Tumor Recurrence Research Articles

Tellurium-Doped Bioactive Glass Induces Ferroptosis in Osteosarcoma Cells Regardless of FSP1

Human osteosarcoma (OS) is a rare tumor predominantly affecting long bones and characterized by a poor prognosis. Currently, the first line of intervention consists of the surgical resection of primary tumors combined with radiotherapy and chemotherapy, with a profound impact on the patient’s life. Since the surgical removal of OS frequently results in a large resection of bones, the use of biomaterials to sustain the stability of the remaining tissue and to stimulate bone regeneration is challenging. Moreover, residual neoplastic cells might be responsible for tumor recurrence. Here, we explored the potential of tellurium-ion-doped bioactive glass as a novel therapeutic intervention to both eradicate residual malignant cells and promote bone regeneration. Bioactive glass (BAG) has been extensively studied and employed in the field of regenerative medicine due to its osseointegration properties and ability to improve bone tissue regeneration. We found that the incorporation of tellurium (Te) in BAG selectively kills OS cells through ferroptosis while preserving the viability of hBMSCs and stimulating their osteodifferentiation. However, the mechanism of Te toxicity is still unclear: (i) Te-BAG generates lipid-ROS through LOXs activity but not iron overload; (ii) Te-dependent ferroptosis is mediated by GPX4 down-regulation; and (iii) the anti-ferroptotic activity of FSP1 is abrogated, whose expression confers the resistance of OS to the canonical induction of ferroptosis. Overall, our data show that Te-doped bioglass could represent an interesting biomaterial with both pro-ferroptotic activity towards residual cancer cells and pro-osteoregenerative activity.

Impact of Nordihydroguaiaretic Acid on Proliferation, Energy Metabolism, and Chemosensitization in Non-Small-Cell Lung Cancer (NSCLC) Cell Lines

Lung cancer (LC) is the leading cause of cancer death worldwide. LC can be classified into small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC), with the last subtype accounting for approximately 85% of all diagnosed lung cancer cases. Despite the existence of different types of treatment for this disease, the development of resistance to therapies and tumor recurrence in patients have maintained the need to find new therapeutic options to combat this pathology, where natural products stand out as an attractive source for this search. Nordihydroguaiaretic acid (NDGA) is the main metabolite extracted from the Larrea tridentata plant and has been shown to have different biological activities, including anticancer activity. In this study, H1975, H1299, and A549 cell lines were treated with NDGA, and its effect on cell viability, proliferation, and metabolism was evaluated using a resazurin reduction assay, incorporation of BrdU, and ki-67 gene expression and glucose uptake measurement, respectively. In addition, the combination of NDGA with clinical chemotherapeutics was investigated using an MTT assay and Combenefit software (version 2.02). The results showed that NDGA decreases the viability and proliferation of NSCLC cells and differentially modulates the expression of genes associated with different metabolic pathways. For example, the LDH gene expression decreased in all cell lines analyzed. However, GLUT3 gene expression increased after 24 h of treatment. The expression of the HIF-1 gene decreased early in the H1299 and A549 cell lines. In addition, the combination of NDGA with three chemotherapeutics (carboplatin, gemcitabine, and taxol) shows a synergic pattern in the decrease of cell viability on the H1299 cell line. In summary, this research provides new evidence about the role of NDGA in lung cancer. Interestingly, using NDGA to enhance the anticancer activity of antitumoral drugs could be an improved therapeutic resource against lung cancer.

Long-Term Outcomes of Minimally Invasive Endoscopic Versus Sternotomy Surgical Resection of Primary Cardiac Tumors.

