ISSN:8756-0437    

DOI:10.1002/ssu.2980080502

出版商:John Wiley&Sons, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractSeveral models of genetic events which define the origin and progression of human tumors have been elucidated over the last several years. These models suggest that the study of tumors at the level of both the chromosome and the gene can be useful in elucidating molecular events in tumor progression and in determining the biologic behavior of individual tumors. The genetics of transitional cell carcinomas are reviewed with emphasis on potential mechanisms of tumorigenicity and the clinical utility of genetic markers.

ISSN:8756-0437    

DOI:10.1002/ssu.2980080503

出版商:John Wiley&Sons, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractBladder tumor has a spectrum of neoplastic activity. Some behave in a benign fashion, and others are highly aggressive and lead rapidly to metastatic disease and death. The processes of metastasis can be described as a sequence of interrelated steps. The processes involve 1) tumor cell adhesion to basement membranes, 2) the degradation of basement membranes, and 3) the migration of tumor cells through the destroyed stroma into blood and lymphatic vessels. Each of these processes involves the expression of molecular factors unique to tumor cells. With better understanding of the molecular basis of these factors, novel prognostic and potential therapeutic agents can be generated and applied to the clinical arena.

ISSN:8756-0437    

DOI:10.1002/ssu.2980080504

出版商:John Wiley&Sons, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractFor transitional cell carcinoma of the bladder, clinical data indicate that invasive, metastatic tumors can arise through at least two different progression pathways. The majority of invasive, metastatic bladder neoplasms clinically present de novo, i.e., the patients have no history of malignant bladder disease. This implies that the highly malignant tumor cells either arise de novo or have undergone a rapid progression. Alternatively, a considerable fraction of patients with superficial bladder cancer process to invasive disease after a history of relatively benign superficial TCC. The molecular and cell biological basis of tumor progression is only poorly understood. Clearly, a better understanding of this progress could have profound clinical implications, since patients with superficial TCC with a high risk for progression would have to be treated more aggressively. We discuss the problems that are associated with tumor biological studies on early steps in the progression of TCC, especially from a “model system point of View

ISSN:8756-0437    

DOI:10.1002/ssu.2980080505

出版商:John Wiley&Sons, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractThe histogenetic relationships between the subtypes of bladder cancer are not known. Each common pattern (transitional cell carcinoma, adenocarcinoma, and squamous carcinoma) can exist independently, although they may coexist in primary or metastatic bladder cancers, and tumors that are predominantly composed of transitional cell carcinoma may have regions of squamous or glandular differentiation. Morphologically identical tumors exhibit marked variation in their natural history and response to treatment. To study these aspects of the biology of human bladder cancer, a series of cell lines have been established and characterized as xenografts and in tissue culture. These studies have shown a likely common origin for transitional cell carcinoma, adenocarcinoma, and squamous carcinoma of the bladder. Morphologically similar xenografts and cell lines in vitro have shown a broad range of functional heterogeneity, including ultrastructure, tumor marker production, ploidy, cell surface characteristics, and response to chemotherapy. These are useful models of heterogeneity of response to treatment with established and new cytotoxic agents.

ISSN:8756-0437    

DOI:10.1002/ssu.2980080506

出版商:John Wiley&Sons, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractGrowth factors (GFs) are a class of proteins that bind to specific cell surface receptors (GF‐Rs), inducing a variety of responses including mitosis, in susceptible target cells. Abnormal production, expression, and/or function of GFs or GF‐Rs can result in unregulated growth, the hallmark of malignant transformation. This chapter reviews those GFs/GF‐Rs that have been linked to human bladder cancer. It focuses particularly on one [epidermal growth factor (EGF), which is excreted in urine in high concentrations] and its possible role in the development and growth of urothelial malignancy. Potential clinical applications in diagnosis, staging, prevention, and treatment are disc

ISSN:8756-0437    

DOI:10.1002/ssu.2980080507

出版商:John Wiley&Sons, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractBladder cancer ranks as the third most common malignancy among men and tenth among women. Superficial transitional cell carcinomas (stage Ta, Tis, and T1) account for approximately 70–40% of these tumors, while the remaining 20–30% are invasive (T2, T3, and T4). Approximately 70% of superficial tumors will have one or more recurrences, with 25% of these expressing a higher histologic grade and 10–15% subsequently developing invasive and/or metastatic disease. The detection and prediction of tumor recurrence and/or tumor progression is crucially important if timely and appropriate therapy is to be instituted. Conventional histopathologic evaluation usually provides definitive diagnosis upon which therapeutic planning is based. However, at present there are no more reliable morphologic indicator to identify which individuals will have recurrent disease or who will progress to invasive and/or metastatic cancer. Recent advances in tumor biology have identified markers that are good candidates for clinical applications in early tumor detection, as well as for the stratification of patients with like‐appearing morphological lesions with different biological and clinical behavior. The ultimate goal is to develop predictive assays that would segregate patients with high probability of failures versus patients who would be cured by localized modes of

