Showing papers in "Journal of Cancer Research and Clinical Oncology in 2021"
TL;DR: Predictive models using eXtreme Gradient Boosting and deep learning based on CT images and 3D-CNN showed considerable efficacy in identifying MVI preoperatively and may facilitate decision-making in HCC treatment but requires further validation.
Abstract: Microvascular invasion (MVI) is a valuable predictor of survival in hepatocellular carcinoma (HCC) patients. This study developed predictive models using eXtreme Gradient Boosting (XGBoost) and deep learning based on CT images to predict MVI preoperatively. In total, 405 patients were included. A total of 7302 radiomic features and 17 radiological features were extracted by a radiomics feature extraction package and radiologists, respectively. We developed a XGBoost model based on radiomics features, radiological features and clinical variables and a three-dimensional convolutional neural network (3D-CNN) to predict MVI status. Next, we compared the efficacy of the two models. Of the 405 patients, 220 (54.3%) were MVI positive, and 185 (45.7%) were MVI negative. The areas under the receiver operating characteristic curves (AUROCs) of the Radiomics-Radiological-Clinical (RRC) Model and 3D-CNN Model in the training set were 0.952 (95% confidence interval (CI) 0.923–0.973) and 0.980 (95% CI 0.959–0.993), respectively (p = 0.14). The AUROCs of the RRC Model and 3D-CNN Model in the validation set were 0.887 (95% CI 0.797–0.947) and 0.906 (95% CI 0.821–0.960), respectively (p = 0.83). Based on the MVI status predicted by the RRC and 3D-CNN Models, the mean recurrence-free survival (RFS) was significantly better in the predicted MVI-negative group than that in the predicted MVI-positive group (RRC Model: 69.95 vs. 24.80 months, p < 0.001; 3D-CNN Model: 64.06 vs. 31.05 months, p = 0.027). The RRC Model and 3D-CNN models showed considerable efficacy in identifying MVI preoperatively. These machine learning models may facilitate decision-making in HCC treatment but requires further validation.
71 citations
TL;DR: The authors in this paper presented an overview on the spectrum of cancers linked to EBV based on observations of associations and proportions in the published literature while also using these observations to estimate the incidence and mortality burden of some of these cancers.
Abstract: More than 90% of the adult population globally is chronically infected by the Epstein–Barr virus (EBV). It is well established that EBV is associated with a number of malignancies, and advances in knowledge of EBV-related malignancies are being made every year. Several studies have analysed the global epidemiology and geographic distribution of EBV-related cancers. However, most have only described a single cancer type or subtype in isolation or limited their study to the three or four most common EBV-related cancers. This review will present an overview on the spectrum of cancers linked to EBV based on observations of associations and proportions in the published literature while also using these observations to estimate the incidence and mortality burden of some of these cancers. We have reviewed the literature on defining features, distribution and outcomes across six cancers with a relatively large EBV-related case burden: Nasopharyngeal carcinoma (NPC), Gastric carcinoma (GC), Hodgkin lymphoma (HL), Burkitt lymphoma (BL), Diffuse large B-cell lymphoma (DLBCL) and Extranodal NK/T-cell lymphoma, Nasal type (ENKTL-NT). We retrieved published region-specific EBV-related case proportions for NPC, GC, HL and BL and performed meta-analyses on pooled region-specific studies of EBV-related case proportions for DLBCL and ENKTL-NT. We match these pooled proportions with their respective regional incidence and mortality numbers retrieved from a publicly available cancer database. Additionally, we also reviewed the literature on several other less common EBV-related cancers to summarize their key characteristics herein. We estimated that EBV-related cases from these six cancers accounted for 239,700–357,900 new cases and 137,900–208,700 deaths in 2020. This review highlights the significant global impact of EBV-related cancers and extends the spectrum of disease that could benefit from an EBV-specific therapeutic.
53 citations
TL;DR: Wu et al. as discussed by the authors explored the role of lung and gut microbiota in lung cancer progression and found that changes in lung and intestinal microbiota are associated with progression of lung cancer.
Abstract: Lung cancer is the leading cause of cancer-related deaths worldwide (Ferlay et al., Int J Cancer 136:E359–386, 2015). In addition, lung cancer is associated with the highest mortality among all cancer types (Wu et al., Exp Ther Med 16:3004–3010, 2018). Previous studies report that microbiota play an important role in lung cancer. Notably, changes in lung and gut microbiota, are associated with progression of lung cancer. Several studies report that lung and gut microbiome promote lung cancer initiation and development by modulating metabolic pathways, inhibiting the function of immune cells, and producing pro-inflammatory factors. In addition, some factors such as microbiota dysbiosis, affect production of bacteriotoxins, genotoxicity and virulence effect, therefore, they play a key role in cancer progression. These findings imply that lung and gut microbiome are potential markers and targets for lung cancer. However, the role of microbiota in development and progression of lung cancer has not been fully explored. The aim of this study was to systemically review recent research findings on relationship of lung and gut microbiota with lung cancer. In addition, we explored gut–lung axis and potential mechanisms of lung and gut microbiota in modulating lung cancer progression. Pulmonary and intestinal flora influence the occurrence, development, treatment and prognosis of lung cancer, and will provide novel strategies for prevention, diagnosis, and treatment of lung cancer.
45 citations
TL;DR: In this article, the piggyBac transposon system was used to generate EGFR-CAR T cells in advanced relapsed/refractory non-small cell lung cancer patients.
Abstract: This phase I clinical trial is designed to assess the safety and feasibility of the epidermal growth factor receptor (EGFR) chimeric antigen receptor (CAR) T-cell generated by the piggyBac transposon system in advanced relapsed/refractory non-small cell lung cancer (NSCLC) patients. Compared to viral systems, the piggyBac transposon system is a simpler, more economical, and alternative way to introduce chimeric antigen receptor (CAR) transgenes into T cells. This study recruited nine patients with advanced relapsed/refractory EGFR-positive NSCLC for two cycles of the piggyBac-generated EGFR-CAR T cells at dose of 1 × 106 cells/kg or 3 × 106 cells/kg of body weight. The patients were monitored for adverse events, clinical response, and persistence of plasma GFR-CAR T cells. Infusions of piggyBac-generated EGFR-CAR T cells were well tolerated in all nine patients. The most common adverse events were grade 1 to 3 fever and there were no patients who experienced grade 4 adverse events or serious cytokine release syndrome. After treatment, eight of nine patients showed detectable EGFR-CAR T cells in their peripheral blood. One patient showed a partial response and lasted for more than 13 months, while six had stable disease, and two had progressed disease. The progression-free survival of these nine patients was 7.13 months (95% CI 2.71–17.10 months), while the median overall survival was 15.63 months (95% CI 8.82–22.03 months). This Phase I clinical trial revealed that the non-viral piggyBac transposon system-engineered EGFR-CAR T-cell therapy is feasible and safe in treatment of EGFR-positive advanced relapsed/refractory NSCLC patients. Future study will assess it in more patients or even possibly with a higher dose. Trial registration number NCT03182816.
