MWA + PO group) versus percutaneous osteoplasty (PO group) for the treatment of flat bone metastases. Patients with flat bone metastases and intractable pain who underwent PO and/or MWA from January 2016 to January 2023 in our hospital were included, with 36 cases in the MWA+PO group and 21 cases in the PO group. Changes in the visual analog scale (VAS), Oswestry Disability Index (ODI), and quality of life assessment scale(QOL) were evaluated regularly. Postoperative complications and target lesion tumor treatment responses were also observed. The VAS and ODI in both the MWA+PO group and the PO group significantly decreased at 1week, 1 month, and 3 months postoperatively, The VAS and ODI in the MWA+PO group were lower than those in the PO group postoperatively. The QOL in both the MWA+PO group and the PO group significantly increased at 1week, 1 month, and 3 months postoperatively, with the QOL in the MWA+PO group being higher than that in the PO group postoperatively. According to the mRECIST criteria (target lesion tumor treatment response), the ORR in the MWA+PO group and PO group was 52.8% and 9.5%, respectively, while the DCR was 94.4% and 57.1%, respectively (P <0.001 and<0.001). Different degrees of bone cement extravasation were observed in both the PO group (38.1%) and MWA+PO group(19.4%)(χ²=2.38, P=0.12), but none of the patients developed clinical symptoms related to bone cement extravasation. The average cost of surgery was ¥10,480.43higher in the MWA+PO group than in the PO group. The MWA+PO treatment is more effective in relieving patients' local pain, improving local dysfunction, and enhancing quality of life, and can effectively improve target lesion tumor ORR and DCR, but it is also more costly.

Discovery of Quinazoline Derivatives as Potent KRASG12C Inhibitors

AbstractRAS proteins are necessary for cell survival, and their mutations are closely related to tumor formation and progression. Mutated RAS proteins were undruggable owing to their smooth surface decades ago. Since chemists found that covalently binding to mutated cysteine (G12 C) was a potential therapy for KRASG12C inhibition. Recently, AMG‐510 and MRTX‐849 were approved in 2021 and 2022 respectively for solid tumor treatment. In this paper, started with KRASG12C inhibitor ARS‐1620, we introduced different hydrophilic fragment on it and reached compound K09, which had the best KRASG12C inhibitory activity and antiproliferation activities. Compound K09 is regarded as a lead compound for further exploration.

Long-Term Survival in Canine Hepatosplenic T-Cell Lymphoma Treated with Toceranib Phosphate Following Splenectomy: A Case of Atypical Lymphoma

Toceranib phosphate (toceranib) is approved for canine mast cell tumor treatment. However, no long-term response to toceranib in canine HSTCL has been reported. Here, we describe a case of a 10-year-old castrated mixed-breed dog that presented with a 3-month history of weight loss, polydipsia, and polyuria. The clinicopathological and imaging abnormalities included icterus, biliary obstruction, and splenomegaly with multiple diffuse splenic hypoechoic nodules. On day 21, a cholecystectomy was performed to remove the obstruction, followed by a liver biopsy and splenectomy. Cytology of the spleen and liver showed many small lymphocytes with intracytoplasmic granules (sGLs). Splenic and hepatic infiltration of neoplastic CD3/granzyme B-positive small cells and lymphocytic cholecystitis with granzyme B-negative small cells were noted. T-cell receptor gene clonal rearrangements were observed in the liver tissues. The dog was diagnosed with a hepatosplenic T-cell lymphoma (HSTCL) of sGLs concurrent with lymphocytic cholecystitis. The icterus resolved after surgery, but there was progressive elevation of liver enzyme levels. Toceranib was administered from day 39, resulting in decreased liver enzyme levels, and the dog remained in good condition. The dog stayed in remission after toceranib administration and survived for 460 days. Toceranib should be considered an effective treatment option for canine HSTCL.

