Tumor Characteristics Research Articles

Rib Hemangiomas: Intriguing Findings from a Systematic Review of Rare Thoracic Tumors.

Background: Bone hemangiomas are rare benign vascular tumors, comprising less than 1% of all bone tumors. They are predominantly found in the vertebral body or skull; rib hemangiomas are particularly rare and are often misdiagnosed as malignant tumors. Given the high malignancy rate of primary rib tumors, understanding rib hemangiomas is crucial to avoid misdiagnosis. Methods: A systematic review was conducted according to PRISMA standards. A comprehensive literature search was performed in PubMed, EMBASE, Web of Science, and Scopus. Data on patient demographics, tumor characteristics, and clinical presentation were analyzed using STATA/SE 17. Results: From 306 articles, 40 studies including 43 patients met the inclusion criteria. Rib hemangiomas showed a bimodal age distribution, with peaks in patients younger than 30 years (mean age 21.43 ± 5.60 years) and ≥30 years (mean age 59.96 ± 9.70 years). Females were more affected (62.79%) than males (37.21%), with a ratio of 1.69:1. The tumors were most frequently located in mid-thoracic ribs (4-8) and predominantly on the left side of the thorax. The mean tumor size was 7.27 cm, with 76.19% exhibiting osteolytic changes. Clinically, 63.41% of cases were asymptomatic, while symptomatic cases mainly presented with pain. Conclusions: Rib hemangiomas, though rare, should be considered in the differential diagnosis of thoracic tumors. They present as well-demarcated lytic lesions with distinct imaging features, and they typically require complete surgical excision, which may be aided with preoperative embolization. Their accurate diagnosis involves a combination of radiologic and clinical evaluation. Further studies are needed to understand the disease's pathophysiology and to refine diagnostic and treatment protocols.

Baseline factors relating to depressive symptoms at one year postoperative in patients with diffuse glioma

Abstract Background Depressive symptoms are common in patients with diffuse glioma, potentially reducing their quality of life. Understanding baseline factors associated with the development of depressive symptoms is important for psychoeducation and early intervention. This study investigates the associations of baseline patient- and tumor-related characteristics and depressive symptoms 1 year after surgery. Methods We combined retrospective longitudinal datasets from Amsterdam UMC and Rigshospitalet Copenhagen. Several characteristics of patients and tumors were retrieved, in particular items of their mood and functioning status. Depression instruments were harmonized to the Patient-Reported Outcomes Measurement Information System Depression scale through previously developed item response theory. Functioning items were harmonized to the International Classification of Functioning, Disability, and Health (ICF) domains using linking methods published previously. We analyzed the associations of 25 baseline factors with depressive symptoms one year after surgery by multivariable stepwise backward linear regression models and verified model robustness using best subset selection. Results We included 118 patients with diffuse glioma with a mean age of 48 years and a glioblastoma in 29%. Baseline depressive symptoms, lower ICF energy, and impaired ICF language functioning were associated with more depressive symptoms at follow-up in the multivariable model (R-squared: 0.379). Conclusions We identified 3 key baseline factors associated with depressive symptoms one year after surgery. Clinically, our findings contribute to the comprehension of predictive factors for depressive symptoms, aiding healthcare providers and patients in understanding and possibly allowing for early intervention.

Pure intertubular seminoma (PITS) of the testis: A multi-institutional cohort of a rare growth pattern of seminoma

Pure intertubular seminoma (PITS) of the testis is described as the presence of seminoma cells within the interstitium of testis without any evidence of diffuse growth pattern or mass lesion of classical seminoma. These tumors are clinically and grossly inconspicuous and are diagnosed incidentally or during investigations for testicular pain, infertility or other symptoms. Rarely metastasis is the first presentation. Microscopic identification can be difficult and poses a diagnostic challenge in the absence of a mass lesion. Seminomas with exclusive intertubular growth patterns were gathered in an international cohort. Diagnoses were confirmed by fellowship-trained or specialized urologic pathologists. Cases with the presence of a classical diffuse or nested pattern of seminoma or any other germ cell tumor component were excluded. The patient's age, tumor characteristics and additional clinicopathologic features were recorded and analyzed. 15 patients of pure intertubular seminoma (PITS) were collated. The mean age of presentation was 29 years. Patients presented with variable symptoms, including undescended testis (26%, n = 4/15), testicular heaviness/pain (20%, n = 3/15) infertility (20%, n = 3/15) and metastasis (6%, n = 1/15); presentation was unknown in 4 patients. Of note, none of the patients presented because of testicular mass. Serum markers were within normal limits in most patients (93%, n = 14/15) with available data. No tumors were identified macroscopically; however, an ill-defined, grey-white, firm area was noted in one orchiectomy specimen. Microscopically, tumor cells were seen in intertubular spaces as dispersed individual cells or small clusters. Tumor cells were round to polygonal with large nuclei and prominent nucleoli. Mild to moderate lymphocytic infiltrates were seen admixed with tumor cells in 40% (n = 6/15) of the tumors. GCNIS was present in association with most PITS (73%, n = 11/15). Tubular atrophy with thickening of the basement membrane and Leydig cell hyperplasia was observed in one tumor. Thirty-three percent (n = 5/15) of the tumors showed pagetoid involvement of rete testis, including the tumor with metastasis. All tumors showed the classical immunohistochemical profile of seminoma, with PLAP, c-KIT, OCT3/4, D2-40 and SALL4 positivity. PITS can be clinically & pathologically inconspicuous, difficult to stage and liable to be misdiagnosed especially if presented with metastasis. Despite the inconspicuousness, PITS may represent an aggressive growth pattern of seminoma with the propensity for rete testis invasion.

