Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the current study, mesenteric and peritumoral lymph nodes surgically removed from patients with colon-rectum cancer were studied. Morphologic and immunocytochemical investigations demonstrated that mesenteric (control) and peritumoral lymph nodes of a same patient showed the same morphologic structure, but a different immunocytochemical pattern. Indeed, an increased immunoreactivity to anti-inducible nitric oxide synthase, anti-tumor necrosis factor-alpha, and anti-adrenocorticotropic hormone antibodies in the lymphatic tissue of peritumoral lymph nodes compared with mesenteric lymph nodes was observed. These findings suggest that in colon-rectum cancer, the pathologic event induces an increased expression of the molecules involved in the processes of inflammation and carcinogenesis that occurs earlier than the appearance of morphologic modifications.
Appl Immunohistochem Mol Morphol 2002 Mar
PMID:Immunocytochemical increased evidence of inducible nitric oxide synthase, tumor necrosis factor-alpha, and adrenocorticotropic hormone in human peritumoral lymph nodes. 1189 36

In this study we evaluated whether positron emission tomography (PET) using the amino acid [11C]methyl- L-methionine (MET) may be used for therapy monitoring in patients with rectal cancer who are undergoing preoperative chemoradiotherapy. A total of 41 MET-PET scans were performed in 26 patients with locally advanced rectal cancers. All patients were examined prior to chemoradiotherapy. In 15 patients, MET-PET was repeated after preoperative chemoradiotherapy (45 Gy radiation dose, 250 mg 5-fluorouracil as continuous infusion). MET uptake prior to and after the completion of chemoradiotherapy was correlated with changes in T stage and histopathological regression. All tumours were visualised with high contrast and had a significantly higher SUV (5.7+/-2.2) than normal rectum (2.7+/-0.9) and all other organs in the field of view except the small intestine (3.9+/-1.7). In all tumours studied prior to and after chemoradiotherapy, MET uptake decreased during therapy (SUV before therapy, 6.2+/-2.3; SUV after therapy, 2.6+/-1.2; P=0.0007). However, the degree of change in MET uptake was not correlated with histopathological tumour response. In conclusion, primary rectal cancer can be imaged with MET-PET. However, for the studied chemoradiotherapy regimen, MET-PET did not allow an assessment of the response to therapy.
Eur J Nucl Med Mol Imaging 2002 Jun
PMID:PET imaging with [11C]methyl- L-methionine for therapy monitoring in patients with rectal cancer. 1202 53

Accurate response assessment after neoadjuvant therapy is essential in patients with rectal cancer. The aim of this study was to assess the value of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting response of locally advanced rectal cancer to preoperative multimodal treatment. Twenty-two consecutive patients with locally advanced (uT3/4) primary rectal cancer were entered in this prospective pilot study. FDG-PET was performed before and after neoadjuvant radiochemotherapy (RCT) with combined regional hyperthermia (RHT). Treatment consisted of external-beam radiotherapy (45 Gy), chemotherapy (folinic acid and 5-fluorouracil) and regional pelvic hyperthermia followed by curative tumour resection 6-8 weeks later. Semi-quantitative measurements (SUV) of tumour FDG uptake were made before and 2-4 weeks after completion of neoadjuvant treatment. Two patients who did not receive post-therapeutic restaging by FDG-PET were excluded from the analysis. Results were correlated with findings on endorectal ultrasound (EUS, n=17 patients) and histopathology. Histopathological evaluation of the resected tumour revealed complete response in one patient, partial response in 12 and stable disease in seven. SUV reduction in tumours was significantly greater in responders than in non-responders [60% (+/-15%) vs 30% (+/-18%), P=0.003, CI=95%). Using a minimum post-therapeutic SUV reduction of 36% to define response, FDG-PET revealed a sensitivity of 100% (EUS: 33%) and a specificity of 86% (EUS: 80%) in response prediction; the corresponding positive and negative predictive values were 93% (EUS: 80%) and 100% (EUS: 33%), respectively. FDG-PET results were statistically significant (P<0.001, CI=95%). FDG-PET has great potential in the assessment of tumour response to neoadjuvant RCT in combination with RHT and is superior to EUS for this purpose.
Eur J Nucl Med Mol Imaging 2004 Jun
PMID:Response prediction by FDG-PET after neoadjuvant radiochemotherapy and combined regional hyperthermia of rectal cancer: correlation with endorectal ultrasound and histopathology. 1476 98

