Browsing by Subject "Malignancy"
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- PublicationOpen AccessA clinicopathologic study of paragangliomas of the urinary bladder: can the clinical behavior of the tumor be predicted?(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Guo, Shuangping; Fan, Chaoliang; Rohr, Joseph; Fan, Linni; Wang, Yingmei; Li, Mingyang; Li, Xia; Guo, Ying; Yan, Qingguo; Wang, Lu; Wang, ZheParaganglioma of the urinary bladder is rare but even more unusual as no singular histologic feature is consistently characteristic of malignancy. Additionally, paragangliomas can manifest in hypertensive crisis for clinicians resecting the tumors in unusual locations without proper histologic diagnosis. Herein we report nine cases of paraganglioma of the urinary bladder with immunohistologic study and follow-up information, including one rare malignant case with liver metastasis. Comparison of the immunohistologic features reveal that the malignant case shows the common features suggested by both the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and Grading of Adrenal Pheochromocytoma and Extraadrenal Paraganglioma (GAPP) system. The predominant histopathologic features of malignant cases were large irregular nests with focal spindle tumor cells and a diffusely infiltrative growth pattern between smooth muscle of the urinary bladder wall with multiple necrotic areas and a high proliferative index. Eight cases without metastasis showed the classic zellballen of benign paragangliomas without irregular nests and welldemarcated nodules either in the submucosa or between smooth muscle bundles with no diffuse infiltration. We discuss the histopathologic and immunohistochemical features detecting malignant behavior, and comprehensively review the previously published cases of malignant paraganglioma of the urinary bladder. In summary, we assess some clinicopathologic features which might help to predict which neoplasms are more likely to behave in a clinically aggressive manner to avoid adverse outcomes in this rare tumor’s resection.
- PublicationOpen AccessAutophagy related markers (Beclin-1 and ATG4B) are strongly expressed in Wilms' tumor and correlate with favorable histology(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Guimei, Maha; Ahmed Eladl, Mohamed; Vinod Ranade, Anu; Manzoor, ShaistaBackground. Wilms’ tumor treatment has achieved great success in the last decade. Nevertheless, some cases still fail to respond to the current multimodality therapy. These cases fall mainly in the unfavorable histology group with very few belonging to the favorable histology group. In recent years, autophagy manipulation whether inhibition or stimulation has been shown to affect cancer cell behavior and has emerged as a novel mechanism to improve cancer cell response to currently used therapeutic regimens. Objective. The current study aimed to investigate the expression of autophagy related markers (ATG4B and Beclin1) in WT, its association with the different clinicpathological parameters and its impact on patient survival. Methods. Twenty-one formalin fixed paraffin embedded (FFPE) WT specimens were immunohistochemically stained using autophagy related markers; Beclin-1 and ATG4B. All clinical, radiological and follow up data were retrieved from the patient records. Results. All specimens showed positive expression of both Beclin-1 and ATG4B. The staining score for Beclin1 varied between 50 and 300, and its expression was significantly associated with favorable histology (p=0.007). Similarly, ATG4B expression was significantly higher in favorable histology tumors compared to unfavorable histology (p=0.046). A statistically significant positive correlation between Beclin-1 and ATG4B expression was observed. The cumulative disease-free survival in patients with favorable histology was significantly higher compared to patients with unfavorable histology (p=0.0027). Conclusions. Beclin-1 and ATG4B expression were both found to be statistically significant discriminators of survival. Collectively these findings suggest that the expression of autophagy-related markers is associated with a favorable histology and could predict better survival in these patients.
