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Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The co-expression of M-CSF (CSF-1) and its receptor in specimens of ovarian cancer has recently been reported. Preliminary results have already suggested a possible influence of steroids on FMS (M-CSF receptor) expression. Fifty-five non-pretreated FIGO stage III/IV ovarian adenocarcinomas were studied for M-CSF transcripts and protein, as well as FMS transcripts and protein, using standard molecular biological techniques (Northern blot, slot blot analysis) and immunocytochemistry (ICC). Steroid receptor content was measured by DCC analysis in 44/55 specimens; in addition, ER/PR (oestrogen/progesterone) ICC was performed in 32/55 specimens. All tumours were shown to contain M-CSF-specific mRNA. Likewise, M-CSF protein was detected by ICC in the stroma and over the epithelium in all specimens. However, while most tumours were shown to contain FMS-specific mRNA, only 64 per cent of cases showed significant expression of FMS protein by tumour epithelium as shown by ICC. A statistically significant positive correlation was found between M-CSF and FMS mRNA expression levels. A week non-significant positive correlation was noted between FMS mRNA expression levels and tumour grade. Carcinomas were ER-positive in 66 per cent (DCC) or 34 per cent (ICC), and PR-positive in 73 per cent (DCC) or 34 per cent (ICC). A statistically significant positive correlation between ER (DCC) and M-CSF mRNA expression levels was found. Weak non-significant correlations were present between ER (ICC) and FMS (ICC), as well as between PR (DCC) and FMS mRNA expression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Co-expression of M-CSF transcripts and protein, FMS (M-CSF receptor) transcripts and protein, and steroid receptor content in adenocarcinomas of the ovary. 796 6

A human macrophage-colony-stimulating-factor (M-CSF) gene inserted into an expression vector (pRc/CMV-MCSF) was transfected into multidrug-resistant (MDR) human ovarian cancer cells (AD10) to induce secretion of human M-CSF into the medium. The M-CSF level in the culture medium of the transfected cells reached 100 ng/ml after 7 days, and the ability of the cells to secrete M-CSF was stable for at least 3 months. Transfection of the M-CSF gene did not result in any change in expression of MDRI (P-glycoprotein), proliferation or chemosensitivity of the cells from those of the parent cells. There was also no difference between the transfected and the parent cells in susceptibility to NK cell- or interleukin-2-activated killer-cell-mediated cytotoxicity. Human blood monocytes that had been incubated for 4 days in medium with the culture supernatant of MH-AD10 cells exhibited higher ADCC activity than untreated monocytes against MDRI-positive cancer cells. This effect of the supernatant of AD10 cells was completely abolished by its treatment with a monoclonal anti-M-CSF antibody (MAb). When transfected human MDR cells were injected into nude mice, an inverse correlation was seen between the ability of the cells to produce M-CSF and their tumorigenicity. Thus, gene modification of MDR cancer cells seems hopeful as a therapeutic method for enhancing anti-MDRI-MAb-dependent macrophage-mediated cytotoxicity against human MDR cancer cells.
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PMID:M-CSF gene transduction in multidrug-resistant human cancer cells to enhance anti-P-glycoprotein antibody-dependent macrophage-mediated cytotoxicity. 810 Aug 9

More fundamental understanding of cell growth regulation will provide novel approaches for detecting, preventing, and treating different cancers. Activation of protooncogenes or loss of tumor-suppressor genes can have both prognostic and therapeutic importance. In epithelial ovarian cancer, poor prognosis is associated with continued expression or overexpression of tyrosine kinase growth factor receptors p170EGFR, p165fms, and p185erbB-2. Over-expression of erbB-2 (HER-2/neu) by breast and ovarian cancers already permits effective targeting of antibodies and immunotoxins. Ultimately, molecular analysis of individual cancers will guide the application of specific therapies to inhibit activated oncogenes or restore the function of tumor-suppressor genes. Circulating growth factors, oncogene products, and tumor-associated antigens may provide markers for earlier detection of some cancers. In epithelial ovarian cancer, concentrations of CA 125 can be increased 1-5 years before clinical diagnosis, and approximately 50% of patients with stage I disease have had an abnormal CA 125 concentration. Combining CA 125 with two novel markers--OVX1 and M-CSF--has retrospectively detected > 98% of stage I ovarian cancers. Although the specificity of the three markers is insufficient for cost-effective screening, serum tests for them could prompt the performance of transvaginal sonography, substantially decreasing the number of sonograms required. Genetic markers in the germ line of patients at increased risk for certain cancers will almost certainly influence strategies for prevention or detection. In familial breast, and ovarian cancer, a locus on chromosome 17q tracks risk of cancer in a fraction of kindreds. How often germline abnormalities will be detected in patients with apparently sporadic cancer remains to be determined.
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PMID:Perspectives on the future of cancer markers. 822 57

