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101.
Avigad S Peleg D Barel D Benyaminy H Ben-Baruch N Taub E Shohat M Goshen Y Cohen IJ Yaniv I Zaizov R 《Journal of pediatric hematology/oncology》2004,26(9):541-545
PURPOSE: The hallmark of Li-Fraumeni syndrome (LFS), a familial cancer syndrome, is constitutional TP53 mutation. The authors addressed the complex question of predictive prenatal genetic testing for cancer risk associated with inheritance of TP53 mutation. METHODS: A classic LFS family including the proband (a 20-month-old boy with rhabdomyosarcoma), his 36-year-old father with osteosarcoma, and his 40-year-old paternal aunt with bilateral breast cancer were identified as carriers of a TP53 germline mutation, a novel 1 base pair deletion in exon 5. A few years later, the mother became pregnant twice, and the parents requested prenatal diagnosis on each occasion. Genetic counseling, psychological evaluation, and support were provided by a multidisciplinary team including a pediatric oncologist, a geneticist, a psychosocial worker, a prenatal care provider, and an ethical representative. After providing overall information on LFS, including the high risk of developing secondary multiple neoplasms in LFS survivors, the committee approved prenatal diagnosis at the request of the family. RESULTS: In the two pregnancies, the two fetuses were found to be carriers of the same mutation. Nine years from diagnosis of the first tumor, the proband, and a month later his father, developed second tumors, multifocal osteosarcoma and leiomyosarcoma, respectively. CONCLUSIONS: Children with primary tumors belonging to LFS should be considered for screening for germline mutations and genetic counseling by a multidisciplinary team. Whether family members are found to be positive or negative as carriers, such measures may provide, by reducing uncertainty, psychological benefit to high-risk families. 相似文献
102.
Mechanism of action of glatiramer acetate in multiple sclerosis and its potential for the development of new applications
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Arnon R Aharoni R 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(Z2):14593-14598
Glatiramer acetate (GA, Copaxone, Copolymer 1) is an approved drug for the treatment of multiple sclerosis and is highly effective in the suppression of experimental autoimmune encephalomyelitis in various species. The mode of action of GA is by initial strong promiscuous binding to MHC molecules and consequent competition with various myelin antigens for their presentation to T cells. A further aspect of its action is potent induction of specific suppressor cells of the T helper 2 (Th2) type that migrate to the brain and lead to in situ bystander suppression. Furthermore, the GA-specific cells in the brain express the antiinflammatory cytokines IL-10 and transforming growth factor beta, in addition to brain-derived neurotrophic factor, whereas they do not express IFN-gamma. Based on this immunomodulatory mode of action, we explored the potential of GA for two other applications: prevention of graft rejection and amelioration of inflammatory bowel diseases. GA was effective in amelioration of graft rejection in two systems by prolongation of skin graft survival and inhibition of functional deterioration of thyroid grafts, across minor and major histocompatibility barriers. In all transplantation systems GA treatment inhibited the detrimental secretion of Th1 inflammatory cytokines and induced beneficial Th2/3 antiinflammatory response. GA was effective also in combination with low-dose immunosuppressive drugs. Inflammatory bowel diseases are characterized by detrimental imbalanced proinflammatory immune reactivity in the gut. GA significantly suppressed the various manifestations of trinitrobenzene sulfonic acid-induced colitis, including mortality, weight loss, and macroscopic and microscopic colonic damage. GA suppressed local lymphocyte proliferations and tumor necrosis factor alpha detrimental secretion but induced transforming growth factor beta, thus confirming the involvement of Th1 to Th2 shift in GA mode of action. 相似文献
103.
Yamaguchi S Kuroda S Ushikoshi S Ishikawa T Nanba R Hokari M Asano T Iwasaki Y 《No shinkei geka. Neurological surgery》2004,32(7):747-751
Combined therapy of direct sinus packing and surgical excision for intracranial dural arteriovenous fistula (dAVF) has not been reported in the literature. A 53-year-old male was admitted to our hospital due to sudden onset of seizure and consciousness disturbance. Plain CT scan showed subcortical hematoma in the right temporal lobe. Cerebral angiography revealed dAVF involved in the right transverse and sigmoid sinuses. The lesion was associated with retrograde venous drainage into the right cerebellum, temporal, and occipital lobes. Positron emission tomography (PET) showed typical findings of venous hypertension in the involved areas. MRI also demonstrated a high intensity lesion in the medulla oblongata, suggesting critical venous congestion. First, we aimed to pack the involved sinus through a minor craniotomy, but cannulation into the sinus was impossible probably because of a marked fibrosis in the involved sinus. Then, we completely exposed the involved sinus through craniotomy. Through a microcatheter inserted into the sinus, the lower part of the sigmoid sinus was directly packed, and the remaining lesion was excised. Postoperative course was uneventful. Disappearance of dAVF resolved the findings on PET and MRI. Combined therapy would be a safe, non-invasive, and useful option for patients with a complex intracranial dAVF. 相似文献
104.
