Zongwen Liu

The extracellular matrix (ECM) is a major component of the tumor microenvironment (TME) and plays an important role in cervical cancer progression. Versican, encoded by the VCAN gene, is a member of the aggrecan/proteoglycan family and has been reported as a marker of poor prognosis in cervical cancer. However, the versican-producing cells in cervical cancer tissue are not clearly identified. To identify the versican-producing cells in cervical cancer tissue, single-cell RNA sequencing (scRNA-seq) data of cervical cancer tissue are re-analyzed, and we find that versican is highly expressed in monocytes and fibroblasts. Immunohistochemical staining of cervical cancer and adjacent normal tissues showed that versican was predominantly expressed in non-parenchymal cells. Multiplex immunofluorescence staining further identified versican-expressing macrophages in cervical cancer tissues. We subsequently collected peripheral blood mononuclear cells (PBMCs) from a patient with cervical cancer before and after radiotherapy and performed scRNA-seq to investigate the highly variable genes in PBMCs. Notably, VCAN was identified as a monocyte-enriched gene and showed relatively high expression in the patient’s circulating monocytes. We further investigated the effect of Versican core protein (VCAN-V3) on macrophages. The results suggest that VCAN-V3 predominantly suppresses M1-associated gene expression and induces a partial shift toward an M2-like transcriptional phenotype in RAW264.7 cells. In conclusion, our study demonstrates that stromal VCAN is upregulated in cervical cancer tissue. VCAN-V3 may influence the tumor microenvironment by modulating macrophage polarization-associated responses.

Background: Exercise rehabilitation during neoadjuvant chemotherapy (NAT) prior to esophageal cancer (EC) surgery has the potential to improve patients’ physical function and accelerate postoperative recovery, but its effect remains unclear. Methods: A systematic review and meta-analysis were conducted to compare the clinical outcomes of exercise rehabilitation and usual care during preoperative NAT in patients with EC. Relevant literature in online databases EMBASE, PubMed, Web of Science, and ScienceDirect were thoroughly searched and then screened. The data related to clinical outcomes were extracted and synthesized by meta-analysis. Results: A total of 10 studies involving 466 participants were included. Meta-analysis revealed significantly higher tumor response rates in the intervention group (risk difference = 0.28, 95% confidence interval [CI] = 0.12–0.44, P < .001), but no significant difference in T-stage downgrading rates between groups (risk difference = 0.11, 95% CI = −0.04 to 0.25, P = .138). The 6-minute walk distance was significantly greater in the intervention group (mean difference [MD] = 26.60 m, 95% CI = 6.61–46.58, P = .009), as was the daily step count (MD = 434.18 steps, 95% CI = 47.79–820.57, P = .028), and the peak oxygen uptake (MD = 2.55 mL/kg/min, 95% CI = 0.72–4.37, P = .023). No difference was found in maximal inspiratory pressure between groups (MD = 4.93, 95% CI = −3.09 to 12.96, P = .651). Conclusion: Exercise rehabilitation during NAT for EC may confer multidimensional benefits to patients’ physical function. However, the current evidence level remains low due to the limited number and small sample sizes of the included studies.

Objective: This study aims to explore the impact of APE1 gene knockout on the transcriptome of esophageal cancer cells and conduct a preliminary screening of APE1-regulated target genes to provide a basis for understanding APE1 target genes and finding new anti-esophageal cancer therapeutic targets.Methods: We collected 100 patients with esophageal squamous cell carcinoma (ESCC), analyzed the expression of APE1 in ESCC by immunohistochemical, and analyzed the overall survival. TE-1 cells with APE1 knockout were used for transcriptome sequencing (RNA sequencing, RNA-Seq) detection, and GO and KEGG enrichment analysis of differentially expressed genes was conducted. Protein-protein interaction (PPI) network analysis was performed on the genes in the intersection of differential genes between the two sequencing datasets. The qRT-PCR and Western blotting experiments were employed to confirm the effect of APE1 knockdown on the expression levels of FN1, TNF, and IL-6 in esophageal cancer cells.Results: APE1 highly expressed in ESCC tissue, and its high expression leads the worse OS. The stable transfected TE-1 cell line with knockdown of the APE1 gene was successfully constructed, with a knockdown efficiency of 100%. RNA-seq analysis revealed that 2,060 differential genes were detected between APE1-KO stably transfected cells and their corresponding APE1-YD cells, with 1,063 upregulated genes and 997 downregulated genes. RNA-seq analysis found that differentially expressed genes after APE1 knockout in TE-1 cells were primarily enriched in pathways related to metabolism, extracellular matrix, inflammatory response, and angiogenesis. PPI network analysis demonstrated that FN1, TNF, and IL-6 may be essential target genes of APE1. The three core genes of FN1, TNF, and IL-6 were confirmed using qRT-PCR and Western blotting, and the results were consistent with the transcriptome sequencing results.Conclusion: Knocking out APE1 can affect the function, related pathways, and downstream target gene expression of ESCC cells. APE1 can promote the transcriptional expressions of FN1 and IL6 genes while inhibiting the TNF gene. FN1, TNF, and IL-6 may be potential target genes regulated by APE1 in esophageal cancer.

