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Dedifferentiated liposarcoma (DDL), a member of malignant mesenchymal tumors, has a high local recurrence rate and poor prognosis. Pyroptosis, a newly discovered programmed cell death, is tightly connected with the progression and outcome of tumor.

Gastrointestinal cancer is a common malignant tumor with a high incidence worldwide. Despite continuous improvements in diagnosis and treatment strategies, the overall prognosis of gastrointestinal tumors remains poor. Carcinoembryonic antigen (CEA) is highly expressed in various types of cancers, especially in gastrointestinal cancers, making it a potential target for therapeutic intervention. Therefore, the expression of CEA can be used as an indication of the existence of tumors, chosen as a target for molecular imaging diagnosis, and effectively utilized in the targeted therapy of gastrointestinal cancers. In this study, we report the selection and characterization of affibody molecules (Z CEA 539, Z CEA 546, and Z CEA 919) specific to the CEA protein. Their ability to bind to recombinant and native CEA protein has been confirmed by surface plasmon resonance (SPR), immunofluorescence, and immunohistochemistry assays. Furthermore, Dylight755-labeled Z CEA affibody showed accumulation within the tumor site 1 h post injection and was continuously enhanced for 4 h. The Dylight755-labeled Z CEA affibody exhibited high tumor-targeting specificity in CEA+ xenograft-bearing mice and possesses promising characteristics for tumor-targeting imaging. Overall, our results suggest the potential use of Z CEA affibodies as fluorescent molecular imaging probes for detecting CEA expression in gastrointestinal cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shao, Lv, Wang, Jin, Cai, Chen, Kamara, Zhu, Zhu and Zhang.)

Despite recent advances in immunotherapy with immune checkpoint inhibitors (ICI), many patients with non-small cell lung cancer (NSCLC) fail to respond or develop resistance after an initial response. In situ vaccination (ISV) with engineered viruses has emerged as a promising antigen-agnostic strategy that can both condition the tumor microenvironment (TME) and augment anti-tumor T cell responses to overcome immune resistance. We engineered a live attenuated viral vaccine, Hyper-Interferon Sensitive virus (HIS), by conducting a genome-wide functional screening and introducing eight interferon (IFN)-sensitive mutations in the influenza genome. Compared to wild-type (WT) influenza, HIS replication was attenuated in immunocompetent hosts, enhancing its potential as a safe option for cancer therapy. HIS ISV elicited robust yet transient type I IFN responses in murine NSCLCs, leading to an enrichment of polyfunctional effector Th1 CD4 and cytotoxic CD8 T cells into the tumor. HIS ISV demonstrated enhanced anti-tumor efficacy compared to WT in multiple syngeneic murine models of NSCLC with distinct driver mutations and varying mutational burden. This efficacy was dependent on host type 1 IFN responses and T lymphocytes. HIS ISV overcame resistance to anti-PD-1 in LKB-1 deficient murine NSCLC, resulting in improved overall survival and enduring systemic tumor-specific immunity. These studies provide compelling evidence to support further clinical evaluation of HIS as a novel 'off-the-shelf' ISV strategy for patients with NSCLC refractory to ICI.

Circular RNA hsa_circ_0001322 (circ1322) was demonstrated to be significantly reduced in expression in gastric cancer patients in our previous study, and changes in its expression were significantly correlated with lymph node metastasis. However, the underlying workings of circ1322 in gastric cancer are still not fully understood. Therefore, to confirm the effect of circ1322 on gastric cancer, we examined the expression of circ1322 in gastric cancer cells and tissues. The results showed that circ1322 was lowly expressed in GC tissues and cells. Subsequently, we further performed cellular assays and animal experiments, which showed that Circ1322 upregulation inhibited GC cell proliferation, migration and invasion. while promoting GC cell apoptosis, and inhibited tumor growth in mice. The direct targeting of circ1322 to miR-1264 was confirmed by bioinformatics prediction and validation of luciferase reporter gene assay. Circ1322 can act as a miR-1264 sponge to alleviate the inhibitory effect of miR-1264 on its target gene, QKI. miR-1264 regulates the expression of QKI and the activity of the hedgehog pathway. That is, circ1322 may act as a competing endogenous RNA (ceRNA) to inhibit the hedgehog pathway by targeting the miR-1264/QKI axis, which in turn promotes GC progression.