Primary cardiac tumors are uncommon, often benign, but can be potentially life threatening. Minimally invasive endoscopic (ENDO) techniques have been shown to be a feasible alternative for tumor resection compared with conventional sternotomy (CS). This study compared the clinical and surgical outcomes of a small series of patients undergoing cardiac tumor resection operations. Between November 2009 and December 2022, 34 consecutive patients underwent cardiac tumor resection using either ENDO (n = 21) or CS (n = 13) techniques. We compared early perioperative outcomes, echocardiographic outcomes, and long-term clinical and tumor recurrence outcomes. Baseline characteristics were similar between groups; however, the ENDO group included younger patients (56 ± 16 vs 62 ± 17 years) and more female patients (83% vs 53%). The tumor was located in the left atrium (n = 19, 56%), right atrium (n = 5, 15%), or either ventricle (n = 4, 12%). In-hospital mortality and stroke frequency were similar for both groups (n = 0). There was no significant difference in cardiopulmonary bypass or cross-clamp times, respiratory or renal failure, or intensive care unit or hospital lengths of stay. At follow-up (ENDO, 42 [2 to 131] months vs CS, 54 [1 to 156] months), there were no deaths in the ENDO group and 2 patients died in the CS group (P = 0.21). No patients in either group experienced tumor recurrence. In selected patients, both ENDO and CS approaches to primary cardiac tumor resection were safe, effective, durable, and associated with similarly good early and late results.

Total resection via right mini-thoracotomy for left atrial myxoma in juvenile Carney complex: a case report

BackgroundCarney complex is a rare syndrome characterized by skin pigmentation, endocrine disorders, and myxomas. It is particularly notorious for its tendency to exhibit aggressive cardiac myxomas. Herein, we present a case of a juvenile female patient diagnosed with Carney complex who underwent a right lateral mini-thoracotomy.Case presentationA 13-year-old girl presented with sudden-onset left hemiplegia and dysarthria. Magnetic resonance imaging revealed multiple areas of restricted diffusion. Echocardiography identified a tumor in the left atrium, suspected to be related to Carney complex based on her medical history and physical examination findings. Surgery was performed via right lateral mini-thoracotomy, which minimized the risk of embolism and ensured a cosmetically favorable outcome. The left atrial wall defect was repaired with autologous pericardium. At 3 years postoperatively, follow-up echocardiography indicated no tumor recurrence and normal cardiac function.ConclusionsOngoing follow-ups are essential due to the aggressive nature of the Carney complex and its high recurrence rates. Right lateral mini-thoracotomy offers the advantage of avoiding re-sternotomy and minimizing adhesion dissection, making it the optimal choice for this case.

The role of surgery in recurrent local cerebral metastases: a multi-institutional retrospective analysis.

Local recurrent brain metastases are defined as lesions that recur in the brain at the same site after a previous local therapy. In patients already submitted to surgery, a second operation may be potentially challenging due to scar formation, infiltration of cerebral vessels or eloquent brain areas and local effect of previous radiotherapy. The aim of this study is to retrospectively review the results and complications of a second surgical treatment in a series of local recurrent lesions and to review the literature on this topic. 37 patients submitted to surgery for a local, histologically confirmed, recurrent brain metastases between 2000 and 2022 were retrospectively analyzed with respect to the following parameters: age, histology, anatomic location, time to recurrence, previous radiotherapy, size of recurrent tumors, preoperative and postoperative Karnofsky Performance Status(KPS) score, recursive partitioning analysis (RPA) class and graded prognostic assessment (GPA) score, surgery-related complications and the presence of further cerebral metastases. Overall survival (OS) was calculated using the Kaplan-Meier method. A multivariate Cox proportional hazard model was developed using stepwise regression (forwards selection) with predictive variables that were significant in the univariate analyses. A significant improvement of post-operative KPS status was obtained after second surgery. At multivariate analysis better results in terms of OS were achieved in patients with a pre-operative KPS ≥ 70 and in patients who had received radiotherapy after the initial surgery. No significant postoperative complications related to previous treatments were observed. Surgical resection of local recurrent brain metastases may improve patients ́ neurologic conditions allowing more time for systemic therapies to act with a low incidence of surgery-related morbidity and mortality. However, careful patient selection with a fair pre-operative clinical status seems mandatory to achieve the best post-operative results, since uniform treatment-paradigms cannot be established yet, due to the highly heterogeneous patient cohort.

