Prognostic significance of urokinase plasminogen activator receptor and its cleaved forms in blood from patients with non‐small cell lung cancer

Urokinase plasminogen activator (uPA) cleaves its three‐domain cell surface receptor, uPAR, liberating domain I [uPAR(I)] and leaving the cleaved uPAR(II‐III) on the cell surface. Both intact and cleaved uPAR can be shed from the cell surface. uPAR(I) was previously shown to be a prognostic factor in lung tumour extracts. Here we analyse uPAR forms in blood from patients with non‐small cell lung cancer (NSCLC). Preoperatively sampled plasma/serum from 32 patients with NSCLC was analysed. Three time‐resolved fluoroimmunoassays (TR‐FIAs) measuring intact uPAR(I‐III) (TR‐FIA 1), uPAR(I‐III) + uPAR(II‐III) (TR‐FIA 2) and uPAR(I) (TR‐FIA 3) were applied. The Spearman rank correlations between plasma and serum levels of uPAR(I‐III), uPAR(I‐III) + uPAR(II‐III), and uPAR(I) were 0.89, 0.94 and 0.68 respectively. Survival analysis demonstrated that high levels of all uPAR forms were associated with shorter survival. Adjusted for histological subtype high plasma uPAR(I‐III) and uPAR(I) levels as well as serum uPAR(I) levels were significantly associated with shorter OS (hazards ratios = 4.3, 2.8 and 3.8 respectively). High blood levels of intact uPAR and its cleaved forms are associated with poor prognosis in NSCLC.     

Combined vascular endothelial growth factor receptor/epidermal growth factor receptor blockade with chemotherapy for treatment of local, uterine, and metastatic soft tissue sarcoma

PURPOSE: Soft tissue sarcoma (STS) is a rare heterogeneous malignancy. Overall survival has been stagnant for decades, primarily because systemic therapies are ineffective versus metastases, the leading cause of STS lethality. Consequently, we examined whether tyrosine kinase receptors active in STS growth signaling might be blockable and whether multireceptor blockade might synergize with low-dose STS chemotherapy by therapeutically affecting STS cells and their associated microenvironment. EXPERIMENTAL DESIGN: Vandetanib (AstraZenca), a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 and epidermal growth factor receptor, was evaluated alone and with chemotherapy in vitro and in vivo in three human STS nude mouse xenograft models of different STS locations (muscle, uterus, lung), stages (primary, metastatic), and subtypes (leiomyosarcoma, fibrosarcoma, uterine sarcoma: luciferase-expressing MES-SA human uterine sarcoma cells surgically implanted into uterine muscularis with bioluminescence tumor growth assessment; developed by us). RESULTS: In vitro, human STS cells were sensitive to vandetanib. Vandetanib alone and with chemotherapy statistically significantly inhibited leiomyosarcoma local growth and fibrosarcoma lung metastasis. Direct injection of MES-SA into nude mice uterine muscularis resulted in high tumor take (88%), whereas s.c. injection resulted in no growth, suggesting microenvironmental tumor growth modulation. Vandetanib alone and with chemotherapy statistically significantly inhibited uterine sarcoma growth. In all models, vandetanib induced increased apoptosis, decreased tumor cell proliferation, and decreased angiogenesis. CONCLUSIONS: Vandetanib has antitumor effects against human STS subtypes in vitro and in vivo, where it also affects the tumor-associated microenvironment. Given the urgent need for better systemic approaches to STS, clinical trials evaluating vandetanib, perhaps with low-dose chemotherapy, seem warranted.     

Determination of the urethral dose in prostate brachytherapy when the urethra cannot be visualized in the postimplant CT scan

This study investigates the feasibility of locating the urethra at the geometric center of peripherally loaded 125I prostate implant when a urinary catheter is not utilized for the postimplant CT scan. Twenty postimplant CT scans utilizing a urinary catheter were randomly selected. The urethra was localized in each study and, in addition, a surrogate urethra was localized at the geometric center of the prostate. Dose-volume histograms of the urethra and surrogate urethra were compiled and compared. The values obtained for the urethra D10, D25, and D50 were in good agreement and demonstrate that the urethral dose can be determined reliably by locating a surrogate urethra at the geometric center of the prostate in a peripherally loaded implant when the urethra cannot be visualized.     

Primary choriocarcinoma of the fallopian tube. Report of a case with survival and postoperative delivery. Review of the literature

A patient is presented with primary choriocarcinoma of the fallopian tube arising from a tubal pregnancy. Treatment consisted of an initial operation including adnexectomy and resection of bilateral ovarian thecalutein cysts, followed by chemotherapy. The patient delivered a healthy infant 2 years later, and is alive and well 5 years after the event.     

Mullerian adenosarcoma of the uterus: report of a rare case and review of the literature

A rare case of Mullerian adenosarcoma of the uterus is described, found during diagnostic curettage. Panhysterectomy was performed. These rare tumors have a low potential for malignancy and are characterized by benign epithelial and malignant stromal elements. They should be distinguished from the highly malignant mixed Mullerian tumors which contain, by definition, both carcinomatous and sarcomatous elements. The literature on the subject has been reviewed.     

Pregnancy Outcome in Gestational Diabetes with Preconceptional Diabetes Counselling

One hundred and thirty-six women with known previous gestational diabetes and normal glucose tolerance between pregnancies attended a preconceptional clinic at least 2 months before conception, and were regularly consulted by a diabetological team. Evaluation consisted of oral glucose tolerance test (OGTT), mean blood glucose, glycosylated haemoglobin and management by self-blood-glucose monitoring (SBGM) and nutritional counselling. When these patients were compared to a group of 154 patients with gestational diabetes who attended our clinic at different stages of pregnancy, the former had improved glucose homeostasis whereas the latter had more frequent elevations of fasting and postprandial glucose levels throughout pregnancy. This group had also more maternal complications and higher Caesarean section rates. Congenital anomalies were 0.65% among offspring of nonattenders, while none occurred in those with preconceptional counselling. Macrosomia and hypoglycaemia were significant neonatal complications in infants of nonattending mothers. We concur with the recommendation that preconceptional counselling in gestational diabetics is required to improve glucose homeostasis throughout pregnancy, and that appropriate evaluation of glucose intolerance should be included as part of prospective family planning.