The aim of this study was to evaluate the efficacy and safety of recombinant human adenovirus-p53 (rhAd‑p53) combined with neoadjuvant chemotherapy in treatment of locally advanced cervical cancer (LACC). A total of 40 patients with LACC (stage IB2 to IIIA) were randomized into 2 groups (n=20 each): PVB group (cisplatin + vincristine + bleomycin, intravenously) and combined group (rhAd‑p53 gene therapy + neoadjuvant chemotherapy). Both groups underwent a course of chemotherapy; the only exception was the injection of the rhAd‑p53 solution 1x1012 VP intratumorally at an interval of three days thrice in the combined group thereafter. The tumor sizes and adverse events in both groups were observed. The expression of vascular endothelial growth factor (VEGF), protein p53 and micro‑vessel density (MVD) in tumor tissue was respectively determined by immunohistochemistry. The evaluation was performed three weeks after the completion of chemotherapy. The efficacy was 75% in the PVB group versus 95% efficacy in the combined group; the tumor size was reduced by 11.42±2.78 cm2 in PVB group versus the significant shrinkage of 15.25±4.00 cm2 in the combined group (P<0.05). The expression of VEGF, p53 and MVD was downregulated in both the PVB and combined groups, with significantly statistical differences versus the control. No additional adverse events were evidenced in the combined group. Therefore, intratumoral injection of rhAd‑p53 combined with neoadjuvant chemotherapy has advantage over conventional chemotherapy for its high efficacy, safety and synergism in the therapy for LACC.
Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. We read with great interest the Zou et al. correspondence and appreciate the important comments on our findings. In this study,1 we used a xenograft model for our investigation on the interactions between hepatocellular carcinoma (HCC) cells and tumor‐associated macrophages (TAMs). This model was established at our institute by Dr. Tang and provides a platform for research on HCC metastasis.2 Although BALB/c nude mice are immunodeficient and lack T cells, other immune cells, such as macrophages and neutrophils, are normal and functional. In the tumor microenvironment, a variety of nonmalignant stromal cells may interact with one another in many ways, which cannot all be investigated in one study. In our study, we emphasized cross‐talk between HCC cells and TAMs. However, the interactions between TAMs and T cells were not within the scope of the study. Furthermore, we confirmed the direct effect of human interleukin‐34 (IL‐34) on the proliferation and chemotactic migration of human macrophages through its receptor, CSF1R. Although the amino acid sequence of human IL‐34 shares only 68.2% homology with mouse IL‐34, animal studies revealed similar results as our in vitro experiments.1 We proposed that the IL‐34 secreted by human HCC cells can be recognized by mouse CSF1R on the cell surface of macrophages, to promote their proliferation and migration. Zou et al. also stated that colony‐stimulating factor 1 (CSF1) should be considered when studying the miR‐28‐5p‐IL‐34‐macrophage feedback loop in HCC cells. In our identification of target genes, alterations of miR‐28‐5p had no effect on expression of CSF1 by HCC cells, so we proposed that although the CSF1/macrophage axis may exist in the HCC microenvironment, the miR‐28‐5p‐IL‐34‐macrophage feedback loop in HCC cells is independent of CSF1. Macrophages in different tumor microenvironments have distinct roles,4 but they have the general characteristic of tumor promotion in HCC cells,5 which we confirmed in our study. The specific role played by TAMs in the HCC microenvironment will be a focus of our future studies.
To explore the potential correlation between three-dimensional color power Doppler ultrasound (3D-CPA) parameters and high-grade cervical lesions and early cervical cancer microvessel density (MVD) and investigate the role of transvaginal three-dimensional power Doppler ultrasonography in the detection of cervical intraepithelial neoplasia.Totally 90 subjects were randomly divided into three groups: the control group (n = 30, including patients with chronic cervicitis), the high-grade cervical intraepithelial neoplasia (CIN) group (n = 30, mainly CIN II-III), and the early cervical cancer group (stage Ia-IIa) (n = 30). All patients received preoperative 3D-CPA, and the cervical blood flow was graded. The cervical and intra-mass parameters including vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) were measured. The immunohistochemistry of the anti-CD34 monoclonal antibody was performed for the post-operative specimens obtained from each group. The MVD of the tumors was calculated. The difference of each parameter was compared among these three groups, and the correlations between the ultrasound vascular parameters and MVD were analyzed. The high-grade CIN group was followed up for 6 months after the loop electrosurgical excision procedure (LEEP) conization surgery with 3D-CPA.Compared with the other two groups, the early cervical cancer group had significantly higher VI, FI, and VFI parameters (p < 0.01). Compared with the control group, all of the three parameters of the high-grade CIN group were significantly higher (p < 0.01). The MVD values increased from the control group to the high-grade CIN group, and in turn to the cervical cancer group, with significant differences between each pair (p < 0.05). MVD was positively correlated with the ultrasound parameters VI and VFI (r = 0.723, r = 0.692). There were significant differences among the three groups in terms of vascular morphology and type. However, the ultrasound parameters and vascular types were not significantly different between the postoperative CIN group and the control group.3D-CPA can be used to assess blood flow in the cervix. It is particularly useful for the early diagnosis of cervical cancer and CIN and for the postoperative follow-up of CIN.
