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1.
Hyaluronan in peritumoral stroma and malignant cells associates with breast cancer spreading and predicts survival 总被引:14,自引:0,他引:14
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Auvinen P Tammi R Parkkinen J Tammi M Agren U Johansson R Hirvikoski P Eskelinen M Kosma VM 《The American journal of pathology》2000,156(2):529-536
Hyaluronan (HA) is an extracellular matrix polysaccharide that promotes cell migration through its cell surface receptors and by effecting changes in the physical environment. HA expression is frequently increased in malignant tumors, whereas its association with the invasive potential and patient outcome in breast cancer has not been reported. The localization and signal intensity of HA was analyzed in 143 paraffin-embedded tumor samples of human breast carcinoma using a biotinylated HA-specific probe. In the immediate peritumoral stroma, HA signal was moderately or strongly increased in 39% and 56% of the cases, respectively. Normal ductal epithelium showed no HA, whereas in 57% of the tumors at least some of the carcinoma cells were HA positive. The intensity of the stromal HA signal and the presence of cell-associated HA were both significantly related to poor differentiation of the tumors, axillary lymph node positivity, and short overall survival of the patients. In Cox's multivariate analysis, both the intensity of stromal HA signal alone and that combined with the HA positivity in tumor cells were independent prognostic factors for overall survival. These results suggest that HA is directly involved in the spreading of breast cancer and may offer a potential target for new therapies. 相似文献
2.
Hirvikoski Tatja Lajic S. Jokinen J. Renhorn E. Trillingsgaard A. Kadesjö B. Gillberg C. Borg J. 《European child & adolescent psychiatry》2021,30(9):1367-1381
European Child & Adolescent Psychiatry - Due to lack of previous studies, we aimed at evaluating the use of the Five to Fifteen (FTF) questionnaire in adults with neurodevelopmental disorders... 相似文献
3.
Membranous location of EGFR immunostaining is associated with good prognosis in renal cell carcinoma
Kallio JP Hirvikoski P Helin H Kellokumpu-Lehtinen P Luukkaala T Tammela TL Martikainen PM 《British journal of cancer》2003,89(7):1266-1269
Epidermal growth factor receptor (EGFR) is a key factor in tumorigenesis. The association between EGFR expression and prognosis in renal cell carcinoma (RCC) is not clear. In our study of 134 RCCs, the cellular location of immunostaining was evaluated and patients with EGFR-positive tumours with prominent membranous staining had a good prognosis. Their overall survival was significantly longer (P=0.004) than that of patients with either EGFR-negative tumours or with mainly cytoplasmic staining. However, further studies on the different EGFR expression patterns in RCC are needed to clarify their role in the progression of the disease. 相似文献
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Moilanen AM Hakkola J Vaarala MH Kauppila S Hirvikoski P Vuoristo JT Edwards RJ Paavonen TK 《Carcinogenesis》2007,28(5):916-921
Testosterone is needed for the growth and development of the prostate. Androgen deprivation therapy is used for the treatment of prostate cancer. CYP3A5 is a human drug-metabolizing cytochrome P450 enzyme that metabolizes testosterone to the inactive 6beta-hydroxylated metabolite. We identified CYP3A5 as a novel androgen-regulated gene in human prostate by GeneChip analysis of human prostate tissues obtained from patients 3 days after therapeutic castration and from control patients. We further showed androgen induction of CYP3A5 messenger RNA (mRNA) in LNCaP prostate cancer cell line. Immunoblotting studies revealed CYP3A5 protein expression in all prostate samples studied. Immunohistochemistry and in situ hybridization was used for localization of CYP3A5 expression in prostate tissue. CYP3A5 was detected both in luminal and in basal epithelial cells of human prostate. Androgen response element was identified in the CYP3A5 proximal promoter and in electrophoretic mobility shift assay androgen receptor was found to bind this element. Androgen induction was abolished by mutation of the response element. We suggest that CYP3A5 is a part of an autoregulatory feedback loop controlling prostate cell exposure to androgens. 相似文献
6.
