Multifocal angiostatic therapy: an update

Multifocal angiostatic therapy (MAT) is a strategy that seeks to impede cancer-induced angiogenesis by addressing multiple targets that regulate the angiogenic capacity of a cancer and/or the angiogenic responsiveness of endothelial cells, using measures that are preferentially, but not exclusively, nutraceutical. A prototype of such a regimen has been proposed previously, composed of green tea polyphenols, fish oil, selenium, and high-dose glycine, complementing a low-fat vegan diet, exercise training, and the copper-sequestering drug tetrathiomolybdate (TM). A review of more recent evidence suggests additional agents that could appropriately be included in this regimen and clarifies to some extent the mechanisms of action of its constituents. Diindolylmethane, a widely available crucifera-derived nutraceutical, has inhibited cancer growth in several mouse xenograft models; this effect may be largely attributable to an angiostatic action, as concentrations as low as 5 to 10 muM inhibit proliferation, migration, and tube-forming capacity of human endothelial cells in vitro, and a parenteral dose of 5 mg/kg markedly impairs matrigel angiogenesis in mice. Silymarin/silbinin, which has slowed the growth of human xenografts in a number of studies, suppresses the proliferation, migration, and tube-forming capacity of endothelial cells and inhibits vascular endothelial growth factor (VEGF) secretion by a range of human cancer cell lines, in concentrations that should be clinically feasible. The angiostatic activity of orally administered green tea now appears likely to reflect inhibition of the kinase activity of VEGFR-2. Glycine's angiostatic activity may be attributable to a hyperpolarizing effect on endothelial cells that decreases the activity of NADPH oxidase, now known to promote tyrosine kinase signaling in endothelial cells. The ability of TM to suppress cancer cell production of a range of angiogenic factors results at least in part from a down regulation of NF-kappaB activation. Dual-purpose molecular targets, whose inhibition could be expected to decrease the aggressiveness and chemoresistance of cancer cells while simultaneously impeding angiogenesis, include NF-kappaB, cox-2, c-Src, Stat3, and hsp90; drugs that can address these targets are now in development, and salicylates are notable for the fact that they can simultaneously inhibit NF-kappaB and cox-2. The potential complementary of the components of MAT should be assessed in nude mouse xenograft models.     

Commentary: the pharmacological antioxidant amifostine -- implications of recent research for integrative cancer care

Amifostine is a pharmacological antioxidant used as a cytoprotectant in cancer chemotherapy and radiotherapy. It is thought to protect normal tissues relative to tumor tissue against oxidative damage inflicted by cancer therapies by becoming concentrated at higher levels in normal tissues. The degree to which amifostine nevertheless accumulates in tumors and protects them against cancer therapies has been debated. Guidelines have been published that direct its use in chemotherapy and radiation, taking into consideration the concerns of tumor protection. In this article, clinical studies of amifostine appearing since the publication of the most recent set of guidelines are reviewed. Randomized and nonrandomized trials of regimens involving chemo-therapeutic agents (chemotherapy, chemoradiation, conditioning regimens for bone marrow transplant) are discussed. Nineteen studies showed positive effects for amifostine reducing the level of side effects of these regimens, while 9 showed no effect and 1 had a questionable result. Clinically relevant levels of amifostine toxicity were observed in several studies, but subcutaneous administration may reduce such toxicity. Amifostine showed protection against mucositis, esophagitis, neuropathy, and other side effects, although protection against cisplatin-induced ototoxicity was not observed. No evidence of tumor protection was observed. Amifostine may enable populations unable to tolerate conventional cancer therapy to receive treatment of their cancers, even if some degree of tumor protection is eventually discovered. The authors discuss the implications of this research for patient populations seen in integrative cancer care centers and for research on phytochemical antioxidants such as vitamins and carotenoids.     

The effects of minor hip flexion, abduction or adduction and x-ray beam angle on the radiographic joint space width of the hip

