British journal of cancer
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British journal of cancer · Jun 1998
Synthesis and breakdown of fibrillar collagens: concomitant phenomena in ovarian cancer.
The synthesis and degradation of type I and type III interstitial collagens releases several antigenic metabolites, whose measurement allows the metabolism of connective tissue to be evaluated under a variety of different conditions. In this study we investigated the influence of benign and malignant ovarian neoplasms on the metabolism of these collagens. The study population comprised patients with benign (n = 53), borderline (n = 6) or malignant (n = 36) ovarian neoplasms. ⋯ The different distributions of PIIINP, PINP and ICTP suggests dominance of synthetic processes or retarded elimination of PIIINP and PINP in ovarian cancer. In advanced malignancies, the accumulation of PINP and PIIINP in abdominal space, possibly due to increased synthesis and/or failed resorption, may promote ascites formation. This study shows that both accelerated synthesis and breakdown of fibrillar collagens are characteristic of ovarian malignancy, and suggests that measurements of cyst fluid or ascitic fluid concentrations of collagen metabolites or CSF-1 could be used in the differential diagnosis of benign and malignant ovarian neoplasms.
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British journal of cancer · Jun 1998
Toxicity to neuroblastoma cells and spheroids of benzylguanidine conjugated to radionuclides with short-range emissions.
Radiolabelled meta-iodobenzylguanidine (MIBG) is selectively taken up by tumours of neuroendocrine origin, where its cellular localization is believed to be cytoplasmic. The radiopharmaceutical [131I]MIBG is now widely used in the treatment of neuroblastoma, but other radioconjugates of benzylguanidine have been little studied. We have investigated the cytotoxic efficacy of beta, alpha and Auger electron-emitting radioconjugates in treating neuroblastoma cells grown in monolayer or spheroid culture. ⋯ In contrast, the Auger electron emitters were ineffective in the treatment of larger spheroids, while the beta emitter showed greater efficacy. These findings suggest that short-range emitters would be well suited to the treatment of circulating tumour cells or small clumps, whereas beta emitters would be superior in the treatment of subclinical metastases or macroscopic tumours. These experimental results provide support for a clinical strategy of combinations ('cocktails') of radioconjugates in targeted radiotherapy.
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British journal of cancer · Jun 1998
Thrombin promotes platelet-mediated melanoma cell adhesion to endothelial cells under flow conditions: role of platelet glycoproteins P-selectin and GPIIb-IIIA.
We investigated the role of platelets in human melanoma cell (line 397) interaction with vascular endothelial cells (ECs) under flow conditions. The ability of the tumour cells to adhere to the EC monolayer was significantly reduced by application of flow at a shear rate of 250 s(-1). A 2.2-fold increase in tumour cell adhesion to ECs under flow was observed upon addition of thrombin receptor agonist peptide (TRAP)-activated platelets but not resting platelets. ⋯ Blockade of GPIIb-IIIa inhibited both platelet-EC and platelet-tumor cell interactions. Our results indicate that tumour cell adhesion to the endothelium under flow is enhanced by platelets under conditions that allow platelet adhesion to ECs. Inhibition studies suggest that activated platelet adhesion to ECs is mediated by P-selectin and GPIIb-IIIA, and tumour cell adhesion to EC-bound platelets--mainly by GPIIb-IIIa.
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British journal of cancer · May 1998
Randomized Controlled Trial Comparative Study Clinical TrialComparison of antiemetic efficacy of granisetron and ondansetron in Oriental patients: a randomized crossover study.
A double-blind randomized crossover trial was performed to compare the antiemetic efficacy of two 5-HT3 receptor antagonists, granisetron and ondansetron, in Chinese patients receiving adjuvant chemotherapy (cyclophosphamide, methotrexate and 5-fluorouracil) for breast cancer. Twenty patients were randomized to receive chemotherapy with either granisetron on day 1 and ondansetron on day 8 of the first cycle followed by the reverse order in the second cycle, or vice versa. The number of vomiting episodes and the severity of nausea in the first 24 h (acute vomiting/nausea) and the following 7 days (delayed vomiting/nausea) were studied. ⋯ However, complete response for delayed vomiting was observed in only 21 (52.5%) cycles with granisetron and 22 (55%) cycles with ondansetron (P = NS), and delayed nausea was completely controlled in only 11 (27.5%) and ten (25%) cycles respectively (P = NS). In conclusion, both granisetron and ondansetron are effective in controlling acute nausea and vomiting in Chinese patients, with equivalent antiemetic efficacy. Control of delayed nausea and vomiting is less satisfactory.
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British journal of cancer · Apr 1998
Randomized Controlled Trial Clinical TrialCombined intravenous and intraperitoneal chemotherapy with fluorouracil + leucovorin vs fluorouracil + levamisole for adjuvant therapy of resected colon carcinoma.
Adjuvant chemotherapy with fluorouracil (FU) and levamisole or FU/leucovorin (LV) has been established as effective adjuvant treatment for patients with stage III colon cancer. Among several other promising treatment strategies in resected colon cancer, intraperitoneal anti-cancer drug administration with its appealing rationale of counteracting microscopic residual disease on peritoneal surfaces and occult metachronous liver metastases by achieving high intraportal drug concentrations has not yet undergone sufficient clinical evaluation. To determine whether a combination of this locoregional therapeutic concept with systemic intravenous administration of FU/LV would yield better results than conventional adjuvant chemoimmunotherapy with FU/levamisole, the present randomized study was initiated. ⋯ In agreement with its theoretical rationale, combined intraperitoneal and intravenous FU/LV was particularly effective in reducing locoregional tumour recurrences with or without liver or other organ site involvement (9 vs 25 patients in the FU/levamisole arm; P = 0.005). Treatment-associated side-effects were infrequent and generally mild in both arms, although a lower rate of severe (WHO grade 3) adverse reactions was noted in patients receiving locoregional plus intravenous chemotherapy (3% vs 12%; P = 0.01). The results of this trial suggest that combined intraperitoneal plus systemic intravenous chemotherapy with FU/LV is a promising adjuvant treatment strategy in patients with surgically resected stage III colon carcinoma.