Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two subtypes of thrombospondin (TSP-1 and TSP-2) have inhibitory roles in angiogenesis in vitro, although the biological significance of these TSP isoforms has not been determined in vivo. We examined TSP-1 and TSP-2 gene expression by reverse transcription polymerase chain reaction (RT-PCR) analysis in 61 colon cancers. Thirty-eight of these 61 colon cancers were positive for TSP-2 expression and showed hepatic metastasis at a significantly lower incidence than those without TSP-2 expression (P = 0.02). TSP-2 expression was significantly associated with M0 stage in these colon cancers (P = 0.03), whereas TSP-1 expression showed no apparent correlation with these factors. The colon cancer patients with TSP-2 expression showed a significantly low frequency of liver metastasis correlated with the cell-associated isoform of vascular endothelial growth factor (VEGF-189) (P = 0.0006). Vascularity was estimated by CD34 staining, and TSP-2(-)/VEGF-189(+) colon cancers showed significantly increased vessel counts and density in the stroma (P < 0.0001). TSP-2(-)/VEGF-189(+) colon cancer patients also showed significantly poorer prognosis compared with those with TSP-2(+)/VEGF-189(-) (P = 0.0014). These results suggest that colon cancer metastasis is critically determined by angiogenesis resulting from the balance between the angioinhibitory factor TSP-2 and angiogenic factor VEGF-189.
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PMID:Thrombospondin 2 expression is correlated with inhibition of angiogenesis and metastasis of colon cancer. 988 80

The purpose of this study was to investigate the clinical usefulness of the color Doppler vascularity index (CDVI) in patients with colon cancer before surgery. Forty-four patients with sonographically visible tumor mass of colon cancer were investigated. The CDVI of each tumor was determined using transabdominal color Doppler ultrasound. The CDVI was defined as the ratio of the number of the colored pixels within a tumor section to the number of total pixels in that specific tumor section and was calculated by using Encomate software (Electronic Business Machine Co. Ltd., Taipei, Taiwan). The correlation between the CDVI and clinicopathological factors, mode of recurrence, and patient survival was studied. For comparison, microvessel density (the mean number of microvessels in three areas of highest vascular density at x200 magnification) of the tumors of these 44 patients was also evaluated by using immunohistochemical staining of surgical specimens with anti-CD34. The microvessel density was not correlated with Dukes' classification, clinicopathological factors, and survival. The CDVI was significantly higher in the patients with lymph node metastases and vascular invasion than in those without such metastases and invasion (P = 0.006 and P = 0.0098, respectively). Moreover, in patients with a high CDVI (> 15%) and positive vascular invasion, survival was significantly poorer than in those with low CDVI (< or = 15%) and negative invasion (P = 0.0037 and 0.0039, respectively). Multivariate analysis indicated that liver metastasis, vascular invasion, and CDVI are independent prognostic factors in the patients with colon cancer. According to the mode of recurrence in 36 patients who underwent curative resection, the frequency of the distant organ recurrence was significantly higher in the high CDVI group (40%) than in the low CDVI group (0%). The CDVI is a good preoperative indicator of recurrence and patient survival in colon cancer. Thus, the CDVI may be helpful in stratifying patients for adjuvant therapy.
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PMID:Color Doppler vascularity index can predict distant metastasis and survival in colon cancer patients. 1085 Apr 34

Angiogenesis is an essential requirement for the development, progression and metastasis of malignant tumors. Vascular endothelial growth factor (VEGF) plays an essential role in the development of angiogenesis of numerous solid malignancies, including colon cancer. The tumor suppressor gene p53 is a potent transcriptional regulator of genes which are involved in many cellular activities, including cell-cycle arrest, apoptosis and angiogenesis. In order to better understand the relation among p53 status, VEGF expression and microvessels count (MVC) in colon cancer, we evaluated immunoreactivity for CD34 endothelium-associated antigen, VEGF and p53 proteins in 43 cases of colon adenocarcinoma. Our results demonstrated an association between VEGF expression, p53 status and angiogenesis, suggesting that mutant p53 plays a central role in promoting angiogenesis in colon cancer progression.
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PMID:Neoangiogenesis in colon cancer: correlation between vascular density, vascular endothelial growth factor (VEGF) and p53 protein expression. 1195 38

