Cancer Management and Research最新文献

Autologous chimeric antigen receptor-modified T-cell therapy (CAR-T) has revolutionized treatment paradigms across multiple lymphoid malignancies, including relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). The introduction of the CD19-directed CAR-T product brexucabtagene autoleucel (brexu-cel; Tecartus) in October 2021 made this treatment approach available for the first time for adults with R/R B-ALL, a historically challenging clinical entity to treat. In this review, we will discuss the pivotal clinical trial data from the ZUMA-3 study that led to the US Food and Drug Administration (FDA) approval of brexu-cel, including clinical outcomes and key toxicity data (most importantly, the incidence and severity of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome). Additionally, we will compare and contrast these data from the ZUMA-3 study with "real-world" data from examinations of patient outcomes with brexu-cel as an FDA-approved therapy in R/R B-ALL, and discuss practical considerations with brexu-cel use in the clinic, including the role of consolidative allografting for patients post-brexu-cel. We finish by discussing future directions for CAR-T use in R/R B-ALL with the anticipated introduction of a new CD19-directed CAR-T product - obecabtagene autoleucel - in the near future.

Background: To analyze the risk factors of cervical lymph node metastasis (LNM) of thyroid papillary carcinoma (PTC) and construct the prediction model.

Methods: Clinical data of 1105 patients with pathologically confirmed PTC in our hospital from February 2019 to May 2024 were retrospectively analyzed, and randomly divided into a training set and validation set according to the proportion of 7:3. With cervical central LNM (CLNM) and lateral LNM (LLNM) as outcome variables respectively, ultrasound characteristics were analyzed and C-TIRADS scores were performed Combined with the general situation of the patient, preoperative serum thyroglobulin (Tg) level, BRAFV600E (hereinafter referred to as BRAF) gene mutation and other characteristics of the patient, analysis was conducted to determine the independent risk factors for cervical CLNM and LLNM of PTC, and establish Nomogram prediction models. The test data set is used to validate the model. The area under the ROC curve (AUC) and the decision curve analysis (DCA) were used to evaluate the prediction efficiency of the model.

Results: The analysis shows that male, age < 55 years old, tumor diameter ≥ 1 cm, capsular invasion, positive serum thyroglobulin (Tg), BRAF gene mutation type and C-TIRADS score are independent risk factors for cervical CLNM in PTC (P < 0.05). Tumor diameter ≥ 1 cm, capsular invasion, tumor located at the upper pole and presence of CLNM are independent risk factors for LLNM in PTC. Based on the above risk factors, Nomogram prediction models for CLNM and LLNM are constructed respectively. The AUC of the CLNM prediction model is 91.5%. LLNM model is 96.1%.

Conclusion: Ultrasound indicators, C-TIRADS score combined with BRAF gene status, Tg and clinical indicators of patients have important value in predicting cervical CLNM and LLNM in PTC. The Nomogram prediction models constructed based on the above indicators can effectively predict the risk of LNM in PTC.

Purpose: The objective of this study was to compare the clinical outcomes of stereotactic body radiation therapy (SBRT) in elderly patients aged 65 or older with clinical stage I-II non-small-cell lung cancer (NSCLC), specifically examining the differences between centrally located lung tumors and peripherally located lung tumors.

Methods: From April 2009 to January 2020, a total of 136 patients with 136 tumors (65 central, 71 peripheral; NSCLC) at an early stage (T1-3N0M0) were treated with SBRT at a single institution. Central/peripheral location was assessed retrospectively on planning CT scans. A propensity score matching analysis was utilized to compare the two groups. In addition, the prognosis and related toxicity were compared between the two study arms.