Injectable Autocatalytic Hydrogel Triggers Pyroptosis to Stimulate Anticancer Immune Response for Preventing Postoperative Tumor Recurrence.

Modulating immunosuppression while eliminating residual microscopic tumors is critical for inhibiting the postoperative recurrence of triple-negative breast cancer (TNBC). Although immunotherapy has shown potential in achieving this goal, due to multiple immunosuppression and poor immunogenicity of apoptosis, a satisfactory anti-recurrence effect still faces the challenge. Herein, an injectable hydrogel-encapsulated autocatalytic copper peroxide (CP@Gel) therapeutic platform is designed and combine it with the clinical-grade DNA methyltransferase inhibitor decitabine (DAC) to effectively inhibit TNBC growth and postoperative recurrence via pyroptosis, killing residual cancer cells that bypass apoptosis resistance while also improving immunogenicity and modulating immunosuppression to achieve an intense anti-tumor immune response. Following injection of the CP@Gel, the sustained release of CP leads to the autocatalytic generation of reactive oxygen species, resulting in caspase-3 activation, and the pre-administered DAC inhibits the methylation of Gsdme to elevate the GSDME protein levels, leading to intense pyroptosis and anti-tumor immune responses. The in vivo results show a 67% elimination of local tumor recurrence via treatment with DAC+CP@Gel, suggesting the successful integration of sustained drug release with autocatalysis and epigenetic modification. The results thus suggest great potential for pyroptosis-based and injectable hydrogel-aided strategies for preventing the postoperative recurrence of TNBC.

HMGB1/TREM1 crosstalk between heat-injured hepatocytes and macrophages promotes HCC progression after RFA

PurposeTumor recurrence after radiofrequency ablation (RFA) affects the survival rate of patients and limits its clinical application. Tumor recurrence around the ablation area may be related to the thermal injury of hepatocytes (HCs) around the tumor, but the specific mechanism is still unclear.MethodsA liver cancer thermal injury mouse model was established via RFA in the C57BL/6 mice. Primary HCs and Kupffer cells (KCs) were isolated and cultured to assess their sensitivity to thermal injury via the MTT assay. Flow cytometry was used to assess macrophage polarization. Furthermore, Western blotting and co-immunoprecipitation (co-IP) were utilized to evaluate the protein expression of intracellular signaling pathway. Finally, Transwell and wound healing assays was conducted to evaluate the invasion potential of liver cancer cells.ResultsOur findings revealed that RFA-induced liver thermal injury promoted the upregulation and secretion of HMGB1 in HCs. HMGB1 had a protective effect on HCs thermal injury, potentially mediated through autophagy regulation. Heat-injured HCs release HMGB1, which activates the TREM1/JAK2/STAT3 signaling pathway in KCs, thus fostering an immunosuppressive tumor microenvironment (TME). Moreover, HMGB1 secretion by heat-injured HCs exacerbates the migration and invasion of HCC cells by influencing macrophage polarization.ConclusionRFA-induced thermal injury triggers HMGB1 release from HCs, driving macrophage M2 polarization and increasing the invasion ability of liver cancer cells. These findings reveal a potential therapeutic target for combating liver cancer recurrence following thermal ablation.

Targeting immunosenescence for improved tumor immunotherapy

AbstractTumor immunotherapy has significantly transformed the field of oncology over the past decade. An optimal tumor immunotherapy would ideally elicit robust innate and adaptive immune responses within tumor immune microenvironment (TIME). Unfortunately, immune system experiences functional decline with chronological age, a process termed “immunosenescence,” which contributes to impaired immune responses against pathogens, suboptimal vaccination outcomes, and heightened vulnerability to various diseases, including cancer. In this context, we will elucidate hallmarks and molecular mechanisms underlying immunosenescence, detailing alterations in immunosenescence at molecular, cellular, organ, and disease levels. The role of immunosenescence in tumorigenesis and senescence‐related extracellular matrix (ECM) has also been addressed. Recognizing that immunosenescence is a dynamic process influenced by various factors, we will evaluate treatment strategies targeting hallmarks and molecular mechanisms, as well as methods for immune cell, organ restoration, and present emerging approaches in immunosenescence for tumor immunotherapy. The overarching goal of immunosenescence research is to prevent tumor development, recurrence, and metastasis, ultimately improving patient prognosis. Our review aims to reveal latest advancements and prospective directions in the field of immunosenescence research, offering a theoretical basis for development of practical anti‐immunosenescence and anti‐tumor strategies.

