American journal of cancer research最新文献

To compare the clinical efficacy, safety, and cost-effectiveness of bispecific antibody teclistamab and chimeric antigen receptor T-cell (CAR-T) therapy in relapsed/refractory multiple myeloma (RRMM) to guide individualized treatment. This retrospective study enrolled 67 RRMM patients (excluded 6 of 73) hospitalized at Xinxiang Central Hospital (December 2024-May 2025), divided into teclistamab (n=32) and CAR-T (n=35) groups. Primary outcomes included overall response rate (ORR) and progression-free survival (PFS). Secondary outcomes comprised complete response rate (CRR), duration of response (DOR), minimal residual disease (MRD) negativity rate, overall survival (OS), adverse events (AEs), hospital stays, direct medical costs, and cost-effectiveness ratio (CER). The CAR-T group showed higher CRR (P=0.011), ORR (P=0.029), MRD negativity rate (P=0.027), longer median DOR [HR: 3.35 (1.838, 6.10), P<0.001], PFS [HR: 4.407 (1.994, 9.74), P<0.001], and better OS (HR: 3.204 (1.015, 10.1), P=0.021) than the teclistamab group. However, the CAR-T group had higher incidences of cytokine release syndrome (P=0.033) and hematological AEs (P=0.040), longer hospital stays, higher direct costs, and higher CER (all P<0.001). Prior treatment lines were independent prognostic factors (P=0.036). CAR-T therapy outperforms teclistamab in efficacy and survival outcomes but has higher AEs and costs. Teclistamab demonstrates superior safety and shorter hospital stays, supporting individualized clinical selection.

This study aimed to assess the impact of Graves' disease (GD) on the clinicopathological characteristics and prognosis of patients with differentiated thyroid cancer (DTC) undergoing initial radioactive iodine (RAI) therapy, as well as to identify factors influencing RAI therapy outcomes. A retrospective analysis was conducted on 959 DTC patients who received initial RAI therapy at the Department of Nuclear Medicine, First Affiliated Hospital of Nanchang University, between January 2021 and December 2023. Patients were divided into two groups based on a history of GD: the GD group (n = 60) and the non-GD group (n = 899). Data on demographics, laboratory tests, clinicopathological features, and RAI-related parameters were collected. Univariate analysis was performed to identify variables associated with treatment response, followed by multivariate logistic regression to determine independent predictors of outcomes after initial RAI therapy. The distribution of treatment responses across the four categories was as follows: in the GD group, excellent response (ER) occurred in 71.67%, indeterminate response (IDR) in 16.67%, biochemical incomplete response (BIR) in 6.67%, and structural incomplete response (SIR) in 5.00%; in the non-GD group, the respective rates were 39.60% (ER), 29.37% (IDR), 17.80% (BIR), and 13.24% (SIR). Statistically significant differences were observed in dichotomous outcomes - ER versus non-excellent response (N-ER), and ideal/acceptable response versus incomplete response - between the two groups (both P < 0.01). Multivariate analysis identified several independent factors associated with favorable RAI outcomes, including younger age, GD (P < 0.001; OR = 0.16; 95% CI: 0.07-0.35), shorter interval between surgery and ¹³¹I administration, fewer metastatic lymph nodes, negative pre-ablation thyroglobulin antibody (pa-TgAb), lower pre-treatment stimulated thyroglobulin (sTg) levels, and higher ¹³¹I dose (all P < 0.05). In contrast, Hashimoto's thyroiditis (HT), maximum diameter of metastatic lymph nodes, body mass index (BMI), tumor multifocality, maximum tumor diameter, tumor location, and ATA recurrence risk stratification were not significantly associated with treatment response (all P > 0.05). Compared to non-GD DTC patients, those with GD exhibited more favorable pathological features and significantly better short-term prognosis following initial RAI therapy, with an 84% reduced likelihood of N-ER. Key predictors of favorable RAI response included GD status, younger age, shorter surgery-to-RAI interval, lower metastatic lymph node burden, pa-TgAb negativity, lower sTg levels, and higher ¹³¹I dose. HT, metastatic lymph node size, BMI, tumor multifocality, tumor size, and tumor location did not significantly influence treatment outcomes.

TMEM121 is a six-pass transmembrane protein consisting of an N-terminal transmembrane domain (TD; residues 1-284) and a C-terminal polyproline sequence (PP; residues 284-319). In this study, publicly accessible databases were utilized to ascertain that TMEM121 correlates with various cytokines associated with the MAPK signaling pathway in cervical cancer. Furthermore, TMEM121 expression was negatively correlated with ERK expression in cervical cancer tissues. Protein interaction prediction using AlphaFold3 suggested an interaction between TMEM121 and ERK1/2, which was experimentally validated through Co-immunoprecipitation and immunofluorescence analyses. Both full-length TMEM121 and the TD truncator interacted with ERK and downregulate p-ERK1/2 protein levels, thereby inhibiting the proliferation and invasion of cervical cancer cells. In contrast, the PP truncator did not exhibit these effects. RNA-seq analysis further confirmed a significant association between TMEM121 and the MAPK signaling pathway in cervical cancer. Additionally, flow cytometry analysis showed that the ERK inhibitor PD98059 reversed the S phase cell cycle arrest induced by TMEM121 overexpression. Collectively, these findings suggest that TMEM121 exerts its inhibitory effects on the growth, proliferation, and invasion of cervical cancer cells through its interaction with ERK, providing a theoretical basis for the development of novel diagnostic and therapeutic strategies for cervical cancer.

[This corrects the article on p. 2180 in vol. 15, PMID: 40520866.].

