Primary Tumor Research Articles

GAD1 ameliorates glioma progression through regulating cuproptosis via RAS/MAPK pathway.

Glioma represents a primary malignant tumor occurring in the central nervous system. Glutamate decarboxylase (GAD1) plays a significant role in tumor development; however, its function of GAD1 and underlying mechanisms in glioma progression remain unclear. Differentially expressed genes (DEGs) obtained from the GSE12657 and GSE15209 datasets that intersected with cuproptosis-related genes and pivot genes were identified using comprehensive bioinformatics methods. The elesclomol (ES) treatment was used to induce cuproptosis in U251 cells, which was validated by detecting intracellular copper levels and cuproptosis marker expression. Lentivirus-mediated gene overexpression was performed to explore the effects of GAD1 using functional assays in vitro and in a mouse xenograft model. The RAS agonist ML098 was used to verify the effect of GAD1 on the RAS/MAPK pathway in glioma cells. A total of 87 cuproptosis-related DEGs and seven hub genes were obtained, with five genes upregulated and two were downregulated in gliomas. Overexpression of GAD1 inhibited proliferation, invasion, and migration, promoted apoptosis of glioma cells, and suppressed tumorigenesis in vivo. In addition, GAD1 overexpression enhanced the sensitivity of glioma cells to cuproptosis. Additionally, ML098 treatment attenuated the inhibitory effect of GAD1 overexpression on the malignant phenotype of ES-treated cells. GAD1 plays an anti-oncogenic role in glioma by regulating apoptosis via inhibition of the RAS/MAPK pathway.

Non-emergent hemoptysis in patients with primary or metastatic lung tumors: The role of transarterial embolization

Non-emergent hemoptysis in patients with primary or metastatic lung tumors: The role of transarterial embolization

Age-specific clinical results in spinal meningioma surgery: should age still be considered detrimental to satisfactory outcomes?

Spinal meningiomas (SMs) are relatively rare primary spinal neoplasms, and the increasingly growing mean age and number of older patients presenting with spinal neoplasms raise questions concerning the costs and benefits of proposing surgical intervention. The aim of this study was to analyze the outcomes and complications of a large cohort of older patients with SMs to define the real benefit of surgery in these patients. A total of 261 SMs were operated on between 1976 and December 2021, and 156 matched the inclusion criteria for the final cohort. Patients were divided into three groups according to age: < 50 years (group A), between 51 and 74 years (group B), and > 75 years (group C). Neurological and clinical outcomes, resection grade, complications, histology, and possible recurrences were evaluated. The final cohort comprised 156 patients (126 females, 30 males) with a mean ± SD age of 55.93 ± 14.80 years. The mean follow-up was 41.5 ± 11.4 months. Group A was found to have a significantly higher Frankel score at follow-up; there was no significant difference between mean scores for groups B and C. Nevertheless, there was no significant difference between the subgroups in patients who showed improvement from their preoperative neurological condition. Only 3 recurrences were recorded, all in group A. Axial topography, level of the lesions, and preoperative symptoms, including impairment of the sphincter functions, demonstrated no statistically significant interaction in the subgroups. The present study supports the concept that older age might not be a contraindication for surgical treatment in SMs because of the important improvements in functional status and quality of life achieved in this population subgroup. Older patients can benefit from prompt assessment and early surgery in cases of acute onset, with a complication rate not higher than that of younger patients.

Xanthogranulomatous osteomyelitis of pubic bone mimicking neoplasm: a case report and literature review

BackgroundXanthogranulomatous osteomyelitis (XO) is a rare disease characterized radiologically by an osteolytic lesion with cortical expansion or disruption. Differentiating this condition from other osteolytic diseases such as primary or metastatic bone neoplasms is imperative. Several case reports have been published on XO, with previous reports predominantly identifying bacteria such as Pseudomonas or Staphylococcus as causative organisms. However, fungal infection-induced XO has not yet been reported.Case presentationWe present the case of a 23-year-old woman with a tumor-like osteolytic lesion in the pubic bone. The patient had experienced pelvic pain and intermittent febrile episodes for 2 months. Plain radiography revealed an osteolytic lesion in the right pubic tubercle. Magnetic resonance imaging suggested a cystic bone tumor or tubercular infection. Surgical intervention included curettage of the lesion and irrigation with normal saline. Histopathological examination of the specimen revealed abundant foamy histiocytes with inflammatory infiltrates consistent with XO. Culture of the osteolytic lesion confirmed an Aspergillus species infection and antifungal treatment was initiated. At 1-year follow-up, no evidence of local recurrence was observed.ConclusionsAlthough rare, XO requires differentiation from similar conditions and is treated with surgical intervention and targeted medical therapy based on the identified organisms. Clinicians should be mindful that XO can also be induced by fungal infections and that combination antifungal treatments may be beneficial in such cases.

