Journal of the Egyptian National Cancer Institute最新文献

Hypothesis: Biological response modifiers (immunotherapy) in combination to chemotherapy are superior to that of chemotherapy in treatment of breast cancer (triple-negative/HER-2 ( +)), multiple myeloma, and non-small-cell lung cancer.

Methods: This review article consists of a total of eighteen independent randomized controlled clinical trials ranging from phases one to three. Patients were randomly selected for immunomodulatory treatment or chemotherapy and assessed for a specific mutation expression that the immunomodulatory agent targets. Kaplan-Meier plots, swimmer plots, and bar graphs depict overall/progression-free survival, objective response, and clinical response rates. The data collected was assessed by using 95% confidence interval and a p value of 0.05. Patients were treated until disease progression.

Results: Biological response modifiers (immunotherapy) resulted in significantly longer median progression-free survival in PD-L1-positive breast cancer (7.5 months compared to 5.0 months in control group), multiple myeloma (60.7% compared to 26.9% in the daratumumab and placebo groups, respectively), and in non-small-cell lung cancer (median progression-free survival was 10.3 months in the pembrolizumab group compared to 6.0 months in the chemotherapy group): higher complete responses in multiple myeloma (79% and 66% in the elotuzumab and control groups, respectively) and lower disease progression in PD-L1-positive non-small-cell lung cancer (62.1% of pembrolizumab versus 50.3% of chemotherapy patients had no disease progression at 6 months).

Conclusion: Combination biological response modifiers (immunotherapy) and chemotherapy displayed benefit in overall/progression-free survival, response rate, duration of response, clinical benefit, and invasive disease-free survival in triple-negative/HER2-2( +) breast cancer, multiple myeloma, and non-small-cell lung cancer.

Background: Gastric cancer (GC) ranks second in mortality among all malignant diseases worldwide. However, the cause and molecular mechanism underlying gastric cancer are not clear. Here, we used integrated bioinformatics to identify possible key genes and reveal the pathogenesis and prognosis of gastric cancer.

Methods: The gene expression profiles of GSE118916, GSE79973, and GSE29272 were available from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between GC and normal gastric tissues were screened by R software and Venn diagram software. GO and KEGG pathway enrichment of DEGs was performed using the DAVID database. A protein-protein interaction (PPI) network was established by STRING and visualized using Cytoscape software. Then the influence of hub genes on expression and survival was assessed using TCGA database.

Results: A total of 83 DEGs were found in the three datasets, including 41 up-regulated genes and 42 down-regulated genes. These DEGs were mainly enriched in extracellular matrix organization and cell adhesion. The enriched pathways obtained in the KEGG pathway analysis were extracellular matrix (ECM)-receptor interaction and focal adhesion. A PPI network of DEGs was analyzed using the Molecular Complex Detection (MCODE) app of Cytoscape. Four genes were considered hub genes, including COL5A1, FBN1, SPARC, and LUM. Among them, LUM was found to have a significantly worse prognosis based on TCGA database.

Conclusions: We screened DEGs associated with GC by integrated bioinformatics analysis and found one potential biomarker that may be involved in the progress of GC. This hub gene may serve as a guide for further molecular biological experiments.

Purpose: The theme of the St. Gallen International Breast Cancer Conference 2021 held virtually for the first time, due to the COVID-19 pandemic, was on tailoring therapies for patients with early breast cancer. A monkey survey that included an Egyptian Panel voted on most of the questions of the original St. Gallen consensus, and some added new questions most relevant to oncology practice in the country, to be able to compare voting results that reflect differences in breast cancer management and decision making.

Methods: The panel included 74 Egyptian scientists from different oncology specialties. Management issues including controversial diagnostic and therapeutic interventions were prepared by a small committee and then projected using the online monkey survey website: https://www.surveymonkey.com . The survey included 130 questions. Results were then analyzed, tabulated, and compared to the voting results of the original St. Gallen consensus.

