Tumor Recurrence Research Articles

The application of nano-hydrid hydrogels in post-surgical tumor recurrence

Surgical resection is one of the main methods for treating solid tumors, but incomplete removal of tumor cells after surgery often leads to tumor recurrence and metastasis. At the same time, the wounds formed during open surgery are susceptible to bacterial infections due to exposure. Therefore, there is an urgent need for an effective method that can be applied to postoperative wounds to suppress tumor recurrence. Hydrogels, as a three-dimensional network crosslinked material with good biocompatibility, possess excellent drug-loading capabilities. Smart hydrogels can respond to stimuli and control drug release through structural changes, promoting wound healing. Integrating tumor therapy with hydrogels can further achieve the clearance of in situ cancer cells and the inhibition of distant cancer recurrence. This article introduces the composition and characteristics of anti-tumor smart hydrogels, their application in drug delivery, and analyzes strategies to suppress tumor recurrence. With in-depth research on nano-hydrogels, it is believed that this platform is poised to significantly contribute to the prevention of tumor recurrence following surgical procedures

Cardiotoxicity as important differential diagnosis for reduced myocardial blood flow during Rubidium cardiac PET/CT : Cardiotoxicity in Rubidium PET/CT.

A 65-year-old woman with a history of ductal mammary carcinoma and recent autonomic dysfunction underwent a Rb-82 chloride (RbCl) cardiac PET/CT scan that showed no ischemia or scarring, but significantly reduced myocardial flow reserve (MFR) (global: 1.5) and a CAC-Score of 0. The patient's chemotherapy history (paclitaxel, carboplatin, epirubicin, pembrolizumab 2 years before) with elevated Troponin T and NT-pro-BNP levels at that time, and now reduced MFR with 0 CAC suggests cancer-therapy-related cardiotoxicity. An important differential diagnosis to the more common CAD-associated microvascular disease. Furthermore, tumor recurrence with a PET-avid lymph node metastasis was found additionally.

Recurrence-free survival after hepatectomy using propofol-based total intravenous anaesthesia and sevoflurane-based inhalational anaesthesia: a randomised controlled study.

While evidence from preclinical and observational cohort studies have suggested potential disparities in tumour behaviour associated with the choice of intra-operative anaesthetics, clinical evidence of tumour recurrence and metastasis remains inconclusive. We aimed to compare the impact of intra-operative anaesthesia on oncologic outcomes following hepatectomy for hepatocellular carcinoma. Adult patients scheduled for elective hepatectomy for hepatocellular carcinoma were assigned randomly (1:1) to either propofol-based total intravenous anaesthesia or sevoflurane-based inhalational anaesthesia. For recurrence-free survival, overall survival, intrahepatic recurrence-free survival and extrahepatic recurrence-free survival, the survival curves of the two groups were estimated using the Kaplan-Meier method and compared with the log-rank test. The primary outcome was one-year recurrence-free survival. Among the 536 patients enrolled, primary analysis comprised 228 and 226 patients in the total intravenous anaesthesia and sevoflurane-based inhalational anaesthesia groups, respectively. The probability of recurrence-free survival at one year was 79.1% (47 events) and 77.7% (50 events) in the total intravenous anaesthesia and sevoflurane-based inhalational anaesthesia groups, respectively (adjusted hazard ratio 1.04, 95%CI 0.72-1.52). The probability of intrahepatic and extrahepatic recurrence-free survival, as well as overall survival at one year, was not significantly different between total intravenous anaesthesia and sevoflurane-based inhalational anaesthesia: 81.3% (42 events) vs. 81.7% (41 events); 91.5% (19 events) vs. 88.8% (25 events); 99.1% (2 events) vs. 100.0% (no event), respectively. Subgroup analyses revealed that in patients undergoing open hepatectomy, total intravenous anaesthesia was associated with a significantly lower hazard of tumour recurrence or death (hazard ratio 0.49, 95%CI 0.25-0.95, p = 0.034), while in patients undergoing laparoscopic surgery, no significant difference was observed (hazard ratio 1.14, 95%CI 0.73-1.80, p = 0.558). Intra-operative anaesthesia technique did not affect postoperative recurrence and overall survival in patients with hepatocellular carcinoma undergoing hepatectomy.

Transplant oncology and anti-cancer immunosuppressants.

