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Journal of Cancer Research and Clinical... Jul 2024To explore the effect and mechanism of relaxin (RLX) in the growth and metastasis of livercancer after combination treatment with transarterial chemoembolization (TACE).
OBJECTIVE
To explore the effect and mechanism of relaxin (RLX) in the growth and metastasis of livercancer after combination treatment with transarterial chemoembolization (TACE).
MATERIALS AND METHODS
HCCLM3 and Huh-7 cells were adopted to evaluate the effect of tumor proliferation, migration, and invasion after RLX administration in vitro. The rabbit VX2 model was used to evaluate the biosafety, doxorubicin penetration, local tumor response, tumor metastasis, and survival benefit of RLX combined with TACE treatment.
RESULTS
RLX did not affect the proliferation, migration, or invasion of HCCLM3 and Huh-7 cells, and the expression of E-cadherin and HIF-1α also remained unchanged while the MMP-9 protein was upregulated in vitro. In the rabbit VX2 model, compared to the normal saline group (NS), RLX group (RLX) and TACE mono-therapy group (TACE), the group that received TACE combined with RLX (TACE + RLX) showed an improved local tumor response and survival benefit. Furthermore, TACE combined with RLX was found to reduce tumor metastasis. This combination therapy reduced the fibrotic extracellular matrix in the tumor microenvironment, allowing for better penetration of doxorubicin, improved infiltration of CD8+ T cells and affected the secretion of cytokines. Additionally, RLX combined with TACE was able to decrease the expression of HIF-1α and PD-L1. The biosafety of TACE combined with RLX was also confirmed.
CONCLUSION
RLX synergized with TACE by mitigating the fibrotic extracellular matrix and tumor hypoxic microenvironment, improving the therapeutic effect and inhibiting metastasis during the treatment of liver cancer.
Topics: Animals; Chemoembolization, Therapeutic; Rabbits; Relaxin; Liver Neoplasms; Doxorubicin; Humans; Combined Modality Therapy; Cell Proliferation; Cell Line, Tumor; Disease Models, Animal; Carcinoma, Hepatocellular; Neoplasm Metastasis
PubMed: 38955827
DOI: 10.1007/s00432-024-05864-6 -
Journal of the American Chemical Society Jul 2024The messenger RNA (mRNA) vaccines hold great significance in contagion prevention and cancer immunotherapy. However, safely and effectively harnessing innate immunity to...
The messenger RNA (mRNA) vaccines hold great significance in contagion prevention and cancer immunotherapy. However, safely and effectively harnessing innate immunity to stimulate robust and durable adaptive immune protection is crucial, yet challenging. In this study, we synthesized a library of stimuli-responsive bivalent ionizable lipids (srBiv iLPs) with smart molecular blocks responsive to esterase, HO, cytochrome P450, alkaline phosphatase, nitroreductase, or glutathione (GSH), aiming to leverage physiological cues to trigger fast lipid degradation, promote mRNA translation, and induce robust antitumor immunity via reactive oxygen species (ROS)-mediated boosting. After subcutaneous immunization, esterase-responsive vaccine (eBiv-mVac) was rapidly internalized and transported into the draining lymph nodes. It then underwent fast decaging and self-immolative degradation in esterase-rich antigen-presenting cells, releasing sufficient mRNA for antigen translation and massive reactive quinone methides to elevate ROS levels. This resulted in broad activation of innate immunity to boost T cell response, prompting a large number of primed antigen-specific CD8 T cells to circulate and infiltrate into tumors (>1000-fold versus unvaccinated control), thereby orchestrating innate and adaptive immunity to control tumor growth. Moreover, by further combining our vaccination strategy with immune checkpoint blockade, we demonstrated a synergism that significantly amplified the magnitude and function of antigen-specific CD8 T cells. This, in turn, caused potent systemic antitumor efficacy and prolonged survival with high complete response rate in xenograft and metastasis models. Overall, our generalized stimuli-responsive mRNA delivery platform promises a paradigm shift in the design of potent vaccines for cancer immunotherapy, as well as effective and precise carriers for gene editing, protein replacement, and cell engineering.
PubMed: 38955767
DOI: 10.1021/jacs.4c04331 -
Clinical Radiology May 2024The objective of this study was to create and authenticate a prognostic model for lymph node metastasis (LNM) in colorectal cancer (CRC) that integrates clinical,...
Deep-learning features based on F18 fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) to predict preoperative colorectal cancer lymph node metastasis.