42 citations
TL;DR: PD-1 inhibitors can serve as one of the treatment options for NSCLCs with an EGFR mutation and high PD-L1 expression and can be a viable option compared to the group with wild-type EGFR and low PD- L1 expression.
Abstract: Several studies have demonstrated that non-small cell lung cancer patients (NSCLCs) harboring epidermal growth factor receptor (EGFR) mutations have poor clinical outcomes in response to treatment with programmed death-1 (PD-1) inhibitors. However, it remains unclear whether EGFR-mutated NSCLCs with a high programmed death-ligand-1 (PD-L1) expression (tumor proportion score ≥ 50%) respond to PD-1 inhibitors. We retrospectively investigated the NSCLCs who had received PD-1 inhibitors between January 2016 and December 2018 to assess the efficacy of PD-1 inhibitors in patients with an EGFR mutation and high PD-L1 expression. There were 153 patients with a high PD-L1 expression level, and the median progression-free survival (mPFS) was 5.3 months [95% confidence interval (CI) 1.3–12.4 months] in the patients with EGFR mutations (n = 17) and 8.3 months (95% CI 6.0–11.7 months) in those with wild-type EGFR (n = 136; hazard ratio (HR) 1.62; 95% CI 0.83–2.87). Among the 110 patients in the low PD-L1 expression group, the mPFS was 1.6 months (95% CI 1.3–5.9 months) in the patients with EGFR mutations (n = 18) and 3.8 months (95% CI 2.5–5.9 months) in those with wild-type EGFR (n = 92; HR 2.59; 95% CI 1.48–4.31). The HR for PFS in the group with EGFR mutations and high PD-L1 expression was 0.97 (95% CI 0.56–1.59) compared to the group with wild-type EGFR and low PD-L1 expression. PD-1 inhibitors can serve as one of the treatment options for NSCLCs with an EGFR mutation and high PD-L1 expression.
39 citations
TL;DR: The proposed DLC model can provide a non-invasive approach to evaluate MVI before surgery, which can help surgeons make decisions of surgical strategies and assess patient’s prognosis.
Abstract: Microvascular invasion (MVI) is a critical determinant of the early recurrence and poor prognosis of patients with hepatocellular carcinoma (HCC). Prediction of MVI status is clinically significant for the decision of treatment strategies and the assessment of patient’s prognosis. A deep learning (DL) model was developed to predict the MVI status and grade in HCC patients based on preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and clinical parameters. HCC patients with pathologically confirmed MVI status from January to December 2016 were enrolled and preoperative DCE-MRI of these patients were collected in this study. Then they were randomly divided into the training and testing cohorts. A DL model with eight conventional neural network (CNN) branches for eight MRI sequences was built to predict the presence of MVI, and further combined with clinical parameters for better prediction. Among 601 HCC patients, 376 patients were pathologically MVI absent, and 225 patients were MVI present. To predict the presence of MVI, the DL model based only on images achieved an area under curve (AUC) of 0.915 in the testing cohort as compared to the radiomics model with an AUC of 0.731. The DL combined with clinical parameters (DLC) model yielded the best predictive performance with an AUC of 0.931. For the MVI-grade stratification, the DLC models achieved an overall accuracy of 0.793. Survival analysis demonstrated that the patients with DLC-predicted MVI status were associated with the poor overall survival (OS) and recurrence-free survival (RFS). Further investigation showed that hepatectomy with the wide resection margin contributes to better OS and RFS in the DLC-predicted MVI present patients. The proposed DLC model can provide a non-invasive approach to evaluate MVI before surgery, which can help surgeons make decisions of surgical strategies and assess patient’s prognosis.
36 citations
TL;DR: In this paper, the authors compared the clinical outcomes of pembrolizumab-lenvatinib-transarterial chemoembolization (TACE) versus lenvatiniv-TACE sequential therapy in selected populations of Chinese patients with initially unresectable hepatocellular carcinoma (uHCC) harboring programmed cell death ligand-1 (PD-L1) expression.
Abstract: The aim of this retrospective study was to compare the clinical outcomes of pembrolizumab-lenvatinib-transarterial chemoembolization (TACE) versus lenvatinib-TACE sequential therapy in selected populations of Chinese patients with initially unresectable hepatocellular carcinoma (uHCC) harbouring programmed cell death ligand-1 (PD-L1) expression. Consecutive patients with initial PD-L1-positive uHCC who received pembrolizumab-lenvatinib-TACE or lenvatinib-TACE sequential therapy were retrospectively identified from three medical institutions during 2016–2020. The primary endpoints included the rate of conversion therapy, defined as converting initially uHCC to hepatectomy, overall survival (OS), and progression-free survival (PFS); secondary endpoint was the frequency of key adverse events (AEs). In total, 220 consecutively recruited patients were retrospectively reviewed, 78 of whom were ineligible according to the current criteria, leaving 142 patients [pembrolizumab-lenvatinib-TACE: n = 70, median age 58 years (range 36–69) and lenvatinib-TACE: n = 72, 57 years (35–68)] who were eligible for the study. The median duration of follow-up was 27 months [95% confidence interval (CI), 26.3–28.7 months]. At the last follow-up, the rate of conversion therapy was 25.7% in the pembrolizumab-lenvatinib-TACE group and 11.1% in the lenvatinib-TACE group (p = 0.025). The median OS was 18.1 months (95% CI 16.5–20.7) in the pembrolizumab-lenvatinib-TACE group versus 14.1 months (95% CI 12.2–16.9) in the lenvatinib-TACE group [hazard ratio (HR) 0.56, 95% CI 0.38–0.83; p = 0.004]. A distinct difference in the median PFS interval between the groups was detected [9.2 months (95% CI 7.1–10.4) in the pembrolizumab-lenvatinib-TACE group vs. 5.5 months (95% CI 3.9–6.6) in the lenvatinib-TACE group (HR 0.60; 95% CI 0.39–0.91; p = 0.006)]. The rates of the key AEs assessed, which were hypertension, nausea, and rash, were higher in the pembrolizumab-lenvatinib-TACE group than in the lenvatinib-TACE group (all p < 0.05). Among the selected populations of patients with initial PD-L1-positive uHCC, pembrolizumab-lenvatinib-TACE sequential therapy may have promising antitumour activity, with an acceptable conversion rate and a well-characterized safety profile.
