Ds-echinoside A, a new triterpene glycoside derived from sea cucumber, exhibits antimetastatic activity via the inhibition of NF-κB-dependent MMP-9 and VEGF expressions

Ds-echinoside A (DSEA), a non-sulfated triterpene glycoside, was isolated from the sea cucumber Pearsonothuria graeffei. In vitro and in vivo investigations were conducted on the effects of DSEA on tumor cell adhesion, migration, invasion, and angiogenesis. In this study, we found that DSEA inhibited the proliferation of human hepatocellular liver carcinoma cells Hep G2, with a half-maximal inhibitory concentration (IC₅₀) of 2.65 μmol/L, and suppressed Hep G2 cell adhesion, migration, and invasion in a dose-dependent manner. DSEA also reduced tube formation of human endothelial cells ECV-304 on matrigel in vitro and attenuated neovascularization in the chick embryo chorioallantoic membrane (CAM) assay in vivo. Immunocytochemical analysis revealed that DSEA significantly decreased the expression of matrix metalloproteinase-9 (MMP-9), which plays an important role in the degradation of basement membrane in tumor metastasis and angiogenesis. DSEA also increased the protein expression level of tissue inhibitor of metalloproteinase-1 (TIMP-1), an important regulator of MMP-9 activation. From the results of Western blotting, the expressions of nuclear factor-kappa B (NF-κB) and vascular endothelial growth factor (VEGF) were found to be remarkably reduced by DSEA. These findings suggest that DSEA exhibits a significant antimetastatic activity through the specific inhibition of NF-κB-dependent MMP-9 and VEGF expressions.     

A Comparative Study of Bone Scan Findings and Serum Levels of Tumor Marker CA15-3 in Patients with Breast Carcinoma

Breast cancer is one of the most frequent malignancies in the world. Available staging procedures to detect breast cancer are bone scan, chest X-ray, liver ultrasonography, computerized tomography, estimation of tumor markers like carbohydrate antigen (CA15-3) and carcino embryonic antigen. These procedures are expensive and may not be required in all cases. Out of 70 patients studied, 55 had normal CA15-3 and 15 had elevated levels of Ca15-3. Eight (14.5%) of the 55 patients with normal CA15-3 had abnormal bone scan. Fifteen patients had CA15-3 levels above the normal range and among these 9 (60%) had abnormal bone scan. While prime facie it would appear that a high level of CA15-3 correlate with abnormal bone scan, it is also true that the numbers are small at present and conclusions about the validity of CA15-3 as marker of bone metastasis may be premature.     

CRISPR/Cas9-mediated activation of CDH1 suppresses metastasis of breast cancer in rats

BackgroundCancer is a life-threatening disease that affects approximately 18 million individuals worldwide. Breast cancer is the most common female neoplasm globally with more than 276,480 new cases of invasive breast cancer expected to be diagnosed in women in the U.S. alone in 2020. Genetic and epigenetic factors play role in the carcinogenesis and progression of this disease. In this study, MCF-7 adenocarcinoma cells were transfected with CRISPR/Cas9 plasmid to either knock out CDK11 or to activate CDH1. Treated cells were allografted into the mammary glands of female rats (150–190 g, 6–8 weeks) to evaluate the capability of these cells to control cancer progression and metastasis.ResultsqPCR data revealed a significant downregulation of CDK11 and upregulation of CDH1. Cell cycle analysis and apoptosis assays indicated the knockout of CDK11 and simultaneous activation of CDH1 resulted in cell cycle arrest at G2/M phase and accumulation of cells at G2. Meanwhile, the percentage of cells that underwent late apoptosis increased in both genome editing hits. Histopathological sectioning data indicated that untransfected MCF-7 cells were capable of developing tumors in the mammary gland and initiation g angiogenesis. Transfected cells significantly restricted cancer cell infiltration/invasion by minimally localizing tumors and inhibiting angiogenesis.ConclusionsAlthough further investigation is needed, the present data indicate the potentiality of using CRISPR/Cas9-based therapy as a promising approach to treat breast cancer. Impact: these data indicate targeting cancer-related genes via any genome editing tool might represent a novel approach to combat cancer.How to cite: Al-Mulhim F, Alqosaibi AI, Al-Muhnna A, et al. CRISPR/Cas9-mediated activation of CDH1 suppresses metastasis of breast cancer in rats. Electron J Biotechnol 2021;53. https://doi.org/10.1016/j.ejbt.2021.06.002     

MACC1 upregulation promotes gastric cancer tumor cell metastasis and predicts a poor prognosis

In various studies, metastasis associated with colon cancer 1 (MACC1) has been frequently reported to be abnormally highly expressed in human lung cancer, colon cancer, and hepatocellular carcinoma. Our study focuses on the association of MACC1 expression with gastric cancer (GC). During our experiment, the MACC1 expression was tested in 105 GC samples using an immunohistochemical (IHC) method. The clinical characteristics and prognosis of these patients were summarized. During analysis, MACC1 distribution in GC samples with distant metastasis was higher than that in normal samples and in tumors with no dissemination. Subsequently, a lower 5-year survival rate had a strong correlation with high MACC1 expression. As a consequence, the present results suggest that MACC1 is more frequently expressed in a poor prognosis phenotype of GC and acts as a promising prognostic prediction parameter for GC.     

