| 1. |
- Faedo, Margaret, et al.
(författare)
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Mouse mammary tumor-like virus is associated with p53 nuclear accumulation and progesterone receptor positivity but not estrogen positivity in human female breast cancer
- 2004
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 10:13, s. 4417-4419
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The purpose is to compare the presence of proteins with known associations with breast cancer-progesterone receptor (PgR), estrogen receptor, and p53, with the prevalence of mouse mammary tumor virus (MMTV)-like DNA sequences in human female breast cancers. EXPERIMENTAL DESIGN: A cohort of 128 Australian female breast cancers were screened for MMTV-like DNA sequences using PCR. The presence of PgR, estrogen receptor, and nuclear accumulation of p53 protein was assessed in the same samples using immunohistochemical staining. RESULTS: Nuclear accumulation of p53 was significantly more prevalent (P = 0.05) in archival human breast cancers containing MMTV-like DNA sequences. The presence of progesterone receptor was significantly higher in MMTV-positive than MMTV-negative breast cancers (P = 0.01). No correlation between estrogen receptor and MMTV-like DNA sequences was found. CONCLUSIONS: MMTV causes breast cancer in mice, and hormones up-regulate expression of virus in mice mammary tissue. It is unknown if this is the case in human breast cancers shown to contain DNA of MMTV-like viruses. The positive association between MMTV-like DNA sequences and PgR indicates hormones and MMTV may play a role in human breast cancer. Mutations of the tumor suppressor gene p53 are common in human breast cancer and are associated with higher grades of cancer. The association of MMTV-like DNA sequences with higher grades of cancer, and the positive association between p53 and MMTV-like DNA sequences clearly warrant additional investigation.
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| 2. |
- Ford, Caroline, et al.
(författare)
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Mouse mammary tumor virus-like RNA transcripts and DNA are found in affected cells of human breast cancer
- 2004
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 10:21, s. 7284-7284
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Tidskriftsartikel (refereegranskat)abstract
- Identifiable risk factors for the development of breast cancer include age, diet, family history, and lifetime estrogen exposure. An infectious agent (mouse mammary tumor virus; MMTV) is known to cause murine breast tumors and may be involved in the pathogenesis of human disease. Multiple studies have detected MMTV-like sequences in 30 to 60% of breast cancer samples and up to 1.8% of samples from normal breast. Using in situ PCR of MMTV-like sequences of formalin-fixed, paraffin-embedded breast tissue, viral sequences have been located in cancerous epithelial cells in breast acini of male and female breast tumors, but not in adjacent nonmalignant cells. MMTV-like sequences were also located in the epithelial cells of male gynecomastia samples. Using reverse transcriptase in situ PCR, RNA transcripts from the env gene were also detected within cancerous epithelial cells of 78% of DNA-positive tumors, 80% of gynecomastia samples, and 0% of normal tissues screened. This suggests the virus may be replicating in these cells. The epidemiologic and histopathological data are consistent with the association of an MMTV-like virus with breast cancers in men and women. The association with gynecomastia, a benign, possibly premalignant condition suggests hormonal influences, rather than cancer per se, may be the dominant factor in determining viral presence and replication.
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| 4. |
- Åkervall, Jan, et al.
(författare)
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Genetic and expression profiles of squamous cell carcinoma of the head and neck correlate with cisplatin sensitivity and resistance in cell lines and patients
- 2004
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 10:24, s. 8204-8213
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The choice of treatment for squamous cell carcinoma of the head and neck (SCCHN) is still primarily based on the tumor-node-metastasis classification. However, it is reasonable to believe that biological profiles of SCCHN may be independently associated with response to therapy. The aim of the present study was to examine genetic changes and gene expression profiles that might correlate with sensitivity to cisplatin [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay] in 10 SCCHN cell lines. Experimental Design: Five cisplatin-sensitive and five cisplatin-resistant cell lines [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay] were studied by comparative genomic hybridization, spectral karyotyping, and cDNA microarray analysis (21,632 sequence-validated human cDNA; confirmation by reverse transcriptase-PCR for selected genes). For the MET proto-oncogene, which showed low expression in the chemosensitive cell lines, we did immunohistochemical staining on SCCHN of 29 patients who received induction chemotherapy. Results: The five cisplatin-resistant cell lines showed significantly more genetic imbalances (regions of loss and amplification) and chromosomal abnormalities by comparative genomic hybridization and spectral karyotyping, respectively, than did the five cisplatin-sensitive cell lines. Microarray studies identified similar to60 genes that clearly distinguish between the two groups of cell lines. Some of these genes are known to be involved in tumor progression, metastasis, and drug resistance. We identified low expression of c-met (immunohistochemistry) as a predictive factor for complete response in nondiploid tumors (P = 0.026). Conclusions: We conclude that cisplatin sensitivity and resistance are related to distinctive differences in the genetic and expression profiles in individual SCCHN tumor cell lines and in SCCHN patients. The genes we have identified may serve as potential targets for novel treatment strategies.
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| 6. |
- Haugen, Hedda, 1970, et al.
(författare)
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Preradiotherapy hemoglobin level but not microvessel density predicts locoregional control and survival in laryngeal cancer treated with primary radical radiotherapy.
