| 1. |
- Adell, Gunnar C. E., 1953-, et al.
(författare)
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Apoptosis in rectal carcinoma : Prognosis and recurrence after preoperative radiotherapy
- 2001
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Ingår i: Cancer. - 0008-543X .- 1097-0142. ; 91:10, s. 1870-1875
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Rectal carcinoma is common, with considerable local recurrence and death rates. Preoperative radiotherapy and refined surgical techniques can improve local control. The aim of this study was to investigate the interaction between apoptosis and the outcome of rectal carcinoma, with and without short-term preoperative radiotherapy.METHODS: Specimens were from 162 patients from the Southeast Swedish Health Care region included in the Swedish Rectal Cancer Trial between 1987-1990. New sections from the paraffin blocks of the preoperative biopsies and the surgical specimens were examined for apoptosis using the terminal deoxynucleotidyl transferase mediated digoxigenin nick end labeling (TUNEL) method.RESULTS: The mean percentage of apoptotic cells was 0.3% (0-4%) and 1.1% (0-14.5%) for the preoperative biopsy and the surgical specimen, respectively. The authors analyzed the surgical specimens from nonirradiated patients and divided them into three groups by apoptotic index (AI) as follows: 0%, 0-1%, and > 1%. A high AI was associated with a decreased local recurrence rate compared with an intermediate or a low AI (P = 0.024). There was no significant relation between AI and survival. There was a significant reduction in the local recurrence rate for irradiated patients compared with the nonirradiated in the low (P = 0.015) and intermediate (P = 0.038) AI groups. In the high AI group, there were few recurrences and no significant difference was observed between irradiated and nonirradiated patients. The relative risk of death from rectal carcinoma in Dukes A-C patients was not significantly decreased by radiotherapy, but, in the intermediate AI group, there was a trend (P = 0.08) in favor of the irradiated patients.CONCLUSION: A high AI in rectal carcinoma indicated a decreased local recurrence rate.
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| 2. |
- Adell, Gunnar, 1953-, et al.
(författare)
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Decreased tumor cell proliferation as an indicator of the effect of preoperative radiotherapy of rectal cancer
- 2001
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - 0360-3016 .- 1879-355X. ; 50:3, s. 659-663
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Rectal cancer is a common malignancy, with significant local recurrence and death rates. Preoperative radiotherapy and refined surgical technique can improve local control rates and disease-free survival.PURPOSE: To investigate the relationship between the tumor growth fraction in rectal cancer measured with Ki-67 and the outcome, with and without short-term preoperative radiotherapy.Method: Ki-67 (MIB-1) immunohistochemistry was used to measure tumor cell proliferation in the preoperative biopsy and the surgical specimen.MATERIALS: Specimens from 152 patients from the Southeast Swedish Health Care region were included in the Swedish rectal cancer trial 1987-1990.RESULTS: Tumors with low proliferation treated with preoperative radiotherapy had a significantly reduced recurrence rate. The influence on death from rectal cancer was shown only in the univariate analysis. Preoperative radiotherapy of tumors with high proliferation did not significantly improve local control and disease-free survival. The interaction between Ki-67 status and the benefit of radiotherapy was significant for the reduced recurrence rate (p = 0.03), with a trend toward improved disease-free survival (p = 0.08). In the surgery-alone group, Ki-67 staining did not significantly correlate with local recurrence or survival rates.CONCLUSION: Many Ki-67 stained tumor cells in the preoperative biopsy predicts an increased treatment failure rate after preoperative radiotherapy of rectal cancer.
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| 3. |
- Andreyev, HJN, et al.
(författare)
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Kirsten ras mutations in patients with colorectal cancer : The 'RASCAL II' study
- 2001
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 85:5, s. 692-696
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Tidskriftsartikel (refereegranskat)abstract
- Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras incolorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P=0.004, HR 1.3) and overall survival (P=0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes' C cancers (failure-free survival, P=0.008, HR 1.5, overall survival P=0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P=0.46, HR 1.12, overall survival P=0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer. ⌐ 2001 Cancer Research Campaign.
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| 4. |
- Chen, Yun, 1966, et al.