34 citations
TL;DR: In this paper, a review of oncological effects of cannabinoids in pre-clinical and clinical studies in various cancer types was carried out using a database search of peer reviewed articles published in English as full texts in Google Scholar, MEDLINE, PubMed and Web of Science.
Abstract: Cannabinoids are a group of terpenophenolic compounds derived from the Cannabis sativa L. plant. There is a growing body of evidence from cell culture and animal studies in support of cannabinoids possessing anticancer properties. A database search of peer reviewed articles published in English as full texts between January 1970 and April 2021 in Google Scholar, MEDLINE, PubMed and Web of Science was undertaken. References of relevant literature were searched to identify additional studies to construct a narrative literature review of oncological effects of cannabinoids in pre-clinical and clinical studies in various cancer types. Phyto-, endogenous and synthetic cannabinoids demonstrated antitumour effects both in vitro and in vivo. However, these effects are dependent on cancer type, the concentration and preparation of the cannabinoid and the abundance of receptor targets. The mechanism of action of synthetic cannabinoids, (−)-trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) has mainly been described via the traditional cannabinoid receptors; CB1 and CB2, but reports have also indicated evidence of activity through GPR55, TRPM8 and other ion channels including TRPA1, TRPV1 and TRPV2. Cannabinoids have shown to be efficacious both as a single agent and in combination with antineoplastic drugs. These effects have occurred through various receptors and ligands and modulation of signalling pathways involved in hallmarks of cancer pathology. There is a need for further studies to characterise its mode of action at the molecular level and to delineate efficacious dosage and route of administration in addition to synergistic regimes.
33 citations
TL;DR: Investigating the prognostic significance and therapeutic potential of VISTA in patients with pancreatic cancer found it to be associated with a favorable prognosis in PDAC, and immunotherapy with anti-VISTA antibodies may potentially be an effective treatment strategy against PDAC.
Abstract: V-domain Ig suppressor of T cell activation (VISTA) is a novel immune checkpoint protein that belongs to the B7 family. The aim of this study was to investigate the prognostic significance and therapeutic potential of VISTA in patients with pancreatic cancer. Using immunohistochemistry (IHC), we examined the expression of VISTA and demonstrated the associations between the VISTA and overall survival in 223 PDAC patients from 2 different unrelated retrospective cohorts. The multiplex immunofluorescence was performed to illuminate the relationship between VISTA expression and tumor-infiltrating immune cell subclusters of PDAC. We also verified the findings in The Cancer Genome Atlas (TCGA) dataset. The anti-tumor effect of anti-VISTA therapy was studied by the mouse model with liver metastases of PDAC. The VISTA protein was highly expressed in 25.6% of tumor cells (TCs), 38.1% of immune cells, and 26.0% of endothelial cells in 223 PDAC tumor tissues. VISTA expression in TCs was significantly associated with prolonged overall survival. Multiplex immunofluorescence analysis revealed that VISTA level was positively correlated with CD68+ macrophages, CD3+ T cells, and CD19+ B cells in PDAC. However, a higher expression level of VISTA was detected in tumor-infiltrating CD68+ macrophages than in CD3+ T and CD19+ B cells. Furthermore, anti-VISTA antibody treatment significantly reduced the number of metastatic nodules in livers of mouse models of PDAC with liver metastases. VISTA expressed in TCs is associated with a favorable prognosis in PDAC. Moreover, immunotherapy with anti-VISTA antibodies may potentially be an effective treatment strategy against PDAC.
33 citations
TL;DR: It is found that WTAP regulated proliferation, tumorigenesis, cell cycle, and differentiation of AML cells and WTAP plays an epigenetic role in AML.
Abstract: Acute myeloid leukemia (AML) is a heterogenous disease and the survival of AML patients is largely attributed to the improvement of supportive treatment. Wilms’ tumor 1-associated protein (WTAP) is a nuclear protein functions in many physiological and pathological processes. Although its expression and function in many malignant diseases have been reported, its prognostic and epigenetic roles in AML are largely unknown. Peripheral blood or bone marrow samples were collected from AML patients. The WTAP expression was detected by western blot. WTAP expression level and patients clinical features were analyzed using statistical methods. WTAP knockdown AML cells were constructed. The experiments on proliferation, tumorigenic ability, cell cycle, and apoptosis were performed. Transcriptome sequencing was performed and analyzed. M6A methylation level was measured and m6A-RIP was performed to quantify m6A methylation level of MYC mRNA. RNA stability assay was performed to measure the half-life of mRNA. WTAP was overexpressed in AML patients and was an independent poor-risk factor in AML (p = 0.0140). Moreover, we found that WTAP regulated proliferation, tumorigenesis, cell cycle, and differentiation of AML cells. Furthermore, WTAP made AML cells resistant to daunorubicin. In further investigations, m6A methylation level was downregulated when knocking down WTAP, and c-Myc was upregulated due to the decreased m6A methylation of MYC mRNA. High WTAP expression predicts poor prognosis in AML and WTAP plays an epigenetic role in AML.
30 citations
TL;DR: In this article, the role of bacterial metabolites, gut bacteria and diet in colorectal carcinogenesis was discussed and possible molecular mechanisms to provide the role and possible mechanisms to investigate the involvement of bacteria and their secreted metabolites in cancer causation.
Abstract: Based on recent research reports, dysbiosis and improper concentrations of microbial metabolites in the gut may result into the carcinogenesis of colorectal cancer. Recent advancement also highlights the involvement of bacteria and their secreted metabolites in the cancer causation. Gut microbial metabolites are functional output of the host–microbiota interactions and produced by anaerobic fermentation of food components in the diet. They contribute to influence variety of biological mechanisms including inflammation, cell signaling, cell-cycle disruption which are majorly disrupted in carcinogenic activities. In this review, we intend to discuss recent updates and possible molecular mechanisms to provide the role of bacterial metabolites, gut bacteria and diet in the colorectal carcinogenesis. Recent evidences have proposed the role of bacteria, such as Fusobacterium nucleaturm, Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis and Clostridium septicum, in the carcinogenesis of CRC. Metagenomic study confirmed that these bacteria are in increased abundance in CRC patient as compared to healthy individuals and can cause inflammation and DNA damage which can lead to development of cancer. These bacteria produce metabolites, such as secondary bile salts from primary bile salts, hydrogen sulfide, trimethylamine-N-oxide (TMAO), which are likely to promote inflammation and subsequently cancer development. Recent studies suggest that gut microbiota-derived metabolites have a role in CRC progression and causation and hence, could be implicated in CRC diagnosis, prognosis and therapy.