Local immunoregulation mediated by infiltration of inflammatory cells into colorectal adenocarcinomas is important for tumour progression. Tumour-associated macrophages and T cells are predominant components of chemokine-guided infiltrate of most colorectal tumours. CXCL16 is a newly discovered CXC chemokine expressed by antigen presenting cells attracting Th1, Tc and NK T cells. In this study, which is the first report on expression of the chemokine CXCL16 in human rectal cancer, CXCL16 gene and protein expression were analysed in cancer and normal adjacent tissue. Immunohistochemistry revealed CXCL16 expression in macrophages in normal tissue. The CXCL16 was found to a very limited extent in tumour-associated macrophages. Western blot analysis showed a suppression of CXCL16 protein in rectal cancer compared to non-cancer tissue in 83% of the patients (n=23, P=0.003). However, with real-time PCR mRNA was not down-regulated in the cancer compared to normal tissue, which may depend on regulated factor(s) at the level of translation and/or post-translation. The results may reflect one of the immunological mechanisms underlying carcinogenesis.
Int J Mol Med 2004 Jul
PMID:Expression of CXCL16 in human rectal cancer. 1520 17

Thymidine phosphorylase (TP) is known to be more concentrated in human cancer tissues than in adjacent normal tissue based on findings using enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. However, the ultrastructural localization of TP in cancer tissues has not previously been demonstrated. We investigated the localization of TP in gastric cancer and colorectal cancer tissue by ELISA, immunohistochemistry, and immunoelectron microscopy. Between April 1997 and May 2000, we obtained surgically resected specimens from 42, 46, and 36 cases of advanced gastric, colon, and rectal cancer, respectively. ELISA demonstrated that the TP level was higher in cancer tissues than in adjacent normal tissue. Immunohistochemically, cancer cells were positive for the enzyme in some cases. However, in a number of cases immunopositive inflammatory cells were also present in cancerous tissues. At the electron microscope level, TP was diffusely distributed in the cytoplasm of cancer cells and in the mitochondria of the neutrophil in gastric cancer tissue. In rectal cancer tissues, cytoplasmic granules in macrophages in cancer tissues were immunoreactive for the TP. These findings suggest that TP is produced by macrophages and exists in neutrophils and cancer cells.
J Mol Histol 2004 Jan
PMID:Localization of thymidine phosphorylase in advanced gastric and colorectal cancer. 1532 51

Many checkpoint proteins that are involved in the control of the cell cycle and apoptosis have been investigated, but only a few studies have evaluated the prognostic significance of multiple factors only in rectal carcinomas. The aim of this study was to determine the role of p53, p21, and p27 protein expression as a prognostic factor in rectal carcinomas. Formalin-fixed, paraffin-embedded tissue blocks from 45 rectal adenocarcinomas with appropriate clinical and prognostic data were examined. The standard streptavidin-biotin immunoperoxidase method was used for immunostaining with p53 protein, p21 WAF1/Cip1 protein, and p27 Kip1 protein. The extent of positive p53, p21, and p27 staining was graded semiquantitatively. The clinicopathologic and prognostic features were statistically analyzed. No significant association was found between p53 status and p21 or p27 protein expression (chi2 test, P=0.42 and P=0.18 respectively). There was no correlation between the expressions of p53, p21, and p27, and conventional clinicopathologic features. The mean time interval to recurrence was 25.7+/-24.7 months (range, 0-54 months). p53, p21, and p27 expression was not associated significantly with recurrence and distant metastasis. However, a significant relationship was found between the expression of p27 protein and hepatic metastasis (independent samples t-test, P=0.007). The authors concluded that p53, p27, and p21 protein expression was not related to the clinicopathologic parameters, tumor aggressiveness, metastatic potential, and survival in rectal carcinomas. Further studies are needed to evaluate the predictors of outcome in rectal cancer, considering a variety of prognosticators.
Appl Immunohistochem Mol Morphol 2005 Mar
PMID:The clinical significance of p53, p21, and p27 expressions in rectal carcinoma. 1572 92

The field of pharmacogenomics has seen some exciting advances in the recent past. The Human Genome Project and International HapMap projects have uncovered a wealth of information for researchers. The discovery of clinically predictive genotypes (e.g. UGT1A1*28, TYMS TSER), haplotypes (e.g. VKORC1 Haplotype A) and somatic mutations (e.g. epidermal growth factor receptor), along with the introduction of FDA approved pharmacogenetic tests (UGT1A1*28) and the initiation of a genotype-guided clinical trial for cancer therapy (TYMS TSER in rectal cancer) have provided the first steps towards the integration of pharmacogenomics into clinical practice. This review describes some of the recent advances in pharmacogenomics research.
Hum Mol Genet 2006 Apr 15
PMID:Pharmacogenomics: from bedside to clinical practice. 1665 74

