Expression of Blood Group Antigens and Lectin Binding in Adenocarcinomas of the Endometrium

To investigate cytoplasmic alterations in cancers of the endometrium, monoclonal antibodies against H, A and B blood group substances and related lectins such as Ulex europaeus agglutinin 1 (UEA-l), Lotus fefragonolobus agglutinin (LTA), and Griffonia simplicifolia 1 (GS1-A4, -B4) were applied to 42 cases of endometrial adenocarcinoma (EAC) and 11 adenomyoses. The control specimens consisted of normal endometria with leiomyoma or adenomyosis from patients of known blood group type. The brightest and most consistent staining was obtained with GS1- A4, showing 98% positivity in EAC in contrast to 18% in normal endometria. In contrast, expression of A antigen was seen in only 24% of EAC and in 13% of normal endometria, UEA-1 binding was seen in 81% of EAC and in 10% of normal endometria, whereas H antigen was seen in 60% of EAC and 0% of normal endometria. In adenocar. cinomas, staining was seen not only along the luminal border of glands but also in the cytoplasm and the lateral or basal cell membranes, whereas in the normal endometrium staining was mostly along the luminal border. Thus, a difference in the positivity and localization of glycoconjugates was observed in neoplastic and non neoplastic endometrium.     

Estrogen synthesis in the brain—Role in synaptic plasticity and memory

Estrogen and androgen are synthesized from cholesterol locally in hippocampal neurons of adult animals. These neurosteroids are synthesized by cytochrome P450s and hydroxysteroid dehydrogenases (HSDs) and 5alpha-reductase. The expression levels of enzymes are as low as 1/200–1/50,000 of those in endocrine organs, however these numbers are high enough for local synthesis. Localization of P450(17alpha), P450arom, 17beta-HSD and 5alpha-reductase is observed in principal glutamatergic neurons in CA1, CA3 and the dendate gyrus. Several nanomolar levels of estrogen and androgen are observed in the hippocampus.Estrogen modulates memory-related synaptic plasticity not only slowly but also rapidly in the hippocampus. Rapid action of 17beta-estradiol via membrane receptors is demonstrated for spinogenesis and long-term depression (LTD). The enhancement of LTD by 1–10 nM estradiol occurs within 1 h. The density of spine is increased in CA1 pyramidal neurons within 2 h after application of estradiol. The density of spine-like structure is, however, decreased by estradiol in CA3 pyramidal neurons. ERalpha, but not ERbeta, induces the same enhancement/suppression effects on both spinogenesis and LTD.     

Expression of MUC1 and MUC2 mucins and relationship with cell proliferative activity in human colorectal neoplasia

Our previous studies on MUC1 and MUC2 mucin expression in various human neoplasms have found that MUC1 expression is related with a poor outcome whereas MUC2 expression is related with a favorable outcome. In the present study, we examined the alteration of MUC1 and MUC2 antigens on malignant transformation of colorectal mucosa, and also its relationship with cell proliferative activity (Ki-67 labeling index) of neoplastic epithelial cells in 200 adenomas and 58 carcinomas. In the 200 adenomas, we analyzed a total of 400 adenomatous lesions (mild dysplasia, 200 lesions; moderate dysplasia, 153 lesions; severe dysplasia, 47 lesions). MUC1 was expressed in carcinomas (24%) and adenomas with severe dysplasia (4%), but was not expressed in adenomas with mild or moderate dysplasia. MUC2 was expressed in a significantly greater number of adenomas with mild dysplasia (72%) than in adenomas with moderate dysplasia (45%) or severe dysplasia (47%), as well as in the carcinomas (38%; P < 0.0001). The Ki-67 labeling index was significantly lower in the MUC2-positive cases than in the MUC2-negative cases in the adenomas with mild dysplasia (13.6 vs 24.2%; P < 0.0001) or moderate dysplasia (25.7 vs 44.4%; P < 0.0001), and in the carcinomas (32.5 vs 48.4%; P < 0.05). In conclusion, the data from our study indicate that increased MUC1 expression and reduced MUC2 expression may be related to malignant transformation of colorectal neoplasia. We also demonstrated that decreased MUC2 expression, which is correlated with increased Ki-67 labeling, may play an important role in the progression of colorectal adenomatous change.     

