Treatment Of Malignant Tumors Research Articles

A near-infrared aggregation-induced emission photosensitizer targeting mitochondria for depleting Cu2+ to trigger light-activated cancer cells oncosis

Abnormally high levels of copper in tumors stimulate malignant proliferation and migration of cancer cells, which proposes a formidable challenge for the thorough therapy of malignant tumors. In this work, we developed a reliable, mitochondria-targeted near-infrared aggregation-induced emission fluorescent probe, TTQ-Th, whose thiourea moiety specifically could recognize mitochondria even both upon loss of mitochondrial membrane potential or in fixated cells, and can capture copper overexpressed by tumor cells, leading to severe copper deficiency. In parallel, TTQ-Th can generate sufficient reactive oxygen species (ROS) upon photoexcitation, while copper deficiency inhibits expression of related copper-based enzymes, resulting in a decline in ATP production. Such energy deficiency, combined with reduced MMP and elevated oxidative stress can lead to critical cell oncosis. Both in vitro and intracellular experiments can illustrate that the elevated ROS has remarkable damage to tumor cells and contributes to the elimination of the primary tumor, while copper deficiency further hinder tumor cell migration and induces G0/G1 cell cycle arrest in a dose-dependent manner, which is an efficacious strategy for the treatment of malignant tumors.

Biomimetic fusion liposomes boosting antitumor immunity and promote memory T cell differentiation to inhibit postoperative recurrence of breast cancer

For most solid tumors, surgery is still the most effective treatment. However, postoperative recurrence is the main reason for the failure of surgical treatment of malignant tumors. It is urgent to develop new nanomedicine systems to inhibit postoperative recurrence. Here, we designed a tumor cell membrane fusion liposome loaded AIE photosensitizer and Metformin named TMFL to inhibit postoperative recurrence. First, thanks to the homing effect of tumor cell membranes, TMFL can enter tumor tissues through active targeting. Under light irradiation, TMFL can produce singlet oxygen (1O2), which promoted immunogenic cell death (ICD) of tumor cells, thereby inducing dendritic cell (DC) maturation and stimulating T cell immunity. Metformin released by TMFL further promoted T cell differentiation into Central Memory T cell (Tcm) and inhibited tumor recurrence. The results of experiments showed that TMFL plus light treatment increased the content of mature DC in lymph nodes. In addition, TMFL can effectively promote the differentiation of T cells into Tcm, increase the content of T cells in recurrent tumor tissue, and inhibit the tumor recurrence. In view of the current major problems such as postoperative tumor recurrence, our TMFL system has a good clinical application potential.

Hafnium (Hf)-Chelating Porphyrin-Decorated Gold Nanosensitizers for Enhanced Radio-Radiodynamic Therapy of Colon Carcinoma.

X-ray-induced radiodynamic therapy (RDT) that can significantly reduce radiation dose with an improved anticancer effect has emerged as an attractive and promising therapeutic modality for tumors. However, it is highly significant to develop safe and efficient radiosensitizing agents for tumor radiation therapy. Herein, we present a smart nanotheranostic system FA-Au-CH that consists of gold nanoradiosensitizers, photosensitizer chlorin e6 (Ce6), and folic acid (FA) as a folate-receptor-targeting ligand for improved tumor specificity. FA-Au-CH nanoparticles have been demonstrated to be able to simultaneously serve as radiosensitizers and RDT agents for enhanced computed tomography (CT) imaging-guided radiotherapy (RT) of colon carcinoma, owing to the strong X-ray attenuation capability of high-Z elements Au and Hf, as well as the characteristics of Hf that can transfer radiation energy to Ce6 to generate ROS from Ce6 under X-ray irradiation. The integration of RT and RDT in this study demonstrates great efficacy and offers a promising therapeutic modality for the treatment of malignant tumors.

Therapeutic Potential of Adipose-Derived Stem Cell-Conditioned Medium and Extracellular Vesicles in an In Vitro Radiation-Induced Skin Injury Model.