Background Esophageal squamous carcinoma (ESCC) is the most prevalent pathological subtype of esophageal cancer (EC). It has the characteristics of significant local invasion, quick disease progression, high recurrence rates, and a dismal prognosis for survival. Phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/AKT) is a signaling system whose aberrant activation regulates downstream factors, leading to the promotion of cancer development. This study looks at a protein called Glycerol-3-phosphate dehydrogenase 1-like (GPD1L), which strongly affects the development of several cancers. However, its association with ESCC development and its underlying mechanisms are not clear. Methods In this paper, we analyzed six ESCC transcriptome data obtained from the GEO database. We utilized bioinformatics technology and immunohistochemistry to differentially analyze GPD1L levels of mRNA and protein expression in ESCC and normal adjacent tissues. Furthermore, we conducted survival, co-expression, enrichment, immune infiltration and drug sensitivity analysis. Moreover, we further investigated the role and mechanism of GPD1L by Western Blot (WB), Cell Counting Kit-8 (CCK8), wound healing assay, Transwell assay, and flow cytometry. Finally, the addition of IGF-1, the activator of PI3K/AKT, could rescue the inhibitory effect of GPD1L on ESCC. Results The findings manifest that the expression of GPD1L was low in ESCC, and functional experiments showed that GPD1L promoted apoptosis in vitro while blocking cell migration, invasion, and proliferation. Based on mechanism research, GPD1L’s impact on ESCC could be explained by its suppression of the PI3K/AKT signaling pathway’s activation. Conclusion To sum up, our findings imply that GPD1L may impede the initiation and advancement of ESCC via modulating the PI3K/AKT signaling pathway. GPD1L is considered to be a promising therapeutic target and biomarker to diagnose and treat ESCC.

Delineating the clinical target volume (CTV) and organs at risk (OARs) is crucial in rectal cancer radiotherapy. However, the accuracy of manual delineation (MD) is variable and the process is time consuming. Automatic delineation (AD) may be a solution to produce quicker and more accurate contours. In the present study, a convolutional neural network (CNN)‑based AD tool was clinically evaluated to analyze its accuracy and efficiency in rectal cancer. CT images were collected from 148 supine patients in whom tumor stage and type of surgery were not differentiated. The rectal cancer contours consisted of CTV and OARs, where the OARs included the bladder, left and right femoral head, left and right kidney, spinal cord and bowel bag. The MD contours reviewed and modified together by a senior radiation oncologist committee were set as the reference values. The Dice similarity coefficient (DSC), Jaccard coefficient (JAC) and Hausdorff distance (HD) were used to evaluate the AD accuracy. The correlation between CT slice number and AD accuracy was analyzed, and the AD accuracy for different contour numbers was compared. The time recorded in the present study included the MD time, AD time for different CT slice and contour numbers and the editing time for AD contours. The Pearson correlation coefficient, paired‑sample t‑test and unpaired‑sample t‑test were used for statistical analyses. The results of the present study indicated that the DSC, JAC and HD for CTV using AD were 0.80±0.06, 0.67±0.08 and 6.96±2.45 mm, respectively. Among the OARs, the highest DSC and JAC using AD were found for the right and left kidney, with 0.91±0.06 and 0.93±0.04, and 0.84±0.09 and 0.88±0.07, respectively, and HD was lowest for the spinal cord with 2.26±0.82 mm. The lowest accuracy was found for the bowel bag. The more CT slice numbers, the higher the accuracy of the spinal cord analysis. However, the contour number had no effect on AD accuracy. To obtain qualified contours, the AD time plus editing time was 662.97±195.57 sec, while the MD time was 3294.29±824.70 sec. In conclusion, the results of the present study indicate that AD can significantly improve efficiency and a higher number of CT slices and contours can reduce AD efficiency. The AD tool provides acceptable CTV and OARs for rectal cancer and improves efficiency for delineation.

