Histology and histopathology Vol.32, nº2 (2017)
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- PublicationOpen AccessAnti-inflammatory effects of enemas containing an oily extract of curcumin in an experimental model of diversion colitis(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Jaoudat Kadri, Caled; Aires Pereira, José; Guilherme Campos, Fábio; Marques Ortega, Manoela; Benediti Bragion, Celene; Real Martinez, Carlos AugustoCurcumin has powerful anti-inflammatory and antioxidant effects and it has been used for treatment of distal ulcerative colitis. The therapeutic effects of curcumin have not yet been evaluated in diversion colitis. The aim of the present study was to evaluate the anti-inflammatory effects of curcumin on colonic mucosa devoid of a faecal stream. Thirty-six rats were subjected to a proximal colostomy and distal colonic fistulation. They were divided into two groups, which were sacrificed two or four weeks after the intervention. Each group was divided into three subgroups treated with the daily application of enemas containing saline or an oily extract of curcumin at 50 mg/kg/day or 200 mg/kg/day. Colitis was diagnosed by histological analysis. Inflammatory grades were assessed using a previously validated scoring system. The infiltration of neutrophils was evaluated based on the tissue expression of myeloperoxidase (MPO), as determined by immunohistochemistry, and a computer-assisted image analysis program. The Mann-Whitney test was used to compare inflammation grades and myeloperoxidase levels among groups, and ANOVA was used to verify the variance over time, with the level of significance set at 5% (p<0.05) for both tests. Enemas containing curcumin improved the inflammation of the mucosa without a faecal stream and reduced the tissue contents of MPO. MPO tissue levels did not vary with time or between the concentrations of curcumin used. Enemas with curcumin improved the inflammation of the colonic mucosa, reduced the inflammatory grade and decreased the tissue content of MPO in colon segments without a faecal stream.
- PublicationOpen AccessmicroRNA expression profiles as decision-making biomarkers in the management of bladder cancer(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Amir, Sharon; Mabjeesh, Nicola J.Bladder cancer (BC) is generally divided into non-muscle-invasive BC (NMIBC) and muscle-invasive BC (MIBC). The standard treatment protocol for MIBC patients is radical cystectomy preceded by neoadjuvant chemotherapy (NAC). About one-half of the MIBC patients show a priori resistance to chemotherapy, and are therefore exposed to the risks of disease progression and toxicity from ineffective NAC. The discovery of microRNA (miRNA) regulation in tumorigenesis has provided new directions for the development of a new type of BC biomarkers. In this review, we describe the emerging miRNAs as BC biomarkers for different purposes, including diagnosis, prognosis and therapeutic response. miRNA expression profile changes with alteration of the tissue phenotype. This phenomenon is utilized to predict tumor diagnosis, cancer subclass, disease stage, prognosis and therapeutic response. We classified the miRNAs which are involved in bladder cancer according to malignant potential, chemoresistance, discrimination between normal to cancerous and clinical outcome. Focusing on the major obstacle regarding MIBC patient's NAC response, we summarized the miRNAs that are deregulated and have the potential to identify the patients resistant to NAC, such as miR-34, miR-100, miR-146b and miR-9 and miR-193a-3p. In conclusion, miRNAs expression profile of bladder cancer patient is a promising tool that can serve as biomarker for different aims. Based on this profile we propose upfront radical cystectomy instead of standard NAC to those MIBC patients who are at higher risk for chemoresistance and poor response.
- PublicationOpen AccessMicrogravity directs stem cell differentiation(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Chen, Zhe; Luo, Qing; Yuan, Lin; Song, Guanbiny. Stem cells are the cell of origin for organisms and their organs. These cells are critical for tissue regeneration, as well as regenerative medicine. Mechanical forces, such as gravity, have been demonstrated to provide important signals for stem cell fate. In fact, the absence of gravity, that is, microgravity, affects almost all aspects of human physiology, which has been partly attributed to changes in the biological behaviors of stem cells. In this review, we summarize the current understanding of the effects of microgravity on stem cell differentiation that control the fate of stem cells.
