Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer

Low-density lipoprotein (LDL) receptors are overexpressed in most neoplastic cell lines and provide a mechanism for the internalization and concentration of drug-laden nanoemulsions that bind to these receptors. The aim of the present study was to determine whether the administration of standard chemotherapeutic schemes can alter the expression of LDL and LDL receptor-related protein 1 (LRP-1) receptors in breast carcinoma. Fragments of tumoral and normal breast tissue from 16 consecutive volunteer women with breast cancer in stage II or III were obtained from biopsies before the beginning of neoadjuvant chemotherapy and after chemotherapy, from fragments excised during mastectomy. Tissues were analyzed by immunohistochemistry for both receptors. Because complete response to treatment was achieved in 4 patients, only the tumors from 12 were analyzed. Before chemotherapy, there was overexpression of LDL receptor in the tumoral tissue compared to normal breast tissue in 8 of these patients. LRP-1 receptor overexpression was observed in tumors of 4 patients. After chemotherapy, expression of both receptors decreased in the tumors of 6 patients, increased in 4 and was unchanged in 2. Nonetheless, even when chemotherapy reduced receptors expression, the expression was still above normal. The fact that chemotherapy does not impair LDL receptors expression supports the use of drug carrier systems that target neoplastic cells by the LDL receptor endocytic pathway in patients on conventional chemotherapy.

Apolipoprotein E polymorphism in cerebrovascular & coronary heart diseases.

The role of apolipoprotein E (apo E) in lipid metabolism and cholesterol transport is well established. About 14 per cent of the variation in plasma cholesterol levels is attributed to polymorphisms in apo E gene (APOapo E). E consists of three common alleles, designated as ε2, ε3 and ε4 which code for E2, E3 and E4 proteins respectively resulting in three homozygous (E2/E2, E3/E3, E4/E4) and three heterozygous (E3/E2, E4/E2 and E4/E3) phenotypes. Different populations studied worldwide inherit variable frequencies of the E alleles and genotypes, with the most frequent allele being ε3.The ε4 allele has been consistently shown to be associated with Alzheimer’s disease, coronary heart disease and cerebrovascular disorders. In this review, we have discussed the role of apo E polymorphisms in cerebrovascular and coronary heart diseases. The status of apo E polymorphisms and their disease associations in Asian Indians besides, other populations has also been discussed. Further, studies elucidating the pathophysiology of apo E deficiency conducted in knock-out mice have been reviewed.