NIR-activatable nitric oxide generator based on nanoparticles loaded small-molecule photosensitizers for synergetic photodynamic/gas therapy

BackgroundTherapeutic approaches that combine conventional photodynamic therapy (PDT) with gas therapy (GT) to sensitize PDT are an attractive strategy, but the molecular structure design of the complex lacks effective guiding strategies.ResultsHerein, we have developed a nanoplatforms Cy-NMNO@SiO2 based on mesoporous silica materials loaded NIR-activatable small-molecule fluorescent probe Cy-NMNO for the synergistic treatment of photodynamic therapy/gas therapy (PDT/GT) in antibacterial and skin cancer. The theoretical calculation results showed that the low dissociation of N-NO in Cy-NMNO enabled it to dissociate effectively under NIR light irradiation, which is conducive to produce Cy and NO. Cy showed better 1O2 generation performance than Cy-NMNO. The cytotoxicity of Cy-NMNO obtained via the synergistic effect of GT and PDT synergistically enhances the effect of photodynamic therapy, thus achieving more effective tumor treatment and sterilization than conventional PDT. Moreover, the nanoplatforms Cy-NMNO@SiO2 realized efficient drug loading and drug delivery.ConclusionsThis work not only offers a promising approach for PDT-GT synergistic drug delivery system, but also provides a valuable reference for the design of its drug molecules.Graphical

Priming of Cancer-Immunity Cycle by Alleviating Hypoxia-induced Ferroptosis Resistance and Immunosuppression

Stimulating a robust cancer-immunity cycle (CIC) holds promising potential for eliciting potent and enduring immune responses for cancer immunotherapy. However, designing a therapeutic nanomaterial capable of both enhancing tumor immunogenicity and mitigating immunosuppression is challenging and often associated with complicated design paradigms and immune-related adverse effects. Herein, a multienzyme-mimetic alloy nanosheet incorporating palladium (Pd) and iron (Fe) is developed, which can prime effective CIC by overcoming ferroptosis resistance for enhancing tumor immunogenicity and reprograming the tumor microenvironment for enhanced second near-infrared (NIR-II) photoimmunotherapy. The nanosheets accumulate in tumors when administered intravenously and counteract hypoxia through catalase-like oxygen production and subsequent reduction of hypoxia-inducible factor-1α, M2-like macrophages, regulatory T-cell, and programmed death-ligand 1 (PD-L1) expression. The surface plasmon resonance of the nanosheets enables NIR-II phototherapy and photoacoustic imaging, coupling with its ferroptosis and tumor microenvironment reprogram properties to synergize with anti-PD-L1 checkpoint blockade therapy to achieve excellent antitumor outcome. This study offers a strategy for localized tumor treatment and boosting the CIC through a straightforward and inexpensive nanomaterial design.

Formulating the Relationship Between Intermolecular Interactions and Photodynamic Effects Based on the Optical Regularity Exhibited by Rare Earth‐BODIPY Crystalline Frameworks System

AbstractThis research commenced with an exploration of how metal nodes in metal‐organic frameworks (MOFs) influence photodynamic therapy (PDT) outcomes. Ultimately, it is revealed that intermolecular interactions are the core mechanism determining the optical properties and PDT efficacy of MOFs. An advanced system of MOFs based on the integration of twelve rare earth ions (RE3+) with boron dipyrromethene (BODIPY)‐derived ligands is reported. Intriguingly, this series of MOFs exhibits a reverse relationship between the radius of RE3+ and PDT efficacy. Single‐crystal X‐ray diffraction analyses along with theoretical calculations indicate that varying RE3+ results in a spatial displacement of the ligands along the dipole direction, diminishing electrostatic (dipole–dipole) interactions while enhancing dispersion (π–π) interactions, thereby enhancing the generation of triplet excitons. Consequently, a novel parameter, Ae‐v = EvdW / Eint × 100%, is proposed to quantify the interplay between non‐radiative energy dissipation via electrostatic interactions and efficient energy utilization in generating singlet oxygen through dispersion interactions. Furthermore, with consistent acoustic sensitivity aligned with the sonoluminescence mechanism, RE‐DCBs are employed in sono‐photodynamic cancer therapy, attaining significant therapeutic results in tumor treatment during in vivo experiments.