Results: A total of 33 central tumors and 33 peripheral tumors were matched and analyzed. The results showed no significant differences in overall survival (OS) and progression-free survival (PFS) between the two groups. The 2-year OS was 71.88% (95% CI, 57.87%-89.27%) in the central lung cancer group, while it was 93.94% (95% CI, 86.14%-100.00%) in the peripheral lung cancer group (P=0.462). The 2-year PFS was 43.75% in the central lung cancer group, while it was 78.79% in the peripheral lung cancer group (P=0.279). Further subgroup analysis indicated that the location of peripheral tumor have a positive impact on OS in patients with adenocarcinoma. The occurrence of local failure, regional failure, or distant failure was comparable between central and peripheral tumors. There was no statistically significant difference in toxicity between the central and the peripheral tumor groups.

Conclusion: The outcomes of SBRT for central tumors versus peripheral lung tumors in elderly patients with early-stage NSCLC were similar. SBRT demonstrated a similar level of safety in terms of toxicity for both central and peripheral lung tumors.

Purpose: Resilience has been suggested as an important predictor of both physical and mental health-related quality of life in breast cancer patients. However, it is unclear why resilient women handle their diagnosis better, not only mentally, but also physically. The aim of this study was to investigate paths between resilience, physical activity, and mental, physical, and global health-related quality of life in breast cancer patients.

Patients and methods: Structural equation modeling was conducted to evaluate the proposed structural paths using a sample of 638 women with newly diagnosed breast cancer patients from Sweden.

Results: Resilience was directly associated with physical activity and mental health-related quality of life. It was indirectly associated with physical functioning, through mental health-related quality of life and physical activity. Resilience was also indirectly associated with global quality of life, through mental health-related quality of life.

Conclusion: Mental health support and encouraging physical activity may be especially relevant to enhance all aspects of health-related quality of life early in the breast cancer process. Results should be replicated longitudinally.

Purpose: The aim of this study was to explore the immune subtypes of endometrial cancer (EC) and its characteristics by immunogenes from the perspective of multidimensional genomics (multi-omics).

Patients and methods: Immune subtypes were carried out using an unsupervised non-negative matrix factorization clustering (NMF) method and their characteristics were analysed. Key genes were identified using random forest analysis. A predictive model for immune subtypes and their clinical prognosis were constructed. The relationship between immune subtypes and molecular subtypes was investigated.

Results: Two immune subtypes C1 and C2 were available. C2 patients were younger, less graded, had significantly higher immune cell infiltration, immune checkpoint expression, tumor neoantigens, tumor mutation load than C1 (P<005). S100A9, CD3D, CD3E, HLA-DRB1 and IL2RB were the key genes with significant survival outcomes. S100A9 expression was lower in C2 than C1, and IL2RB, HLA-DRB1, CD3E and CD3D expression was higher than C1 (P<0.05). The predictive accuracy of five key genes for immune subtypes was good, with a Receiver operating characteristic of 0.941. The incidence of TP53abn type in C2 was significantly lower than that of C1, and the incidence of POLE type was significantly higher than that of C1 (P<0.0001).

Conclusion: EC can be divided into two immune subtypes based on immunogenes. Low expression of S100A9 and high expression of IL2RB, HLA-DRB1, CD3E, and CD3D suggest sensitivity to immunotherapy and a good prognosis.

Introduction: Incidental Enhancement Lesions (IELs) complicate patient management but may be detected through multiparameter MRI including dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) and synthetic magnetic resonance imaging (syMRI). The multiparameter MRI model gave greater objectivity to avoid unnecessary biopsy.

Case presentation: A 60 year-old woman had a history of occasional right breast pain and a mass was identified in the right breast. A thickening in the upper quadrant of the right outer breast was found during physical examination but no mass was palpable. Breast dynamic contrast enhancement MRI and synthetic MRI were performed prior to ultrasound-guided biopsy of the right breast lesion. Resection of the right breast lesion and sentinel lymph node was performed 2 days later. Chronic inflammation, locally invasive ductal carcinoma and high-grade ductal carcinoma in situ were found by pathological examination.

Discussion: Differentiation between benign and malignant breast IELs was facilitated by use of a multiparameter MRI model with DCE-MRI and syMRI, giving greater objectivity in differentiating between benign and malignant lesions.