Multiple organ dysfunction syndrome (MODS) is a key factor that leads to death in elderly patients with sepsis. Therefore, early prevention and treatment of gastrointestinal dysfunction (GIDF) in elderly patients with sepsis is an important measure to prevent MODS occurrence. This research explores the correlation between intestinal microflora and GIDF in elderly patients with sepsis and provides ideas for the prevention and treatment of GIDF in elderly patients with sepsis. In this study, 152 patients with sepsis (122 patients with sepsis and GIDF) treated in the Third Affiliated Hospital of Yunnan University of Chinese Medicine from January to September 2019 were selected as the sepsis group and 100 elderly who had normal physical examination results were selected as the control group. The common intestinal microflora of the two groups was compared. Patients with sepsis and GIDF were treated as the GIDF group and the other patients with sepsis were treated as the non-GIDF group. The common intestinal microflora, gastrointestinal indicators, serum inflammatory factors, and immune function indices were compared between the two groups. Correlation analysis of the observed indices with statistical significance was carried out. The results showed 152 patients with sepsis and 122 patients with sepsis and GIDF; thus, the incidence of sepsis with GIDF was 80.26%. The total average score of sepsis with GIDF was 3.61±0.09. There was no statistically significant difference in GIDF scores of patients ages 65–75 and > 75 years old. The number of Bifidobacterium and Lactobacillus in elderly patients with sepsis was lower and the number of Escherichia coli was higher than in the control group. In elderly patients with sepsis, the number of Bifidobacterium and Lactobacillus in the GIDF group was lower and the number of E. coli was higher than in the non-GIDF group. White blood cell (WBC) count, procalcitonin (PCT), C-reactive protein (CRP), tumor necrosis factor- α (TNF- α ), gastrin (GAS), and diamine oxidase (DAO) in GIDF patients were higher and motilin (MOT), CIT (CIT), CD4 + , and CD8 + were lower than in the non-GIDF group. WBC count, PCT, CRP, TNF- α , GAS, and DAO were negatively correlated with the number of Bifidobacterium and Lactobacillus but positively correlated with E. coli . MOT, CIT, CD4 + , and CD8 + were positively correlated with the number of Bifidobacterium and Lactobacillus but negatively correlated with E. coli . There was a negative correlation between Bifidobacterium and Lactobacillus and GIDF score and a positive correlation between E. coli and GIDF score. Therefore, the change in the intestinal microflora in elderly patients with sepsis is related to GIDF.
Some non-structural carbohydrates, especially starch, escape ruminal fermentation, are converted into glucose, and are absorbed from the small intestine. This glucose provides an important source of energy, and its usage is more efficient than glucose from carbohydrates which are fermented as short chain fatty acids in the rumen and, subsequently, undergo hepatic gluconeogenesis. Tibetan sheep graze on the harsh Qinghai-Tibetan Plateau (QTP) all year round and their carbohydrate and energy intakes fluctuate greatly with seasonal forage availability. Consequently, a high capacity to absorb glucose from the small intestine would be particularly beneficial for Tibetan sheep to allow them to cope with the inconsistent dietary intakes. This study examined how the small intestinal morphology and sugar transporters' expression of Tibetan and Small-tailed Han (Han) sheep respond to fluctuating energy intakes under the harsh conditions of the QTP. Han sheep graze on the QTP only in summer and are generally raised in feedlots. Twenty-four Tibetan sheep and 24 Han sheep, all wethers, were assigned randomly to four groups (n = 6 per breed/group), with each group offered a diet differing in digestible energy content: 8.21, 9.33, 10.45 and 11.57 MJ/kg DM. After 49 d, all sheep were slaughtered, tissues of the small intestine were collected, and measurements were made of the morphology and glucose transporters and the related regulation gene expressions. At intakes of low energy levels, Tibetan sheep had a greater villus surface area in the duodenum, jejunum and ileum and higher mRNA expression of sodium-dependent glucose transporter 1 in the duodenum and ileum (P < 0.05) than Han sheep. In the glucose transporter 2 (GLUT2) mediated glucose absorption pathway, Tibetan sheep had higher GLUT2 and taste receptor family 1 member 2 and 3 mRNA expressions than Han sheep in the duodenum, jejunum and ileum (P < 0.05). We concluded that the differences between breeds indicated a greater glucose absorption capacity in the small intestine of Tibetan than Han sheep, which would confer an advantage to Tibetan over Han sheep to an inconsistent energy intake on the harsh QTP. These findings suggested that ruminants raised under harsh environmental conditions with highly fluctuating dietary intakes, as is often the case in grazing ruminants worldwide, are able to absorb glucose from the small intestine to a greater extent than ruminants raised under more moderate conditions.