ISSN:8756-0437    

DOI:10.1002/ssu.2980080508

出版商:John Wiley&Sons, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractFlow Cytometry (FCM) DNA assays of bladder irrigation specimens are now recognized as a clinically useful and reliable means of detecting and monitoring carcinoma of the bladder. This technique, which identifies carcinoma by the presence of an aneuploid population of cells, can be carried out on specimens obtained in an outpatient or hospital setting and is easily performed in any medium‐sized laboratory. It is most sensitive to superficial and high grade tumors. Overall, nearly 80% of superficial carcinomas of bladder will have positive flow cytometry, comparing very favorably with conventional cytology. Until now, the widest clinical application of FCM has been in monitoring the conservative treatment of stage 0–1 flat and papillary carcinomas, but newly developed dual parameter measurements are capable of quantifying proliferative activity, oncogene expression, growth factor receptors, and other cellular features that may better characterize the biologic potential of these tumors and can be expected to aid in the selection and timing of treatm

ISSN:8756-0437    

DOI:10.1002/ssu.2980080509

出版商:John Wiley&Sons, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractBlood group antigens are a group of carbohydrate structures bound to membrane lipids or proteins of erythrocytes and certain epithelial tissues including urothelium. The Lewis antigens are structures that are genetically and biochemically related to the ABO blood group. The ABO and Lewis blood group systems are differentially expressed in the normal urothelium of “secretors” versus “nonsecretor” individuals. The normal urothelium of “secretors” is rich in ABH, Leb, and Leyantigens while the urothelium of “nonsecretors” does not express these antigens. Therefore, deletion of ABH antigens, commonly noted in TCC, can only be reliably ascertained in “secretor” individuals. Neo‐expression of the Lewis X antigen (which is absent in normal urothelium) is noted in over 85% of TCC regardless of tumor stage and grade. Immunocytological detection of the Lewis X antigen on exfoliated bladder epithelial cells enhances the detection of urothelial tumor cells, particularly from low grade an

ISSN:8756-0437    

DOI:10.1002/ssu.2980080510

出版商:John Wiley&Sons, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractChemotherapy treatments for urothelial tract tumors have improved to the point that some patients are enjoying long‐term disease‐free survival. Moreover, with currently available agents and combinations, and with our increased application of clinical and biologic prognostic factors, we are refining our ability to select appropriate therapies for individual patients. We have learned that once the decision is made to use combination chemotherapy, adequate doses should be used. This can be facilitated by the coadministration of hematopoeitic growth factors. Recently completed phase II trials have confirmed that higher doses and dose rates may increase response proportions of and in particular, the proportion of complete responses. The finding that granulocyte colony stimulating factor enhances the sensitivity of tumor cells to methotrexate in vitro and to other agents studied against urothelial tumors implanted in nude mice implies an expanded role for these compounds. However, because non‐hematologic toxicities are still important, it is unlikely that simple escalation of all components a four drug regimen such as of M‐VAC (cisplatin, methotrexate, vinblastine, and doxorubicin) will have a significant impact on survival.In addition, as more is learned about the pharmacokinetic and pharmacodynamic relationships of the active agents, it appears that better schedules can be designed to improve the therapeutic index of the compounds. Ultimately we will be able to determine drug sensitivities, both at the start of therapy and as it evolves during treatment, that will allow a better selection of a particular chemotherapeutic regimen. For example, mdr1 induction appears to play a significant role in the therapy for treatment‐resistant tumors. The availability of a number of active salvage regimens that are not constrained by this mechanism hints that changes in drug sequencing and drug scheduling may provide a significant improvement in outcome.While established combination chemotherapy regimens should be considered standard therapy in appropriately selected patients, promising strategies and new agents need to be investigated if we are to “break the deadlock” that has appeared in the treatment of urothelial tumors. These investigations can be performed safely in a well‐controlled fashion to enable the identification of new regimens and to compare promising strategies with appropriate control populations in ra

ISSN:8756-0437    

DOI:10.1002/ssu.2980080511

出版商:John Wiley&Sons, Inc.    

年代:1992

数据来源: WILEY