TL;DR: Results suggest that real-world outcomes in this community oncology setting improved with the introduction of immuno-oncology therapies, however, clinical benefits are limited in certain subgroups and tend to be reduced compared with clinical trial observations.
Abstract: Treatments for advanced non-small cell lung cancer (NSCLC) have evolved to include targeted and immuno-oncology therapies, which have demonstrated clinical benefits in clinical trials. However, few real-world studies have evaluated these treatments in the first-line setting. Adult patients with advanced NSCLC who initiated first-line treatment with chemotherapy, targeted therapies (TT), or immuno-oncology–based regimens in the US Oncology Network (USON) between March 1, 2015, and August 1, 2018, were included and followed up through February 1, 2019. Data were sourced from structured fields of USON electronic health records. Patient and treatment characteristics were assessed descriptively, with Kaplan-Meier methods used to evaluate time-to-event outcomes, including time to treatment discontinuation (TTD) and overall survival (OS). Adjusted Cox regression analyses and inverse probability of treatment weighting (IPTW) were performed to control for covariates that may have affected treatment selection and outcomes. Of 7746 patients, 75.6% received first-line systemic chemotherapy, 11.7% received immuno-oncology monotherapies, 8.5% received TT, and 4.2% received immuno-oncology combination regimens. Patients who received immuno-oncology monotherapies had the longest median TTD (3.5 months; 95% confidence interval [CI], 2.8–4.2) and OS (19.9 months; 95% CI, 16.6–24.1). On the basis of multivariable Cox regression and IPTW, immuno-oncology monotherapy was associated with reduced risk of death and treatment discontinuation relative to other treatments. These results suggest that real-world outcomes in this community oncology setting improved with the introduction of immuno-oncology therapies. However, clinical benefits are limited in certain subgroups and tend to be reduced compared with clinical trial observations.
TL;DR: A review of the existing literature on the radiomic approach in predicting the lymph node status of the axilla in breast cancer (BC) is presented in this paper, where two reviewers conducted the literature search on MEDLINE databases independently.
Abstract: To create a review of the existing literature on the radiomic approach in predicting the lymph node status of the axilla in breast cancer (BC). Two reviewers conducted the literature search on MEDLINE databases independently. Ten articles on the prediction of sentinel lymph node metastasis in breast cancer with a radiomic approach were selected. The study characteristics and results were reported. The quality of the methodology was evaluated according to the Radiomics Quality Score (RQS). All studies were retrospective in design and published between 2017 and 2020. The majority of studies used DCE-MRI sequences and two investigated only pre-contrast images. The sample size was lower than 200 patients for 7 studies. The pre-processing used software, feature extraction and selection methods and classifier development are heterogeneous and a standardization of results is not yet possible. The average RQS score was 11.1 (maximum possible value = 36). The criteria with the lowest scores were the type of study, validation, comparison with a gold standard, potential clinical utility, cost-effective analysis and open science data. The field of radiomics is a diagnostic approach of relative recent development. The results in predicting axillary lymph node status are encouraging, but there are still weaknesses in the quality of studies that may limit the reproducibility of the results.
TL;DR: In this paper, the effect of resveratrol on immune checkpoint pathways was assessed by using Western blot and flow cytometry, and it was shown that reserveratrol dose-dependently upregulates PD-L1 expression at the range of pharmacologic-achievable concentrations in lung cancer cells.
Abstract: Recent clinical trials with agents targeting immune checkpoint pathway have emerged as an important therapeutic approach for a broad range of cancer types. Resveratrol has been shown to possess cancer preventive and therapeutic effects and has potential to be chemotherapeutic agent/adjuvant. Here, we assessed the effect of resveratrol on immune checkpoint pathways. The expression patterns of Wnt components and PD-L1 were examined by Western blot, Chromatin immunoprecipitation (ChIP) was used for analysis of DNA–protein interaction, the promoter activity was determined by luciferase reporter assay, apoptosis was analyzed by flow cytometry and the ability of the resveratrol to modulate T cell function was assessed in a co-culture system. Although the dose-, and cell-type dependent effects of resveratrol on PD-L1 expression have been reported, we show here that resveratrol dose-dependently upregulates PD-L1 expression at the range of pharmacologic-achievable concentrations in lung cancer cells and that is essential for suppression of T-cell-mediated immune response. We also found that Wnt pathway is critical for mediating resveratrol-induced PD-L1 upregulation. Mechanistically, resveratrol activates SirT1 deacetylase to deacetylate and stabilize transcriptional factor Snail. Snail in turn inhibits transcription of Axin2, which leads in disassembly of destruction complex and enhanced binding of β-catenin/TCF to PD-L1 promoter. We conclude that resveratrol is capable to suppress anti-tumor immunity by controlling mainly PD-L1 expression. This finding will extend the understanding of resveratrol in regulation of tumor immunity and is relevant to the debate on resveratrol supplements for lung cancer patients.
TL;DR: In this article, the role of Ephrin-A2 in prostate cancer is investigated and it was shown that the ectopic expression of ephrin A2 facilitated cell migration and invasion in vitro and promoted tumor metastasis and angiogenesis in vivo.
Abstract: Ephrin-A2, a member of the Eph receptor subgroup, is used in diagnosing and determining the prognosis of prostate cancer. However, the role of ephrin-A2 in prostate cancer is remains elusive. We established stable clones overexpressing or silencing ephrin-A2 from prostate cancer cells. Then, CCK-8 was used in analyzing the proliferation ability of cells. CD31 staining was used in evaluating angiogenesis. Migration and invasion assay were conducted in vivo and in vitro. The expression of EMT-related markers was evaluated in prostate cancer cells through Western blotting. We revealed that the ectopic expression of ephrin-A2 in prostate cancer cells facilitated cell migration and invasion in vitro and promoted tumor metastasis and angiogenesis in vivo and that the silencing of ephrin-A2 completely reversed this effect. Although ephrin-A2 did not affect tumor cell proliferation in vitro, ephrin-A2 significantly promoted primary tumor growth in vivo. Furthermore, to determine the biological function of ephrin-A2, we assayed the expression of EMT-related markers in stable-established cell lines. Results showed that the overexpression of ephrin-A2 in prostate cancer cells down-regulated the expression of epithelial markers (ZO-1, E-cadherin, and claudin-1) and up-regulated the expression of mesenchymal markers (N-cadherin, β-catenin, vimentin, Slug, and Snail), but the knocking out of ephrin-A2 opposed the effects on the expression of EMT markers. These findings indicate that ephrin-A2 promotes prostate cancer metastasis by enhancing angiogenesis and promoting EMT and may be a potentially therapeutic target in metastatic prostate cancer.