Pituitary neuroendocrine tumors treated with stereotactic radiosurgery.

Pituitary neuroendocrine tumors (pitNETs) are benign tumors that may recur after surgical resection or persist following medical management. The objective of this study was to evaluate outcomes and toxicities of patients with pitNETs treated with stereotactic radiosurgery (SRS) at a single institution. We completed a retrospective, single-institution study of patients with pitNETs treated with frame-based, single-fraction, cobalt-60 SRS between September 2005 and June 2023. The primary endpoint was local tumor control. Secondary endpoints included endocrine control (for functional tumors), overall survival, and toxicities. A total of 88 lesions in 83 patients were treated with SRS. Most lesions (70%) were non-functional tumors. Of the 26 functioning tumors, 6 patients achieved endocrine remission with SRS alone (23%), and the remainder achieved remission with combined medical management. With a median patient follow-up of 4.7 years, no local tumor recurrences were observed with an estimated local control probability of 100%. Two- and five-year overall survival estimates were 97% (95% confidence interval [CI] 89-99) and 95% (95% CI 84-98), respectively. Causes of death were unrelated to PitNET or SRS. Twelve patients (14%) developed hypopituitarism after SRS. Despite the 34 lesions that were ≤ 3mm from optic structures, no patients developed any optic neuropathy or visual decline post SRS. SRS is a highly effective modality for recurrent or residual pitNETs. This study observed a local control of 100% with no cases of optic toxicities after a median follow-up of 4.7 years. These observed findings suggest that dose de-escalation may be possible for future treatment of pitNETs.

Engineering Docetaxel Micelles for Enhanced Cancer Therapy Through Intermolecular Forces

Docetaxel has exhibited excellent therapeutic effects in cancer treatment; however, its hydrophobicity, short blood circulation time, and high blood toxicity restrict its clinical application. The use of mPEG-PLA micelles to deliver docetaxel into the body has been verified as an effective approach to enhance its therapeutic efficacy. However, mPEG-PLA micelles are easily disassembled in the bloodstream, which can easily lead to premature drug release. To broaden the application scenarios of mPEG PLA micelles, we utilized the π–π stacking effect as an intermolecular force to design a novel mPEG-PLA-Lys(Fmoc) micelle to enhance the blood stability and permeability of drug-loaded micelles. The result showed that drug-loaded micelles for injection did not alter the tissue selectivity of docetaxel. Intravenous injection of the micelles in nude mice showed better antitumor efficacy than docetaxel injection and tumor recurrence rate is 0%, which is significantly lower than that of docetaxel injection (100%). The micelles designed by this research institute are anticipated to improve the clinical therapeutic effect of docetaxel.

Early result of minimally invasive cardiac myxoma resection at University Medical Center, Ho Chi Minh City