Plasminogen activator inhibitor-1 (PAI-1) is up-regulated strongly in various cancer tissues, including colon cancer tissue. Highly specific rabbit polyclonal antibodies against PAI-1 were used for immunohistochemical localization of PAI-1 in 12 invasive colorectal adenocarcinomas. PAI-1 immunoreactivity was observed in endothelial cells of some vessels located in the submucosa and in several fibroblast-like cells located at the invasive front. No PAI-1 immunoreactivity was seen in cancer cells in any of the 12 cases. Double immunofluorescence using the PAI-1 antibodies together with antibodies against alpha-smooth muscle actin for myofibroblast/smooth muscle cells and CD34 for endothelial cells showed that more than 80% of the PAI-1-positive fibroblast-like cells in all 12 cases were myofibroblasts. In 4 of 12 cases, a few of the PAI-1-positive fibroblast-like cells in the invasive front were CD34+. We conclude that the majority of PAI-1-positive fibroblast-like cells located at the leading edge of the invasive colon cancers are myofibroblasts.
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PMID:Leading-edge myofibroblasts in human colon cancer express plasminogen activator inhibitor-1. 1532 43

ZCH-2B8a (IgG2a) is a novel monoclonal antibody (McAb) generated in laboratory of Children Hospital of Medical College, Zhejiang University recently using human myeloblastic leukemia cell line KG1a as immunogen. This antibody has been submitted to the 8th International Workshop and Conference on Human Leukocyte Differentiation Antigens (HLDA8) and the results showed that the antibody recognized an unknown molecule on the surface of some blood cells. The aim of this study was to investigate the reactivity of this antibody on normal blood cells and malignant cell lines and to explore its possible application in clinical practice. The multi-parameter flow cytometry was used to analyze the expression pattern of 2B8a antigen in triplicate on normal blood components including T cells, B cells, natural killers (NK), neutrophils, monocytes, dendritic cells (DC), red blood cells (RBC), platelets (Plt), hematopoietic stem/progenitor cells derived from either bone marrow or G-CSF mobilized peripheral blood CD34(+) cells and malignant cell lines including 14 hematopoietic, 5 neuroblastoma, 1 colon cancer and 1 amniotic epithelium cell lines. The amount of positive cells > or = 20% was considered as positivity. The results showed that 2B8a antibody reacted to 3/3 specimens of blood B cells with a positive rate of 26.29% and 2/3 specimens of monocytes with an average positive rate of 59.84%. 2B8a was weakly reactive to neutrophils (23.72%) and negative for T cells, NK, DC, RBC and Plt. The antibody reacted to all 3 marrow CD34(+) cells with an average positive rate of 39.33% while it was negative for G-CSF-mobilized CD34(+) peripheral blood stem/progenitor cells (PBSC, 1.25%). Cell line analysis showed that the antibody notably reacted to three out of 4 cell lines (Raji, SMS-SB, Nalm-6 and Nall-1) with the positive rates of 98.78%, 98.61%, 94.93% respectively and weakly to one of them with 5.68% in B lineage cell lines and monoblastic cell line (U937, 67.78%) while it was only weakly positive or negative for other myeloid leukemia cell lines including Meg01 (33.40%), HL-60 (29.70%), K562 (28.19%), KG1a (16.23%) and HEL92.1.7 (8.02%). Among 4 T lineage leukemia, 5 neuroblastoma and 1 colon cancer cell lines tested, only Molt-3 was found weakly positive (31.40%) for 2B8a, while the remaining 3 T cell lines (Molt4, JM and CCRF-CEM), 5 neuroblastoma cell lines (LA-N1, KCNR, BE, SK-N-SH, SK-N-AS) and the colon cancer cell line (HR8348) tested were negative. An amniotic epithelium cell line (FL) was showed positive for the antibody (45.03%). It is concluded that 2B8a antibody primarily reacts to B lineage and monocytic lineage cells which may bear the diagnostic and therapeutic applications among different types of hematopoietic malignancies.
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PMID:[Reactivity of a novel monoclonal antibody ZCH-2B8a on normal hematopoietic cells and malignant cell lines and its significance]. 1709 4