TL;DR: It is suggested that TMT can be a useful prognostic biomarker for clinical outcomes in GBM patients and further preclinical and clinical studies could help elucidate this association of sarcopenia with clinical outcome in patients with newly diagnosed glioblastoma.
Abstract: Temporal muscle thickness (TMT) has been suggested as a novel biomarker that can represent sarcopenia in head and neck malignancies. This study investigated the association of TMT with clinical outcomes in patients with newly diagnosed glioblastoma (GBM). Using electronic medical records, all GBM patients between 2008 and 2018 at Seoul St. Mary’s Hospital were reviewed. Total 177 patients met our eligibility criteria. The thinner group who had TMT less than the median showed shorter overall survival (OS) and progression-free survival (PFS) than the thicker group who had TMT more than median (OS; 11.0 versus 18.0 months, p < 0.001, and PFS; 6.0 versus 11.0 months, p < 0.001). In the multivariate analysis, the thinner group had negative associations with OS and PFS (OS; HR 2.63 (1.34–2.63), p < 0.001, and PFS; HR 2.21 (1.34–2.50), p = 0.002). We also performed propensity score matching between the thinner and thicker groups to minimize the potential bias. The thinner group showed shorter OS and PFS (OS; 13.5 versus 19.0 months, p = 0.006, and PFS; 6.5 versus 9.0 months, p = 0.028) and had negative associations with OS and PFS than the thicker group (OS; HR 1.90 (1.19–3.03), p = 0.008, and PFS; HR 1.70 (1.07–2.70), p = 0.026) in matched patients. Our findings suggest that TMT can be a useful prognostic biomarker for clinical outcomes in GBM patients. Further preclinical and clinical studies could help elucidate this association of sarcopenia with clinical outcomes in GBM patients.
TL;DR: In this article, the authors performed a meta-analysis to identify the potential cardiotoxicity risks when using Vascular Endothelial Growth Factor Receptor Tyrosine kinase inhibitors (VEGFR-TKIs) as anticancer drugs in patients with solid tumors.
Abstract: The present meta-analysis study was performed to identify the potential cardiotoxicity risks when using Vascular Endothelial Growth Factor Receptor Tyrosine kinase inhibitors (VEGFR-TKIs) as anticancer drugs in patients with solid tumors. Pubmed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for the randomized controlled trials. We have included 45 randomized controlled trials (RCTs) associated with nine VEGFR-TKIs Food and Drug Administration (FDA)-approved drugs used to treat patients with solid tumors. To evaluate the trials’ risk of bias, Cochrane Risk of Bias Tool was assessed. A direct comparison was assessed by RevMan5.3 software, calculating the odds ratio (OR) and 95% confidence interval (CI). Heterogeneity was tested by the I2 statistic and Chi-square test for P value. Bayesian network meta-analysis was performed using Stata 15.0 and GeMTC 0.14.3 software, calculated OR along with corresponding 95% credible interval (CrI). The model’s convergence was evaluated by the potential scale reduced factor (PSRF). Consistency between direct and indirect comparisons was assessed by the “node-splitting” method. In this network meta-analysis, a total of 20,027 patients from 45 randomized controlled trials and associated with nine FDA-approved VEGFR-TKIs (axitinib, cabozantinib, lenvatinib, nintedanib, pazopanib, regorafenib, sorafenib, sunitinib, vandetanib), were enrolled. Findings indicated that lenvatinib had the most significant probability of provoking all grades cardiovascular incident and hypertension, followed by vandetanib, cabozantinib, axitinib, pazopanib, sorafenib, sunitinib, regorafenib and nintedanib. The nine agent’s severe cardiovascular and severe hypertension risk was probably similar. The ranking probability of cardiac toxicity shows that vandetanib ranked most likely to have the highest risk for cardiotoxicity among all the VEGFR-TKIs reviewed, followed by pazopanib, axitinib, sorafenib, sunitinib. In contrast, regorafenib and nintedanib did not exhibit an increased risk of cardiac damage. The association between the nine VEGFR-TKIs with potential cardiotoxicity occurrence was reviewed. Both the regorafenib and nintedanib did not display detectable signs of cardiotoxic damage. In contrast, lenvatinib and vandetanib are ranked to have the most severe cardiotoxicity side impacts. These results may provide information for clinical practice guidelines, implementing strategies in selecting the adequate VEGFR-TKIs, and understanding the cardiovascular toxicity inflicted by the VEGFR-TKIs. CRD 42,020,167,307.
TL;DR: In this article, a meta-analysis was conducted to assess the associations between inflammatory bowel disease (IBD) and risk of the gastric, small bowel and colorectal cancer.
Abstract: The purpose of this meta-analysis was to assess the associations between inflammatory bowel disease (IBD) and risk of the gastric, small bowel and colorectal cancer. We searched the PubMed and Web of Science for observational studies published before June 2020, and the quality of each included study was evaluated according to the Newcastle–Ottawa–Scale. Twenty-six studies comprising 531 449 IBD patients and more than 65 million reference individuals were included. Although IBD was significantly associated with 67% increased risk of the total gastric, small bowel and colorectal cancer. After stratifying by cancer location, IBD mainly increased the risk of intestinal cancer instead of gastric cancer. Furthermore, Crohn’s disease (CD) significantly increased the risk of both small bowel cancer and colorectal cancer, while ulcerative colitis (UC) only increased the risk of colorectal cancer. In subgroup analysis, associations between IBD and risk of total gastric, small bowel and colorectal cancer were similar between male and female, except for that male IBD patients but not female had a significantly higher risk of small bowel cancer. Additionally, IBD patients in different geographical areas had different associations with risk of various gastrointestinal tract cancers. IBD is mainly associated with increased risk of cancers in the lower gastrointestinal tract, including small bowel cancer and colorectal cancer. Because studies about the association between IBD and risk of gastric cancer and the populations in Asia are limited, more observational studies are required in the future.
