Search Results (28,677)

In today’s oncology, immunotherapy arises as a potent complement for conventional cancer treatment, allowing for obtaining better patient outcomes. B7-H3 (CD276) is a member of the B7 protein family, which emerged as an attractive target for the treatment of various tumors. The molecule modulates anti-cancer immune responses, acting through diverse signaling pathways and cell populations. It has been implicated in the pathogenesis of numerous malignancies, including melanoma, gliomas, lung cancer, gynecological cancers, renal cancer, gastrointestinal tumors, and others, fostering the immunosuppressive environment and marking worse prognosis for the patients. B7-H3 targeting therapies, such as monoclonal antibodies, antibody–drug conjugates, and CAR T-cells, present promising results in preclinical studies and are the subject of ongoing clinical trials. CAR-T therapies against B7-H3 have demonstrated utility in malignancies such as melanoma, glioblastoma, prostate cancer, and RCC. Moreover, ADCs targeting B7-H3 exerted cytotoxic effects on glioblastoma, neuroblastoma cells, prostate cancer, and craniopharyngioma models. B7-H3-targeting also delivers promising results in combined therapies, enhancing the response to other immune checkpoint inhibitors and giving hope for the development of approaches with minimized adverse effects. However, the strategies of B7-H3 blocking deliver substantial challenges, such as poorly understood molecular mechanisms behind B7-H3 protumor properties or therapy toxicity. In this review, we discuss B7-H3’s role in modulating immune responses, its significance for various malignancies, and clinical trials evaluating anti-B7-H3 immunotherapeutic strategies, focusing on the clinical potential of the molecule. Full article

Background/Objectives: The detection of ovarian cancer remains challenging due to the lack of reliable serum biomarkers that reflect malignant transformation rather than mere tumor presence. We developed a novel biotest using an immortalized human fallopian tube epithelial cell line (TY), which exhibits anchorage-independent growth (AIG) in response to cancer-associated serum factors. Methods: Sera from ovarian and breast cancer patients, non-cancer controls, and ID8 ovarian cancer-bearing mice were tested for AIG-promoting activity in TY cells. Results: TY cells (passage 96) effectively distinguished cancer sera from controls (68.50 ± 2.12 vs. 17.50 ± 3.54 colonies, p < 0.01) and correlated with serum CA125 levels (r = 0.73, p = 0.03) in ovarian cancer patients. Receiver operating characteristic (ROC) analysis showed high diagnostic accuracy (AUC = 0.85, cutoff: 23.75 colonies). The AIG-promoting activity was mediated by HGF/c-MET and IGF/IGF-1R signaling, as inhibition of these pathways reduced phosphorylation and AIG. In an ID8 mouse ovarian cancer model, TY-AIG colonies strongly correlated with tumor burden (r = 0.95, p < 0.01). Conclusions: Our findings demonstrate that the TY cell-based AIG assay is a sensitive and specific biotest for detecting ovarian cancer and potentially other malignancies, leveraging the fundamental hallmark of malignant transformation. Full article

Tumor heterogeneity encompasses genetic, epigenetic, and phenotypic diversity, impacting treatment response and resistance. Spatial heterogeneity occurs both inter- and intra-lesionally, while temporal heterogeneity results from clonal evolution. High-throughput technologies like next-generation sequencing (NGS) enhance tumor characterization, but conventional biopsies still do not adequately capture genetic heterogeneity. Liquid biopsy (LBx), analyzing circulating tumor DNA (ctDNA), provides a minimally invasive alternative, offering real-time tumor evolution insights and identifying resistance mutations overlooked by tissue biopsies. This study evaluates the capability of LBx to capture tumor heterogeneity by comparing genetic profiles from multiple metastatic lesions and LBx samples. Eight patients from the Augsburger Longitudinal Plasma Study with various types of cancer provided 56 postmortem tissue samples, which were compared against pre-mortem LBx-derived circulating-free DNA sequenced by NGS. Tissue analyses revealed significant mutational diversity (4–12 mutations per patient, VAFs: 1.5–71.4%), with distinct intra- and inter-lesional heterogeneity. LBx identified 51 variants (4–17 per patient, VAFs: 0.2–31.1%), which overlapped with mutations from the tissue samples by 33–92%. Notably, 22 tissue variants were absent in LBx, whereas 18 LBx-exclusive variants were detected (VAFs: 0.2–2.8%). LBx effectively captures tumor heterogeneity, but should be used in conjunction with tissue biopsies for comprehensive genetic profiling. Full article

