DigitalUM :: Browsing by Subject "Pathogenesis"

Browsing by Subject "Pathogenesis"

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Open Access
A brief review of chordomas: pathogenesis, prognostic factors and therapeutic targets
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Hai, Bao; Ma, Yunlong; Liu, Xiaoguang
Chordomas are rare but locally aggressive cancer, which originate from primitive notochord remnants. Guidelines have recently been proposed to include the option of choosing chordomas in different locations. However, there is still a great challenge in the modern management of chordomas, primarily due to the high recurrence rate and poor prognosis. On this basis, there is a high demand for new therapeutic approaches and reliable prognostic factors. Recent progress in studying the molecular basis of this specific type of cancer has deepened the understanding of this mechanism, which overall facilitates the discovery of specific biomarkers or indicators of the disease. It also gives rise to potential targeted therapies against chordomas as evidenced by the fact that some RTK inhibitors in a clinical context have been evaluated in relation to chordomas. This article summarizes these achievements including the studies relative to pathogenesis, prognostic factors, and targeted therapies for chordomas. The theme of existing problems is also mentioned, which would facilitate general future efforts in this field.
Open Access
Barrett esophagus and cancer: pathogenesis, carcinogenesis, and diagnostic dilemmas
(Murcia : F. Hernández, 1999) Polkowski, W.; Van Lanschot, J.J.B.; Offerhaus, G.J.A.
A metaplastic process, in which native squamous epithelium of the distal esophagus is replaced by columnar epithelium, is known as Barrett esophagus (BE). Over the past years, intestinal metaplasia was recognized as a marker for BE. The risk for the development of esophageal adenocarcinoma in a patients with BE is much hi"gh er when com~aredto the normal population. Duodeno-gastro-esophageal reflux is supposed to play a role in the pathogenesis of BE and rising incidence of adenocarcinoma of the esophagus. With current therapeutic options, when clinical manifestation of this cancer occurs, it is too late for cure in the majority of patients. Therefore, attention should be focused on early diagnosis, for which molecular genetic techniques might become available. Current data on genetic alterations involved in carcinogenesis of BE are discussed. Grading of dysplasia in BE carries important clinical consequences for the individual patient: intensification of endoscopic surveillance or 'prophylactic esophagectomy'. Several morpho- andlor cytometric parameters may be used for discrimination between different grades of dysplasia in BE. Therefore, a new and original algorythm for the potential application of quantitative pathology in grading of dysplasia in patients with BE has been proposed. Molecular biology together with image analysis of histological spectrum of BE enable better understanding of the mechanisms of malignant degeneration and might ultimately lead to targeted cancer prevention andlor therapeutic interventions.
Open Access
Current concepts in ovarian epithelial tumorigenesis: correlation between morphological and molecular data
(Murcia : F. Hernández, 2006) Scott, Mike; McCluggage, W.G
Ovarian carcinoma is the most lethal gynaecological malignancy, most tumours being advanced at presentation. However, little is known about precursor lesions and the cell of origin of epithelial ovarian malignancy. In this review, the proposed cell of origin is discussed as well as recent molecular data relating to ovarian cancers of different morphological types. It is stressed that ovarian carcinoma is a heterogeneous group of neoplasms with several different morphological types, each with their own underlying molecular genetic events. Recent data suggest that mucinous ovarian cancers and a small subset of serous cancers (low grade ovarian serous carcinoma) develop through a well-defined adenoma-carcinoma sequence while the much more common high grade ovarian serous carcinoma develops de novo from the ovarian surface epithelium or the epithelium of cortical inclusion cysts. The realisation that various morphological types of epithelial ovarian cancer are associated with different molecular genetic events is a major advance in the study of ovarian cancer. It can be anticipated that this will lead to the development of specific therapeutic agents of value against a specific tumour type.
Open Access
Diabetic nephropathy, the modulating influence of glucose on transforming factor D production
(Murcia : F. Hernández, 1998) Phillips, A.O.
