Malignant Involvement Research Articles

Sarcoid Nodule or Lung Cancer? A High-Resolution Computed Tomography-Based Retrospective Study of Pulmonary Nodules in Patients with Sarcoidosis

Background: The objective of this retrospective study was to compare the characteristics of sarcoid nodules and neoplastic nodules using high-resolution computed tomography (HRCT) in sarcoidosis patients. Methods: This is a single-center retrospective study. From 2010 to 2023, among 685 patients affected by pulmonary sarcoidosis, 23 patients developed pulmonary nodules of a suspicious malignant nature. The HRCT characteristics of biopsy-proven malignant (Group A) vs. inflammatory (Group B) nodules were analyzed and compared. Results: A significant difference was observed between the groups in terms of age (p = 0.012). With regard to HRCT features, statistical distinctions were observed in the appearance of the nodule, more frequently spiculated in the case of lung cancer (p < 0.01), in the diameter of the nodule (Group A: 23.5 mm; Group B: 12.18 mm, p < 0.02), in the median nodule density (Group A: 60.0 HU, Group B: −126.7 HU, p < 0.01), and in the number of pulmonary nodules, as a single parenchymal nodule was more frequently observed in the neoplastic patient group (p = 0.043). In Group A, the 18-PET-CT demonstrated hilar/mediastinal lymphadenopathy in 100% of cases; histology following surgery did not report any cases of malignant lymph node involvement. Conclusions: An accurate clinical evaluation and HRCT investigation are crucial for diagnosing lung cancer in patients with sarcoidosis in order to determine who requires surgical resection. The spiculated morphology of the nodule, greater size, the number of pulmonary nodules, and density using HRCT appear to correlate with the malignant nature of the lesion.

Pheochromocytoma-Paraganglioma Syndrome: A Multiform Disease with Different Genotype and Phenotype Features.

Pheochromocytoma and paraganglioma (PPGL) are rare tumors derived from the adrenal medulla and extra-adrenal chromaffin cells. Diagnosis is often challenging due to the great variability in clinical presentation; the complexity of management due to the dangerous effects of catecholamine excess and the potentially malignant behavior require in-depth knowledge of the pathology and multidisciplinary management. Nowadays, diagnostic ability has certainly improved and guidelines and consensus documents for treatment and follow-up are available. A major impulse to the development of this knowledge has come from the new findings on the genetic and molecular characteristics of PPGLs. Germline mutation in susceptibility genes is detected in 40% of subjects, with a mutation frequency of 10-12% also in patients with sporadic presentation and genetic testing should be incorporated within clinical care. PPGL susceptibility genes include "old genes" associated with Neurofibromatosis type 1 (NF1 gene), Von Hippel Lindau syndrome (VHL gene) and Multiple Endocrine Neoplasia type 2 syndrome (RET gene), the family of SDHx genes (SDHA, SDHB, SDHC, SDHD, SDHAF2), and genes less frequently involved such as TMEM, MAX, and FH. Each gene has a different risk of relapse, malignancy, and other organ involvement; for mutation carriers, affected or asymptomatic, it is possible to define a tailored long-life surveillance program according to the gene involved. In addition, molecular characterization of the tumor has allowed the identification of somatic mutations in other driver genes, bringing to 70% the PPGLs for which we know the mechanisms of tumorigenesis. This has expanded the catalog of tumor driver genes, which are identifiable in up to 70% of patients Integrated genomic and transcriptomic data over the last 10 years have revealed three distinct major molecular signatures, triggered by pathogenic variants in susceptibility genes and characterized by the activation of a specific oncogenic signaling: the pseudo hypoxic, the kinase, and the Wnt signaling pathways. These molecular clusters show a different biochemical phenotype and clinical behavior; they may also represent the prerequisite for implementing customized therapy and follow-up.

Clinical data and MRI features-based nomogram for differentiation of central nervous system infection and central nervous system involvement in hematological malignancy.