Background/Objectives: Neoadjuvant radiochemotherapy and perioperative chemotherapy are both well-established treatment strategies for locally advanced adenocarcinoma of the esophagus (EAC) and the esophagogastric junction (AEGJ). However, recent knowledge controversially discusses whether neoadjuvant radiotherapy or perioperative chemotherapy represents superior therapeutic options to prolong survival or cause less toxicity. Methods: We retrospectively analyzed 76 patients with locally advanced EAC or AEGJ treated at our tertiary cancer center between January 2015 and March 2023. Patients received either perioperative FLOT chemotherapy (n = 36) or neoadjuvant radiochemotherapy following the CROSS protocol (n = 40), followed by surgical resection and standardized follow-up. We compared survival outcomes, toxicity profiles, treatment compliance, and surgical results between the two groups. Results: There were no statistically significant differences between FLOT and CROSS treatments in five-year loco-regional controls (LRC: 61.5% vs. 68.6%; p = 0.81), progression-free survival (PFS: 33.9% vs. 42.8%; p = 0.82), overall survival (OS: 60.2% vs. 63.4%; p = 0.91), or distant controls (DC: 42.1% vs. 56.5%; p = 0.39). High-grade hematologic toxicities did not significantly differ between groups (p > 0.05). Treatment compliance was lower in the FLOT group, with 50% (18/36) not completing all the planned chemotherapy cycles, compared to 17.5% (7/40) in the CROSS group. All the patients in the CROSS group received the full radiotherapy dose. Surgical outcomes and post-surgical tumor status were comparable between the groups. Conclusions: Although perioperative chemotherapy with FLOT has recently become a standard of care for locally advanced EAC and AEGJ, neoadjuvant radiochemotherapy per the CROSS protocol remains a well-tolerated alternative. In appropriately selected patients, both approaches yield comparable oncological outcomes. Full article

Gastric adenocarcinoma is a malignant tumor that develops from the glandular cells of the inner wall of the stomach. The prevalence of this type of disease varies from 90 to 95% of all types of gastric cancer. The aim of our study was to investigate the differences in the content of cytokines and oxidative stress markers in patients with gastric adenocarcinoma associated with H. pylori infection depending on the stage. The study included 281 patients with gastric cancer. At stage I of the disease—75 people, stage II—70 people, stage III—69 people, and stage IV of the disease—67 people. The levels of TNF-α, IL-2, IL-8, IFNγ, TNF-β, IL-17A, IL-6, IL-10, and IL-4 in the blood serum of patients and healthy individuals were determined by enzyme immunoassay and plasma oxidative stress scores (MDA, SOD, CAT, GST, GPO, CP). The present study revealed that H. pylori-infected gastric adenocarcinoma at different stages is associated with different plasma levels of cytokines, lipid peroxidation products, and antioxidant defense factors. Further studies are needed to evaluate the effectiveness of therapeutic strategies combining cytokine regulation and oxidative stress to improve clinical outcomes in gastric cancer. Full article

Background/Objectives: The TOPAZ-1 phase III trial reported a survival benefit of using durvalumab, an anti-programmed death ligand 1 (anti-PD-L1) antibody, in combination with gemcitabine and cisplatin (GCD) treatment in patients with advanced biliary tract cancer. This retrospective study investigated the efficacy and safety of GCD treatment for advanced biliary tract cancer in real-world conditions. Methods: The study subjects were 52 patients with biliary tract cancer who received GCD therapy between January 2023 and May 2024. The observation parameters included the modified Glasgow Prognostic Score (mGPS), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), tumor markers (CEA, CA19-9), overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events. Results: The cohort included 36 men and 16 women, with a median age of 73.0 years. There were 36 cases of cholangiocarcinoma (distal: 10, perihilar: 19, intrahepatic: 7), 13 cases of gallbladder cancer, and 3 cases of ampullary carcinoma. The stages were locally advanced in 30 cases and metastatic in 22 cases. Biliary drainage was performed in 30 cases. There were 38 cases receiving first-line therapy and 14 cases receiving second-line or later treatments. The median values at the start of GCD therapy were ALB 3.7 g/dL, CRP 0.39 mg/dL, NLR 2.4, PLR 162.5, CEA 4.8 ng/mL, and CA19-9 255.9 U/mL. The mGPS distribution was 0:23 cases, 1:18 cases, and 2:11 cases. The treatment outcomes were ORR 25.0% (CR 2 cases, PR 11 cases), DCR 78.8% (SD 28 cases, PD 10 cases, NE 1 case), median PFS 8.6 months, and median OS 13.9 months. The PLR was suggested to be useful for predicting PFS. A decrease in CEA at six weeks after the start of treatment was a significant predictor of PFS and OS. Gallbladder cancer had a significantly poorer prognosis compared to other cancers. The immune-related adverse events included hypothyroidism in two cases, cholangitis in one case, and colitis in one case. Conclusions: The ORR, DCR, and PFS were comparable to those in the TOPAZ-1 trial. Although limited by its retrospective design and small sample size, this study suggests that GCD therapy is an effective treatment regimen for unresectable biliary tract cancer in real-world clinical practice. Full article