Organ transplantation is a life-saving intervention that enhances the quality of life for patients with end-stage organ failure. However, long-term immunosuppressive therapy is required to prevent allogeneic graft rejection, which inadvertently elevates the risk of post-transplant malignancies, especially for liver transplant recipients with a prior history of liver cancer. In response, the emerging field of transplant oncology integrates principles from oncology and immunology to improve outcomes for patients at high risk of tumor occurrence or recurrence following transplantation. Therefore, it is of substantial clinical significance to develop immunosuppressants that possess both immunosuppressive and anti-tumor properties. For instance, mTOR inhibitors demonstrate anti-tumor effects among antimetabolite immunosuppressive drugs, and recent studies indicate that capecitabine, an antimetabolite chemotherapeutic, may also exhibit immunosuppressive activity in the clinic for liver transplants suffering from hepatocellular carcinoma. This review systematically explores potential immunosuppressants with dual anti-tumor and immunosuppressive effects to support the management of transplant patients at elevated risk of tumor occurrence or recurrence.

An Advanced Multivalent Ligand-Decorated Microsphere Enrichment System Efficiently Captures Circulating Tumor Cells In Vivo.

Capturing circulating tumor cells (CTCs) in vivo from the bloodstream lessens tumor metastasis and recurrence risks. However, the absence of CTC receptors due to epithelial-mesenchymal transition (EMT), the limited binding capacity of a single ligand, and the complexity of the blood flow environment significantly reduce the efficiency of CTC capture in vivo. Herein, a multivalent ligand-decorated microsphere enrichment system (MLMES) is crafted that incorporates a capture column replete with an immunosorbent that precisely recognizes and binds the stably expressed cluster of differentiation 44 (CD44) and glucose transporter protein 1 (GLUT1) receptors present on the exterior of CTCs. As peripheral blood flows through the column, CTCs are efficiently captured, achieving an in vivo capture rate of up to 64.2%, the highest reported to date. Moreover, the MLMES demonstrates excellent biocompatibility, broad-spectrum tumor cells capture, and storage stability. Importantly, it significantly eliminates a substantial quantity of CTCs from peripheral blood, reducing the risk of metastasis. This breakthrough method has broad clinical application potential in preventing tumor metastasis and recurrence, bringing new possibilities for improving cancer treatment.

A novel oncolytic Vaccinia virus armed with IL-12 augments antitumor immune responses leading to durable regression in murine models of lung cancer.

Oncolytic vaccinia viruses (VVs) are potent stimulators of the immune system and induce immune-mediated tumor clearance and long-term surveillance against tumor recurrence. As such they are ideal treatment modalities for solid tumors including lung cancer. Here, we investigated the use of VVL-m12, a next-generation, genetically modified, interleukin-12 (IL-12)-armed VV, as a new therapeutic strategy to treat murine models of lung cancer and as a mechanism of increasing lung cancer sensitivity to antibody against programmed cell death protein 1 (α-PD1) therapy. The cytotoxicity and replication of VVL-m12, VVL-h12 and control VVs were assessed in lung cancer cell lines. Subcutaneous lung cancer mouse models were established to investigate the anti-tumor activity of the viruses after intratumoral delivery in an immunocompetent disease model. Synergy with α-PD1 or a VV armed with soluble PD-1 (VV-sPD1) was investigated and functional mechanisms behind efficacy probed. Tumor-targeted VVL-m12 replicated to high levels, was cytotoxic in lung cancer cell lines. VVL-m12 demonstrated superior antitumor efficacy in subcutaneous lung cancer models compared with other VVs examined. Importantly, rational combination of VVL-m12 and PD-1 blockade worked synergistically to significantly enhance survival of animals and safely cured lung cancer with no evidence of recurrence. VVL-m12 therapy induced increased intratumoral infiltration of CD4+ and CD8+ T cells and was able to clear tumor at early time points via increased induction and infiltration of effector T cells and central memory T cells (TCM). In addition, VVL-m12 increased dendritic cell activation, induced polarization of M2 macrophages towards an M1 phenotype, and inhibited tumor angiogenesis in vivo. These results demonstrate that VVL-12 has strong potential as a safe and effective antitumor therapeutic for lung cancer. Importantly, VVL-12 can sensitize lung cancers to α-PD1 antibody therapy, and the combined regime creates a highly effective treatment option for patients.

Real-world experience with TTFields in glioma patients with emphasis on therapy usage.