Objective: The study aimed to evaluate various clinical and paraclinical characteristics, as well as early surgical outcomes of minimally invasive cardiac myxoma resection at University Medical Center HCMC. Subjects and methods: This is a retrospective descriptive case series study involving all patients diagnosed with cardiac myxomas who underwent minimally invasive surgery at University Medical Center HCMC from January 2020 to June 2024. Results: There were 31 patients, consisting of 22 females and 9 males. The mean age was 56,2 ± 10,7 years old (from 37 to 77 years old). The clinical manifestations were diverse: asymptomatic (45,2%), cerebral embolism (6,4%), fatigue (29,0%), dyspnea (35,5%), palpitations (12,9%), and dizziness (12,9%). Echocardiographic results: 90,3% left atrial myxoma, 9,7% right atrial myxoma. The tumor attachment sites: interatrial septum (93,6%), left atrial wall (6,4%). The average tumor size was 36,3 ± 15,1 mm. All tumors were completely resected (100%). Additional surgical procedures: mitral valve repair (3,2%), interatrial septum repair (6,4%). Cardiopulmonary bypass time was 82,4 ± 31,1 minutes (from 49 to 199 minutes), cross - clamp time was 39,2 ± 17,6 minutes (from 18 to 85 minutes), with 3 cases not requiring cardiac arrest. Ventilation time was 13,2 ± 6,3 hours (from 6,7 to 32,4 hours), intensive care unit stay was 52,6 ± 28,1 hours (from 13 to 113,7 hours), postoperative recovery time was 6,9 ± 2,3 days (from 4 to 16 days). Early outcomes: 3 cases of atrial fibrillation with rapid ventricular response, treated medically (9,7%), 1 case of acute kidney injury (3,2%), 4 cases of pleural effusion (12,9%), 3 cases of pneumothorax (9,7%), 1 case of right external iliac artery thrombosis requiring surgical thrombectomy (3,2%), and 2 cases of deep vein thrombosis (6,4%). No surgical site infections, cerebrovascular accidents, or mortality within 30 days post-surgery were reported. Conclusion: Minimally invasive cardiac myxoma resection demonstrates a low complication rate, with no reported tumor recurrence or early postoperative mortality. This technique offers a safe and effective alternative to traditional median sternotomy and may be gradually adopted and implemented in lower - level healthcare facilities.

Response to furmonertinib in a patient with non-small cell lung cancer harboring HER2 exon 21 insertion mutation: a case report

BackgroundThis is the first case report describing a patient with non-small cell lung cancer (NSCLC) harboring two rare human epidermal growth factor receptor 2 (HER2) exon 21 insertion mutations, who responded to furmonertinib treatment. Furmonertinib maybe one effective and economical treatment for NSCLC patients harboring HER2 mutations with minor side effects.Case descriptionWe present a case report of a 49-year-old female diagnosed with stage IV lung adenocarcinoma who complained of irritating dry cough symptoms followed by chest tightness. Firstly, we describe the patient’s treatment history, including failed third-line combination treatments of systemic chemotherapy with bevacizumab or carrelizumab or anlotinib, primary lung tumor recurrence, bilateral lung metastases progression, and new brain metastatic lesion detection. Next, we detail the patient’s fourth-line treatment with radiotherapy for brain metastases and two cycles of bevacizumab plus Abraxane and cisplatin, however, the disease progressed and relapsed. After that, comprehensive genomic profiling revealed two HER2 exon 21 insertion mutations. Subsequently, the patient received targeted therapy with furmonertinib and achieved 11 months of progression-free survival. The patient received pyrrotinib therapy for 2 months after disease progression, but the disease continued to progress. In October 2023, the patient received therapy with furmonertinib again, and a month later, the disease went into partial remission. However, the patient died due to hypoproteinemia combined with severe pneumonia in December 2023.ConclusionFurmonertinib may be effective for NSCLC patients with HER2 T8962A and L869R mutations and further studies are needed to confirm these results in prospective clinical trials.

Spleen-Targeted mRNA Vaccine Doped with Manganese Adjuvant for Robust Anticancer Immunity In Vivo.

