Cancer Biology & Medicine最新文献

Objective: CLT-003 is a novel phenylphthalimide derivative encapsulated in poly (lactate-glycolic acid) copolymer nanoparticles using nanotechnology techniques. CLT-003 possesses anti-angiogenetic and antitumor activities. Nevertheless, the role and molecular mechanism underlying CLT-003 in pancreatic cancer remain to be elucidated.

Methods: Cell proliferation and apoptosis were detected using CCK-8, real-time cell analysis (RTCA), EdU, and flow cytometric assays. Cellular mobility and invasive capacity were detected using wound-healing, Transwell, and cell motility assays. Tumor growth and metastasis were determined using the mouse subcutaneous and pancreatic cancer orthotopic liver metastasis models. The antitumor effects of CLT-003 were evaluated using patient-derived organoid (PDO) and patient-derived xenograft (PDX) models.

Results: CLT-003 significantly inhibited cellular proliferation, enhanced cellular apoptosis, and attenuated cellular invasion and migration of pancreatic cancer cells. Mechanistically, CLT-003 suppressed the translation of HIF-1α by inhibiting the PI3K/AKT/mTOR signaling pathway. In the mouse tumor models, CLT-003 significantly inhibited the growth and metastasis of pancreatic tumors. Moreover, the PDO and PDX models showed increased sensitivity to CLT-003 in pancreatic cancer with high HIF-1α expression compared to pancreatic cancer with low HIF-1α expression.

Conclusions: This study delineated the role and molecular mechanism of CLT-003 action in impeding the progression of pancreatic cancer and indicated its robust potential for the treatment of pancreatic cancer.

Objective: To describe temporal changes associated with deployment of an optical character recognition (OCR)-enabled One-Identity (One-ID) digital platform for rural cervical cancer screening, focusing on over-screening rates, CIN2+ detection, colposcopy follow-up, and CIN2+ management.

Methods: A multi-county pre-post observational study was conducted in six rural counties in Shanxi, Yunnan, and Sichuan Provinces (2021-2024), encompassing 153,978 encounters. The digital platform integrates OCR identity capture, deterministic One-ID linkage, and real-time duplicate alerts. Over-screening proportions before and after digital deployment were compared, changes in CIN2+ detection rate were evaluated, and colposcopy follow-up and CIN2+ management were assessed. Differences were tested with χ² or Fisher's exact tests.

Results: Among 153,978 encounters, the proportion of over-screening decreased from 12.64% in 2023 to 0.17% in 2024 with an absolute reduction of 12.17% (95% CI: 11.94-12.40; P < 0.001). The share of women receiving a first screening within the preceding 3 y increased from 78.3% to 88.2% (P < 0.001). Colposcopy completion improved from 64.1% to 84.9%. The CIN2+ detection rate rose from 0.35% (2021-2023 pooled) to 0.67% in 2024 (P < 0.001) and CIN2+ management completion increased from 56.0% to 76.2% (95% CI: 13.3-27.2; P < 0.001). These improvements were consistent across age groups, counties, and screening strategies.

Conclusions: The OCR-enabled One-ID platform substantially reduced over-screening, increased CIN2+ detection rate, and strengthened case follow-up/management, particularly where baseline tracking was weak, supporting scalable digital reinforcement of rural screening programmes.

Immunotherapy, particularly immune checkpoint inhibitors (ICIs) programmed death-ligand 1/programmed death-1 (PD-L1/PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), has heralded a new era of tumor treatment. Although ICIs have clinical benefits, their complex heterogeneity and diverse resistance mechanisms critically limit their efficacy. Neoantigens, arising from tumor-specific alterations, offer novel targets for individualized immunotherapy, because of their high immunogenicity and tumor specificity. In the past decade, neoantigen-based tumor vaccines have been demonstrated to be a promising immunotherapy strategy to prime the tumor-specific immune response. These therapeutic vaccines include peptide vaccines, nucleic acid vaccines, and dendritic cell (DC) vaccines, and are categorized according to the neoantigen source and delivery method. In vivo, neoantigens are processed and presented by antigen-presenting cells (APCs) via the peptide-Major Histocompatibility Complex (pMHC) for T cell recognition, thereby triggering specific immune responses. Because DCs, the most potent APCs, play crucial roles in antitumor immunity, neoantigen-based DC vaccines provide a promising therapeutic strategy. A series of global clinical trials are exploring the safety, feasibility, and efficacy of neoantigen-based DC vaccines in tumors. This review focuses on current progress in clinical research on neoantigen-based DC vaccines in the treatment of solid tumors.