Radiotherapy (RT) is one of three major treatments for malignant tumors, and one of its most common side effects is skin and soft tissue injury. However, the treatment of these remains challenging. Several studies have shown that mesenchymal stem cell (MSC) treatment enhances skin wound healing. In this study, we extracted human dermal fibroblasts (HDFs) and adipose-derived stem cells (ADSCs) from patients and generated an in vitro radiation-induced skin injury model with HDFs to verify the effect of conditioned medium derived from adipose-derived stem cells (ADSC-CM) and extracellular vesicles derived from adipose-derived stem cells (ADSC-EVs) on the healing of radiation-induced skin injury. The results showed that collagen synthesis was significantly increased in wounds treated with ADSC-CM or ADSC-EVs compared with the control group, which promoted the expression of collagen-related genes and suppressed the expression of inflammation-related genes. These findings indicated that treatment with ADSC-CM or ADSC-EVs suppressed inflammation and promoted extracellular matrix deposition; treatment with ADSC-EVs also promoted fibroblast proliferation. In conclusion, these results demonstrate the effectiveness of ADSC-CM and ADSC-EVs in the healing of radiation-induced skin injury.

P-288 - Alpha particle therapy for the treatment of metastatic tumors of prostate cancer

P-288 - Alpha particle therapy for the treatment of metastatic tumors of prostate cancer

Advances of cell therapy in lung cancer: a narrative review.

Lung cancer is the second most prevalent malignancy and has the highest death rate. The main approaches for lung cancer treatment include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, the treatments of the disease need to be further improved. An increasing number of scientific investigations indicated cell therapy to be a successful new treatment for lung cancer. Cell therapy can improve the host's immunity to disease and can compensate for the shortcomings in the therapeutic effects of traditional treatments, particularly in the case of cancer treatment. However, due to its recent development, its clinical efficacy still needs to be further examined. In order to provide an updated source on cell therapy for lung cancer, this paper summarizes the clinical use of chimeric antigen receptor T cells (CAR-Ts), stem cells, cytokine-induced killer cells (CIKs), and tumor-infiltrating lymphocytes (TILs) and discusses recent clinical advancements. We performed a search of the PubMed database on March 28, 2023, and again on June 10, 2023. A review of retrieved literature related to cell therapy and treatments for lung cancer was completed. Cell therapy has been applied in clinical studies on the treatment of disorders of the hematologic system, digestive system, respiratory system, and other systems. CAR-T therapy has been successfully used in the treatment of B-cell malignancies, which suggests that cell therapy has broad prospects in the treatment of malignant tumors. CAR-T, stem cells, CIKs, and TILs exert antitumor activity and can recognize and could be used to treat lung cancer. Cell therapy represents a novel solution in the treatment of lung cancer. Cell therapy, when combined with traditional therapies, can compensate for the shortcomings of these methods. Further research is needed to reduce the occurrence of adverse reactions and provide a more effective approach in treating lung cancer.

Cold Atmospheric Plasma Jet Irradiation Decreases the Survival and the Expression of Oncogenic miRNAs of Oral Carcinoma Cells

Despite recent advancements, therapies against advanced oral squamous cell carcinoma (OSCC) remain ineffective, resulting in unsatisfactory therapeutic outcomes. Cold atmospheric plasma (CAP) offers a promising approach in the treatment of malignant neoplasms. Although the effects of CAP in abrogating OSCC have been explored, the exact mechanisms driving CAP-induced cancer cell death and the changes in microRNA (miRNA) expression are not fully understood. We fabricated and calibrated an argon-CAP device to explore the effects of CAP irradiation on the growth and expression of oncogenic miRNAs in OSCC. The analysis revealed that, in OSCC cell lines following CAP irradiation, there was a significant reduction in viability; a downregulation of miR-21, miR-31, miR-134, miR-146a, and miR-211 expression; and an inactivation of the v-akt murine thymoma viral oncogene homolog (AKT) and extracellular signal-regulated kinase (ERK) signals. Pretreatment with blockers of apoptosis, autophagy, and ferroptosis synergistically reduced CAP-induced cell death, indicating a combined induction of variable death pathways via CAP. Combined treatments using death inhibitors and miRNA mimics, alongside the activation of AKT and ERK following the exogenous expression, counteracted the cell mortality associated with CAP. The CAP-induced downregulation of miR-21, miR-31, miR-187, and miR-211 expression was rescued through survival signaling. Additionally, CAP irradiation notably inhibited the growth of SAS OSCC cell xenografts on nude mice. The reduced expression of oncogenic miRNAs in vivo aligned with in vitro findings. In conclusion, our study provides new lines of evidence demonstrating that CAP irradiation diminishes OSCC cell viability by abrogating survival signals and oncogenic miRNA expression.

