摘要:

We established a new complex three-dimensional in vitro model called artificial tumor (ArT), which simulates individual human solid tumors. In contrast to the generally used spheroid models consisting of tumor cells only, the model described in the present report is composed of both tumor cells and tumor stromal cells. We created ArTs as a replica of colon carcinomas, composed of colon carcinoma cells, colon fibro-blasts, and as supportive skeleton fibrous tissue from human colon. All cellular components were established from the same surgically obtained colon carcinoma specimen. The ArTs studied came from 4 types of colon carcinomas; mucinous, well, moderately and undifferentiated colon carcinomas. Among all types of colon carcinomas ArTs could be established with a high rate of success, i.e. 81 %. Cells growing for 5 days on the fibrous tissue under normal culture conditions formed tumors up to 2,000 μm in diameter. Morphological studies showed that tumor cells grown as ArTs maintained the individual characteristics of the original tumor; for example, a comparable heterogeneity in CEA expression and/or maintenance of the differentiation stage. Polarized tumor cells were linked with the tumor stroma-simulating structure by their basal cell membrane, and formed central lumina lined by the apical membranes of the tumor cells, a structure quite similar to the tissue architecture of colon carcinomas in vivo

ISSN:1010-4283    

DOI:10.1159/000217938

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Heterogeneity of progesterone receptor (PR) expression in MCF-7 cells is generally attributed to the coexistence of several sublines, each possessing different stages of differentiation. One hypothesis is that the variation of PR distribution relates to the genotype cell heritage and cell cycle phases. The aim of this study was to demonstrate the implication of cell subclones in PR heterogeneity. MCF-7 cell line subclones were obtained initially by the limit dilution method on microscopic slides. On these slides PR was assessed by immunofluorescence. 20 of the subclones were PR-negative, 10 were positive with varying degrees of PR expression. As these cell populations arose from a single cell, they can be considered as monoclonal. These results show that PR heterogeneity (positive vs. negative clones) is based on a clonal origin and could be genotypically explained. In a second experiment four PR-positive MCF-7 cell subclones were maintained in continuous culture and studied. On each one a triple fluorescent staining (PR, Ki-67 antigen and DNA) was performed and the reactions were quantified by videofluoro microscopy. These results demonstrated that a relation between cell PR content and cell cycle stages exists in these four subclones. Cells in G0 express only little PR; PR level increases during the S phase to reach a maximum in the G2 phase; after mitosis PR level decreases with cell division and degradation may occur in G1: PR level reaches a minimum in late G1 and in the early S phase. The doubling times of the different MCF-7 subclones shows that those that are rapidly cycling were preferentially PR-positive, whereas slowly cycling MCF-7 subclones were PR-negative. We conclude that in MCF-7 cells some subclones are able or not able to synthesize PR; PR content is directly dependent on cell cycle phase and population doubling time.

ISSN:1010-4283    

DOI:10.1159/000217939

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Prostaglandin E2 (PGE2) is known to downregulate the generation of lymphokine-activated killer (LAK) cell activity. Indomethacin, an inhibitor of cyclooxygenase catalyzing the biosynthesis of PGE2, has been shown to augment LAK cell activities generated from peripheral blood mononuclear cells of normal healthy individuals. This study was undertaken to examine whether or not this augmentation is also a common phenomenon in cancer patients. LAK cell activities generated in the presence and the absence of indomethacin were examined in 15 normal healthy individuals and in 83 cancer patients. Paired data analysis revealed that indomethacin exhibited a significant augmentation of LAK activity generated from healthy individuals. Indomethacin enhanced LAK activity in patients with no distant metastases (TxNxM0); but depressed LAK activity in patients with distant metastases (TxNxM1). In patients without distant metastases, indomethacin showed an upregulating effect on LAK activity in those with an early T stage (T1-2NxM0), and no such effect was detected in those with a late T stage (T3-4NxM0). Indomethacin also significantly enhanced LAK cell generation in cancer patients with an ECOG performance status of 1, but significantly inhibited LAK cell generation in patients with a performance status of 4. These results indicated that indomethacin inhibited generation of LAK cell activity in cancer patients with a poor performance status or with distant metastatic disease, who normally would be the subjects of adoptive immunotherapy. Further, PGE2 production in cultured LAK cell medium was suppressed by indomethacin in all 20 cancer patients that were examined, suggesting that other yet to be identified factors or mechanisms may be responsible for the paradoxical effects of indomethacin on LAK cell activity.

ISSN:1010-4283    

DOI:10.1159/000217940

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The role of CA 15-3 in breast cancer has been widely studied by several authors. This study was designed to describe the predictivity of CA 15-3 determinations for the metastasis or second primary tumor in patients subjected to follow-up for breast cancer. All the 1,123 determinations of CA 15-3 carried out during 1991 in a hospital laboratory were analyzed. By cross-matching anagraphic items of patients with clinical data from different hospital databases, it was possible to reconstruct the clinical history. At the cutoff point of 40 U/ml, the positive predictive value of the CA 15-3 was 99.4%. This study shows the very close association between CA 15-3 ≥ 40.0 U/ml and disease, suggesting a careful restaging when the marker increases without clinical evidence of metastases. Hormonal treatment should also be considere

ISSN:1010-4283    

DOI:10.1159/000217941

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

This study was designed to examine the biological implication of progesterone receptor (PR) forms A and B mRNA expressions in gynecologic cancers. The ratio of PR form A to form B in mRNA expression was approximately 1:1 in all endometria studied. The predominant expressions of form B transcript occurred in 6 out of 7 cases of advanced stages (stages III and IV) in ovarian cancers, in 5 out of 9 cases of cervical cancers, and in 5 out of 11 cases of endometrial cancers. In conclusions, the dominancy of PR form B mRNA expression might be associated with the expression of a malignant phenotype in gynecologic cancers, and advanced clinical stage in ovarian cancers, suggesting a biological marker of malignant phenotype in these three types of cancer cell.

ISSN:1010-4283    

DOI:10.1159/000217942

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Somatostatin has been demonstrated to activate phosphotyrosine phosphatases (PTPases) in pancreatic cells. In this work we studied the effect of a tumor-selective somatostatin structural derivative, TT2–32, on the PTPase activity in the SW620 human colon tumor cell line. TT2–32 caused a strong inhibition of cell proliferation. In response to TT2–32 we found a rapid and sustained increase (5–30 min) in PTPase activity showing two maxima at 0.1 and 30 μM concentrations, respectively. During short-term incubation tyrosine kinase activity was much less affected by TT2–32. TT2–32-induced activation of PTPases may be an important early step in the signaling cascade in the inhibition of cell proliferation in colo

ISSN:1010-4283    

DOI:10.1159/000217943

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

In this study the role of gonadotropins for the induction of ovarian tumors in rats was examined. The rats were castrated and one ovary was transplanted under the splenic capsule. Rats remained untreated or received a GnRH analog for gonadotropin suppression either immediately, 90 or 180 days after castration. Under these conditions the untreated rats developed ovarian tumors while the treated rats only developed tumors when the stimulation of gonadotropins lasted for more than 90 days. The first appearing tumors were theca cell tumors while during the further course of the experiment the granulosa cell compartment increased; however, no histological signs of malignancy could be detected in these tumors. GnRH analogs could block the induction of granulosa cell tumors when administered 150 days after transplantation. After a period of 210–240 days the tumors grew independently of elevated LH and FSH levels. The causes of this growth autonomy need to be studied furthe

ISSN:1010-4283    

DOI:10.1159/000217944

出版商:S. Karger AG    

年代:1995

数据来源: Karger