Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biology of the fibroblast growth factor (FGF) gene family is reviewed. The structure, expression and known and putative functions of the seven members of this family characterized to date are discussed. These genes include: acidic and basic FGF, the INT.2 and HST proto-oncogenes and the recently characterized FGF.5, FGF.6 and KGF genes. These genes play a role in various processes such as cell proliferation, angiogenesis and embryogenesis, and possibly carcinogenesis.
 ...
PMID:Biology of the fibroblast growth factor gene family. 169 62

Upregulation of acidic and basic fibroblast growth factors (FGF-1 and -2), and their cognate receptors FGFR-1 and -2, has been demonstrated in a variety of epithelial malignancies. However, the patterns of FGF/FGFR expression at specific stages of epithelial carcinogenesis have not been extensively characterized. In this report, the levels of FGF-1, FGF-2, FGF-7 mRNA and their receptors FGFR-1 and FGFR-2, were investigated during epidermal carcinogenesis in transgenic mice expressing the early region of the 'high risk' papillomavirus type 16 (HPV16) under control of the human keratin-14 enhancer/promoter (K14-HPV16 transgenic mice). FGF-1 was first upregulated in dysplasias, while FGF-2 was constitutively expressed in non-transgenic, neoplastic, and malignant keratinocytes throughout carcinogenesis. Expression of FGF-7 was undetectable in non-transgenic epidermis, and remained at threshold levels at all stages of progression. In well differentiated squamous cancers, FGFR-1 was upregulated and co-localized with angiogenic capillaries in the dermis underlying dysplastic lesions and within papillary fronds of invasive cancers. In contrast, FGFR-1 was upregulated specifically within the malignant squamous cells of moderate-poorly differentiated squamous cancers. The expression of FGFR-2 was essentially constitutive in both non-transgenic and neoplastic epidermis. Collectively the data suggest that the FGF/FGFR signaling pathways may potentially contribute to several facets of multi-stage epithelial carcinogenesis, including auto- or paracrine growth stimulation, upregulation of angiogenesis, and stromal remodeling.
 ...
PMID:Upregulation of fibroblast growth factors and their receptors during multi-stage epidermal carcinogenesis in K14-HPV16 transgenic mice. 893 30

A review is presented on the role of conventional and molecular tumour markers (TM) in diagnosis and monitoring of patients with biliopancreatic malignancies. For biliopancreatic malignancy, following CEA as more historical and basic TM of gastrointestinal diseases, the mainstay marker is CA 19-9 as monosialo-ganglioside/glycolipid and sialyl derivative of lacto-N-fucopentaose II (sialyl-Lewis(a), hapten of human Lewis(a) bloodgroup determinant). It is detected in serum of healthy individuals at low concentration < 40 U/ml, with lower and often transitional elevation in benign hepatobiliary diseases and with highest levels in excretory ductal pancreatic adenocarcinoma (s = 70%-95%, sp = 72%-90%), biliary (s = 55%-79%), hepatocellular and cholangiocellular cancer (s = 22%-51%) besides gastric, colorectal and ovarian cancer and occasionally in lung, breast and uterine cancer. Physiologically elevated concentrations in healthy individuals have to be considered in all sorts of secretions (e.g. sputum, saliva, bronchial/gastric secretions, bile juice) of individuals with Lewis(a)-positive secretor status in contrast with low or lacking serum levels of CA 19-9 in patients with Lewis(a-/b-) status (7%-10% of population). In biliopancreatic malignancies, especially pancreatic cancer, CA 19-9 correlates well with clinical course of disease following surgical, chemo- or radiotherapy by a quick normalisation within 2-4 weeks after complete surgery, a transient decrease with successful palliative therapy and an often anticipated increase (lead time up to 6 months) before clinical detection in case of relapse or progressive disease. From CA 19-9 related TM tests some are detecting in addition to sialyl-Lewis(a) (sialyllacto-N-fucopentaose II) also the non-fucosylated precursor sialyl-Lewis(c) (sialyllacto-N-tetraose: CA 50, CA 242, Span-1) solely detected by the DUPAN-2 test and independent of the Lewis(a) secretor status. Some other markers comprise in addition to sialyl-Lewis(a) partially the non-sialylated Lewis(a) antigen (CA 195, CAM 43, CA 494) or are less related (CAM 17.1). The initial phase of screening and early detection is hoped to be better assessed by using molecular markers detecting gene mutations (p53, K-ras), growth factors (EGF, TGF-alpha, TGF-beta, HB-EGF, a/bFGFs, KGF) and growth factor receptor alterations (EGFr, c-erbB2/3/4). From these, K-ras mutations detected in blood, stool and bile juice of patients at risk for pancreatic cancer seem to be more promising than p53 alterations as a more later step in carcinogenesis, although they are neither yet well established nor standardised by reliable assays. In contrast growth factor and growth factor receptor alterations mainly concerning signal transducing systems seem to reflect increased tumour aggressiveness, thus shorter survival and poorer prognosis thereby contributing in the selection of patients for more aggressive therapy.
 ...
PMID:Role of tumour markers, cytogenetics. 1043 9