- 2004
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Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1078-0432. ; 10:23, s. 7941-9
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate the roles of preradiotherapy hemoglobin level and microvessel density (MVD) as predictive factors for tumor control and survival in patients with laryngeal cancer treated with primary radiotherapy. EXPERIMENTAL DESIGN: Two hundred and fourteen patients with stage I-IV laryngeal cancer were included in the analysis. Patients were treated with once daily fractionated radiotherapy over 6.5 weeks or twice daily fractionated radiotherapy over 4.5 weeks up to total doses of 62 to 68 Gy. Preradiotherapy hemoglobin levels were obtained from patient journals, and pretreatment tumor biopsies were stained with CD34 antibody for the counting of microvessels. The prognostic implication of preradiotherapy hemoglobin level and MVD on tumor control and survival was tested. RESULTS: Five-year locoregional control probability was 88.9% for patients with preradiotherapy hemoglobin levels >137.5 g/L (median) and 64.4% for patients with preradiotherapy hemoglobin levels <137.5 g/L (P = 0.01). The corresponding figures for disease-free survival were 87.8 and 62.8% (P = 0.007), respectively, and for overall survival 58.1 and 40.3% (P < 0.001), respectively. In multivariate analysis, tumor stage and preradiotherapy hemoglobin level were significant prognostic factors for locoregional control and disease-free survival, whereas tumor stage, preradiotherapy hemoglobin-level, gender, and age were significant prognostic factors for overall survival. No correlation was found between MVD and tumor control and survival. CONCLUSION: Preradiotherapy hemoglobin level, but not MVD, predicts locoregional control and survival in patients with laryngeal cancer treated with radiotherapy.
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| 8. |
- Ullenhag, Gustav J, et al.
(författare)
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Durable carcinoembryonic antigen (CEA)-specific humoral and cellular immune responses in colorectal carcinoma patients vaccinated with recombinant CEA and granulocyte/macrophage colony-stimulating factor.
- 2004
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 10:10, s. 3273-3281
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Previous studies have indicated that carcinoembryonic antigen (CEA) might be a suitable immunotherapeutic target in colorectal carcinoma (CRC). The aim of the present study was to analyze the immunological and clinical effects of vaccination with CEA together with the adjuvant granulocyte/macrophage colony-stimulating factor (GM-CSF).EXPERIMENTAL DESIGN: Twenty-four resected CRC patients without macroscopic disease were immunized seven times with recombinant CEA at four different dose levels over a 12-month period. Half of the patients received GM-CSF (80 microg/day for 4 consecutive days) at each immunization. Patients were monitored immunologically for 36 months and clinically for 76 months. T-cell response was evaluated by a [(3)H]thymidine incorporation assay, and IgG response was determined by ELISA.RESULTS: Minor local side effects were common. All 12 patients (100%) in the GM-CSF group developed a CEA-specific T-cell as well as an IgG response. The corresponding figures in the CEA alone group were 9 of 12 (75%) and 8 of 12 (66%), respectively. GM-CSF significantly augmented the amplitude of the T-cell response and the IgG titers. No dose-response relationship was noted. The immune responses at 12 months persisted 24 months after the last vaccination. Anti-CEA IgG titers were associated with increased survival (P < 0.05), whereas standard prognostic factors had no relationship, with the exception of serum CEA value.CONCLUSIONS: Vaccination with recombinant CEA and GM-CSF appears to be a nontoxic regimen inducing potent and durable antigen-specific IgG and T-cell response. The results of this study justify more extensive trials with recombinant CEA protein for immunotherapy of CRC.
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| 9. |
- Uramoto, Hidetaka, et al.
(författare)
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Expression of deltaNp73 predicts poor prognosis in lung cancer.
- 2004
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Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1078-0432. ; 10:20, s. 6905-11
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: DeltaNp73 is an isoform of the p53 homologue p73, which lacks an NH(2)-terminal transactivation domain and antagonizes the induction of gene expression by p53/p73. The aim of this study was to detect DeltaNp73 expression in lung cancer and to evaluate the relationship between the DeltaNp73 expression level and the prognosis of patients with resected lung cancer. EXPERIMENTAL DESIGN: We used immunohistochemistry to analyze the protein expression of DeltaNp73 in paraffin-embedded tumor samples from 132 well-characterized lung cancer patients and compared the expression level of DeltaNp73, clinical variables, and survival outcome. RESULTS: Positive expression of DeltaNp73 was detected mainly in the cytoplasm of tumor cells in 77 of 132 patients (58.3%) with lung cancer. The incidence of positive expression of DeltaNp73 was 52.2, 50.0, and 70.2% in patients with stage I, II, and III, respectively (P = 0.04). Positive expression of DeltaNp73 was associated with gender but not associated with age, histologic type, pathological stage, pathological T status, and pathological N status. Lung cancer patients with positive DeltaNp73 expression had a poorer prognosis than those with negative DeltaNp73 expression. In addition, multivariate analysis of the clinicopathological characteristics of lung cancer indicated that positive expression of DeltaNp73 was a significant independent factor for predicting poor prognosis (P < 0.0001, risk ratio = 3.39). CONCLUSIONS: Expression of DeltaNp73 may be a useful marker for predicting poor prognosis of patients who underwent resection of lung cancer.
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