Ovarian tumor cells produce macrophage colony stimulating factor, a potent chemoattractant for monocytes. Monocytes and macrophages produce tumor necrosis factor alpha (TNF-alpha) and interleukin 1 alpha or interleukin 1 beta (IL-1 beta) that can stimulate ovarian tumor cell growth. The present study has explored whether paracrine stimulation by monocyte derived cytokines might induce autocrine growth stimulation of normal and malignant ovarian epithelial cells. Endogenous expression of TNF-alpha mRNA was detected in ascites ovarian cancer cells isolated directly from patients, but not in established cultures of normal or malignant ovarian epithelial cells. When ascites tumor cells were cultured for 7 days, TNF-alpha expression ceased but could be reinduced by treatment with TNF-alpha or IL-1 beta. Ascites fluid contained concentrations of the cytokines that could mediate these effects. Similarly, treatment of normal or malignant ovarian epithelial cells with purified recombinant IL-1 beta or TNF-alpha induced transcription of TNF-alpha mRNA within 1 h. TNF-alpha protein could be detected by enzyme-linked immunosorbent assay in conditioned medium from IL-1 beta treated ovarian cancer cells. [3H]thymidine incorporation by normal or malignant ovarian epithelial cells was stimulated by a 24-h incubation with IL-1 beta or TNF-alpha. Stimulation of proliferation by IL-1 beta could be partially blocked by an antibody against TNF-alpha or by soluble TNF-alpha-receptor. Thus, TNF-alpha may function as both an autocrine and a paracrine growth factor in ovarian cancer.
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PMID:Tumor necrosis factor alpha as an autocrine and paracrine growth factor for ovarian cancer: monokine induction of tumor cell proliferation and tumor necrosis factor alpha expression. 838 77

The discovery of peptide growth factors and cancer-causing genes (oncogenes and tumor-suppressor genes) has provided us with the exciting opportunity to begin to understand the molecular pathology of human ovarian cancer. Activation of several genes, including HER-2/neu, myc, ras, and p53 have been described in some ovarian cancers. In addition, some protooncogenes such as the epidermal growth factor receptor (erbB) and the M-CSF receptor (fms) are expressed along with the respective ligands (peptide growth factors) in some ovarian cancers. Although the studies reviewed in this paper represent a promising beginning, we remain far from a comprehensive understanding of growth regulation and transformation of human ovarian epithelium.
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PMID:Growth regulation and transformation of ovarian epithelium. 842 Jun 75

We studied the production of macrophage colony-stimulating factor (M-CSF) and the expression of c-fms mRNA, an M-CSF receptor, in four human ovarian cancer cell lines. All four cell lines expressed c-fms mRNA while three secreted M-CSF into the culture medium. The exogenous administration of M-CSF caused no significant enhancement of cellular proliferation in any cell line. Interestingly, the proliferation of KK cells was not affected by anti-M-CSF antibody. These results, taken together with the fact that ovarian cancer cells simultaneously produce M-CSF and c-fms, suggest that an autocrine mechanism may modulate cellular proliferation.
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PMID:Expression of c-fms proto-oncogene product by ovarian cancer cell lines with effects of macrophage colony-stimulating factor on proliferation. 860 48

To develop a therapeutic modality for overcoming multidrug-resistant (MDR) cancer with anti-MDR1 antibody, we examined the effect of macrophage colony-stimulating factor (M-CSF) gene transfection into MDR AD10 cells on therapy of MDR cancer with anti-MDR1 antibody (MRK17) in nude mice. MDR human ovarian cancer (AD10) cells were transduced with the human M-CSF gene inserted into an expression vector to establish gene-modified cells capable of producing low (ML-AD10), intermediate (MM-AD10) nd high (MH-AD10) amounts of M-CSF. Systemic administration of MRK17 resulted in significant dose-dependent inhibition of subcutaneous growth of ML-AD10 tumors. In contrast, systemic administration of recombinant M-CSF in combination with MRK17 did not augment the therapeutic efficacy of MRK17 alone, but rather promoted the growth of the parent AD10 cells. To test the efficacy of in vivo M-CSF gene therapy combined with antibody, we mixed the parent AD10 cells with MH-AD10 cells producing a large amount of M-CSF, and inoculated the mixed cells subcutaneously. Treatment with MRK17 inhibited growth of the mixed cells more than that of the parent cells alone. Thus, combined therapy with anti-MDR1 mAb and M-CSF gene modification of MDR cancer cells may provide a new immunotherapeutic modality for overcoming MDR in humans.
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PMID:Transduction of the macrophage colony-stimulating factor gene into human multidrug resistant cancer cells: enhanced therapeutic efficacy of monoclonal anti-P-glycoprotein antibody in nude mice. 869 27