Central nervous system leukemia (CNSL) and central nervous system infection (CNSI) are the most important complications in patients with acute leukemia (AL). However, the differential diagnosis could represent a major challenge since the two disorders are all heterogeneous entities with overlapping clinical characteristics and radiological appearances. In this paper, we conduct a retrospective study to develop a model based on clinical data and magnetic resonance imaging (MRI) to distinguish CNSL from CNSI. A total of 108 patients with AL who underwent cranial MRI between January 2020 and December 2023 in our hospital were included. Univariate and multivariate logistic regression analyses were used to determine the independent predictors. A nomogram was developed based on the predictors, and the performance of the nomogram was evaluated by the area under the receiver operating characteristic (ROC) curve. The validation cohort was used to test the predictive model. Hyperleukocytosis at initial diagnosis, marrow state, fever, conscious disturbance, coinfection in other sites and MRI (parenchyma type) were identified as independent factors. A nomogram was constructed and the discrimination was presented as AUC = 0.947 (95% CI 0.9105-0.984). Calibration of the nomogram showed that the predicted probability matched the actual probability well.

Early palliative care involvement in gastrointestinal malignancies: A community cancer center perspective.

198 Background: Early involvement of palliative care (PC) specialists enhances quality of life for patients with advanced gastrointestinal (GI) cancer. Methods: This retrospective study evaluated patients with newly diagnosed stage III and IV GI cancer seen at a large community cancer center between 10/1/22 and 9/30/23. We compared patients seen by a PC provider in clinic at least once to those without an outpatient PC visit within the one-year study period. Results: 283 patients with stage III/IV colorectal (42%), gastroesophageal (23%), pancreatic (16%), hepatobiliary (12%), and other GI cancers (8%) received care within the study period (Table). Of these, 49 (17%) had at least one PC clinic visit, and 234 (83%) had no PC visits. Patients with pancreatic (35% vs 12%) and hepatobiliary cancer (20% vs 10%) were over-represented in the group receiving PC vs those without PC, while patients with colorectal cancer were under-represented (20% vs 47%). Greater percentages of patients in the group receiving PC completed advanced care planning (ACP) documents (63% vs 24%) and died during the study period (65% vs 15%). Conclusions: A minority of patients with GI malignancies at a large community cancer center are seen by an outpatient PC provider during the first year after diagnosis. These patients are more likely to have tumor types associated with worse prognosis, to complete ACPs, and to die within one year. Broader delivery of early PC will require expanded services in community cancer centers and continued development of tools for identifying patients most likely to benefit. The distribution of gastrointestinal cancer between outpatient palliative care visit and no outpatient palliative care visit. Primary cancer PC No PC Total Colorectal 10 (20% | 8%) 110 (47% | 92%) 120 (42% | 100%) Gastroesophageal 10 (20% | 16%) 54 (23% | 84%) 64 (23% | 100%) Pancreatic 17 (35% | 39%) 27 (12% | 61%) 44 (16% | 100%) Hepatobiliary 10 (20% | 30%) 23 (10% | 70%) 33 (12% | 100%) Other GI 2 (4% | 9%) 20 (9% | 91%) 22 (8% | 100%) Total 49 (100% | 17%) 234 (100% | 83%) 283 (100% | 100%) PC: Palliative care.

A-151 Secondary Malignancy and Visceral Involvement in Cutaneous T-Cell Lymphoma: Diagnostic Differentiation

A-151 Secondary Malignancy and Visceral Involvement in Cutaneous T-Cell Lymphoma: Diagnostic Differentiation

Prognostic significance of diffuse increased fluorine-18-fluorodeoxyglucose (18F-FDG) uptake within the reticuloendothelial system in lymphoma patients.

