Steengraves3641

Deregulation of HER2 expression could affect the biological characteristics of gastric cancer cells and treatment option for gastric cancer patients. This research aims to investigate the impact of HER2 on biological characteristics of gastric cancer stem cells (GCSCs) and prognosis of gastric cancer patients.

HER2 knockdown in GCSCs were constructed by lentivirus transfection. Alterations of proliferation, self-renewal, invasion, migration, colony formation, and tumorigenicity of GCSCs were examined. The changes of gene expressions after HER2 interference in GCSCs were detected by gene microarray. The impact of concentration of serum HER2 and expression of HER2 in tumor tissues on survival of 213 gastric cancer patients was also analyzed.

Down-regulation of HER2 decreased the self-renewal, colony formation, migration, invasion, proliferation, and chemotherapy resistance of GCSCs. However, the tumorigenicity of GCSCs

was increased after down-regulation of HER2. The results of gene microarray showed that HER2 gene might regulate the signal transduction of mTOR, Jak-STAT, and other signal pathways and affect the biological characteristics of GCSCs. Furthermore, survival analyses indicated that patients with high concentration of HER2 in serum had a favorable overall survival. However, there was no significant correlation between expression of HER2 in tumor tissue and overall survival.

Interference of HER2 in GCSCs decreased the capacity of self-renewal, proliferation, colony formation, chemotherapy resistance, invasion, and migration but might increase the tumorigenicity

. Patients with high concentration of HER2 in serum seemed to have a favorable prognosis.

Interference of HER2 in GCSCs decreased the capacity of self-renewal, proliferation, colony formation, chemotherapy resistance, invasion, and migration but might increase the tumorigenicity in vivo. Patients with high concentration of HER2 in serum seemed to have a favorable prognosis.

Our previous study suggested cyclin-dependent kinase-like 3 (CDKL3) acts as a new oncogene in esophageal squamous cell carcinoma (ESCC) cell line TE-1. However, the molecular mechanisms and biological effects of CDKL3 in ESCC remain unknown. In the present study, we aimed to explore the clinical significance of CDKL3 in ESCC and how CDKL3 regulates the malignant behavior of ESCC.

ESCC samples were stained by immunohistochemical staining (IHC) and analyzed for the expression of CDKL3. The functions of CDKL3 on proliferation, apoptosis, migration, invasion, and colony formation were investigated by celigo assay, MTT assay, colony formation, caspase 3/7 activity analysis, transwell migration and invasion assay, respectively. A transplanted tumor model was established to study the functions of FLVCR1 on the tumorigenesis of ESCC cells. Microarray analysis was utilized to identify the CDKL3-regulated genes in ESCC cells.

ESCC tumor tissues possessed a significantly higher expression of CDKL3 and autophagy-restasis, and prohibit tumor apoptosis partly by ATG5 activation.

CDKL3 can be utilized as an independent poor prognostic marker in ESCC patients. Furthermore, CDKL3 may promote tumor profession, invasion, metastasis, and prohibit tumor apoptosis partly by ATG5 activation.Meningiomas are one of the most prevalent primary brain tumors. Our study aims to obtain mechanistic insights of meningioma pathobiology using mass spectrometry-based label-free quantitative proteome analysis to identifying druggable targets and perturbed pathways for therapeutic intervention. Label-free based proteomics study was done from peptide samples of 21 patients and 8 non-tumor controls which were followed up with Phosphoproteomics to identify the kinases and phosphorylated components of the perturbed pathways. In silico approaches revealed perturbations in extracellular matrix remodeling and associated cascades. To assess the extent of influence of Integrin and PI3K-Akt pathways, we used an Integrin Linked Kinase inhibitor on patient-derived meningioma cell line and performed a transcriptomic analysis of the components. Furthermore, we designed a Targeted proteomics assay which to the best of our knowledge for very first-time enables identification of peptides from 54 meningioma patients via SRM assay to validate the key proteins emerging from our study. This resulted in the identification of peptides from CLIC1, ES8L2, and AHNK many of which are receptors and kinases and are difficult to be characterized using conventional approaches. Furthermore, we were also able to monitor transitions for proteins like NEK9 and CKAP4 which have been reported to be associated with meningioma pathobiology. We believe, this study can aid in designing peptide-based validation assays for meningioma patients as well as IHC studies for clinical applications.Orbital rhabdomyosarcoma (RMS) is a relatively rare primary malignancy occurring in children. The objective of this study was to evaluate the cumulative incidence of cancer-specific death and competing risk of death among RMS patients after surgery and to build nomograms to predict overall survival (OS) and cancer-specific survival (CSS) based on a large population-based cohort. The records of 217 patients who were pathologically diagnosed with an orbital RMS between 1973 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively analyzed. The 10-, 20-, and 40-years OS rates and cancer-specific mortality were 82.5, 72.2, and 48.9%, respectively, and 14.8, 21.7, and 21.7%, respectively. The established nomograms were well-calibrated and validated, with a concordance index (C-index) of 0.901 and 0.944 for OS prediction, 0.923 and 0.904, for CSS prediction in the training and validation cohorts, respectively. The values of area under the receiver operating characteristic curve (AUC) for 10-, 20-, and 40-years OS and CSS prediction were 0.908, 0.826, and 0.847, and 0.924, 0.863, and 0.863, respectively. The established nomogram showed relatively good performances and could be convenient individualized predictive tools for prognostic prediction in RMS patients.