The successful application of mRNA vaccines in preventing and treating infectious diseases highlights their potential as therapeutic vaccines for cancer treatment. However, unlike infectious diseases, effective antitumor therapy, particularly for solid tumors, necessitates the activation of more powerful cellular and humoral immunity to achieve clinical efficacy. Here, we report a spleen-targeted mRNA vaccine (Mn@mRNA-LNP) designed to deliver tumor antigen-encoding mRNA and manganese adjuvant (Mn2+) simultaneously to dendritic cells (DCs) in the spleen. This delivery system promotes DC maturation and surface antigen presentation and stimulates the production of cytotoxic T cells. Additionally, Mn2+ codelivered in the system serves as a safe and effective immune adjuvant, activating the stimulator of interferon genes (STING) signaling pathway and promoting the secretion of type I interferon, further enhancing the antigen-specific T cell responses. Mn@mRNA-LNP effectively inhibits tumor progression in established melanoma and colon tumor models as well as in a model of tumor recurrence after resection. Notably, the combination of Mn@mRNA-LNP with immune checkpoint inhibitors further enhances complete tumor suppression and prolonged the overall survival in mice. Overall, this "All-in-One" mRNA vaccine significantly boosts antitumor immunity responses by improving spleen targeting and immune activation, providing an attractive strategy for the future clinical translation of therapeutic mRNA vaccines.

Feasibility analysis of using patient-derived tumour organoids for treatment decision guidance in locally advanced head and neck squamous cell carcinoma

BackgroundCurrent treatment for head and neck squamous cell carcinoma (HNSCC) involves surgery, radiotherapy, and chemotherapy. Despite aggressive multimodal approaches, tumour recurrence occurs in 40–60 % of cases, leading to poor survival outcomes. HNSCC lacks common genetic drivers for tailored therapies, and reliable biomarkers for treatment selection are scarce. We investigated the procedural requirements for incorporating drug- and radiosensitivity screens in patient-derived organoids (PDOs) within a clinical trial framework. Patients and methodsFresh tumour samples (N = 198) from 186 HNSCC patients were included. Success rates of organoid establishment were correlated with clinical and procedural parameters. Timelines for establishment of PDO cultures were determined, and their long-term growth potential assessed by serial passaging. Additionally, we conducted whole exome sequencing on matched tumour-organoid pairs. Three PDO models were employed to establish radiosensitivity assays. ResultsIn total, PDO models displaying histomorphological features and genomic alterations of parental tumours were successfully established for 35 % of patient tumours. Success rates rose to 77 % for samples with a tumour cell content of 30 % or higher. Advanced patient age, prior radiotherapy, and delays in tissue processing were identified as negative predictors for engraftment. The estimated time interval needed for screens was compatible with PDO-guided selection of curative-intent radiotherapy regimens. ConclusionsOur findings suggest that with high-quality samples and efficient tissue processing, PDO screens can be successfully performed in 77 % of HNSCC patients. Given the procedural challenges involved, future clinical trials aiming to the utility of PDOs for guiding treatment decisions should consider implementing centralised PDO screening.

Primary orbital and adnexal rhabdomyosarcoma: a study of 54 Asian Indian patients

ABSTRACT Purpose To describe the clinical presentation, management, and outcomes of orbital and adnexal rhabdomyosarcoma (RMS) in an Asian-Indian cohort and analyze the factors predictive of outcomes. Methods Retrospective interventional case series of 54 patients of histopathology-proven RMS Results The mean age of presentation with RMS was 10 years (median, 7 years; range, <1–54 years). The most common tumor location was the superonasal quadrant (n = 21, 39%). Extensions beyond the orbit into the sinuses, temporal fossa, and brain were seen in 15 (28%), 3 (6%), and 8 (15%), respectively. First-line treatment modalities included a combination of surgical debulking, chemotherapy, and external beam radiotherapy in 20 (37%) patients; chemotherapy and radiation in 20 (37%); complete surgical excision and chemotherapy in 3 (6%); orbital exenteration, chemotherapy, and external beam radiotherapy in 1 (2%); chemotherapy alone in 1 (2%) patient, and 9 (17%) patients were lost to follow up. By Intergroup Rhabdomyosarcoma Study Group (IRSG) grouping, tumors belonged to groups I (n = 2,4%), II (n = 13, 29%), and III (n = 30, 67%). Kaplan-Meier survival estimates for tumor recurrence, lymph node metastasis, systemic metastasis, and death (n = 45) were 84%, 82%, 95%, and 95% at 1 year, 69%, 76%, 81%, and 77% at 5 years, 69%, 76%, 81%, and 77% at 10 years, respectively. On multivariate regression, age >18 years was found to have a significantly increased risk of locoregional LN metastasis (p = 0.005). Conclusion Despite aggressive treatment modalities, the 5–year disease-specific survival rate was 77% in Asian-Indian cohort. Age > 18 years at presentation was associated with a poorer prognosis.