As constituents of the reticuloendothelial system, the spleen and bone marrow (BM) have been recognized as integral components of the systemic inflammatory response in cancer contexts, thereby serving as predictive indicators for assessing cancer prognosis. Fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) has attained widespread utilization for staging, assessing treatment response, and prognostication in lymphoma patients. Several investigations have proposed that focal increased 18F-FDG uptake in the BM or spleen may correlate with malignant involvement in lymphoma. However, scant data exist regarding the implications of diffuse BM and splenic uptake. This study aimed to explore the relationships between metabolic parameters of the spleen and BM on 18F-FDG PET/CT and inflammatory markers, and to assess their prognostic value in patients with lymphoma. A retrospective analysis was conducted on 118 patients newly diagnosed with malignant lymphoma, who underwent 18F-FDG PET/CT and exhibited diffuse increased splenic or BM uptake in 18F-FDG PET/CT imaging. The mean standardized uptake value (SUV) of the spleen, BM, and liver was calculated. The association between metabolic variables and systemic inflammatory markers was investigated, and the prognostic significance of clinicopathological and PET parameters was assessed using overall survival (OS) and progression-free survival (PFS). A statistically significant correlation was found between the spleen-to-liver SUV ratio (SLR) and inflammatory markers such as C-reactive protein (r=0.264, P=0.007) and platelet-to-lymphocyte ratio (r=0.227, P=0.021). No significant correlation was observed between BM-to-liver SUV ratio (BLR) and hematologic parameters, while concordance analysis revealed a fair agreement between BLR and bone marrow biopsy (BMB) (Cohen's Kappa-κ =0.271, P=0.002). In patients with aggressive non-Hodgkin lymphoma, both SLR [P=0.017, HR 2.715, 95% confidence interval (CI): 0.875-8.428] and BLR (P=0.044, HR 0.795, 95% CI: 0.348-1.813) were significantly linked to OS, while SLR (P=0.019, HR 2.223, 95% CI: 1.139-4.342) emerged as a significant prognostic factor for PFS. This study highlighted that diffuse increased splenic 18F-FDG uptake in lymphoma patients was closely associated with inflammation, whereas diffuse BM uptake was likely attributable to BM infiltration rather than inflammatory changes. Furthermore, both parameters held promise as prognostic indicators for patients with aggressive lymphoma.

777. COMBINED OESOPHAGEAL AND AIRWAY STENTING FOR MALIGNANT OESOPHAGEAL STRICTURES: THE UK’S LARGEST TERTIARY CENTRE EXPERIENCE AND DEVELOPMENT OF A NOVEL ALGORITHM

Abstract Background Malignant oesophageal strictures can cause airway compromise and fistula formation. Combined oesophageal and airway stenting is a potential treatment yet no guidelines exist. This study aims to describe the outcomes of same-session oesophageal and airway endoscopic stenting for malignant strictures and propose an algorithm for intervention. Methods A retrospective study on patients undergoing same-session gastroenterology (GI) and respiratory endoscopy at University College London Hospital, 2019-2023. All procedures were with anaesthetic-led propofol sedation. Endoscopic decision making was based on pre-procedure multidisciplinary team meeting (MDM) and intra-procedure clinical assessment. Data collected included malignancy type, luminal narrowing, complications, and mortality. Results 26 patients were identified. Mean age was 63 years. Cancer type was oesophageal (81%) or lung (19%). The most common referral indication was dysphagia (42%); airway compromise was often seen on imaging (65%). Stent insertion was oesophageal only (35%), airway only (19%) and dual (27%). Airway stenting was common (80%) if airway stenosis was >50%. No airway stenting occurred if stenosis was <50%. After oesophageal stenting, repeat bronchoscopy showed increased airway stenosis in 4 patients (25%). The only intraoperative complication was one oesophageal perforation. New tracheooesophageal fistula was the most common post-intervention complication (15%). Median time from malignancy diagnosis to death was 7.9 weeks. Conclusion We present the first algorithm (Figure 1) for endoscopic stenting in patients with malignant oesophageal stricture and airway involvement. We suggest upper GI and respiratory MDM to plan same-session endoscopy with decision-making framed by patient-centred goals given their poor prognosis.