Results and conclusions: Voting questions and resulting percentages of answers from the Egyptian panel were summarized. There was no consensus between the Egyptian and the original St. Gallen panels on 28/130 statements. They mostly included genetic and pathologic aspects, specifically the routine use of gene signature assays and a few queries involving surgical, radiotherapeutic, and systemic interventions. Probably, available resources and healthcare system differences in Egypt compared to European and the USA were the cause of these differences. This would also be applicable to other low- and low-middle-income healthcare scenarios present in many countries, especially with the present constraints of the COVID-19 pandemic.

Background: Gastric adenocarcinoma is one of the most aggressive forms of cancer. Despite marked advancements in radiological techniques, peritoneal deposits are still only discovered during laparotomies in a significant number of cases. The role of surgery in the management of metastatic gastric cancer is very limited, reducing the value of conducting laparotomies. In addition, conducting laparoscopies for the purposes of properly staging every case of gastric cancer is difficult, especially in healthcare systems with limited resources. It is thus crucial to investigate all possible predictors of peritoneal metastasis of gastric cancer, with the aim of reserving the use of laparoscopies to cases known to have high incidences of peritoneal metastasis despite negative radiological results.

Patients and methods: This is a case control study that included all cases of gastric adenocarcinoma that had presented to the National Cancer Institute-Cairo University between January 2018 and December 2019. The 'cases' group encompassed all gastric adenocarcinoma patients who were found to have peritoneal metastasis, whilst the 'control' group included those patients who were apparently metastasis-free. Comparisons were made between the two groups in terms of demographics, tumor characteristics, and results of laboratory tumor marker investigations.

Results: Patients with peritoneal metastasis were statistically significantly younger than those who had no apparent metastasis (mean ± SD 51.4 ± 12.5 and 56.2 ± 12.6 respectively; P = 0.020). Significant associations were found between a finding of peritoneal metastasis and (i) a middle tumor site (P = 0.002); (ii) tumor thickening morphology (P < 0.001); (iii) undifferentiated histopathology (P = 0.040); (iv) tumor grade III (P < 0.001); (v) lower lymphocyte counts of < 1.9/ml (P = 0.030); and (vi) high levels of CA 19-9 of > 37 units/ml (P = 0.032).

Conclusion: Tumor pathological criteria, including tumor site, degree of differentiation, shape, and grading, as well as laboratory findings of low lymphocytic counts and high levels of CA 19-9 appear to be reliable predictors of the presence of peritoneal metastasis from a gastric adenocarcinoma.

Background: The bladder cancer (BC) pathology is caused by both exogenous environmental and endogenous molecular factors. Several genes have been implicated, but the molecular pathogenesis of BC and its subtypes remains debatable. The bioinformatic analysis evaluates high numbers of proteins in a single study, increasing the opportunity to identify possible biomarkers for disorders.

Methods: The aim of this study is to identify biomarkers for the identification of BC using several bioinformatic analytical tools and methods. BC and normal samples were compared for each probeset with T test in GSE13507 and GSE37817 datasets, and statistical probesets were verified with GSE52519 and E-MTAB-1940 datasets. Differential gene expression, hierarchical clustering, gene ontology enrichment analysis, and heuristic online phenotype prediction algorithm methods were utilized. Statistically significant proteins were assessed in the Human Protein Atlas database. GSE13507 (6271 probesets) and GSE37817 (3267 probesets) data were significant after the extraction of probesets without gene annotation information. Common probesets in both datasets (2888) were further narrowed by analyzing the first 100 upregulated and downregulated probesets in BC samples.

Results: Among the total 400 probesets, 68 were significant for both datasets with similar fold-change values (Pearson r: 0.995). Protein-protein interaction networks demonstrated strong interactions between CCNB1, BUB1B, and AURKB. The HPA database revealed similar protein expression levels for CKAP2L, AURKB, APIP, and LGALS3 both for BC and control samples.

Conclusion: This study disclosed six candidate biomarkers for the early diagnosis of BC. It is suggested that these candidate proteins be investigated in a wet lab to identify their functions in BC pathology and possible treatment approaches.