Background/Objectives: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents; the survival rate is as low as 24%. Accurate prediction of clinical outcomes remains a challenge due to tumor heterogeneity and the complexity of pediatric cases. This study aims to improve predictions of progressive disease, therapy response, relapse, and survival in pediatric OS using MRI-based radiomics and machine learning methods. Methods: Pre-treatment contrast-enhanced coronal T1-weighted MR scans were collected from 63 pediatric OS patients, with an additional nine external cases used for validation. Three strategies were considered for target region segmentation (whole-tumor, tumor sampling, and bone/soft tissue) and used for MRI-based radiomics. These were then combined with clinical features to predict OS clinical outcomes. Results: The mean age of OS patients was 11.8 ± 3.5 years. Most tumors were located in the femur (65%). Osteoblastic subtype was the most common histological classification (79%). The majority of OS patients (79%) did not have evidence of metastasis at diagnosis. Progressive disease occurred in 27% of patients, 59% of patients showed adequate therapy response, 25% experienced relapse after therapy, and 30% died from OS. Classification models based on bone/soft tissue segmentation generally performed the best, with certain clinical features improving performance, especially for therapy response and mortality. The top performing classifier in each outcome achieved 0.94–1.0 validation ROC AUC and 0.63–1.0 testing ROC AUC, while those without radiomic features (RFs) generally performed suboptimally. Conclusions: This study demonstrates the strong predictive capabilities of MRI-based radiomics and multi-region segmentations for predicting clinical outcomes in pediatric OS. Full article

Background: Pancreatic adenocarcinoma (PDAC) with liver oligometastases (LOM) presents a therapeutic challenge, with optimal management strategies remaining uncertain. This study evaluates the long-term outcomes, patterns of disease progression, and potential factors influencing prognosis in this patient subset. Methods: Patients diagnosed with PDAC and LOM were retrospectively analyzed. Disease progression patterns, causes of death, and predictors of long-term outcomes were assessed. Results: Among 1442 patients diagnosed with metastatic PDAC between November 2009 and July 2024, 129 (9%) presented with LOM, defined as ≤3 liver lesions each measuring <2 cm. Patients with LOM had significantly improved overall survival (OS) compared to those with high-burden disease (p = 0.026). The cause of death (local regional disease vs. systemic disease) could be determined in 74 patients (57%), among whom age at diagnosis, history of smoking, and white blood cell (WBC) count differed significantly between groups. However, no significant difference in OS was observed between the two groups (p = 0.64). Sixteen patients (22%) died from local complications of the primary tumor, including 6 patients (7%) who showed no evidence of new or progressive metastases. In competing risk and multivariable analysis, a history of smoking remained the only factor significantly associated with death due to local complications. Conclusions: Approximately one in five patients with PDAC-LOM died from local tumor-related complications—some without metastatic progression—highlighting a potential role for surgical intervention. Further multicenter studies are warranted to refine diagnostic criteria and better identify patients who may benefit from surgery. Full article

A 51-year-old female presented to the emergency department with vertigo, visual disturbances, involuntary rapid repetitive eye movements, incoordination, and imbalance. Physical examination revealed opsoclonus, myoclonus, and bilateral limb and gait ataxia. Initial workup was negative for intracranial abnormalities, and no abnormalities were noted on blood work or cerebrospinal fluid analysis. Tumor markers were within normal limits. As part of her diagnostic workup, a positron emission tomography (PET) scan was performed, which showed a highly FDG-avid solitary 7 mm left axillary lymph node. Ultrasound-guided percutaneous biopsy revealed metastatic poorly differentiated carcinoma. Histopathological examination could not conclusively distinguish between adenocarcinoma and squamous cell carcinoma. She was diagnosed with seronegative opsoclonus-myoclonus ataxia syndrome of paraneoplastic origin from an occult primary malignancy and started on pulsatile corticosteroids and intravenous immunoglobulin (IVIG), with only moderate symptomatic improvement. Given the anatomic location and immunohistochemical staining pattern of the lymph node, the malignancy was considered as being of primary breast origin. A left axillary lymph node dissection was performed, with 1/12 nodes testing positive for poorly differentiated carcinoma. The patient experienced significant improvement in her neurological symptoms 2–3 days following resection of the solitary malignant lymph node, largely regaining her functional independence. She went on to receive adjuvant radiotherapy to the breast and axilla, as well as adjuvant hormonal therapy. Full article