Tumor Treating Fields (TTFields) has emerged as a significant adjunctive component in the treatment of high-grade gliomas following the EF-14 trial in 2017. The incorporation of TTFields, alongside cyclic temozolomide therapy, has demonstrated improved patient outcomes when the usage exceeds 18 h per day (75% usage). Post-hoc analysis of the EF-14 trial has demonstrated that therapy usage exceeding 90% is associated with an additional benefit, while rates above 50% have also proven effective in literature. Given the cost-intensive nature and mild- to- moderate constraints associated with the therapy, our objective is to generate real-world data on therapy usage through a retrospective analysis at a high-throughput academic center. Between June 2015 and February 2022, a total of 113 high-grade glioma patients received TTFields therapy. Eight patients discontinued TTFields therapy within 2 months with less than 50% usage and were excluded from further analysis. For the remaining patients, the median age was 51 years (range: 20-76 years) and the mean preoperative Karnofsky index was 80%-90%. Most of the patients (75.2%) initiated therapy concurrently with first-line treatment, of whom 27.6% started TTFields therapy concomitant to the first cycle of temozolomide. 15.2% started TTFields therapy in the second-line and 9.5% in the third-line setting. The study cohort had an average therapy duration of 9.3 months with 3.2 break days per month. The mean therapy usage was 65.5% (SD 17.6%). Usage was highest during the first 3 months, with rates of 77.7%, 72.3%, and 71.6%, and then dropped to around 60% in the following 6 months. Linear regression found no predictors of usage, such as age, timing of therapy initiation, and duration or gender. 55% of patients continued TTFields beyond the first recurrence. Interestingly, no drop in usage rates was observed before tumor recurrence was communicated. However, after diagnosis, patients exhibited a significant drop in usage to an average of 52.3%. This high-volume, real-world TTFields usage data reveal that the extent of usage falls short of the intended 75%. It highlights the importance of monitoring and promoting adherence to maximize its potential benefits in managing high-grade glioma patients. Furthermore, strategies to expedite therapy initiation and improve long-term adherence are warranted.

Evaluation of pharyngeal and laryngeal squamous cell carcinoma after neoadjuvant immunochemotherapy by narrow band imaging

Objective: To investigate the changes in the narrow band imaging (NBI) phenotypes of oropharyngeal, hypopharyngeal, and laryngeal squamous cell carcinoma after neoadjuvant immunochemotherapy, and to explore the clinical value of NBI endoscopy in re-evaluation and follow-up of pharyngeal and laryngeal squamous cell carcinoma after neoadjuvant immunochemotherapy. Methods: Twenty-nine patients diagnosed with locally advanced pharyngeal or laryngeal squamous cell carcinoma in the First Affiliated Hospital of Xiamen University from November 2021 to January 2024 and receiving 2 cycles of neoadjuvant immunochemotherapy were selected, including 26 males and 3 females, aged 43-80 years. Regular NBI and white light (WL) endoscopy examinations, as well as imaging examinations such as CT scans, were performed. After the neoadjuvant immunochemotherapy, 36 specimens from suspected lesions of the pharynx or the larynx were obtained through surgical resection. The NBI findings of the pharyngeal or laryngeal lesions and their relationships with corresponding pathological and imaging results were analyzed with kappa test, Pearson correlation analysis, McNemar test, and Wilcoxon Signed Rank Test. Results: After neoadjuvant immunochemotherapy, primary lesions showed pathological complete response (pCR) in 9 cases, partial response (PR) in 19 cases, and progressive disease (PD) in one case. The NBI phenotypes of pharyngeal and laryngeal malignant tumors after treatment showed high consistency (kappa=0.818, P<0.01) and significant correlations (r=0.852, P<0.01) with their pathological results. WL endoscopic examinations showed inconsistency (kappa=0.239, P=0.12) with their pathological results. NBI endoscopy was more effective in identifying benign lesions after treatment than WL endoscopy (P=0.031). In cases of both PR and pCR of the primary lesion, there were significant differences in NBI phenotypes before and after neoadjuvant immunochemotherapy (all P<0.05), with phenotypes transitioning to lower malignancy and benign lesions, respectively. Among 19 cases with PR, 16 showed concentric/eccentric regression, and 3 showed multipoint focal regression. NBI endoscopy was more accurate in diagnosing benign or malignant lesions, pCR or PR after treatment compared to CT (all P<0.05). Conclusions: The present NBI microvascular classification of the pharyngeal and laryngeal lesions is still applicable for the diagnosis and evaluation in pharyngeal and laryngeal squamous cell carcinoma after neoadjuvant immunochemotherapy. The changes in NBI phenotypes and ranges can indicate tumor regression, progression, and recurrence. NBI is more accurate in diagnosing pharyngeal and laryngeal squamous cell carcinoma after neoadjuvant immunochemotherapy compared to WL endoscopy and imaging examinations such as CT.