Hospital admissions for pyoderma gangrenosum in Spain (1999-2021): Epidemiological and clinical characteristics, temporal trends, and factors associated with poor prognosis and higher cost.

Pyoderma gangrenosum (PG) is a neutrophilic inflammatory dermatosis that can be idiopathic or associated with other diseases. The aim was to analyze the epidemiological and clinical characteristics, temporal trends, risk factors for poor prognosis, and admission costs associated with PG in Spain. We conducted a retrospective study, based on the Hospital Discharge Registry of the Spanish National Health System in Spain from 1999 to 2021. Of 82,161,670 admissions during the study period, 4901 were for PG (hospitalization rate of 59.7/1,000,000 admissions). PG hospitalizations increased from 28.8/1,00,000 in 1999 to 91.9/1,000,000 in 2021. PG was a primary cause of admission in 60.5% of cases, and 58.4% of patients were women. The main PG-related comorbidities were inflammatory bowel disease (15.7%) and neoplasms (10%). There was a significant increase over the years in admissions for inflammatory bowel disease, monoclonal gammopathy of undetermined significance, and lymphoma, as well as an increase in diseases unrelated to PG, such as hypertension, diabetes, and chronic kidney disease. The hospital mortality rate was 5.6%. Death was associated with PG being a primary diagnosis, older age, leukemia, neoplasms, diabetes, and chronic kidney disease. The cost of treatment increased over the years and was higher in older people. PG cases in the inpatient setting in Spain over the past 23 years make up a tiny proportion of all hospital admissions, although the rate of hospitalization for PG has increased in the last two decades.

A comparative study on the efficacy of different treatment methods for preventing vocal cord adhesion after laser treatment for glottic cancer

Objective:Comparing the primary tumor control, vocal function recovery, postoperative adhesion rate and degree of adhesion in early glottic cancer involving the anterior commissure treated with CO₂ laser staged and lateral surgery, one-stage surgery combined with laryngeal stent placement, and simple CO₂ laser excision. Methods:This study focuses on 83 patients with T1-2N0M0 stage glottic squamous cell carcinoma involving the anterior commissure who underwent CO₂ laser treatment. The study was divided into three groups: Group A with 15 cases, treated with staged resection surgery; Group B with 18 cases, treated with one-stage surgery combined with the placement of a silicone laryngeal stent; and Group C with 50 cases, treated with simple CO₂ laser excision. The Voice Handicap Index-10（VHI-10）, the GRBAS auditory-perceptual assessment, and the maximum phonation time（MPT） were used to evaluate the vocal function of the patients before and six months after surgery. The degree of vocal cord adhesion was assessed using the Cohen classification of vocal cord adhesion. Statistical analysis was performed to determine the differences in each indicator before and after surgery, and the primary tumor control rates among the three groups. Results:Local recurrence occurred in 1 case each in Groups A and B, and in 4 cases in Group C, with no distant metastasis observed. Postoperative vocal cord adhesion of varying degrees occurred in a total of 77 cases, with an adhesion rate of 73.3%（11/15） in Group A, 88.9%（16/18） in Group B, and 100%（50/50） in Group C. The postoperative vocal cord adhesion rate and degree in Group C were significantly higher than in Groups A and B. The postoperative VHI-10 scores in all three groups were significantly increased compared to preoperative scores（P<0.05）, and when compared between groups postoperatively, Group C was significantly worse than Groups A and B （P<0.05）. The postoperative maximum phonation time（MPT） in Group C was significantly reduced compared to preoperative and was markedly shorter than that of Groups A and B postoperatively（P<0.05）. The postoperative grades of G（Grade） and R（roughness） in Group C were significantly higher than preoperatively, indicating a noticeable deterioration in voice quality, and were also significantly worse than those postoperatively in Groups A and B, with all differences（P<0.05）. Conclusion:For early glottic cancer involving the anterior commissure, choosing staged surgery or one-stage surgery combined with the placement of a silicone anterior commissure laryngeal stent were better than simple laser tumor excision in terms of secondary vocal cord adhesion and voice function preservation.