(författare)
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Neonatal losartan treatment suppresses renal expression of molecules involved in cell-cell and cell-matrix interactions
- 2004
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Ingår i: Journal of the American Society of Nephrology. - : Lippincott Williams & Wilkins. - 1046-6673 .- 1533-3450. ; 15:5, s. 1232-43
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Tidskriftsartikel (refereegranskat)abstract
- Lack of neonatal angiotensin II type 1 receptor (AT(1)) stimulation produces renal abnormalities characterized by papillary atrophy and impaired urinary concentrating ability, but the mechanisms involved are still unclear. DNA microarray was used to identify genes that are differentially expressed in renal medulla in response to neonatal treatment with AT(1) receptor antagonist losartan (30 mg/kg per d), which commenced within 24 h after birth. The data showed that losartan treatment for 48 h downregulated 68 genes, approximately 30% of which encode various components of cytoskeleton and cytoskeleton-associated proteins, extracellular matrix, and enzymes involved in extracellular matrix maturation or turnover. With the use of immunohistochemistry and Western immunoblot, the microarray data were confirmed and it was demonstrated that losartan suppressed renal expression of syndecan 2, alpha-smooth muscle actin, MHC class II, and leukocyte type 12-lipoxygenase by day 4. In addition, losartan inhibited medullary expression of integrin alpha6 and caused relocalization of integrins alpha6 and alpha3. Moreover, losartan inhibited cell proliferation in medullary tubules by day 9, as detected by Ki-67 immunostaining. This study provides new data supporting the contention that a lack of AT(1) receptor stimulation results in abnormal matrix assembly, disturbed cell-cell and cell-matrix interactions, and subsequent abnormal tubular maturation. Moreover, regulation of the expression of leukocyte type 12-lipoxygenase and alpha-smooth muscle actin by the renin-angiotensin system in the immature kidney adds new knowledge toward the understanding of renal vascular development.
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| 5. |
- Emterling, A, et al.
(författare)
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Clinicopathological significance of microsatellite instability and mutated RIZ in colorectal cancer
- 2004
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 15:2, s. 242-246
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several studies have shown that microsatellite instability (MSI) is related to favourable survival in colorectal cancer patients but there are controversial results. Tumour suppressor gene RIZ is a susceptible mutational target of MSI. However, its clinicopathological significance has not been investigated. We investigated the prognostic significance of MSI in Swedish colorectal cancer patients and the clinicopathological significance of RIZ mutations. Patients and methods: We analysed 438 colorectal adenocarcinomas for MSI by microsatellite analysis. Among them, 29 MSI and 28 microsatellite stable (MSS) tumours were examined for RIZ mutations by DNA sequencing. Results: MSI (13% of 438 cases) was not associated with survival (rate ratio=0.97, 95% confidence interval =0.57-1.64, P=0.90), although it was related to proximal tumour (P <0.001), poor differentiation and mucinous carcinomas (P <0.001), multiple tumours (P=0.01) and negative/weak expression of hMLH1 (P=0.03). RIZ mutations were detected in 31% of 29 MSI tumours but in none of the 28 MSS tumours. The mutations were related to female (P=0.01), proximal tumour (P=0.01), stage B (P=0.01) and poor differentiation (P=0.047). Conclusions: MSI was not a prognostic factor in the Swedish patients included in this study. Clinicopathological variables associated with RIZ mutations might be a consequence of the MSI characteristics.
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| 6. |
- Emterling, Anna, et al.
(författare)
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Clinicopathological significance of Nup88 expression in patients with colorectal cancer
- 2003
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Ingår i: Oncology. - : S. Karger AG. - 0890-9091 .- 0030-2414 .- 1423-0232. ; 64:4, s. 361-369
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The nucleoporin Nup88 is overexpressed in a series of human malignancies, however, its clinicopathological significance has not been studied. Our aims were to analyze Nup88 expression in normal mucosa, primary tumors and metastases from colorectal cancer patients and further to identify relationships of Nup88 expression with clinicopathological and other factors.Materials and Methods: Using immunohistochemistry, we investigated Nup88 expression in 198 primary colorectal tumors, 96 normal mucosa samples and 35 lymph node metastases.Results: The results showed that the intensity of Nup88 expression increased from the normal mucosa to the primary tumors (p < 0.0001) and tended to increase from the primary tumors to the metastases (p = 0.15). Both primary tumors and metastases presented stronger expression in the invasive margin and vascular-invaded areas. Nup88 expression was positively related to distal tumor location (p = 0.01), infiltrative growth pattern (p = 0.04) and higher proliferative activity (p = 0.04) and reversely to the grade of differentiation (p = 0.02) and apoptosis (p = 0.049). Strong expression of Nup88 predicted a worse outcome in the patients with distal tumors during the follow-up period of up to 3 years (p = 0.02).Conclusions: It seems that overexpression of Nup88 was involved in the tumorigenesis and aggressiveness of colorectal cancers, and Nup88 may be used as a prognostic factor in patients with distal tumors.