TL;DR: YAP/TAZ are the core molecules of the Hippo pathway and regulate related target genes to promote tumor invasion and metastasis as mentioned in this paper, which can induce the formation of invasive pseudopodia in tumor cells.
Abstract: The Hippo pathway is widely considered to inhibit cell growth and play an important role in regulating the size of organs. However, recent studies have shown that abnormal regulation of the Hippo pathway can also affect tumor invasion and metastasis. Therefore, finding out how the Hippo pathway promotes tumor development by regulating the expression of target genes provides new ideas for future research on targeted drugs that inhibit tumor progression. PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched. The search strategy identified 1892 hits and 196 publications were finally included in this review. As the core molecule of the Hippo pathway, YAP/TAZ are usually highly expressed in tumors that undergo invasion and migration and are accompanied by abnormally strong nuclear metastasis. Through its interaction with nuclear transcription factors TEADs, it directly or indirectly regulates and the expressions of target genes related to tumor metastasis and invasion. These target genes can induce the formation of invasive pseudopodia in tumor cells, reduce intercellular adhesion, degrade extracellular matrix (ECM), and cause epithelial-mesenchymal transition (EMT), or indirectly promote through other signaling pathways, such as mitogen-activated protein kinases (MAPK), TGF/Smad, etc, which facilitate the invasion and metastasis of tumors. This article mainly introduces the research progress of YAP/TAZ which are the core molecules of the Hippo pathway regulating related target genes to promote tumor invasion and metastasis. Focus on the target genes that affect tumor invasion and metastasis, providing the possibility for the selection of clinical drug treatment targets, to provide some help for a more in-depth study of tumor invasion and migration mechanism and the development of clinical drugs.
TL;DR: The 4SCAR-GD2 T cell therapy demonstrated antitumor effect and manageable toxicities, indicating its potential to benefit children with refractory and/or recurrent NB.
Abstract: This study aimed to evaluate the safety and efficacy of chimeric antigen receptor (CAR) disialoganglioside 2 (GD2)-specific (4SCAR-GD2) T cells for treatment of refractory and/or recurrent neuroblastoma (NB) in pediatric patients. A phase I clinical study using 4SCAR-GD2 T cells for the treatment of NB in pediatric patients was conducted. This study was registered at www.clinicaltrials.gov
(NCT02765243). A lentiviral CAR with the signaling domains of CD28/4-1BB/CD3ζ-iCasp9 was transduced into activated T cells. The response to 4SCAR-GD2 T-cell treatment, and 4SCAR-GD2 T-cell expansion and persistence in patients were evaluated. Toxicities were determined based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Twelve patients were enrolled and finally ten patients were included in this clinical trial which started from January 1, 2016, to August 1, 2017. These patients had progressive disease (PD) before CAR T-cell infusion. After 4SCAR-GD2 T-cell treatment, 6 (6/10) had stable disease (SD) at 6 months, and 4 (4/10) remained SD at 1 year and alive after 3–4 years of follow-up. Six patients died due to disease progression by the end of July 1, 2020. The median overall survival (OS) time was 25 months (95% CI, 0.00–59.43), and the median progression-free survival (PFS) time was 8 months (95% CI, 0.25–15.75). Grade 3 or 4 hematological toxicities were the common adverse events frequently occurred after fludarabine and cyclophosphamide (Flu/cy) chemotherapy. Grade 1–2 toxicities such as cytokine release syndrome (CRS) and neuropathic pain were common, but were transient and mild. The 4SCAR-GD2 T-cell therapy demonstrated antitumor effect and manageable toxicities, indicating its potential to benefit children with refractory and/or recurrent NB.
TL;DR: The role of exosomes in cancer pathophysiology and their clinical potential are discussed in detail in this article, where the results of studies examining the role of Exosomes and exosomal microRNAs are discussed.
Abstract: Exosomes are extracellular nanometric vesicles used by cells to communicate with each other. They are responsible for many pathological conditions, including tumors by transferring regulatory biomolecules that impact target cell activity. Because of their high concentration in exosomes compared with parental cells and the rest of exosomal content, specificity to the cell of origin, and their well-organized sorting mechanism, microRNAs (miRNAs) are thought to be the most potent exosomes cargo and used by scientists to track exosomes and to detect cell activity changes and prognosis in cancer early. In this review, the results of studies examining the role of exosomes in cancer pathophysiology and their clinical potential are discussed in detail. Tumor-derived exosomes (TDEs) mediate the dynamic changes of cancer growth and invasion, including local microenvironment remodeling, distance metastasis, angiogenesis, and tumor-associated immunosuppression. They also contribute to hypoxia-induced tumor progression and cancer cell drug resistance. As a result of exosomes being present in all body fluids, it is possible to have early accessible and less-invasive diagnostic and prognostic measures by forming a table for each cancer type and its matched specific miRNAs. Under testing, available therapeutic uses of exosomes include interference of exosomes biogenesis, secretion, or uptake, and recruitment of exosomes as target-specific drug delivery vehicles, and immunostimulatory agents for both cancer patients and healthy population to avoid cancer development from the start. These data suggest that exosomes and exosomal microRNA are directly related to cancer progression mechanisms, and could be used in cancer early diagnosis, prognosis, and therapy.
TL;DR: Overall, the IRG-related 11-gene signature can be used as a reliable ES prognostic biomarker and can provide guidance for personalized ES therapy.
Abstract: Ewing sarcoma (ES) is one of the most common malignant bone tumors in children and adolescents. The immune microenvironment plays an important role in the development of ES. Here, we developed an optimal signature for determining ES patient prognosis based on immune-related genes (IRGs). We analyzed the ES gene expression profile dataset, GSE17679, from the GEO database and extracted differential expressed IRGs (DEIRGs). Then, we conducted functional correlation and protein–protein interaction (PPI) analyses of the DEIRGs and used the machine learning algorithm-iterative Lasso Cox regression analysis to build an optimal DEIRG signature. In addition, we applied ES samples from the ICGC database to test the optimal gene signature. We performed univariate and multivariate Cox regressions on clinicopathological characteristics and optimal gene signature to evaluate whether signature is an important prognostic factor. Finally, we calculated the infiltration of 24 immune cells in ES using the ssGSEA algorithm, and analyzed the correlation between the DEIRGs in the optimal gene signature and immune cells. A total of 249 DEIRGs were screened and an 11-gene signature with the strongest correlation with patient prognoses was analyzed using a machine learning algorithm. The 11-gene signature also had a high prognostic value in the ES external verification set. Univariate and multivariate Cox regression analyses showed that 11-gene signature is an independent prognostic factor. We found that macrophages and cytotoxic, CD8 T, NK, mast, B, NK CD56bright, TEM, TCM, and Th2 cells were significantly related to patient prognoses; the infiltration of cytotoxic and CD8 T cells in ES was significantly different. By correlating prognostic biomarkers with immune cell infiltration, we found that FABP4 and macrophages, and NDRG1 and Th2 cells had the strongest correlation. Overall, the IRG-related 11-gene signature can be used as a reliable ES prognostic biomarker and can provide guidance for personalized ES therapy.