Intracerebroventricular B7-H3-targeting CAR T cells for diffuse intrinsic pontine glioma: a phase 1 trial.

Diffuse intrinsic pontine glioma (DIPG) is a fatal central nervous system (CNS) tumor that confers a median survival of 11 months. As B7-H3 is expressed on pediatric CNS tumors, we conducted BrainChild-03, a single-center, dose-escalation phase 1 clinical trial of repetitive intracerebroventricular (ICV) dosing of B7-H3-targeting chimeric antigen receptor T cells (B7-H3 CAR T cells) for children with recurrent or refractory CNS tumors and DIPG. Here we report results from Arm C, restricted to patients with DIPG. The primary objectives were to assess feasibility and tolerability, which were both met. Secondary objectives included assessments of CAR T cell distribution and survival. A total of 23 patients with DIPG enrolled, and 21 were treated with repeated doses of ICV B7-H3 CAR T cells using intra-patient dose-escalation regimens without previous lymphodepletion. Concurrent tumor-directed therapy, including re-irradiation, was not allowed while on protocol therapy. We delivered a total of 253 ICV doses and established the highest planned dose regimen, DR4, which escalated up to 10 × 107 cells per dose, as the maximally tolerated dose regimen. Common adverse events included headache, fatigue and fever. There was one dose-limiting toxicity (intratumoral hemorrhage) during DR2. For all treated patients (n = 21), the median survival from their initial CAR T cell infusion was 10.7 months and the median survival from diagnosis was 19.8 months with 3 patients still alive at 44, 45 and 52 months from diagnosis. Ultimately, this completed first-in-human trial shows that repetitive ICV dosing of B7-H3 CAR T cells in pediatric and young adult patients with DIPG is tolerable, including multiyear repeated dosing, and may have clinical efficacy that warrants further investigation on a multisite phase 2 trial. ClinicalTrials.gov registration: NCT04185038 .

HIFU-CCL19/21 Axis Enhances Dendritic Cell Vaccine Efficacy in the Tumor Microenvironment.

Effectively targeting treatment-resistant tumor cells, particularly cancer stem cells (CSCs) involved in tumor recurrence, remains a major challenge in immunotherapy. This study examines the potential of combining mechanical high-intensity focused ultrasound (M-HIFU) with dendritic cell (DC) vaccines to enhance immune responses against OLFM4-expressing tumors, a CSC marker linked to immune evasion and tumor growth. M-HIFU was applied to induce immunogenic cell death by mechanically disrupting tumor cells, releasing tumor-associated antigens and creating an immunostimulatory environment. DC vaccines loaded with OLFM4 were then administered to boost the immune response within this primed environment. The combination of M-HIFU and DC vaccine significantly inhibited tumor growth and metastasis, with enhanced T-cell activation and increased recruitment of immune cells due to elevated chemokines CCL19 and CCL21. This synergy promoted immune memory, reducing the likelihood of recurrence. M-HIFU effectively promotes the migration of DC vaccines through CCL19/21, presenting a promising approach for cancer treatment. Further studies are recommended to optimize this combination for clinical applications, with potential to improve patient outcomes in challenging cancer types.

Fe/Mo‐Based Lipid Peroxidation Nanoamplifier Combined with Adenosine Immunometabolism Regulation to Augment Anti‐Breast Cancer Immunity