淋巴血管在肿瘤转移和免疫生物学中的作用（英文）

淋巴系统被认为是肿瘤转移的重要途径之一,所以通常情况下肿瘤引起的淋巴血管增生会降低肿瘤预后,治疗上也建议淋巴清扫。但是最新的研究显示,淋巴系统可能对肿瘤免疫治疗有促进作用。这篇综述的主要目的是对相关领域做一个简短总结,以期待将来有更多的研究来关注淋巴系统对肿瘤治疗的影响。文章首先介绍肿瘤淋巴血管增生和淋巴转移的分子机制,然后介绍淋巴系统在肿瘤免疫中的作用,最后利用最新研究来证明淋巴系统有增强肿瘤免疫治疗的作用。     

Chemokines and their receptors in lung cancer progression and metastasis

Lung cancer is the leading cause of cancer-related mortality around the world. Despite advancements in diagnosis, surgical techniques, and neoadjuvant chemoradiotherapy over the last decade, the mortality rate is still high and the 5-year survival is a dismal 15%. Fortunately, early detection by low-dose computed tomography (LDCT) scans has reduced mortality by 20%; yet, overall, 5-year-survival remains low at less than 20%. Therefore, in order to ameliorate this situation, a thorough understanding of the underlying molecular mechanisms is urgently needed. Chemokines and their receptors, crucial microenvironmental factors, play important roles in lung tumor genesis, progression, and metastasis, and exploring the mechanisms of this might bring new insights into early diagnosis and precisely targeted treatment. Consequently, this review will mainly focus on recent advancements on the axes of chemokines and their receptors of lung cancer.     

P53基因蛋白在消化道肿瘤中的表达同浸润深度与转移的相关性观察

目的探讨P53基因表达与胃癌、肠癌、食管癌的相互关系.方法采用SP免疫组化染色方法.检测了消化道癌中(胃癌22例、肠癌22例、食管癌60例)P53蛋白的表达率.结果P53蛋白在胃癌中表达率最高达63.6%,肠癌中表达率为55.0%,食管癌中的表达率为61.7%.结论P53蛋白在消化道肿瘤中普遍表达并且当癌浸润较深和有淋巴结转移者阳性率较高.     

Malignant peritoneal mesothelioma presenting with persistent high fever

Malignant peritoneal mesothelioma (MPM) is a rare tumor that develops in the peritoneum. In this paper, we describe an extremely rare case of MPM metastasizing to the appendix in a 48-year-old female who initially presented with a persistent high fever. The woman reported a slight lower abdominal discomfort which had been relieved by urination for four months. She had lost 5 kg of weight. There was no nausea, vomiting, diarrhea, abdominal pain, or abdominal distension. Many broad spectrum antibiotics were given without relief of fever. Computed tomography (CT) scans revealed a thickened omentum majus and diffused multiple omental nodules. An omentectomy, appendectomy, and adnexectomy were carried out. A gross pathologic specimen of omentum tissue revealed a firm gray-white mass. Microscopic and immunohistochemical examinations confirmed the diagnosis of appendiceal and bilateral adnexal metastases of an MPM. These results suggest that MPM should be considered in the differential diagnosis of unexplained persistent high fever. Awareness of such atypical presentations of mesothelioma may help to make a correct diagnosis.     

MMP 9 Gene Promoter Polymorphism in Gastric Cancer

Matrix metalloproteinase-9 (gelatinase B) plays a key role in cancer invasion and metastasis by degrading the extracellular matrix and basement membrane barriers. A cytosine (C) > thymidine (T) single nucleotide polymorphism (SNP) at position −1562 in the MMP-9 promoter is reported to influence the expression of the gene. Genotyping of MMP-9 −1562 C→T promoter polymorphism in 140 gastric cancer patients and 132 healthy control subjects was carried out in order to evaluate its association with progression and development of gastric cancer. The SNP was genotyped by tetra-primer amplification refractory mutation system-polymerase chain reaction followed by agarose gel electrophoresis. Statistical methods were adopted to test for the significance of the results. Risk factor profile of the patients revealed age above 50 years, smoking, alcoholism as the factors associated with the disease. The distribution of genotype frequencies in gastric cancer patients were 28.7 % of CC, 45.5 % of CT and 25.7 % of TT, whereas in control subjects 31.8 % of CC, 53.03 % of CT and 15.15 % of TT, respectively. The allelic frequencies were 51.51 % of C and 48.48 % of T in patient group and 58.33 % of C and 41.66 % of T in controls respectively. The present study shows the possible association of epidemiological risk factors with gastric cancer. There is an increased frequency of T allele in the disease compared to control subjects. However, there is no association of the MMP-9 −1562 C→T promoter polymorphism in the development of gastric cancer.