The expression of thymidine phosphorylase correlates with angiogenesis and the efficacy of chemotherapy using fluorouracil derivatives in advanced gastric carcinoma

The expression of thymidine phosphorylase (TP) and the density of microvessel in advanced gastric carcinoma were examined by immunohistochemistry to evaluate the significance of TP. The expression of TP was negative in 72 cases, positive in 54. The microvessel density correlated with the expression of TP. In total cases, patients with TP-positive tumours survived longer than those with TP-negative tumours. In patients treated with fluorouracil derivatives (FUs), the expression of TP significantly correlated with favourable prognosis and with unfavourable prognosis in those not treated with FUs. The patients with TP-positive tumours, the prognosis of patients treated with FUs was significantly better than that of those not treated with FUs. In patients with TP-positive tumours, treatment with FUs and lymph node metastasis were independent prognostic factors according to the Cox proportional hazards model. Depth of invasion and lymph node metastasis were independent prognostic factors in patients with TP-negative tumours. The determination of the expression of TP might be useful for predicting the efficacy of post-operative chemotherapy using FUs to prevent recurrence in advanced gastric carcinoma patients who undergo curative gastrectomy. © 1999 Cancer Research Campaig

Tracking tumor evolution via prostate-specific antigen: an individual post-operative study

<p>Abstract</p> <p>Background</p> <p>The progress of the prostate-specific antigen (PSA) level after radical prostatectomy is observed for a patient in order to extract information about the mode of tumor cell growth. Although PSA values are determined routinely to find the doubling time of the prostate marker, to our knowledge, this analysis is the first in the literature.</p> <p>Results</p> <p>The prostate tumor marker values were determined regularly after the surgery and plotted on a logarithmic scale against time. An initial rapid-growth mode changed to a slower power-law regime within two years of surgery. Our analysis associates this observation with a transition in the growth mode from unrestricted growth of dispersed cells to their clumping into macroscopic structures.</p> <p>Conclusions</p> <p>Such studies may help determine the appropriate time window for postoperative therapies in order to increase the life expectancy of the patient.</p

The influence of tumor size and environment on gene expression in commonly used human tumor lines

BACKGROUND: The expression profiles of solid tumor models in rodents have been only minimally studied despite their extensive use to develop anticancer agents. We have applied RNA expression profiling using Affymetrix U95A GeneChips to address fundamental biological questions about human tumor lines. METHODS: To determine whether gene expression changed significantly as a tumor increased in size, we analyzed samples from two human colon carcinoma lines (Colo205 and HCT-116) at three different sizes (200 mg, 500 mg and 1000 mg). To investigate whether gene expression was influenced by the strain of mouse, tumor samples isolated from C.B-17 SCID and Nu/Nu mice were also compared. Finally, the gene expression differences between tissue culture and in vivo samples were investigated by comparing profiles from lines grown in both environments. RESULTS: Multidimensional scaling and analysis of variance demonstrated that the tumor lines were dramatically different from each other and that gene expression remained constant as the tumors increased in size. Statistical analysis revealed that 63 genes were differentially expressed due to the strain of mouse the tumor was grown in but the function of the encoded proteins did not link to any distinct biological pathways. Hierarchical clustering of tissue culture and xenograft samples demonstrated that for each individual tumor line, the in vivo and in vitro profiles were more similar to each other than any other profile. We identified 36 genes with a pattern of high expression in xenograft samples that encoded proteins involved in extracellular matrix, cell surface receptors and transcription factors. An additional 17 genes were identified with a pattern of high expression in tissue culture samples and encoded proteins involved in cell division, cell cycle and RNA production. CONCLUSIONS: The environment a tumor line is grown in can have a significant effect on gene expression but tumor size has little or no effect for subcutaneously grown solid tumors. Furthermore, an individual tumor line has an RNA expression pattern that clearly defines it from other lines even when grown in different environments. This could be used as a quality control tool for preclinical oncology studies

The optimal starting time of postoperative intraperitoneal mitomycin-C therapy with preserved intestinal wound healing

BACKGROUND: There is controversy about the effect of the timing of intraperitoneal administration of chemotherapeutic agents on the healing of intestinal anastomosis. We have investigated the effect on intestinal wound healing of mitomycin-C administered at different times post-operatively. METHODS: Eighty-four Wistar-Albino female rats underwent ileal resection and end-to-end anastomosis. The rats were randomly selected for intraperitoneal administration of mitomycin-C or saline as follows: mitomycin-C group (n = 65), 2 mg/kg mitomycin-C; control group (n = 13), 10 ml saline. The former was sub-divided into 5 equal groups (A 1–5) and mitomycin-C was administered postoperatively as follows: day 0 (A1), day 3 (A2), day 5 (A3), day 7 (A4) and day 10 (A5). All the rats were sacrificed on the 14th postoperative day and anastomotic bursting pressures and tissue hydroxyproline levels were determined. RESULTS: Five of the animals died postoperatively: 2 (15.4%) in group A1, 2 (15.4%) in group A2 and 1(7.7%) in group A3. Non-lethal anastomotic leakage was observed in a further five animals: 1 in group A1, 2 in group A2, 1 in group A5 and 1 in the control group. Groups A1 and A2 had significantly lower anastomotic bursting pressures than the other groups (P was <0.05 for each comparison). The anastomotic bursting pressures of group A3, A4 and A5 were comparable with those of the controls (P was >0.05 for each comparison). Tissue hydroxyproline levels in group A1 and A2 were significantly lower than in the controls (P values were <0.05 for each comparison) or the other mitomycin-C sub-groups (P was <0.05 for each comparison). CONCLUSIONS: Intraperitoneal chemotherapy impairs intestinal wound healing when applied before the 5th postoperative day. Additional therapeutic approaches are needed to prevent this potentially lethal side effect of early intraperitoneal mitomycin-C administration

Species-Specific Therapy of Acute Lymphoid Leukemia

Forty years ago, Farber and associates described temporary remissions of acute leukemia in children produced by folic acid antagonists [13]. This ignited the hope that this most frequent and always fatal childhood cancer might be curable by drugs. Twenty years ago, Aur and as-sociates completed accession of patients to total therapy study V, the first treat-ment protocol to result in 50 % cure of acute lymphoid leukemia (ALL) [3]. Their results stand 20 years later (Fig. 1), and have been reproduced throughout the world in many thousands of children [6]. More important, recent national vital statistics of the United States and the United Kingdom indicate a 50 % reduc-tion in childhood leukemia mortality [4, 29]. Further, the cured children generally enjoy a normal life-style without need for medication. In the past 20 years, efforts have been directed at improving the cure rate of ALL while simplifying curative treat-ment, reducing its side effects, and im-proving its availability and accessibility. In a Stohlman Lecture at Wilsede 10 years ago the following statement was made [32]:- The most significant opportunity for improving the treatment of acute lymphoid leukemia in the past five years has been its biological and clini-cal classification by immunological cell surface markers. This allows spe-cies identification of the leukemia cells, the first step toward developing specific cytocidal or cytostatic therapy