Tumour stemness and poor clinical outcomes in haemochromatosis patients with hepatocellular carcinoma

AimsPatients with haemochromatosis (HFE) are known to have an increased risk of developing hepatocellular carcinoma (HCC). Available data are conflicting on whether such patients have poorer prognosis, and there is...

Diagnosis and Management of Intrascrotal Nerve Tumors: A Prospective Study

Background: Intrascrotal nerve tumors, though rare, are significant due to their potential impact on patient health and the complexities in management, especially in distinguishing benign from malignant tumors.Objective: The study aimed to evaluate the diagnosis and management of intrascrotal nerve tumors, focusing on clinical presentation, tumor characteristics, and treatment outcomes.Methods: This prospective study was conducted at the Urology Department, Institute of Kidney Diseases, HMC, Peshawar, from January to June 2023. Fifty-five male patients with confirmed intrascrotal nerve tumors were included. Data were collected from medical records, including demographic information, clinical symptoms, imaging findings, biopsy results, and treatment details. Tumor characteristics were assessed through ultrasonography and MRI. Statistical analysis was performed using SPSS version 25, with significance set at p < 0.05.Results: The mean age was 45.23±2.78 years. Benign tumors accounted for 65% of cases with a mean size of 2.8 cm, while malignant tumors (MPNSTs) accounted for 35% with a mean size of 4.5 cm. Complete excision was achieved in 95% of cases; recurrence was 32% in malignant tumors (p = 0.001). The overall survival rate for malignant tumors was 58% (p = 0.002).Conclusion: Intrascrotal nerve tumors present diagnostic and management challenges, particularly MPNSTs, which require aggressive treatment and close follow-up due to high recurrence rates.

COVID-19 vaccination anti-cancer impact on the PI3K/AKT signaling pathway in MC4L2 mice models

The most promising method of containing the COVID-19 pandemic is considered to be vaccination against SARS-CoV-2 infection. However, research on the relationship between vaccination against COVID-19 and cancer has primarily examined induced immunity rather than the disease itself. Considering that breast cancer is the most common cancer among women, the main goal of this study was to examine the impact of the Sinopharm and AstraZeneca vaccination on tumor characteristics such as tumor size, important tumor markers, tumor-infiltrating lymphocytes, metastasis to vital organs, and investigation of the PI3K/AKT signaling pathway, and the expression levels of relevant genes (PTEN, mTOR, AKT, PI3K, GSK3, and FoxO1) of the luminal B (MC4L2) mouse model. The tumor size of the mice was measured and monitored every two days, and after thirty days, the mice were euthanized. Remarkably, after vaccination, all vaccinated mice showed a decrease in the size of their tumor and an increase in the number of lymphocytes that had invaded the tumors. Tumor marker levels (VEGF, Ki-67, MMP-2/9), CD4/CD8 ratio, metastasis to vital organs, hormone receptors (ER, PR, and HER-2), and expression of genes related to the advancement of the PI3K/AKT signaling pathway were lower in vaccinated mice. Our research showed that the COVID-19 vaccine can have an anti-cancer effect by slowing the tumor progression and metastasis.