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| 7. |
- Evertsson, Sofia, 1972-, et al.
(författare)
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APC I1307K and E1317Q variants are rare or do not occur in Swedish colorectal cancer patients
- 2001
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 37:4, s. 499-502
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a germ line mutation of the APC gene, I1307K, was discovered in a subset of Ashkenazi jews. The mutation involves an amino acid exchange and creates a tract consisting of eight contiguous adenosine residues believed to cause hypermutability in this region. Another germ line missense variant, E1317Q, not restricted to a certain ethnic population, could functionally alter the protein. These APC variants have been linked with increased colorectal cancer risk in several studies. However, they have not yet been investigated in Swedish colorectal cancer patients. Thus, our aim was to investigate the prevalence of I1307K and E1317Q in Swedish colorectal cancer patients in order to determine if these genetic variants are important predisposing factors to colorectal cancer in this population. To this end, sequence analysis was carried out of the APC gene in order to identify any I1307K and E1317Q variants in 106 unselected cases and 88 hereditary/familial colorectal cancer cases including 22 cases of hereditary non-polyposis colorectal cancer (HNPCC) fulfilling the Amsterdam criteria. Out of a total of 194 cases examined, we did not find any variants. It seems that these alterations are rare or absent in the Swedish population.
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| 8. |
- Evertsson, Sofia, 1972-, et al.
(författare)
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Microsatellite instability and MBD4 mutation in unselected colorectal cancer
- 2003
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 23:4, s. 3569-3574
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We investigated the prognostic significance of microsatellite instability (MSI) and the association with clinicopathological factors in colorectal cancer, and further identified MBD4 mutations and their clinicopathological significance.PATIENTS AND METHODS: MSI was analyzed in 201 colorectal cancers. Sequencing analysis of MBD4 was performed in 26 MSI and 28 microsatellite stable (MSS) tumors.RESULTS: Twenty-seven tumors (13.4%) were MSI but did not correlate with improved survival. MSI was significantly correlated with proximal colon tumors (p < 0.001), poor differentiation or mucinous type (p = 0.005) and multiple tumors (p = 0.04). MBD4 mutations were found in 15% MSI but not in MSS tumors. The mutated cases showed female overrepresentation, proximal site and poorly-differentiated/mucinous type.CONCLUSION: MSI was not correlated with survival, but shared other features associated with MSI in colorectal cancer as demonstrated by others. The clinicopathological variables associated with the MBD4 mutations were probably the reflection of MSI features.
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| 9. |
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| 10. |
- Gao, Jingfang, et al.
(författare)
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Stromal staining for PINCH is an independent prognostic indicator in colorectal cancer
- 2004
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Ingår i: Neoplasia. - : Elsevier BV. - 1522-8002 .- 1476-5586. ; 6:6, s. 796-801
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Tidskriftsartikel (refereegranskat)abstract
- Particularly interesting new cysteine-histidine-rich protein (PINCH), a LIM domain adapter protein that functions in the integrin and growth factor signal transduction pathway, is upregulated in stroma associated with many common cancers. The finding suggested that PINCH may be involved in promoting tumor-stromal interactions that support tumor progression, and, if so, tumors with abundant PINCH stromal staining may have a worse prognosis. To test this hypothesis, 174 primary colorectal adenocarcinomas with 39 distant normal mucosa samples and 26 metastases in the lymph nodes were studied by immunohistochemistry, and 7 additional colon tumors were studied by Western blot analysis and immunofluorescence. The abundance of PINCH protein in stroma increased from normal mucosa to primary tumor to metastasis (P < .05), and was more intense at the invasive margin than it was in the intratumoral stroma. Strong stromal immunostaining for PINCH was shown to predict a worse outcome (rate ratio 2.1, 95% CI 1.16-3.37, P = .01), independent of Dukes stage, growth pattern, and tumor differentiation. PINCH was detected in fibroblasts, myofibroblasts, and a proportion of endothelial cells of the tumor vasculature, supporting the involvement of PINCH in promoting tumor-stromal interactions that support tumor progression. Interestingly, stromal staining for PINCH was an independent prognostic indicator in colorectal cancer.