- PublicationOpen AccessBone remodelling and tumour grade modifications induced by interactions between bone and swarm rat chondrosarcoma(Murcia : F. Hernández, 2002) Grimaud, E.; Damiens, C.; Rousselle, A.V.; Passuti, N.; Heymann, D.; Gouin, F.Chondrosarcoma is currently defined as a malignant cartilage tumour arising de novo or within a pre-existing benign cartilage tumour. Chondrosarcoma can be surgically resected, but all grades have significant rates of local recurrence. The purpose of the present study was to develop an animal intraosseous chondrosarcoma model simulating the progression of human chondrosarcoma and elucidating its behaviour and biology. An intraosseous Swarm rat model was designed to assess interactions between bone and chondrosarcoma. A comparison of tumour grading was carried out according to transplantation site. The effects of chondrosarcoma cells (SRC cells) on the mineralisation capacities of osteoblasts and on osteoclast differentiation were studied in relation to modifications observed in vivo at the cellular level. Transplantation of Swarm rat chondrosarcoma within bone marrow or contiguous to induced periosteal lesions led to extensive bone remodelling with trabecular bone rarefaction and periosteal apposition. Transplantation in close contact to bone but without any periosteal lesion had no effect on bone, suggesting that bone healing factors interact with tumour development. With the intramedullary model, the development of tumours of different grade confirms that bone environment is an important factor in malignancy. A decrease of bone nodule formation was noted after cocultures of SRC cells with rat bone marrow, but there was no modification of osteoclast differentiation after cultures of total rabbit bone cells with SRC cells. These data reveal the importance of interactions between bone environment and tumour in inducing bone remodelling and variations in tumour malignancy.
- PublicationOpen AccessExpression of Ccdc85C, a causative protein for murine hydrocephalus, in the mammary gland tumors of dogs(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Tanaka, Natsuki; Izawa, Takeshi; Takenaka, Shigeo; Akiyoshi, Hideo; Yamate, Jyoji; Kuwamura, MitsuruCoiled-coil domain containing 85c (Ccdc85c) is a causative gene for hemorrhagic hydrocephalus mouse which shows hydrocephalus with frequent brain hemorrhage and formation of subcortical band heterotopia. A previous study revealed that Ccdc85C protein is expressed in the systemic simple epithelial cells with proliferative activity in rats and suggested that Ccdc85C expression may be related to the cell proliferation of simple epithelial cells. To reveal the roles of Ccdc85C in the proliferative lesion, we examined the expression patterns of Ccdc85C in the mammary gland tumor of dogs, a common representative tumor derived from simple epithelial cells. In canine mammary gland tumors, Ccdc85C was expressed at the apical junctions of the luminal epithelial cells. Ccdc85C was also distributed throughout the entire cytoplasm of the myoepithelial cells. Ccdc85C expression was observed at the epithelial cells with luminal structures, but was not observed at the epithelial cells forming sheet growth pattern without luminal structure. In carcinomas, Ccdc85C expression in mammary tumor tissue tended to be weaker than that in surrounding normal mammary gland tissue. Ccdc85C is known to cause neurological diseases such as hydrocephalus, and subcortical heterotopia, and the present study is the first to demonstrate Ccdc85C expression in canine mammary tumors and a relationship between Ccdc85C expression and tumor malignancy
- PublicationOpen AccessMDM2 beyond cancer: podoptosis, development, inflammation, and tissue regeneration(Universidad de Murcia. Departamento de Biología Celular e Histología, 2015) Ebrahim, Martrez; Mulay, Shrikant R.; Anders, Hans-Joachim; Thomasova, DanaMurine double minute (MDM)-2 is an intracellular molecule with diverse biological functions. It was first described to limit p53-mediated cell cycle arrest and apoptosis, hence, gain of function mutations are associated with malignancies. This generated a rationale for MDM2 being a potential therapeutic target in cancer therapy. Meanwhile, several additional functions and pathogenic roles of MDM2 have been identified that either enforce therapeutic MDM2 blockade or raise caution about potential side effects. MDM2 is also required for organ development and tissue homeostasis because unopposed p53 activation leads to p53-overactivation-dependent cell death, referred to as podoptosis. Podoptosis is caspaseindependent and, therefore, different from apoptosis. The mitogenic role of MDM2 is also needed for wound healing upon tissue injury, while MDM2 inhibition impairs re-epithelialization upon epithelial damage. In addition, MDM2 has p53-independent transcription factor-like effects in nuclear factor-kappa beta (NFκB) activation. Therefore, MDM2 promotes tissue inflammation and MDM2 inhibition has potent antiinflammatory effects in tissue injury. Here we review the biology of MDM2 in the context of tissue development, homeostasis, and injury and discuss how the divergent roles of MDM2 could be used for certain therapeutic purposes. MDM2 blockade had mostly antiinflammatory and anti-mitotic effects that can be of additive therapeutic efficacy in inflammatory and hyperproliferative disorders such as certain cancers or lymphoproliferative autoimmunity, such as systemic lupus erythematosus or crescentic glomerulonephritis.