Prognostic value of ABO blood groups in upfront operated pancreatic ductal adenocarcinomas

PurposePancreatic ductal adenocarcinoma (PDAC) has been shown to have a lower incidence in patients with blood group O. It is currently uncertain if patients with group O have a better prognosis after pancreatectomy. This study assessed the overall survival (OS) and disease-free survival (DFS) of PDAC patients who underwent upfront pancreatoduodenectomy based on ABO blood groups.MethodsA cross-sectional study was performed including patients from two university centers. All consecutive head PDAC patients who underwent upfront pancreatoduodenectomy from 2000 to 2016 were included. OS and DFS were compared between blood groups A, B, AB, and O using Kaplan-Meier curves and log-rank tests.ResultsA total of 438 patients were included (215 women, median age 67). Pre- and intraoperative details were comparable between all subgroups. Median OS did not differ between the four blood groups (A: 23 months, 95% CI 18–28; B: 32, 95% CI 20–44; AB: 37, 95% CI 18–56 and O: 26, 95% CI 20–32, p = 0.192). Median DFS were also similar (A: 19 months, 95% CI 15–23; B: 26, 95% CI 19–33; AB: 35, 95% CI 15–55 and O: 22, 95% CI 15–29, p = 0.441). There was no OS difference between O and non-O groups (median: 26 months, 95% CI 20–33 vs. 25 months, 95% CI 20–30, p = 0.773). On multivariable analysis blood groups were not prognostic of OS. Only lymph node involvement, tumor differentiation, and adjuvant chemotherapy were independent prognostic factors.ConclusionOS and DFS were similar between all four blood groups after pancreatoduodenectomy. Independent predictors of OS were associated with tumor characteristics and adjuvant treatment.

The impact of basal cell carcinoma on the quality-of-life in older patients

Basal cell carcinoma (BCC) is the most frequent malignant tumour worldwide and incidences are rising rapidly. BCC grow locally, but can invade surrounding tissues. Little is known concerning their impact on the health-related quality of life (HrQoL), and limited available data reports contradicting results. Measuring HrQoL in BCC patients should be done using disease-specific questionnaires such as the Basal and Squamous cell carcinoma Quality of Life (BaSQoL) questionnaire. The aim of this study was to assess the BCC-related HrQoL by examining all relevant patient, tumour and treatment characteristics to identify the main factors for the BCC-related impact. Specific attention for older BCC patients wass brought forward because of the often complex decisions in this subgroup. Patients ≥ 18 years with a history of BCC were asked to fill in the BaSQoL questionnaire, consisting of 5 subdomains. Multivariable analyses were done using a generalized additive model (GAM) because of the need for incorporation of non-linear functions. The study obtained approval of the Ethics Committee of the Ghent University Hospital (EC/2019/1352). Informed consent was obtained from all subjects. All experiments were performed in accordance with relevant guidelines and regulations. Four hundred patients with a median age of 66 were enrolled. Mean BaSQoL subscores were 0.78 (SD 0.63) for ‘behaviour’, 1.01 (SD 0.73) for ‘diagnosis&treatment’, 0.90 (SD 0.73) for ‘worries’, 0.40 (SD 0.63) for ‘appearance’ and 1.20 (SD 0.75) for ‘other people’, illustrating the low to moderate impact of BCC on the HrQoL. A GAM with subsequent ANOVA testing was done for all relevant variables. In 4 out of 5 BaSQoL subdomains ‘age’ showed a significant correlation (‘behaviour’ p = 0.007; ‘diagnosis&treatment’ p = 0.026; ‘worries’ p = 0.003; ‘appearance’ p = 0.008). Lower BaSQoL scores were seen in older patients, meaning less BCC-impact on their HrQoL. There was a clear non-linear correlation between BaSQoL scores and age, illustrating that the impact of BCC on the HrQoL shows a rapid decrease starting around the age of 70. This study is the first to illustrate the relation between the BCC-related HrQoL and the age of patients with the use of a disease-specific HrQoL instrument. We found a lower BaSQoL score in older adults, with a specific age group of interest starting around the age of 70–75. This is an argument for a potential wait-and-see strategy for BCC in these patients.

Characterizing m6A modification factors and their interactions in colorectal cancer: implications for tumor subtypes and clinical outcomes

