Tumor markers defined

In phase I clinical trials 47 patients, all of whom had previously failed standard treatments for solid tumors, received the drug in the UK, Italy, and Switzerland on three different schedules.123,124 Dose-limiting toxicities have been defined as bone marrow depression and diarrhea. The latter is treatable with loperamide. Signs of biological activity were seen. Notably one patient with metastatic pancreatic cancer showed a partial response (for 4 months) and two further patients, one with metastatic melanoma and one with bronchoalveolar carcinoma, also showed partial responses. In a phase I trial in combination with 5-FU, a partial response in breast cancer was observed.125 Furthermore, a reduction in tumor marker levels was observed in two patients, one with ovarian cancer, and one with colon cancer. Phase II studies have shown partial responses in cisplatin-resistant ovarian and nonsmall-cell lung cancer.126,127 The indications are that the profile of clinical activity is different and complementary to the mononuclear platinum agents. 

For non-SI traceable quantities the strategy for introducing traceability has to be different. This concerns a large number of analytes for which no defined molecular structure can be assigned, such as for many enzymes, proteo-homones, tumor markers and cardiac markers. The first and most important step must be the definition of the quantity before it is possible to establish reference systems (reference procedures, materials and reference network laboratories). Whenever possible, a global consensus on the definition of the measurand should be achieved. Consequently, definition of the measurand and establishment of reference systems is the objective of several working groups and committees of the Scientific Division of IFCC. 

Evaluation of CA 125 tests has shown moderate sensitivity, higher specificity, and predictive values in ovarian cancer patients when determining the presence of an intraperitoneal tumor or future occurrence at the time of second-look procedures. Studies have shown that the CA 125 level obtained at the time of a second-look procedure correlates reasonably well with the size of the tumor. As mentioned before, the predictive value of a marker depends on the prevalence of a particular type of malignancy in the intended population. Thus, evaluating a marker s diagnostic potential must be based on prevalence in a well-defined group for results to be generally applicable (i.e., prevalence of ovarian cancer in women with pelvic masses). 

Eppenberger U, Kueng W, Schlaeppi JM, et al. Markers of tumor angiogenesis and proteolysis independently define high- and low-risk subsets of node-negative breast cancer patients. J Clin Oncol 1998 16 3129-3136. 

Margin of A ratio defined by EPA as a dose derived from a tumor bioassay, exposure - epidemiological study, or biological marker study, such as the dose associated with a 10% response rate divided by an actual or projected human exposure. 

The Ewing family of tumors comprises small round cell neoplasms of bone and soft tissue that are, in part, defined by a particular chromosomal aberration [t(ll 22)] and variants thereof. Over the past 15 years, it has become clear that ES and peripheral PNET are part of the same spectrum of neoplastic proliferations. Besides the karyotypic marker just mentioned, both of those tumor types also show neuroectodermal features in tissue culture and similarities in proto-oncogene expression. As classically defined, ES was distinguished from PNET by an absence of pseudorosettes and the lack of ultrastructurally or immunohistochemically detectable neuroectodermal features. However, this diagnostic separation is now considered to be antiquated and has been abandoned. 

The previous discussion is especially apropos to the consideration of whether or not another tumor—pleomorphic leiomyosarcoma (PLMS)—can be defined as different from MFH. As described, PLMS is said to be immunoreactive for desmin or MSA or alpha-isoform actin, all of which may be seen in myofibroblastic elements as well (as in MFH). For now, a working definition of PLMS might require that positivity for at least two smooth muscle markers be observed. However, this stipulation is still not absolutely exclusionary with... 

Because it is an in situ carcinoma, the nests of tumor cells are surrounded by a well-defined myoepithelial cell layer that can be detected with typical myoepithelial cell im-munohistochemical markers. 

It is likely that MFH is not a unified entity in the skin or elsewhere, but instead represents a histologic pattern that is a common final pathway of differentiation for several modes of mesenchymal neoplasia. That concept was first espoused by Brooks. Thus an MFH-like pattern may be seen in conjunction with other mesenchymal images in the same tumor mass, as a consequence of clonal evolution. An unqualified diagnosis of MFH can be made immunohistologically only if one is dealing with a pleomorphic malignant tumor that is vimentin reactive and lacks epithelial, myogenous, neural, and endothelial markers. At present, there are no proactive determinants that define this neoplasm. 

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