Surgical excision of eyelid tumorsand subsequent ophthalmoplastic reconstruction.

In recent years new modern therapeutic concepts have been developed in the treatment of malignant eyelid tumors; however, surgical restoration remains an important component of the therapeutic options addressed, which include microsurgical tumor excision into healthy tissue and subsequent coverage of the defects. An ophthalmic surgeon experienced in oculoplastic surgery is responsible for the recognition and evaluation of the existing alterations and planning aprocedure together with the patient that meets the patient's expectations. The planning of surgery must always be individualized and fit the initial findings. Depending on the defect size and localization, different coverage strategies are available to the surgeon. To ensure successful reconstruction, every surgeon should master awide range of reconstructive techniques.

Activatable biomimetic raspberry-like nanoplatform enabled robust cascade therapy via spatiotemporal regulation of tumor immunogenicity and immunosuppression

Smart nanomedicine capable of stimulating the immunity cycle and synchronously modulating the tumor immunosuppressive microenvironment is highly desirable for treatment of malignant solid tumor. Herein, an activable biomimetic raspberry like nanoplatform (abbreviated as RCuS@tMCP) was created for photothermal cascade immunotherapy by the spatiotemporal control of immunogenic tumor cell death (ICD) and tumor associated macrophages (TAMs) reprogramming. RCuS@tMCP was developed by conjugating the second near-infrared (NIR-II) photothermal agent copper sulfide nanoparticles (CuS NPs) as the “raspberry seeds” on the surface of biomimic CpG/protamine immunocore (denoted as tMCP) through matrix metalloproteinase-2 cleavable peptide. In the tumor microenvironment, RCuS@tMCP enzymatically unlocked the small sized RGDK peptide modified CuS NPs (ca.12 nm), which penetrated deeply and specifically to αvβ3 overexpressed tumor cells and elicited in situ ICD under NIR-II laser irradiation, thus triggering an effective antitumor immune response. Meanwhile, the remaining tMCP precisely recognized TAMs under the guidance of M2 peptide and reeducated them to tumoricidal ones, thereby boosted the power of cytotoxic T lymphocytes. By the spatiotemporal cooperation, RCuS@tMCP significantly inhibited the tumor growth of both primary and distant 4T1 tumors and prevented malignant metastasis as demonstrated both in vitro and in vivo data. This study provides an appealing and intelligent therapeutic toolbox for efficient immunological cascade therapy.

Primary malignant phyllodes tumors of the breast: A retrospective analysis from a referral center

BackgroundThe treatment for primary malignant phyllodes tumors of the breast (B-MPT) consists of wide local excision with negative margins (≥1 cm). However, because of their rarity, prognostic factors, type of surgery and adjuvant treatments are still a matter of debate. MethodsWe conducted a single-center retrospective study to describe outcomes and prognostic factors of patients with primary B-MPT, who underwent breast surgery from January 2000 to December 2021. The primary endpoint was the cumulative incidence of any recurrence. Secondary endpoints were the cumulative incidences of distant and local recurrences. Results131 patients were included, of whom all received surgery, 5 adjuvant anthracycline-based chemotherapy and 15 radiation therapy. After a median follow-up of 6.4 years, the cumulative incidences at 5-years of any, local and distant recurrences were of 26% (95% Confidence Interval [CI], 4–34%), 16% (95%CI, 10–24%) and 10% (95%CI, 5.3–16%), respectively. Tumor size ≥ 5 cm was associated with higher distant recurrences (p = 0.05); instead, among small tumors (<5 cm), distant recurrences were higher in those with heterologous differentiation and/or multifocal disease (p = 0.06). Type of breast surgery (mastectomy vs. lumpectomy/excision) was not found to be significantly associated with distant (p = 0.32) or local (p = 0.17) recurrence, even after controlling local recurrence incidence for negative pathologic prognostic factors (p = 0.17). ConclusionsThe natural history of B-MPT is burdened by local and distant recurrences. Pathologic prognostic factors (i.e., tumor size, heterologous differentiation and multifocal disease) more than the type of wide breast surgery (mastectomy vs. lumpectomy) seem to represent the most significant prognostic factor for recurrences.

