摘要:

AbstractThe termcancer chemopreventionrefers to the prevention of prolongation of carcinogenesis by intervention with drugs prior to the malignant (i.e., invasive) stage. The development of chemopreventive drugs is the major objective of the Chemoprevention Branch of the National Cancer Institute. Neoplastic lesions of the urinary bladder present a unique opportunity for evaluating chemopreventive agents because of (1) the accessibility of the lesions to observation and biopsy, and (2) those patients who have been successfully treated for a primary lesion represent a population at unusually high risk for recurrence and/or progression.Although 70–80% of bladder cancers initially present as superficial, papillary transitional cell neoplasms with limited potential for invasion, the incidence of recurrence is high after resection (60–75%). Recurrent tumors are highly unpredictable, and may be of higher grade of stage (progression). Although recurrence is responsible for high treatment‐related morbidity, progression represents the greatest potential for mortality. Thus, potential chemopreventive agents considered here would modulate bladder carcinogenesis from initiation of normal‐appearing tissue through progression of superficial tumors.Clinical trials of chemopreventive drugs involve healthy target populations, and the endpoints are reduced cancner incidence or mortality, reduced/eliminated precancerous lesions or increased latency, with none to minimal toxicity. Since cancers may not appear for 20–30 years, two of the most difficult aspects of testing these drugs in intervention trials are the long observation poeriods and large study populations required to measure cancer incidence reduction. However, observing the regression or recurrence of superficial bladder lesions (TIS, T1, Ta) requires relatively short time periods. Thus, these lesions lend themselves to the investigation ofintermediate biomarkers, defined as morphologic and/or molecular alterations in tissue between initiation and tumor invasion. It is hypothesized that modulation of one or more biomarkers would interrupt carcinogenesis and result in a decrease in cancer incidence. Thus, evaluation of biomarkers as surrogate endpoints would allow bladder trials to be of even shorter duration, use fewer subjects and be lower in cost. In addition, intermediate biomarkers could predict which superficial lesions (or normal‐appearing tissue) have the greatest potential for neoplastic progression. Development of strategies for the design of intrvention trials for bladder cancer and review of the current status of intermediate biomarkers in the bladder, and methods for their validation, are major objectives of th

ISSN:0730-2312    

DOI:10.1002/jcb.240501303

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractIn the United States, over 51,000 new cases of urinary bladder tumors are diagnosed annually, Approximately 75–85% of all newly diagnosed cases are superficial transitional cell carcinomas (TCCs). Incidence is highest (80% of the cases) in the 50–79 year age group. Recent studies have reported that 21–25% of risk for bladder cancer among United States white males is due to occupational exposure. The DuPont Chambers Works in Deepwater, New Jersey, was a major producer of two chemicals now known to be human bladder carcinogens (β‐naphthylamine and benzidine) as well as two suspected human bladder carcinogens [ortho‐toluidine and 4,4′‐methylene‐bis,2‐chloroaniline (MOCA®)]. Between 1954 and 1982, DuPont screened 1723 exposed employees annually at the Chambers Works using the Papanicolaou test for urinary cytology and mocroscopic urinalysis. A review of the prior screening program found that employees who developed bladder cancer during this time period were approximatly twice as likely to have had hematuria than those comparably exposed who did not deveolop bladder cancer.Building on this finding, a three‐year screening study evaluated a home self‐test for mocroscopic hematuria to aid early detection of treatable urologic conditons among exposed workers at this chemical plant. Every six months, subjects tested their urine at home for 14 consecutive days, for the presence blood. A high degree of adherence to our protocol (over 92% completed and returned the self‐testing record) as well as high compliance with repeat screening (85% returned for screening jin subsequent quaerterws) demonstrated good aceptance and performance of the recommended schedule of self‐testing. Through the first 7 periods of screening, two new cases and one recurrence of TCC of the bladder were detec