Oxidative/nitrosative stress and peroxiredoxin 2 are associated with grade and prognosis of human renal carcinoma 总被引:3,自引:0,他引:3
Soini Y Kallio JP Hirvikoski P Helin H Kellokumpu-Lehtinen P Kang SW Tammela TL Peltoniemi M Martikainen PM Kinnula VL 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2006,114(5):329-337
Peroxiredoxins (Prxs) 1-6 were assessed in 138 renal cell carcinomas (RCC) using immunohistochemistry and selected samples by Western blotting analysis. Oxidative/nitrosative damage was evaluated using nitrotyrosine immunoreactivity. The expressions of Prxs were correlated with tumor grade and survival and nitrotyrosine reactivity. Non-malignant kidney tubular cells showed positivity with variable intensity for all six Prxs. In RCCs, most cases were positive for Prxs 1 and 2, while only 15-20% of tumors showed expression for Prxs 3 and 4. Prx 2 was associated with tumors of a lower grade (p=0.009) and with a lower frequency of distant metastases (p=0.046). Patients with tumors expressing Prx2 had better prognosis (p=0.027). Instead, nitrotyrosine was significantly associated with high grade tumors (p=0.001). Compared with the non-malignant kidney tubular cells, low Prx expression in the tumor cells can make them more susceptible to oxidative damage. Prx 2 was more abundantly expressed in low grade tumors, suggesting that this protein could play a role in preventing the development of oxidative damage, which in turn can lead to the activation of pathways leading to aggressive tumors. 相似文献
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Hanna Ronkainen Saila Kauppila Pasi Hirvikoski Markku H Vaarala 《Journal of experimental & clinical cancer research : CR》2010,29(1):2
Background
Renal cell carcinoma (RCC) is a cancer of increasing incidence and mortality. Currently, there are no immunohistochemical prognostic markers for RCCs in routine use. The aim of this study was to examine for the first time the immunostaining of myosin VI in RCCs as well as its association with E-cadherin and beta-catenin immunostaining and the prognostic significance of these markers in RCCs.Methods
Our study population consisted of 152 patients who underwent surgery for RCCs between 1990 and 1999. The tumours were examined with three immunohistochemical markers: myosin VI, E-cadherin and beta-catenin.Results
The immunostaining for cytoplasmic myosin VI was common (72%). One-third of the tumours were immunopositive for nuclear myosin VI. Cytoplasmic myosin VI immunopositivity and nuclear beta-catenin immunostaining were associated with lower Fuhrman grades (p = 0.04 and p = 0.005, respectively), but not stages. There was no significant association between myosin VI immunostaining and the histological subtype of RCC. Nuclear myosin VI was associated with the nuclear expression of beta-catenin. A direct association could also be proven between membranous E-cadherin and cytoplasmic beta-catenin. Cytoplasmic myosin VI immunostaining was a marker of poorer prognosis in multivariate Cox regression model adjusted with stage and Fuhrman grade with hazard ratio 2.4 (95% confidence interval 1.1 to 5.0 with p = 0.024).Conclusions
Cytoplasmic myosin VI immunopositivity and nuclear beta-catenin immunostaining were associated with lower Fuhrman grades, and there was a strong positive relationship between E-cadherin immunostaining and beta-catenin immunostaining in RCCs. Cytoplasmic myosin VI immunostaining was associated with poorer prognosis in RCCs. 相似文献9.
Irregular expression of hyaluronan and its CD44 receptor is associated with metastatic phenotype in laryngeal squamous cell carcinoma 总被引:3,自引:0,他引:3
Hirvikoski P Tammi R Kumpulainen E Virtaniemi J Parkkinen JJ Tammi M Johansson R Agren U Karhunen J Kosma VM 《Virchows Archiv : an international journal of pathology》1999,434(1):37-44
The distributions of hyaluronan (HA) and its CD44 receptor were studied in 24 normal, 27 dysplastic samples of laryngeal
epithelium and in 172 squamous cell carcinomas (LSCC), using a specific probe prepared from cartilage proteoglycan (bHABC,
biotinylated hyaluronan binding complex) and a monoclonal antibody (Hermes 3). HA and CD44 were expressed similarly in all
normal and about 90% of dysplastic and neoplastic laryngeal epithelia. In the normal epithelium HA and CD44 were homogeneously
distributed throughout the epithelium, whereas the most superficial layers were negative. This was in contrast to the picture
in dysplastic epithelium and well-differentiated invasive carcinomas, which were entirely HA and CD44 positive. Local areas
with a low signal for HA and CD44 were present in 11% and 22% of the samples with dysplasia, and in 27% and 28% of those with
carcinoma, respectively. The presence of this staining irregularity was associated with poor differentiation of the carcinoma,
a significantly elevated mitotic index and a high frequency of nodal spreading and metastases. Furthermore, the irregular
staining showed a trend towards poor disease-free survival, suggesting that an altered metabolism of HA is a common feature
in LSCC and is associated with an aggressive growth pattern.
Received: 9 June 1998 / Accepted: 28 September 1998 相似文献
10.
Lehtonen ST Svensk AM Soini Y Pääkkö P Hirvikoski P Kang SW Säily M Kinnula VL 《International journal of cancer. Journal international du cancer》2004,111(4):514-521
Cigarette smoke, the major risk factor for lung cancer, induces an accumulation of reactive oxygen species. These have multiple effects on cell defense, cell proliferation and cell death. Thus, compounds involved in the regulators of redox balance can be hypothesized to play a fundamental role in both carcinogenesis and tumor progression. Here, we have evaluated the expressions of all 6 peroxiredoxins (Prxs I-VI) in lung carcinomas. Prxs represent a protein family with the capability of breaking down hydrogen peroxide; thus, they can participate in cellular antioxidant defense, regulate cell proliferation and increase drug resistance of cultured cells. Altogether 92 cases were investigated by immunohistochemistry, including 32 adenocarcinomas, 45 squamous cell, 9 small cell and 6 other carcinomas. Additionally, 11 cases with adenocarcinoma or squamous cell carcinoma were studied by Western analysis and/or by RT-PCR. Prxs I, II, IV and VI were particularly elevated in lung carcinomas as assessed by immunohistochemistry and/or RT-PCR. Western analysis revealed that Prxs I and IV were significantly elevated in tumors compared to nonmalignant tissue (p = 0.04 and 0.002, respectively). There were remarkable variations in Prx expression in various tumor subtypes, the most striking being Prx IV expression, which was mainly associated with adenocarcinoma. Elevated Prx VI expression was associated with high-grade squamous cell carcinoma (p = 0.03) and Prx II expression, with advanced tumor stage (p = 0.01). Our results suggest that Prxs may have effects on the progression of lung cancer. 相似文献