TL;DR: A comprehensive review of 3D tumor vascular model systems can be found in this paper, which includes tissue engineering-based tumor models, vascular organoid models, and organ-on-chip (OCP) models.
Abstract: The development of blood vessels, referred to as angiogenesis, is an intricate process regulated spatially and temporally through a delicate balance between the qualitative and quantitative expression of pro and anti-angiogenic molecules. As angiogenesis is a prerequisite for solid tumors to grow and metastasize, a variety of tumor angiogenesis models have been formulated to better understand the underlying mechanisms and associated clinical applications. Studies have demonstrated independent mechanisms inducing angiogenesis in tumors such as (a) HIF-1/VEGF mediated paracrine interactions between a cancer cell and endothelial cells, (b) recruitment of progenitor endothelial cells, and (c) vasculogenic mimicry. Moreover, single-cell sequencing technologies have indicated endothelial cell heterogeneity among organ systems including tumor tissues. However, existing angiogenesis models often rely upon normal endothelial cells which significantly differ from tumor endothelial cells exhibiting distinct (epi)genetic and metabolic signatures. Besides, the existence of intra-individual variations necessitates the development of improved tumor vascular model systems for personalized medicine. In the present review, we summarize recent advancements of 3D tumor vascular model systems which include (a) tissue engineering-based tumor models; (b) vascular organoid models, and (c) organ-on-chips and their importance in replicating the tumor angiogenesis along with the associated challenges to design improved models.
TL;DR: In this paper, the authors identified randomized controlled trials (RCTs) comparing ICIs combined with NACT to NACT in early-stage triple-negative breast cancer (TNBC) and found that the combination treatment resulted in higher odds of any grade 3/4 adverse events (AEs), serious AEs, AEs leading to death, common and meaningful AEs associated with chemotherapy and immune-related AEs.
Abstract: There is uncertainty regarding the role of adding immune checkpoint inhibitors (ICIs) to neoadjuvant chemotherapy (NACT) in early-stage triple-negative breast cancer (TNBC). We identified randomized controlled trials (RCTs) comparing ICIs combined with NACT to NACT in early-stage TNBC. Efficacy outcomes included pathological complete response (pCR) and event-free survival (EFS). Toxicity data included any grade 3/4 adverse events (AEs), serious AEs, AEs leading to death, common and meaningful AEs associated with chemotherapy and immune-related AEs. Odds ratio (ORs), hazard ratios (HR) and their respective 95% confidence intervals (CI) for efficacy and toxicity were extracted and pooled in a meta-analysis. Differences in the odds for pCR between programmed death ligand 1 (PD-L1) status and between PD-L1 and PD-1 inhibitors were also assessed. Five RCTs comprising 2,075 patients were analyzed. Compared to NACT alone, combination of ICIs and NACT significantly improved pCR (OR 1.75, 95% CI 1.25–2.47, p = 0.001) and EFS (HR 0.66, 95% CI 0.48–0.91, p = 0.01). Magnitude of effect on pCR was similar between PD-L1-positive and PD-L1-negative tumors (p for the subgroup difference = 0.80) and between PD-L1 and PD-1 inhibitors (p = 0.27). The combination treatment resulted in higher odds of any grade 3/4 AEs (OR 1.31, p = 0.02) and serious AEs (OR 1.84, p = 0.006), with no statistically significant difference in AEs leading to death (OR 1.67, p = 0.51). Higher magnitude of toxicity was observed for immune-related AEs. Combination of ICIs and NACT were associated with improved outcome in early-stage TNBC while increasing toxicity significantly. Longer follow-up is desired to better understand the risk and benefit ratio of this combination.
TL;DR: International regulatory agencies (FDA, EMA) have concluded that the use of RAAS blockers is not associated with an increased risk of developing lung cancer and there is no need to change clinical practise.
Abstract: The blockade of the renin–angiotensin–aldosterone system (RAAS) by angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) is one of the most common treatments for hypertension, heart failure and renal diseases. However, concerns have been raised about a possible link between RAAS-blockers and an increased risk of cancer, particularly of lung cancer. This narrative review aims to give a critical appraisal of current evidence and to help physicians understand potential links between RAAS blockade and de novo lung cancer development. Numerous pharmaco-epidemiologic studies, mostly retrospective cohort analyses, evaluated the association of RAAS blockade with lung cancer incidence and reported inconsistent findings. Meta-analyses could not further clarify a possible link between RAAS blockade and the risk of lung cancer. International regulatory agencies (FDA, EMA) have concluded that the use of RAAS blockers is not associated with an increased risk of developing lung cancer. Co-administration of RAAS blockers to systemic therapy of advanced non-small cell lung cancer seems to have positive effects on the outcome. Until more comprehensive analyses have been completed, there is no need to change clinical practise. Additional prospective randomized trials with long-term follow-up are needed to investigate the effects of these drugs on the development and progression of lung cancer.
TL;DR: This survey assessed oncological patients’ information needs and satisfaction, their preferred information in patient decision aids (PDAs), and their preferred way of making decisions regarding their treatment.
Abstract: Shared Decision-Making (SDM) enhances patients’ satisfaction with a decision, which in turn increases compliance with and adherence to cancer treatment. SDM requires a good patient-clinician relationship and communication, patients need information matching their individual needs, and clinicians need support on how to best involve the individual patient in the decision-making process. This survey assessed oncological patients’ information needs and satisfaction, their preferred information in patient decision aids (PDAs), and their preferred way of making decisions regarding their treatment. Questionnaires were distributed among attendees of a lecture program on complementary and alternative medicine in oncology of which 220 oncological patients participated. Participants reported a generally high need for information—correlating with level of education—but also felt overwhelmed by the amount. The latter proved particularly important during consultation. Use of PDAs increased satisfaction with given information but occurred in less than a third of the cases. Most requested contents for PDAs were pros and cons of treatment options and lists of questions to ask. The vast majority of patients preferred SDM to deciding alone. None wanted their physician to decide for them. There is a high demand for SDM but a lack of conclusive evidence on the specific information needs of different types of patients. Conversation between patients and clinicians needs encouragement and support. PDAs are designed for this purpose and have the potential to increase patient satisfaction. Their scarce use in consultations calls for easier access to and better information on PDAs for clinicians.