Surgical management and histopathological patterns of periampullary cancers in Sudanese patients: A single‐center prospective study

AbstractBackgroundHistopathological patterns of periampullary cancers (PAC) provide valuable information for clinicians in the selection of effective postoperative therapies and serve as a prognostic marker for patients. Therefore, this study was conducted to determine the surgical management and histopathological patterns of PAC necessary to achieve excellent surgical outcomes.MethodsThis prospective study was conducted from October 2021 to September 2023 at Ibn Sina Specialized Hospital, Khartoum, Sudan. Eighty patients diagnosed with resectable PAC were enrolled.ResultsPAC was more prevalent in male patients (52.5%), with a male: female ratio of 1.1:1.0. The peak incidence occurred between 46 and 60 years, representing 38.75% of patients. The most significant reported comorbidity was cigarette smoking (36.25% of patients). Scleral icterus was found in 47.5% of patients. Pancreatic head cancer was found in 55% of patients. Histopathological analysis revealed adenocarcinoma in 82.5% of patients. R0 resection (tumor‐free margins) was the most common resection category (87.5% of patients). Lymphovascular invasion was detected in 37.5% of patients. Malignant lymph node involvement (1–3 nodes) was found 47.5% of patients. Perineural invasion was found in 55%. Finally, the most common histopathological differentiation of PAC was well‐differentiated (Grade I) in 67.5% of patients. The mortality rate was 0%.ConclusionsUpdated knowledge regarding the management modalities of PAC is a prerequisite for accurate histopathological assessment and good surgical outcomes. Furthermore, histopathological analysis helps clinicians to select effective postoperative therapies for greater improvement in survival outcomes.

Classic Hodgkin Lymphoma presenting as ANA positive chronic papular urticaria like skin lesions – A case report

The skin acts as a natural barrier between internal organs and the external environment. Many haematological neoplasms occur in the skin as a primary malignant transformation, as secondary involvement, or as paraneoplastic cutaneous manifestations. Malignant skin involvement in Hodgkin lymphoma is uncommon while paraneoplastic cutaneous involvement can occur as eczema, pruritus, erythema nodosum, and icthyosiform atrophy.1This case report describes a 25-year-old woman with a persistent pruritic rash, who was treated as chronic papular urticaria, before finally being diagnosed as Classic Hodgkin Lymphoma. This highlights the challenge of early diagnosis of cutaneous manifestations of Hodgkin lymphoma and the importance of considering malignancies in refractory dermatological conditions. This case also suggests a potential role for ANA patterns as diagnostic markers in Hodgkin lymphoma.

Contrast-enhanced US in Renal Transplant Complications: Overview and Imaging Features.

Renal transplant is the first-line treatment of end-stage renal disease. The increasing number of transplants performed every year has led to a larger population of transplant patients. Complications may arise during the perioperative and postoperative periods, and imaging plays a key role in this scenario. Contrast-enhanced US (CEUS) is a safe tool that adds additional value to US. Contrast agents are usually administered intravenously, but urinary tract anatomy and complications such as stenosis or leak can be studied using intracavitary administration of contrast agents. Assessment of the graft and iliac vessels with CEUS is particularly helpful in identifying vascular and parenchymal complications, such as arterial or venous thrombosis and stenosis, acute tubular injury, or cortical necrosis, which can lead to graft loss. Furthermore, infectious and malignant graft involvement can be accurately studied with CEUS, which can help in detection of renal abscesses and in the differentiation between benign and malignant disease. CEUS is also useful in interventional procedures, helping to guide percutaneous aspiration of collections with better delimitation of the graft boundaries and to guide renal graft biopsies by avoiding avascular areas. Potential postprocedural vascular complications, such as pseudoaneurysm, arteriovenous fistula, or active bleeding, are identified with CEUS. In addition, newer quantification tools such as CEUS perfusion are promising, but further studies are needed to approve its use for clinical purposes. ©RSNA, 2024 Supplemental material is available for this article.