Prostate cancer is the most common malignancy in males. Despite the efforts for an early diagnosis, approximately one third of the cases are diagnosed in advanced clinical stages. Prostatic cancer, as the function of normal prostate is dependent upon androgens. So, androgenic deprivation represents an effective treatment especially in advanced cases. Although, the majority of patients will initially respond to androgen blockade, consequently the hormone-resistance will develop and the tumor will progress. The mechanism that determines tumoral progression during the endocrine treatment is driven by genomic instability, characterized by activating mutations of androgen receptor gene (AR), progression of some cellular clones possible of neuroendocrine origin that become adapted to low concentrations of residual adrenal androgens, suppression of apoptosis, by bcl-2 oncogene overexpression and p53 mutations, and growth factors (IGF-1--Insulin-like growth factor, KGF--keratinocyte growth factor, EGF--Epidermal growth factor, TGF a, b- Transforming growth factor a and b, bFGF--Fibroblastic growth factor type b) regulatory effect through either a paracrine or an autocrine mechanism. The identification of molecular alterations that appear during prostate carcinogenesis, may lead to the identification of new molecular targets to prevent hormone-resistance and to improve the prognosis in prostate cancers.
 ...
PMID:Molecular mechanisms in hormone-resistant prostate cancer. 1660 54

This study investigates the influence of fibroblast growth factor receptor type B (FGFRb) and fibroblast growth factor on cervical carcinogenesis associated with HPV16 E6/7 infection, using primary cancer cells isolated from Taiwanese patients with cervical cancer. Functional interaction between FGFRb in Cx cells and HPV16 E6/7 transfected Cx cells (CxWJ cells) following treatment with FGF-7, according to cell growth, invasive ability, and tumor growth in SCID mice. Our results indicate that the downregulation of FGFRb gene expression in CxWJ cells partially represses proliferation and the invasive ability provided by FGF-7 stimulation. In SCID mice, the FGF2 and FGFR1 gene expression ascend in CxWJ tumor nodule. These data provide evidence of a functional interaction between HPV16 E6/7 in FGFRb and FGF2, suggesting that cooperative stimulation of HPV E6/7 in inactivated FGFRb and the upregulation of FGF2 may be necessary to completely overcome the oncogenic function associated with the progression of cervical carcinogenesis.
 ...
PMID:Influence of HPV16 E6/7 on the expression of FGF2 and FGFR type B in cervical carcinogenesis. 2242 47

Keratinocyte growth factor (KGF, fibroblast growth factor-7) is a fibroblast-derived mitogen, which stimulates proliferation of epithelial cells. The expression of KGF by dermal fibroblasts is induced following injury and it promotes wound repair. However, the role of KGF in cutaneous carcinogenesis and cancer progression is not known. We have examined the role of KGF in progression of squamous cell carcinoma (SCC) of the skin. The expression of KGF receptor (KGFR) mRNA was lower in cutaneous SCCs (n = 6) than in normal skin samples (n = 6). Expression of KGFR mRNA was detected in 6 out of 8 cutaneous SCC cell lines and the levels were downregulated by 24-h treatment with KGF. KGF did not stimulate SCC cell proliferation, but it reduced invasion of SCC cells through collagen. Gene expression profiling of three cutaneous SCC cell lines treated with KGF for 24 h revealed a specific gene expression signature characterized by upregulation of a set of genes specifically downregulated in SCC cells compared to normal epidermal keratinocytes, including genes with tumor suppressing properties (SPRY4, DUSP4, DUSP6, LRIG1, PHLDA1). KGF also induced downregulation of a set of genes specifically upregulated in SCC cells compared to normal keratinocytes, including genes associated with tumor progression (MMP13, MATN2, CXCL10, and IGFBP3). Downregulation of MMP-13 and KGFR expression in SCC cells and HaCaT cells was mediated via ERK1/2. Activation of ERK1/2 in HaCaT cells and tumorigenic Ha-ras-transformed HaCaT cells resulted in downregulation of MMP-13 and KGFR expression. These results provide evidence, that KGF does not promote progression of cutaneous SCC, but rather suppresses the malignant phenotype of cutaneous SCC cells by regulating the expression of several genes differentially expressed in SCC cells, as compared to normal keratinocytes.
 ...
PMID:Keratinocyte growth factor induces gene expression signature associated with suppression of malignant phenotype of cutaneous squamous carcinoma cells. 2242 41