Despite significant advances in prostate cancer treatment over the past two decades, metastatic castration-resistant prostate cancer (mCRPC) remains incurable. We present the case of a patient with aggressive prostate cancer diagnosed 20 years ago, underscoring the value of longitudinal genomic profiling and advanced imaging to guide clinical decisions. After multiple treatment failures, genomic analyses of tissue and liquid biopsies revealed dynamic changes in tumor biology and the emergence of resistance mechanisms, particularly AR amplification, identified with a liquid biopsy test and validated by [¹⁸F]-FDHT PET scan. This finding guided treatment with bipolar androgen therapy (BAT), which achieved a dramatic clinical response, reduced AR expression, improved symptoms, and restored sensitivity to enzalutamide. This case exemplifies the utility of serial liquid biopsies in uncovering mechanisms of tumor evolution and resistance, and the crucial role of cutting-edge diagnostics in personalized cancer treatment. Full article

Background and Clinical Significance: Osteonevus of Nanta is a rare histological phenomenon characterized by bone formation within a benign melanocytic nevus, most commonly in intradermal nevi of the head and neck. Although osteonevus of Nanta is rare, ossification in a cellular blue nevus is even more uncommon. To date, only one case of a cellular blue nevus with ossification has been documented. This case report adds to the limited literature and emphasizes the clinical importance of recognizing this rare phenomenon, as osteonevus of Nanta has been potentially associated with malignant melanoma. Case Presentation: A 72-year-old woman presented with an asymptomatic, pigmented scalp lesion that had recently increased in size. On clinical examination, the tumor appeared as a well-demarcated, firm, and nodular mass with dark blueish to violet pigmentation that measured 15 × 12 × 7 mm. To ensure a definitive diagnosis and rule out malignancy, the lesion was excised with narrow margins. Histological examination revealed a cellular blue nevus with prominent osseous metaplasia. Due to the absence of clear margins, a wider re-excision was performed. No residual tumor was found, and the patient remained asymptomatic with no recurrence. Conclusions: This case represents only the second published example of a cellular blue nevus with ossification. While osteonevus of Nanta is benign, its potential association with malignant melanoma, as well as its clinical resemblance to malignant entities such as nodular melanoma, malignant blue nevus, and pigmented basal cell carcinoma, underscores the need for thorough clinical and histopathologic evaluation. Full article

Background/Objectives: The quality of surgical margins has been shown to be a prognostic factor in many sarcoma entities, yet its role in osteosarcoma remains controversial. While previous studies have shown that the outcome was not related to the margin width in bone, the impact of the extraosseous margin width (margin at the soft tissue invasion)—which needs to be close sometimes due to neurovascular structures—needs to be assessed. This study aims to evaluate the influence of soft tissue surgical margins on local recurrence and overall survival in patients with high-grade osteosarcoma. Methods: We conducted a retrospective, single-center study including 75 patients treated for high-grade osteosarcoma. All patients underwent standardized neoadjuvant chemotherapy followed by complete surgical resection. Patients were stratified into three groups based on the histological margin width of the extraosseous parts: group 1 (<1 mm), group 2 (1–5 mm), and group 3 (≥5 mm). Primary endpoints were local recurrence and overall survival (OS), analyzed using Kaplan–Meier estimates, log-rank tests, and Cox regression. Results: Local recurrence occurred in seven patients (9%). Although the overall comparison between the three groups was not statistically significant (p = 0.074), a subgroup analysis revealed a significantly higher recurrence rate in patients with margins < 1 mm compared to those with wider margins (p = 0.024). No significant differences in overall survival (OS) were observed between the groups (p = 0.896). Tumor location, metastatic status, and UICC stage were significant predictors for both endpoints in univariate analysis. However, none of these association were confirmed in multivariate analyses. Conclusions: Very close surgical margins (<1 mm) may increase the risk of local recurrence in high-grade osteosarcoma; however, they do not appear to affect overall survival. Full article