TL;DR: In this paper, a comprehensive understanding of EGFR-TKIs resistance mechanisms is of vital importance for clinical management of non-small cell lung cancer (NSCLC) patients.
Abstract: Non-small cell lung cancer (NSCLC) accounts for about 85% in all cases of lung cancer. In recent years, molecular targeting drugs for NSCLC have been developed rapidly. The epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have changed the paradigm of cancer therapy from empirical cytotoxic chemotherapy to molecular-targeted cancer therapy. Currently, there are three generations of EGFR-TKIs, all of which have achieved good efficacy in clinical therapy. However, most patients developed drug resistance after 6–13 months EGFR-TKIs treatment. Therefore, a comprehensive understanding of EGFR-TKIs resistance mechanisms is of vital importance for clinical management of NSCLC. Relevant data and information about the topic were obtained by searching PubMed (Medline), Web of Science and Google Scholar using the subject headings, such as “NSCLC”, “EGFR-TKIs resistance”, “EGFR mutations”, “human epidermal growth factor receptor-2 (HER2/erbB-2)”, “hepatocyte growth factor (HGF)”, “vascular endothelial growth factor (VEGF)”, “insulin-like growth factor 1 (IGF-1)”, “epithelial–mesenchymal transition (EMT)”, “phosphatase and tensin homolog (PTEN)”, “RAS mutation”, “BRAF mutation”, “signal transducer and activator of transcription 3 (STAT3)”, and “tumor microenvironment”, etc. The mechanisms for EGFR-TKIs resistance include EGFR mutations, upregulation of HER2, HGF/c-MET, VEGF IGF1, EMT and STAT3 pathways, mutations of PTEN, RAS and BRAF genes, and activation of other by-pass pathways. These mechanisms are interconnected and can be potential targets for the treatment of NSCLC. In this review, we discuss the mechanisms of EGFR-TKIs drug resistance and the clinical strategies to overcome drug resistance from the perspective of EGFR-TKIs combined treatment.
TL;DR: In this article, the authors focused on the process of tumor vascularization; potential therapeutic targets, including cells, metabolism, signaling pathways, and angiogenesis-related genes; and possible strategies to normalize blood vessels through regulating tumor vessel generation, the development of tumor vessels, and blood vessel fusion and pruning.
Abstract: Tumor recurrence after the clinical cure of tumor often results from the presence of an abnormal microenvironment, including an aberrant vasculature. The tumor microenvironment is rich in pro-angiogenic factors but lacks pro-maturation factors. Pro-angiogenic conditions in the tumor microenvironment, such as hypoxia, are double-edged swords, promoting both the repair of normal tissues and the development of an abnormal blood vessel network. The coexistence of perfusion and hypoxic zones and uneven blood vessel distribution in tumor tissues profoundly influence tumor deterioration, recurrence, and metastasis. Traditional anti-angiogenic therapies have shown limited efficacy, and promote drug resistance, and even metastasis. In contrast, vascular normalization therapy induces a more physiological-like state, leading to better outcomes and fewer side effects. Vascular normalization entails modifying the tumor vascular system to improve tumor oxygenation and substance transport, thereby contributing to improving the efficacy of radiotherapy, chemotherapy, and immunotherapy. This review mainly focuses on the process of tumor vascularization; potential therapeutic targets, including cells, metabolism, signaling pathways, and angiogenesis-related genes; and possible strategies to normalize blood vessels through regulating tumor vessel generation, the development of tumor vessels, and blood vessel fusion and pruning.
TL;DR: In this paper, a cross-sectional study at two time periods (May to June, sample 1) and September to November 2020 (sample 2) with standardized questionnaires (i.e., WHO-5, MLQ, PCQ-12) was conducted to analyze whether these perceptions may differ between patients from waves 1 and 2 of the COVID-19 pandemic.
Abstract: During the COVID-19 pandemic, tumor patients not only perceived fears and worries but were experiencing also positive changes as the perception of nature and silence, moments of wondering awe, and more intense relationships. We intended to analyze whether these perceptions may differ between patients from waves 1 and 2 of the pandemic. Cross-sectional study at two time periods (May to June, sample 1) and September to November 2020 (sample 2) with standardized questionnaires (i.e. WHO-5, MLQ, PCQ-12). Patients from sample 1 (n = 292) and sample 2 (n = 221) did not differ with respect to gender, age, partner or tumor status. Most are still “irritated by statements about danger and course of the infection” (58%) and are “worrying to be infected and to have complicated course of disease” (55%). Neither their well-being nor meaning in life nor fears and worries were significantly different. In sample 2 patients, Worrying reflections and loneliness scored significantly lower, while their Perception of nature and silence was lower in trend only; more intense relationships are still relevant. Moments of wondering awe and religious trust were perceived less often during wave 2. Particularly religious patients scored stronger for Perception of nature and silence and Worrying reflections and loneliness. Oncologists/psychologist have to know that patients’ situation has not changed within the time of pandemic and that they still require information, close support and encouragement to rely on their resources to cope. Perceived changes are reflecting coping strategies that could be trained to increase patients’ resilience during further pandemic waves.
TL;DR: In this paper, the authors summarized the new methods and advances of targeted therapy for gastric cancer, including novel molecular targeted therapeutic agents and drug delivery systems, with a major focus on the development of drug delivery system (drug carriers and targeting peptides).
Abstract: Gastric cancer is still a major cancer worldwide. The early diagnosis rate of gastric cancer in most high incidence countries is low. At present, the overall treatment effect of gastric cancer is poor, and the median overall survival remains low. Most of the patients with gastric cancer are in an advanced stage when diagnosed, and drug treatment has become the main means. Thus, new targeted drugs and therapeutic strategies are the hope of improving the therapeutic effect of gastric cancer. In this review, we summarize the new methods and advances of targeted therapy for gastric cancer, including novel molecular targeted therapeutic agents and drug delivery systems, with a major focus on the development of drug delivery systems (drug carriers and targeting peptides). Elaborating these new methods and advances will contribute to the management of gastric cancer.