The choice of treatment for chemorefractory colon cancer

Metastatic colorectal cancer (mCRC) is a major challenge in the treatment of malignant neoplasms. However, with the development of cytotoxic chemotherapy, targeted therapy and local therapies, survival rates have improved significantly. Treatment of patients with CRC in the third and subsequent lines of therapy suggests the use of regorafenib / TAS102, as well as a return to previously used chemotherapy. Late-line treatment with anti-EGFR antibodies (cetuximab, panitumumab) is the choice for mCRC as it has been shown to improve survival rates. BRAF inhibitor and an anti-EGFR antibody is effective in BRAF mutations. A feature of the HER2 / neu mutation is the requirement for dual blockade with trastuzumab + lapatinib or pertuzumab + trastuzumab. For MSI-high, anti-PD therapy (nivolumab, pembrolizumab, or nivolumab + ipilimumab combination therapy) is highly effective. Adagrasib and sotorasib have demonstrated their value in the treatment of CRC with the KRAS G12C mutation. Two inhibitors are approved for NTRK-positive colorectal cancer — larotrectinib and entrectinib. It is also worth noting that one of the local options for the treatment of mCRC is stereotactic radiation therapy. This article presents the current possibilities of therapy for chemoresistant CRC.

Biomaterials Elicit Pyroptosis Enhancing Cancer Immunotherapy

AbstractCancer immunotherapy has the potential to revolutionize the treatment of malignant tumors, but its effectiveness is limited by the low immune response rate and immune‐related adverse events. Pyroptosis, as an inflammatory programmed cell death type, triggers strong acute inflammatory response and antitumor immunity, converting “cold” tumors to “hot”. Particularly, biomaterials loading pyroptosis inducers targeting the tumor microenvironment to engineer pyroptosis, have achieved great progress in recent years. Herein, the design strategy, mechanism pathway, and role of biomaterials to induce pyroptosis in cancer immunotherapy are comprehensively reviewed. The present review focuses on the application of biomaterials‐induced pyroptosis in cancer immunotherapy, including nanogel, polymer prodrug, nanovesicle, and mesoporous material. Additionally, the synthesis of a series of stimuli‐responsive nanoplatforms, including glutathione‐responsive, pH‐responsive, reactive oxygen species‐responsive, and enzyme‐mimicking catalytic performance, is described. Meanwhile, it augments multiple immune response processes of cell uptake, antigen presentation, T‐cell activation, and expansion. Finally, the perspectives of pyroptosis‐mediated inflammation to break through the tumor vascular basement membrane barrier achieving efficient volcanic penetration of biomaterials are discussed. Artificial intelligence, multi‐omics analysis, and anthropogenic animal models of organoids are presented, aiming to provide guidance and assistance for constructing effective and controllable pyroptosis‐engineered biomaterials and improving tumor immunotherapy.

Clinical Advances and Future Directions of Oncolytic Virotherapy for Head and Neck Cancer.

Oncolytic viruses (OVs), without harming normal tissues, selectively infect and replicate within tumor cells, to release immune molecules and tumor antigens, achieving immune-mediated destruction of tumors and making them one of the most promising immunotherapies for cancer. Many clinical studies have demonstrated that OVs can provide clinical benefits for patients with different types of tumors, at various stages, including metastatic and previously untreatable cases. When OVs are used in combination with chemotherapy, radiotherapy, immunotherapy, and other treatments, they can synergistically enhance the therapeutic effects. The concept of oncolytic virotherapy (OVT) was proposed in the early 20th century. With advancements in genetic engineering, genetically modified viruses can further enhance the efficacy of cancer immunotherapy. In recent years, global research on OV treatment of malignant tumors has increased dramatically. This article comprehensively reviews the findings from relevant research and clinical trials, providing an overview of the development of OVT and its application in the clinical treatment of head and neck cancer. The aim is to offer insights for future clinical and fundamental research on OVT.

