Journal of Cancer Research and Clinical Oncology最新文献

Purpose: Colorectal-based brain metastasis formation is a rare and late event in colorectal cancer (CRC) patients and is associated with poor survival. Compared with other metastatic sites, the knowledge about copy number variation (CNV) in brain metastases is still very limited. To get more information about CNVs, we applied SNP array to analyze chromosomal regions with a higher density of SNP markers.

Methods: Genome-wide high resolution single nucleotide polymorphism (SNP) array (CytoScan™ HD) analyses were carried out in matched colorectal-based lung and brain metastases of two patients.

Results: Brain metastases harbored more CNVs (77 CNVs) than pulmonary metastases (24 CNVs). Not previously described specific CNVs were: gain of 1p36.33-p36.32, 4p16.3-p16.1, 6q27, 12q24.33, 16p13.3, as well as 16p12.1-p11.2 in lung metastases and gain of 1p36.33-p36.21, 5q11.1-q13.2, 21q22.2-q22.3, 22q11.21-q12.2, as well as 22q12.3-q13.33 in brain metastases. Furthermore, we found 20 copy-neutral loss of heterozygosity (cn-LOH) regions exclusively in brain metastases, of which 11 cn-LOH regions have not been previously described.

Conclusion: Brain metastases of CRC showed more cn-LOH regions than lung metastases. Potentially affected genes within these regions could influence signaling pathways (e.g., PI3K/AKT signaling) as well as transcriptional processes. Perspectively, increased awareness of specific genetic characteristics can potentially increase the chance of early diagnosis of brain metastases, which could contribute to improved treatment options.

Purpose: Informed consent in medical care is supposed to guarantee patient autonomy. However, in practice, written consent is often inadequate for this purpose: In an effort to meet legal requirements, consent forms are often comprehensive and complex. They cover all information that could potentially be relevant, possibly overwhelming patients rather than addressing their concerns. Thus, there is an urgent need for more patient-centered consent forms. As a first step toward this goal, this study assessed the importance of various aspects of consent to genetic testing from the patients' perspective.

Methods: A cross-sectional online study was conducted with 224 participants at elevated risk for hereditary breast and/or ovarian cancer. Participants rated the importance of 14 aspects typically covered on the consent form. Each aspect was compared with all other aspects using multiple contrast tests for repeated measures. Participants also provided hypothetical consent to each aspect. Voluntary comments to the consent aspects were analyzed using qualitative content analysis.

Results: Although the majority of consent aspects were rated important in absolute terms, we observed relative differences. Specifically, consent aspects reflecting a clinical benefit for the patient and her family were rated as more important relative to all other aspects. This included, for example, consent to receiving additional test results which could imply further clinical consequences.

Conclusion: Our results may inform the communication between patients and their counseling physicians prior to genetic testing. They also provide an empirical basis for revising consent forms to better align with patients' needs while remaining legally sound.

Purpose: Salivary gland carcinomas (SGC) are rare, heterogenous malignancies with limited treatment options in recurrent or metastatic (r/m) disease. We investigated the impact of immunohistochemical and molecular markers on treatment choice and patient outcomes.

Methods: We retrospectively investigated clinical, pathological and molecular characteristics of 51 patients (pts) with r/m SGC treated at the University Hospital Zurich between 2010 and 2024. Immunohistochemical and molecular profiles were evaluated in respect to treatment selection, response and survival.

Results: Salivary duct carcinoma (SDC) and adenoid-cystic carcinoma (AdCC) were the most common subtypes. In the SDC group, in 15/20 pts personalized first-line treatment based on immunohistochemical or molecular findings resulted in higher response rates and longer duration of response compared to chemotherapy. In 20 pts of the AdCC group, no actionable alterations were identified. Yet, pts in this group demonstrated the longest overall survival despite low response rates. Among 11 pts with other subtypes, one pt with secretory carcinoma and ETV6::NTRK3 fusion experienced a sustained response to larotrectinib. HER2 IHC2 + expression without gene amplification was observed in 15 pts. Two pts responded to trastuzumab deruxtecan (TDxd) after progression on first line therapy.

Conclusions: The impact of immunohistochemical or molecular markers on treatment selection and response was most pronounced in SDC. HER2 IHC2 + expression was observed across multiple subtypes, indicating that TDxd may represent a potential treatment option for more pts than previously anticipated. The impact of comprehensive genomic profiling on targeted treatment options is currently still modest.

Purpose: Colorectal cancer (CRC) stands as a significant contributor to cancer-related mortality. Owing to its prognostic and therapeutic implications, intratumoural heterogeneity (ITH) presents a considerable challenge. We have developed an experimental framework integrating single-cell derived spheroids with proteomic profiling to facilitate a molecular, proteomic, and therapeutic characterization of intratumoural heterogeneity during CRC progression.

Methods: Single cells from the commercially available colorectal cancer cell lines SW480 (primary colorectal adenocarcinoma) and SW620 (locoregional lymph node metastasis of the same donor) were isolated using fluorescence-activated cell sorting (FACS) and subsequently cultured forming spheroids. This platform allowed controlled interrogation of clonal diversity through proliferation and viability assays, alongside deep proteomic characterization using label-free liquid chromatography-mass spectrometry (LC-MS) with data-independent acquisition. To evaluate its utility for therapeutic testing, chemotherapy response was measured after 72 h of incubation with 5-fluorouracil (5-FU).

Results: The single-cell derived spheroid system demonstrated significant heterogeneity, as evidenced by variations in morphology, growth dynamics, viability, and proteomic signatures. Protein profiling identified ITH-associated proteins (WDR5, CKB, IPO11, ATP6V1F, DCXR and PCCB) and underscored pathway variations including tumour suppressor and proto-oncogenic signalling, vascularization and metabolic regulation. Furthermore, individual spheroids exhibited differential sensitivities to 5-fluorouracil, demonstrating the platform's capacity to resolve heterogeneous therapeutic responses.

Conclusion: Our study establishes a robust and scalable method that integrates single-cell spheroids with proteomics to model and quantify ITH in CRC. By capturing clinically relevant diversity across morphology, viability, proteomic profiles and drug response, this approach provides a foundation for translating spheroid- and proteomics-based assays into personalized therapeutic testing.

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.