BackgroundThe study aims to comprehensively combine colorectal cancer data cohorts in order to analyze the effects of various DNA methylation-coding genes on colorectal cancer patients. The annual incidence and mortality of colorectal cancer are very high, and there are no effective treatments for advanced colorectal cancer. DNA methylation is a method widely used to regulate epigenetics in the molecular mechanism study of tumors.MethodThree single-cell cohorts GSE166555, GSE146771, and EMTAB8107, and five transcriptome cohorts GSE17536, GSE39582, GSE72970, and TCGA-CRC (TCGA-COAD and TCGA-READ) were applied in this study. 2 erasers (ALKBH5 and FTO), There are 7 writers (METTL3, METTL14, WTAP, VIRMA, RBM15, RBM15B, and ZC3H13) and 11 readers (YTHDC1, IGF2BP1, IGF2BP2, IGF2BP3, YTHDF1, YTHDF3, YTHDC2, and HNRNPA2B1, YTHDF2, HNRNPC and RBMX), a total of 20 M6A regulators, were used as the basis of the dataset in this study and were applied to the construction of molecular typing and prognostic models. Drugs that are differentially sensitive in methylation-regulated gene-related prognostic models were identified using the ConsensusClusterPlus package, which was also used to identify distinct methylation regulatory expression patterns in colorectal cancer and to model the relationship between tissue gene expression profiles and drug IC50 values. Finally, TISCH2 assessed which immune cells were significantly expressed with M6A scores. The immunosuppression of M6A methylation is spatially explained.ResultsThis study used data from 583 CRC patients in the TCGA-CRC cohort. Firstly, the mutation frequency and CNV variation frequency of 20 m6A modification-related factors were analyzed, and the corresponding histogram and heat map were drawn. The study next analyzed the expression variations between mutant and wild forms of the VIRMA gene and explored differences in the expression of these variables in tumor and normal tissues. In addition, the samples were divided into different subgroups by molecular clustering method based on m6A modification, and each subgroup’s expression and clinicopathological characteristics were analyzed. Finally, we compared prognostic differences, tumor microenvironment (TME) characteristics, immune cell infiltration, and gene function enrichment among different subpopulations. We also developed a colorectal cancer m6A-associated gene signature and validated its prognostic effects across multiple cohorts. Finally, using single-cell RNA sequencing data, we confirmed that tumor cells show elevated expression of m6A-related gene signatures.DiscussionThis study explored the mutation frequency, expression differences, interactions, molecular clustering, prognostic effect, and association with tumor characteristics of m6A modification-related factors in CRC and validated them at the single-cell level. These results clarify the association between m6A alteration and colorectal cancer (CRC) and offer important insights into the molecular recognition and management of cancer.

Treatment outcomes in retinoblastoma and the effect of tumor topography.

Retinoblastoma, the most common intraocular malignancy in children, has high fatality rates if untreated. It is crucial to monitor treatment effectiveness and explore factors influencing favorable outcomes. Our study aims to examine how tumor location impacts the response to standard treatments and the achievement of favorable outcomes among retinoblastoma patients, while controlling for other tumor-related factors. This retrospective study analyzed medical records of retinoblastoma patients from November 2012 to December 2022 enrolled in the retinoblastoma program at the Children's Cancer Center of Lebanon (established in collaboration with St.yJude Children's Research Hospital, Memphis, TN). Data were extracted from the electronic chart reviews and operative reports of examinations under anesthesia (EUAs), and included patient's demographics, tumor characteristics (size, location), and treatment parameters (treatment type, resolution, recurrence). The study included 42 patients with retinoblastoma, with a total of 57 eyes and 115 tumors/lesions. The median age at diagnosis was 12months (range: 2-36months). Among the patients, 26 (61.9%) were males and 16 (38.1%) were females. A minority of patients (21.4%) presented with unilateral involvement, whereas the majority (78.6%) had bilateral involvement. The locations of retinoblastoma lesions were distributed as follows: optic nerve (4.4%), macula (19.1%), superior (16.5%), inferior (17.4%), nasal (27.8%), and temporal (14.8%). Resolution rate tended to be highest for tumors close to optic nerve and temporal lesions, but no statistical significance was attained (p=.45). Macular lesions tended to have the fastest resolution, but again not significantly (p=.5). Multiple logistic regression revealed that the odds for resolution of tumor was not significantly associated with tumor size (p=.57) or location (p=.52). Location of retinoblastoma lesions was not directly associated with recurrence-free resolution in our cohort. Further research in large retinoblastoma databases is needed to explore the association of tumor characteristics with recurrence and the need for secondary therapeutic interventions.

Surgical management of pancreatic neoplasms in children: a single-institution experience over 15 years.