An immunotherapeutic artificial vitreous body hydrogel to control choroidal melanoma and preserve vision after vitrectomy.

Choroidal melanoma, a common intraocular malignant tumor, relies on local radiotherapy and enucleation for treatment. However, cancer recurrence and visual impairment remain important challenges. Here, a therapeutic artificial vitreous body (AVB) hydrogel based on tetra-armed poly(ethylene glycol) was developed to control the recurrence of choroidal melanoma and preserve vision after vitrectomy. AVB loaded with melphalan (Mel) and anti-programmed cell death ligand-1 (αPDL1), was injected after surgical resection in the choroidal melanoma mouse model. Afterwards, the sequentially released Mel and αPDL1 from AVB could achieve a synergistic antitumor effect to inhibit tumor recurrence. AVB with similar physical properties to native vitreous body could maintain the normal structure and visual function of eye after vitrectomy, which has been evidenced by standard examinations of ophthalmology in the mouse model. Thus, the immunotherapeutic AVB may be a promising candidate as an infill biomaterial to assist surgical treatment of intraocular malignant tumors.

Cucurbitacin B suppresses hepatocellular carcinoma progression through inducing DNA damage-dependent cell cycle arrest

BackgroundThe mortality rate of liver cancer ranks third in the world, and hepatocellular carcinoma (HCC) is a malignant tumor of the digestive tract. Cucurbitacin B (CuB), a natural compound extracted from Cucurbitaceae spp., is the main active component of Chinese patent medicine the Cucurbitacin Tablet, which has been widely used in the treatment of various malignant tumors in clinics, especially HCC. PurposeThis study explored the role and mechanism of CuB in the suppression of liver cancer progression. MethodsCell Counting Kit-8 (CCK-8) and colony formation assays were used to detect the inhibitory function of CuB in Huh7, Hep3B, and Hepa1/6 hepatoma cells. Calcein-AM/propidium iodide (PI) staining and lactate dehydrogenase (LDH) measurement assays were performed to determine cell death. Mitochondrial membrane potential (Δψm) was measured, and flow cytometry was performed to evaluate cell apoptosis and cell cycle. Several techniques, such as proteomics, Western blotting (WB), and ribonucleic acid (RNA) interference, were utilized to explore the potential mechanism. The animal experiment was performed to verify the results of in vitro experiments. ResultsCuB significantly inhibited the growth of Huh7, Hep3B, and Hepa1/6 cells and triggered the cell cycle arrest in G2/M phage without leading to cell death, especially apoptosis. Knockdown of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), a target of CuB, did not reverse CuB elicited cell cycle arrest. CuB enhanced phosphorylated ataxia telangiectasia mutated (p-ATM) and phosphorylated H2A histone family member X (γ-H2AX) levels. Moreover, CuB increased p53 and p21 levels and decreased cyclin-dependent kinase 1 (CDK1) expression, accompanied by improving phosphorylated checkpoint kinase 1 (p-CHK1) level and suppressing cell division cycle 25C (CDC25C) protein level. Interestingly, these phenomena were partly abolished by a deoxyribonucleic acid (DNA) protector methylproamine (MPA). Animal studies showed that CuB also significantly suppressed tumor growth in BALB/c mice bearing Hepa1/6 cells. In tumor tissues, CuB reduced the expression levels of proliferating cell nuclear antigen (PCNA) and γ-H2AX but did not change the terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL) level. ConclusionThis study demonstrated for the first time that CuB could effectively impede HCC progression by inducing DNA damage-dependent cell cycle arrest without directly triggering cell death, such as necrosis and apoptosis. The effect was achieved through ataxia telangiectasia mutated (ATM)-dependent p53-p21-CDK1 and checkpoint kinase 1 (CHK1)-CDC25C signaling pathways. These findings indicate that CuB may be used as an anti-HCC drug, when the current findings are confirmed by independent studies and after many more clinical phase 1, 2, 3, and 4 testings have been done.

