Solid tumors detection

The group at Pharmacyclics developed a related phenyl hydroxamic add HDACi, PCI-34051 (27e) and demonstrated this to display greater than 200-fold selectivity for HDAC8 (IC5o = 10nM) over the other HDAC isoforms [40b]. Interestingly, this compound induced caspase-dependent apoptosis in T-cell lymphomas and leukemias at low micromolar concentrations, but not in other hematopoietic or solid tumor cell lines. Furthermore, PCI-34051 does not cause detectable tubulin or histone acetylation. 

FI.W. Salmon, D.W. Siemann, Utility of F MRS detection of the hypoxic cell marker EF5 to assess cellular hypoxia in solid tumors, Radiother. Oncol. 73 (2004) 359-366. 

It has been pointed our above that solid tumors may have a hypoxic core (for the detection of hypoxic regions see Porschen et al. 1977 Chapman 1984), and that it would be highly desirable to sensitize these areas with a drug that is not as rapidly metabolized as 02 and therefore can reach the site of action and mimic O2 with respect to its capability to fix DNA damage. Many of the drugs that have been... 

The optimal composition of a FISH probe mixture for detection of changes in gene copy number in solid tumors includes two labeled probes. One probe directed towards the gene of interest and one probe directed towards a reference sequence for the chromosome on which the target gene is located. Traditionally, the reference probes are directed towards the non-coding centromere sequences. 

Broxterman, H. J., Schuurhuis, G. J., Lankelma, J., Oberink, J. W., Eekman, C. A., Claessen, A. M. E., Hoekman, K., Poot, M., and Pinedo, H. M. (1997) Highly sensitive and specific detection of P-glycoprotein function for hematological and solid tumor cells using a novel nucleic acid stain. Br. J. Cancer 76, 1029-1034. 

A second member of the parathyroid hormone family, parathyroid hormone-related protein (PTHrP), is quite similar to PTH in amino acid sequence and protein structure. Like PTH, it activates the parathyroid hormone receptor causing increased bone resorption and renal tubular calcium reabsorption. Increased serum concentrations of parathyroid hormone-related protein are the predominant cause of hypercalcemia in cancer patients with solid tumors. This observation led to its discovery and to the elucidation of its many cellular functions in normal tissues. In contrast to PTH, which is expressed only in parathyroid glands, PTHrP is detected in many tissues in fetuses and adults it is found in epithelia, mesenchymal tissues, endocrine glands, and the central nervous system. This protein is also the principal regulator of placental calcium transport to the fetus. 

Cancer is a major health issue worldwide. The most common solid tumors are breast, colorectal, ovarian, prostate and lung cancer, which account for more than 3.2 million new cases annually, and 1.7 million deaths each year [1]. In addition, large numbers of individuals are diagnosed with and die each year from hematological malignancies such as lymphomas (>166000 new cases and 93 000 deaths, respectively) or leukemias (144000 new cases and 109000 deaths, respectively). Early detection combined with advances in surgery and external radiotherapy have improved the prognosis for many patients with solid tumors in which the disease is confined to the primary anatomical site, but the outlook for patients with advanced disseminated cancer remains poor. Lymphomas and leukemias are more... 

Many tumors contain IL-6 detected by immunohistochemical techniques and elevated semm levels have been reported in various solid tumors (S24). In mice the growth of several transplantable tumors is associated with increased plasma levels of IL-6, which is correlated with cachexia, one of the effects of this cytokine (see earlier) (GIO, Ml9). 

Since the publication of the original articles by Smith et al. in 1991 on the detection of circulating tumor cells in the malignant melanoma patients (SIO), many investigators have analyzed circulating tumor cells in the peripheral blood of patients with a variety of solid tumors by conventional RT-PCR. In this section, we first summarize the results from conventional RT-PCR studies and then refer to recent advances in the detection of circulating tumor cells with the quantitative real-time RT-PCR method. We selected melanoma and colorectal cancers, mainly the latter, which is one of the most extensively studied cancers in this compartment. 

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