The chemokine CXCL12, also known as stromal cell-derived factor-1 (SDF-1), is a small protein that regulates leukocyte trafficking and is variably expressed in a number of normal and cancer tissues. CXCL12 as ligand and its receptor CXCR4 have been implicated in colorectal cancer (CRC) progression including angiogenesis and metastasis. A CXCL12 gene variant CXCL12-A (CXCL12-G801A, a single nucleotide polymorphism in the 3' untranslated region) is associated with increased susceptibility to breast cancer. Based on the suggested role of CXCL12 in the pathogenesis of cancer we examined the association of the gene variant CXCL12-A with CRC. The polymorphism was analysed with PCR and RFLP methods. Furthermore, the plasma CXCL12 levels from patients with CRC were also examined. There was no significant difference in genotype distribution and allelic frequencies between CRC patients (n=151) and controls (n=141). On the other hand, we found that the carrying rate of allele CXCL12-A was higher in colon cancer patients compared with rectal cancer patients (P=0.017). Analyses by ELISA showed that CRC patients (n=63) had a lower CXCL12 plasma level compared with controls (P<0.0001). Moreover, patients with tumours classified as Dukes' stage B and C revealed lower levels than patients with tumours in Dukes' stage A. Further studies with larger samples of patients are necessary to determine whether the CXCL12 polymorphism and plasma level reflect the clinical outcome of CRC and have an impact on CRC progression.
Int J Mol Med 2007 Jan
PMID:Polymorphism and circulating levels of the chemokine CXCL12 in colorectal cancer patients. 1714 42

Much information has been reported on the genetic and genomic alterations in colorectal cancer (CRC) in literature; however, nonrandom chromosomal alterations in Chinese CRC patients have only one report in Hong Kong. To further identify genomic alteration in primary sporadic colorectal carcinomas (SCRC) in Chinese patients and understand the molecular mechanisms in CRC development, progress, and metastasis, we used comparative genomic hybridization to screen for losses and/or gains of DNA copies along chromosomes in 24 SCRC tissues from 24 patients. Comparative genomic hybridization was applied to investigate the genomic imbalance in 24 cases of primary SCRC and compared the differences between tumors in different loci and between tumors with and without metastasis. The common chromosomal alterations in the SCRC included gains of chromosomes 1q, 2q, 4q, 7q, 8q, 11q, 13q, 20q and also losses of chromosomes 9p, 16q, 17p, 18q. Among them, gains of 1q, 7q, 20q and losses of 17p, 18q were related with lymph node metastasis of SCRC (P<0.05). The gains of 4q, 7q, 20q and losses of 9p, 18q were related with the sites (P<0.05), colon and rectum, respectively; gain of 20q and loss of 9p were commonly found in the colon cancer; gain of 4q, 7q and loss of 18q were easily seen in the rectal cancer. There are multiple regions of chromosomes with copy-number changes in SCRC. The tumor suppressor genes and oncogenes on these regions may be involved in the development and progress of SCRC. The chromosome 1q, 2q, 4q, 7q, 8q, 11q, 13q, 20q regions may have oncogenes such as epidermal growth factor, MET, platelet-derived growth factor receptor A, and 9p, 16q, 17p, 18q regions may have tumor suppressor genes such as p53,DCC, IGFR1 associated with occurrence of SCRC. The chromosome 1q, 7q, 20q, 17p, 18q regions may have genes related with metastasis of SCRC. The development mechanisms of colon cancer and rectal cancer may not be completely similar. Additionally, gain of chromosome 1q was verified by the second technique-Real-time reverse transcription PCR.
Diagn Mol Pathol 2007 Jun
PMID:Chromosomal alteration in Chinese sporadic colorectal carcinomas detected by comparative genomic hybridization. 1752 79

Colon cancer remains a leading cause of mortality worldwide despite the well-characterized molecular events in the adenoma-to-carcinoma sequence. There has been a strong emphasis on early detection of colon cancer, and fecal DNA-based methods have been developed to assist with early screening. Tissue-based assays have been utilized for many years to assess tumor aggressiveness and to determine prognosis and response to chemotherapeutic interventions. The most widely used serum marker for colon cancer (carcinoembryonic antigen) remains a useful modality to assess for occult disease following curative resection. Identification of tumor mutations in circulating tumor cells and microarray analysis holds a great deal of promise in the diagnosis and prognosis of patients with colorectal cancer. The inhibitors of apoptosis may be important markers to determine resistance to radiation cytotoxicity in rectal cancer. This report presents a summary of the current status of the molecular markers of colorectal cancer to establish a diagnosis, determine prognosis and chemoradiotherapeutic interventions, and assess relapse following curative surgery.
Expert Rev Mol Diagn 2008 May
PMID:Recent advances in the molecular diagnosis and prognosis of colorectal cancer. 1859 7


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