- PublicationOpen AccessPredictive values of clinical and pathological parameters for malignancy of gastrointestinal stromal tumors(Murcia : F. Hernández, 2009) Hou, Ying-Yong; Lu, Shao-Hua; Zhou, Yang; Xu, Jian-Fang; Ji, Yuan; Hou, Jun; Qi, Wei-Dong; Shi, Yuan; Tan, Yun-Shan; Zhu, Xiong-ZengGastrointestinal stromal tumors (GISTs) possess a wide spectrum of biological properties, from indolent to highly aggressive. In this study, we evaluated a set of clinical and pathological parameters for their predicative values for malignancy of GISTs by retrospective reviews of tumor specimens and their relevant medical records from 840 patients. All GIST cases were first assigned as malignant if they met any of the following criteria: gross spreads, including liver metastassis and/or peritoneal dissemination, microscopic spreads, including lymph node metastasis, infiltrations to vascular, fat, nerve and muscularis mucosal tissues, or relapse. The remaining cases were recorded as biological behavior uncertain. This initial assignment revealed a set of five morphological features to be associated with malignancy. They were: mitotic counts greater than 10 per 50HPFs (P<0.0001), muscularis propria infiltration (P<0.0001), coagulative necrosis (P<0.0001), perivascular growth pattern (P=0.005), and severe nuclear atypia (P=0.014). Therefore, a new classification system, including criteria of 2 gross spreads, 5 microscopic spreads, and 5 histopathological parameters was developed. All the GIST cases were re-classified into a group of 485 malignant tumors, and a group of 355 nonmalignant tumors. Patient follow-up data revealed 5-year disease-free and overall survival rates as high as 99.3% and 100% for the nonmalignant group, but low rates of 43.9% and 59.7% for the malignant group. These results demonstrated a correlation of the new classification with clinical outcomes. Therefore, this set of 12 parameters has predictive values for malignancy of GISTs, and is potentially useful in the grading of the tumors.
- PublicationOpen AccessThe “early birds”: natural IgM antibodies and immune surveillance(Murcia : F. Hernández, 2005) Vollmers, H.P.; Brändlein, S.Precancerous epithelial lesions are sites of uncontrolled cellular proliferation generated by irreversible genetic alterations. Not all of those lesions progress to invasive cancer, some may even regress, but the early detection of abnormal cells can be crucial for patient survival. Immune surveillance mechanisms are responsible for the removal of transformed cells and antibodies play an important role in these immune processes. In the past, analysis of the immunoglobuline repertoire has focused mainly on xenoimmunizations or the investigation of cancer patient immunity. The human hybridoma technology (Trioma technique) offers the unique possibility to study the humoral immunity of healthy people. Using this technique a series of tumorbinding antibodies could be isolated which all have several features in common: they are germ-line coded IgM antibodies, they predominantly bind to carbohydrates on post-transcriptionally modified antigens, they induce apoptosis and, most importantly, they detect not only malignant cells but also precursor stages. These data demonstrate that the body has a comprehensive defense system against malignant cells based on the production of natural antibodies.