| 81. |
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| 82. |
- Ferreri, AJM, et al.
(författare)
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Anthracycline-based chemotherapy as primary treatment for intravascular lymphoma
- 2004
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 15:8, s. 1215-1221
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Tidskriftsartikel (refereegranskat)abstract
- Background: Optimal therapeutic management of intravascular lymphoma (IVL) lacks precise guidelines. Patients and methods: The clinico-pathological features of 38 HIV-negative patients with IVL were reviewed to define efficacy of chemotherapy in these malignancies. Clinical characteristics of 22 patients treated with chemotherapy and of 16 untreated patients were compared in order to understand better the impact and causes of potential patient selection. Results: Median age was 70 years (range 34-90), with a male/female ratio of 0.9; 23 (61%) patients had Eastern Cooperative Oncology Group performance status (ECOG-PS) >1;21 (55%) had systemic symptoms. Cutaneous lesions and anemia were significantly more common among patients treated with chemotherapy; central nervous system (CNS) and renal involvement were significantly more common among untreated patients. Chemotherapy was associated with a response rate of 59% and a 3-year overall survival of 33 +/- 11%. Five of six patients with CNS involvement received chemotherapy: four of them died early; only one patient, treated with adriamycin, cyclophosphamide, vincristine, methotrexate, bleomycin and prednisolone (MACOP-B) followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT), was alive at 19 months. High-dose chemotherapy supported by ASCT was indicated at diagnosis in another patient (43 years of age, stage 1), who was alive at 71 months, and at relapse after cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) in two patients who died early after transplantation. PS less than or equal to 1, disease limited to the skin, stage 1, and use of chemotherapy were independently associated with better outcome. Conclusions: Anthracycline-based chemotherapy is the standard treatment for IVL. However, survival is disappointing, with a relevant impact of diagnostic delay and lethal complications. More intensive combinations, containing drugs with higher CNS bioavailability, are needed in cases with brain involvement, and the role of high-dose chemotherapy supported by ASCT should be further investigated in younger patients with unfavorable features.
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| 83. |
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| 84. |
- 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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| 85. |
- Ford, Caroline, et al.
(författare)
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Progression from normal breast pathology to breast cancer is associated with increasing prevalence of mouse mammary tumor virus-like sequences in men and women
- 2004
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Ingår i: Cancer Research. - 1538-7445. ; 64:14, s. 4755-4759
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Tidskriftsartikel (refereegranskat)abstract
- Mouse mammary tumor virus (MMTV)-like sequences have been found in up to 40% of breast cancer samples but in <2% of normal breast tissue samples from Australian women studied by our group. Screening of a larger and more diverse cohort of female breast cancer samples has now shown a correlation of MMTV-like sequences with the severity (grade) of breast cancer. Thirty-two percent (43 of 136) of female breast cancer samples were positive for MMTV-like sequences when screened using PCR. A significant gradient of MMTV positivity was observed with increasing severity of cancer from 23% of infiltrating ductal carcinoma (IDC) grade I tumors to 34% of IDC grade II tumors (P = 0.00034) and 38% of IDC grade III tumors (P = 0.00002). We also report for the first time the detection of MMTV-like sequences in 62% (8 of 13) of male breast cancer samples and 19% (10 of 52) of male gynecomastia samples screened. MMTV-like sequences were demonstrated in various premalignant breast lesions of females, including fibroadenoma (20%) and fibrocystic disease (28%) samples, at a significantly higher prevalence than that seen in normal breast tissue (1.8%; P = 0.00001). Study of a longitudinal cohort of female breast cancer patients indicated that MMTV was co-incident with tumor but was not present when tumor was absent on histology. These results support the association of MMTV-like sequences with development of breast tumors in men and women and suggest association of MMTV with increasing severity of cancer.
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| 86. |
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| 87. |
- Fransson, Johan, et al.