105.
Evidence report on the treatment of pain in cancer patients 总被引:5,自引:1,他引:4
Carr DB Goudas LC Balk EM Bloch R Ioannidis JP Lau J 《Journal of the National Cancer Institute. Monographs》2004,2004(32):23-31
Pain associated with cancer is of widespread concern. We conducted a systematic review to evaluate the best available evidence on the efficacy of treatments of cancer-related pain. The sources used were MEDLINE, CancerLit, and the Cochrane Library from 1966 through April 2001, as well as bibliographies of meta-analyses and review articles. We selected randomized controlled trials (RCTs) reporting on cancer pain treatment. We recorded the study characteristics, patient and disease characteristics, treatment comparisons, outcome measures, and results. The methodological quality, applicability, and magnitude of treatment effect for each study were graded. We screened 24 822 titles and selected 213 RCTs to address specific questions. RCTs of cancer pain control often enroll few subjects, have low methodological quality, offer little detail about pain characteristics and mechanisms, and involve heterogeneous interventions and outcomes. Nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, selected adjuvant medications, bisphosphonates, radionuclides, external radiation, palliative chemotherapy, and neurolytic celiac plexus block are each efficacious in relieving cancer pain. However, the retrieved RCTs indicate no difference in the analgesic efficacies of NSAIDs versus other NSAIDs, NSAIDs plus opioids versus NSAIDs alone, or NSAIDs versus opioids. Studies of adjuvant medications and behavioral therapies are too few and varied to synthesize. RCTs of the analgesic effects of corticosteroids were not retrieved in our review, although we did conduct supplemental evidence reviews concerning pain control in oral mucositis, acute herpes zoster, or postherpetic neuralgia. RCTs confirm the efficacy of diverse interventions in relieving cancer pain. The optimal initial and subsequent sequence of choices among analgesic drug types cannot be inferred from the retrieved RCTs. Patient preferences, the relative efficacy of different routes of drug administration, the side effects of analgesics, and the relation of pain control to quality of life have not been studied comprehensively. The quantity and quality of scientific evidence on cancer pain relief compare unfavorably with evidence related to treatment of other high-impact conditions, including cancer itself. One contributor to this gap is the heterogeneity of outcomes instruments employed: of 218 retrieved trials, there were 125 distinct pain outcomes assessed. In the current era of patient-centered care, improving the quality and combinability of trials on cancer pain relief should be a high research priority. 相似文献
106.
Adipocyte-fatty acid binding protein induces apoptosis in DU145 prostate cancer cells 总被引:4,自引:0,他引:4
De Santis ML Hammamieh R Das R Jett M 《Journal of experimental therapeutics & oncology》2004,4(2):91-100
Adipocyte-fatty acid binding protein (A-FABP) is a 14-15 kDa cytoplasmic protein that binds unesterified fatty acids (FA). It is believed that A-FABP is present in normal cells and disappears in cancer cells. Prostate cancer DU145 cells lack expression of A-FABP. Here, we report that transfection of A-FABP blocked growth of DU145 cells suggesting its role as a tumor suppressor. A-FABP transfected- prostate cancer DU145 cells underwent apoptosis when induced to overexpress A-FABP using an ecdysone-controlled expression system. DU145 cell cultures in complete medium exhibited a maximum of approximately 28% of apoptotic cells after 96 h of exposure to an ecdysone analog, Ponasterone A. We found that the possible mechanisms leading to the observed apoptotic effect may be due, in part, to an overexpression of tumor necrosis factor-alpha (TNF-alpha) and a moderate downregulation of transforming growth factor-alpha (TGF-alpha) in DU145 cells overexpressing A-FABP. The epidermal growth factor receptor (EGFR)/phosphatidyl inositol 3-kinase (PI 3-kinase) signaling pathway was not altered in these cells, suggesting that A-FABP may cause apoptosis by inducing downregulation of essential autocrine growth factors and/or upregulation of pro-apoptotic ones. 相似文献
107.