Objective: To evaluate the impact of government-organized screening on the economic burden among patients with cervical cancer and precancerous lesions, and explore mediating pathways across diagnosis, initial treatment, radiotherapy/chemotherapy, follow-up, and recurrence/progression/metastasis.

Methods: A multicentre, nationwide survey across 5 disease courses was conducted from 26 hospitals in China. Multivariable regression and structural equation modeling were used to assess the effects of government-organized screening on economic burden by comparing government-organized screening with workplace check-up, self-paid check-up, and symptom-based detection.

Results: Workplace check-up, self-paid check-up, and symptom-based detection were associated with progressively higher costs across diagnosis [β: 1.10, 95% confidence interval (CI): 0.54-1.67; β: 1.46, 95% CI: 1.00-1.92; and β: 1.68, 95% CI: 1.25-2.11, respectively], initial treatment (β: 0.36, 95% CI: 0.18-0.55; β: 0.51, 95% CI: 0.35-0.66; and β: 0.56, 95% CI: 0.42-0.70, respectively), and follow-up (β: 0.63, 95% CI: 0.38-0.88; β: 0.83, 95% CI: 0.61-1.04; and β: 0.85, 95% CI: 0.65-1.06, respectively) compared to government-organized screening (all P < 0.05). Earlier clinical staging and greater use of lower-level hospitals mediated 44.74%-54.97% of cost differences in diagnosis, 73.27%-85.04% in initial treatment, and 30.38%-54.73% in follow-up. Fifteen percent of the cost differences during initial treatment were related to lower overtreatment for precancerous lesions.

Conclusions: Government-led cervical cancer screening was associated with lower economic burden with pathways involving earlier-stage diagnosis, reduced overtreatment, and decreased reliance on higher-level hospitals, suggesting potential clinical benefits, efficient resource use, and improved equity in cancer care.

A significant number of anticancer drugs fail to treat primary and metastatic brain tumors primarily because of the complex blood-brain barrier (BBB) and overexpression of ATP-binding cassette (ABC) transporters, which decrease drug penetration into the central nervous system and ultimately into tumors. It is noteworthy that the ABC transporters, ABCB1 [known as P-glycoprotein (P-gp)] and ABCG2 [known as breast cancer resistance protein (BCRP)], are overexpressed in brain tumors, including common gliomas. The co-presence of these transporters may negate the inhibition of either transporter, particularly if both transport the same anticancer drug. The cellular export of drugs by ABC transporters has been implicated in mediating resistance to anticancer drugs. However, the clinical relevance as a therapeutic target in human tumors remains a matter of contention. Although effective and clinically approved ABC transporter inhibitors could potentially overcome drug resistance, none are currently approved. Furthermore, the ABC transporter inhibitors in clinical trials produced low or no clinical efficacy, significant toxicities, and unsuitable pharmacokinetic profiles. Therefore, innovative approaches are needed to efficaciously and simultaneously inhibit these transporters to surmount anticancer drug resistance. This review emphasizes the clinical significance of ABC transporters in diminishing the efficacy of brain tumor treatments. The molecular alterations in BBB following brain tumor development, which are linked to various cancer therapies, are discussed. The overexpression of ABCB1 and ABCG2 at the BBB is discussed, potential strategies to decrease the export of chemotherapeutics by these transporters and the associated challenges and failures are discussed, and the implementation of novel approaches is considered.