Induction of Cancer in the Rat Bladder: Pathogenesis, Role of Cell Proliferation, and Relevance to Human Disease

Author(s):  
Samuel M. Cohen
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Mengdie Cao ◽  
Xiangyuan Luo ◽  
Kongming Wu ◽  
Xingxing He

AbstractIn recent years, accumulating evidence has elucidated the role of lysosomes in dynamically regulating cellular and organismal homeostasis. Lysosomal changes and dysfunction have been correlated with the development of numerous diseases. In this review, we interpreted the key biological functions of lysosomes in four areas: cellular metabolism, cell proliferation and differentiation, immunity, and cell death. More importantly, we actively sought to determine the characteristic changes and dysfunction of lysosomes in cells affected by these diseases, the causes of these changes and dysfunction, and their significance to the development and treatment of human disease. Furthermore, we outlined currently available targeting strategies: (1) targeting lysosomal acidification; (2) targeting lysosomal cathepsins; (3) targeting lysosomal membrane permeability and integrity; (4) targeting lysosomal calcium signaling; (5) targeting mTOR signaling; and (6) emerging potential targeting strategies. Moreover, we systematically summarized the corresponding drugs and their application in clinical trials. By integrating basic research with clinical findings, we discussed the current opportunities and challenges of targeting lysosomes in human disease.


2020 ◽  
Author(s):  
Lungwani Muungo

TRIM44 has oncogenic roles in various cancers. However, TRIM44 expression andits function in renal cell carcinoma (RCC) are still unknown. Here in this study, weinvestigated the clinical significance of TRIM44 and its biological function in RCC.TRIM44 overexpression was significantly associated with clinical M stage, histologictype (clear cell) and presence of lymphatic invasion (P = .047, P = .005, and P = .028,respectively). Moreover, TRIM44 overexpression was significantly associated withpoor prognosis in terms of cancer-specific survival (P = .019). Gain-of-function andloss-of-function studies using TRIM44 and siTRIM44 transfection showed thatTRIM44 promotes cell proliferation and cell migration in two RCC cell lines, Caki1and 769P. To further investigate the role of TRIM44 in RCC, we performed integratedmicroarray analysis in Caki1 and 769P cells and explored the data in the Oncominedatabase. Interestingly, FRK was identified as a promising candidate target gene ofTRIM44, which was downregulated in RCC compared with normal renal tissues. Wefound that cell proliferation was inhibited by TRIM44 knockdown and then recoveredby siFRK treatment. Taken together, the present study revealed the associationbetween high expression of TRIM44 and poor prognosis in


2021 ◽  
Vol 13 (1) ◽  
pp. 17-29
Author(s):  
Emann M Rabie ◽  
Sherry X Zhang ◽  
Andreas P Kourouklis ◽  
A Nihan Kilinc ◽  
Allison K Simi ◽  
...  

Abstract Metastasis, the leading cause of mortality in cancer patients, depends upon the ability of cancer cells to invade into the extracellular matrix that surrounds the primary tumor and to escape into the vasculature. To investigate the features of the microenvironment that regulate invasion and escape, we generated solid microtumors of MDA-MB-231 human breast carcinoma cells within gels of type I collagen. The microtumors were formed at defined distances adjacent to an empty cavity, which served as an artificial vessel into which the constituent tumor cells could escape. To define the relative contributions of matrix degradation and cell proliferation on invasion and escape, we used pharmacological approaches to block the activity of matrix metalloproteinases (MMPs) or to arrest the cell cycle. We found that blocking MMP activity prevents both invasion and escape of the breast cancer cells. Surprisingly, blocking proliferation increases the rate of invasion but has no effect on that of escape. We found that arresting the cell cycle increases the expression of MMPs, consistent with the increased rate of invasion. To gain additional insight into the role of cell proliferation in the invasion process, we generated microtumors from cells that express the fluorescent ubiquitination-based cell cycle indicator. We found that the cells that initiate invasions are preferentially quiescent, whereas cell proliferation is associated with the extension of invasions. These data suggest that matrix degradation and cell proliferation are coupled during the invasion and escape of human breast cancer cells and highlight the critical role of matrix proteolysis in governing tumor phenotype.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tiantian Tang ◽  
Guiying Wang ◽  
Sihua Liu ◽  
Zhaoxue Zhang ◽  
Chen Liu ◽  
...  

AbstractThe role of organic anion transporting polypeptide 1B3 (SLCO1B3) in breast cancer is still controversial. The clinical immunohistochemical results showed that a greater proportion of patients with negative lymph nodes, AJCC stage I, and histological grade 1 (P < 0.05) was positively correlated with stronger expression of SLCO1B3, and DFS and OS were also increased significantly in these patients (P = 0.041, P = 0.001). Further subgroup analysis showed that DFS and OS were significantly enhanced with the increased expression of SLCO1B3 in the ER positive subgroup. The cellular function assay showed that the ability of cell proliferation, migration and invasion was significantly enhanced after knockdown of SLCO1B3 expression in breast cancer cell lines. In contrast, the ability of cell proliferation, migration and invasion was significantly reduced after overexpress the SLCO1B3 in breast cancer cell lines (P < 0.05). Overexpression or knockdown of SLCO1B3 had no effect on the apoptotic ability of breast cancer cells. High level of SLCO1B3 expression can inhibit the proliferation, invasion and migration of breast cancer cells, leading to better prognosis of patients. The role of SLCO1B3 in breast cancer may be related to estrogen. SLCO1B3 will become a potential biomarker for breast cancer diagnosis and prognosis assessment.


1991 ◽  
Vol 266 (7) ◽  
pp. 4214-4219
Author(s):  
H Tomoda ◽  
K Igarashi ◽  
J C Cyong ◽  
S Omura

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