Pancreatic neoplasms are rare among children and very few studies have reported on surgical outcomes for pediatric pancreatic neoplasms. Therefore, we aimed to describe patient and tumor characteristics and report on the surgical outcomes of pediatric pancreatic neoplasm. In this retrospective single-center study, we reviewed and analyzed the data of patients who underwent surgery for pediatric pancreatic neoplasms at Severance Children's Hospital between January 2007 and December 2022. Clinical data including demographics, surgical procedures, and postoperative and long-term outcomes were evaluated. A total of 28 patients underwent surgical treatment for pancreatic neoplasms with a median age of 11.7 years (range: 0.4-17.8). The most common histological diagnosis among benign tumors was solid pseudopapillary neoplasm (SPN), which occurred in 20 patients (71.4%). This was followed by a mucinous cyst, nesidioblastosis, pseudocyst, duplication cyst, and benign cyst, each occurring in one patient (3.5%). Regarding malignant tumors, pancreatoblastoma, solid pseudopapillary carcinoma, and malignant pheochromocytoma were noted in one patient each (3.5%). Tumor locations included the head in 4 patients (14.2%), the body in 7 (25%), and the tail in 16 (57.1%), and was diffuse in 1 (3.5%). The most common surgical resection range was distal pancreatectomy, found in 22 patients (78.5%), followed by pylorus-preserving pancreaticoduodenectomy, found in 2 (7.2%); duodenum-preserving pancreatic resection, central pancreatectomy, tumor enucleation, and near-total pancreatectomy were performed in one patient each (3.5%). Overall, 4 patients developed grade B or C postoperative pancreatic fistulas, and 1 experienced postoperative mortality due to uncontrollable bleeding. The mean follow-up period was 6.1 years (range: 1-15.6 years), during which no significant impact on growth after surgery was detected. Among the 20 patients with SPN, tumor rupture occurred in 4 (20%), among whom 2 experienced tumor recurrences. Histological diagnosis of benign tumors was predominant in this case series and various extents of surgical resection were performed. Surgical treatment for pediatric pancreatic neoplasms appears to be safe and effective. However, considering the long-term prognosis of these patients, it is essential to determine the appropriate extent of surgical resection based on the location of the tumor.

Factors Affecting the Response of Triple-Negative Breast Cancer (TNBC) to Neoadjuvant Chemotherapy: A Meta-Analysis

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options. Neoadjuvant chemotherapy (NAC) is often used to downstage tumors before surgery, but response rates vary. This meta-analysis aims to identify factors that influence TNBC’s response to NAC. Methods: PubMed, Embase, and Cochrane Library databases were searched (2018-2024) for studies evaluating factors associated with TNBC response to NAC. Data on patient demographics, tumor characteristics, NAC regimens, and response rates were extracted. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects models. Results: Twenty-three studies (n=4,512 patients) were included. Younger age (OR 1.82, 95% CI 1.35-2.46), smaller tumor size (OR 0.58, 95% CI 0.41-0.82), lower clinical stage (OR 0.39, 95% CI 0.27-0.56), and absence of lymph node involvement (OR 0.42, 95% CI 0.31-0.57) were associated with improved pathological complete response (pCR) rates. NAC regimens containing platinum agents (OR 2.15, 95% CI 1.54-2.99) and immune checkpoint inhibitors (OR 1.78, 95% CI 1.23-2.58) also showed higher pCR rates. Conclusion: This meta-analysis identified several factors associated with improved TNBC response to NAC, including younger age, smaller tumor size, lower clinical stage, absence of lymph node involvement, and use of platinum-based or immunotherapy-containing NAC regimens. These findings can inform patient selection and treatment optimization for NAC in TNBC.

Transarterial Radioembolization Can Downstage Intermediate and Advanced Hepatocellular Carcinoma to Liver Transplantation.

Transarterial radioembolization (TARE) is an effective treatment to control tumor growth and improve survival in hepatocellular carcinoma (HCC). The role of TARE in downstaging patients to liver transplantation (LT) is unclear. The aim of this study was to investigate the downstaging efficacy of TARE for intermediate and advanced HCC. Intention-to-treat analysis with multistate modeling was performed. Patients moved through 5 health states: (1) from TARE to listing, (2) from TARE to death without listing, (3) from listing to LT, (4) from listing to death without LT, and (5) from transplant to death. Factors affecting the chance of death after TARE were considered to stratify outcomes. Two hundred fourteen patients underwent TARE. Of those, 43.9% had radiological response, 29.9% were listed, and 22.8% were transplanted. The probability of being alive without LT was 40.5% 1 y after TARE and 11.5% at 5 y. The chance of being listed was 9.4% at 1 y and 0.9% at 5 y. The probability of dying after TARE without LT was 38% at 1 y and 73% at 5 y. The overall survival of patients receiving LT was 61% at 5 y after transplant. Tumor beyond up-to-seven criteria, alfafetoprotein >400 ng/mL, and albumin-bilirubin ≥2 were associated with death. Three risk groups were associated with different response, chances of being listed, and receiving LT. Median survival was 3 y for low-risk, 1.9 y for intermediate-risk, and 9 mo for high-risk patients (P < 0.001). In intermediate and advanced HCC, TARE allows for a 44% chance of response, 30% downstaging, and 23% probability of permitting LT. Patient's and tumor's characteristics allow for risk stratification and predict survival from TARE.

PCSK1N as a tumor size marker and an ER stress response protein in corticotroph pituitary adenomas.