Multifunctional biomimetic nanosystem for retinoblastoma treatment

The nanodelivery carrier was modified with tumor cell membrane and dendritic cell membrane to create a double-membrane fusion biomimetic nanomedicine, termed FM@mPDA/DOX/JQ-1. This research introduces a biologically inspired platform for multimodal combined tumor therapy. Because fusion membrane nanomedicines inherit the homologous targeting properties of tumor cells, chemotherapy drugs can be delivered to tumor lesions. In addition, the fusion membrane carries abundant and complete tumor cell membrane antigens. Based on the professional antigen presentation characteristics of dendritic cells, it directly or indirectly promotes the uptake of cell membrane-bound tumor antigens and downstream immune responses. In ectopic and orthotopic tumor-bearing mouse models, FM@mPDA/DOX/JQ-1 can induce a durable immune response to inhibit the rebound of primary tumors after chemotherapy and photothermal therapy (PTT). FM@mPDA/DOX/JQ-1 demonstrates no adverse impact on liver and kidney function, as well as blood indicators in mice, affirming its excellent safety profile. This tumor-specific immunotherapy-based nanoplatform holds promise for extension across various tumor types, offering a viable approach for multimodal combined tumor therapy.

Imaging Descriptors of Human Papilloma Virus-mediated and Human Papilloma Virus-negative Oropharyngeal Cancers in Indian Subcontinental Patients

Abstract Background: Nearly 24,000 new cases of oropharyngeal cancers (OPCs) are reported per year in India, constituting 3.9% of cancers in all sites. By 2009, Human papilloma virus (HPV), in particular HPV-16, was established as an etiological factor and even a causative agent in OPCs being associated with up to 70% OPCs. Prior imaging-based studies have described certain differentiating factors between HPV-mediated and HPV-negative OPC, highlighting computed tomography and magnetic resonance characteristics that could help differentiate the two groups. Our study aimed to evaluate any imaging differences between HPV-mediated and non-HPV-mediated oropharyngeal malignancies in the Indian subcontinent population. Methods: Seventy-nine patients from the Indian subcontinent who were referred to a tertiary center in southern India between the period of January 2019 to September 2020 (19 months) were included in the study. Imaging descriptors were documented by blinded radiologists, and univariate and multivariate analysis of various imaging descriptors and imaging differences between HPV-mediated and non-HPV cases were attempted to be identified. Results: We found no statistically significant imaging differences between HPV-mediated and non-HPV-mediated oropharyngeal malignancies. The only epidemiologically significant difference in the two groups was that in women and nonsmokers, HPV-mediated malignancies were more common. Conclusion: HPV-mediated and HPV-negative malignancies have similar primary tumor as well as nodal imaging characteristics. Previously cited differences in the two groups, in Western literature, could not be demonstrated in our population. It implores further research into whether downstaging of treatment and better prognosis of HPV-mediated malignancies is actually applicable in the Indian subcontinent setting.

Temporal Effect on PD-L1 Detection and Novel Insights Into Its Clinical Implications in Non-Small Cell Lung Cancer.

Several studies rely on archived tissue blocks to assess the PD-L1 scores; however, a detailed analysis of potential variations of scores between fresh and archived tissue blocks still lacks. In addition, the prognostic implications of PD-L1 in lung cancers have not yet been completely understood. Here, we aimed to investigate the temporal variation in PD-L1 scores from clinical samples and the clinical implications of PD-L1 in non-small cell lung cancer (NSCLC). NSCLC cases from January 2005 to June 2023 were considered for this study, and PD-L1 scores in archived and fresh tissue blocks were analyzed. Association of PD-L1 with various driver mutations was explored, and implications of PD-L1 in progression-free survival (PFS) and overall survival (OS) were analyzed. Our study revealed a significant disparity in PD-L1 scores between archived and fresh tissue blocks, and a temporal variation in scores within 6 months of tissue acquisition. Advanced-stage primary tumors, metastatic lymph nodes, and visceral pleural invasion revealed higher PD-L1 expression as presented by tumor proportion score (TPS). Notably, in fully resected stage I/II NSCLC cases, OS was better in the high PD-L1 (≥ 50% TPS) cohort with driver mutations compared to cases without driver mutations (hazard ratio-0.5129, 95% confidence interval 0.2058-1.084, p = 0.0779). In contrast, high PD-L1 was associated with worse OS compared to no PD-L1 (< 1% TPS) (hazard ratio-2.431, 95% confidence interval 1.144-6.656, p = 0.0242) in the cohort without driver mutations. Furthermore, the presence of a KRAS mutation favored the outcome of anti-PD-L1/PD1 immunotherapy in advanced NSCLC. PD-L1 detection from tissue blocks was found to vary temporally, urging for a prioritized consideration for patients with marginal scores when archived blocks are employed for its detection. Prognostic roles of PD-L1 were associated with driver mutations, and KRAS mutations favored the outcome of anti-PD-L1/PD1 therapy in advanced NSCLC.