AbstractImmunogenic cell death (ICD)‐mediated immunization strategies have great potential against breast cancer. However, traditional strategies neglect the increase in the immunosuppressive metabolite, adenosine (ADO), during ICD, leading to insufficient therapeutic outcomes. In this study, it is found that the adenosine A2A receptor (A2AR) is significantly expressed in breast cancer and positively associated with regulatory T (Treg) cells. Herein, a strategy combining Fe/Mo‐based lipid peroxidation (LPO) nanoamplifiers and A2AR blockade is reported to maximize ICD‐mediated anti‐tumor immunity. This LPO nanoamplifier causes LPO explosion by the Fe (II)‐mediated Fenton reaction and Mo(V)‐mediated Russell mechanism. Subsequently, it elicits the ICD magnification of tumor cells by inducing multiple regulated cell death patterns of ferroptosis, apoptosis, and necroptosis. Additionally, the A2AR antagonist (SCH58261), an immunometabolic checkpoint blocker, is found to relieve ADO‐related immunosuppression, amplify anti‐tumor immunological effects, and elicit immune memory responses. This robust anti‐tumor immunity is observed in primary, distant, pulmonary metastatic, and recurrent tumors. This study provides a novel strategy for optimizing ICD‐mediated immunotherapy and highlights the benefits of combining LPO explosion with A2AR blockade to enhance breast cancer immunotherapy.

In Vitro Investigation of the Anti-Hepatocellular Carcinoma Activity of Peptides Derived From Quinoa (Chenopodium quinoa Willd) Bran.

Hepatocellular carcinoma (HCC) is the most common and highly aggressive tumor in the world. Although immunotherapy, surgical resection, targeted therapy and HCC transplantation could improve the prognosis for HCC patients, the tumor recurrence rate of the tumor remains high due to its insidious and invasive nature. Therefore, the development of new HCC therapeutic agents has become particularly important. Quinoa is abundant in bioactive peptides, proteins, and other functional ingredients that confer various health benefits to humans. Quinoa bran, the outer seed coat of quinoa, like quinoa, has extremely high nutritional value and rich protein content. This study firstly found that hydrolysate from quinoa bran protein (QBPP) exhibited targeting anti-HCC effect on the proliferation of HepG2 and Bel-7402 HCC cells in a concentration dependent manner, without significant toxic side effects on normal human liver cells L02. Further, QBPP exerted anti-HCC effect through mitochondria-mediated apoptosis and inhibition of HCC cells migration. Collectively, QBPP shows potential as a next-generation dietary supplement for the prevention and treatment of HCC.

Glutathione-Responsive Metal-Organic-Framework-Derived MnxOy/(A/R)TiO2 Nanoparticles for Enhanced Synergistic Sonodynamic/Chemodynamic/Immunotherapy.

Despite the potential of sonodynamic therapy (SDT) in treating malignant tumors, the lack of effective sonosensitizers has limited its clinical implementation. In this study, we explored the relationship between the heteroatom doping concentration in metal-organic frameworks and interface formation after pyrolysis by regulating the addition of manganese sources and successfully derived Z-scheme heterojunctions MnxOy/(A/R)TiO2 (MTO) in situ from MIL-125-NH2 (Ti/Mn). The electron transfer pathway introduced by interfacial contact promoted carrier separation and greatly preserved the effective redox components, significantly influencing the performance of reactive oxygen species generation. Upon reaching the tumor sites, MTO effectively depleted glutathione to alleviate the suppressive tumor environment, and the heterojunctions and MnxOy in MTO facilitated SDT and synergistic chemodynamic therapy (CDT), respectively, leading to enhanced immunogenic cell death (ICD). Furthermore, Mn2+ uptake by dendritic cells (DCs) and the tumor-associated antigens released due to ICD activated the stimulator of interferon genes pathway, which elicited a robust tumor-specific immune response by driving the maturation of DCs and the activation of T cells. In addition, the activated T cells secreted high levels of interferon-γ to enhance Mn3+/Mn2+-mediated ferroptosis in metastatic tumor cells. The combination of MTO-mediated synergistic therapy and PD-L1 checkpoint blockade exhibited vaccine-like functions, inducing stronger systemic immunity and durable immune memory to inhibit tumor progression, metastasis, and recurrence. To summarize, we synthesized a self-enhancing nanoplatform for synergistic SDT/CDT/immunotherapy using multifunctional MOF-derived Z-scheme heterojunctions. This study provides an experimental basis for amplifying the potential of sonosensitizers while optimizing SDT-mediated systemic immunity while avoiding interference caused by additional adjuvants.

GM-CSF and IL-21-armed oncolytic vaccinia virus significantly enhances anti-tumor activity and synergizes with anti-PD1 immunotherapy in pancreatic cancer.