Analysis of the clinical efficacy of laparoscopic middle pancreatectomy in the treatment of benign or low-grade malignant tumors of the pancreas.

The aim of this study was to investigate the clinical efficacy of laparoscopic middle pancreatectomy in the treatment of benign and junctional tumors of the pancreas. Retrospective analysis of basic data, tumor diameter, statistical analysis, and evaluation of efficacy-related indicators such as operative time, intraoperative bleeding, pathological findings, postoperative hospital stay, postoperative pancreatic fistula incidence, and pancreatic endocrine function was carried out on 17 patients diagnosed with benign or low-grade malignant tumors of the pancreas and laparoscopic middle pancreatic resection from January 2018 to January 2023 at the First Affiliated Hospital of Hunan Normal University. A total of 17 patients were screened. There were eight males and nine females; mean age was 42.8 ± 17.4 years (range: 15-69 years); BMI was 22.6 ± 2.5 kg/m2 (range: 18.4-27.5 kg/m2), and the tumor size was 3.4 ± 1.2cm (range: 1.5-5.5 cm). Preoperative glycan antigen CA19-9 was negative and CA125 was negative. Surgical time was 393.2 ± 57.9min; intraoperative bleeding was 211.7 ± 113.9ml; tumor diameter size was 3.4 ± 1.2cm; postoperative admission time was 19.4 ± 7.6 days; postoperative pancreatic fistula (POPF) grading was 17 cases, including nine cases of A-grade fistula, three cases of B-grade fistula, and none of C-grade fistula; postoperative pathology results were five cases of plasmacytoma, three cases of mucinous cystadenoma, four cases of SPN (solid pseudopapillary neoplasm), one case of Intraductal Papillary Mucinous Neoplasm (IPMN), three cases of pancreatic Neuroendocrine Neoplasm (pNEN), one case of inflammatory myofibroblastic osteoblastoma. All cases did not develop pancreatic origin diabetes or exacerbation of previous diabetes, and no cases presented symptoms of exocrine insufficiency such as dyspepsia and diarrhea. Laparoscopic middle pancreatectomy is safe and feasible in the treatment of benign or low-grade malignant tumors in the body of the pancreatic neck and is not accompanied by increased risk of intraoperative and postoperative complications and endocrine dysfunction of the pancreas.

Development of a Gadolinium-Boron-Conjugated Albumin for MRI-Guided Neutron Capture Therapy.

Noninvasive monitoring of boron agent biodistribution is required in advance of neutron capture therapy. In this study, we developed a gadolinium-boron-conjugated albumin (Gd-MID-BSA) for MRI-guided neutron capture therapy. Gd-MID-BSA was prepared by labeling bovine serum albumin with a maleimide-functionalized gadolinium complex and a maleimide-functionalized closo-dodecaborate orthogonally. The accumulation of Gd-MID-BSA in tumors in CT26 tumor-bearing mice reached a maximum at 24 h after the injection, as confirmed by T1-based MRI and biodistribution analysis using inductively coupled plasma optical emission spectrometry. The concentrations of boron and gadolinium in the tumors exceeded the thresholds required for boron neutron capture therapy (BNCT) and gadolinium neutron capture therapy (GdNCT), respectively. The boron concentration ratios of tumor to blood and tumor to normal tissues satisfied the clinical criteria, indicating the reduction of undesired nuclear reactions of endogenous nuclei. The molar ratio of boron to gadolinium in the tumor was close to that of Gd-MID-BSA, demonstrating that the accumulation of Gd-MID-BSA in the tumor can be evaluated by MRI. Thermal neutron irradiation with Gd-MID-BSA resulted in significant suppression of tumor growth compared to the group injected with a boron-conjugated albumin without gadolinium (MID-BSA). The neutron irradiation with Gd-MID-BSA did not cause apparent side effects. These results demonstrate that the conjugation of gadolinium and boron within the albumin molecule offers a novel strategy for enhancing the therapeutic effect of BNCT and the potential of MRI-guided neutron capture therapy as a promising treatment for malignant tumors.

