Gastrointestinal permeability in ovarian cancer and breast cancer patients treated with paclitaxel and platinum

Background  

Combination of platinum derivatives with paclitaxel is currently the standard front line regimen for patients with epithelial ovarian carcinoma, and represents also an active regimen in patients with metastatic breast or unknown primary carcinomas. Measurement of intestinal permeability represents one of the potential methods of noninvasive laboratory assessment of gastrointestinal mucositis induced by chemotherapy, but little is known about intestinal permeability in patients treated with paclitaxel or platinum.     

Congenital segmental aplasia of the intestinal muscularis: a rare disorder mimicking necrotizing enterocolitis

Both infants of a pair of dizygotic twins born in the 26th week of gestation presented with intolerance of feedings, bilious gastric aspirates, abdominal distension, and fixed, dilated bowel loops on X-ray. Necrotizing enterocolitis (NEC) was suspected. Medical treatment failed, and the infants were operated upon on days 12 and 19 of life. Ballon-like dilated segments of ileum were removed and ileostomies performed. The diagnosis of congenital segmental aplasia of the intestinal muscularis was made from histologic examination in both cases. This disorder is a rare cause of intestinal obstruction or perforation in premature babies. Its course may resemble NEC; medical therapy inevitably fails; and surgical treatment is associated with a favorable outcome. The literature on absence of the intestinal muscularis in neonates is reviewed and possible etiologies are discussed.     

Complete response of multiple melanoma brain metastases after treatment with temozolomide

BACKGROUND: Inoperable melanoma brain metastases are usually uniformly fatal, and complete response after cytotoxic therapy is rare. CASE REPORT: A patient with multiple inoperable melanoma brain metastases was treated with 6 cycles of oral temozolomide (300 mg once daily over 5 days every 28 days). A complete response was documented by magnetic resonance. CONCLUSIONS: The present observation suggests that temozolomide may be an active and well tolerated treatment for malignant melanoma brain metastases.     

Erythropoietin stimulates vasculogenesis in neonatal rat mesenteric microvascular endothelial cells

Human breast milk is a rich source of growth factors, including erythropoietin (Epo), the endogenous hormonal stimulant of erythropoiesis. Recombinant human Epo (rhEpo) has been shown to stimulate 1) angiogenesis, the process of new blood vessel growth from preexisting vessels; 2) vasculogenesis, tubule formation from single-cell suspensions; and 3) endothelial cell proliferation in immortalized endothelial cells and vessel explants. We hypothesized that Epo would induce mitogenesis and stimulate vasculogenesis in primary cultures of microvascular endothelial cells (MVECs) from neonatal rat mesentery. Isolation, purification, characterization, and culture of MVECs were performed. Cell proliferative effects of rhEpo were studied by 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in cultured MVECs. Vasculogenic effects of rhEpo were examined on cultured MVECs plated on either hormone-rich Matrigel substratum or the extracellular matrix protein, type I collagen. Our findings show that MVECs are isolated and purified, and that rhEpo stimulates MVEC proliferation, with maximal proliferation seen with a concentration of 50 IU/mL rhEpo. Tubule formation assays reveal that an rhEpo concentration of 50 IU/mL produces maximal tubule formation after 12 h on both Matrigel and the simple substratum, type I collagen. Our study is the first to examine the effects of rhEpo on the endothelium of the neonatal gastrointestinal tract. These data suggest that Epo may have a trophic effect on the vasculature of the gastrointestinal tract early in development. Furthermore, as Epo has been measured in breast milk, and its receptor has been shown to exist on the mucosa and gastrointestinal vasculature, Epo may be an endogenous stimulant of vessel growth during neonatal gastrointestinal development.     

THE PERIPHERAL BLOOD LEUKOCYTE PHENOTYPE IN PATIENTS WITH BREAST CANCER: EFFECT OF DOXORUBICIN/PACLITAXEL COMBINATION CHEMOTHERAPY

Presence of functional immune system is critical for any attempt aimed at improving survival of breast cancer patients by strategies based on immune system manipulation. We evaluated by flow cytometry the phenotype of peripheral blood leukocyte of 43 breast cancer patients. In 11 patients, the phenotype was evaluated before and during the chemotherapy by combination of doxorubicin and paclitaxel (AT). Compared with controls breast cancer patients had significantly higher relative and absolute numbers of CD3^-HLADR⁺, CD3^-CD69⁺ and CD14⁺CD16^-, and significantly lower percentages of CD3^- and CD8^-CD28⁺ cells. After one cycle of AT, the absolute numbers of CD3⁺, CD3^-CD4^-, CD3⁺CD8⁺ and CD8^-CD28⁺ cells increased significantly. Present data show a presence of T-cell activation in breast cancer patients. Administration of AT may lead to an increase in functional T-cells in peripheral blood, indicating a potential for combining chemotherapy with immunotherapy in the treatment of breast cancer patients.     

Deterioration of hearing function in mice with neural crest defect

Cochlear potentials were recorded in black-eyed white-mutant mice (strains W/Wv and S1/S1d) during the first months of postnatal life. In these animals melanocytes from the neural crest do not reach the stria vascularis. Hearing thresholds indicated by the compound action potential of the auditory nerve progressively increased. Hearing loss in comparison with the control CBA mice amounted 40 dB six weeks after birth, at eight months practically all mutants were deaf. Endocochlear potential was near zero already in the majority of 6 week-old animals. Abnormalities were observed also in intracellular potentials of the stria vascularis cells which were recorded in vitro and dye-marked. While in marginal cells of CBA mice positive potentials of about 10 mV were recorded, potentials of marginal cells in mutants were near zero. Basal cell potentials were negative in CBA mice (approximately -25 mV) and positive in young mutants (approximately +12 mV). However, in mutants older than 3 months the intracellular potentials of basal cells changed to negativity (approximately -10 mV). The results demonstrate gradual deterioration of hearing function observed in both W/Wv and S1/S1d mutants during first months of the postnatal life. In addition to the dysfunction of stria vascularis, where intermediate cells are missing, also the function of receptors progressively deteriorates.