Diabetes in now the commonest cause of renal failure in the western world. Furthermore the survival of diabetic patients requiring dialysis treatment for renal failure is far less than patients with renal failure secondary to all other diseases. It is therefore important to identify the factors that control the development of progressive renal disease to allow targeted therapeutic interventions which would have major implications both to patient well-being and also to the provision of health care world wide. In this review we discuss possible metabolic consequences of hyperglycemia and their role in the pathogenesis of diabetic nephropathy. We also focus on the involvement of the pro-fibrotic cytokine Transforming Growth Factor B, and contrast its role in the pathogenesis of glomerular and tubulo-interstitial changes seen in diabetic nephropathy.
Open Access
E2F1-induced upregulation of TROAP contributes to endometrial cancer progression
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Wang, Shanshan; Sun, Yidan; Guo, Minjing; Zhu, Ping; Xin, Beibei
Purpose. To investigate the role of Trophinin-associated protein (TROAP) in endometrial cancer (EC) progression and elucidate how the transcription factor E2F transcription factor 1 (E2F1) modulates EC by upregulating TROAP expression. Methods. TROAP expression in EC tissues and cell lines was analyzed using bioinformatics databases, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and immunohistochemistry. TROAP was knocked down in EC cells to assess its effects on proliferation, migration, invasion, and glycolysis. Potential transcription factors regulating TROAP were identified, and the relationship between E2F1 and TROAP gene regulation was examined using dual luciferase assay. In vivo tumor growth was evaluated using a mouse xenograft model. Results. TROAP was overexpressed in EC tissues and cell lines compared with normal controls. High TROAP expression correlated with poor differentiation, advanced stage, lymph node metastasis, and worse overall survival in EC patients. Knockdown of TROAP inhibited the proliferation, migration, invasion, and glycolytic capacity of EC cells. E2F1 was identified as a transcriptional activator of TROAP. E2F1 over-expression enhanced TROAP expression and promoted EC cell proliferation, migration, and glycolysis in a TROAP-dependent manner. TROAP knockdown suppressed tumor growth in vivo. Conclusion. TROAP is transcriptionally activated by E2F1 and promotes EC progression by enhancing cell proliferation, metastasis, and glycolysis. The E2F1-TROAP axis may serve as a potential therapeutic target for EC treatment.
Open Access
Immunohistochemical assessment of cell populations in leprosy-spectrum lesions and reactional forms
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Fachin, Luciana Raquel Vincenzi; Soares, Cleverson Teixeira; Belone, Andrea de Faria Fernandes; Trombone, Ana Paula Favaro; Rosa, Patrícia Sammarco; Guidella, Cássio Cesar; Franco, Marcello Fabiano
In situ immunophenotyping of leprosy lesions can improve our understanding of the biology of inflammatory cells during the immune response to Mycobacterium leprae antigens. In the present study, biopsies from 10 healthy controls and 70 leprosy patients were selected, 10 for each of the following conditions: clinical tuberculoid (TT), borderline tuberculoid (BT), borderline borderline (BB), borderline lepromatous (BL), lepromatous (LL), reversal reaction (R1), and erythema nodosum leprosum (R2). Qualitative and quantitative immunohistochemical analyses were performed to detect CD3, CD4, CD8, FoxP3, CD20, CD138, CD1a, CD57, CD15, CD117, CD68, and CD163. In addition, histochemistry was employed to identify eosinophils. The amount of CD3+ and CD4+ T cells was higher in TT than in LL patients. CD8+ T cells were predominant in T lymphocyte infiltrations in the basal layer of the epidermis. The number of FoxP3+ cells was similar among different forms of the disease, but was higher in BL and LL than in R2 individuals. CD20+ lymphocytes were most abundant in TT samples, while CD138+ plasma cells displayed no detectable differences. Epithelioid macrophages from the center of TT and R1 granulomas exhibited the M1 phenotype (CD68+CD163- ), whereas those in LL granulomas showed the M2 phenotype (CD68+CD163+). There was a gradual decrease in the amount of CD1a+ cells from the TT towards the LL form of the disease. A significant increase in the number of neutrophils was observed only in R2 samples. All the cells investigated, except eosinophils, participated in the immunopathogenesis of leprosy.
