Journal of Cancer Research and Clinical Oncology最新文献

Background: Gastric cancer (GC) is one of the most prevalent and aggressive malignancies globally, characterized by high morbidity and mortality rates despite advancements in medical technologies and screening methods. Recent studies have suggested that long non-coding RNAs (lncRNAs), particularly aspartyl-tRNA synthetase antisense RNA 1 (DARS-AS1), may play significant roles in tumor progression; however, its specific function in GC remains unclear. Therefore, this study aimed to clarify the contribution of DARS-AS1 to the progression and prognosis of GC.

Methods: We utilized quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) to assess DARS-AS1 and CD31 expression levels in GC tissues derived from various cohorts. Additionally, functional studies involving knockdown of DARS-AS1 in GC cells were conducted to evaluate the effects on migration and angiogenesis in human umbilical vein endothelial cells (HUVECs) mediated by exosomes.

Results: Our analyses revealed that DARS-AS1 is significantly upregulated in GC tissues and is associated with malignant progression and poor prognosis. Furthermore, elevated DARS-AS1 levels correlated positively with tumor microvessel density (MVD). The knockdown of DARS-AS1 resulted in decreased migration and tube-forming ability of HUVECs in vitro. Mechanistically, we demonstrated that the exosomal transfer of DARS-AS1 from GC cells activates the Wnt/β-catenin signaling pathway by targeting miR-605-5p, thus promoting angiogenesis.

Conclusion: Our findings highlight the pivotal role of DARS-AS1 in enhancing GC progression through the activation of angiogenesis via the Wnt signaling pathway. By elucidating the mechanism underlying DARS-AS1-mediated tumorigenesis, we posit that DARS-AS1 could serve as a prognostic biomarker and a potential therapeutic target for GC intervention, warranting further exploration in clinical settings.

Purpose: To describe Undifferentiated Pleomorphic Sarcoma of Bone (UPSB) treated in Germany, Austria, or Switzerland and using the same treatment-approach as for osteosarcoma.

Patients and methods: The database of the Cooperative Osteosarcoma Study Group (COSS) was screened for UPSB. Eligible patients were evaluated for patient, tumor, and treatment related variables, and outcomes.

Results: One-hundred thirty-two eligible patients were identified (median age 41.7 (range: 10.3-74.6) years; males 58%; preceding malignancies 11%; tumor-sites extremities 86%, trunk 12%, head & neck 2%). Relative tumor size was < 1/3 of the involved bone in 83% of evaluable cases, pathologic fractures were present in 14% (limb-primaries only), and primary distant metastases in 6%. All patients received chemotherapy and 96% surgery for their primary (81% limb-salvage for extremity lesions). The response rate to preoperative chemotherapy was 38%. After a median follow-up of 3.9 (1 day-34.1) years for event-free and 5.2 (0.2-34.1) years for overall survival, the 5 year event-free and overall survival probabilities were 63% (standard error: 5%) and 70% (4%), respectively. Younger patient age, an extremity tumor, and localized disease predicted superior outcomes, pathologic fractures and limb-salvage surgery worse. The extent of tumor response to pre-operative chemotherapy seemed to have no impact on prognosis.

Discussion: UPSB generally affects considerably older persons than does the more frequent osteosarcoma. Despite a lower response rate to preoperative chemotherapy, its prognosis is at least comparable, if not better. Several prognostic factors impacting outcome could be defined. These results provide a benchmark for this rare disease.

Introduction: BCR::ABL1-negative myeloproliferative neoplasms are chronic diseases characterized by high symptom burden due to systemic inflammation. Treatment objectives include cytoreduction and alleviation of symptoms. Besides standard therapies, complementary and alternative medicine (CAM) methods are frequently used and requested by cancer patients. Aim of this study was to assess the interest in and use of CAM by patients diagnosed with MPN.

Methods: This study was conducted as a patient-reported, paper-and-pencil-based questionnaire.

Results: 166 patients with MPN were included, 72 (43.4%) male and 94 (56.6%) female. Median age was 65.0 years. Diagnoses included ET 66/166 (39.8%), PV 40/166 (24.1%), MF 51/166 (30.7%) MPN-U 8/166 (4.8%) and SM-AHN 1/166 (0.6%). Overall, more frequent use of CAM was documented in females (59.6%) compared to males (41.7%), p = 0.022. A significant proportion of patients reported on the ingestion of nutritional supplements: 44/163 (26.5%) vitamin D, 26/165 (15.7%) vitamin C, 19/165 (11.4%) zinc, 13/165 (7.8%) secondary plant products, 12/165 (7.2%) selenium, and 19/165 (11.4%) multivitamin preparations. Regarding other CAM-related measures: 5/164 (3.0%) used amygdalin, 4/164 (2.4%) mistletoe therapy, 11/165 (6.6%) acupuncture, 6/165 (3.6%) homeopathy, 11/165 (6.6%) yoga, 10/165 (6%) reported receiving spiritual support, while 3/165 (1.8%) used the services of "healers". A higher rate of CAM use was found among patients with longer disease duration.