To test the hypothesis that increased serum levels of vascular endothelial growth factor (VEGF) in women with polycystic ovaries or the polycystic ovary syndrome (PCOS) result from excess release by ovarian granulosa cells.Prospective study.Academic research setting.Twenty women undergoing IVF treatment, of whom 10 had normal ovaries and 10 had polycystic ovaries.Human granulosa lutein cells were isolated from follicular fluid obtained on the day of oocyte retrieval. Release of VEGF was assessed after co-incubation of granulosa lutein cells with gonadotropins and insulin. Serum and follicular fluid concentrations of VEGF were measured.Release of VEGF from granulosa lutein cells and serum levels of VEGF.Incubation with human hCG, and luteinizing hormone increased release of VEGF into the culture medium. Insulin alone did not increase release of VEGF, but addition of insulin increased hCG-stimulated release of VEGF. Serum and follicular fluid VEGF concentrations and the amount VEGF released from granulosa lutein cells obtained from women with polycystic ovaries or PCOS and those who developed the ovarian hyperstimulation syndrome were greater than those from granulosa lutein cells obtained from women with normal ovaries and those who did not develop the ovarian hyperstimulation syndrome.The amount of VEGF released by granulosa lutein cells is gonadotropin dependent and is augmented by insulin. The increased circulating concentrations of VEGF in women with PCOS may not only be due to an increased number of actively secreting granulosa lutein cells but also due to increased secretory capacity of each granulosa cell. 相似文献
108.
Matsuura T Chinen Y Arashiro R Katsuren K Tamura T Hyakuna N Ohta T 《Molecular genetics and metabolism》2002,76(3):207-210
Fructose-1,6-bisphosphatase (FBPase) (EC 3.1.3.11) catalyzes the splitting of fructose-1,6-bisphosphate into fructose 6-phosphate and inorganic phosphate. FBPase deficiency is an autosomal recessive inherited disorder caused by distraction of the fructose-1,6-bisphosphatase 1 gene (FBP1) and features severely impaired gluconeogenesis. We studied a female patient with typical FBPase deficiency symptoms. The FBPase activity of her peripheral white blood cells was undetectable. Genetic analyses of FBP1 revealed her to be a compound-heterozygote of two new mutations F194S and P284R. Gene tracking in the family revealed the mother to be a heterozygote of F194S, and the father and a sister to be heterozygotes of P284R. As both Phe194 and Pro284 of FBPase are highly conserved in many species and close to crucial amino acid residues to FBPase functions, these mutations could be responsible for the loss of FBPase activities. 相似文献
109.
110.
Nemoto K Seiji K Sasaki K Kasamatsu N Fujishima T Ogawa Y Ariga H Takeda K Kimura T Yamada S 《International journal of radiation oncology, biology, physics》2003,55(4):1102-1108
PURPOSE: To develop a method for quick and smooth transportation of patients from a computed tomography (CT) table to a linear accelerator (linac) table for confirming tumor center before radiation therapy. MATERIALS AND METHODS: We developed a system using a subtable for patient immobilization that is transported via a customized stretcher. The patient lies on the subtable and is immobilized by a vacuum cushion and thermoplastic body cast. The subtable stretcher is used to carry the subtable from the CT table to the linac table. During transportation, the subtable is kept flat and shock to the subtable is carefully avoided. Between August 2001 and September 2002, a total of 9 patients with solitary upper lung tumors (superior to carina) were treated using this system. RESULTS: Intrafractional tumor motion along the x (left-right), y (anterior-posterior), and z axis (superior-inferior) ranged from -2 mm to 2 mm, -2 mm to 2 mm, and -5 mm to 3 mm, respectively. The standard deviation of intrafractional tumor motion along the x, y, and z axis ranged from 0.5 mm to 1.5 mm, 0 mm to 1.7 mm, and 0.6 mm to 3.5 mm, respectively. Interfractional setup errors along the x, y, and z axis ranged from -5 mm to 4 mm, -6 mm to 8 mm, and -6 mm to 6 mm, respectively, and we could reduce interfractional setup errors in the majority of treatment sessions. CONCLUSIONS: We developed a system that allows patients to be immobilized and transported to verify tumor location on a daily basis. This system is highly useful for reducing setup errors. 相似文献