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| 11. |
- Jansson, Agneta, 1973-, et al.
(författare)
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Bax expression decreases significantly from primary tumor to metastasis in colorectal cancer
- 2002
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 20:3, s. 811-816
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Bax is a proapoptotic member of the bcl-2 family. Previous studies about Bax have shown that the expression increases from normal to tumor tissue, but the clinical significance is contradictory. Our aims were to analyze the expression of Bax from normal mucosa to primary tumor and to metastases in colorectal cancer patient. We further investigated whether low Bax expression in the primary tumor or changed expression from normal mucosa to primary tumor and to metastases had biologic and clinical significance.PATIENTS AND METHODS: The study included 135 patients with primary colorectal adenocarcinoma, of whom 31 had metastases in the lymph nodes and 75 had normal mucosa. Immunohistochemistry, DNA sequencing, and microsatellite analysis were used to detect Bax expression, mutations, and microsatellite instability.RESULTS: The protein was observed in 132 of 135 tumors, all normal epithelial cells and metastases. The frequencies of weak expression were greater from well/moderately to poorly differentiated and to mucinous carcinomas. Bax expression was stronger from normal to tumor tissue, but subsequently decreased in metastases. The matched cases with lower expression in the metastases than in the primary tumor showed a more infiltrative growth pattern and more distal metastases.CONCLUSION: The association of Bax expression with tumor differentiation/histologic types and a decreased expression in the metastases, suggests that Bax expression may be involved in tumor differentiation/histologic types and metastatic progression. We also propose the novel notion that changed Bax expression in the metastases compared with the primary tumors might provide information to determine the clinicopathologic characteristics of the tumor.
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| 12. |
- Jansson, Agneta, 1973-, et al.
(författare)
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Combined deficiency of hMLH1, hMSH2, hMSH3 and hMSH6 is an independent prognostic factor in colorectal cancer
- 2003
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Ingår i: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 22:1, s. 41-49
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Tidskriftsartikel (refereegranskat)abstract
- We examined biological and clinicopathological significance of individual and combined hMLH1, hMSH2, hMSH3 and hMSH6 expression with immunohistochemistry in 301 unselected colorectal cancers. Weak hMLH1 expression was correlated to microsatellite instability (P=0.04), negative p53 expression (P=0.005) and mucinous carcinomas (P=0.02). Weak hMSH2 expression was related to negative ras (P<0.001) and p53 expression (P=0.005), and better survival (P=0.03). hMSH2, hMSH3 and hMSH6, as well as hMLH1, hMSH2, hMSH3 and hMSH6, were combined into a 'functional' and a 'less-functional' group, respectively. Both 'less-functional' groups were/tended to be associated with microsatellite instability, negative ras and p53 expression, and better survival. In summary, hMLH1 and hMSH2 were more important when investigated individually, and the combined groups were more related to the mutator pathway, suggesting that combined deficiencies of the proteins are more efficiently involved in the mutator pathway. Our result from weak versus strong staining may suggest that the intensity of staining should be considered in future studies on mismatch repair proteins.
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| 13. |
- Jansson, Agneta, 1973-, et al.
(författare)
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mRNA and protein expression of PUMA in sporadic colorectal cancer.