Nucleotide binding and oligomeric domain‑like receptor X1 (NLRX1), a member of the NLR family, is associated with the physiological and pathological processes of inflammation, autophagy, immunity, metabolism and mitochondrial regulation, and has been demonstrated to have pro‑ or antitumor effects in various tumor types. However, the biological function of NLRX1 in esophageal squamous cell carcinoma (ESCC) has remained elusive. In the present study, by using bioinformatics methods, the differential expression of NLRX1 at the mRNA level was examined. Overall survival, clinical correlation, receiver operating characteristic curve, Cox regression, co‑expression, enrichment, immune infiltration and drug sensitivity analyses were carried out. A nomogram and a calibration curve were constructed. Changes in protein expression levels were investigated by immunohistochemistry and western blotting. The impact of NLRX1 on i) cell proliferation was evaluated by Cell Counting Kit‑8 assays; ii) migration was examined by wound‑healing assays; iii) migration and invasion were evaluated by Transwell assays; and iv) apoptosis was assessed by Annexin V/PI staining and flow cytometry. The results revealed that, compared to normal adjacent tissue, NLRX1 was lowly expressed in ESCC, and patients with low NLRX1 expression had a shorter survival time. NLRX1 was an independent prognostic factor for ESCC and was associated with tumor grading. Patients in the low‑NLRX1 group showed a decrease in the infiltration of activated natural killer cells, monocytes and M0 macrophages, and these immune‑cell infiltration levels were positively correlated with NLRX1 expression. Knocking down NLRX1 promoted the proliferation of KYSE450 cells, while overexpression of NLRX1 inhibited the proliferation of ECA109 cells. NLRX1 negatively regulated the PI3K/AKT signaling pathway in ESCC. These findings indicate that, through several mechanisms, NLRX1 suppresses tumor growth in ESCC, which offers new insight for investigating the causes and progression of ESCC, as well as for identifying more efficient therapeutic approaches.

Background: This study aimed to investigate the impact of ovary-sparing intensity-modulated radiotherapy (IMRT) on plan quality, treatment time, and gamma passing rates for stage I/II cervical cancer patients. Methods: Fifteen stage I/II cervical cancer patients were retrospectively enrolled, and a pair of clinically suitable IMRT plans were designed for each patient, with (Group A) and without (Group B) ovary-sparing. Plan factors affecting plan quality, treatment time, and gamma passing rates, including the number of segments, monitor units, percentage of small-area segments (field area < 20 cm²), and percentage of small-MU segments (MU < 10), were compared and statistically analyzed. Key plan quality indicators, including ovarian dose, target dose coverage (D_98%, D_95%, D_50%, D_2%), conformity index, and homogeneity index, were evaluated and statistically assessed. Treatment time and gamma passing rates collected by IBA MatriXX were also compared. Results: The median ovarian dose in Group A and Group B was 7.61 Gy (range 6.71–8.51 Gy) and 38.52 Gy (range 29.84–43.82 Gy), respectively. Except for monitor units, all other plan factors were significantly lower in Group A than in Group B (all P < .05). Correlation coefficients between plan factors, treatment time, and gamma passing rates that were statistically different were all negative. Both Groups of plans met the prescription requirement (D_95% ≥ 45.00 Gy) for clinical treatment. D_98% was smaller for Group A than for Group B (P < .05); D_50% and D_2% were larger for Group A than for Group B (P < .05, P < .05). Group A plans had worse conformity index and homogeneity index than Group B plans (P < .05, P < .05). Treatment time did not differ significantly (P > .05). Gamma passing rates in Group A were higher than in Group B with the criteria of 2%/3 mm (P < .05) and 3%/2 mm (P < .05). Conclusion: Despite the slightly decreased quality of the treatment plans, the ovary-sparing IMRT plans exhibited several advantages including lower ovarian dose and plan complexity, improved gamma passing rates, and a negligible impact on treatment time.

