Epidermal Growth Factor

Ureteral obstruction (UO) is one of the most common problems confronting the urologist. Although large amounts of animal and clinical research have been done, the pathophysiologic mechanisms accompanying UO are not fully elucidated. Most of our knowledge on UO has been derived from experimental studies in a variety of animal models. Both antenatal and postnatal UO models have been developed mainly by ligation of the ureter or by burying the ureter into the psoas muscle. Most experimental studies have focused on short-term complete ureteral obstruction. The long-term effects of partial ureteral obstruction have been less intensively studied. It is now clear that obstructive nephropathy is not a simple result of mechanical impairment to urine flow but a complex syndrome resulting in alterations of both glomerular hemodynamics and tubular function caused by the interaction of a variety of vasoactive factors and cytokines that are activated in response to UO. Leukocyte infiltration appears to play an important role in obstructive nephropathy suggesting that UO also has an immunological component. Growth factors such as platelet-derived growth factor, transforming growth factor-beta, epidermal growth factor and insulin-like growth factor I may all play a role in the development and progression of fibrotic and sclerotic changes in the obstructed kidney. At present, the selection of patients with congenital hydronephrosis for operative treatment is controversial. Studies in animals and patients have shown that partial unilateral UO does not always cause a loss of renal function or progression in urinary tract dilation during long-term follow-up. The implications of UO continue to raise many questions and further work is necessary to achieve a better understanding of the pathogenesis in obstructive nephropathy.

Necrotizing enterocolitis (NEC) is the leading cause of death for preterm infants resulting from gastrointestinal disease. This review will focus on several components of human breast milk that may be beneficial in the prevention and treatment of NEC. The severe pathological features of NEC include inflammation, mucosal ulceration and disruption of the intestinal barrier. Despite maximal neonatal intensive care, the incidence and mortality rate of the disease remains high. Administration of breast milk, as well as donor breast milk, to preterm infants has been shown to reduce the incidence of NEC. Beyond this, there is no disease specific treatment for NEC. The immunomodulatory and protective properties of human breast milk have been evaluated in search of key components that may be utilized for the effective prevention and treatment of NEC.

The implantation process involves complex and synchronized molecular and cellular events between the uterus and the implanting embryo. These events are regulated by paracrine and autocrine factors. Trophoblast invasion and migration through the uterine wall is mediated by molecular and cellular interactions, controlled by the trophoblast and the maternal microenvironment. This review is focused on the molecular constituents of the human trophoblast, their actions and interactions, including interrelations with the uterine endometrium.

In this paper the results of investigations on the effect of interferon-alpha (IFN-alpha) on the growth of meningioma cells in culture is reported. A consecutive series of six meningiomas and one meningioma/neurofibroma derived from a patient with neurofibromatosis type 2 was investigated and it was found that the growth of all seven tumours in response to mitotic stimuli (fetal bovine serum or epidermal growth factor) is strongly inhibited by IFN-alpha. Maximal response varied between 100% and 70% inhibition of the incorporation of tritiated thymidine. In some cases an inhibitory response was obtained already at very low doses (less than or equal to 10 U of IFN-alpha per ml). These results indicate that further clinical investigation of the application of IFN-alpha to the treatment of meningioma is warranted.

A human salivary intercalated duct cell line (HSG) is capable of morphological change to acinar-type cells, and of salivary amylase (AMY1) expression, by culturing on basement membrane extracts (BME). The aim of this study was to determine the critical conditions for functional and morphological differentiation of HSG cells and to establish if the processes are related. Cells were grown on BMEs that had different protein concentrations and growth factor content, and then examined with respect to morphology and AMY1 expression. To investigate the role of intracellular calcium in amylase expression, a pcDNA3.1-TRPC1alpha construct was used to overexpress htrp1alpha, which mediates the store-operated calcium entry in HSG cells. Expression of the AMY1, TRPC1alpha and beta genes was quantified by means of real time RT-PCR. Growth factor-reduced BME (12.8 mg/ml) induced multicellular acinar structures with lumen formation but without stimulation of either AMY1 or TRPC1. HSG cells cultured on higher concentration BME (17.5 or 16.4 mg/ml) formed reticular networks. AMY1 expression increased both on growth factor-reduced BME (17.5 mg/ml: 3.0-fold, P < 0.001) and on regular BME (16.4 mg/ml: 3.7-fold, P < 0.001) accompanied by a slight increase in expression of TRPC1alpha and TRPC1beta. Overexpression of htrp1alpha did not cause any significant changes in AMY expression, though it attenuated the BME (17.5 mg/ml)-induced AMY1 upregulation. Overall, the higher protein concentration BME favors amylase expression in HSG cells, whereas the lower concentration causes marked morphological changes.

Guided bone regeneration is an accepted surgical method employed in implant dentistry to increase the quantity and quality of the host bone in areas of localized alveolar defects. The lack of predictability in osseous regenerative procedures with various grafting materials suggests that improvement in the osteoinductive properties of these materials is highly desirable. Platelet-rich plasma (PRP), a modification of fibrin glue made from autologous blood, is being used to deliver growth factors in high concentration to sites requiring osseous grafting. Growth factors released from the platelets include platelet-derived growth factor, transforming growth factor beta, platelet-derived epidermal growth factor, platelet-derived angiogenesis factor, insulin-like growth factor 1, and platelet factor 4. These factors signal the local mesenchymal and epithelial cells to migrate, divide, and increase collagen and matrix synthesis. PRP has been suggested for use to increase the rate of bone de...

Colorectal cancer (CRC) is common in North America. Metastatic disease is present at diagnosis in 30% of the patients, and approximately half of early-stage patients will eventually present with metastatic disease. Until recently, few chemotherapy options were available to treat metastatic CRC. The authors review the results of recent clinical trials and the design of ongoing trials in the management of patients with metastatic colorectal cancer. Fluorouracil (5-FU) with leucovorin (LV) modulation has a marginal but positive effect on survival in those patients. The recent incorporation of irinotecan (CPT-11) and oxaliplatin for the management of advanced CRC has generated further improvement in survival. The development of oral fluoropyrimidines, mimicking continuous infusion 5-FU, is convenient. In randomized trials, capecitabine was equally effective to bolus 5-FU and LV in the management of metastatic CRC. Recently completed or ongoing clinical trials to study novel targeting ag...

This study was undertaken to examine the role fibroblasts play in the formation of the basement membrane (BM) in human skin equivalents. For this purpose, keratinocytes were seeded on top of fibroblast-free or fibroblast-populated collagen matrix or de-epidermized dermis and cultured in the absence of serum and exogenous growth factors. The expression of various BM components was analyzed on the