- 2004
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Ingår i: Oncology Reports. - 1021-335X .- 1791-2431. ; 12:6, s. 1245-1249
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Tidskriftsartikel (refereegranskat)abstract
- PUMA is a BH3-only member of the Bcl-2 family, up-regulated by p53 as a response to DNA damage. We have investigated the mRNA expression of PUMA with real-time PCR in 94 colorectal adenocarcinomas and the corresponding normal mucosa. Among them PUMA protein expression was investigated with immunohistochemistry in 23 tumours and 17 corresponding normal mucosa samples. The mRNA expression of PUMA decreased in 4% and increased in 4% of the tumours compared with the normal mucosa. The protein expression of PUMA decreased in 6% and increased in 29% of the tumours compared with the normal mucosa. Decreased PUMA expression in the tumour compared with the corresponding mucosa was correlated with the distal colon and rectum (P=0.02). We did not find any other relationship to clinical or pathological features. We suggest that the changes in PUMA expression may be of minor importance in the development of colorectal cancer.
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| 14. |
- Jansson, Agneta, 1973-, et al.
(författare)
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Noxa in colorectal cancer : A study on DNA, mRNA and protein expression
- 2003
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 22:30, s. 4675-4678
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Tidskriftsartikel (refereegranskat)abstract
- Noxa is a BH3-only member of the Bcl-2 family, upregulated by p53 as a response to DNA damage. Mutations in the BH3-only region of other BH3-only members lead to an inactive protein. We have investigated the mRNA expression of Noxa with real-time PCR in 94 unselected colorectal adenocarcinomas and the corresponding normal mucosa. Among them, Noxa protein expression was investigated with immunohistochemistry in 16 tumors and six corresponding normal mucosa samples. Further, we searched for Noxa mutations in all the cases using single-stranded conformation polymorphism and DNA sequencing. The mRNA expression of Noxa was weak in 9% and strong in 2% of the tumors, and decreased in 9% and increased in 16% of the tumors compared with the normal mucosa, however, these changes did not have any clinical or pathological significance. The protein level in most of the cases investigated was correlated with the mRNA level. We did not find any mutations in the Noxa gene. Thus, we suggest that Noxa may not be of importance in the development of colorectal cancer.
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| 15. |
- Jansson, Agneta, 1973-, et al.
(författare)
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p53 mutations are present in colorectal cancer with cytoplasmic p53 accumulation
- 2001
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 92:3, s. 338-341
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have shown that nuclear p53 over-expression is an indicator of p53 mutations whereas cytoplasmic p53 accumulation is related to wild-type p53 in several kinds of tumors. Cytoplasmic p53 accumulation has been demonstrated to be an independent prognostic factor in colorectal adenocarcinomas. The purpose was to examine whether mutations occur in cases with p53 accumulated in the cytoplasm and whether there are any differences in the frequency and characteristics of p53 mutations in different staining patterns. In the present study, we identified p53 mutations using PCR single-strand conformation polymorphism (SSCP) and DNA sequencing in 75 primary colorectal adenocarcinomas with different staining patterns (negative, nucleus, cytoplasm, nucleus and cytoplasm). The results show that the frequency and nature of mutations in tumors with cytoplasmic p53 accumulation were similar to those with nuclear p53 expression. However, the tumors with accumulation in both the nucleus and cytoplasm demonstrated a higher mutation rate. We suppose that the role of cytoplasmic p53 accumulation in predicting prognosis in patients with colorectal cancer may be dependent on both mutational and non-mutational mechanisms.
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| 16. |
- Knutsen Holmqvist, Annica, et al.
(författare)
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Survivin expression is an independent prognostic factor in rectal cancer patients with and without preoperative radiotherapy
- 2004
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Ingår i: Journal of chromatography. B. - 1570-0232 .- 1873-376X. ; 60:1, s. 149-155
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Survivin, as an inhibitor of apoptosis, is undetectable in normal tissues but expressed in tumors. Survivin expression in rectal cancer patients who have undergone preoperative radiotherapy (RT) alone has not been studied. We analyzed the relationships of survivin expression to RT, clinicopathologic variables, apoptosis, and p53 expression in rectal cancer patients who participated in a trial of preoperative RT. Methods and Materials: Survivin was immunohistochemically examined in 98 rectal tumors (74 had adjacent normal mucosa). Of 98 patients, 57 underwent surgery alone and 41 underwent RT before surgery. Results: Survivin positivity was related to worse survival, independent of Dukes' stage, local and distant recurrence, differentiation, gender, age, apoptosis, and p53 expression (p = 0.02). Survivin was not associated with survival in the patients without (p = 0.08) or with (p = 0.19) RT. After RT, survivin tended to be increased in adjacent normal mucosa (p = 0.057) but not in tumors (p = 0.71). Conclusion: Survivin was independently related to survival in rectal cancer patients who participated in a trial of preoperative RT, but not in either treatment group (surgery alone or surgery plus RT). Whether the effect of survivin on tumors is associated with RT and further related to patient survival needs to be investigated in a larger number of patients. (C) 2004 Elsevier Inc.