Pancreatic cancer is one of the most aggressive cancers and poses significant challenges to current therapies because of its complex immunosuppressive tumor microenvironment (TME). Oncolytic viruses armed with immunoregulatory molecules are promising strategies to overcome limited efficacy and target inaccessible and metastatic tumors. In this study, we constructed a tumor-selective vaccinia virus (VV) with deletions of the TK and A49 genes (VVLΔTKΔA49, VVL-DD) using CRISPR-Cas9-based homologous recombination. VVL-DD exhibited significant tumor selectivity in vitro and anti-tumor potency in vivo in a murine pancreatic cancer model. Then, VVL-DD was armed with an optimal combination of immunomodulatory molecules, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-21 (IL-21), to produce VVL-GL21. VVL-GL21 induced significant tumor regression after intratumoral and systemic administration. Moreover, VVL-GL21 increased the infiltration of dendritic cells (DCs), macrophages, and T cells; induced DC maturation; increased the transition from M2 to M1 macrophages; improved the formation of immune memory; prevented tumor recurrence; and effectively bolstered the immune response against tumors in multiple key immune compartments. Interestingly, mice bearing-pancreatic cancer tumors treated with VVL-GL21 showed anti-tumor immunity against lung and colon cancer tumors. Importantly, treatment with VVL-GL21 enhanced the responsiveness of tumors to the immune checkpoint inhibitor anti-PD1. Taken together, VVL-GL21 remodels the suppressive TME and has powerful anti-tumor activities as monotherapy or in combination with anti-PD1 by intratumoral or systemic delivery for the treatment of pancreatic cancer. VVL-GL21 could be used as a therapeutic cancer vaccine.

Ultrasound-triggered drug-loaded nanobubbles for enhanced T cell recruitment in cancer chemoimmunotherapy.

Chemotherapy combined with immunotherapy is a highly promising approach for treating tumors. However, chemotherapeutic drugs often fail to accumulate effectively at the tumor site after systemic administration and they lack sufficient immunogenicity to activate adaptive immunity, making an effective T-cell immune response within the tumor microenvironmentdifficult to achieve. Here, this work developed drug-loaded nanobubbles (DTX-R837@NBs) that encapsulate the chemotherapy drug docetaxel and the immune adjuvant R837 via a thin-film hydration method. Ultrasound-targeted nanobubble destruction promoted drug accumulation within tumor tissues and damaged tumor cells through the cavitation effect, inducing immunogenic cell death and releasing damage-associated molecular patterns to augment dendritic cell maturation. Notably, DTX-R837@NBs exhibited excellent contrast-enhanced ultrasound imaging capabilities, enabling the seamless integration of diagnosis and treatment. In combination with immune checkpoint blockade targeting programmed cell death protein 1 (PD-1), the generated immunological responses attacked residual tumor cells and ameliorated the immunosuppressive tumor microenvironment, inhibiting distant tumor growth and metastasis. Moreover, this strategy exhibited robust immune memory effects, effectively protecting the host and preventing tumor recurrence upon rechallenge. Overall, ultrasound-mediated DTX-R837@NBs combined with anti-PD-1 immune checkpoint blockade therapy exhibits robust antitumor efficiency, represent a promising strategy for overcoming immunotherapy resistance in cold tumors, and warrant further investigation for clinical translation.

Exploring the mechanisms by which common inhalational anesthetics influence malignant tumor metastasis: A data mining study based on comparative toxicogenomic databases.

Surgery remains the primary treatment for solid malignant tumors, but controlling postoperative tumor recurrence and metastasis continues to be a major challenge. Understanding the factors that influence tumor recurrence and metastasis after surgery, as well as the underlying biological mechanisms, is critical. Previous studies suggest that anesthetic agents may increase the risk of tumor recurrence and metastasis in patients with cancer, but the mechanisms underlying these findings remain unclear. In this study, we utilized toxicogenomics and comparative toxicogenomic databases to analyze data and explore the potential mechanisms by which three commonly used inhalational anesthetics-sevoflurane, isoflurane, and halothane-might promote malignant tumor metastasis. The results identified 18 genes that may be associated with tumor metastasis. Functional enrichment analysis revealed that these anesthetics could influence tumor cell migration by activating signaling pathways such as the IL-17 and tumor necrosis factor signaling pathways, thereby potentially inducing tumor metastasis. Moreover, by constructing a TF-mRNA network, we predicted several transcription factors that might play key roles in anesthetic-induced tumor metastasis. The analysis revealed a total of 87 regulatory relationships between transcription factors and mRNA. These findings offer new insights for future in vivo or in vitro studies and contribute to a better understanding of the relationship between inhalational anesthetics and tumor metastasis, providing valuable reference points for clinical decision-making. The results of this study also provide a reference for the determination of subsequent clinical treatment targets. Hence, future laboratory studies should prioritize investigating the specific genes and common mechanisms identified in this study.