- PublicationOpen AccessStandardized grossing protocol is useful for the pathology reporting of malignant neoplasms other than adenocarcinomas(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Liszka, Łukasz; Mrowiec, Sławomir; Kuśnierz, Katarzyna; Kajor, MaciejBackground: There is no universally accepted protocol for gross examination of pancreaticoduodenectomy specimens. Standardized protocol (SP), known as Leeds Pathology Protocol, was previously validated in pancreatic adenocarcinoma. In this study we aimed to assess usefulness of SP in a series of specimens with pancreatic, ampullary, and duodenal malignant neoplasms other than adenocarcinomas. Materials and methods: SP was based on multi-colour inking and serial slicing of the specimens in a plane perpendicular to the duodenal axis. SP was used in a prospective cohort of 35 neoplasms of neuroendocrine, acinar, and solidpseudopapillary lineage (SP cohort). Surgical margin status, primary tumour stage, and lymph node yield in SP group were compared with corresponding data of a historical cohort of 19 cases examined using nonstandardized protocol (NSP). Samples examined in NSP and SP cohorts were comparable in terms of basic clinical characteristics, median tumour diameter, and distribution of histopathological diagnostic categories. Results: In SP cohort we noticed: (1) higher rate of detection of tumour tissue at surgical margins, (2) more frequent peripancreatic fat tissue invasion, (3) higher percentage of perineural invasion, (4) larger number of lymph nodes retrieved from the specimen, in comparison to NSP group. Application of SP was associated with significantly higher number of tissue blocks taken for histology. Conclusions: SP can be successfully applied for macroscopical examination of pancreaticoduodenectomy specimens with malignant pancreatic, ampullary, and duodenal neoplasms other than adenocarcinomas. SP with proper microscopical diagnosis enables an appropriate schedule of patients with these neoplasms to adjuvant therapy and surveillance programmes.
PublicationMetadata onlyAn immunohistochemical study of NFE2L2, KEAP1 and 8-hydroxy-2'-deoxyguanosine and the EMT markers SNAI2, ZEB1 and TWIST1 in metastatic melanoma(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Hintsala, Hanna Riikka; Haapasaari, Kirsi Maria; Soini, Ylermi; Karihtala, PeeterBackground: Little is known regarding the role of redox balance regulators in metastatic melanomas, but there is some evidence for a link between epithelial-to-mesenchymal transition (EMT) and cellular redox status. Methods: We compared the immunohistochemical expression of nuclear factor erythroid-2-related factor 2 (NFE2L2), Kelch-like ECH-associated protein 1 (KEAP1), 8-hydroxy-2'-deoxyguanosine (8-OHdG), TWIST1, SNAI2 and ZEB1 between primary melanomas and metastases in a cohort of 23 nevi, 66 malignant melanomas and 22 metastases. Results: Nuclear NFE2L2 expression was higher (p=0.003) and cytoplasmic KEAP1 lower (p=0.026) in metastatic lesions than at primary sites. Nuclear NFE2L2 expression was associated with the presence of distant metastases (p=0.040) and with nuclear TWIST1 expression (p=0.002). Patients having both NFE2L2 and TWIST1 expression in nuclei had an extremely poor prognosis (p=0.0003). In multivariate analysis nuclear TWIST1 expression was an independent predictor of a poorer prognosis (HR 2.99, 95% CI 1.17-7.69; p=0.023) and the invasive TWIST1/ZEB1 phenotype showed poorer melanoma-specific survival (HR 7.28, 95% CI 2.23-23.77; p=0.001). Nuclear expression of 8-OHdG (p=0.001) was lower at metastatic sites than in primary lesions. Conclusions: EMT signalling and the KEAP1/NFE2L2- axis are likely to be involved in metastatic spread of malignant melanoma and also appear to have potential interactions.- PublicationOpen AccessHAVcR-1 involvement in cancer progression(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Telford, Emily J.A.; Jiang, Wen G.; Martin, Tracey A.Formerly known for its importance in the immune system and kidney regeneration, it is becoming more apparent that HAVcR-1 is an important protein in cancer biology. HAVcR-1 is overexpressed in numerous cancers and associates with critical molecules of tight junctions. Tight junctions are critical in homeostasis of cellular compartments via the maintenance of epithelia and endothelia however it has also be suggested that via the prevention of dissemination, intravasation and extravasation, tight junctions play a critical role in the prevention of cancer metastasis. HAVcR-1 shedding and the production of the HAVcR-1 ectodomain has been linked to increased IL-6 thus implicated it in the process of angiogenesis via the activation of the STAT3 pathway leading to increased HIF-1α. The HAVcR-1 ectodomain has also been shown to be a potential urinary biomarker in certain cancers. HAVcR-1 is potentially important molecule both for the detection of cancer and the treatment of cancer by being a novel target for anticancer therapeutics.