Tracking changes in image-defined risk factors during neoadjuvant chemotherapy and their predictive value for surgical outcomes based on the International Neuroblastoma Surgical Report Form.

The capacity of presurgical image-defined risk factors (IDRFs) to predict secondary surgical outcomes in patients with neuroblastoma is controversial. The International Neuroblastoma Surgical Report Form (INSRF) was employed to retrospectively collect the clinical data of 53 patients diagnosed with neuroblastoma at our hospital from April 2014 to April 2020. IDRFs were identified at the time of diagnosis and reassessed during the course of neoadjuvant chemotherapy. Various statistical tests were used to evaluate the correlation between IDRFs and secondary surgical outcomes. A total of 195 IDRFs were identified. Notably, by two courses of neoadjuvant chemotherapy, the number of "two body compartments," "intraspinal tumor extension," and "trachea-compressing" IDRFs decreased significantly (p=.001). The primary tumor volumes and the number of IDRFs decreased significantly by four courses of neoadjuvant chemotherapy, especially in "intraspinal tumor extension" IDRFs (p=.034). The median number of IDRF per patient was four (interquartile range [IQR]: 1-5) at diagnosis, which diminished to one (IQR: 1-3) subsequent to neoadjuvant chemotherapy. The presence of preoperative IDRFs was not associated with surgical complications (p=.286) or the extent of surgery (p=.188). However, the number of preoperative IDRFs linked to the extent of surgery (p=.002), not to operative complications (p=.669). Specifically, presurgery "renal vessel contact" IDRFs were predictive of surgical complications, while presurgery "infiltration of vital structures" IDRFs were associated with the extent of surgery. The number of IDRFs decreased significantly by four courses of neoadjuvant chemotherapy. The number and type of presurgery IDRFs may predict secondary surgical outcomes, surpassing the mere consideration of their presence or absence.

Recurrence risk analysis for stage II and III colorectal cancer, and the implications of diabetes mellitus as a risk factor for the recurrence of stage III colorectal cancer.

The present study investigated the risk factors for recurrence in patients with stage II-III colorectal cancer (CRC) who underwent colorectal surgery. Data from 232 patients with stage II and III CRC who underwent primary tumor resection were retrospectively analyzed. Univariate and multivariate analyses were performed to determine the risk factors for recurrence. The overall recurrence rate was 21.6% (n=50/232). Univariate Cox regression analysis identified diabetes mellitus (DM) (P=0.032) as a risk factor for recurrence. In addition, multivariate Cox regression analysis showed that DM was an independent risk factor for recurrence-free survival (RFS) (hazard ratio 2.40, P=0.016). The RFS curve obtained using the Kaplan-Meier method indicated that in patients with stage III colon cancer, the non-DM group demonstrated a significantly longer RFS than the DM group (P=0.012). In conclusion, the present study demonstrated that DM may be an independent risk factor for recurrence in patients undergoing curative resection for stage III CRC. Consequently, better postoperative therapy and careful monitoring might be required, especially in patients with stage III CRC and preoperative DM.

Simple theranostics nanoagent for precision suppression of tumor growth and Metastasis: A traditional fermented product having a novel functional breakthrough

