Skovsgaardvalenzuela7778
In this review, we briefly discuss the mechanisms underlying various novel immune checkpoint blockade therapies and combination modalities along with recent/ongoing clinical trials which may generate innovative new treatment approaches with potential new FDA approvals for HCC treatment in the near future.Approximately 60%-70% of patients with malignant tumours require radiotherapy. The clinical application of immune checkpoint inhibitors (ICIs), such as anti-PD-1/PD-L1, has revolutionized cancer treatment and greatly improved the outcome of a variety of cancers by boosting host immunity.However, radiotherapy is a double-edged sword for PD-1/PD-L immunotherapy. Research on how to improve radiotherapy efficacy using PD-1/PD-L1 inhibitor is gaining momentum. Various studies have reported the survival benefits of the combined application of radiotherapy and PD-1/PD-L1 inhibitor. To fully exerts the immune activation effect of radiotherapy, while avoiding the immunosuppressive effect of radiotherapy as much as possible, the dose selection, segmentation mode, treatment timing and the number of treatment sites of radiotherapy play a role. Therefore, we aim to review the effect of radiotherapy combined with anti-PD-1/PD-L1 on the immune system and its optimization.
Of gynecologic malignancies, ovarian cancer is the leading cause of death, mainly due to the lack of sensitive tumor markers, which means it almost always presents at an advanced stage. Exosome Component 4 (EXOSC4) is involved in RNA degradation, but its role in epithelial ovarian cancer (EOC) is unclear.
The expression levels of EXOSC4 in EOC and normal ovarian tissue specimens were determined by immunohistochemical staining. The overall survival (OS) and progression-free survival (PFS) of patients with EOC were evaluated after patients were classified into high and low EXOSC4 expression groups, and the Cox regression model was established to identify independent predictors of patient prognosis. The effects of EXOSC4 on proliferation, colony formation, migration, and invasion were examined in the SKOV-3 and HO8910 cell lines by lentivirus-mediated shRNA knockdown. Flow cytometry was used to detect cell cycle changes. The mRNA levels of cyclin D1, CDK4, and c-myc were detected by RT-PCR. The protein expreC4 is expected to be a novel biomarker and molecular target in EOC.
EXOSC4 is involved in EOC. Knockdown of EXOSC4 can inhibit the proliferation, migration, and invasion ability of EOC by suppressing the Wnt pathway. 5-(N-Ethyl-N-isopropyl)-Amiloride EXOSC4 is expected to be a novel biomarker and molecular target in EOC.The management of patients with relapsed or refractory (R/R) acute myeloid leukaemia (AML) remains a challenge with few reliably effective treatments. Chidamide, a new selective HDAC inhibitor, has demonstrated some effectiveness in AML patients. Herein, we reported three patients with R/R AML who were unresponsive to venetoclax plus azacitidine (VA) but were successfully treated with VA when chidamide was added to the regimen. MCL1 is one of the anti-apoptotic proteins. Chidamide targets the MCL1 protein, which may permit venetoclax resistance when upregulated. We determined MCL1 protein expression in different AML cell lines, and chidamide could downregulate MCL1 expression in venetoclax resistance AML cells. In general, our experience showed that the chidamide/VA combination could improve the condition of R/R AML patients who are resistant to VA. Formally evaluating this regimen in R/R AML patients may be meaningful.Although the association of MEG3 gene rs7158663 polymorphism with cancer susceptibility has been investigated, the findings are inconsistent. The aim of this study was to analyze the association between the rs7158663 polymorphism and cancer susceptibility through a case-control study and meta-analysis. In a case-control study with 430 colorectal cancer (CRC) cases and 445 healthy controls, the rs7158663 polymorphism was genotyped by direct sequencing. STATA software was used to calculate the pooled odds ratio and 95% confidence interval in a meta-analysis including 4,649 cancer cases and 5,590 controls. Both the case-control study and meta-analysis showed that the rs7158663 polymorphism was associated with increased susceptibility to CRC. Individuals carrying the AA or GA genotype were more likely to develop CRC than those carrying the rs7158663 GG genotype. Interestingly, MEG3 expression was significantly lower in colorectal tissues of the AA or GA genotype compared to those of the rs7158663 GG genotype. In addition, the meta-analysis suggested that the rs7158663 polymorphism was also associated with increased susceptibility to breast cancer and gastric cancer. Bioinformatics analysis showed that the rs7158663 A allele contributed to the binding of hsa-miR-4307 and hsa-miR-1265 to MEG3. In conclusion, the current findings suggest that the MEG3 gene rs7158663 polymorphism may serve as a genetic marker for predicting the risk of cancers, such as breast cancer, gastric cancer and CRC. However, the sample size of the current study is still insufficient, especially in the subgroup analysis. Therefore large and well-designed studies are needed to validate our findings.
Ovarian cysts are very common diseases of the female reproductive system. Giant ovarian cysts refer to the tumors with diameters greater than 10 cm. In recent years, due to the development of clinical diagnosis, imaging modalities, and the improvement of patients' cognition of the diseases, the occurrence of giant ovarian cysts has become rare. The purpose of this study was to show a new operation method of single-port laparoscopy to treat giant ovarian cysts.