- PublicationOpen AccessHippocampal expressions of metallothionein I/II and glycoprotein 96 in EAE-prone and EAE-resistant strains of rats(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Grubić Kezele, Tanja; Blagojević Zagorac, Gordana; Jakovac, Hrvoje; Domitrović, Robert; Radošević Stašić, BiserkaInflammatory demyelinating diseases such as multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) are often followed by cognitive deficits associated with the neuronal injury, synaptic loss and altered neurogenesis within the hippocampus. Changes depend on the genetic and epigenetic factors that ensure the cellular and environmental homeostasis and regulate the interactions of immunocompetent, glial and neural cells. Owing to high impact of stress proteins on these processes, in this study we compared the protein content of interleukin-6, transforming growth factor-β1, metallothioneins I/II (MTs) and glycoprotein 96 (gp96) in the hippocampus of DA and AO rats that differ in the susceptibility to the induction of EAE, and tested the relationship of MTs and gp96 to granule neurons, glial cells and neural progenitors in different subfields of dentate gyrus. Rats were immunized with bovine brain homogenate emulsified in complete Freund’s adjuvant or only with CFA. The data showed that acute attack of EAE in DA rats was followed by accumulation of IL-6, TGF-β1 and MTs proteins, by increased expression of MTs in molecular and granular cell layer, by reduced expression of gp96/granular cell, by apoptosis and by microgliosis with appearance of Iba-1+ cells, co-expressing MT I/II and gp96. Furthermore, in subgranular zone (SGZ) of DA rats an augmented number of GFAP+ precursors, but decreased number of doublecortin (DCX)+ neuroblasts and immature NeuN+ neurons were found, implying that in DA rats the neurogenesis was delayed or reduced. Besides, in SGZ of both strains several DCX+ and NeuN+ cells co-expressing gp96 and MT I/II were found.
- PublicationOpen AccessEffect of coenzyme A on outer hair cells in cisplatin ototoxicity: functional and ultrastructural study(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Fernández Cervilla, Francisco; Martínez Martínez, María; Fernández Segura, Eduardo; Cañizares García, Francisco Javier; Crespo Ferrer, Pascual VicenteThe aim of this study was to use functional and morphological analyses to evaluate the protective effect of coenzyme A (CoA) in cisplatin-induced toxicity in outer hair cells (OHC). Three groups of 8 guinea pigs were used: control (group I), cisplatin-treated (group II) and cisplatin + CoA-treated (group III). In groups II and III, a single ototoxic dose of cisplatin (10 mg/kg) was injected intraperitoneally. Group III was co-treated with CoA (900 μg/kg per day for 7 consecutive days). Electrocochleography (ECoG) recordings were made before and after the 7-day treatment period in all groups. After ECoG on day 7, all animals were anesthetized and the cochleae were removed and fixed for ultrastructural analysis. Cell damage in OHC was observed with transmission electron microscopy. Cisplatin induced a significant increase in auditory thresholds (p<0.001) compared to group I (control). In contrast, group III (cisplatin + CoA) had significantly reduced thresholds (p<0.001) compared to the group treated with cisplatin alone (group II). We found no significant differences between the control group and animals co-treated with cisplatin and CoA. The electron microscopy findings in OHC were consistent with these results. Ultrastructural analysis of OHC in group II showed morphological indications of necrosis, i.e. cytoplasmic swelling and vacuolation, and mitochondrial swelling. In group III the cell morphology of OHC was preserved, with ultrastructural characteristics similar to the control group. In conclusion, co-treatment with cisplatin with CoA inhibited antineoplastic-induced cytotoxicity in OHC in a guinea pig model.