(författare)
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Profiling of internalizing tumor-associated antigens on breast and pancreatic cancer cells by reversed genomics
- 2004
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Ingår i: Cancer Letters. - : Elsevier BV. - 1872-7980 .- 0304-3835. ; 208:2, s. 235-242
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Tidskriftsartikel (refereegranskat)abstract
- Human antibodies directed towards functionally associated tumor antigens have great potentials as adjuvant treatment in cancer therapy. Here we describe an efficient subtractive approach to select single chain Fv (scFv) antibodies, specifically binding to unknown rapidly internalizing tumor-associated antigens (TAA) on human breast and pancreatic carcinoma cell lines. After re-engineering the scFv into intact IgG molecules, these fully human antibodies displayed individual binding profiles to TAAs on breast, pancreatic, colorectal and prostate carcinomas, while showing no reactivity to lymphomas. The ability of the selected antibodies to undergo receptor-mediated internalization was verified by confocal microscopy, thus proving our strategy to provide a unique set of human antibodies, potentially useful in immunotherapy. (C) 2003 Elsevier Ltd. All rights reserved.
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| 88. |
- Furuhashi, Masao, et al.
(författare)
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Platelet-derived growth factor production by B16 melanoma cells leads to increased pericyte abundance in tumors and an associated increase in tumor growth rate
- 2004
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Ingår i: Cancer Research. - : American Association for Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 64:8, s. 2725-2733
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Tidskriftsartikel (refereegranskat)abstract
- Platelet-derived growth factor (PDGF) receptor signaling participates in different processes in solid tumors, including autocrine stimulation of tumor cell growth, recruitment of tumor stroma fibroblasts, and stimulation of tumor angiogenesis. In the present study, the B16 mouse melanoma tumor model was used to investigate the functional consequences of paracrine PDGF stimulation of host-derived cells. Production of PDGF-BB or PDGF-DD by tumor cells was associated with an increased tumor growth rate. Characterization of tumors revealed an increase in pericyte abundance in tumors derived from B16 cells producing PDGF-BB or PDGF-DD. The increased tumor growth rate associated with PDGF-DD production was not seen in mice expressing an attenuated PDGF beta-receptor and was thus dependent on host PDGF beta-receptor signaling. The increased pericyte abundance was not associated with an increased tumor vessel density. However, tumor cell apoptosis, but not proliferation, was reduced in tumors displaying PDGF-induced increased pericyte coverage. Our findings thus demonstrate that paracrine PDGF production stimulates pericyte recruitment to tumor vessels and suggest that pericyte abundance influences tumor cell apoptosis and tumor growth.
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| 89. |
- Gadjieva, Rena, et al.
(författare)
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Nonsense-mediated mRNA decay in barley mutants allows the cloning of mutated genes by a microarray approach.
- 2004
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Ingår i: Plant Physiology and Biochemistry. - : Elsevier BV. - 1873-2690 .- 0981-9428. ; 42:7-8, s. 681-685
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Tidskriftsartikel (refereegranskat)abstract
- We have previously described a microarray approach to identify and clone genes from mutants of higher organisms. In the method cDNA of two mutants with similar phenotype are competitively hybridized to DNA clones arrayed on a glass slide. Clones corresponding to an mRNA that is not expressed in one of the strains due to a mutation will be specifically highlighted in the hybridization, which provides a possibility to identify and eventually clone the mutated gene. The approach is dependent on mutations that affect the amount of mRNA. Nonsense mutations, which prematurely terminate translation, can be such mutations as a surveillance system known as nonsense-mediated decay (NMD) has been developed by organisms to reduce the abundance of mRNA with nonsense codons. In the present study, we have analysed the barley (Hordeum vulgare L.) magnesium chelatase mutants xantha-f 26, xantha-f 27 and xantha-f 40 in order to investigate the presence of NMD in barley, as well as the importance of the position of the stop codon for NMD. Both nonsense-mutants xantha-f 27 and xantha-f 40, but not the missense mutant xantha-f 26, showed NMD. This was not expected for xantha-f 27 as its mutation is in the last exon of the gene. We conclude the NMD expands the number of mutants that can be used for gene cloning by our described microarray approach.
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| 90. |
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