Biomedical subjects

S Nandi

Publications and source records attributed to S Nandi.

256 records · Page 15Linked to original sources

PubMedDate not supplied

Beware of contaminating mouse cells in human xenografts from nude mice.

Human tumor xenografts in nude mice are widely utilized model system for the transplantation of human surgical specimens and human established cell lines. Gene expression studies are often carried out in these model systems. With an increasing use of PCR based analyses, the extreme sensitivity of this technique poses a serious challenge with regards to the extent of contaminating host mouse cells in the human tumor xenografts. These xenografts are never free of host cell contamination. We detected mouse estrogen receptor expression in several human tumor xenografts using RT-PCR demonstrating that precaution is necessary when utilizing PCR based analyses in human tumor xenografts. A cytologically based methodology which distinguishes human versus mouse cells will be more suitable for ER expression studies using human xenograft models. Both (1) in situ hybridization using human probe and (2) immunocytochemistry using a monoclonal antibody directed against human cytokeratin have been used successfully to distinguish human cells versus host mouse cells in human xenografts in nude mice. Immunostaining of ER can then be utilized to determine the expression pattern of ER in the transplanted human cells.

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PubMedDate not supplied

Reconstituted normal human breast in nude mice: estrogen and progesterone receptors regulation.

Actions of estrogen and progesterone on normal human breast are mediated by their respective receptors. Since receptor regulation studies in humans are difficult to perform, we have utilized our model system of reconstituted normal human breast in nude mice to determine expression of estrogen and progesterone receptors in response to exogenous estrogen and progesterone. In normal human breast in situ, only a subset of epithelial cells (about 10%) are positive for estrogen receptor. These cells which remain positive after transplantation into nude mice can be completely downregulated by administration of exogenous estrogen resulting in all transplanted human breast epithelial cells now being negative for estrogen receptor. Exogenous estrogen also upregulates the progesterone receptor in a subset of human breast epithelial cells rather than in all cells. Exogenous progesterone, alone or in combination with estrogen, did not affect the estrogen or progesterone receptors. Double immunofluorescent labelings for a proliferation marker and progesterone receptor in both surgical specimens and nude mice transplants demonstrate that proliferation and progesterone receptor expression do not take place in the same cell. Our in vivo model system enables studies on the biology of primary normal human breast epithelial cells which otherwise are difficult to perform in humans.

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PubMedDate not supplied

Hormonal carcinogenesis: a novel hypothesis for the role of hormones.

A testable hypothesis on the role of hormones in carcinogenic processes is presented. The hypothesis has been based on the findings that (1) hormones regulate cell division in normal cells, (2) successful neoplastic transformation requires hormonal stimulation of cells receiving carcinogenic insult, (3) normal cells have finite divisional capabilities, whereas neoplastic cells possess infinite divisional capabilities, and (4) normal cells, when present in high ratio, inhibit the growth of neoplastic cells. According to the hypothesis, hormones are considered to be neither mutagenic nor carcinogenic. (Carcinogen is defined as an agent which initiates normal-to-neoplastic transformation). Instead, they play a dual role in carcinogenesis. First, hormones are considered necessary for the fixation of the cell genome neoplastically transformed by carcinogens. Second, hormones, by enhancing the rate of cell division, shorten the life span of normal cells, thus causing a reduction of the normal- to tumor-cell ratio in the population--a condition which facilitates growth of tumor cells.

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PubMedDate not supplied

Changes in the parous rat mammary gland environment are involved in parity-associated protection against mammary carcinogenesis.

Parity in rats results in protection from methylnitrosourea (MNU)-induced mammary cancer. Our goal was to determine if systemic alterations in the mammary gland environment after a full-term pregnancy rendered the parous rat an inadequate host for promotion of initiated mammary epithelial cells to become cancerous. Lewis rat MNU-treated mammary epithelial cells were transplanted into uniparous (UP), age-matched virgin (AMV) (both 130-150 d), or young virgin (YV) (50-60 d) syngeneic hosts to examine if differences in the systemic environments of the three hosts had an effect on hyperplasia and cancer formation. More transplants in YV and AMV hosts contained hyperplasias and adenocarcinomas as compared to transplants in UP hosts. In addition, UP host transplants had significantly fewer numbers of hyperplastic lesions than transplants from the virgin hosts. The evidence presented here shows that the uniparous host environment is less supportive than that of the virgin host for hyperplasia and cancer development.

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