Lung cancer remains one of the most prevalent and lethal malignancies worldwide. Although conventional treatments such as surgery, chemotherapy, and radiotherapy have modestly improved patient survival, their overall efficacy remains limited, and the prognosis is generally poor. In recent years, immunotherapy, particularly immune checkpoint inhibitors, has revolutionized cancer treatment. Nevertheless, the immunosuppressive tumor microenvironment, tumor heterogeneity, and immune escape mechanisms significantly restrict the clinical benefit, which falls short of expectations. Within this context, cancer vaccines have emerged as a promising immunotherapeutic strategy. By activating the host immune system to eliminate tumor cells, cancer vaccines offer high specificity, low toxicity, and the potential to induce long-lasting immune memory. These advantages have positioned them as a focal point in cancer immunotherapy research. This paper provides a comprehensive overview of recent clinical advances in lung cancer vaccines, discusses the major challenges impeding their clinical application, and explores potential strategies to overcome these barriers. Full article

Background/Objective: Sepsis-associated acute kidney injury (SA-AKI) is a substantial contributor to mortality in critically ill patients. This study aimed to investigate the impact of gum acacia (GA) and dexamethasone (DEX) combination on lipopolysaccharide (LPS)-induced SA-AKI in rats. Methods: Thirty-six male Sprague Dawley rats were separated into six groups, including the control, GA group, LPS-induced AKI group, DEX + LPS group, GA + LPS group, and GA + DEX + LPS group. AKI was induced in rats using LPS (10 mg/kg, i.p.). GA was administered orally (7.5 g/kg) for 14 days before LPS injection, and DEX was injected (1 mg/kg, i.p.) 2 h after LPS injection. Results: LPS injection significantly (p < 0.05, vs. control group) impaired renal function, as evidenced through increased levels of kidney function biomarkers, decreased creatinine clearance, and histopathological alterations in the kidneys. LPS also significantly (p < 0.05, vs. control group) elevated levels of oxidative stress markers, while it reduced levels of antioxidant enzymes. Furthermore, LPS triggered an inflammatory response, manifested by significant (p < 0.05, vs. control group) upregulation of Toll-like receptor 4, myeloid differentiation primary response 88, interleukin-1β, tumor necrosis factor-α, and nuclear factor-κB, along with increased expression of high-mobility group box 1. Administration of GA significantly ameliorated LPS-induced renal impairment by enhancing antioxidant defenses and suppressing inflammatory pathways (p < 0.05, vs. LPS group). Furthermore, GA-DEX-treated rats showed improved kidney function, reduced oxidative stress, and attenuated inflammatory markers (p < 0.05, vs. LPS group). Conclusions: The GA-DEX combination exhibited potent renoprotective effects against LPS-induced SA-AKI, possibly due to their antioxidant and anti-inflammatory properties. These results suggest that the GA-DEX combination could be a promising and effective therapeutic agent for managing SA-AKI. Full article

Background/Objectives: Breast cancer was the leading cause of malignant tumors among women in 2022. About two-thirds of breast cancer cases are hormone-receptor-positive. In these patients, aromatase inhibitors are a mainstay of treatment, but associated musculoskeletal symptoms can negatively affect patient compliance. Aromatase-inhibitor-induced carpal tunnel syndrome represents one of the main causes of aromatase inhibitor discontinuation, with a non-compliance rate of up to 67%, potentially leading to increased cancer mortality. This study investigates estrogen receptor expression in aromatase-inhibitor-induced carpal tunnel syndrome tissues, in order to better define its etiopathogenesis and derive preventive or therapeutic measures that can improve aromatase inhibitor patient compliance. To our knowledge, there is no study on this subject in the literature. Methods: Between 2023 and 2024, we recruited 14 patients at the Jewish Hospital of Rome, including seven patients with aromatase-inhibitor-induced carpal tunnel syndrome (study group) and seven with postmenopausal idiopathic carpal tunnel syndrome (control group). Each patient was evaluated based on a clinical visit, a questionnaire, instrumental exams, and serum hormone dosages and were treated with open carpal tunnel release surgery, during which transverse carpal ligament and flexor tenosynovium samples were collected. For immunohistochemical experiments, sections were treated with anti-estrogen receptor α and anti-estrogen receptor β antibodies. Results: The immunohistochemical features in the study and control groups were similar, demonstrating that tissues affected by aromatase-inhibitor-induced carpal tunnel syndrome are targets of direct estrogen action and that estrogen deprivation is correlated with disease etiogenesis. Surgery was effective in patient treatment. Conclusions: Aromatase-inhibitor-induced carpal tunnel syndrome represents a newly defined form of the disease. This syndrome represents one of the main causes of aromatase inhibitor discontinuation, due to its negative impact on the patient’s quality of life. The identification by clinicians of aromatase inhibitor use as a possible risk factor for carpal tunnel syndrome development is of essential importance, as early diagnosis and prompt management can improve patient compliance and overall breast cancer treatment outcomes. Full article