Five human renal carcinoma cell lines have been established in long-term tissue culture. Two of the cell lines, UM-RC-2 and UM-RC-3, produced clear cell tumors in athymic nude mice. The cell lines have been characterized by staining with oil red O, doubling time in vitro, and number of chromosomes. Although protein A assay reactivity of autologous combinations of patient's sera and tumor cells were seen with all five cell lines, similar binding was also found with autologous normal kidney cultures. However, the immune adherence assay demonstrated low titer autologous reactivity with two renal carcinoma cell lines but not with the corresponding normal kidney cultures. This strongly suggest host recognition of tumor-associated antigens. Characterization of cell surface antigens with murine monoclonal antibodies demonstrated shared reactivity between normal kidney tubular cells and renal carcinoma cells. Antibody A68.11 reacted strongly with all five cell lines. Antibody A80 bound to only UM-RC-3 and UM-RC-6.
The uptake and efflux of doxorubicin (Dox) were investigated in a human bladder cancer cell line (UM-UC-6) and in a multi-drug resistant (mdr) subline (UM-UC-6Dox). Unlike previous reports, the initial uptake kinetics of Dox, and its accumulation and retention to steady-state were modelled mathematically. Cells were incubated with Dox and the amount of Dox in the cellular and medium phases was measured by a specific HPLC method. When monitored for 1 min from 0.02 microM to 25 microM Dox, the uptake was very rapid but was significantly faster in the resistant cell line. The initial rate of uptake at t = 0 followed Michaelis-Menten kinetics yielding Vmax values (the maximal rate of uptake) of 15.0 +/- 1.7 and 12.9 +/- 1.2 nmol/10(6)/min and Km (rate at Vmax/2) of 25.2 +/- 4.7 and 16.4 +/- 2.9 microM for UM-UC-6 and UM-UC-6Dox, respectively. There was no metabolism of Dox by keto-reduction or reductive hydrolysis. At 1.0 microM the uptake of Dox to steady-state was biexponential but there was no difference in total cellular Dox concentration between the two cell lines at equilibrium. A 3 compartment sequential closed model was fitted yielding significantly different values for the intercompartmental and hybrid rate constants, indicating altered intracellular distribution in resistant cells. Verapamil (10 microM), trifluoperazine (10 microM) or Tween 80 (0.005%) had no effect on the uptake or efflux of Dox. The UM-UC-6Dox line appeared to show atypical mdr characteristics since net drug accumulation was not lowered and classic P-glycoprotein inhibitors were not effective. The primary mechanism of Dox resistance is not enhanced metabolism or lowered intracellular concentrations.
Bladder cancer can be viewed as a prototype for carcinogen-induced neoplasia. This has been demonstrated experimentally in a variety of systems and in man through epidemiological studies of occupational exposure to putative carcinogens. The natural history of this neoplasm demonstrates recurrence in time and space, i.e., multifocal disease. This clinical scenario is precisely what would be expected if a target tissue, e.g., urothelium, was continuously exposed to a weak carcinogen. The detection of gross disease is clinically easy. However, the ability to intervene at early stages and monitor the success of this treatment requires the definition of early markers for bladder cancer.lntegrins are a family of cell surface proteins, many of which function as receptors for extracellular matrix components.Normal epithelial cells express the integrin a6P4 in association with an anchoring structure known as the hemidesmosome. Urothelium expresses a6P4 on the basal layer of cells similar to the distribution seen on other epithelial surfaces. Even early stages of bladder cancer demonstrate an alteration in the expression of this integrin. Low-stage bladdertumors express asp4 diffusely throughout the tumor as well as at the invading margin. Altered expression of a6P4 may be an early marker for bladder cancer which may contribute to an invasive phenotype. A second potential marker is detected by DD23, an lgGl murine monoclonal antibody triggered by the immunization of a BALBk mousewith afresh human bladdertumor specimen. The antigen detected by DD23 is not present on normal urothelial specimens. It is expressed on 81 %of bladder tumors tested and is present on both low-grade, non-invasive and high-grade, invasive tumors. Although no normal bladder or ureteral tissues were DD23-positive, two of five histologically normal bladder areas from patients who had radical cystectomies for bladder cancer expressed the DD23 antigen. The significance of this finding has not yet been completely evaluated; however, it may represent an early neoplastic change prior to obvious histologic abnormality.Antigens associated with bladder cancer may be helpful in the early detection of bladder cancer and in providing markers useful in future chemoprevention trials. o 1992 Wiley-Liss, Inc. including cytology, flow cytometry, cystoscopy, and a variety of imaging techniques. However, the detection of sub-clinical changes has proved t o be a significant challenge.Cancer is manifested as alterations in the morphology and behavior of normal cells. At a sub-microscopic level, these changes are associated with modifications in cellular proteins and lipids. Some of these abnormally expressed cellular constituents have been used as tumor markers. One example of this phenomenon is the altered blood group antigen expression associated with bladder cancer cells [3]. We have focused our efforts on evaluating alter- ations in antigen expression in bladder cancer to determine how these changes result in the malignant phenotype. Our laboratory has develope...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.