Association of the Low-density Lipoprotein Cholesterol/High-density Lipoprotein Cholesterol Ratio with Glecaprevir-pibrentasvir Treatment

Objective The change in serum lipid levels by direct-acting antiviral (DAA) treatment for chronic hepatitis C varies depending on the type of DAA. How the lipid level changes induced by glecaprevir-pibrentasvir (G/P) treatment contribute to the clinical outcome remains unclear. We conducted a prospective observational study to evaluate the effectiveness of G/P treatment and the lipid level changes. Methods The primary endpoint was a sustained virologic response at 12 weeks (SVR12). The total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels and LDL-C/HDL-C (L/H) ratio were measured every two weeks. Patients This study included 101 patients. Seventeen cases of liver cirrhosis and nine cases of DAA retreatment were registered. The G/P treatment period was 8 weeks in 74 cases and 12 weeks in 27 cases. Results SVR12 was evaluated in 96 patients. The rate of achievement of SVR12 in the evaluable cases was 100%. We found significantly elevated TC and LDL-C levels over the observation period compared to baseline. The serum levels of HDL-C did not change during treatment but were significantly increased after treatment compared to baseline. The L/H ratio was significantly increased two weeks after the start of treatment but returned to the baseline after treatment. Conclusion The primary endpoint of the SVR12 achievement rate was 100%. G/P treatment changed the serum lipid levels. Specifically, the TC and LDL-C levels increased during and after treatment, and the HDL-C levels increased after treatment. G/P treatment may be associated with a reduced thrombotic risk. Therefore, validation in large trials is recommended.     

Mucin expression profile in pancreatic cancer and the precursor lesions

In this review article, we demonstrate the mucin expression profile in normal tissue, invasive ductal carcinoma (IDC), two subtypes of intraductal papillary–mucinous neoplasm (IPMN dark cell type and IPMN clear cell type), pancreatic intraepithelial neoplasia (PanIN), and mucinous cystic neoplasm (MCN) of the pancreas. In MUC1, there are various glycoforms, such as poorly glycosylated MUC1, sialylated MUC1, and fully glycosylated MUC1. IDCs showed high expression of all the glycoforms of MUC1. IPMNs dark cell type showed no expression or low expression of all the glycoforms of MUC1. IPMNs clear cell type showed low expression of poorly glycosylated MUC1, but expression of sialylated MUC1 and fully glycosylated MUC1. Expression of MUC2 was negative in IDCs, high in IPMNs dark cell type and low in IPMNs clear cell type. MUC5AC was highly expressed in IDCs, IPMNs dark cell type, and IPMNs clear cell type. MUC6 expression was higher in IPMNs clear cell type than in IDCs and IPMNs dark cell type. Our recent study demonstrated that high expression of MUC4 in IDCs is correlated with a poor outcome for patients. In PanINs, expression of both MUC5AC and MUC6 are an early event, whereas up-regulation of MUC1 is a late event. MCNs do not look as if they will show a specific mucin expression profile according to the literature review.     

Microsomal prostaglandin E synthase protein levels correlate with prognosis in colorectal cancer patients

The aim of this study is to investigate the expression of three prostaglandin E synthase (PGES) isomers in colorectal cancer (CRC) tissue and to evaluate their relationship to clinicopathological factors and patient prognosis. Microsomal PGES (mPGES)-1, mPGES-2, cytosolic PGES (cPGES) and cyclooxygenase (COX)-2 protein expression were analyzed by real-time polymerase chain reaction and Western blot. The localization of each PGES and COX-2 protein was examined by immunohistochemistry in 155 surgical resections and correlated to clinicopathological factors and patient prognosis. mPGES-1 mRNA and protein levels were significantly higher in CRC than in paired normal tissues. mPGES-1 immunoreactivity localized in cancer cells in 43% of cases. mPGES-2 immunoreactivity was significantly more pronounced in cancer cells than in adjacent normal epithelium in 36% of cases. cPGES immunoreactivity was homogeneous in cancer cells and thus determined constitutive. mPGES-1 and mPGES-2 correlated with significantly worse prognosis in stage I–III patients. These results indicate that mPGES-1 and mPGES-2 may each play a role in CRC progression.