Mantle cell lymphoma (MCL) is a rare type of mature B-cell lymphoma. This multicenter retrospective cohort study aimed to analyze the epidemiological characteristics, treatment patterns, and survival outcomes of patients with MCL in Taiwan. We collected baseline information, treatment modalities, and response evaluation of patients with MCL. A total of 204 patients who were diagnosed with mantle cell lymphoma between November 2001 and July 2022 were included. When divided into low, intermediate, and high-risk groups according to the Mantle Cell Lymphoma International Prognostic Index, their median overall survival times were 83.7 (95% confidence interval [CI]: 77.7-NR), 72.7 (95% CI: 30.7-NR), and 19.3 (95% CI: 14.2-45.6) months, respectively. In this multicenter retrospective cohort, first line rituximab containing regimens, higher chemotherapy intensity, and ASCT were associated with longer PFS/OS, although the magnitude and statistical significance varied after adjustment and by transplant eligibility. Given potential confounding by indication, era effects, and missing data, these findings should be interpreted as observational associations rather than causal effects. Prospective or target trial emulation studies are warranted.

Trichilemmal carcinoma (TC) is a rare malignant cutaneous appendage neoplasm originating from the epithelium of the outer root sheath of hair follicles. TC is generally non-invasive, causing only localized damage, and can be successfully managed with wide excision. Although recurrence and metastasis are rare, such cases often exhibit high malignancy, necessitating regular follow-up. Here, a retrospective study was conducted to review the clinical and histopathological features, diagnosis, and treatment of TC. Seven TC patients were enrolled in this study with 3 female and 4 male patients. The average age was 56.14±20.72 years old and the average year of lesion onset to clinic visit was 3.91±5.07 years. All patients received enlarged excision therapy. Six of Seven patients were followed for at least two years. Only one reported lesion relapse one year after surgery with 0.5 cm enlarged margin. In conclusion, surgery is a great method for TC treatment with at least 1 cm margin. Long-term post operative follow-up is necessary to screening recurrence.

ITGB6, the gene encoding the β6 subunit of integrin αvβ6, is a potent prognostic marker across multiple cancer types. As a major activator of latent TGFβ and a potent modulator of the tumor immune environment, αvβ6, and consequently, ITGB6, has considerable therapeutic implications. ITGB6 is highly upregulated in squamous cell carcinomas and pancreatic adenocarcinomas, where it disrupts tumor-immune cell signaling. We identify ITGB6 as a potent clinical prognostic marker of anti-tumor immune response and were able to recapitulate the immune-mediated anti-tumor effect of ITGB6 in pre-clinical mouse models. Genetic knockout of ITGB6 in heterotopically-injected head and neck squamous cell carcinoma and pancreatic adenocarcinoma cell lines shows markedly reduced tumor progression and immunogenic cytokine profiles in immunocompetent mice. Additionally, co-cultures of human head and neck squamous cell carcinoma and pancreatic adenocarcinoma with human T-cells show increased T-cell killing upon cancer cell ITGB6 inhibition. Colony formation experiments give further evidence that the reduced tumor growth observed upon ITGB6 inhibition in vivo is through immunological clearance of cancer cells and not merely through intrinsic factors. Analysis of The Cancer Genome Atlas (TCGA) reveals the high prognostic value of ITGB6 on overall survival and that high ITGB6 expression in patients is associated with an inferior response to α-PD-1 and α-PD-L1 immune checkpoint blockade. The potent anti-tumor immune response observed both in vitro and in vivo upon ITGB6 inhibition, combined with analysis of RNA-seq data from immune checkpoint blockade-treated patients, encourages the development of ITGB6 blockade and immunotherapy combination regimens. Further pre-clinical studies should facilitate translation of our findings into therapeutic clinical trials for treating immunotherapy-resistant cancers.

Objective: This study aimed to investigate the mechanism underlying the role of Zinc finger protein 710 (ZNF710) in gastric cancer (GC).

Methods: The level of ZNF710 expression in GC and its prognosis were examined based on the public databases and clinical samples. Cell models of lentivirus-mediated overexpression (oeZNF710) and knockdown (shZNF710) of ZNF710 were developed on the AGS and HGC-27 GC cell lines. The biological behaviors of these cells were analysed systematically, comprising proliferation (as measured by CCK-8 assay and plate cloning experiment), apoptosis (measured by flow cytometry), and migration (measured by Transwell assay). To confirm the expression of the main proteins of the Wnt/β-catenin system, western blotting analysis was conducted. Besides, functional rescue experiments of Wnt signaling agonist SKL2001 and Wnt signaling inhibitor XAV939 were performed. The in vivo activity of ZNF710 was tested in a nude mouse subcutaneous xenograft model.

Results: The expression of ZNF710 was significantly increased in GC tissues and cell lines compared to standard controls, whereas high levels of ZNF710 were associated with a poor prognosis in GC patients. ZNF710 knockdown of HGC-27 cells significantly reduced cell proliferation, migration, and invasion and increased apoptosis. On the contrary, overexpression of ZNF710 in AGS cells produced the reverse effects. Mechanistically, ZNF710 overexpression increased the expression of Wnt/β-catenin pathway-related regulatory proteins, and ZNF710 knockdown reduced their expression.

Conclusion: ZNF710 is highly expressed in GC and promotes GC cell proliferation, migration, and invasion while inhibiting apoptosis by activating the Wnt/β-catenin pathway, suggesting it may serve as a potential therapeutic target for GC.

[This corrects the article on p. 2752 in vol. 10, PMID: 33042615.].