OBJECTIVE: Joint pain may cause patients to hold their limbs in mild flexion, abduction or adduction to minimize pain, regardless of the extent of articular pathology, and these positional changes may have substantial effects on the interpretation of radiographic joint space. We aimed to study the impacts of minor degrees of flexion, abduction or adduction of the hip, as well as the angle of the x-ray beam on the radiographic joint space width (JSW) of the hip joint. METHODS: In the first part of the study, 65 patients (44 males, 21 females, mean+/-SD age 49+/-17) without clinical evidence of hip osteoarthritis (OA) who underwent intravenous pyelography (IVP) were studied. The hips were differentially positioned during the sequential radiographs required for the IVP procedure. Baseline radiographs were taken at 15 degrees internal rotation of the hips [the standard position for anteroposterior (AP) pelvis radiography]; additional positions included the hips at 15 degrees and/or 30 degrees flexion, and 15 degrees adduction and/or 30 degrees abduction. Radiographic JSWs were measured at three sites using a dial caliper: superomedial, superolateral, and the point of narrowest JSW. In the second part, 15 patients without clinical evidence of hip OA who underwent supine abdominal radiography for non-rheumatological indications were evaluated by standard (AP) pelvis x-ray in the same setting and JSW measurements were made as described above. RESULTS: When the average of the three measurements of the JSW was taken for each hip, baseline JSW was 4.38+/-0.55 mm (mean+/-SD). Positioning of the hip significantly (P<0.01) affected the radiographic JSW, with apparent widening during adduction and 30 degrees flexion, (JSW 4.56+/-0.51 mm and 4.53+/-0.58 mm, mean+/-SD), respectively, but narrowing during abduction (4.17+/-0.59 mm, mean+/-SD). Fifteen degree flexion of the hip did not result in statistically significant change in JSW measurements. Upon comparison of the AP pelvis view with the supine abdominal view, neither the average JSW nor the point of narrowest JSW differed significantly, although the superolateral JSW was significantly greater on the AP pelvis view (P=0.02). CONCLUSIONS: Subtle positional changes in the hip, such as may occur during pain or in OA, may artifactually alter the measured radiographic JSW. Thus, longitudinal studies which employ hip JSW to assess disease progression may yield biased results due to changes in pain rather than structure unless care is taken to ensure constant positioning of the hip.     

The association of time in the US and diet during pregnancy in low-income women of Mexican descent

This study compared nutritional intake during pregnancy among women of Mexican descent according to country of birth (US vs. Mexico) and, for Mexico-born women, according to number of years lived in the US (or= 11 years). A 72-item food frequency questionnaire (FFQ) was used to assess dietary intake in 474 pregnant Mexico-born immigrants and US-born Mexican-Americans. Mexico-born women had significantly higher intakes of calories (P = 0.02), fibre (P < 0.001), vitamin A (P < 0.001), vitamin C (P = 0.03), vitamin E (P < 0.01), folate (P < 0.01), calcium (P < 0.001) and zinc (P = 0.02) from their diets than US-born women. Intakes of all nutrients except vitamin C and zinc remained significantly higher in Mexico-born women when nutrients from both diet and vitamin supplements were considered. Among Mexico-born women, increasing years of residence in the US was associated with lower intake of calories (P(trend) < 0.01), fibre (P(trend) < 0.01), folate (P(trend) = 0.03), iron (P(trend) = 0.05) and zinc (P(trend) = 0.03), although only the trend for iron remained significant when vitamin supplement sources were included. A large percentage of women had inadequate intake of vitamin E (58%), folate (61%), iron (77%) and zinc (47%) from their diets during pregnancy and these rates were higher in US-born women than Mexico-born women.     

The value of mentorship within nursing organizations

PROBLEM: Hospitals are facing nurse retention challenges in the new millennium. Nurses are abandoning the bedside because of job dissatisfaction. Mentorship programs should be developed to enhance nursing satisfaction and thus improve retention and ultimately patient outcomes. FINDINGS: Mentorship training in hospitals and the support of formal mentorship programs for new nurses are ways in which hospitals can meet this challenge. CONCLUSIONS: This paper offers an overview of recent research on the value mentoring has for participants and healthcare organizations. The components of successful mentorship programs are discussed, and guidelines for implementation are recommended.     

Cardiovascular tissues contain independent circadian clocks

Acute cardiovascular events exhibit a circadian rhythm in the frequency of occurrence. The mechanisms underlying these phenomena are not yet fully understood, but they may be due to rhythmicity inherent in the cardiovascular system. We have begun to characterize rhythmicity of the clock gene mPer1 in the rat cardiovascular system. Luciferase activity driven by the mPer1 gene promoter is rhythmic in vitro in heart tissue explants and a wide variety of veins and arteries cultured from the transgenic Per1-luc rat. The tissues showed between 3 and 12 circadian cycles of gene expression in vitro before damping. Whereas peak per1-driven bioluminescence consistently occurred during the late night in the heart and all arteries sampled, the phases of the rhythms in veins varied significantly by anatomical location. Varying the time of the culture procedure relative to the donor animal's light:dark cycle revealed that, unlike some other rat tissues such as liver, the phases of in vitro rhythms of arteries, veins, and heart explants were affected by culture time. However, phase relationships among tissues were consistent across culture times; this suggests diversity in circadian regulation among components of the cardiovascular system.