Yuji Miyagi

Vascular endothelial growth factor and platelet-derived endothelial cell growth factor expression are implicated in the angiogenesis of endometrial cancer.

Although many angiogenic factors have been described, it is not well defined which factors are expressed in endometrial cancer. The object of this study was to examine mRNA levels of the two angiogenic factors, vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) in endometrial cancer tissues and their association with clinicopathological features including microvessel density. The level of VEGF and PD-ECGF mRNAs was assessed by semi-quantitative reverse transcription-polymerase chain reaction using beta-actin as an internal standard in 38 patients with endometrial cancer. Microvessel counts were also assessed by immunostaining for factor VIII-related antigen in the most vascularised area of the specimen. VEGF/beta-actin ratios of non-endometrioid tumours were significantly higher than those of endometrioid tumours (P = 0.013). VEGF/beta-actin ratios of cases with lymph-vascular space involvement were significantly higher than those of cases without lymph-vascular space involvement (P = 0.021). Although it was not statistically significant, PD-ECGF/beta-actin ratios in grade 3 tumours were higher than those in grade 1 and 2 tumours (P = 0.066). The microvessel density was significantly correlated with the level of VEGF and PD-ECGF mRNA expression (P = 0.041 and P < 0.0001, respectively). Our findings provide evidence that the expression of both VEGF and PD-ECGF is involved in the promotion of angiogenesis in endometrial cancer. In addition, VEGF and PD-ECGF might contribute to the aggressive potential of high grade tumours or certain histological subtypes with unfavourable prognosis through the induction of angiogenesis.

Malignant Melanoma of the Uterine Cervix: A Case Report

We present case of a 57‐year‐old Japanese woman a 9 cm‐size primary malignant melanoma of the uterine cervix. MRI demonstrated a low‐signal T1‐weighted spin echo image and hyperperfusion indicated by Gd‐DTPA enhancement. The sequence! analysis of the MTS1/CDK4I gene revealed no deletion or mutation. The results of cytological, pathological, and electron microscopy tests are also presented.

Cytocidal effect and DNA damage of nedaplatin : a mathematical model and analysis of experimental data

Abstract.Purpose: Cell cycle non-specific anticancer agents such as cis-diamminedichloroplatinum(II) are believed to depend linearly on the value of the area under the drug concentration time curve, which is supported by a mathematical model. However, the quantitative non-linear phenomena of both the cytocidal effect and DNA crosslink formation by cis-diammine(glycolato)platinum (nedaplatin) have been shown in vitro. Therefore, we developed a new mathematical model to explain these phenomena. Methods: We assumed that nedaplatin enters intracellular fluid from medium through simple diffusion to form DNA crosslinks that kill cells. We developed a mathematical model to represent this assumption using differential equations that we then solved using an original computer program. The calculated results were compared with the experimental data. Results: The drugs simple diffusion rate constant, the DNA crosslink formation rate constant, and the crosslink-dependent cell death rate constant in the model were 1.8×10–14 (l h–1), 1.6×108 (l mol–1/2 h–1), 5.45×101 (mol–1), respectively. The model fits the experimental results statistically. The model also demonstrated theoretical proof that continuous exposure at a low dose was superior to the short exposure at a high dose seen in published experimental data. Conclusions: We developed a mathematical model to describe the non-linear pharmacodynamic effect of nedaplatin in vitro. This model may provide a novel drug infusion procedure for cancer patients.

Multivariate assessment of cervical invasion of endometrial carcinoma: Comparison of transvaginal ultrasonography, hysteroscopy, and magnetic resonance imaging

BackgroundPreoperative assessment of cervical invasion of endometrial cancer is important in terms of surgical planning. It is of value to compare the usefulness of transvaginal ultrasonography, hysteroscopy, and magnetic resonance imaging (MRI) for evaluating the extent of the invasion. This study evaluated these 3 examinations by univariate and multivariate analysis, retrospectively, and investigated the factors responsible for misdiagnosis.MethodsFrom 1991 to 1995, 71 patients with endometrial cancer at Okayama University Medical School underwent transvaginal ultrasonography with a 6.5-MHz transducer, MRI at 1.5 T, and hysteroscopy using a rigid hysteroscope. The findings of these examinations were compared against pathologic results.ResultsThe sensitivity/specificity/accuracy were 0.73/0.89/0.86 for transvaginal ultrasonography, 0.73/0.88/0.85 for MRI, and 0.73/0.80/0.79 for hysteroscopy. The coefficient values for transvaginal ultrasonography/MRI/hysteroscopy were 0.69/0.62/–0.21 and 1.99/1.89/0.79 in quantification theory second family analysis and logistic regression, respectively. Misdiagnosed cases had the following factors: (1) large tumor volume; (2) tumor near the internal os; (3) tumor descending from the uterine cavity; (4) polypoid tumor in the endocervix; (5) artifacts due to the use of a cervix dilator made from stems of the seaweed,Laminaria japonica; (6) endocervical glandular involvement only; and (7) atypical signals on MRI.ConclusionFor the preoperative assessment of cervical invasion, transvaginal ultrasonography and MRI were the most reliable. Hysteroscopy was least reliable, because of a large number of false-positive results. The use of these examinations in combination, especially transvaginal ultrasonography and MRI, would be of great value in surgical planning for endometrial cancer, considering the factors responsible for misdiagnosis.

Assessment of myometrial invasion at the invasion site of an endometrial carcinoma by ultrasonography along with an intrauterine catheter.

Objectives: To evaluate by transvaginal ultrasonography (TVU) the thickness of the intact myometrium at the presumed tumor‐origin site and to establish criteria for a half myometrial invasion.