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Tumour Proliferation (tumour + proliferation)
Selected AbstractsThe effect of thiamine supplementation on tumour proliferationFEBS JOURNAL, Issue 15 2001A metabolic control analysis study Thiamine deficiency frequently occurs in patients with advanced cancer and therefore thiamine supplementation is used as nutritional support. Thiamine (vitamin B1) is metabolized to thiamine pyrophosphate, the cofactor of transketolase, which is involved in ribose synthesis, necessary for cell replication. Thus, it is important to determine whether the benefits of thiamine supplementation outweigh the risks of tumor proliferation. Using oxythiamine (an irreversible inhibitor of transketolase) and metabolic control analysis (MCA) methods, we measured an in vivo tumour growth control coefficient of 0.9 for the thiamine-transketolase complex in mice with Ehrlich's ascites tumour. Thus, transketolase enzyme and thiamine clearly determine cell proliferation in the Ehrlich's ascites tumour model. This high control coefficient allows us to predict that in advanced tumours, which are commonly thiamine deficient, supplementation of thiamine could significantly increase tumour growth through transketolase activation. The effect of thiamine supplementation on tumour proliferation was demonstrated by in vivo experiments in mice with the ascites tumour. Thiamine supplementation in doses between 12.5 and 250 times the recommended dietary allowance (RDA) for mice were administered starting on day four of tumour inoculation. We observed a high stimulatory effect on tumour growth of 164% compared to controls at a thiamine dose of 25 times the RDA. This growth stimulatory effect was predicted on the basis of correction of the pre-existing level of thiamine deficiency (42%), as assayed by the cofactor/enzyme ratio. Interestingly, at very high overdoses of thiamine, ,,2500 times the RDA, thiamine supplementation had the opposite effect and caused 10% inhibition of tumour growth. This effect was heightened, resulting in a 36% decrease, when thiamine supplementation was administered from the 7th day prior to tumour inoculation. Our results show that thiamine supplementation sufficient to correct existing thiamine deficiency stimulates tumour proliferation as predicted by MCA. The tumour inhibitory effect at high doses of thiamine is unexplained and merits further study. [source] Factors influencing the incidence and prognosis of canine mammary tumoursJOURNAL OF SMALL ANIMAL PRACTICE, Issue 7 2000M. D. Perez Alenza Factors relating to the incidence of canine mammary tumours are reviewed. Increased age, intact status or ovariectomy after 2.5 years of age, as well as progestagen treatment, can all lead to an increased risk of mammary neoplasia in the bitch. In addition, obesity early in life, and a habitual diet based on home-made food (rich in beef and pork, and poor in chicken) as opposed to commercial food, are also associated with the occurrence of mammary tumours. Other aspects related to incidence are also discussed. Increased age at diagnosis, invasive growth (fixed to adjacent tissues), large tumour size, ulceration of skin, and axillary or inguinal node involvement are clinical parameters associated with a low chance of survival after surgical excision of mammary tumours. Histological typing and grading of the tumour allows the establishment of a prognosis, which is poor where there is tumour proliferation as measured by S-phase fraction determination and Ki-67 immunostaining. [source] Expression of minichromosome maintenance proteins in Merkel cell carcinomaJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2009T Gambichler Abstract Objective, Minichromosome maintenance (MCM) nuclear proteins have barely been employed in the diagnosis of skin malignancies. We aimed to assess whether MCM immunohistochemistry can be utilized to examine tumour proliferation in Merkel cell carcinoma (MCC). Methods, In this pilot study, we studied skin specimens of eight patients with MCC. As a control, eight patients with cutaneous malignant melanoma (MM) were included. Immunohistochemistry was performed for MCM4, MCM6, MCM7, Ki-67, p53, and p21. Results, Protein expression of MCM4 (66.0 ± 26.5% vs. 33.9 ± 22.4%; P = 0.017), MCM6 (70.9 ± 11.9 vs. 31.7 ± 22.7; P = 0.0031), and