AIM
The objective of this study was to create and authenticate a prognostic model for lymph node metastasis (LNM) in colorectal cancer (CRC) that integrates clinical, radiomics, and deep transfer learning features.
MATERIALS AND METHODS
In this study, we analyzed data from 119 CRC patients who underwent F18 fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) scanning. The patient cohort was divided into training and validation subsets in an 8:2 ratio, with an additional 33 external data points for testing. Initially, we conducted univariate analysis to screen clinical parameters. Radiomics features were extracted from manually drawn images using pyradiomics, and deep-learning features, radiomics features, and clinical features were selected using Least Absolute Shrinkage and Selection Operator (LASSO) regression and Spearman correlation coefficient. We then constructed a model by training a support vector machine (SVM), and evaluated the performance of the prediction model by comparing the area under the curve (AUC), sensitivity, and specificity. Finally, we developed nomograms combining clinical and radiological features for interpretation and analysis.
RESULTS
The deep learning radiomics (DLR) nomogram model, which was developed by integrating deep learning, radiomics, and clinical features, exhibited excellent performance. The area under the curve was (AUC = 0.934, 95% confidence interval [CI]: 0.884-0.983) in the training cohort, (AUC = 0.902, 95% CI: 0.769-1.000) in the validation cohort, and (AUC = 0.836, 95% CI: 0.673-0.998) in the test cohort.
CONCLUSION
We developed a preoperative predictive machine-learning model using deep transfer learning, radiomics, and clinical features to differentiate LNM status in CRC, aiding in treatment decision-making for patients.
PubMed: 38955636
DOI: 10.1016/j.crad.2024.05.017 -
Journal of Pediatric Surgery Jun 2024Predicted 1-year survival of children with trisomy 18 (T18) has increased to 59.3%. We aimed to systematically review the characteristics, management, and outcomes of... (Review)
Review
INTRODUCTION
Predicted 1-year survival of children with trisomy 18 (T18) has increased to 59.3%. We aimed to systematically review the characteristics, management, and outcomes of children with T18 and hepatoblastoma.
METHODS
A systematic literature review of the PubMed, Embase, Scopus, Web of Science, and Cochrane Library databases was performed according to the PRISMA 2020 statement (end-of-search date: 03/03/2024).
RESULTS
Fifty studies reporting on 70 patients were included. The median age at diagnosis was 11.5 months, 85.9% were female (n = 55/64), and 15.0% had mosaic T18 (n = 6/40). Diagnosis was made during symptom evaluation (most commonly hepatomegaly or abdominal mass) in 45.5% (n = 15/33), incidentally in 24.2% (n = 8/33), during surveillance with abdominal ultrasound in 18.2% (n = 6/33), and at autopsy in 12.1% (n = 4/33). The median tumor size was 6.4 cm, 33.3% had multiple tumors (n = 14/42), and metastasis was present in one patient (3.8%; n = 1/26). Neoadjuvant chemotherapy was administered in 42.6% (n = 26/61) and adjuvant chemotherapy in 31.6% (n = 18/57). Surgical treatment was performed in 64.2% (n = 43/67). Of the patients not diagnosed on autopsy, overall mortality was 35.5% (n = 22/62) over a median follow-up of 11.0 months. Among the 26 deceased patients (including those diagnosed on autopsy), the most common causes of death were cardiopulmonary disease (38.5%, n = 10/26) and tumor progression (30.8%, n = 8/26).
CONCLUSIONS
T18 does not preclude resection with curative intent for hepatoblastoma. Combination of surgery and chemotherapy should be considered in children on an individualized basis depending on tumor characteristics and underlying cardiopulmonary comorbidities. Locoregional modalities may have a role in the setting of severe comorbidities.
LEVEL OF EVIDENCE
Level IV evidence.
PubMed: 38955626
DOI: 10.1016/j.jpedsurg.2024.06.005 -
European Journal of Surgical Oncology :... Jun 2024
PubMed: 38955583
DOI: 10.1016/j.ejso.2024.108493 -
Biochimica Et Biophysica Acta. Reviews... Jun 2024The cell division cycle-associated protein (CDCA) family is important in regulating cell division. High CDCA expression is significantly linked to tumor development.... (Review)
Review
The cell division cycle-associated protein (CDCA) family is important in regulating cell division. High CDCA expression is significantly linked to tumor development. This review summarizes clinical and basic studies on CDCAs conducted in recent decades. Furthermore, it systematically introduces the molecular expression and function, key mechanisms, cell cycle regulation, and roles of CDCAs in tumor development, cell proliferation, drug resistance, invasion, and metastasis. Additionally, it presents the latest research on tumor diagnosis, prognosis, and treatment targeting CDCAs. These findings are pivotal for further in-depth studies on the role of CDCAs in promoting tumor development and provide theoretical support for their application as new anti-tumor targets.