Distribution and predictors of F-18-FDG uptake values of non-malignant cervical lymph nodes in pediatric patients

BackgroundF-18-flurodeoxyglucose (FDG) PET/CT is routinely used for staging, evaluation of response to treatment and follow-up of most pediatric malignancies. Cervical lymph nodes can be involved in some pediatric malignancies, but increased uptake in non-malignant cervical lymph nodes is not exceptional in this population. The aim of the present study is to identify predictors of the maximum uptake in non-malignant cervical lymph nodes in the pediatric population.Methods191 FDG PET/CT studies of pediatric patients without malignant involvement of cervical lymph nodes were retrospectively reviewed. The maximal Standard Uptake Value in the hottest cervical lymph node (SUVmaxCLN), as well as demographic, technical and imaging variables were recorded. The predictive effect of those variables on SUVmaxCLN was estimated using linear regression models.ResultsIncreased FDG activity in cervical nodes was observed in 136/191 studies (71%). The mean SUVmaxCLN was 2.2 ± 1.3. Ipsilateral palatine tonsil SUVmax, mean liver uptake, and treatment status were all statistically significant predictors of SUVmaxCLN. However, in multivariate regression analysis, only ipsilateral palatine tonsil SUVmax was found to be significant. In addition, SUVmaxCLN was greater than the mean liver uptake in 50% of all studies. This proportion was higher in younger children, reaching 77% of studies of children younger than six years.ConclusionSUVmax in ipsilateral palatine tonsil is a strong predictor of the maximal uptake value of non-malignant cervical lymph nodes in children. The intensity of uptake in non-malignant cervical lymph nodes is frequently higher than liver uptake in children, and this tendency increases for younger patients.Trial was registeredIn the internal hospital registry under TRN 0209-22-HMO on date 23.04.2022.

Secondary cardiac lymphoma presenting with cardiac tamponade and cardiac mass: a case report

BackgroundCardiac tamponade as the presenting manifestation of systemic lymphoma is relatively uncommon. Pericardium is the commonest site of involvement in secondary malignancies with systemic lymphoma involving the heart in 20% of the cases.Case presentationWe describe a case of a 78-year-old gentleman, who presented with symptoms of new onset cardiac failure, and hemodynamic compromise. An echocardiography revealed cardiac tamponade, necessitating an emergency pericardiocentesis. With the aid of multimodality imaging, he was found to have a right atrioventricular groove mass, widespread lymph node enlargement with bone and peritoneal involvement. Ultimately, a histopathological evaluation revealed a diagnosis of Diffuse Large B Cell Lymphoma (DLBCL).ConclusionsOur case illustrates that a patient with DLBCL may present with cardiac tamponade as a result of metastasis. This diagnosis, although rare, is likely to be missed, which can cause fatal complications, such as cardiac tamponade, fatal arrhythmias or sudden cardiac death.

Abstract PO5-19-01: The HER2-RADiCAL study (Response ADaptive CAre pLan) – Tailoring treatment for HER2 positive early breast cancer