ISSN:0730-2312    

DOI:10.1002/jcb.240501304

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe key events of leading to better understanding of the natural history of urothelial tumors of the bladder are summarized. These were: the recognition of flat carcinomain situand related lesions (intraurothelial neoplasia) as principal sources of invasive cancer; identification of the unique structure of the urothelium; analysis of DNA content and the recognition of two pathways of urothelial tumors. A brief comment on the current status of immunologic and molecular genetic markers is appended. © 1992 Wiley‐Liss, I

ISSN:0730-2312    

DOI:10.1002/jcb.240501305

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

ISSN:0730-2312    

DOI:10.1002/jcb.240501306

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractNon‐invasive transitional cell carcinoma (TCC) occurs as two distinct growth patterns, papillary and non‐papillary (flat), which display significant differences in biologic potential. Papillary carcinoma usually presents as a low‐grade lesion which frequently recurs multiple times prior to invasion; conversely, non‐papillary (flat) carcinomain situis usually high‐grade at presentation (carcinomain situ) and frequently associated with invasion. These lesions may occur together, although papillary cancer is more easily visualized cystoscopically due to its exophytic growth; flat carcinomain situis often vystoscopically invisible.This report reviews existing data concerning the prognostic value of pathologic grading and staging of non‐invasive and early invasive TCC. Emphasis is placed on those studies reporting surgical treatment rather than other forms of treatment. © 1992 Wil

ISSN:0730-2312    

DOI:10.1002/jcb.240501307

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractIn the united States, nearly all cases of bladder cancer are of the transitional cell type, and epidemiological evidence indicates that among these, approximately 80% present initially as more or less well‐differentiated, superficial papillary neoplasms with a tendency for multifocal or diffuse involvement of the urothelial surface and/or recurrent tumor episodes, but with limited potential for invasive growth or a lethal outcome. Bladder tumors with lethal potential generally begin as poorly differentiated, sessile growths that are usually invasive at first diagnosis. Carcinomain situis a change that must be elicited among intact surface cells before progressive proliferation results in a tumor mass. Evidence for such an association is both temporal and spatial. Since most transitional cell carcinomas begin as well‐differentiated tumors.i.e., resembling normal urothelium, recognition of early neoplastic alteration before a papillary structure forms is unlikely and most of the evidence is spatial based upon urothelial changes adjacent to papillary tumors. The morphologic definition of carcinomain situis arbitrary and generally defined as a total replacement of the urothelial surface by cells which bear morphologic features of carcinoma, but which lack architectural alteration other than an increase in the number of cell layers,i.e., a flat lesion. The Union Internatiaàle Contra Cancer/American Joint Committee on Cancer (UICC/AJCC) staging scheme for bladder cancer distinguishes non‐invasive papillary growths as Ta and carcinomain situas Tis. Because detection of carcinomain situ, either by cytology or biopsy, depends upon recognizable malignant morphologic characteristics, studies of the lesion tend to be limited to the higher grade or more anaplastic examples. Carcinomain situmay exist in the urothelium adjacent to a papillary or invasive bladder cancer in which case the term “concomitant” has been used. If at initial presentation the bladder cancer is detected while still entirelyin situ, the term “primary” carcinomain situis used. Primary carcinoma in situ tends to be more indolent than the concomitant type. The lesion is usually widespread in the urothelium, and can involve the epithelium of the distal ureters, Brunn nests in the lamina propria, and the periurethral prostatic ducts and glands. Static image cytometry with DNA analysis has indicated that the cells of primary carcinomain situdiffer from muscle invasive transitional cell carcinoma by exhibiting a considerably greater nuclear DNA content. © 1992

ISSN:0730-2312    

DOI:10.1002/jcb.240501308

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe most common neoplasms of the urinary bladder are papillary tumors that vary histologically and cytologically from very well differentiated to highly anaplastic patterns. Biologic behavior of these tumors is closely correlated with morphology, so that cytologically benign tumors (papillomas) are benign in behavior, and increasing anaplasia is associated with increasing clinical aggressiveness. By this definition, 20% or more of bladder tumors should be classified as papillomas. The development of carcinoma occurs in a series of steps, progressing through atypia and carcinomain situto invasion. Finally, evidence is presented to show that invasive carcinoma often begins from areas of flat carcinomain situassociated with, but not within, co‐existing papillary tumors. © 1992 Wiley‐Liss,