Immediate second resection versus restage transurethral resection of bladder tumor: A prospective randomized clinical trial (IMMERSE trial).

The role of repeat transurethral resection of bladder tumor (TURBT) for the management of nonmuscle invasive bladder carcinoma is debated, especially when initial resections include detrusor muscle. This study compares immediate second resection (additional deep biopsies in the same session) with standard restage TURBT performed 2-6 weeks post-initial TURBT to determine adequacy in detrusor muscle sampling and compare the disease rate at restage TURBT in both groups. A randomized trial was conducted at a tertiary care hospital, including patients aged ≥18 years undergoing TURBT with complete primary tumor resection. Cases were randomized into two groups i.e., 'standard TURBT' (complete tumor resection with a deep biopsy) and "immediate second resection" (complete tumor resection, deep biopsy and additional deep biopsies). The primary endpoint was the presence of detrusor muscle in biopsy specimens, analyzed by a single pathologist. Secondary endpoints included perioperative complications, residual/ recurrent tumors, and factors affecting these recurrences. The study included 83 patients: 44 in the 'standard TURBT' group and 39 in the 'immediate second resection' group. The detrusor muscle was present in 66% of standard TURBT cases and 97% of immediate second resection cases, showing a statistically significant improvement (P = 0.000). Residual disease was found in 41% of restage TURBT patients in the standard group and 15% in the immediate second resection group, the majority being high-grade and T1 tumors (P = 0.028). There were no significant differences in tumor grade or perioperative complications between the groups. However, immediate second resection showed 18% higher detrusor muscle sampling rates than standard re-stage TURBT done at 2-6 weeks (P = 0.021). Immediate second resection at the time of initial TURBT significantly improves detrusor muscle sampling rates and decreases residual tumors at restage. Despite higher muscle sampling, a considerable proportion of patients still exhibited residual or recurrent tumors in both groups, emphasizing the need for improved detection and biopsy techniques during primary TURBT.

Survival outcomes comparing minimally invasive versus open cytoreductive surgery in recurrent adult-type granulosa cell tumors.

Adult-type granulosa cell tumors are a rare form of ovarian cancer, 30% of which will recur. Cytoreductive surgery is often performed at the time of a first recurrence, but little is known about the impact of open versus minimally invasive surgical approaches on survival outcomes. To examine associations between surgical approach, clinical variables, and survival outcomes among patients with adult-type granulosa cell tumors who underwent cytoreductive surgery at the time of first recurrence. This is a retrospective cohort study of patients with adult-type granulosa cell tumors enrolled in the MD Anderson Rare Gynecologic Malignancy Registry as of April 2024. Included patients had at least one documented recurrence and underwent secondary cytoreductive surgery as part of their treatment plan. Patients were excluded if surgery was performed prior to January 1, 2000, or if surgery was not intra-abdominal. Demographics and clinical variables were compared using descriptive statistics. Surgical complexity was classified as either low, intermediate, or high based on procedures performed. Progression-free and overall survival outcomes were stratified by surgical approach and estimated using Kaplan-Meier curves. A multivariable Cox proportional hazards model was used to adjust progression-free survival at time of first recurrence for age, year of surgery, and extent of disease. 485 patients with adult granulosa cell tumors were identified, 108 met inclusion criteria. Seventy-eight (72%) had open and 30 (28%) had minimally invasive secondary cytoreductive surgery. Baseline characteristics, including initial stage, self-identified race, or age at diagnosis, did not differ between open and minimally invasive surgery groups. Patients undergoing minimally invasive surgery were significantly younger at the time of surgery than the open group, with a median age of 42 vs 49, respectively (p=0.03). For the open group, 33% of surgeries were considered intermediate complexity and 4% high complexity, compared to 7% and 0% in the MIS group, respectively (p=0.004). There was no difference in achieving optimal cytoreduction, 85% in the open group and 88% in the MIS group (p=0.68). Following secondary cytoreductive surgery, there was no difference in overall survival, median overall survival of 166 months in the open group and 94 months in the minimally invasive group (p=0.27), or progression-free survival after first recurrence, 26 months in the open group compared to 21 months in the minimally invasive group (p=0.42). The difference in progression-free survival after the first recurrence remained non-significant after adjustment for key potential variables, including age, surgical approach, year of surgery, and extent of disease. There was no difference in incisional or port site recurrences at the time of second recurrence among those undergoing open (8.3%) compared to minimally invasive surgery (7.4%) at time of first recurrence (p=0.89). In patients with a first recurrence of adult-type granulosa cell tumors, open secondary cytoreductive surgery did not achieve superior outcomes compared to surgery via a minimally invasive approach. Minimally invasive surgery should be considered for carefully selected patients with recurrent adult-type granulosa cell tumors. Future research is needed on patient factors important to the selection of surgical approach in this setting.