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| 17. |
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| 18. |
- Skoglund, Johanna, et al.
(författare)
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Clinicopathological significance of stromelysin-3 expression in colorectal cancer
- 2004
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Ingår i: Oncology. - : S. Karger AG. - 0890-9091 .- 0030-2414 .- 1423-0232. ; 67:1, s. 67-72
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Stromelysin-3 (ST3) is a member of the matrix metalloproteinases and suggested to play a role in tissue remodeling observed in growth and metastasis of tumors. ST3 overexpression in breast cancer is associated with a worse outcome. Our aims were to analyze ST3 expression in primary colorectal tumors and metastases, and further to identify relationships of the expression to clinicopathological factors. Materials and Methods: ST3 expression was immunohistochemically analyzed in 200 primary colorectal adenocarcinomas and 36 corresponding lymph node metastases. Results: Scoring was performed by counting the percentages of positive cells and the percentages of positive areas. One hundred and one (51%) cases showed ≤5% positive cells and 99 (49%) >5% positive cells. One hundred and two (51%) cases showed ≤30% positive area and 98 (49%) >30% positive area. ST3 expression determined by both scoring methods was individually related to females, distally located tumors, infiltrative growth pattern and microsatellite stability. No relationship was found with age, Dukes' stage, differentiation and survival. Conclusions: These results suggest that ST3 protein was more involved in the pathway of colorectal cancer development in females, distal locations, infiltrative growth patterns and microsatellite stability. Copyright © 2004 S. Karger AG, Basel.
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| 19. |
- Sun, Xiao-Feng, 1959-, et al.
(författare)
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Bcl-2 expression is a prognostic factor in the subgroups of patients with colorectal cancer.
- 2003
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Ingår i: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 23:5, s. 1439-1443
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Tidskriftsartikel (refereegranskat)abstract
- The prognostic significance of Bcl-2 expression in colorectal cancer has been intensively studied, however, the results were controversial in the whole group of colorectal cancer patients. We proposed that one of the main reasons for such controversial results may be that Bcl-2 played variable roles in the subgroup of patients. We, therefore, investigated the prognostic importance of Bcl-2 expression by using immunohistochemistry in the various subgroups of 147 patients with colorectal cancer. Among these tumours, 85 (58%) expressed Bcl-2 protein and 62 (42%) were negative. Bcl-2 expression was positively related to DCC expression (p=0.0002). Survival analyses in the subgroups of the patients showed that lack of Bcl-2 expression was related to a worse prognosis in the male patients (p=0.02) but not in female patients (p=0.53), in the patients with DNA diploid tumours (p=0.005) not in the patients with non-diploid tumours (p=0.46), and in the patients with ras negative tumours (p=0.01) not in the patients with ras positive tumours (p=0.25). Bcl-2 expression was not related to prognosis in the total group of the patients (p=0.20). In conclusion, Bcl-2 protein may play variable prognostic roles in the subgroups of the patients with colorectal cancer. Analysis of Bcl-2 expression in the tumour may be of value in predicting prognosis and therapeutic response.
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| 20. |
- Sun, Xiao-Feng
(författare)
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p73 overexpression is a prognostic factor in patients with colorectal adenocarcinoma
- 2002
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 8:1, s. 165-170
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To examine the expression of p73 in the different stages of colorectal cancer development and the association of p73 expression with patient survival. Experimental Design: Expression of p73 protein was evaluated by immunohistochemistry in 221 primary colorectal cancer patients, including 58 patients with matched normal mucosa and metastases in the regional lymph nodes. Results: Frequency and intensity of p73 expression were markedly increased from the normal samples (19%) to primary tumors (67%) and to metastases (95%). Overexpression of p73 predicted poor outcome in the whole group of patients (P = 0.014) and the subgroups with left-sided (P = 0.002) or ras-positive tumors (P = 0.019). The prognostic significance remained in the whole group (P = 0.008) and the subgroup with left-sided tumors (P = 0.019) after adjustment for the patient's sex, age, tumor stage, growth pattern, and differentiation. The p73 expression was positively correlated with ras expression (P = 0.006). The 5-year survival rates were 37, 53, 72, and 74% for the patients with p73+/ras+, p73+/ras-, p73-/ras+, and p73-/ras- tumors, respectively (P = 0.007). Conclusion: Our data indicate that overexpression of p73 independently predicted poor prognosis in the patients with colorectal cancer.