MCM7 (76.5 ± 16.4% vs. 34.9 ± 25.5%; P = 0.0013) was significantly increased in tumour cells of MCC when compared to tumour cells of MM. Ki-67 immunoreactivity was also significantly higher in MCC than in MM (28.7 ± 7.9 vs. 11.0 ± 9.2; P = 0.0012). Immunolabelling of p53 (68.6 ± 26.2 vs. 58.4 ± 28.8; P = 0.46) and p21 (40.1 ± 38.8 vs. 25.8 ± 16.1; P = 0.35) was relatively high but not significantly increased in MCC when compared to MM. Conclusion, Our preliminary data indicate that MCM immunohistochemistry may be a useful tool for the determination of tumour cell proliferation in MCC. [source] Significance of CD 105 expression for tumour angiogenesis and prognosis in endometrial carcinomasAPMIS, Issue 11 2003HELGA B. SALVESEN Angiogenesis is a key process in tumour growth and metastasis, and Factor-VIII microvascular density has been found to influence prognosis among endometrial carcinoma patients. The CD105/endoglin antibody has been reported to preferentially bind to activated endothelial cells in tissues participating in angiogenesis, and we therefore wanted to compare the prognostic significance of CD105/endoglin to that of Factor-VIII. In a population-based endometrial carcinoma study with long (median 11.5 years) and complete patient follow-up, mean intratumour microvascular density (MVD) assessed using CD105/endoglin was investigated and compared with previous data for MVD assessed using Factor-VIII. MVD by CD105/endoglin was significantly correlated with MVD by Factor-VIII (p=0.001). However, tumours within the two groups defined by the upper and lower quartiles for CD105/endoglin-MVD were both significantly more often metastatic (FIGO-stage III/IV; p=0.03), with high tumour cell proliferation by Ki67 (p=0.007) and with reduced survival (p=0.036) as compared with the intermediate groups. In Cox regression analysis, CD105/endoglin-MVD showed independent prognostic influence when analysed together with patient age, FIGO stage, histologic subtype, histologic grade and Factor-VIII-MVD, while the latter lost its prognostic impact when CD105/endoglin was included. In the subgroup with high MVD, there was a tendency towards improved response to radiation therapy. In conclusion, CD105/endoglin-MVD is significantly associated with FIGO stage, tumour proliferation and prognosis in endometrial carcinoma, indicating that this is a better angiogenic marker in these tumours. [source] 3465: Medical cancer therapy of lacrimal gland tumoursACTA OPHTHALMOLOGICA, Issue 2010C LE TOURNEAU Purpose The most common malignant epithelial cancer of the lacrimal gland is the adenoid cystic carcinoma (ACC). Despite a slow growth, ACCs are ultimately associated with a poor outcome. Methods Given the rarity of this disease, there are actually no conclusive recommendations for optimal therapy of this tumor. Results Surgery and postoperative radiation therapy is commonly used in the initial local treatment of ACC of the lacrimal gland. In high-risk recurrence patients, concomitant platinum-based chemoradiation should be discussed in an attempt to enhance radiosensitivity. While encouraging responses were reported with intraarterial neoadjuvant chemotherapy, this strategy was associated with substantial toxicity and should not be recommended outside of clinical trials. In the metastatic setting, systemic therapy is the only available option if no surgery and/or radiation is feasible. Although some tumour shrinkage has been reported with intravenous chemotherapy, only dismal objective response rates were achieved. Most active drugs remain anthracyclines and platinum compounds. Drug combinations do not seem to add much efficacy. More recently, non-cytotoxic molecularly targeted agents have emerged and demonstrated significant efficacy in several tumour types. These agents modulate specific targets thought to be essential for tumour proliferation and/or angiogenesis. c-KIT, PDGFR,, EGFR, and VEGFR are transmembrane receptors with oncogenic tyrosine kinase activity that are commonly overexpressed in ACC. The use of drugs triggering these targets has been disappointing so far. Conclusion The recent identification of a hallmark gene fusion transcript thought to activate critical targets involved in apoptosis, cell cycle control, cell growth and angiogenesis, heralds new treatment promise. [source] | ||||||||||