A Comprehensive Pan-Cancer Analysis Identifies CEP55 as a Potential Oncogene and Novel Therapeutic Target.

Emerging research findings have shown that a centrosomal protein (CEP55) is a potential oncogene in numerous human malignancies. Nevertheless, no pan-cancer analysis has been conducted to investigate the various aspects and behavior of this oncogene in different human cancerous tissues. Numerous databases were investigated to conduct a detailed analysis of CEP55. Initially, we evaluated the expression of CEP55 in several types of cancers and attempted to find the correlation between that and the stage of the examined malignancies. Then, we conducted a survival analysis to determine the relationship between CEP55 overexpression in malignancies and the patient's survival. Furthermore, we examined the genetic alteration forms and the methylation status of this oncogene. Additionally, the interference of CEP55 expression with immune cell infiltration, the response to various chemotherapeutic agents, and the putative molecular mechanism of CEP55 in tumorigenesis were investigated. The current study found that CEP55 was upregulated in cancerous tissues versus normal controls where this upregulation was correlated with a poor prognosis in multiple forms of human cancers. Additionally, it influenced the level of different immune cell infiltration and several chemokines levels in the tumor microenvironment in addition to the response to several antitumor drugs. Herein, we provide an in-depth understanding of the oncogenic activities of CEP55, identifying it as a possible predictive marker as well as a specific target for developing anticancer therapies.

Integration of Chemoinformatics and Multi-Omics Analysis Defines ECT2 as a Potential Target for Cancer Drug Therapy.

Epithelial cell transforming 2 (ECT2) is a potential oncogene and a number of recent studies have correlated it with the progression of several human cancers. Despite this elevated attention for ECT2 in oncology-related reports, there is no collective study to combine and integrate the expression and oncogenic behavior of ECT2 in a panel of human cancers. The current study started with a differential expression analysis of ECT2 in cancerous versus normal tissue. Following that, the study asked for the correlation between ECT2 upregulation and tumor stage, grade, and metastasis, along with its effect on patient survival. Moreover, the methylation and phosphorylation status of ECT2 in tumor versus normal tissue was assessed, in addition to the investigation of the ECT2 effect on the immune cell infiltration in the tumor microenvironment. The current study revealed that ECT2 was upregulated as mRNA and protein levels in a list of human tumors, a feature that allowed for the increased filtration of myeloid-derived suppressor cells (MDSC) and decreased the level of natural killer T (NKT) cells, which ultimately led to a poor prognosis survival. Lastly, we screened for several drugs that could inhibit ECT2 and act as antitumor agents. Collectively, this study nominated ECT2 as a prognostic and immunological biomarker, with reported inhibitors that represent potential antitumor drugs.

Evaluation of the effect of COVID-19 mandated shift to virtual teaching on medical students' performance at King Khalid University, Abha.

Objectives: The rapid spread of the COVID-19 pandemic required populations in most parts of the world to take drastic precautions. Face-to-face teachings were suspended, and the teaching and learning process was shifted to the virtual mode. This was a formidable challenge for students, teachers, parents, guardians, and academic administrators. The main objective of this study was to assess the impact of the shift to virtual mode on medical students' academic performance in general and systemic pathology courses. Methods: The grades achieved in a quiz and practical test taken before the shift to virtual classes were compared to another quiz and practical exam taken by the same groups of students after several weeks of virtual teaching. The paired t-test was conducted to test the hypotheses, and SPSS software was used for data analyses. A short electronic survey was designed and sent to the targeted students (N = 103). The targeted students were also surveyed to understand their experience with e-learning during this time. Results: In total, 60% of the students reported their e-learning experience as valuable, and 84% prefer to have e-learning as part of the teaching and learning process even after normalcy is restored. The students' performance in the post-virtual tests was significantly better than that in the pre-virtual tests. Conclusion: The virtual learning format was well received by the students and influenced their academic outcomes. Institutes should provide training sessions for staff and students to address potential education drawbacks and provide modern educational technologies and simulation labs to enhance the educational systems.

Signet ring cell component predicts the response to neoadjuvant chemoradiotherapy in rectal cancer. Long interim results of a single institution experience.