CD34 is commonly used as an endothelial cell marker of tumor vessels. However, this marker detects not only newly formed, but also pre-existing large blood vessels. Nestin, a class VI intermediate filament protein, has recently received attention as a marker for detecting newly formed endothelial cells. In this study, whether nestin is a novel angiogenesis marker in colorectal cancer was examined. HCT-15, a human colon cancer cell line, was subcutaneously implanted into the dorsum of nude mice. After the tumor grew, the mice were perfused with fluorescent beads (Fluospheres). Then, the tumor tissues were used for immunofluorescence staining using nestin and the CD34 antibody. Immunohistochemistry was performed with nestin and CD34 on 101 human colorectal cancer tissue samples. Proliferating endothelial cells were detected immunohistochemically by a proliferating cell nuclear antigen (PCNA) antibody. Clinicopathological factors and prognosis were compared between two groups: that with a microvessel density (MVD) higher than the median MVD and that with MVD lower than the median MVD, as detected by nestin and CD34 labellings. Nestin was localized in endothelial cells in small blood vessels (median, 9.06 microm), whereas CD34 was localized in large blood vessels (median, 9.67 microm) in nude mice. The diameter of nestin-positive vessels was smaller than that of CD34-positive vessels in human colorectal cancer. The number ratio of PCNA-positive cells to nestin-positive vascular endothelial cells was higher than that of PCNA-positive to CD34-positive cells (p=0.002). There were no correlations between nestin-positive blood vessels and clinicopathological factors, but the prognosis was worse in the highly nestin-positive MVD group (p=0.071). Nestin is considered a novel angiogenesis marker of proliferating endothelial cells in colorectal cancer tissue.
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PMID:Identification of neovasculature using nestin in colorectal cancer. 1727 60

Insulin-like growth factors are known to inhibit apoptosis and promote tumour angiogenesis. Previously we have shown that insulin-like growth factor binding protein-4 (IGFBP-4) gene therapy increased apoptosis and decreased mitosis in colon cancer. In this experiment we used HT-29 colon cancer cells to induce subcutaneous cancers in nude mice and administered either the mammalian expression vector with IGFBP-4 insert or vector only around the tumour site. Three weeks after gene transfer, tumours were harvested and expressions of Bax, Bcl-2 and IGF-I receptor in tumours were determined by Western blotting and immunofluorescence. Micro-vessel counting was performed by immunostaining with CD34 and von Willebrand antibodies. Results showed that tumours treated with IGFBP-4 gene had higher expression of Bax, lower expression of Bcl-2 and IGF-I receptor. Bcl-2 was localised to tumour cell cytoplasm while Bax was expressed both in the interstitial area and cytoplasm. IGFBP-4 treatment also decreased micro-vessel count in tumour tissues. Micro-vessels were mainly located in the periphery and interstitial area. This experiment shows that IGFBP-4 gene therapy increases tumour apoptosis via altering the expressions of Bcl-2 and Bax and decreasing the angiogenesis in colorectal cancer.
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PMID:Insulin-like growth factor binding protein-4 gene therapy increases apoptosis by altering Bcl-2 and Bax proteins and decreases angiogenesis in colorectal cancer. 1733 27