More than 90% of epithelial ovarian cancers arise from single cells. Malignant transformation can be associated with a number of molecular alterations including upregulation of tyrosine kinases and phosphatases, physiologic activation o ras, mutation of p53, amplification of myc, and increased activity of matrix metalloproteinases 2 and 9. Proliferation of transformed epithelial cells can be enhanced through the persistence of autocrine growth stimulation by TGF-alpha, loss of autocrine growth inhibition by TGF-beta, as well as paracrine growth stimulation by macrophage derived cytokines and OCAF, a novel lyso-phospholipid. Ascites tumor cells retain responsiveness to growth inhibition by TGF-beta which induces apoptosis in malignant ovarian epithelial cells, but not in normal ovarian surface epithelium. Proliferation of surface epithelial cells following ovulation may contribute to the pathogenesis of ovarian cancer. Use of oral contraceptives that suppress ovulation has been associated with reduced risk of ovarian cancer in later life. Retinoids also deserve further evaluation for chemoprevention. Treatment with fenretinide was associated with decreased incidence of ovarian cancer. Additive or synergistic inhibition of ovarian tumor cell proliferation has been observed with TGF-beta in combination with all-trans-retinoic acid. Early detection of ovarian cancer could improve survival. Transvaginal sonography (TVS) and serum markers such as CA-125 have been evaluated in multiple clinical trials. The former lacks adequate specificity, whereas the latter is not sufficiently sensitive. Use of multiple serum markers can improve sensitivity. A combination of CA-125, M-CSF and OVX-1 has detected > 95% of Stage I ovarian cancers. If similar results are obtained with different data sets, multiple serum markers could be used to trigger the performance of TVS, providing a potentially cost effective screening strategy. Prospective trials will be required to demonstrate that screening for early stage ovarian actually impacts on survival.
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PMID:Molecular approaches to prevention and detection of epithelial ovarian cancer. 874 99

We defined a cytokine mRNA profile of 12 ovarian cancer biopsies, 10 normal/benign biopsies, six ovarian cancer cell lines and three ovarian cancer xenografts, using RT-PCR. The profile, based on screening for 25 cytokines and 12 receptor mRNAs, was rich in growth factors, pro-inflammatory cytokines and chemokines, but weak in lymphocyte-associated cytokines. The pattern was unique to ovarian tissue, but similar in normal, benign and malignant biopsies, with > 80% samples expressing 16 cytokines in common. Fourteen of these were also expressed by > 65% cell lines, but fewer were detected in xenografts. Potential autocrine loops existed for IL-1, IGF-1, M-CSF, GM-CSF and TNF-alpha. IL-4 and IFN-gamma receptors were expressed in absence of ligand. Chemokines RANTES, MIP-1 alpha and MIP-1 beta were expressed in biopsies, but were rarely detected in cell lines and absent from xenografts. IGF-1 and its receptor was expressed in every sample, as was IFN-gamma receptor. Another 10 cytokine mRNAs and six receptors were expressed in > 80% samples. These may contribute to key survival/growth loops. Similarities between normal and malignant biopsies suggest that analogous processes of remodelling and repair occur. RT-PCR proved a rapid, reproducible screen, but further assays are required to detect quantitative differences between normal and malignant tissues and tumour models.
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PMID:A cytokine profile of normal and malignant ovary. 889 39

It has been proposed that epithelial ovarian cancers are of unifocal origin and arise from a single cell. Many alterations occur during the multistep carcinogenesis including interaction of peptide growth factors, activation of protooncogenes, and loss of tumor-suppressor genes. Increased activity of TGF-alpha and decreased activity of TGF-beta may contribute to the development of many ovarian cancers. Loss of TGF-beta responsiveness has been associated with the downregulation of c-myc expression in the development of ovarian cancer. Alternative expression of many oncogenes including ras, erbB2 and c-myc, were detected in many studies. p53 mutation was detected in 50% of advanced ovarian cancer, suggesting that loss of tumor-suppressor gene function facilitates transformation. Serum parameters like AFP, CEA, CA-125, IAP, LDH, SA, TGF-alpha, and M-CSF have been used as ovarian tumor markers. None of these biochemical markers is presently consistent and specific enough to be an early detection for ovarian cancers.
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PMID:Molecular biology of human ovarian cancer. 891 82


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