Basket study of oral progesterone antagonist onapristone extended-release in combination with anastrozole in progesterone receptor-positive recurrent adult-type granulosa cell tumor of the ovary.

We sought to determine the safety and efficacy of the oral progesterone antagonist onapristone in combination with anastrozole in patients with recurrent progesterone receptor-positive adult-type granulosa cell tumor of the ovary. This was a single-institution phase II study of patients with progesterone receptor-positive adult-type granulosa cell tumor who received at least 1 prior line of chemotherapy. Patients were enrolled from November 2021 to August 2022 and tissue was evaluated for progesterone receptor status via immunohistochemistry. Eligible patients had progesterone receptor expression ≥1% on tissue collected within 3 years of enrollment. Patients received 50 mg of onapristone extended-release twice daily and 1 mg of anastrozole by mouth daily until progression of disease or discontinuation of treatment. Adverse events were graded by Common Terminology Criteria for Adverse Events version 5.0. The primary end point was the overall response rate by Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points were response duration, clinical benefit rate, progression-free survival, and safety. Fourteen patients with adult-type granulosa cell tumor enrolled and completed stage 1 accrual. There were no objective responses seen during the study period. The study was closed when further development of onapristone extended-release was discontinued. All 14 patients were evaluable, with median progression-free survival of 3.6 months (range; 1.7-7.1), a 6-month progression-free survival rate of 28.6% (range; 8.8%-52.4%), a 12-month progression-free survival rate of 10.7% (range; 0.8%-35.4%), and a clinical benefit rate of 42.9% (range; 17.7%-71.7%). The study did not meet its primary end point. Although the combination of onapristone extended-release and anastrozole was well-tolerated, there were no objective responses in patients with progesterone receptor-positive adult-type granulosa cell tumor.

Carrier-free nanoparticles for cancer theranostics with dual-mode magnetic resonance imaging/fluorescence imaging and combination photothermal and chemodynamic therapy.

Both photothermal therapy (PTT) and chemodynamic therapy (CDT) are designed to focus their antitumor effect on only the tumor site, thereby minimizing unwanted severe damage to healthy tissue outside the tumor. However, each monotherapy is limited in achieving complete tumor eradication, resulting in tumor recurrence. The combination of multiple therapies may help to overcome the limitations of single therapy, improve the chances of complete tumor eradication, and reduce the risk of recurrence. Here, we report a novel multifunctional carrier-free nanoparticle, namely Mn-TPP@ICG, prepared through the self-assembly of ICG and 5,10,15,20-Tetraphenyl-21H,23H-porphine manganese (III) chloride (Mn-TPP). The prepared Mn-TPP@ICG allowed dual-mode imaging in the form of magnetic resonance imaging (MRI) and near-infrared (NIR) fluorescence imaging, as well as combination therapy in the form of CDT and PTT. In vitro experiments revealed that Mn-TPP@ICG nanoparticles can enable CDT by converting intratumoral hydrogen peroxide (H2O2) to highly cytotoxic hydroxyl radicals (·OH) and PTT through photothermal conversion, resulting in a strong synergistic antitumor effect. Furthermore, in vivo experiments revealed that CDT and PTT with Mn-TPP@ICG nanoparticles effected a synergistically enhanced therapeutic effect in 4 T1 tumor-bearing mice, significantly inhibiting tumor growth compared with monomodal treatments with no treatment, only CDT, or only PTT. Lastly, imaging experiments unveiled the exceptional capability of Mn-TPP@ICG nanoparticles in enabling fluorescence imaging and high-resolution MRI upon their intravenous administration. Thus, a meaningful carrier-free nanoparticle strategy for the synergistic combination of CDT and PTT was provided in our study, broadening the applications of nanotheranostics.