Polydopamine Nanoformulations Induced ICD and M1 Phenotype Macrophage Polarization for Enhanced TNBC Synergistic Photothermal Immunotherapy.

Photothermal therapy (PTT) is a promising technology that can achieve the thermal ablation of tumors and induce immunogenic cell death (ICD). However, relying solely on the antitumor immune responses caused by PTT-induced ICD is insufficient to suppress tumor metastasis and recurrence effectively. Fortunately, multifunctional nanoformulation-based synergistic photothermal immunotherapy can eliminate primary and metastatic tumors and inhibit tumor recurrence for a long time. Herein, we select polydopamine (PDA) nanoparticles to serve as the carrier for our nanomedicine as well as a potent photothermal agent and modulator of macrophage polarization. PDA nanoparticles are loaded with the insoluble immune adjuvant Imiquimod (R837) to construct PDA(R837) nanoformulations. These straightforward yet highly effective nanoformulations demonstrate excellent performance, allowing for successful triple-negative breast cancer (TNBC) treatment through synergistic photothermal immunotherapy. Moreover, experimental results showed that PDA(R837) implementation of PTT is effective in the thermal ablation of primary tumors while causing ICD and releasing R837, further promoting dendritic cell (DC) maturation and activating the systemic antitumor immune response. Furthermore, PDA(R837) nanoformulations inhibit tumor metastasis and recurrence and achieve M1 phenotype macrophage polarization, achieving long-term and excellent antitumor efficacy. Therefore, the structurally simple PDA(R837) nanoformulations provide cancer treatment and have excellent clinical translational application prospects.

Multifunctional Nanocomposite Hydrogel with Enhanced Chemodynamic Therapy and Starvation Therapy for Inhibiting Postoperative Tumor Recurrence

Surgical resection is the primary treatment for melanoma; however, preventing tumor recurrence after resection remains a significant clinical challenge. To address this, we developed a multifunctional nanocomposite hydrogel (H-CPG) composed of glucose oxidase (GOx)-coated CuS@PDA@GOx (CPG) nanoparticles, aminated hyaluronic acid (HA-ADH), and oxidized rhizomatous polysaccharides (OBSP), which are interconnected through hydrogen bonds and dynamic Schiff base linkages. In the acidic tumor micro-environment, the hydrogel releases GOx, catalyzing the production of hydrogen peroxide (H2O2), which enhances chemokinetic activity through a Cu2+-mediated Fenton-like reaction. This process generates hydroxyl radicals that intensify oxidative stress and promote macrophage polarization from the M2 to M1 phenotype. This polarization triggers the release of pro-inflammatory cytokines, thereby inhibiting tumor recurrence. Additionally, the hydrogel induces photothermal effects that help eradicate residual bacteria at the wound site. Overall, the H-CPG hydrogel offers a dual mechanism to prevent melanoma recurrence and reduce resistance to monotherapy, presenting a promising strategy for postoperative tumor management.

HBcrAg is associated with prognosis of hepatitis B virus-related hepatocellular carcinoma in patients after hepatectomy undergoing antiviral therapy.