Silent corticotroph adenoma (SCA) exhibits more tumor aggressiveness features than functioning adenomas (FCA). We aimed to investigate PCSK1N expression in CA and examine if ER stress-induced responses affect cell survival in a corticotroph tumor cell model. Clinical and imaging characteristics were recorded in 33 patients with FCA (20 women, 11 macroadenomas) and 18 SCA (8 women, all macroadenomas). Gene expression of proopiomelanocortin (POMC), T-box transcription factor 19(TBX19)/TPIT, proprotein convertase subtilisin/kexin type 1(PCSK1)/PC1/3, and its inhibitor PCSK1N, was measured by RT-qPCR in adenoma tissue.Mouse pituitary corticotroph tumor (AtT-20) cells were treated with tanespimycin (17-AAG), a HSP90 chaperone inhibitor, to induce ER stress, followed by gene and protein analyses. POMC, TPIT, and PCSK1 expression were higher, whereas PCSK1N was lower in FCA compared to SCA. PCSK1N correlated with POMC (rs= -0.514, p <0.001), TPIT (rs= -0.386, p = 0.005), PCSK1 (rs= -0.3691, p = 0.008), and tumor largest diameter (rs= 0.645, p <0.001), in all CA. Induction of ER stress by 17-AAG in AtT-20 cells led to a decrease of POMC and an increase of PCSK1N gene expression at 24h. Moreover, a downregulation of cell cycle, apoptosis, and senescence pathways, and alterations in cell adhesion and cytoskeleton were observed at the protein level. PCSK1N is higher in SCA compared with FCA, and associated with corticotroph cell markers and tumor size. PCSK1N is likely to be part of the adaptive response to ER stress, potentially conferring a survival advantage to the corticotroph tumor cell in conjunction with other proteins.

Circulating Exosomal miRNA Profiles in Non-Small Cell Lung Cancers.

A growing number of studies have shown that microRNAs (miRNAs) can exert oncogenic or tumor suppressor activities in a variety of cancers, including lung cancer. Given their presence in exosome preparations, microRNA molecules may in fact participate in exosomal intercellular transfers and signaling. In the present study, we examined the profile of 25 circulating exosomal microRNAs in ostensibly healthy controls compared to patients with squamous cell lung cancers (SQCLC) or lung adenocarcinomas (LUAD). Eight miRNAs, namely, miR-21-5p, miR-126-3p, miR-210-3p, miR-221-3p, Let-7b-5p, miR-146a-5p, miR-222-3p, and miR-9-5p, were highly enriched in the cohort and selected for further analyses. All miRNAs were readily detected in non-small cell lung cancer (NSCLC) patients of both sexes at all cancer stages, and their levels in exosomes correlated with the clinicopathological characteristics of tumors. Thus, the presence of these miRNAs in circulating exosomes may contribute to the regulation of oncogenic activity in patients with NSCLC.

Extended Endoscopic Endonasal Approach for Tuberculum Sella Meningiomas: Lessons Learned

Midline meningiomas arising from the anterior skull base, particularly the planum sphenoidale and tuberculum sellae (TSM), present unique challenges due to their proximity to vital structures such as the optic apparatus. Traditionally approached via transcranial routes, these lesions often lead to chronic compression of optic nerves, resulting in visual impairment. With advancements in endoscopic skull base surgery, extended endonasal endoscopic (EEE) approaches have emerged as a viable alternative. This study aims to analyze the technical nuances and outcomes of EEE approach for excision of anterior skull base meningiomas presenting with visual impairment. Thirteen patients with TSM and visual impairment underwent EEE surgery at a single institute. Clinical, radiological, and ophthalmological evaluations were conducted pre- and post-operatively. Surgical techniques involved meticulous tumor excision, preservation of vital structures, and multi-layer skull base reconstruction. Visual outcomes, extent of resection, complications, and endocrine function were assessed. The study demonstrated significant visual improvement in 76.9% of patients, with no cases of permanent visual deterioration. Complete tumor excision was achieved in the majority, with near-total excision in selected cases due to adhesions or tumor characteristics. Complications included CSF rhinorrhea, meningitis, and transient visual field defects, all managed effectively. Endocrine function remained largely unaffected postoperatively, except for one case of diabetes insipidus. The EEE approach offers distinct advantages in accessing and excising anterior skull base meningiomas, particularly in achieving optic nerve decompression while preserving vision. Despite challenges associated with larger tumors and adhesions, careful surgical planning and techniques can optimize outcomes. This study contributes to the growing evidence supporting the efficacy and safety of EEE approaches in treating anterior skull base meningiomas, emphasizing the importance of surgical expertise and patient selection.