5525 Background: To evaluate the efficacy and safety of recombinant adenovirus-p53 (rAd-p53) combined with chemotherapy in treatment of locally advanced cervical cancer. Methods: Forty patients with stage IIb2 IV locally advanced cervical cancer were randomly divided into 2 groups: 20 patients receiving gene plus chemotherapy (PCG) and 20 receiving sole chemotherapy (CG). The patients in PCG were given one course of PVB (cisplatin + vincristine + pingyangmycin) and 5 times intratumoral injections of rAd-p53 at a dose of 2 x 10 12 viral particles once per 3 days. The CG patients received a sole course of PVB. The study patients were followed up for at least one year. The VEGF, p53, Bax, and p21 protein expression in pre- and post-treatment tumor tissues were examined by immunohistochemistry. Results: The response was evaluated at 3 months after treatments. The response rates (CR + PR) were 95% and 75% for the PCG and CG patients, respectively. P53 proteins were strongly expressed in the tumor tissues from both groups. There were no significant changes in expression level of the p53 protein in the tumor tissue from pre- and post-treatment. However, the VEGF, Bax, and p21 protein expressions significantly increased in PCG after treatment. The overall one-year survive rates were 90% and 65%, respectively. A mild to medium grade of fever was found in 90% of the PCG patients. No serious of adverse events relative to rAd-p53 were observed. Conclusions: Combined the rAd-p53 gene with chemotherapy is an effective treatment for the patients with advanced cervical cancer. The rAd-p53 gene therapy is a safe treatment.
Although M2 tumour-associated macrophages (M2 TAMs) have been shown to be associated with the progression and metastasis of breast cancer, their role in oesophageal squamous cell carcinoma (ESCC) remains less well understood. Therefore, to understand the clinicopathological significance of infiltrated M2 TAMs in ESCC, statistical analysis was performed after immunohistochemical evaluation of CD163 expression, a well-accepted surface marker of M2 TAMs in ESCC. To gain insight into the effect of M2 TAMs, ESCC cell lines Eca109 and KYSE150 cells were co-cultured with M2 TAMs artificially induced from THP-1 cells. The variations in the proliferation, migration and invasion were assessed using the MTT, wound-healing and Transwell assays, respectively. The variation in the typical biomarkers of the epithelial-mesenchymal transition (EMT) was evaluated using western blotting. Infiltrated M2 TAMs were confirmed to predominate in the stroma of ESCC relative to normal controls. Moreover, it turned out that M2 TAMs were shown to promote the migration and invasion of ESCC cells but not proliferation. Furthermore, M2 TAMs were observed to induce EMT in ESCC cells. Together, our results showed that infiltrated M2 TAMs in the stroma is a feature accompanying ESCC metastasis and that M2 TAMs can promote the migration and invasion, but not proliferation, of ESCC cells, thereby inducing EMT. Thus, M2 TAMs could be an alternative therapeutic target in ESCC.
Gastric cancer (GC) is one of the most lethal malignant tumors worldwide with poor outcomes. Vascular mimicry (VM) is an alternative blood supply to tumors that is independent of endothelial cells or angiogenesis. Previous studies have shown that VM was associated with poor prognosis in patients with GC, but the underlying mechanisms and the relationship between VM and immune infiltration of GC have not been well studied.In this study, expression profiles from VM-related genes were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Cox regression was performed to identify key VM-related genes for survival. Subsequently, a novel risk score model in GC named VM index and a nomogram was constructed. In addition, the expression of one key VM-related gene (serpin family F member 1, SERPINF1) was validated in 33 GC tissues and 23 paracancer tissues using immunohistochemistry staining.Univariate and multivariate Cox regression suggested that SERPINF1 and tissue factor pathway inhibitor 2 (TFPI2) were independent risk factors for the prognosis of patients with GC. The AUC (> 0.7) indicated the satisfactory discriminative ability of the nomogram. SsGESA and ESTIMATE showed that higher expression of SERPINF1 and TFPI2 is associated with immune infiltration of GC. Immunohistochemistry staining confirmed that the expression of SERPINF1 protein was significantly higher in GC tissues than that in paracancer tissues.A VM index and a nomogram were constructed and showed satisfactory predictive performance. In addition, VM was confirmed to be widely involved in immune infiltration, suggesting that VM could be a promising target in guiding immunotherapy. Taken together, we identified SERPINF1 and TFPI2 as immunologic and prognostic biomarkers related to VM in GC.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)