Background: Mature B-cell non-Hodgkin lymphomas are one of the most common hematological malignancies with a divergent clinical presentation, phenotype, and course of disease regulated by underlying genetic mechanism.

Main body: Genetic and molecular alterations are not only critical for lymphomagenesis but also largely responsible for differing therapeutic response in these neoplasms. In recent years, advanced molecular tools have provided a deeper understanding regarding these oncogenic drives for predicting progression as well as refractory behavior in these diseases. The prognostic models based on gene expression profiling have also been proved effective in various clinical scenarios. However, considerable overlap does exist between the genotypes of individual lymphomas and at the same time where additional molecular lesions may be associated with each entity apart from the key genetic event. Therefore, genomics is one of the cornerstones in the multimodality approach essential for classification and risk stratification of B-cell non-Hodgkin lymphomas.

Conclusion: We hereby in this review discuss the wide range of genetic aberrancies associated with tumorigenesis, immune escape, and chemoresistance in major B-cell non-Hodgkin lymphomas.

Background: Mammosphere formation assay has become a versatile tool to quantify the activity of putative breast cancer stem cells in non-adherent in vitro cultures. However, optimizing the suspension culture system is crucial to establish mammosphere cultures from primary breast tumors.

Methods: This study aimed at determining the self-renewal and sphere-forming potential of breast cancer stem-like cells derived from human primary invasive ductal carcinoma and normal breast tissue samples, and MCF-7 breast cancer cell line using an optimal suspension culture system. Mammosphere-forming efficiency of the mammospheres generated from the tissue samples and cell line were compared. We evaluated the expression of CD44⁺/CD24^-/^low and CD49f⁺/EpCAM^-/^low phenotypes in the stem-like cells by flow cytometry. CK-18, CK-19, α-SMA, and EpCAM marker expression was assessed using immunohistochemical staining.

Results: Breast epithelial cells isolated from the three samples formed two-dimensional spheroids in suspension cultures. Interestingly, mammospheres formed from patient-derived primary breast tumors were enriched in breast cancer stem-like cells with the phenotype CD44⁺/CD24^-/^low and exhibited a relatively more number of large spheres when compared to the normal breast stem cells. MCF-7-derived SCs were more aggressive and resulted in the formation of a significantly higher number of spheroids. The expression of CK-18/CK-19 and α-SMA/EpCAM proteins was confirmed in breast cancer tissues.

Conclusions: Thus, the use of primary tumor specimens and breast cancer cell lines as suitable models for elucidating the breast cancer stem cell activity was validated using mammosphere culture system.

Background: Colorectal cancer (CRC) is one of the most important cancers in the world, and its prevalence varies depending on the geographical area. Genetically, tumor regeneration in CRC as a multi-step process involves activating mutations in protocogenes and losing the function of tumor suppressor genes as well as DNA repair and recovery genes. Occur in this way, our goal was to investigate the expression of KLF6 genes as a tumor suppressor and MUTYH involved in the DNA repair process in colorectal cancer.

Methods: This research was conducted during the years 2019-2018 in Razi Hospital, Rasht. The subjects included 30 tumoral and 30 non-tumoral tissues of colorectal cancer and 20 healthy controls. The real-time PCR method was used to investigate the gene expression. For data analysis by SPSS, parametric statistical tests ANOVA and T test and regression analysis were used and p value values less than 0.05 were considered significant.

Results: The expression of KLF6 gene in tumoral tissues showed a significant decrease compared to non-tumoral tissues (P = 0.04). Also, the expression of MUTYH gene in tumor tissue showed a significant decrease compared to non-tumoral (P = 0.02) and this decrease in MUTYH gene expression had a significant relationship with increasing tumor stage (P = 0.01).

Conclusion: These findings suggest that decreased expression of KLF6 and MUTYH genes in the study population has a significant relationship with colorectal cancer and can be considered as tumor marker in diagnostic purpose.