There are limited studies evaluating the correlation between the presence of signet ring carcinoma and tumor response to neoadjuvant therapy in the rectum. Hereby, we aimed to report for the first time our experience from Upper Egypt through assessing the predictive role of signet ring cell component (SRCC) in the response to preoperative chemoradiotherapy (PCRT) and the impact of histological types (SRCC versus other types) on survival. This retrospective study analysed the medical records of 195 patients with locally advanced rectal cancer treated from 2011, to 2018. Patients were divided into two groups according to histological types: SRCC group and non SRCC group. All patients received PCRT followed by surgery. SRCC group was associated with significant higher rate of complete clinical response (cCR) and pathologic complete response (pCR) (83.3% and 88.9% respectively) as compared to non SRCC group (9.0% and 10.2% respectively); P<0.0001. Fifteen cases (93.8%) who were diagnosed by magnetic resonance tumor regression grade (mrTRG) and diffusion weighted imaging (DWI) as cCR after PCRT, also achieved pCR, in contrast to 88.9% of cases without SRCC. Signet ring histology was the only predictor of pCR in multivariate analysis (P=0.027). There was no statistically significant difference between both histological groups as regard to survival. SRCC is an important predictor of pCR and assessing their response to PCRT using mrTRG and DWI showed high sensitivity for the detection of cCR, making them good candidates for watch-and-wait approach. Histological types did not significantly affect the survival outcome.

A Simple Immunohistochemical Panel Could Predict and Correlate to Clinicopathologic and Molecular Subgroups of Urinary Bladder Urothelial Carcinoma.

BACKGROUND: Although gene expression profiling provided a comprehensive molecular characterization of different subtypes of bladder urothelial carcinoma (UC), which are distinct in their biological features and prognosis, such a system is not yet applicable for routine clinical practice. This study aimed to examine the expression of these molecular classes of UC using simple panel of immunohistochemical markers. MATERIALS AND METHODS: Tissue sections from 192 specimens of UC were stained with FGFR3, CK5, CCNB1, HER-2, and P53. The molecular classes identified were correlated with clinicopathologic characteristics and patient survival. RESULTS: The most frequent class in our cohort was urobasal B (UroB) (44.1%), followed by squamous cell carcinoma-like (SCCL) (22%), genomically unstable (GU) (20.3%), and urobasal A (UroA) (13.6%). Patients with SCCL were significantly younger (P < .0001). Both the SCCL and GU types were of significantly higher histopathologic grade (P < .0001). UroA tumors were mainly of the T1 stage (75%), whereas 61.5% of the SCCL and 58.3% of the GU types were of stage T2 (P < .001). Prognosis was significantly different among groups. The SCCL class showed the lowest overall survival (38.5%; P = .030) and metastasis-free survival (69.2%; P = .017). The best prognosis was for UroA, with an overall survival of 75% and no metastatic events. CONCLUSION: The distribution of UC subtypes in our study was uniquely different from other studies. This simple immunohistochemical panel could be suggested as a clinically applicable tool that has the potential to be used routinely in guiding individualized treatment of UC.

Modulation of p73 isoforms expression induces anti-proliferative and pro-apoptotic activity in mantle cell lymphoma independent of p53 status.

Mantle cell lymphoma (MCL) is characterized by a clinically aggressive course with frequent relapse and poor survival. The p53 pathway is frequently dysregulated and p53 status predicts clinical outcome. In this report, we investigated whether modulation of p73 isoforms by diclofenac inhibits cell growth, induces apoptosis and/or cell cycle arrest in MCL relative to p53 status. Wild-type p53 [Granta-519 and JVM-2], mutant p53 [Jeko-1 and Mino-1] expressing cells, therapy resistant cell lines, and primary human cells isolated from MCL patients were used. Overexpression of pro-apoptotic TAp73 enhanced MCL cell apoptosis. Diclofenac induced a concentration- and duration-dependent increase in TAp73, cell cycle arrest, cell death, and inhibited MCL cell growth independent of p53 status. Diclofenac treatment was associated with increased activity of caspases 3, 7, and 8 and induction of p53 transcriptional target genes. These studies demonstrate the potential for diclofenac as novel therapeutic agent in MCL independent of p53 status.

Disruption of chromosomal locus 1p36 differentially modulates TAp73 and ΔNp73 expression in follicular lymphoma.

The TP73 gene is located at the chromosome 1p36 locus that is commonly disrupted or deleted in follicular lymphoma (FL) with poor prognosis. Therefore, we analyzed the expression of the pro-apoptotic TAp73 and anti-apoptotic ΔNp73 isoforms in cases of FL with normal or abnormal 1p36. We observed a significant increase in ΔNp73 expression and ΔNp73:TAp73 ratio, lower expression of cleaved caspase-3 and a higher frequency of Ki-67 and proliferating cell nuclear antigen (PCNA) positive cells in cases of FL with abnormal 1p36. A negative correlation between the ΔNp73:TAp73 ratio and cleaved caspase-3 expression, and a positive correlation between ΔNp73 expression and Ki-67 or PCNA, were observed. The expression of TAp73 and its pro-apoptotic transcriptional targets BIM. PUMA and NOXA were significantly lower in FL compared to reactive follicular hyperplasia. Together, our data demonstrate that 1p36 disruption is associated with increased ΔNp73 expression, decreased apoptosis and increased proliferation in FL.