Background NOD-like receptor X1 (NLRX1), a member of the nucleotide binding and oligomeric domain (NOD) like receptor (NLR) family, is connected to the physiological and pathological processes of inflammation, autophagy, immunity, metabolism, and mitochondrial regulation. It has been discovered to have pro- or anti-tumor effects in various tumor types. However, the biological function of NLRX1 in esophageal squamous cell carcinoma (ESCC) is still unknown. Methods Using bioinformatics methods, the differential expression of NLRX1 at the mRNA level was examined. OS analysis, clinical correlation analysis, ROC analysis, Cox analysis, coexpression analysis, enrichment analysis, immune infiltration analysis, and drug sensitivity analysis were carried out. A nomogram and calibration curve were constructed. Investigating changes in protein expression levels using IHC and WB, assessing the impact on proliferation using CCK-8 assays, examining migration using scratch healing assays, examining migration and invasion using transwell assays, and analyzing apoptosis using fluorescence and flow cytometry. Results Compared to normal tissue adjacent to cancer, NLRX1 is low expressed in ESCC, and patients with low NLRX1 expression have a shorter survival period. NLRX1 is an independent prognostic factor for ESCC and is connected to tumor grading. The low NLRX1 group showed a decrease in NK cells activated, Monocytes, and Macrophages M0 infiltration, and these immune cell infiltration levels were positively correlated with NLRX1 expression. Knocking down NLRX1 promotes the growth and development of KYSE450 cells, while overexpression of NLRX1 inhibits the growth and development of ECA109 cells. NLRX1 negatively regulates the PI3K/AKT pathway in ESCC. Conclusions Through several mechanisms, NLRX1 suppresses tumor growth in ESCC. This offers a fresh viewpoint for investigating the causes and progression of ESCC as well as for searching for more potent therapeutic approaches.

PARP was an enzyme found in the nucleus of eukaryotic cells that played a crucial role in repairing damaged DNA. Recently, PARP inhibitors have demonstrated great potential in cancer treatment. Thus, the FDA has approved several small-molecule PARP inhibitors for cancer maintenance therapy. The combination of PARP inhibitors and radiotherapy relies on synthetic lethality, taking advantage of the flaws in DNA repair pathways to target cancer cells specifically. Studies conducted prior to clinical trials have suggested that the combination of PARP inhibitors and radiotherapy can enhance the sensitivity of cancer cells to radiation, intensify DNA damage, and trigger cell death. Combining radiotherapy with PARP inhibitors in clinical trials has enhanced the response rate and progression-free survival of diverse cancer patients. The theoretical foundation of PARP inhibitors combined with radiotherapy is explained in detail in this article, and the latest advances in preclinical and clinical research on these inhibitors for tumor radiotherapy are summarized. The problems in the current field are recognized in our research and potential therapeutic applications for tumors are suggested. Nevertheless, certain obstacles need to be tackled when implementing PARP inhibitors and radiotherapies in clinical settings. Factors to consider when using the combination therapy are the most suitable schedule and amount of medication, identifying advantageous candidates, and the probable adverse effects linked with the combination. The combination of radiotherapy and PARP inhibitors can greatly enhance the effectiveness of cancer treatment.

With the advancement of radiotherapy equipment, stereotactic radiotherapy (SRT) has been increasingly used. Among the many radiotherapy devices, Halcyon shows promising applications. This article reviews the dosimetric performance such as plan quality, plan complexity, and gamma passing rates of SRT plans with Halcyon to determine the effectiveness and safety of Halcyon SRT plans. This article retrieved the last 5 years of PubMed studies on the effectiveness and safety of the Halcyon SRT plans. Two authors independently reviewed the titles and abstracts to decide whether to include the studies. A search was conducted to identify publications relevant to evaluating the dosimetric performance of SRT plans on Halcyon using the key strings Halcyon, stereotactic radiosurgery, SRT, stereotactic body radiotherapy, and stereotactic ablative radiotherapy. A total of 18 eligible publications were retrieved. Compared to SRT plans on the TrueBeam, the Halcyon has advantages in terms of plan quality, plan complexity, and gamma passing rates. The high treatment speed of SRT plans on the Halcyon is impressive, while the results of its plan evaluation are also encouraging. As a result, Halcyon offers a new option for busy radiotherapy units while significantly improving patient comfort in treatment. For more accurate results, additional relevant publications will need to be followed up in subsequent studies.