Open Access
MiRNAs participate in the diagnosis, pathogenesis and therapy of Parkinson's disease
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Lu, Xuexin; Cui, Zhijie; Liu, Shuang; Yin, Feng
MicroRNAs (miRNAs), one kind of posttranscriptional modification, mediate transcriptional silencing of various metabolic enzymes that are involved in various life processes, including Parkinson’s disease. At present, the pathogenesis of Parkinson's disease is not clear, although many studies suggest that miRNAs play a very important role in the progress of Parkinsonism. This paper reviews the biological characteristics of miRNAs and summarizes the progress of miRNAs in reference to the diagnosis and pathogenesis of Parkinson’s disease. It even considers miRNAs as a potential target for Parkinson’s disease therapy
Open Access
Molecular pathology of adenoid cystic carcinoma
(Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Wei Shuanzeng; Pei Jianming; Zhang Paul J.L.; Biología Celular e Histología
Adenoid cystic carcinoma (ACC) is a slow-growing but locally aggressive salivary gland tumor. ACC is composed of ductal/tubular epithelial cells and basal/myoepithelial cells, which form cribriform, tubular, and solid growth patterns in variable combinations and dominance. ACC from different anatomic sites have similar morphological, molecular, and genetic changes. The key molecular alteration in ACC is chromosomal fusion/rearrangement/trans-location involving MYB or MYBL1, usually with NFIB as a fusion partner. In this review, we summarize the pathology and molecular alterations in ACC and their clinical significance
Open Access
Ovarian cancer: insights into genetics and pathogeny
(F. Hernandez y JuanF. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología., 2012) Liliac, Ludmila; Amălinei, Cornelia; Balan, Raluca; Grigoraş, Adriana; Căruntu, Irina-Draga
Starting from the information on ovarian cancer provided by the mainstream publications, we construct a review focusing on the following issues: (i) the genetic profile, (ii) the role of the epithelial-mesenchymal transition in the acquirement of malignant features, (iii) the controversial hypothesis regarding the origin, and (iv) the involvement of the immune system in the tumoral microenvironment. Advances in the decipherment at the genetic level in the pathogenic mechanisms progressively lead to the idea of a genetic signature for the ovarian cancer. Moreover, the complementary approaches oriented towards the decryption of the intrinsic structure of the expressed molecules and, implicitly, the development of proteomics open new perspectives for an early diagnosis and an appropriate treatment. The research on the epithelial-mesenchymal transition (mainly those exploring the signaling pathways responsible for the switch between the loss of the epithelial characteristics and the gain of a mesenchymal cell phenotype, with results in the amplification of differentiation, motility and tumoral invasion) allow a deeper understanding of the complex pathogenic mechanism which governs ovarian carcinogenesis. The classic conception of ovarian cancer pathogeny, based on the role of the ovarian surface epithelium, is currently reconsidered, and a novel hypothesis is formulated, which supports direct involvement of the Fallopian tubes for the serous type. Although recent research suggests the implication of immune/inflammatory cells by specific mechanisms in ovarian cancer pathogenesis, there is yet reliable evidence concerning their modality of direct action and/or modulation of tumoral growth. Thus, ovarian carcinogenesis remains a research challenge, due to still numerous unknown factors involved in the malignant transformation sequences, originating from the genetic-molecular alterations and reflected by cellular and tissue expression patterns.