“Lily of the valley”-like Au@RCA-AS1411 nanoplatforms polyvalent aptamers-targeted drug delivery system for combined photothermal and chemo-tumor cell therapy

The combined photothermal and chemo- therapy overcomes the limitations of single one, and enhances the therapeutic efficiency which holds broad prospects in tumor treatment. Herein, the “Lily of the valley”-like Au@RCA-AS1411 nanoplatform with polyvalent aptamers-targeted capability has been designed based on rolling circle amplification (RCA) for dual-treating of liver cancer through photothermal and chemotherapy. Polyvalent aptamers can be effectively constructed by the Au@RCA-AS1411 nanoplatform, bolstering the capacity for targeting cancer cell and reducing the toxic side effects on normal cells. Meanwhile, multiple gold nanoparticles (AuNPs) have been successfully linked to the nanoplatform via SH, which realized the aggregation of AuNPs and the photothermal conversion efficiency is improved to 69.7 %. In addition, the photothermal enhancement of Dox release was demonstrated by Au@RCA-AS1411. This nanoplatform was used to treat L929 and HepG2 cells, and found that it had no toxic and side effects on cells and had good biocompatibility. Au@RCA-AS1411 nanoplatform with polyvalent aptamers showed stronger specific targeting ability to HepG2 cells than Au@RCA without aptamers and Au@DNA-AS1411 containing only one aptamer. After laser irradiation, the survival rate of HepG2 cells in the presence of Au@RCA-AS1411 decreased to 27.8 %, which was lower than that of normal L929 cells and other controls. Encouragingly, when combined with drugs, the survival rate of HepG2 cells was significantly reduced to 11.2 %, indicating that the nanoplatform combination therapy enhanced and showed synergistic effects.

Chlorin e6-Loaded Nanostructured Lipid Carriers Targeted by Angiopep-2: Advancing Photodynamic Therapy in Glioblastoma.

Glioblastoma (GBM) is a highly aggressive brain tumor known for its resistance to standard treatments. Despite surgery being a primary option, it often leads to incomplete removal and high recurrence rates. Photodynamic therapy (PDT) holds promise as an adjunctive treatment, but safety concerns and the need for high-power lasers have limited its widespread use. This research addresses these challenges by introducing a novel PDT approach, using chlorin e6 (Ce6) enclosed in nanostructured lipid carriers (Ang-Ce6-NLCs) and targeted to GBM with the angiopep-2 peptide. Remarkably, a single 5-min irradiation session with LEDs at 660nm and low power density (10mW cm- 2) proves effective against GBM, while reducing safety risks associated with high-power lasers. Encapsulation improves Ce6 stability and performance in physiological environments, while angiopep-2 targeting enhances delivery to GBM cells, maximizing treatment efficacy and minimizing off-target effects. The findings demonstrate that Ang-Ce6-NLCs-mediated PDT brings about a significant reduction in GBM cell viability, increases oxidative stress, reduces tumor migration, and enhances apoptosis. Overall, such treatment holds potential as a safe and efficient intraoperative removal of GBM infiltrating cells that cannot be reached by surgery, using low-power LED light to minimize harm to surrounding healthy tissue while maximizing tumor treatment.