Background: Prostate cancer (PCa) is not well understood because of its enormous biological heterogeneity and unreliable progression. We conducted this retrospective analysis to examine the variables predicting early and late progression to castration-resistant PCa (CRPC) for better management of this disease.

Methods: This single institutional retrospective study was conducted from January 2018 to January 2022. A total of 98 consecutive men meeting with the diagnosis of CRPC as per the inclusion criteria were included in the study and were stratified in four quartiles on the basis of time to CRPC (time to castration resistance [TTCR]) development. Early CRPC (1^st quartile, TTCR = 6-12 months) and late CRPC (4^th quartile, TTCR = 38-120 months) were then compared on the basis of different clinical, pathological and AR-LBD sequence to find the correlation with response duration.

Results: Median time to develop castration resistance was 25 ± 26.44 months. The mean age of the patients was 66.8 ± 9.20 years and median baseline PSA was calculated 100±685.06 ng/mL respectively. Higher Gleason score (≥7-10) was found to be significantly associated with early development of CRPC (p<0.001) and lower nadir PSA was significantly indicating late CRPC progression (p<0.005). No mutations were found in androgen receptor exon-5, 6, 7 except a homozygous mutation in the 7^th intronic region, which is involved in splice variants formation playing noteworthy role in CRPC development.

Conclusion: Time for metastatic PCa to CRPC ranges from 6-120 months revealing its heterogeneous nature. Early age presentation in the clinic and high initial PSA and high grade (GS>7) at diagnosis were positively associated with early CRPC while lower nadir PSA was correlated with late CRPC progression. No remarkable genomic mutations were discovered. Therefore, more data are needed and further research is required with large no. of patients to discover the predictive prognostic biomarkers for better patients' management.

Introduction: Breast cancer is highly metastatic. One protein that may participate in breast cancer cell migration is the actin motor protein myosin 6 (MYO6), which is likely regulated by the GIPC1 protein. Additionally, septins (SEPTs) appear to participate in breast cancer motility. Here, we investigated the effects of loss of MYO6 on cell morphology, migration, and expression of GIPC1, SEPT2, and SEPT7 in two breast cancer cell lines.

Material and methods: The research material consisted of two breast cancer cell lines, MCF-7 and MDA-MB-231, in which the level of MYO6 was reduced and the effect of knockdown on the migration potential and the expression of GIPC1, SEPT2 and SEPT7 was determined. The levels of these proteins were also analyzed in silico.

Results: siRNA-mediated knock down of MYO6 altered the morphology of MCF-7 cells and reduced the expression of GIPC1 and SEPT7 in both MCF-7 and MDA-MB-231 cells. In in silico data, GIPC1, SEPT2, and SEPT7 were all overexpressed in breast cancer tissue samples from patients. Finally, MYO6 knock down impaired migration and adhesion in both MCF-7 and MDA-MB-231 cells.

Conclusion: Our study substantiates that downregulation of MYO6 diminishes the migratory abilities of breast cancer cell lines with varying invasiveness. Furthermore, we have demonstrated that decreased MYO6 protein leads to reduced expression of GIPC1, SEPT2, and SEPT7 in breast cancer cells. These findings contribute to a more comprehensive understanding of the pathways influencing breast cancer cell migration, a critical aspect of metastasis.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Tumor immune microenvironment (TIME), angiogenesis, epithelial-mesenchymal transformation (EMT), invasion, metastasis, metabolism, and drug resistance are the main factors affecting the development and treatment of tumors. MiRNAs play crucial roles in almost all major cellular biological processes. Studies have been carried out on miRNAs as biomarkers and therapeutic targets. Their dysregulation contributes to the progression and prognosis of HCC. This review aims to explore the molecular cascades and corresponding phenotypic changes caused by aberrant miRNA expression and their regulatory mechanisms, summarize and analyze novel biomarkers from somatic fluids (plasma/serum/urine), and highlight the latent capacity of miRNAs as therapeutic targets.