Abstract B093: The evaluation of the gene expression profile of pancreatic ductal adenocarcinomas (PDACs) in 3D cell culture vs in vivo and development of new 3D PDACs' models for an evaluation of anti-cancer drug testing

Abstract In the ever-evolving landscape of biomedical research, 3D Cell Culture (3DCC) systems have emerged as pivotal tools for mimicking in vivo environments and fostering more physiologically relevant cellular responses. Despite promises, 3DCC based drug discovery efforts didn’t fulfil the hopes. The classic way 3DCC is done, always starts with 2D cell culture (2DCC) followed by brief 3 day 3DCC and finally drug testing. Following those observations we decided to mimic much more than just brief 3DCC state but enhance the culture by constant 3DCC to 3DCC passages. We characterized the gene expression profiles and proteomic characteristics of pancreatic tumors concluding that prolonged 3DCC is the closest to an in vivo model. The protracted cultivation periods mimic the intricacies of the in vivo environment, enabling a more accurate representation of the molecular dynamics within pancreatic tumors. In our study, we identified a panel of genes characterized by similar expression levels between prolonged 3D cell culture and in vivo conditions, while displaying significant divergence between 2D cultures and short-term 3D cultures when compared to in vivo. These genes play a pivotal role in the progression and treatment of cancer, underscoring the potential of prolonged 3DCC of LifeGel® significance in understanding tumor biology and devising therapeutic strategies. Furthermore, we also investigated the implications of prolonged 3D in vitro cultures on evaluating anti-cancer drug activities. The findings highlight the significance of 3DCC in enhancing our understanding of pancreatic tumor biology and in refining drug screening methodologies for more effective therapeutic interventions. By providing a biomimetic microenvironment, our hydrogels facilitate the formation of complex cellular structures, enabling more accurate representation of tissue architecture and cellular interactions. We delivered LifeGel® platform which presents a myriad of opportunities for researchers seeking to enhance the fidelity and translatability of their in vitro studies into pre-clinial models. Citation Format: Marcin Krzykawski, David Earnshaw, Krzysztof Kus, Artur Pirog, Sachin Kote, Mark Treherne, Justyna Kocik-Krol. The evaluation of the gene expression profile of pancreatic ductal adenocarcinomas (PDACs) in 3D cell culture vs in vivo and development of new 3D PDACs' models for an evaluation of anti-cancer drug testing [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B093.

Abstract A061: DKK3 in pancreatic cancer – Elucidating the roles of a double-edged sword

Abstract Pancreatic ductal adenocarcinoma (PDAC) remains a highly challenging disease with a poor prognosis due to lack of diagnostic biomarkers and high tumor heterogeneity. Therefore, it is crucial to meticulously examine the intricate molecular mechanisms in PDAC. We previously identified DKK3 (Dickkopf-3) as a novel factor promoting organ regeneration during pancreatitis and established a previously unknown link between DKK3 and the Wnt and Hedgehog signaling. Given that pancreatitis is a significant risk factor for pancreatic cancer, we were motivated to investigate the potential role of DKK3 in PDAC development. We utilized PDAC mouse models driven by LSL-KrasG12D/+; Ptf1aCre/+ with wildtype, homozygous/heterozygous DKK3 deletion in both epithelial and stromal compartment while employing in vitro and ex vivo systems to examine the stage and compartment-specific roles of the same. Through a comprehensive and time-resolved analysis of tumor characteristics, we discovered that the loss of DKK3 led to rapid oncogenic transformation, marked by a significant increase in metaplasia and desmoplasia starting at an early stage (10 weeks). Ex vivo acinar-to-ductal metaplasia assay and rescue experiments with wildtype and DKK3-null acinar cells revealed that secreted DKK3 operates as a tumor suppressive roadblock in PDAC-initiating steps. This advanced preneoplastic stage translated into accelerated progression toward invasive tumors at 36 weeks, a shortened overall survival, and a higher liver metastasis incidence in the DKK3-null animals at the endpoint. Interestingly, transcriptomic analyses further validated our observation and revealed the involvement PI3-AKT signaling pathway as an underlying mechanism. Further characterization of isolated tumor cells confirmed our observations, revealing prominent mesenchymal features and enhanced migratory capacities upon loss of DKK3. Interestingly, DKK3-null PDACs exhibited a pronounced stroma remodeling with a myofibroblastic cancer-associated fibroblast-enriched environment, as well as an immunosuppressive stroma with abundant regulatory T cells and cytotoxic T cell depletion, as substantiated by coculture experiments. Intriguingly, while displaying similar phenotypic features to DKK3-null tumors, Dkk3+/- heterozygotes exhibited the most aggressive outcome. To further dissect this finding, we conducted a set of in silico approaches and immunostainings revealing persistent stromal DKK3 expression in DKK3- proficient PDACs. This suggested a possible dual role of DKK3 that could operate either as a friend or a foe depending on its spatiotemporal expression in PDAC. In line, in vitro systems demonstrated a distinct oncogenic effect of DKK3 on endpoint tumor cells, particularly promoting malignant cell migration. In summary, we propose that epithelial DKK3 exerts cell-autonomous tumor suppressive functions during the onset of PDAC, while stromal DKK3 acts as an oncogenic cue driving cancer progression. These findings highlight DKK3 as a promising biomarker and a novel therapeutic target for PDAC tumors. Citation Format: Dharini Srinivasan, Frank Arnold, Elodie Roger, Anna Härle, Michael K Melzer, Chantal Allgöwer, Patrick C Hermann, Lukas Perkhofer, Johann Gout, Alexander Kleger. DKK3 in pancreatic cancer – Elucidating the roles of a double-edged sword [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A061.