Survival rates and prognostic factors of cortical ependymomas (CEs) remain elusive. This study aimed to perform a comprehensive analysis of prognostic factors, treatment, and outcomes for patients with CEs based on institutional and literature case series.

Thirty patients with CEs from our department were included in this study. Furthermore, a systemic review of the literature yielded an additional 106 patients with CEs. Clinical data including patient age, sex, symptoms, tumor location, World Health Organization (WHO) grade, extent of surgery, radiation, recurrence, and survival were recorded and statistically analyzed.

From January 2009 to October 2019, 30 (4.2%) cases were diagnosed as CEs in our department. These series consisted of 19 males and 11 females, 10 continuous patients after 2017 screened for C11orf95-RELA fusion, and 9 patients (90%) were RELA fusion positive. During the follow-up period, nine (30%) patients depicted tumor recurrence or progression; four (13.3%) patients died of tumor pry have higher rate of RELA fusions, but generally favorable prognosis. The extent of surgery and WHO tumor grade were significant prognostic factors for PFS and OS in multivariate analysis. GTTR or WHO grade II tumors had better overall outcome in patients with CEs.

CEs accounted for only 3.5 to 5.7% of ependymomas, with seizures the most common symptom and the frontal lobe the most frequent location. CEs may have higher rate of RELA fusions, but generally favorable prognosis. The extent of surgery and WHO tumor grade were significant prognostic factors for PFS and OS in multivariate analysis. GTTR or WHO grade II tumors had better overall outcome in patients with CEs.Ionizing radiation (IR) creates lethal DNA damage that can effectively kill tumor cells. However, the high dose required for a therapeutic outcome also damages healthy tissue. Thus, a therapeutic strategy with predictive biomarkers to enhance the beneficial effects of IR allowing a dose reduction without losing efficacy is highly desirable. NAD(P)Hquinone oxidoreductase 1 (NQO1) is overexpressed in the majority of recalcitrant solid tumors in comparison with normal tissue. Studies have shown that NQO1 can bioactivate certain quinone molecules (e.g., ortho-naphthoquinone and β-lapachone) to induce a futile redox cycle leading to the formation of oxidative DNA damage, hyperactivation of poly(ADP-ribose) polymerase 1 (PARP1), and catastrophic depletion of NAD+ and ATP, which culminates in cellular lethality via NAD+-Keresis. However, NQO1-bioactivatable drugs induce methemoglobinemia and hemolytic anemia at high doses. To circumvent this, NQO1-bioactivatable agents have been shown to synergize with PARP1 inhibitors, pyrimidine radiosensitizers, and IR. This therapeutic strategy allows for a reduction in the dose of the combined agents to decrease unwanted side effects by increasing tumor selectivity. In this review, we discuss the mechanisms of radiosensitization between NQO1-bioactivatable drugs and IR with a focus on the involvement of base excision repair (BER). This combination therapeutic strategy presents a unique tumor-selective and minimally toxic approach for targeting solid tumors that overexpress NQO1.

The purpose of this study is to investigate the current status of clinical target volume (CTV) delineation for primary site of nasopharyngeal cancer (NPC) among five large tertiary cancer centers in China.

The simulation CT and MR images of a patient with T3N2M0 NPC were sent to the centers participating. selleck kinase inhibitor Fourteen experienced physicians contoured the targets independently, and the outlined structures were compared. The consistency and differences among these 14 CTVs are discussed.

Two different CTV designs were used in the centers. "One-CTV" design defines one CTV with a dose of 60 Gy, whereas "two-CTV" design has a high-risk CTV with dose of 60 Gy and a medium risk CTV with dose of 54 Gy. We found that the coverage of prophylactic area is very consistent between these two designs. The variances on the coverage of some sites were also significant among physicians, including covering cavernous sinus at un-involved side, posterior space of styloid process, and caudal border on posterior pharyngeal wall.

Standardization is the main requirement for personalization of care; our study shows that among the 14 physicians in the five centers the coverage of prophylactic areas is in excellent agreement. Two distinct strategies on CTV design are currently being used, and multiple controversies were found, suggesting further optimization of CTV for primary site of NPC is needed.

Standardization is the main requirement for personalization of care; our study shows that among the 14 physicians in the five centers the coverage of prophylactic areas is in excellent agreement. Two distinct strategies on CTV design are currently being used, and multiple controversies were found, suggesting further optimization of CTV for primary site of NPC is needed.Drug resistance, whether intrinsic or acquired, often leads to treatment failure in esophageal squamous cell carcinoma (ESCC). Clarifying the mechanism of drug resistance in ESCC has great significance for reversing drug resistance, as well as improving the prognosis of patients. Previously, we demonstrated that etoposide-induced 2.4-kb mRNA (EI24) is the target of miR-483-3p, which promoted the growth, migration, and drug resistance in ESCC, suggesting that EI24 participates in repressing the tumorigenesis and progression of ESCC. Here, we observed that EI24 was remarkably decreased in ESCC tissues. Moreover, its expression was directly linked to the prognosis of patients. We then confirmed that the forced overexpression of EI24 repressed cell growth and sensitized ESCC cells to chemotherapeutic agents, whereas EI24 silencing had the opposite effect. Furthermore, gene microarray and ingenuity pathway analysis (IPA) were performed to establish the potential mechanisms and indicated that EI24 exerts a tumor-suppressive role via suppressing the acute phase response signaling pathway or IL-1 signaling pathway in ESCC.