Conclusions: Use of CAM was recorded in the majority of patients with MPN. Higher use of CAM-related measures was reported by women and patients with longer disease duration. Patients should be regularly consulted about the use of CAM, its risks should be considered and pointed out, and safe methods should be recommended.

Purpose: Beyond standardized screenings, clinical assessments by psycho-oncologists during initial consultations play a key role in guiding psychosocial cancer care. Despite their relevance, these assessments have rarely been systematically examined. The aim of this study was to analyze psycho-oncologists' assessments of psychological distress and support needs and to identify factors influencing their assessments.

Methods: In a cross-sectional study, N = 9 psycho-oncologists retrospectively evaluated N = 1048 initial psychooncological consultations. The perceived psychological distress, depression, anxiety, health literacy and support needs of patients were recorded, as well as consultation-related conditions and the psycho-oncologists' own stress levels. Analyses involved descriptive statistics, group comparisons, correlations, and a binomial logistic regression.

Results: A distress score ≥ 5 was observed by psychooncologists in 74.7% of patients; 44.5% were rated as anxious, 28.6% as depressed. Mental health diagnoses were made in 25% of cases, mainly adjustment or affective disorders. Psycho-oncological support needs were identified in 75.6% of patients. Key predictors for identifying distress and needs included patients' desire for support (OR = 45.06), Knowledge and information about the consultation (OR = 2.66), and psycho-oncologists' own stress levels (OR = 1.53).

Conclusion: Psycho-oncological initial assessments are clinically relevant, but are subject to contextual and personal influences. The structured collection of consultation requests, information awareness, and health literacy, as well as interdisciplinary collaboration, can improve the assessment. The psychological stress of psycho-oncologists should also be systematically taken into account.

Leptomeningeal metastasis in patients with Epidermal Growth Factor Receptor-mutant non-small cell lung cancer carries a dismal prognosis and is associated with profound neurological morbidity. Historically, therapeutic efficacy has been severely limited, leading to poor overall survival. This review aims to synthesize the recent, albeit incremental, advances in the multidisciplinary management of this devastating complication. We delve into the evolving landscape of treatment modalities, with a particular focus on the latest generation of tyrosine kinase inhibitors and their superior central nervous system penetration. The roles of conventional approaches, including radiotherapy (both whole-brain and focal) for symptom palliation and tumor control, and intrathecal chemotherapy, are critically re-evaluated in the modern context. Furthermore, we explore the rationale and early evidence for novel combination strategies. A significant portion of our analysis is dedicated to evaluating the pharmacodynamic mechanisms of action, optimizing dosing strategies, and interpreting clinical outcomes from key trials and real-world evidence. Central to the discussion are the persistent challenges of adequate blood-brain barrier penetration, the emergence of therapeutic resistance, and the management of overlapping toxicities. We also address the parallel progress in diagnostic neuro-imaging and cerebrospinal fluid liquid biopsies, which are enhancing early detection and disease monitoring. Finally, this review outlines future research directions, emphasizing the need for randomized controlled trials and a deeper understanding of the tumor microenvironment to foster a paradigm shift in the care of patients with leptomeningeal metastasis.

Background/objectives: Malignant melanoma is an aggressive skin cancer with significant metastatic potential. Immune checkpoint inhibitors (ICIs), particularly those targeting the PD-1 pathway, have revolutionized treatment, improving survival rates. A PD-1 inhibitor, Nivolumab, has demonstrated durable responses in advanced melanoma patients. However, response variability necessitates predictive biomarkers for patient stratification.

Methods: The Gustave Roussy Immune Score (GRIm Score) is a prognostic tool integrating lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), and albumin levels to predict ICI efficacy. This retrospective study evaluated the association between the GRIm Score and response to nivolumab monotherapy in 40 patients with stage IV malignant melanoma treated between 2020 and 2024. Patients were classified into low-risk (score 0-1) and high-risk (score 2-3) groups.

Results: Results showed that patients with a low GRIm Score had significantly longer median progression-free survival (21.4 vs. 6.3 months, p = 0.003) and overall survival (26.5 vs. 7.2 months, p < 0.001). Multivariate analysis confirmed the GRIm Score as an independent prognostic factor (HR: 1.593, 95% CI: 1.156-2.197, p = 0.004), surpassing the predictive power of its components.

Conclusions: This study is the first to validate the GRIm Score in malignant melanoma, suggesting it is a valuable biomarker for patient selection in immunotherapy trials. The findings highlight its potential in refining treatment decisions, though further validation in larger, multicenter cohorts is required.