Abstract Background The presence or absence of residual disease following neoadjuvant systemic anti-cancer therapy (neoSACT) for HER2-positive early breast cancer (HER2+ EBC) provides powerful prognostic information. Pathological complete response (pCR) following neoSACT, particularly in patients with earlier clinical TNM stage at diagnosis, identifies a population with excellent survival outcomes in whom the balance of toxicity associated with the current treatment pathway may be disproportionate to absolute clinical benefit. Aims >HER2-RADiCAL seeks to reduce the treatment burden and healthcare costs of treating HER2+ EBC by testing the hypothesis that pCR can be used as a functional response biomarker to select patients who can safely receive less systemic therapy with minimal/no loss of efficacy. Trial design and eligibility criteria HER2-RADiCAL is a response-directed interventional cohort/threshold-crossing design study embedded within a real-world data-driven clinical pathway model. Patients with ER-positive or negative HER2+ EBC with cT1N1 or cT2N0-1 stage at diagnosis are eligible after completion of standard of care neoSACT and locally determined pCR (ypT0/Tis ypN0). Patients with pathological features consistent with previous malignant involvement in >4 nodes are not eligible. Adjuvant trastuzumab +/- pertuzumab may have continued prior to study entry provided no more than 9 cycles of trastuzumab are received. After registration all participants receive a total of 9 cycles of trastuzumab including those administered prior to study entry. Participants receive no further pertuzumab and no adjuvant chemotherapy. Adjuvant endocrine therapy and radiotherapy are given as per standard of care. Central pathology review of pCR status will be conducted in a subset of cases. A Study Within a Trial (SWAT) will explore identification of factors influencing patient decision-making for participation in studies of response-adapted treatment. Statistical methods The primary endpoint is relapse-free interval. Recruitment of 720 participants over 3.5 years will provide 90% power to exclude an event rate >6.5% at 3 years (expected event rate ≤4%). Secondary endpoints include relapse-free survival, invasive breast cancer-free survival, invasive disease-free survival, distant recurrence-free interval, breast cancer-free interval, overall survival, treatment pathway adherence and cost-effectiveness. An interventional cohort is preferred to a randomised non-inferiority trial based on the known event rate in this population which is sufficiently low such that any deviation from this expected event rate would indicate failure of the reduced therapy strategy. Real-world data driven clinical pathway model Health economic modelling will compare the protocol-driven study cohort with two comparator pathways: a non-response adapted maximum therapy pathway (the standard clinical pathway prior to the study) and a real-world representative pathway derived from anonymised data for all patients treated for HER2+ EBC within the UK NHS. Patient and public involvement Our PPI partners continue to shape this research, holding key roles as trial management group members, overseeing progress of the study, contributing to protocol amendment development, and design and implementation of the SWAT. Current status The first patient was enrolled in December 2021. At 10th July 2023, 25 research sites have opened with 39 participants recruited. Site opening continues with a minimum target of 40. Responding to continued use of anthracycline-based regimens in UK practice, eligibility criteria have recently been extended to permit entry of patients who have received anthracycline-containing neoSACT. For further information contact her2radical-icrctsu@icr.ac.uk. Citation Format: Iain Macpherson, Stuart McIntosh, Lucy Kilburn, Holly Tovey, Laura Moretti, Katie Goddard, Indrani Bhattacharya, Clinton Boyd, Cliona Kirwan, Ciara O'Brien, Duncan Wheatley, Jennifer Glendenning, Mairead MacKenzie, Hilary Stobart, Claire Snowdon, Andrew Wardley, Abeer Shaaban, Peter Hall, David Cameron, Judith Bliss. The HER2-RADiCAL study (Response ADaptive CAre pLan) – Tailoring treatment for HER2 positive early breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-19-01.

Pan-Cancer Analysis Shows that KIFC2 is a Potential Prognostic and Immunotherapeutic Biomarker for Multiple Cancer Types Including Bladder Cancer.

KIFC2 plays an important role in prostate cancer progression and chemotherapy resistance, but the mechanism of its involvement in other malignancies remains unclear. Therefore, this study aimed to analyze and validate the mechanism of effect of KIFC2 in multiple tumors. Bioinformatic analysis was performed in conjunction with multiple databases (The Cancer Genome Atlas, Genotype-Tissue Expression Project, Human Protein Atlas, etc.) to fully explore the potential role of KIFC2 within individual tumors and to analyze the correlation with major research components such as prognosis, mutations, and the tumor microenvironment. The expression of KIFC2 demonstrates a significant correlation with the prognosis, clinical phenotype, tumor mutational burden, microsatellite instability, and tumor microenvironment across various malignancies and is associated with the modulation of diverse functional and signaling pathways. The differences in the expression of KIFC2 in the bladder cancer tissues (14 pairs) were statistically significant. The pan-cancer analysis in this study revealed the multifunctionality of KIFC2 in a variety of tumors, indicating a possible prognostic predictor and potential therapeutic target for tumors.

Open versus robot-assisted retroperitoneal tumors resection involving inferior vena cava, abdominal aorta, and renal hilum: a comparative study