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| 21. |
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| 22. |
- Zhang, Hong, 1957-, et al.
(författare)
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Codon 201 polymorphism of DCC gene is a prognostic factor in patients with colorectal cancer
- 2003
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Ingår i: Cancer Detection and Prevention. - 0361-090X .- 1873-443X. ; 27:3, s. 216-221
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Tidskriftsartikel (refereegranskat)abstract
- The polymorphism at codon 201 of the "deleted in colorectal carcinoma" (DCC) gene has been liked to susceptibility to colorectal cancer. However, its clinicopathological significance has not been reported. We examined the codon 201 polymorphism and loss of heterozygosity (LOH) by PCR-restriction fragment length polymorphism (PCR-RFLP) in 59 colorectal cancers, 48 samples from transitional mucosa and 67 samples from normal mucosa. The frequencies of the polymorphism did not significantly differ from normal to transitional mucosa and to tumor, but LOH was increased from transitional mucosa to tumor. Almost all of the LOH cases showed the polymorphism. The polymorphism was increased from well/moderately to poorly differentiated and to mucinous carcinoma (P = 0.03). The polymorphism was more frequently seen in advanced stages than in earlier stages (P = 0.02), and further predicted worse survival (P = 0.04). The data suggest that the codon 201 polymorphism of the DCC gene was a target of LOH, and predicted prognosis in colorectal cancer patients. ⌐ 2003 International Society for Preventive Oncology. Published by Elsevier Science Ltd. All rights reserved.
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| 23. |
- Zhang, Hong, 1957-, et al.
(författare)
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Loss of p27 expression predicts poor prognosis in patients with Dukes' B stage or proximal colorectal cancer.
- 2001
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Ingår i: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 19:1, s. 49-52
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Tidskriftsartikel (refereegranskat)abstract
- p27 is a cyclin-dependent kinase inhibitor which regulates progression of cells from G1 into S phase in a cell cycle. Loss of the negative regulator may contribute to oncogenesis and tumor progression. The aim of this study was to examine p27 expression in normal mucosa, primary and metastatic tumors from patients with colorectal adenocarcinomas and to analyze association of p27 with patient survival and clinicopathological variables. p27 expression was estimated by immunohistochemistry in 178 primary colorectal cancers, 34 lymph node metastases and 48 normal mucosa samples from patients with colorectal adenocarcinoma. Associations of p27 with patient survival, clinicopathological characteristics and expression of p53, p73 and DCC were analyzed. Loss of p27 was found in 51% of primary tumors, 68% of metastases and 56% of normal samples. The intensity of p27 staining was similar in the matched primary tumor, metastasis and normal mucosa. In patients with Dukes' B or with proximal tumors, the loss of p27 predicted poorer prognosis (p = 0.03 and p = 0.05, respectively). However, there were no significant differences in the patients with other individual Dukes' stage or distal tumors. No relationships were found between p27 and patients' gender, age, tumor location, growth pattern and expression of p53, p73 and DCC (p > 0.05). The data suggest that loss of p27 was associated with poor prognosis in patients with Dukes' B tumor or those with proximal tumor. p27 might be a useful marker to identify the more progressive tumors in these groups.
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| 24. |
- Zhang, Hong, 1957-, et al.
