Clinical significance of CD166 and HER-2 in different types of gastric cancer

Introduction Cluster of differentiation 166 (CD166), a cancer stem cell (CSC) marker, and human epidermal growth factor receptor 2 (HER-2) are expressed in a diversity of malignancies and is associated with tumor progression. Although studies regarding the importance of CSC markers and HER-2 in gastric cancer (GC) have rapidly developed, their clinicopathological, prognosis, and diagnosis value still remain unsatisfying in GC. Therefore, the present study aims to investigate the clinical, prognostic, and diagnostic significance of CD166 and HER-2 in different histological types of GC. Materials and methods Bioinformatic analysis was applied to determine the clinical importance of CD166 and HER-2 expression based on their tissue localization in primary GC tumors and the normal adjacent samples. The expression patterns, clinical significance, prognosis, and diagnosis value of CD166 and HER-2 proteins in tissue microarrays (TMAs) of 206 GC samples, including Signet Ring Cell (SRC) and intestinal types and also 28 adjacent normal tissues were evaluated using immunohistochemistry (IHC). Results The results indicated that the expression of CD166 (membranous and cytoplasmic) and HER-2 were significantly up-regulated in tumor cells compared to adjacent normal tissues (P = 0.010, P < 0.001, and P = 0.011, respectively). A statistically significant association was detected between a high level of membranous expression of CD166 and lymphovascular invasion (P = 0.006); We also observed a statistically significant association between high cytoplasmic expression of CD166 protein and more invasion of the subserosa (P = 0.040) in the SRC type. In contrast, there was no correlation between the expression of HER-2 and clinicopathologic characteristics. Both CD166 and HER-2 showed reasonable accuracy and high specificity as diagnostic markers (AU)

The Prognostic Importance of Ki-67 in Gastrointestinal Carcinomas: A Meta-analysis and Multi-omics Approach.

PURPOSE: This study aimed to determine if Ki-67, a commonly used marker to measure tumor proliferation, is a reliable prognostic factor in various types of gastrointestinal (GI) cancers based on current high-quality multivariable evidence. METHODS: A comprehensive search was conducted in PubMed, Embase, Scopus, and ISI Web of Science databases to investigate the association between Ki-67 positivity and overall survival (OS) and disease/recurrence-free survival (DFS/RFS) in GI cancers. Heterogeneity was assessed using Chi-square-based Q and I2 analyses and publication bias using funnel plots and Egger's analysis. In addition, Ki-67 levels in different GI cancers were examined by different platforms. The prognostic capability of Ki-67, gene ontology (GO), and pathway enrichment analysis were obtained from GEPIA2 and STRING. RESULTS: Totally, 61 studies, involving 13,034 patients, were deemed eligible for our evaluation. The combined hazard ratios (HRs) demonstrated the prediction ability of overexpressed Ki-67 for a worse OS (HR: 1.67, P < 0.001; HR: 1.37, P = 0.021) and DFS/RFS (HR: 2.06, P < 0.001) in hepatocellular and pancreatic malignancies, respectively, as confirmed by multi-omics databases. However, similar correlation was not found in esophageal, gastric, and colorectal cancers. Furthermore, most of the associations were identified to be robust based on different subcategories and publication bias assessment. Finally, enriched Ki-67-related genes were found to be involved in various important signaling pathways, such as cell cycle, P53 signaling network, and DNA damage responses. CONCLUSION: This study supports that Ki-67 can serve as an independent prognostic biomarker for pancreatic and hepatocellular malignancies in clinical settings.

Clinical significance of CD166 and HER-2 in different types of gastric cancer.

INTRODUCTION: Cluster of differentiation 166 (CD166), a cancer stem cell (CSC) marker, and human epidermal growth factor receptor 2 (HER-2) are expressed in a diversity of malignancies and is associated with tumor progression. Although studies regarding the importance of CSC markers and HER-2 in gastric cancer (GC) have rapidly developed, their clinicopathological, prognosis, and diagnosis value still remain unsatisfying in GC. Therefore, the present study aims to investigate the clinical, prognostic, and diagnostic significance of CD166 and HER-2 in different histological types of GC. MATERIALS AND METHODS: Bioinformatic analysis was applied to determine the clinical importance of CD166 and HER-2 expression based on their tissue localization in primary GC tumors and the normal adjacent samples. The expression patterns, clinical significance, prognosis, and diagnosis value of CD166 and HER-2 proteins in tissue microarrays (TMAs) of 206 GC samples, including Signet Ring Cell (SRC) and intestinal types and also 28 adjacent normal tissues were evaluated using immunohistochemistry (IHC). RESULTS: The results indicated that the expression of CD166 (membranous and cytoplasmic) and HER-2 were significantly up-regulated in tumor cells compared to adjacent normal tissues (P = 0.010, P < 0.001, and P = 0.011, respectively). A statistically significant association was detected between a high level of membranous expression of CD166 and lymphovascular invasion (P = 0.006); We also observed a statistically significant association between high cytoplasmic expression of CD166 protein and more invasion of the subserosa (P = 0.040) in the SRC type. In contrast, there was no correlation between the expression of HER-2 and clinicopathologic characteristics. Both CD166 and HER-2 showed reasonable accuracy and high specificity as diagnostic markers. CONCLUSION: Our results confirmed that increased membranous and cytoplasmic expression of CD166 showed clinical significance in the SRC type and is associated with the progression of the disease and more aggressive tumor behaviors. These findings can be used to assist in designating subgroups of patients that require different follow-up strategies, and also, they might be utilized as the prognostic or diagnostic biomarkers in these types of GC for prospective clinical application.