Abstract B088: Epigenetic reprograming in ATM-deficient pancreatic cancer: targeting EZH2- mediated oncogenic traits

Abstract Despite extensive research, the complex biology of pancreatic ductal adenocarcinoma (PDAC) continues to impede progress in improving its prognosis. Its resistance to conventional therapies, along with diverse mutations, necessitate improved molecular stratification to develop tailored approaches and to improve survival of PDAC patients. Our previous studies on ATM- deficient models revealed that serine/threonine kinase ATM loss induces homologous recombination deficiency (HRD), promoting invasiveness and desmoplastic reactions, while also sensitizing tumors to platinum-based therapies and PARP1 inhibition. Interestingly, our data also identified the histone-methyltransferase EZH2 as a direct ATM substrate to operate as a crucial regulator of ATM-specific oncogenic traits. In detail, murine and human ATM-deficient tumors accumulated EZH2, suggesting that ATM status contributes to rewiring the epigenetic landscape of pancreatic tumors, subsequently supporting oncogenic features. To investigate how EZH2 impacts ATM-deficient PDAC pathogenesis, we generated conditional double ATM and EZH2-knockout in the Kras G12D/+ ; Ptf1a Cre/+ mice (AKC, Atm fl/fl ; LSL-Kras G12D/+ ; Ptf1a Cre/+ , and EAKC, Ezh2 fl/fl ; Atm fl/fl ; LSL-Kras G12D/+ ; Ptf1a Cre/+ ). EZH2 depletion in AKC mice prolonged overall survival and reinstated a differentiated phenotype. Furthermore, PDAC patients with negative ATM and EZH2 expression from the TCGA-PAAD cohort (PanCancer Atlas) also showed significantly extended progression-free survival compared to ATM neg EZH2 pos patients. In line, CRISPR/Cas9-mediated EZH2 depletion in ATM-deficient pancreatic cancer cells affected their epigenetic landscape and significantly upregulated transcriptomic programs associated with cell differentiation, thereby restoring differentiated tumor features ex vivo. We showed that ATM status significantly impacts EZH2 activity through a post-translational pathway, promoting tumor supportive EZH2 activity in pancreatic cancer. ATM kinase facilitates EZH2 ubiquitination and degradation by recruiting the Cullin1 E3-ubiquitin ligase complex. Additionally, combining an EZH2 inhibitor with PARP inhibition enhances cytotoxicity in ATM- deficient HRD PDAC. Overall, our findings demonstrate that ATM deficiency drives a pro- oncogenic mesenchymal differentiation program via the histone-methyltransferase EZH2. We emphasize the importance of stratifying patients based on ATM status before considering pharmacological interference with EZH2, offering a promising approach for targeting ATM- deficient HRD tumors. Citation Format: Elodie Roger, Anna Härle, Lukas Perkhofer, Elisabeth Hessmann, Alexander Kleger, Johann Gout. Epigenetic reprograming in ATM-deficient pancreatic cancer: targeting EZH2- mediated oncogenic traits [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B088.

Organ-preserving treatment for urothelial carcinoma of the upper urinary tract

Urothelial carcinoma of the upper urinary tract is rare but the incidence is currently increasing in western countries. Radical nephroureterectomy has long been the standard treatment; however, it can lead to chronic kidney failure and also the necessity for dialysis. Therefore, organ-preserving treatment is now recommended for selected patients with low-risk tumors. The choice of treatment depends on the tumor characteristics, comorbidities and individual risk factors. Surgical options for organ preservation include ureterorenoscopy (URS), percutaneous treatment and partial ureteral resection. The URS is the most frequently used method for organ preservation. Photodynamic diagnostics (PDD) and narrow band imaging (NBI) can potentially also be used for tumor detection in the upper urinary tract. Conservative options such as topical treatment with mitomycinC or Bacillus Calmette-Guérin (BCG) and systemic treatment options are also possible.