Biomass-based nanoagents constitute a focal point in the clinical development of tumor nanotheranostics, characterized by their high biocompatibility, biodegradability, controllability, and sustainability. However, achieving satisfactory nanoagents with biological safety and high theranostic efficacy for clinical translation remains a significant challenge. Herein, based on the design concept of medicine food homology, we developed a simple, mass-produced theranostics nanoagent (HSAVMn@CM NA) using Shanxi aged vinegar (SAV) as the raw material, enabling second near-infrared fluorescence/photoacoustic (NIR-II FL/PA) imaging-guided photo/catalytic/chemodynamic synergistic tumor therapy. A novel strategy involving the hydrolysis of SAV (HSAV) via the hydrolysis-acidification method has been developed to enhance NIR-II FL imaging performance. The HSAVMn@CM NAs have improved tumor-targeted efficiency through biomimetic modification of tumor membranes. Guided by NIR-II FL/PA dual-modal imaging, the HSAVMn@CM NAs achieve targeted photothermal/photodynamic synergistic phototherapy. Notably, the employment of a single laser source for simultaneous photothermal/photodynamic therapy has led to an enhancement in the efficacy of phototherapy. Moreover, the HSAVMn@CM NAs effectively chelated Zn2+ ions within the tumor microenvironment, to inhibit matrix metalloproteinase 2/9 (MMP 2/9) activity, thereby synergistically suppressing primary tumor growth and metastasis. Taken together, this research provides a novel design strategy for biomass-based nanoagents with potential clinical translation in precise tumor theranostics.

Development of a predictive model for patients with bone metastases referred to palliative radiotherapy: Secondary analysis of a multicenter study (the PRAIS trial).

The decision to administer palliative radiotherapy (RT) to patients with bone metastases (BMs), as well as the selection of treatment protocols (dose, fractionation), requires an accurate assessment of survival expectancy. In this study, we aimed to develop three predictive models (PMs) to estimate short-, intermediate-, and long-term overall survival (OS) for patients in this clinical setting. This study constitutes a sub-analysis of the PRAIS trial, a longitudinal observational study collecting data from patients referred to participating centers to receive palliative RT for cancer-induced bone pain. Our analysis encompassed 567 patients from the PRAIS trial database. The primary objectives were to ascertain the correlation between clinical and laboratory parameters with the OS rates at three distinct time points (short: 3 weeks; intermediate: 24 weeks; prolonged: 52 weeks) and to construct PMs for prognosis. We employed machine learning techniques, comprising the following steps: (i) identification of reliable prognostic variables and training; (ii) validation and testing of the model using the selected variables. The selection of variables was accomplished using the LASSO method (Least Absolute Shrinkage and Selection Operator). The model performance was assessed using receiver operator characteristic curves (ROC) and the area under the curve (AUC). Our analysis demonstrated a significant impact of clinical parameters (primary tumor site, presence of non-bone metastases, steroids and opioid intake, food intake, and body mass index) and laboratory parameters (interleukin 8 [IL-8], chloride levels, C-reactive protein, white blood cell count, and lymphocyte count) on OS. Notably, different factors were associated with the different times for OS with only IL-8 included both in the PMs for short- and long-term OS. The AUC values for ROC curves for 3-week, 24-week, and 52-week OS were 0.901, 0.767, and 0.806, respectively. We successfully developed three PMs for OS based on easily accessible clinical and laboratory parameters for patients referred to palliative RT for painful BMs. While our findings are promising, it is important to recognize that this was an exploratory trial. The implementation of these tools into clinical practice warrants further investigation and confirmation through subsequent studies with separate databases.

Administration, Marketing, Pharmacotherapy of Medicines in Neuro-Oncology

Primary tumors make up 1.5% of all clinical cases. The most vulnerable group is children. Brain neoplasms are the second most common after acute leukemia. According to WHO statistics, men suffer 1.5 times more often than women. Administration, marketing, and pharmacotherapy of medicines in neuro-oncology were carried out. The administration of medicines for neuro-oncology pharmacotherapy in the USA and Ukraine was analyzed. Bevacizumab, Everolimus, Lomustine, Temozolomide were found to be approved in both countries. The issue of administration of medicines for neuro-oncology pharmacotherapy other than as prescribed by a doctor has been studied. The possibility of combined pharmacotherapy in neuro-oncology is indicated. Marketing studies of medicines for neuro-oncology pharmacotherapy have been conducted. The medicines are presented in different dosage forms: solutions for infusions, injections, capsules and lyophilisates. The manufacturers of these medicines are pharmaceutical companies from different countries: India, Germany, Austria, the Netherlands, Ukraine. The majority of medicinal products have indefinite registration in Ukraine, which indicates their availability on the pharmaceutical market for the treatment of neuro-oncological diseases. Causes of tumors, main histological groups of neoplasms, their degree of malignancy, symptoms of tumors, diagnostic methods, therapy and pharmacotherapy in neuro-oncology are given. Further research on the development of methods and preparations of pharmacotherapy for neuro-oncology is relevant and ongoing.