Serum hepatitis B core-related antigen (HBcrAg) is considered a surrogate marker of the amount and activity of intrahepatic covalently closed circular DNA. This study aimed to explore the prognostic value of HBcrAg on patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative hepatectomy undergoing antiviral therapy (AVT). Data of 949 consecutive patients with HBV-related HCC undergoing curative resection between 2010 and 2013 were reviewed. Serum HBcrAg levels were measured at surgery (baseline) for all patients and at the time of 2 years postoperatively (on-treatment) for those without recurrence. Primary endpoint was tumor recurrence. High HBcrAg levels are associated with malignant phenotypes. HBcrAg independently affected both recurrence and overall survival (OS) in patients with negative hepatitis B e antigen (HBeAg-, p = .007 and p = .042, respectively) but not in their positive HBeAg (HBeAg+) counterparts (p = .100 and p = .075, respectively). Patients with high baseline HBcrAg had higher late, but not early recurrence rates than those with low baseline HBcrAg levels, regardless of HBeAg status (HBeAg+: p = .307 for early, p = .001 for late; HBeAg-: p = .937 for early, p < .001 for late). On-treatment HBcrAg independently affected late recurrence in patients stratified by both cirrhosis and HBeAg (p < .001 for all). The predictive power of HBcrAg kinetics for late recurrence was better than that of the baseline and on-treatment HBcrAg. High HBcrAg levels during long-term AVT are associated with late recurrence of HCC after hepatectomy. Combining baseline and on-treatment HBcrAg might be valuable in identifying patients at a high risk of relapse and stratifying surveillance strategies postoperatively.

A rare case of trapezium osteochondroma: unveiling a unique tumour with clinical implications

Osteochondroma is a benign bone tumour commonly found on the metaphysis of long bones. The presentation of osteochondroma on the trapezoid bone, a carpal bone in the wrist, is exceptionally rare. To our knowledge, no such cases have been reported in India. This report details a rare case of osteochondroma located on the trapezoid bone and its successful surgical management. A 55-year-old female presented with pain and swelling in the wrist. Radiological imaging, including X-rays and MRI, revealed a well-defined, pedunculated mass arising from the trapezoid bone. The patient underwent surgical resection of the tumour. Histopathological examination confirmed the diagnosis of osteochondroma. Postoperatively, the patient experienced significant relief from symptoms and showed no evidence of tumour recurrence during follow-up. This case contributes to the limited body of literature on osteochondromas in rare locations, particularly on the trapezoid bone. It illustrates the successful outcome of surgical treatment for rare bone tumours and emphasizes the need for heightened awareness and comprehensive diagnostic approaches in similar cases.

Combined analysis of a serum mRNA/miRNA marker signature and CA 19-9 for timely and accurate diagnosis of recurrence after resection of pancreatic ductal adenocarcinoma: A prospective multicenter cohort study.

Timely and accurate detection of tumor recurrence in pancreatic ductal adenocarcinoma (PDAC) patients is an urgent and unmet medical need. This study aimed to develop a noninvasive molecular diagnostic procedure for the detection of recurrence after PDAC resection based on quantification of circulating mRNA and miRNA biomarkers in serum samples. In a multicentric study, serum samples from a total of 146 patients were prospectively collected after resection. Samples were classified into a "No Evidence of Disease" and a "Recurrence" group based on clinical follow-up data. A multianalyte biomarker panel was composed of mRNAs and miRNA markers and simultaneously analyzed in serum samples using custom microfluidic qPCR arrays (TaqMan array cards). A diagnostic algorithm was developed combining a 7-gene marker signature with CA19-9 data. The best-performing marker combination achieved 90% diagnostic accuracy in predicting the presence of tumor recurrence (98% sensitivity; 84% specificity), clearly outperforming the singular CA 19-9 analysis. Moreover, time series data obtained by analyzing successively collected samples from 5 patients during extended follow-up suggested that molecular diagnosis has the potential to detect recurrence earlier than routine clinical procedures. TaqMan array card measurements were found to be biologically valid and technically reproducible. The BioPac multianalyte marker panel is capable of sensitive and accurate detection of recurrence in patients resected for PDAC using a simple blood test. This could allow a closer follow-up using shorter time intervals than currently used for imaging, thus potentially prompting an earlier work-up with additional modalities to allow for earlier therapeutic intervention. This study provides a promising approach for improved postoperative monitoring of resected PDAC patients, which is an urgent and unmet clinical need.