Zum Steroidhormonrezeptorenstatus kolorektaler Karzinome

Mentges, B.; Cn, Gutt; M, von Bülow; Pollow, K.; Hj, Grill; Bätz, W

doi:10.1159/000216713

Cited by 4 publications

(4 citation statements)

References 8 publications

(8 reference statements)

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“…Additional studies have confirmed androgen receptor (AR) to be present in the sigmoid (7 specimens) of nonhereditary rectal cancer patients. majority of analyzed colorectal carcinomas, with ER identified in Ͻ50% of cases [3, [24][25][26][27][28]. Some investigators, Cell Culture and Isolation of Colonocytes however, have reported negative results [29,30].…”

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confidence: 99%

Molecular study of sex steroid receptor gene expression in human colon and in colorectal carcinomas

et al. 1997

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Background Sex steroid hormones influence function of the human gastrointestinal tract. Although the specific receptor proteins have been identified in surgical specimens of both intestinal mucosa and colorectal carcinomas, it is still unknown whether they are expressed in intestinal epithelial cells. Methods Expression of androgen receptor (AR) protein and estrogen receptor (ER) protein was studied by Scatchard analysis and ELISA (for ER only) in surgical specimens of normal‐appearing mucosa, colorectal carcinomas, isolated colonocytes, and human colorectal carcinoma cell lines. Northern analysis was applied to identify the appropriate mRNAs, followed by the sensitive technique of reverse transcription‐polymerase‐chain‐reaction (RT‐PCR). Results AR protein was identified in all surgical specimens analyzed and ER protein in 10 out of 13 normal‐appearing mucosa specimens and 4 out of 7 colorectal carcinomas. The receptor proteins were not found in isolated colonocytes or in the transformed cell lines. RT‐PCR confirmed that none of the isolated normal colonocytes or transformed colorectal carcinoma‐derived cells expressed these mRNAs. Intestinal smooth muscle cells and fibroblasts were found to express sex steroid receptor mRNAs. Conclusions Both receptors are present in human large intestine but are expressed in stromal cells and not in intestinal epithelial cells. We hypothesize that sex steroids may influence the function of colonocytes indirectly through stromal‐epithelial interactions. J. Surg. Oncol. 64:3–11 © 1997 Wiley‐Liss, Inc.

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confidence: 99%

Molecular study of sex steroid receptor gene expression in human colon and in colorectal carcinomas

et al. 1997

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“…Thus it seems to be highly necessary to develop new therapeutic strategies and, last but not least, to study unconventional concepts, too, even if the probability of being successful is low. One of those concepts is outlined on the presence of hormone receptors of colon and rectum carcinom cell lines as observed by different authors [3,4], However, it is important to point out that receptor activity in colorectal carcinoma is considerably low compared to breast carcinoma. Accordingly, pilot studies using Tamoxifen for treatment of colorectal carcinoma revealed only marginal effects such as decrease of CEA level and alkaline phos phatase in patients with liver métastasés and objective tumor regression in a small number of patients [3, 5.6).…”

Section: Discussionmentioning

confidence: 99%

“…Within a series of 24 patients studied by ourselves [3], three showed estrogen receptor and 13 proges terone receptor-binding activity. In a recent publication of this journal [4], 26 consecutive colorectal carcinomas were studied. In all cases the estradiol receptor binding capacity was below 2 fmol/mg cytosol protein, and in four samples, progesterone receptor levels from 13 to 23 fmol/mg cytosol protein were observed.…”

Section: Introductionmentioning

confidence: 99%

Phase-II Study of Droloxifene for Treatment of Metastatic Colorectal Carcinoma

Nienhaus¹,

Queißer²,

Heim³

et al. 1991

Oncol Res Treat

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Droloxifene (3-hydroxytamoxifen citrate) is a new synthetic non-steroidal antiestrogen which has been developed with high receptor binding affinity and possibly improved antiestrogenic activity in man. Recently, hormone receptors were observed in human colorectal carcinoma cell lines. For this reason, we treated 24 patients with advanced colorectal carcinoma and progressive disease with Droloxifen in a Phase-II trial. All patients exept three had been pretreated by cyto-toxic chemotherapy. The dose of Droloxifene was 100 mg orally/day for at least eight weeks. Fifteen patients were evaluable for response. No complete or partial remission was observed. However, there were six patients (40%) showing tumor stabilization. The time to progression was twelve to 29 weeks. The toxicity of treatment was low and consisted of only few episodes of nausea, constipation and pain. The data suggest that Droloxifene has marginal activity for treatment of colorectal carcinoma.

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“…1987;Weinstein et al 1991;Lai et al 1991;Stein et al 1996). The steroid-hormonebinding capacity ofcolorectal carcinomas and occasional responses to antiestrogens noted in men (Mentges et al 1990) This treatment has been reported to result in effective in vitro and in vivo inhibition of P-glycoprotein function (Ramu et al 1984;Berman et al 1991), fairly good tolerance (Figueredo et al 1990;Trump et al 1992) and a potentially synergistic action in terms of multidrug resistance reversal when combined with racemic verapamil (Berman et al 199l;Figueredo et al 1990).…”

Section: Introductionmentioning

confidence: 99%

Treatment of advanced colorectal cancer with doxorubicin combined with two potential multidrug-resistance-reversing agents: high-dose oral tamoxifen and dexverapamil

Weinländer

Kornek

Raderer

et al. 1997

J Cancer Res Clin Oncol

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On the basis of the overexpression of the MDR1 gene in human colorectal cancer, which may constitute a molecular basis for intrinsic drug resistance that can be reversed, and because of the limited therapeutic value of conventional cytotoxic treatment in this common disease, the present phase II study of P-glycoprotein-directed double modulation was initiated. Fifteen patients with measurable metastatic colorectal cancer, all of whom were refractory to first-line chemotherapy with 5-fluorouracil/leukovorin, were entered in this trial. Treatment consisted of 80 mg tamoxifen twice daily on days 1-9, oral dexverapamil every day on days 7-9, and 60 mg/m2 doxorubicin given by intravenous bolus injection on day 8. Courses were repeated every 4 weeks. After a median of three (between one and six) courses, none of the 14 evaluable patients had objective response, and 4 had stable disease. Adverse reactions consisted mainly of myelosuppression (WHO grade IV granulocytopenia was noted in 40%), and mild and reversible dexverapamil-related cardiovascular side-effects, specifically hypotension (47%). Our results suggest that, despite the histological demonstration of high levels of P-glycoprotein in colorectal cancer and administration of two potentially synergistic chemosensitizers, we were unsuccessful in circumventing its primary resistance to chemotherapy.

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Zum Steroidhormonrezeptorenstatus kolorektaler Karzinome

Cited by 4 publications

References 8 publications

Molecular study of sex steroid receptor gene expression in human colon and in colorectal carcinomas

Molecular study of sex steroid receptor gene expression in human colon and in colorectal carcinomas

Phase-II Study of Droloxifene for Treatment of Metastatic Colorectal Carcinoma

Treatment of advanced colorectal cancer with doxorubicin combined with two potential multidrug-resistance-reversing agents: high-dose oral tamoxifen and dexverapamil

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