MOLECULAR CELLULAR EFFECTS BY PROTON AND γ-IRRADIATION IN THE B16 MURINE MELANOMA MODEL IN VIVO

Proton and photon (γ-) radiation is widely used in modern clinical practice for the treatment of malignant tumors of various locations. The relative biological effectiveness (RBE) of accelerated protons is about 1.1, as follows from the results of experimental studies of clonogenic survival of tumor cells in vitro. But however, despite the low RBE of proton radiation, a number of clinical studies have shown a significant increase in relapse-free and overall survival of patients after proton therapy compared with that after standard radiotherapy using photon radiation. The mechanisms, on which the differences recorded in vivo are based, are of significant scientific and practical interest, but have been poorly studied.

Clinical benefits of intraoperative radiotherapy for the recurrence of centrally located hepatocellular carcinoma with microvascular invasion.

Although the efficacy and safety of intraoperative radiotherapy (IORT) in the treatment of malignant tumours, such as breast cancer, have been documented, it remains unclear whether this treatment is effective for centrally located hepatocellular carcinoma (HCC) with microvascular invasion (MVI). This study aimed to explore the efficacy and safety of IORT in the treatment of centrally located HCC with MVI. Patients with centrally located HCC, who underwent surgery between January 2016 and January 2020, were enrolled. The patient cohort was then allocated to two groups: those who underwent IORT combined with liver resection (IORT+LR); or LR alone (LR). Propensity score matching and Cox proportional hazards regression analyses were performed. The Kaplan-Meier method was used to estimate recurrence-free survival (RFS), and the log-rank test was used to determine whether RFS differed between the groups. Subgroup analysis was performed to evaluate differences in RFS and early recurrence rates in patients with different MVI grades. E-values were generated to measure the sensitivity to unmeasured confounding factors. In total, 97 patients were enrolled, 27 of whom underwent IORT+LR and 70 underwent LR alone. The 1-, 3-, and 5-year RFS rates in the IORT+LR group were 66%, 50%, and 32%, respectively, whereas those in the LR group were 54%, 37%, and 26%, respectively. After matching analysis, 23 patients were successfully matched, and RFS was found to be significantly different between the two groups (p = .04). IORT was an independent prognostic factor for RFS (hazard ratio 0.46 [95% confidence interval 0.21-0.99]). In subgroup analysis, RFS between the IORT+LR and LR groups was significantly different in patients with MVI (M1 grade) (p = .0067). The postoperative early recurrence rate was significantly reduced with IORT (p < .05). No serious complications were reported in either group following surgery. Based on E-values, the results appeared to be robust against unmeasured confounding factors. IORT+LR provided safe, feasible treatment for patients with centrally located HCC with MVI, along with an improvement in prognosis and lower early recurrence rates.

Nitrogen-doped reduced graphene oxide/black phosphorus quantum dot composites for electrocatalytic treatment of choroidal melanoma

Choroidal melanoma (CM) is a melanocyte-derived intraocular malignancy that poses a great threat to patients’ vision and life. Electrochemical therapy, which relies on the generation of reactive oxygen species via an oxygen reduction reaction (ORR) to kill target cells, has emerged as a promising approach for the local treatment of malignant tumors. In this study, nitrogen-doped reduced graphene oxide (N-rGO) was electrostatically bound with black phosphorus (BP) quantum dots to form a composite system (N-rGO-BP) for tumor therapy. Owing to the synergistic effect of the two components, the optimal catalyst (N-rGO-BP-12) exhibits improved electrochemical properties and stability, achieving a more positive half-wave potential of 0.66 V and a larger steady-state current density of 2.76 mA cm−2 compared with the N-rGO precursor. In electrochemical therapy, N-rGO-BP-12 undergoes ORR via a two-electron pathway in the acidic microenvironment of the tumor, producing large amounts of hydrogen peroxide and hydroxyl radical to kill tumor cells; only 25 % of the human CM cells survive after 3 h of the treatment. This study provides a new approach for the synthesis and application of electrochemical catalysts for clinical tumor therapy.