Invasive micropapillary carcinoma has recently been reported in various anatomic sites. In this article, we report a case of micropapillary carcinoma of the sigmoid colon. A 70-year-old Japanese woman presented with bloody stool for 2 months. Detailed examination disclosed ulcerative and localized tumor in the sigmoid colon. Histological examination of the colon tumor showed a combination of conventional adenocarcinoma (60%) and micropapillary carcinoma (40%). Immunohistochemically, micropapillary carcinoma cells were positive for cytokeratin (CK) 20, carcinoembryonic antigen, and CA125, but negative for CK7, thyroid transcription factor-1, surfactant apoprotein A, estrogen receptor, and progesterone receptor. Additionally, the immunohistochemistry of epithelial membrane antigen revealed reverse polarity of neoplastic cells. Results of conventional adenocarcinoma were basically identical to those of micropapillary carcinoma. In the stroma of both conventional adenocarcinoma and micropapillary carcinoma, many myofibroblasts were present and CD34-positive stromal cells were absent. Finally, we report the fourth case of micropapillary carcinoma arising in the colon. Immunohistochemical results of CK7(-)/CK20(+) strongly suggest the colon as a primary site of micropapillary carcinoma. Additionally, micropapillary carcinoma of the colon may cause a similar stromal reaction to conventional adenocarcinoma of the colon.
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PMID:Invasive micropapillary carcinoma of the colon: an immunohistochemical study. 1808 84

Acute myeloid leukemia (AML) is the most frequently diagnosed adulthood leukemia, yet current therapies offer a cure rate of less than 30%. This may be due in part to the fact that the leukemia-initiating cells in AML reside within the rare and highly primitive CD34(+)CD38(-) hematopoietic stem/progenitor cell (HSC) population that are often resistant to chemotherapy. Docosahexanoic acid (DHA), a major component of fish oil, has previously been shown to inhibit the induction and progression of breast, prostate and colon cancer, and increase the therapeutic effects of numerous chemotherapeutics, often by enhancing apoptosis. In the present studies, we investigated DHA's effect on the primitive and undifferentiated AML cell line KG1a, to explore the potential of this fatty acid to serve as adjuvant therapy for AML. Treatment of KG1a cells with DHA for 96 hours did not lead to maturation or cell cycle modification when compared to an untreated KG1a control (n = 4). However, DHA treatment of KG1a cells resulted in a progressive loss of viability, DNA fragmentation, and an increase in Annexin V expression, demonstrating DHA-induced apoptosis (n = 4). Moreover, expression of the pro-apoptotic protein Bax was increased, with resultant skewing in the Bax/bcl-2 ratio, providing a mechanistic explanation for the observed DHA-induced increase in apoptosis. Since we also show that DHA does not have a detrimental effect on normal hematopoiesis our results suggest that DHA could potentially serve as an well-tolerated adjuvant in the treatment of AML patients.
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PMID:Docosahexaenoic acid induces dose dependent cell death in an early undifferentiated subtype of acute myeloid leukemia cell line. 1919 47

Recent reports have suggested critical roles of myeloid cells in tumor invasion and metastasis, although these findings have not led to therapeutics. Using a mouse model for liver dissemination, we show that mouse and human colon cancer cells secrete CC-chemokine ligands CCL9 and CCL15, respectively, and recruit CD34(+) Gr-1(-) immature myeloid cells (iMCs). They express CCL9/15 receptor CCR1 and produce matrix metalloproteinases MMP2 and MMP9. Lack of the Ccr1, Mmp2, or Mmp9 gene in the host dramatically suppresses outgrowths of disseminated tumors in the liver. Importantly, CCR1 antagonist BL5923 blocks the iMC accumulation and metastatic colonization and significantly prolongs the survival of tumor-bearing mice. These results suggest that CCR1 antagonists can provide antimetastatic therapies for patients with disseminated colon cancer in the liver.
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PMID:Inactivation of chemokine (C-C motif) receptor 1 (CCR1) suppresses colon cancer liver metastasis by blocking accumulation of immature myeloid cells in a mouse model. 2061 8


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