PubMed: 38955314
DOI: 10.1016/j.bbcan.2024.189147 -
International Journal of Biological... Jun 2024Inulin as a natural polysaccharide regulates intestinal microorganisms, and improves the immune and gastrointestinal function. In order to explore the effect of inulin...
Inulin as a natural polysaccharide regulates intestinal microorganisms, and improves the immune and gastrointestinal function. In order to explore the effect of inulin on pulmonary metastasis of colon cancer, we set up a CT26 injected pulmonary metastatic model. The results showed that inulin used alone did not improve pulmonary metastasis of colon cancer, while inulin combined with rifaximin significantly prolonged the survival time of mice, and inhibited pulmonary metastasis compared with model and inulin groups. Inulin treatment increased the abundance of harmful bacteria such as Proteobacteria and Actinobacteria, while combined treatment decreased their abundance and increased the abundance of beneficial bacteria containing Firmicutes and Eubacterium which belonged to the bile acid-related bacteria. The combination treatment decreased the content of primary bile acids and secondary bile acids in the feces of mice, especial for DCA and LCA which were the agonists of TGR5. Furthermore, the combination treatment reduced the mRNA expression of the TGR5, cyclin dependent kinase 4, cyclin 1 and CDK2, increased the mRNA expression of p21 in the lung, down-regulated the level of NF-κB p65, and up-regulated the level of TNF-α compared with the model group. The above may be the reason for the better use of the combination treatment.
PubMed: 38955301
DOI: 10.1016/j.ijbiomac.2024.133582 -
Laryngo- Rhino- Otologie Jul 2024
Topics: Humans; Lymphatic Metastasis; Prognosis; Neoplasm Staging; Lymph Nodes; Squamous Cell Carcinoma of Head and Neck
PubMed: 38955153
DOI: 10.1055/a-2298-8010 -
Laryngo- Rhino- Otologie Jul 2024
Topics: Humans; Lymphatic Metastasis; Prognosis; Neoplasm Staging; Male; Lymph Nodes; Female; Head and Neck Neoplasms; Middle Aged; Carcinoma, Squamous Cell; Aged
PubMed: 38955152
DOI: 10.1055/a-2298-8077 -
Translational Oncology Jul 2024Small cell lung cancer (SCLC) is a high-grade neuroendocrine tumor characterized by initial sensitivity to chemotherapy, followed by the development of drug resistance....
OBJECTIVE
Small cell lung cancer (SCLC) is a high-grade neuroendocrine tumor characterized by initial sensitivity to chemotherapy, followed by the development of drug resistance. The underlying mechanisms of resistance in SCLC have not been fully elucidated. Aldo-keto reductase family 1 member C3 (AKR1C3), is known to be associated with chemoradiotherapy resistance in diverse tumors. We aim to evaluate the prognostic significance and immune characteristics of AKR1C3 and investigate its potential role in promoting drug resistance in SCLC.
METHODS
81 postoperative SCLC tissues were used to analyze AKR1C3 prognostic value and immune features. The tissue microarrays were employed to validate the clinical significance of AKR1C3 in SCLC. The effects of AKR1C3 on SCLC cell proliferation, migration, apoptosis and tumor angiogenesis were detected by CCK-8, wound healing assay, transwell assay, flow cytometry and tube formation assay.
RESULTS
AKR1C3 demonstrated the highest expression level compared to other AKR1C family genes, and multivariate cox regression analysis identified it as an independent prognostic factor for SCLC. High AKR1C3 expression patients who underwent chemoradiotherapy experienced significantly shorter overall survival (OS). Furthermore, AKR1C3 was involved in the regulation of the tumor immune microenvironment in SCLC. Silencing of AKR1C3 led to the inhibition of cell proliferation and migration, while simultaneously promoting apoptosis and reducing epithelial-mesenchymal transition (EMT) in SCLC.
CONCLUSION
AKR1C3 promotes cell growth and metastasis, leading to drug resistance through inducing EMT and angiogenesis in SCLC.
PubMed: 38954974
DOI: 10.1016/j.tranon.2024.102027