We report a case series of five patients with giant ovarian cysts who underwent single-port laparoscopic surgery in the gynecology department of the Shengjing Hospital of China Medical University between June 2020 and March 2021. The inclusion criteria were ovarian cysts at least 20 cm in diameter, and cases when the tumor might be malignant were excluded.
The patients' mean age was 26.2years. The most common clinical presentation was progressive abdominal distension. Median size of the cysts at imaging was 39.2 cm (range 21-63 cm). All patients underwent single-port laparoscopic surgery, and none of them converted to laparotomy. On final pathological reports, two cysts were serous cystadenomas, and three were mucinous cystadenomas. All patients recovered well and were discharged on time.
Giant ovarian cysts can be treated by single-port laparoscopic surgery. In addition to the well-known advantages of laparoscopic surgery (e.g., small pelvic interference, fast postoperative recovery), it can also play the role of perfect cosmetic results, which has more advantages for young women.
Giant ovarian cysts can be treated by single-port laparoscopic surgery. In addition to the well-known advantages of laparoscopic surgery (e.g., small pelvic interference, fast postoperative recovery), it can also play the role of perfect cosmetic results, which has more advantages for young women.
Immunotherapy for gastrointestinal stromal tumors (GISTs) remains a clinical challenge. The present study aimed to explore the clinical and prognostic significance of immune cell infiltration and PD-L1 expression in GISTs.
A total of 507 clinical tissue specimens of primary GISTs were collected for immunohistochemical analysis of immune cell infiltration and PD-L1 expression. Influencing factors of survival were evaluated by Kaplan-Meier analysis. Univariate and multivariate analyses were performed using the Cox regression model.
There were significant differences in sex, tumor location, size, mitotic index, NIH risk grade, and cell morphology between different gene mutation types of GISTs. Immune cell infiltration in GISTs mainly involved macrophages and T cells. PD-1 was expressed in 48.5% of the tissue specimens, and PD-L1 expression was detected in 46.0% of the samples. PD-L1 expression was negatively correlated with the tumor size and mitotic index but positively correlated with the number of CD8+ T cells. There were significant differences in the number of CD8+ T cells between different gene mutation types. Wild type-mutant GISTs were enriched with CD8+ T cells as compared with KIT- and PDGFRA-mutant GISTs. The number of CD8+ T cells was higher in non-gastric GISTs. PD-L1 and CD8+ T cells were independent predictors for better relapse-free survival of GISTs.
PD-L1 expression is a predictive biomarker for better prognosis of GISTs. link2 Non-gastric GIST patients with wild-type mutations may be the beneficiaries of PD-1/PD-L1 inhibitors.
PD-L1 expression is a predictive biomarker for better prognosis of GISTs. Non-gastric GIST patients with wild-type mutations may be the beneficiaries of PD-1/PD-L1 inhibitors.
Malignant mesothelioma (MM) is a highly aggressive cancer with a poor prognosis. link3 Despite the use of several well-known markers, the diagnosis of MM is still challenging in some cases. we applied bioinformatics to identify key genes and screen for diagnostic and prognostic markers of MM.
The expression profiles of GSE2549 and GSE112154 microarray datasets from the Gene Expression Omnibus database contained 87 cases of MM tissue and 8 cases of normal mesothelial tissue in total. The GEO2R tool was used to detect differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were performed using DAVID Bioinformatics Resources. The DEGs protein-protein interaction networks were constructed from the STRING database. Cytoscape was used to identify significant modules and hub genes. The GEPIA database was used to explore relationships between hub genes and prognosis of MM. Immunohistochemistry was used to analyze protein expressionein expression and overall survival but did not confirm a correlation with GAPDH. The receiver operating characteristic curves of Aurora-A protein expression suggested acceptable accuracy (AUC=0.827; 95%CI [0.6686 to 0.9535];
=0.04). The sensitivity and specificity of Aurora-A were 83.33% and 77.78%, respectively.
Aurora-A could be an optimal diagnostic biomarker and a potential prognostic marker for MM.
Aurora-A could be an optimal diagnostic biomarker and a potential prognostic marker for MM.
Patients suffering from inflammatory bowel disease (IBD) have an increased risk of cancer. However, the risk of malignancy in patients with elderly-onset IBD (≥60 years) remains controversial. Hence, we aimed to identify and compare the dissimilarities in morbidity and related risk factors between patients with elderly-onset and adult-onset (18-59 years) IBD in a Chinese cohort.
Patients with confirmed IBD, diagnosed at age ≥18 years, between January 1998 and December 2020 at the Peking Union Medical College Hospital were enrolled. The yearly incidence rates (IRs) for cancer were calculated, and the characteristics were analyzed in these patients.
A total of 1,480 patients suffering from adult-onset IBD and 129 patients suffering from elderly-onset IBD with a median follow-up period of 4.9 years and 4.8 years, respectively, were included. Patients in the elderly-onset IBD group demonstrated an increased overall incidence of cancer than that demonstrated by patients in the adult-onset group (IR 26.9 versus 9.