ISSN:0730-2312    

DOI:10.1002/jcb.240501309

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

ISSN:0730-2312    

DOI:10.1002/jcb.240501310

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe ABO and Lewis blood group antigens are cell surface carbohydrate determinants formed by the sequential addition of saccharides to precursor backbone structures of membrane lipids and proteins. Suppression of normally active glycosyltransferases results in the absence of antigens that are normally expressed. ABH antigen deletion in malignant and premalignant urothelium has been extensively evaluated; it appears to correlate with significantly higher rates of tumor recurrence and disease progression. However, we have recently shown that the ABH blood group system is differentially expressed in thenormalurothelium of secretors in contrast to nonsecretor individuals. The normal urothelium of nonsecretors does not express A, B or H determinants; therefore, deletion of ABH antigens canonlybe ascertained in secretor individuals. Although nonsecretors only comprise 22–24% of the population, this observation mandates a reevaluation of earlier studies. Deletion of A, B or H antigens is noted in carcinomain situ(CIS), and in invasive and metastatic transitional cell carcinoma (TCC) of secretor individuals. Increased synthesis or activation of normally quiescent glycosyltransferases in bladder tumors can result in the expression of aberrant tumor‐associated blood group antigens. Immunohistochemical analysis has demonstrated that Lewis X (Lex) is not detected in normal adult urothelium except for occasional umbrella cells. However, papillomas, CIS and TCC expressed Lexin 84% of cases, regardless of grade, stage, blood type or secretor status of the individual. The presence of Lexpositive cells in bladder lavage specimens enhanced the detection of urothelial tumor cells, correctly identifying bladder tumors in 253/293 (86%) cases compared to a 63% sensitivity for cytology alone. The specificity of Leximmunocytology was 87%; 57 of 65 control subjects were negative for the Lexantigen. Furthermore, the detection of the Lexantigen in exfoliated bladder cells is a useful marker for predicting bladder tumor relapse in high risk, disease‐free patients. All 17 Lex‐positive patients recurred with clinical evidence of disease between 2 and 33 months (mean 8.4 month), while only 8 of 39 Lex‐negative patients recurred; 31 patients remain NED (2–40 months, mean 16.2 months). © 1992 Wil

ISSN:0730-2312    

DOI:10.1002/jcb.240501311

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractEpidermal growth factor (EGF) is excreted in urine in high concentrations in a biologically active form. Several lines of evidence indicate that EGF plays a role in transitional cell carcinoma (TCC) development and growth. These include:(1) EGF in the normal urine of rats promotes chemically initiated TCC; (2) EGF in normal human urine stimulates the clonal growth of human TCC cellsin vitro; (3) EGF stimulates thein vitrogrowth of human TCC cells, but not normal human urothelial cells; (4) the density and distribution of the EGF receptor (EGF‐R) on human urothelial tissues permits significant access of premalignant, dysplastic, and malignant cells to EGF; and (5) the concentration of EGF in the voided urine of patients with TCC is reduced, implying that EGF may be “extracted” from urine by the greater number of EGF‐Rs in patients with urothelial malignancy.Abnormal expression of the urothelial EGF‐R and/or altered excretion of EGF may well precede overt evidence of TCC and thus may serve as markers of risk or exposure. Similarly, reversion of EGF‐R expression or the return of excreted EGF to normal levels may provide a marker of response for preventive and therapeutic strategies. Interference with the EGF/EGF‐R interaction through dietary or pharmacological manipulations of the urine, or via targeting strategies employing intravesical administration of conjugated toxins or isotopes is already being employed in experimental and clinical studies. These approaches offer promising new tools in the detection, monitoring, prevention, and management of early stage bladder cancer. © 1992 W

ISSN:0730-2312    

DOI:10.1002/jcb.240501312

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY