Histology and histopathology Vol.34, nº4 (2019)

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  • Publication
    Open Access
    APOBEC3B protein expression and mRNA analyses in patients with high-grade serous ovarian carcinoma
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Rüder, Ulrike; Denkert, Carsten; Alisa Kunze, Catarina; Jank, Paul; Lindner, Judith; Jöhrens, Korinna; Kulbe, Hagen; Sehouli, Jalid; Dietel, Manfred; Braicu, Elena; Darb Esfahani, Silvia
    APOBEC3 enzymes are part of the innate immune system and they are important in retroviral defense. The number of mutations in ovarian cancer increases with rising levels of APOBEC3B mRNA. We could confirm that APOBEC3B mRNA is upregulated in ovarian cancer cell lines and in ovarian cancer tissue. We evaluated APOBEC3B expression in histologically defined subtypes of ovarian cancer to identify its influence on overall survival (OS) and progression-free survival (PFS). Tissue microarrays from 219 patients with highgrade serous (HGSC), 61 with low-grade serous (LGSC), 62 with endometrioid (EC) and 55 with clear cell (CCC) ovarian carcinoma were stained using an antibody against APOBEC3B. Real-time quantitative PCR was performed to detect APOBEC3B mRNA levels in 274 cases of HGSC, in 11 cases of LGSC, in 47 cases of EC and in 29 cases of CCC. Tumor-infiltrating lymphocytes (TILs) have been evaluated in a previous project. APOBEC3B staining was cytoplasmic as well as nuclear and both were positively correlated (P<0.001). In HGSC a trend was detectable for positive cytoplasmic staining as favorable regarding OS (P=0.283) and PFS (P=0.137). High levels of APOBEC3B mRNA were associated with prolonged PFS in HGSC in univariate analyses (P=0.043) and multivariate analyses (HR 0.55; 95% CI 0.35-0.88; P=0.012). APOBEC3B cytoplasmic staining and APOBEC3B mRNA were positively correlated with TILs. APOBEC3B in HGSC is related to an active immune infiltrate. However, there is no evidence for APOBEC3B as a clinically relevant prognostic biomarker.
  • Publication
    Open Access
    Protective effect of alpha-mangostin on thioacetamide-induced liver fibrosis in rats as revealed by morpho-functional analysis
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Rodniem, Siripa; Tiyao, Vilailak; Nilbu nga, Cheng; Poonkhum, Raksawan; Pongmayteegul, Sirinun; Pradidarcheep, Wisuit
    Liver fibrosis is an excessive accumulation of scar tissue resulting from inflammation and cell death. Thioacetamide (TAA) is a well-known hepatotoxin that induces liver fibrosis. A marker of injured hepatocytes is transforming growth factor-beta 1 (TGF-β1), while alpha-smooth muscle actin (α-SMA) and tissue inhibitor of metalloproteinase 1 (TIMP-1) are markers of activated hepatic stellate cells. Alpha-mangostin, a major xanthone derivative from the mangosteen pericarp, has been shown to have anti-oxidant and anti-inflammatory activities. The objective of this study was to determine whether alpha-mangostin has a protective effect on TAA-induced liver fibrosis in rats. The rats were treated by intraperitoneal injection of compounds for eight weeks. For the control group a mixture of dimethyl sulfoxide and phosphate buffered saline was administered. Two hundred mg/kg BW of TAA was administered three times weekly. Alpha-mangostin was administered at 5 mg/kg BW and silymarin at 100 mg/kg BW, both twice weekly. TAA induced histologically recognizable liver damage and fibrosis, as anticipated. Furthermore, it increased immunohistochemically detectable TGF-β1, α-SMA, and TIMP-1. Coadministration of alpha-mangostin or silymarin with TAA prevented or ameliorated the effects of TAA administration alone. The anti-fibrotic effect of alphamangostin was stronger than that of silymarin.
  • Publication
    Open Access
    The effect of 2.45 GHz non-ionizing radiation on the structure and ultrastructure of the testis in juvenile rats
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Šimaiová, Veronika; Almášiová, Viera; Holovská, Katarína; Kisková, Terézia; Horváthová, Františka; Ševčíková, Zuzana; Tóth, Štefan; Raček, Adam; Račeková, Enikő; Beňová, Katarína; Dvořák, Petr; Cigánková, Viera
  • Publication
    Open Access
    Clinical significance and EZH2, ERG and SPINK1 protein expression in pure and mixed ductal adenocarcinoma of the prostate
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Patil, Pallavi A.; McKenney, Jesse K.; Reynolds, Jordan P.; Przybycin, Christopher G.; Magi Galluzzi, Cristina
    Background: Although ERG and SPINK1 molecular alterations have been studied in acinar and ductal adenocarcinoma of the prostate, EZH2 expression has not been previously evaluated in ductal adenocarcinoma. Methods: We collected cases of pure and mixed ductal adenocarcinoma of the prostate and evaluated clinical significance and EZH2, ERG, and SPINK1 protein expression. Results: We investigated 61 ductal adenocarcinomas, 22 pure and 39 mixed ductal/acinar. Except for tumor growth pattern, none of the clinical parameters studied significantly differed between pure and mixed tumors. Thirty-five percent of ductal adenocarcinomas were organ confined, 15% displayed seminal vesicle invasion. Lymph node and distal metastasis occurred in 13% and 24% of cases, respectively; 34% of patients experienced biochemical failure, 7% died of disease. Ninety-eight percent of tumors expressed EZH2; in 80% of cases >50% of tumor cells were positive. ERG and SPINK1 were expressed in 20% and 36% of cases, respectively. There was no difference in protein expression between pure and mixed ductal adenocarcinomas. ERG expression tended to be lower, and SPINK1 higher than reported for acinar tumors. Biochemical failure, metastasis and death did not differ between EZH2, ERG, and SPINK1 positive and negative patients, nor between <50% versus >50% expression of SPINK1 and EZH2, respectively. Conclusions: Pure and mixed ductal adenocarcinomas have similar clinical behavior and molecular alterations. Higher EZH2 and SPINK1 protein expression, compared to acinar prostatic adenocarcinoma, might account for the more aggressive clinical course of ductal adenocarcinoma
  • Publication
    Open Access
    4-(3,4-dihydroxybenzoyloxymethyl)phenyl-O-β-D-glucopyranoside effect in liver regeneration
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Firat, Tülin; Söyler, Gizem; Töre, Fatma; Șit, Mustafa; Kiyan, Aysu; Özgen, Ufuk; Kükner, Aysel
    Following an injury or resection, the mammalian liver has the capacity to regain its former volume and functioning by restoring itself. Studies have demonstrated that antioxidants play a role in hepatic regeneration. This study investigated the effect of 4-(3,4- dihydroxybenzoyloxymethyl)phenyl-O-ß-D-glucopyranoside (PG) obtained from Origanum micranthum on liver regeneration. Sixty Wistar Albino rats were used. In the sham-operated group, a midline abdominal laparotomy was performed without hepatectomy. In the partial hepatectomy (PHx) group, the median and left lateral lobes were removed. Rats in the PHx group received 20 mg/kg/day PG intraperitoneally before being sacrificed at 24, 48, and 72 hrs, and 7 days later. Liver tissues were collected for immunohistochemical analysis and electron microscopic evaluation. We found an increase in mitotic index, and the numbers of Ki-67 stained hepatocytes in all PHx early stage groups (24 hr, 48hr, 72 hr), but not in 7-day groups. The regeneration mediators eNOS, iNOS, TNF-α and NF-kB were shown to increase in PHx groups. This increase was more prominent dependening on time. In the PHx treatment (PHx+PG) groups, while eNOS was still high, iNOS, TNF-α and NF-kB had decreased. The apoptotic index was markedly high in the PHx groups; this was prevented by PG treatment. These findings were supported by the ultrastructural results. Our findings indicate that PG supports liver regeneration, hepatocyte proliferation, reduced liver damage, and inflammatory mediators following PHx.