Purpose: For non-muscle invasive bladder cancer (NMIBC), instillation with Bacillus Calmette-Guérin (BCG) is a standard therapy. With a still unclear mechanism, instillation activates the innate immune system, resulting in an immunological effect on the tumour. The aim of this work was to investigate which bladder cancer (BLCA) cells can be activated by interferon (IFN) exposure.

Methods: The BLCA cell lines RT4 and SW780 were stimulated with IFN-α2, -β and -λ1 over 4-72 h. Quantitative PCR (qPCR) was used to determine the expression of IFN receptor subunits (RS) and selected interferon-stimulated genes (ISGs). Luciferase reporter assay was performed to detect the activation of the IFN responsive element (ISRE). Different signal transduction molecules of the JAK/STAT pathway were assessed by Western Blot to prove its activation in BLCA cells. The viability of the stimulated cells was measured by WST-1 assay and the apoptosis induction by caspase-3/7 assay.

Results: The JAK/STAT pathway was activated via the four RS. Upon long-term treatment, type I and type III IFNs significantly induced increased ISG expression and apoptosis induction of RT4 and SW780 cells, emphasising their antiproliferative and immunomodulatory activity. This activation was mediated by ISRE. IFN-β activated the JAK/STAT pathway with the greatest potency, highlighting its superior efficacy in modulating cellular responses in BLCA.

Conclusion: Activation of the innate immune system has the ability to trigger further infiltration of the tumour microenvironment (TME) with immune cells, which positively influence the TME in its type, density and immunofunctional orientation against BLCA.

Purpose: Multidisciplinary team (MDT) consultations are crucial for managing pulmonary nodules, yet face challenges in efficiency, evidence-based decision support, and data utilization within the MDT process. We present an integrated artificial intelligence (AI)-MDT platform that serves as an assistive tool for lung cancer MDT workflows by incorporating AI across various processes.The aim of this study is to evaluate the clinical utility and preliminary efficacy of the AI-MDT platform.

Methods: The platform comprises three core modules: process automation, intelligent decision support, and diagnostic assistance. It integrates a real-time, evidence-based knowledge base powered by large language models and deep learning, with computer vision for automatic lesion detection and feature analysis. A web-based interface allows users to interact seamlessly with the AI-MDT platform.

Results: Since its implementation in November 2023 at a tertiary Grade A hospital in China, the platform has been involved in 879 consultations, including 811 patients. AI-generated diagnostic recommendations were utilized 852 times, and decision-making support was used in 744 cases. The platform significantly increased consultation volume, reduced expert time, and enhanced data utilization compared to traditional MDT.

Conclusions: It offers clinicians tools to improve diagnostic quality and work efficiency, highlighting its significant clinical application value. These findings suggest that the proposed platform contributes to the emerging research on advances precision lung cancer management by integrating a continually updated evidence base and intelligent imaging methodologies, having potential implications for MDT processes across various medical specialties.

Background: Albumin in combination with other inflammatory markers has shown prognostic value in malignancy, including biliary tract cancer (BTC). This study aimed to evaluate the prognostic value of hypoalbuminemia alone in patients with BTC, with stratified analyses according to tumor type, treatment and sex.

Methods: A retrospective regional referral center cohort study was conducted, including consecutive patients with a measurement of preoperative albumin and intended resection of suspected BTC: intrahepatic cholangiocarcinoma (iCCA), perihilar cholangiocarcinoma (pCCA) or gallbladder cancer (GBC) between 2009 and 2017. The primary outcome was overall survival (OS), analyzed by Kaplan-Meier estimate and Cox regression.

Results: Out of 221 patients, 191 underwent resection, while 30 patients were diagnosed with unresectable BTC (14%). In the resection group, 147 patients had confirmed BTC, while 44 (20%) were postoperatively diagnosed with a benign lesion. Hypoalbuminemia (< 35 g/L) was more frequent in pCCA (75%) and GBC (59%), compared to iCCA (34%, p < 0.001). The preoperative albumin level was positively associated with resectability (p = 0.025). In patients with resection, hypoalbuminemia was associated with a tumor positive resection margin (p < 0.001). Hypoalbuminemia was a negative prognostic factor in resectable (p < 0.001) and unresectable BTC (p < 0.001), and in both women (p = 0.002) and men (p = 0.004). Hypoalbuminemia was negatively associated with OS in iCCA (p < 0.001) and GBC (p = 0.022), but not in pCCA (p = 0.210).

Conclusion: Preoperative albumin was prognostic for survival in patients with iCCA and GBC, in both women and men and regardless of tumor resectability. Patients with pCCA more often had low albumin, and hypoalbuminemia alone was not prognostic in this subgroup.