Surgery enhances the effectiveness of peptide receptor radionuclide therapy in metastatic gastroenteropancreatic neuroendocrine tumors

BackgroundWith the advent of peptide receptor radionuclide therapy, the timing and sequence of surgery in the treatment of metastatic gastroenteropancreatic neuroendocrine tumors merits further study. We hypothesized that surgery before peptide receptor radionuclide therapy might enhance its effectiveness in patients with metastatic gastroenteropancreatic neuroendocrine tumors. MethodsEighty-nine patients with metastatic well-differentiated gastroenteropancreatic neuroendocrine tumors treated with 177Lutetium-dotatate peptide receptor radionuclide therapy between 2018 and 2023 were included. Fifty-six patients underwent surgery (primary tumor resection and/or liver debulking) before peptide receptor radionuclide therapy and 33 patients did not. Primary outcome was progression-free survival according to Response Evaluation Criteria in Solid Tumors. Pretreatment dotatate positron emission tomography/computed tomography was used to calculate tumor volumes. ResultsThe surgery and no-surgery groups were well-matched. Median progression-free survival after peptide receptor radionuclide therapy was 15.6 months (interquartile range, 9.1–22.7 months) in the no-surgery group compared with 26.1 months (interquartile range, 12.7–38.1 months) in the surgery group (P = .04). On subgroup analysis, median progression-free survival was 18.1 months (interquartile range, 11.9–38.4 months) in patients who underwent primary tumor resection only compared with 26.2 months (interquartile range, 14.0–38.1 months) in patients who underwent liver debulking (P = .04). Tumor volume was lowest in patients who underwent liver debulking (median 146.07 mL3) compared with no surgery (median 626.42 mL3) (P = .001). On univariable analysis, a tumor volume <138.8 mL3 was associated with longer progression-free survival (hazard ratio, 2.03; 95% confidence interval, 0.95–4.34, P = .05), with a median progression-free survival of 38.1 months (interquartile range, 16.9–41.3 months) compared with 17.8 months (interquartile range, 10.8–28.7 months). ConclusionSurgery may enhance the effectiveness of 177Lutetium-dotatate in the treatment of metastatic well-differentiated gastroenteropancreatic neuroendocrine tumors. This positive effect may be the result of a lower tumor volume in patients after surgery. Our findings fortify the concept of using surgical debulking to improve systemic therapies such as peptide receptor radionuclide therapy.

A Multifunctional Biomimetic Nanoplatform for Dual Tumor Targeting-Assisted Multimodal Therapy of Colon Cancer.

The biomimetic nanoparticles (NPs) possessing abilities of tumor targeting and multimodal therapy show great potential for efficient combat of colon cancer. Herein, we developed a multifunctional biomimetic nanoplatform (Fe3O4@PDA@CaCO3-ICG@CM) based on CaCO3-modified magnetic polydopamine (PDA) loaded with indocyanine green (ICG), which was encapsulated by a mouse lymphoma cell (EL4) membrane (CM) expressing functional proteins (i.e., lymphocyte function-associated antigen 1, LFA-1; transforming growth factor-β receptor, TGF-βR; programmed cell death protein 1, PD-1; and factor related apoptosis ligand, FasL). Under magnetic attraction and LFA-1/PD-1-mediated endocytosis, Fe3O4@PDA@CaCO3-ICG@CM efficiently targeted CT26 colon tumor cells. The released calcium ion (Ca2+) from the NPs triggered by acidic tumor microenvironment, the enhanced photothermal effect contributed by the combination of PDA and ICG, and FasL's direct killing effect together induced tumor cells apoptosis. Moreover, the apoptosis of CT26 cells induced immunogenic cell death (ICD) to promote the maturation of dendritic cells (DCs) to activate CD4+/CD8+ T cells, thereby fighting against tumor cells, which could further be boosted by programmed death-ligand 1 (PD-L1) blockage and transforming growth factor-β (TGF-β) scavenging by Fe3O4@PDA@CaCO3-ICG@CM. As a result, in vivo satisfactory therapeutic effect was observed for CT26 tumor bearing-mice treated with Fe3O4@PDA@CaCO3-ICG@CM under laser irradiation and magnetic attraction, which could eradicate primary tumors and restrain distant tumors through dual tumor targeting-assisted multimodal therapy and eliciting adaptive antitumor immune response, generating the immune memory for inhibiting tumor metastasis and recurrence. Taken together, the multifunctional biomimetic nanoplatform exhibits superior antitumor effects, providing an insightful strategy for the field of nanomaterial-based treatment of cancer.