- PublicationOpen AccessImmunohistochemical analysis of thymidylate synthase expression in gastric carcinoma: correlation with clinicopathological parameters and survival(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Rogoza Mateja, Wiesława; Domagala, Pawel; Kaczmarczyk, Mariusz; Mieżyńska Kurtycz, Joanna; Ławniczak, Małgorzata; Sulżyc Bielicka, Violetta; Bielicki, Dariusz; Karpińska Kaczmarczyk, Katarzyna; Domagala, WenancjuszThe correlation of thymidylate synthase (TS) expression in gastric cancers with tumor histology and prognostic or predictive information remains unclear. Most studies have involved Asian populations, with few conducted in European cohorts. Moreover, all published studies analyze TS expression using semi-quantitative methods. This retrospective study evaluated the association of TS expression in tumor cells with gastric carcinoma histological type, with selected clinicopathological parameters, and with the prognosis of patients who underwent surgical treatment. TS expression was detected using immunochemistry and objectively assessed by computerized image analysis of tumor cells in 100 gastric cancers. We found that high TS expression was significantly more common in intestinal than in diffuse type of gastric cancer according to Lauren classification (P=0.0003); in type I carcinomas compared to type IV according to Goseki classification (P=0.002); and in gastric cancers in men than women (P=0.04). Low TS expression was found more often in carcinomas in the middle and lower third of the stomach than in cancers in the upper third of the stomach (P=0.009 and P=0.001, respectively). In the subgroup of 25 patients without lymph node metastases (stage I+II), high TS expression was associated with better DFS (83% for high TS expression versus 38,5% for low TS expression, P=0.03). The results: (1) indicate significant correlation between the Lauren and Goseki histopathological classifications of gastric cancer and TS expression in tumor cells, (2) suggest that high TS expression may be a positive prognostic marker with regard to DFS in patients with gastric cancer without involvement of regional lymph nodes who underwent radical surgical treatment and were not treated with preoperative chemotherapy. Prognostic results need confirmation in larger cohorts.
- PublicationOpen AccessSmoothelin and WT-1 expression in glomus tumors and glomuvenous malformations(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Aneiros Fernandez, Jose; Retamero, Juan Antonio; Husein ElAhmed, Husein; Carriel, Víctor; Ruiz Villaverde, Ricardo; O’Valle, Francisco; Aneiros Cachaza, JoseBackground: Smoothelin is a specific marker for smooth muscle cells with contractile capacity which has not been widely studied in glomus lesions. In the same way, the expression for Wilms tumor 1 (WT1) has only been studied occasionally in the endothelial cells of glomovenous malformations and in the glomus cells of glomus tumours. Objective: We studied the significance of immunohistochemical expression of smoothelin and WT1 in 25 glomus lesions. Methods: We assessed 9 cases of solid glomus tumors (SGT), 8 cases of glomus tumors with vascular ectasia (VEGT), 2 cases of glomangiomyomas (GMM) and 6 cases of glomuvenous malformation (GM). Immunohistochemistry was performed, evaluating the expression of WT1, smoothelin, smooth muscle actin (SMA), smooth muscle myosin (SMM), h-caldesmon and desmin. Results: Glomic cells showed cytoplasmic positivity for smoothelin, and WT1 expression was present in all studied cases. SGT showed WT1 positivity in all endothelia. However, in regarding VEGT and GMM, WT1 endothelial expression was positive in some areas, but not in others. GM did not show endothelial cell positivity for WT1. Conclusions: Smoothelin expression in glomic cells indicates that they are contractile smooth muscle cells, and thus its role in routine diagnosis should be considered. The absence of WT1 expression in the endothelium of the vascular structures of the GM is a differential characteristic between SGT, VEGT and GMM.