IntroductionSurgery is currently the only effective treatment for retroperitoneal tumors that do not involve any specific organ. The use of robots for removing both benign and malignant retroperitoneal tumors is considered safe and feasible. However, there is insufficient evidence to determine whether robotic retroperitoneal tumor resection (RMBRs) is superior to open retroperitoneal malignant resection (OMBRs). This study compares the short-term outcomes of robotic excision of benign and malignant retroperitoneal tumors with open excision of the same-sized tumors.MethodsThe study compared demographics and outcomes of patients who underwent robotic resection (n = 54) vs open resection (n = 54) of retroperitoneal tumors between March 2018 and December 2022. A 1:1 matching analysis was conducted to ensure a fair comparison.ResultsThe study found that RBMRs resulted in reduced operative time (OT), estimated blood loss (EBM), and postoperative hospital stay (PSH) when compared to OBMRs. Additionally, RBMRs reduced EBL, PHS, and OT for patients with malignant tumor involvement in major vessels. No significant differences were found in tumor size, blood transfusion rate, and morbidity rate between the RBMRs and OBMRs groups.ConclusionWhen comparing RMBRs to OMBRs, it was observed that RMBR was associated with lower (EBL), shorter postoperative hospital stays (PHS), and reduced operative time (OT) in a specific group of patients with both benign and malignant tumors.

Abnormal upregulation of NUBP2 contributes to cancer progression in colorectal cancer.

Colorectal cancer (CRC), a digestive tract malignancy with high mortality and morbidity, lacks effective biomarkers for clinical prognosis due to its complex molecular pathogenesis. Nucleotide binding protein 2 (NUBP2) plays a vital role in the assembly of cytosolic Fe/S protein and has been implicated in cancer progression. In this study, we found that NUBP2 was highly expressed in CRC by TCGA database analysis. Subsequently, we verified the expression ofNUBP2 in CRC tumor tissues and para-carcinoma tissues using IHC staining, andfurther investigated its association with clinicopathological parameters. In vitro cell experiments were conducted to assess the role of NUBP2 in CRC by evaluating cell proliferation, migration, and apoptosis upon NUBP2 dysregulation. Furthermore, we established a subcutaneous CRC model to evaluate the impact of NUBP2 on tumor growth in vivo. Additionally, we performed mechanistic exploration using a Human Phospho-Kinase Array-Membrane. Our results showed higher expression of NUBP2 in CRC tissues, which positively correlated with the pathological stage, indicating its involvement in tumor malignancy. Functional studies demonstrated that NUBP2 knockdown reduced cell proliferation, increased apoptosis, and impaired migration ability. Moreover, NUBP2 knockdown inhibited tumor growth in mice. We also observed significant changes in the phosphorylation level of GSK3β upon NUBP2 knockdown or overexpression. Additionally, treatment with CHIR-99021 HCl, an inhibitor of GSK3β, reversed the malignant phenotype induced by NUBP2 overexpression. Overall, this study elucidated the functional role of NUBP2 in CRC progression both in vitro and in vivo, providing insights into the molecular mechanisms underlying CRC and potential implications for targeted therapeutic strategies.

Exploring the potential of EphA2 receptor signaling pathway: a comprehensive review in cancer treatment.

The protein encoded by the ephrin type-A receptor 2 (EphA2) gene is a member of the ephrin receptor subfamily of the receptor tyrosine kinase family (RTKs). Eph receptors play a significant role in various biological processes, particularly cancer progression, development, and pathogenesis. They have been observed to regulate cancer cell growth, migration, invasion, tumor development, invasiveness, angiogenesis, and metastasis. To target EphA2 activity, various molecular, genetic, biochemical, and pharmacological strategies have been extensively tested in laboratory cultures and animal models. Notably, drugs, such as dasatinib, initially designed to target the kinase family, have demonstrated an additional capability to target EphA2 activity. Additionally, a novel monoclonal antibody named EA5 has emerged as a promising option to counteract the effects of EphA2 overexpression and restore tamoxifen sensitivity in EphA2-transfected MCF-7 cells during in vitro experiments. This antibody mimicked the binding of Ephrin A to EphA2. These methods offer potential avenues for inhibiting EphA2 activity, which could significantly decelerate breast cancer progression and restore sensitivity to certain drugs. This review article comprehensively covers EphA2's involvement in multiple malignancies, including ovarian, colorectal, breast, lung, glioma, and melanoma. Furthermore, we discuss the structure of EphA2, the Eph-Ephrin signaling pathway, various EphA2 inhibitors, and the mechanisms of EphA2 degradation. This article provides an extensive overview of EphA2's vital role in different types of cancers and outlines potential therapeutic approaches to target EphA2, shedding light on the underlying molecular mechanisms that make it an attractive target for cancer treatment.