8598 Heterogeneous course of ectopic Cushing's syndrome (EAS) - does the location of the primary tumor affect the clinical picture and the outcome?

8598 Heterogeneous course of ectopic Cushing's syndrome (EAS) - does the location of the primary tumor affect the clinical picture and the outcome?

Acetate utilization promotes hormone therapy resistance in prostate cancer through neuroendocrine differentiation

AimsTumor fatty acid (FA) metabolic plasticity plays a pivotal role in resistance to therapy and poses limitations to anticancer strategies. In this study, our aim is to uncover the role of acetate metabolism in neurodifferentiation (NED)-mediated castration-resistant prostate cancer (CRPC). MethodsWe conducted analyses using LC-MS/MS on clinical prostate cancer tissue before and after hormone therapy. We established tumor xenograft mouse models, primary tumor cells, and human-derived organoids to detect the novel mechanism of NED and to identify potential therapies. ResultsThe hormone therapy-induced upregulation of acetate metabolism was mediated by acyl-CoA synthetase short-chain family member 2 (ACSS2), which increased c-MYC expression for NED induction. Notably, combined treatment with an ACSS2 inhibitor and enzalutamide significantly reduced the xenograft tumor volume. ConclusionOur findings uncovered the critical role of acetate metabolism in NED-mediated CRPC and suggest that ACSS2 inhibitors may represent a novel, low-toxicity strategy when combined with hormone therapy for treating patients with NED-mediated CRPC.

Blood and cerebrospinal fluid biomarkers in neuro-oncology.

The purpose of this review is to discuss the value of blood and CSF biomarkers in primary CNS tumors. Several analytes can be assessed with liquid biopsy techniques, including circulating tumor cells, circulating cell-free tumor DNA, circulating cell-free RNA, circulating proteins and metabolites, extracellular vesicles and tumor-educated platelets. Among diffuse gliomas of the adult, ctDNA in blood or CSF has represented the most used analyte, with the detection of molecular alterations such as MGMT promoter, PTEN, EGFRVIII, TERT promoter mutation and IDH R132H mutation. In general, CSF is enriched for ctDNA as compared with plasma. The use of MRI-guided focused ultrasounds to disrupt the blood-brain barrier could enhance the level of biomarkers in both blood and CSF. The detection of MYD88 L265P mutation with digital droplet PCR and the detection of ctDNA with next generation sequencing represent the best tools to diagnose and monitoring CNS lymphomas under treatment. In meningiomas, the low concentration of ctDNA is a limiting factor for the detection of driver mutations, such as NF2, AKTs, SMO, KLF4, TRAF7, SMARCB1, SMARCE1, PTEN, and TERT; an alternative approach could be the isolation of ctDNA through circulating extracellular vesicles. Liquid biopsies are being used extensively for diagnosis and surveillance of diffuse midline gliomas, in particular with the detection of the driver mutation H3K27M. Last, specific methylome patterns in CSF may allow the distinction of glioblastomas from CNS lymphomas or meningiomas. This review summarizes the current knowledge and future perspectives of liquid biopsy of blood and CSF for diagnosis and monitoring of primary CNS tumors.

Primary Aortic Malignant Peripheral Nerve Sheath Tumor.

A 74year-old woman suffering 1month persisting lumbago was referred with diagnosis of thoracic aortic aneurysm. Blood examinations indicated slightly or moderately elevated noradrenaline, dopamine, and homovanillic acid with normal-range vanillylmandelic acid. Contrast-enhanced CT scans revealed a tumor, protruding both intra- and extra-luminally, in the wall of the distal descending thoracic aorta without any primary focuses in the whole body. Primary aortic sarcoma or periaortic catecholamine-producing paraganglioma infiltrating the aorta was suspected. The tumor with the normal proximal and distal aorta 2-3cm apart from it was completely resected under femoro-femoral partial cardiopulmonary bypass. Macroscopically, the tumor was originated from the aortic wall and protruded both intra- and extra-luminally. Immunohistochemically, positive S-100 and vimentin; Ki67 levels of 40%; and negative CD34, CK AE1/AE3, and SMA were identified. The aforementioned findings definitively diagnosed primary aortic malignant peripheral nerve sheath tumor, which has been never reported in the literature.