(författare)
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Overexpression of cyclooxygenase-2 correlates with advanced stages of colorectal cancer
- 2002
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Ingår i: American Journal of Gastroenterology. - 0002-9270 .- 1572-0241. ; 97:4, s. 1037-1041
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We aimed to investigate the associations of cyclooxygenase-2 (COX-2) with pathological features and survival in patients with colorectal cancer. METHODS: The expression of COX-2 was examined by immunohistochemistry in 112 primary colorectal cancers, with 64 samples from the corresponding normal mucosa and 16 metastases in the regional lymph nodes of patients with colorectal cancer. The associations of COX-2 expression with clinico-pathological features, including survival, were analyzed. RESULTS: The frequency and intensity of COX-2 staining were remarkably increased from the normal samples (17%) to the primary tumors (72%) and to the metastases (100%). Expressions of COX-2 were 25%, 74%, 78%, and 67% in Dukes' A, B, C, and D tumors, respectively (p = 0.005), and positively related to proliferative activity (p = 0.003). COX-2 expressions were 80% in colonic tumors and 60% in rectal tumors (p = 0.03). The expression of COX-2 was positively related to the better differentiated tumors in the colon (p = 0.04). We were unable to find any relationship of COX-2 with patient age, sex, tumor growth pattern, apoptosis, and patient survival (p > 0.05). CONCLUSION: We found that the expression of COX-2 was upregulated from normal cells to primary tumors and to metastases, and related to proliferative activity, tumor location, Dukes' stage, and differentiation. These results further support the evidence that COX-2 may be involved in tumorigenesis and development of colorectal cancer. ⌐ 2002 by Am. Coll. of Gastroenterology.
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| 25. |
- Zhang, X. F., et al.
(författare)
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catena-Poly (1,10-phenanthroline-kappa N-2,N ')manganese(II) -mu-L-tartrato-kappa O-4(1),O-2 : O-3,O-4 hexahydrate
- 2003
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Ingår i: Acta Crystallographica Section C. - 0108-2701 .- 1600-5759. ; 59, s. M402-M404
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Tidskriftsartikel (refereegranskat)abstract
- The title compound, {[Mn(C4H4O6)(C12H8N2)] . 6H(2)O}(n), has a linear chain structure containing monomeric [ Mn( C4H4O6)( C12H8N2)] repeat units. Each manganese ion is six-coordinate, with the two phenanthroline N atoms [Mn - N = 2.229 (2) and 2.235 (2) Angstrom] and four O atoms from two tartrate anions [Mn - O-COO = 2.1252 (19) and 2.1310 (19) Angstrom, and Mn - O-OH = 2.2404 (19) and 2.2424 (19) Angstrom] forming a seriously distorted octahedral coordination environment. Six water molecules exist outside every repeat unit as solvate molecules. Extensive hydrogen-bonding interactions and pi-pi stacking of the phenanthroline moieties exist between the chains.
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| 26. |
- Zhou, Xiao-Lei, et al.
(författare)
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Definition of candidate low risk APC alleles in a Swedish population.
- 2004
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Ingår i: International journal of cancer. Journal international du cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 110:4, s. 550-7
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Tidskriftsartikel (refereegranskat)abstract
- Many families experience an apparently inherited increased risk of colorectal cancer (CRC) similar to the known syndromes familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC). Besides these high-risk syndromes, approximately 10% of all CRC cases come from families with 2 affected 1st-degree relatives, and even 1st-degree relatives to a single case of CRC are at increased risk. Risk subjects from these families frequently show polyps at colonoscopy, which suggests the APC gene as a good candidate susceptibility gene for these attenuated polypotic syndromes. We used the sensitive DHPLC technique to search for possible predisposing germline mutations in the entire APC gene in 91 risk subjects from these high- and low-risk syndromes with unknown predisposing genes. Most exons were also screened for mutations in 96 normal controls and 96 colorectal cancer cases. In our study we probably have identified the most common APC variants in a Swedish population. Among 30 germline variants identified, 1 clearly pathogenic nonsense mutation and 11 putative pathogenic variants (10 missense and one 3' UTR) were found in 20 index patients (22%). Twelve silent as well as 5 intronic variants were considered nonpathogenic. Two of the missense variants found here, E1317Q and D1822V, have previously been related to a difference in risk of colorectal cancer. One variant, 8636C>A, located within the 3' UTR region of the APC gene, was suggested to constitute an additional low risk allele with a similar relative risk as the Jewish I1307K mutation (OR = 1.8; 95% CI, 0.96-3.40). The question of whether all the other variants confer an increased colorectal cancer risk warrants future large association studies.
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