Background: Lymph node involvement significantly impacts the survival of gastric cancer patients and is a crucial factor in determining the appropriate treatment. This study aimed to evaluate the potential of enhanced computed tomography (CT)-based radiomics in predicting lymph node metastasis (LNM) and survival in patients with gastric cancer before surgery., Methods: Retrospective analysis of clinical data from 192 patients diagnosed with gastric carcinoma was conducted. The patients were randomly divided into a training cohort ( n  = 128) and a validation cohort ( n  = 64). Radiomic features of CT images were extracted using the Pyradiomics software platform, and distinctive features were further selected using a Lasso Cox regression model. Features significantly associated with LNM were identified through univariate and multivariate analyses and combined with radiomic scores to create a nomogram model for predicting lymph node involvement before surgery. The predictive performance of radiomics features, CT-reported lymph node status, and the nomogram model for LNM were compared in the training and validation cohorts by plotting receiver operating characteristic (ROC) curves. High-risk and low-risk groups were identified in both cohorts based on the cut-off value of 0.582 within the radiomics evaluation scheme, and survival rates were compared., Results: Seven radiomic features were identified and selected, and patients were stratified into high-risk and low-risk groups using a 0.582 cut-off radiomics score. Univariate and multivariate analyses revealed that radiomics features, diabetes mellitus, Nutrition Risk Screening (NRS) 2002 score, and CT-reported lymph node status were significant predictors of LNM in patients with gastric cancer. A predictive nomogram model was developed by combining these predictors with the radiomics score, which accurately predicted LNM in gastric cancer patients before surgery and outperformed other models in terms of accuracy and sensitivity. The AUC values for the training and validation cohorts were 0.82 and 0.722, respectively. The high-risk and low-risk groups in both the training and validation cohorts showed significant differences in survival rates., Conclusion: The radiomics nomogram, based on contrast-enhanced computed tomography (CECT ), is a promising non-invasive tool for preoperatively predicting LNM in gastric cancer patients and postoperative survival., Competing Interests: The authors declare there are no competing interests., (©2024 Zhang et al.)

Introduction: The infiltration of immune cells in tumor tissue is affected by the tumor microenvironment. However, the relationship between the infiltration of regulatory T cells (Tregs), tumor-associated neutrophils (TANs) and tumor-associated macrophages (TAMs) in colorectal cancer (CRC) remains unclear., Material and Methods: Tissue microarray and immunohistochemistry were used to detect the infiltration of FoxP3 + Tregs, CD66b + TANs and CD163 + TAMs in 249 CRC samples (training cohort) and 243 CRC samples (validation cohort). The relationship between two cells was evaluated by Spearman's rank correlation coefficient and comparison between two groups was analyzed by Mann-Whitney U test., Results: The continuous variable positive cell numbers were non-normally distributed. Spearman correlation analysis showed that CD66b + TAN level in cancer tissues was negatively related to FoxP3 + Treg level (correlation coefficient: -0.495, p < 0.05) and CD163 + TAM level (correlation coefficient: -0.266, p < 0.05), and FoxP3 + Treg level was positively related to CD163 + TAM level (correlation coefficient: 0.467, p < 0.05) in the training cohort. The numbers of FoxP3 + Tregs were significantly different between low and high CD66b + TAN level groups (p < 0.001), as well as that of CD66b + TANs in low and high CD163 + TAM level groups and CD163 + TAMs in different FoxP3 + Treg level groups. The results of the validation cohort were similar to those of the training cohort., Conclusions: There is a negative correlation between infiltration of CD66b + TANs and that of FoxP3 + Tregs or CD163 + TAMs, and a positive correlation between infiltration of FoxP3 + Tregs and CD163 + TAMs in CRC tissues., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Termedia.)

Background: High risk type 16 of human papillomavirus (HPV16) is associated with 50% of cervical cancer, for which reliable targeted therapies are lacking. HPV early protein 7 (E7) is an oncoprotein responsible for cell malignant transformation. In our previous work, a highly specific affibody targeting HPV16E7 (ZHPV16E7) was developed., Objective: In order to improve the targeted therapeutic effect, the present study prepared an affitoxin consisting of ZHPV16E7 fused with granzyme B (GrB), namely, ZHPV16E7-GrB, and evaluated its targeting action in vitro and in vivo., Methods: The ZHPV16E7-GrB fusion protein was produced in a prokaryotic expression system. The targeted binding properties of the ZHPV16E7-GrB to the HPV16E7 were confirmed by immunofluorescence assay (IFA) in cervical cancer cell lines, by immunohistochemical assay (IHA) in cervical cancer tissue from clinical specimens and by near-infrared imaging in tumour-bearing mice. The anti-tumour effect on both cervical cancer cells in vitro and tumour-bearing mice in vivo were further evaluated., Results: A 34-kDa ZHPV16E7-GrB fusion protein was produced in E. coli and displayed corresponding immunoreactivity. IFA revealed that ZHPV16E7-GrB bound specifically to HPV16-positive TC-1 and SiHa cells. IHA showed that ZHPV16E7-GrB also bound specifically to HPV16-positive clinical tissue specimens. In addition, the near-infrared imaging results showed that ZHPV16E7-GrB was enriched in tumour tissues. Moreover, both the ZHPV16E7-GrB affitoxin and ZHPV16E7 affibody (without GrB) significantly reduced the proliferation of cervical cancer cells in vitro and tumour-bearing mice in vivo, and the antiproliferative effect of ZHPV16E7-GrB was higher than that of the ZHPV16E7 affibody., Conclusions: The affitoxin by coupling the affibody with GrB is a promising targeted therapeutic agent with the dual advantages of the targeted affibody and the GrB cytotoxin., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)