Cancer Biology & Medicine最新文献

Objective: Our previous studies have indicated potentially higher proliferative activity of tumor cells in Chinese patients with mantle-cell lymphoma (MCL) than those in Western. Given the success and tolerability of R-DA-EDOCH immunochemotherapy in treating aggressive B-cell lymphomas, we designed a prospective, phase 3 trial to explore the efficacy and safety of alternating R-DA-EDOCH/R-DHAP induction therapy for young patients with newly diagnosed MCL. The primary endpoint was the complete remission rate (CRR) at the end of induction (EOI).

Methods: A total of 55 patients were enrolled. The CRR at the EOI was 89.1% [95% confidence interval (CI) 78%-96%], and the overall response rate was 98.1% (95% CI 90%-100%). Most patients with bone marrow involvement quickly attained minimal residual disease (MRD) negative status, with a 95.7% rate at the EOI.

Results: The 3-year progression-free survival (PFS) and overall survival rates were 66.3% and 83.2%, respectively. No patients discontinued treatment because of adverse events. Univariate analysis identified pathologic morphology and TP53 mutations as risk factors for PFS. However, high tumor proliferative activity and certain cytogenetic abnormalities showed no significant adverse prognostic significance.

Conclusions: Intensive therapy based on a high cytarabine dose and continuously administered EDOCH achieved a high MRD-negative rate and provides an optional induction choice for young patients with MCL with high-risk factors.

Colorectal cancer (CRC) is a major contributor to global cancer-related mortality with increasing incidence rates in both developed and developing regions. Therefore, CRC presents a significant challenge to global health. The development of innovative tools for enhancing early CRC screening and diagnosis, along with novel treatments and therapies for improved management, remains an urgent necessity. CRC is intricately associated with the gut microbiota, which is integral to food digestion, nutrient generation, drug metabolism, metabolite production, immune enhancement, endocrine regulation, neurogenesis modulation, and the maintenance of physiologic and psychological equilibrium. Dysbiosis or imbalances in the gut microbiome have been implicated in various disorders, including CRC. Emerging evidence highlights the critical role of the gut microbiome in CRC pathogenesis and treatment, which presents potential opportunities for early detection and diagnosis. Despite substantial advances in understanding the relationship between the gut microbiota and CRC, significant challenges persist. Gaining a deeper and more detailed understanding of the interactions between the human microbiota and cancer is essential to fully realize the potential of the microbiota in cancer management. Unlike genetic factors, the gut microbiome is subject to modification, offering a promising avenue for the development of CRC treatments and drug discovery. This review provides an overview of the interactions between the human gut microbiome and CRC, while examining prospects for precision management of CRC.

Objective: Erianin has potential anticancer activities, especially against lung cancer. The specific mechanisms underlying the anti-cancer effects, including the molecular targets and signaling pathways in lung cancer, remain poorly understood and necessitate further investigation.

Methods: Lung cancer cell viability was evaluated using the CCK-8 assay. Flow cytometry was used to examine the effects of erianin on apoptosis and cell cycle progression. mRNA sequencing and metabolomics analysis were utilized to explore erianin-induced biological changes. Potential targets were identified and validated through molecular docking and Western blot analysis. The roles of mammalian target of rapamycin (mTOR) and carbamoyl-phosphate synthetase/aspartate transcarbamylase/dihydroorotase (CAD) in erianin-induced growth inhibition were studied using gene overexpression/knockdown techniques with uridine and aspartate supplementation confirming pyrimidine metabolism involvement. Additionally, lung cancer-bearing nude mouse models were established to evaluate the anti-lung cancer effects of erianin in vivo.

Results: Erianin significantly inhibits the proliferation of lung cancer cells, induces apoptosis, and causes G₂/M phase cell cycle arrest. Integrative analysis of mRNA sequencing and metabolomics data demonstrated that erianin disrupts pyrimidine metabolism in lung cancer cells. Notably, uridine supplementation mitigated the inhibitory effects of erianin, establishing a connection between pyrimidine metabolism and anticancer activity. Network pharmacology analyses identified mTOR as a key target of erianin. Erianin inhibited mTOR phosphorylation, thereby blocking downstream effectors (S6K and CAD), which are essential regulators of pyrimidine metabolism.

Conclusions: Erianin is a promising therapeutic candidate for lung cancer. Erianin likely inhibits lung cancer cell growth by disrupting pyrimidine metabolism by suppressing mTOR activation.

Objective: The aim of the study was to evaluate the feasibility of functional MR in predicting the clinical response to chemotherapy in patients with colorectal liver metastases (CLM).

Methods: A total of 196 eligible patients were enrolled in the study between August 2016 and January 2023. Functional MR was performed at baseline and after one cycle of chemotherapy. The diffusion kurtosis radiomic texture features were extracted and a signature model was built using the R package. The initial 100 cases were designated as the training set, the following 48 cases were designated as the validation set, and the final 48 cases were designated as the intervention validation set.

Results: Good performance for the response prediction (AUC = 0.818 in the training set and 0.755 in the validation set) was demonstrated. The objective response rates (ORRs) in the high-risk subgroup were significantly lower than the low-risk subgroup in the training and validation sets. Worse progression-free survival and overall survival rates were noted in the high-risk population. In the intervention set 22.9% (11/48) of the chemotherapy regimens for patients were changed in response to the model-predicted results and the ORR reached 77.1% (37/48), which was significantly higher than the training and validation sets [47.97% (71/148); P = 0.000].

Conclusions: A functional MR signature effectively predicted the chemotherapy response and long-term survival. The adjustment of the regimen guided by the model significantly improved the ORR.

Intra-tumoral bacteria are pivotal in the initiation and progression of head and neck squamous cell carcinoma (HNSCC), exerting a significant influence on tumor cell biology, immune responses, and the tumor microenvironment (TME). Different types and distribution of bacteria threaten the balance of metabolism and the immune environment of tumor cells. Taking advantage of this disrupted homeostasis, intra-tumoral bacteria stimulate the secretion of metabolites or influence specific immune cell types to produce inflammatory or chemokines, thereby influencing the anti-tumor immune response while regulating the level of inflammation and immunosuppression within the TME. Some intra-tumoral bacteria are used as diagnostic and prognostic markers in clinical practice. Based on the unique characteristics of bacteria, the use of engineered bacteria and outer membrane vesicles for drug delivery and biological intervention is a promising new therapeutic strategy. The presence of intra-tumoral bacteria also makes chemoradiotherapy tolerable, resulting in a poor treatment effect. However, due to the immune-related complexity of intra-tumoral bacteria, there may be unexpected effects in immunotherapy. In this review the patterns of intra-tumoral bacteria involvement in HNSCC are discussed, elucidating the dual roles, while exploring the relevance to anti-tumor immune responses in the clinical context and the prospects and limitations of the use of bacteria in targeted therapy.