Schwann cells in pancreatic cancer: Unraveling their multifaceted roles in tumorigenesis and neural interactions

Pancreatic ductal adenocarcinoma (PDAC), characterized by heightened neural density, presents a challenging prognosis primarily due to perineural invasion. Recognized for their crucial roles in neural support and myelination, Schwann cells (SCs) significantly influence the process of tumorigenesis. This review succinctly outlines the interplay between PDAC and neural systems, positioning SCs as a nexus in the tumor-neural interface. Subsequently, it delves into the cellular origin and influencers of SCs within the pancreatic tumor microenvironment, emphasizing their multifaceted roles in tumor initiation, progression, and modulation of the neural and immune microenvironment. The discussion encompasses potential therapeutic interventions targeting SCs. Lastly, the review underscores pressing issues, advocating for sustained exploration into the diverse contributions of SCs within the intricate landscape of PDAC, with the aim of enhancing our understanding of their involvement in this complex malignancy.

Clinical Significance and Functional Insights of Tesmin in Hepatocellular Carcinoma.

Tesmin, a 60 kDa protein encoded by the metallothionein-like 5 (MTL5) gene, plays a vital role in spermatogenesis and oogenesis. Recent research has unveiled its potential involvement in malignancies, although its impact on HCC remains poorly understood. In this study, we sought to elucidate the clinical significance of tesmin in HCC patients. We investigated the relationship between tesmin expression and the prognosis of individuals with hepatocellular carcinoma (HCC), as well as its potential role in tumor proliferation and invasion. Immunohistochemistry (IHC) was employed to assess the expression of tesmin in HCC tissues. Chi-square tests were conducted to analyze the correlation between tesmin expression and various clinicopathological features among HCC patients. For survival analysis, we employed the Kaplan-Meier method and conducted Cox regression analyses. To investigate the functional role of tesmin, we utilized shRNA constructs for transfection-mediated knockdown. Proliferation was assessed using the CCK-8 assay, and invasive capability was determined through Matrigel Transwell assays. IHC results indicated that tesmin expression was prominently observed in cancerous tissue. Notably, we observed a significant association between tesmin expression and tumor stage and invasion in HCC patients from both our medical center and TCGA dataset. Survival analysis further revealed that tesmin expression emerged as an independent prognostic factor for overall survival among individuals with HCC. Furthermore, cellular experiments demonstrated that knockdown of tesmin led to decreased proliferation and invasion of HCC cells. Our findings suggest that tesmin may serve as a novel prognostic marker for HCC, highlighting its potential as a target for further research into HCC treatment. Additionally, the functional experiments support the notion that tesmin may participate in promoting the proliferation and invasion of HCC cells, warranting further investigations into its mechanistic involvement in HCC progression.

Identification and validation of prognostic genes and immune landscape signatures based on a fatty acid oxidation‑related risk score model in glioma.

Fatty acid oxidation (FAO) plays a crucial role in glioma metabolism and its interaction with the immune microenvironment. The aim of the present study was to investigate the relationship between FAO-related genes and glioma by constructing gene clusters using a glioma cohort. A total of 287 differentially expressed genes related to FAO were identified and the top 50 genes were selected based on their P-values. Subsequently, patients were classified into two distinct gene subtypes (A and B) based on these genes. Scores for each patient were calculated using the 50 genes and the patients were divided into the high and low-score groups accordingly. Patients in subtype B exhibited higher tumor grades and poor prognostic factors such as older age and worse survival rates. The high-score subgroup had unfavorable indicators, including isocitrate dehydrogenase 1 wild-type, high tumor grade and 1p19q non-codeleted, while immune checkpoint expression was generally higher in the high-score subgroup. The constructed scoring model was validated using an external dataset, and the tissue inhibitor of metalloproteinase 1 gene was identified through protein interaction analysis, suggesting its potential involvement in glioma malignancy and promotion of glioblastoma proliferation. In conclusion, FAO-related genes may contribute to tumor development through immune mechanisms and the present study may provide novel insights for potential therapeutic strategies in glioma treatment.