Immunogenicity regulation of genetically engineered vaccine and its potential in tumor treatment

In this study, the strategy of enhancing immunogenicity of genetically engineered vaccine and its application potential in tumor treatment were discussed. Firstly, the study explained the principle that genetic engineering vaccine designed antigen by gene recombination technology to trigger strong immune response. By adjusting gene combination, improving vaccine delivery system and using adjuvant, the immune stimulation ability and delivery efficiency of vaccine were improved. Especially in tumor therapy, these vaccines stimulate specific immune responses against specific or related tumor antigens. This paper also summarizes the clinical manifestations of mRNA cancer vaccine and individualized cancer vaccine, and discusses the combined application with traditional treatment methods such as chemotherapy, radiotherapy, targeted therapy and immune checkpoint inhibitors, in order to improve the treatment effect and the diversity of patients' treatment options.

A glutathione-activated bismuth-gallic acid metal-organic framework nano-prodrug for enhanced sonodynamic therapy of breast tumor

Sonodynamic therapy is a promising, noninvasive, and precise tumor treatment that leverages sonosensitizers to generate cytotoxic reactive oxygen species during ultrasound stimulation. Gallic acid (GA), a natural polyphenol, possesses certain anti-tumor properties, but exhibits significant toxicity toward normal cells, limiting its application in cancer treatment. To overcome this issue, we synthesized a bismuth-gallic acid (BGA), coordinated metal–organic framework (MOF) nano-prodrug. Upon encountering glutathione (GSH), BGA gradually dissociated and depleted GSH, releasing GA, which had anti-tumor effects. As an MOF with semiconductor properties, BGA primarily produced superoxide anion radical upon ultrasound excitation. After the release of GA, GA generated superoxide anion radical and further produced high toxic singlet oxygen under ultrasound stimulation, while further oxidizing and consuming GSH, enhancing sonocatalytic performance. Additionally, the released GA induced cell cycle arrest, ultimately leading to apoptosis. Our results revealed that BGA, as a GSH-activated, metal-polyphenol MOF nano-prodrug, showed potential for use in breast tumor sonodynamic therapy, providing a novel strategy for precise tumor treatment.

Research Progress of TCM External Treatment on Opioid-related Constipation in Cancer Pain

Pain is one of the most common symptoms of malignant tumors. Opioids are the first-line drugs for the treatment of moderate to severe cancer pain. At present, there is no clear, effective and safe method for the prevention and treatment of its adverse reactions. Opioid-inducedconstipation (OIC) is a very common symptom of cancer patients who use opioids. An opioid inducedConstipation (OIC) has a great impact on patients' quality of life, tumor treatment and many other aspects. Therefore, an effective prevention and treatment of cancer pain OIC is of great clinical significance. The traditional Chinese medicine external treatment method is simple, convenient, testing and cheap, and has unique advantages in the treatment of OIC. In this paper, we summarized and analyzed the research on the treatment of opioid-related constipation by external treatment of traditional Chinese medicine in recent years, in order to provide reference value for clinical treatment.

Computational immune synapse analysis reveals T-cell interactions in distinct tumor microenvironments.

The tumor microenvironment (TME) and the cellular interactions within it can be critical to tumor progression and treatment response. Although technologies to generate multiplex images of the TME are advancing, the many ways in which TME imaging data can be mined to elucidate cellular interactions are only beginning to be realized. Here, we present a novel approach for multipronged computational immune synapse analysis (CISA) that reveals T-cell synaptic interactions from multiplex images. CISA enables automated discovery and quantification of immune synapse interactions based on the localization of proteins on cell membranes. We first demonstrate the ability of CISA to detect T-cell:APC (antigen presenting cell) synaptic interactions in two independent human melanoma imaging mass cytometry (IMC) tissue microarray datasets. We then verify CISA's applicability across data modalities with melanoma histocytometry whole slide images, revealing that T-cell:macrophage synapse formation correlates with T-cell proliferation. We next show the generality of CISA by extending it to breast cancer IMC images, finding that CISA quantifications of T-cell:B-cell synapses are predictive of improved patient survival. Our work demonstrates the biological and clinical significance of spatially resolving cell-cell synaptic interactions in the TME and provides a robust method to do so across imaging modalities and cancer types.