Open Access
Overexpression of GRP78 and GRP94 is involved in colorectal carcinogenesis
(Editores F. Hernandez y Juan F. Madrid. Murcia, Universidad de Murcia, Departamento de Biologia Celular e Histologia, 2011) Takahashi, Hiroyuki; Wang, Jian-ping; Zheng, Hua-Chuan; Masuda, Shinji; Takano, Yasuo
Glucose-related proteins (GRPs) are ubiquitously expressed in the endoplasmic reticulum and assist in protein folding and assembly, consequently considered to be molecular chaperones. GRP78 and GRP94 expression was induced by glucose starvation and up-regulated in samples taken from several different malignant tissues. To clarify the roles of both molecules in tumorigenesis and progression of colorectal carcinomas, immunohistochemistry (IHC) was performed on tissue microarrays containing colorectal carcinomas, adenomas and the non-neoplastic mucosa (NNM) using antibodies against GRP78 and GRP94. Their expression was correlated with the clinicopathological parameters of carcinomas. Both proteins were also studied in colorectal carcinoma cell lines (DLD-1, HCT-15, SW480 and WiDr) by IHC and Western blot. There was a gradually increased GRP78 expression from colorectal NNMs, carcinomas, to low-grade and high-grade adenomas (P<0.05), while up-regulated GRP94 expression from NNM, low-grade adenoma, high-grade adenoma, to carcinoma (P<0.05). The expression was similar in all the carcinoma cell lines. GRP78 expression was negatively correlated with lymphatic invasion or low GRP94 expression of the carcinomas (P<0.05), while there was no correlation of GRP94 expression with other parameters of carcinomas (P>0.05). Multivariate analysis showed that venous invasion, lymph node metastasis and UICC staging (P<0.05), but not age, sex, tumor size, differentiation, depth of invasion, lymphatic invasion, GRP78 and GRP94 expression (P>0.05), were independent prognostic factors for carcinomas. It is suggested that up-regulated expression of GRP78 and GRP94 could possibly be involved in the pathogenesis of colorectal carcinomas.
Open Access
Parafibromin expression in lung normal tissue and carcinoma: its comparison with clinicopathological parameters of carcinoma
(Murcia: F. Hernández y Juan F. Madrid, Universidad de Murcia, Departamento de Biología Celular e Histología, 2011) Xia, Pu; Wang, Wei; Xu, Xiao-yan; Wang, Jian-ping; Takano, Yasuo; Zheng, Hua-Chuan
Parafibromin is a protein encoded by the hyperparathyroidism 2 oncosuppressor gene and its down-regulated expression is involved in the pathogenesis of parathyroid, gastric and colorectal carcinomas. To clarify the roles of parafibromin expression in lung carcinomas, it was examined by immunohistochemistry and in situ hybridization on tissue microarray containing lung carcinomas (n=144) and normal lung tissue (n=20), with a comparison to clinicopathological parameters of carcinomas. Lung carcinoma cell lines and tissues were studied for parafibromin expression by Western blot and RT-PCR. Down-regulated expression of parafibromin mRNA was found in lung carcinoma in comparison with matched normal tissue (p<0.05). Parafibromin protein was found in the cilia and nuclei of pseudo-stratified columnar epithelium, and the nuclei of lung carcinoma. According to immunostaining and in situ hybridization, there was no difference in parafibromin expression between histological subtypes of lung carcinoma (p>0.05). The Kaplan-Meier method indicated that nuclear parafibromin expression was positively correlated with adenocarcinoma patients (p<0.05). Down-regulated parafibromin mRNA expression might play an important role in lung carcinogenesis, but not in its histogenesis. Strong parafibromin expression in cilia of the pseudostratified columnar epithelium indicated its possible involvement in cell mobility. Parafibromin expression could be employed to indicate the favorable prognosis of patients with adenocarcinoma.
Open Access
The role of chaperone-mediated autophagy in tissue homeostasis and disease pathogenesis.
(MDPI, 2024-01-23) Martínez Vicente, Marta; Valdor Alonso, Rut; Bioquímica y Biología Molecular B e Inmunología
Open Access
Trophoblast-derived proteins and their effects on the pathogenesis of preeclampsia
(Editum, 2026) Yanan Wang; Xueling Chen; Haifeng Zhang; Yunshan Xue; Haibin Chen; Ju Yang; Biología Celular e Histología
Trophoblast cells are crucial structural units of the placenta, responsible for maintaining its integrity and function. These cells synthesize and secrete specific proteins that play essential roles in placental vascularization, maternal and fetal immune tolerance, and other critical processes. An abnormal level of trophoblast-derived secreted proteins has been closely linked to pregnancy-related diseases. Preeclampsia, a severe complication of pregnancy characterized by de-novo development of hypertension and proteinuria after 20 weeks of gestation, poses significant health risks to both the mother and fetus. This article reviews several key trophoblast-derived proteins that are widely recognized for their roles in preeclampsia. The specific mechanisms of action and interconnections among these proteins in preeclampsia are discussed, along with novel insights into the underlying pathological mechanisms of this disease.

Browsing by Subject "Pathogenesis"

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