Efficacy of Whole Cancer Stem Cell-Based Vaccines: A Systematic Review of Preclinical and Clinical Studies.

BACKGROUND: Despite the conventional cancer therapeutic, cancer treatment remains a medical challenge due to neoplasm metastasis and cancer recurrence; therefore, new approaches promoting therapeutic strategies are highly desirable. As a new therapy, the use of whole neoplastic stem cells or cancer stem cell (CSC)-based vaccines is one strategy to overcome these obstacles. We investigated the effects of whole CSC-based vaccines on the solid tumor development, metastasis, and survival rate. METHODS: Primary electronic databases (PubMed/MEDLINE, Scopus, Embase, and Web of Science) and a major clinical registry were searched. Interventional studies of whole CSC-based vaccines in rodent cancer models (38 studies) and human cancer patients (11 studies) were included; the vaccine preparation methodologies, effects, and overall outcomes were evaluated. RESULTS: Preclinical studies were divided into 4 groups: CSC-lysates/ inactivated-CSC-based vaccines, CSC-lysate-loaded dendritic cell (CSC-DC) vaccines, cytotoxic T-cell (CTL) vaccines generated with CSC-DC (CSC-DC-CTL), and combinatorial treatments carried out in the prophylactic and therapeutic experimental models. The majority of preclinical studies reported a promising effect on tumor growth, survival rate, and metastasis. Moreover, whole CSC-based vaccines induced several antitumor immune responses. A small number of clinical investigations suggested that the whole CSC-based vaccine treatment is beneficial; however, further research is required. CONCLUSIONS: This comprehensive review provides an overview of the available methods for assessing the efficacy of whole CSC-based vaccines on tumor development, metastasis, and survival rate. In addition, it presents a set of recommendations for designing high-quality clinical studies that may allow to determine the efficacy of whole CSC-based-vaccines in cancer therapy.

The Potential Relationship Between Different Human Female Reproductive Disorders and Sperm Quality in Female Genital Tract.

Spermatozoa should travel throughout the female reproductive tract to reach its ultimate goal, fertilization of the oocyte. At the ejaculation moment, millions of sperm within a few milliliters of the ejaculate are deposited at the cranial segment of vagina and make their journey to the fertilization site. This is done by means of various factors, such as sperm motility, the uterine and fallopian tubes contractility, and the ciliary movement of the lining cells. During this migration, spermatozoa interact with the female microenvironment both physically and molecularly. In this regard, the quality of the environmental conditions may affect this interaction. Therefore, some alterations in women's genital tract microenvironment, such as conditions that occur in female reproductive disorders, may have detrimental effects on sperm reproductive function. In this review, human sperm migration through the female tract is described, and the potential effects of different reproductive disorders at reproductive organs, such as vagina, uterine cervix, uterus, fallopian tubes, and ovary on sperm survival and quality, are also argued. The understanding of those conditions that may impair sperm fertility in the female genital tract can provide a more accurate diagnosis of the causes of infertility in couples. This can ultimately lead to the discovery of effective treatment approaches.

Immunomodulatory-based therapy as a potential promising treatment strategy against severe COVID-19 patients: A systematic review.

The global panic of the novel coronavirus disease 2019 (COVID-19) triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an urgent requirement for effective therapy. COVID-19 infection, especially in severely ill patients, is likely to be associated with immune dysregulation, prompting the development of novel treatment approaches. Therefore, this systematic review was designed to assess the available data regarding the efficacy of the immunomodulatory drugs used to manage COVID-19. A systematic literature search was carried out up to May 27, 2020, in four databases (PubMed, Scopus, Web of Science, and Embase) and also Clinicaltrials.gov. Sixty-six publications and 111 clinical trials were recognized as eligible, reporting the efficacy of the immunomodulatory agents, including corticosteroids, hydroxychloroquine, passive and cytokine-targeted therapies, mesenchymal stem cells, and blood-purification therapy, in COVID-19 patients. The data were found to be heterogeneous, and the clinical trials were yet to post any findings. Medicines were found to regulate the immune system by boosting the innate responses or suppressing the inflammatory reactions. Passive and cytokine-targeted therapies and mesenchymal stem cells were mostly safe and could regulate the disease much better. These studies underscored the significance of severity profiling in COVID-19 patients, along with appropriate timing, duration, and dosage of the therapies. Therefore, this review indicates that immunomodulatory therapies are potentially effective for COVID-19 and provides comprehensive information for clinicians to fight this outbreak. However, there is no consensus on the optimal therapy for COVID-19, reflecting that the immunomodulatory therapies still warrant further investigations.