Simple Synthesis of Aldehyde and Carboxylic Acid Terminated Methoxypoly(ethylene glycol)

mPEG‐aldehydes and activated mPEG‐carboxylic acids on which the polymer and the reactive functional group are separated by aliphatic chains of different lengths, are well known reagents of widespread application in PEGylation technology. The syntheses of these functional polymers are not easy and usually the preparation of each of these compounds requires a very specific set of reagents and experimental conditions. In fact, a general method for their preparation is, still nowadays, unavailable. In this work a simple synthetic method is developed for preparation of mPEG‐aldehydes and carboxylic acids with excellent yields. The key step of the method involves a substitution reaction of mPEG‐mesylate with mono‐alkoxides of symmetrical diols to afford hydroxyl‐terminated polymers, which are converted to the aldehydes and acids by mild oxidation reactions.

     

Pentraxin 3 (PTX3) inhibits plasma cell/stromal cell cross‐talk in the bone marrow of multiple myeloma patients

Pentraxin 3 (PTX3) is a soluble pattern recognition receptor that binds with high affinity and selectivity to fibroblast growth factor‐2 (FGF2), thus inhibiting its pro‐angiogenic activity. Here we investigated the effects of PTX3 on monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patient‐derived bone marrow (BM) plasma cells (PCs), endothelial cells (ECs), and fibroblasts (FBs), and assessed whether PTX3 can modulate the cross‐talk between PCs and those microenvironment cells. PTX3 and FGF2 expression was evaluated by ELISA. Functional studies, including cell viability, wound healing, chemotaxis, and Matrigel^® assays, were performed on MGUS and MM ECs and FBs upon the PTX3 treatment. Through western blot PTX3‐induced modulation in FGF2/FGF receptor signalling pathways was evaluated in MGUS and MM ECs and FBs through western blot. Co‐cultures between MM ECs/FBs and human PC lines were used to evaluate possible PTX3 indirect effects on MM PCs. Adhesion molecules were studied by flow cytometry. PTX3 provides a direct time‐ and dose‐dependent apoptotic effect on MM ECs and FBs, but not on either MM primary PCs or human PC lines. PTX3 inhibits migration of MM ECs and FBs in a dose‐dependent manner, and impacts in vitro and in vivo FGF2‐mediated MM angiogenesis. Co‐cultures of PCs and ECs/FBs show that PTX3 treatment indirectly impairs PC viability and adhesion. We conclude that PTX3 is an anti‐angiogenic factor in MM and behaves as a cytotoxic molecule on MM cells by inhibiting the cross‐talk between PCs and ECs/FBs. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

A Lot of Action,But Not in the Right Direction: Systematic Review and Content Analysis of Smartphone Applications for the Prevention,Detection, and Management of Cancer

Background

Mobile phones have become nearly ubiquitous, offering a promising means to deliver health interventions. However, little is known about smartphone applications (apps) for cancer.

Objective

The purpose of this study was to characterize the purpose and content of cancer-focused smartphone apps available for use by the general public and the evidence on their utility or effectiveness.

Methods

We conducted a systematic review of the official application stores for the four major smartphone platforms: iPhone, Android, Nokia, and BlackBerry. Apps were included in the review if they were focused on cancer and available for use by the general public. This was complemented by a systematic review of literature from MEDLINE, Embase, and the Cochrane Library to identify evaluations of cancer-related smartphone apps.

Results

A total of 295 apps from the smartphone app stores met the inclusion criteria. The majority of apps targeted breast cancer (46.8%, 138/295) or cancer in general (28.5%, 84/295). The reported app purpose was predominantly to raise awareness about cancer (32.2%, 95/295) or to provide educational information about cancer (26.4%, 78/295), followed by apps to support fundraising efforts (12.9%, 38/295), assist in early detection (11.5%, 34/295), promote a charitable organization (10.2%, 30/295), support disease management (3.7%, 11/295), cancer prevention (2.0%, 6/295), or social support (1.0%, 3/295). The majority of the apps did not describe their organizational affiliation (64.1%, 189/295). Apps affiliated with non-profit organizations were more likely to be free of cost (χ² ₁=16.3, P<.001) and have a fundraising or awareness purpose (χ² ₂=13.3, P=.001). The review of the health literature yielded 594 articles, none of which reported an evaluation of a cancer-focused smartphone application.

Conclusions

There are hundreds of cancer-focused apps with the potential to enhance efforts to promote behavior change, to monitor a host of symptoms and physiological indicators of disease, and to provide real-time supportive interventions, conveniently and at low cost. However, there is a lack of evidence on their utility, effectiveness, and safety. Future efforts should focus on improving and consolidating the evidence base into a whitelist for public consumption.     

Long-term effects of transdermal and oral estrogens on serum lipids and lipoproteins in postmenopausal women

The transdermal and oral administration of estrogens for one year were compared with respect to the effects on lipid metabolism. Eighty-one postmenopausal women (1.5-3 years after menopause) were randomly divided into three groups. The first two groups received sequential estrogen treatment with either transdermal estradiol (Estraderm TTS, Ciba Geigy; 50 μg/day; 24 women) or 0.625 mg/day conjugated estrogens (Premarin, Wyeth; 20 subjects), respectively. In both groups medroxyprogesterone (10 mg/day per os) was added for 12 days of each cycle. Thirty-five subjects served as control group without therapy. No significant changes in the lipid profile was observed in control subjects after 1 year of follow-up. Serum triglycerides decreased significantly (-10.9 ± 26% S.D.; P < 0.05) in transdermal treated women, whereas it slightly rose in oral estrogen group. Comparable significant decreases in total and low density lipoprotein (LDL) cholesterol (mean range -6.5/-18.0%) were observed in women on estrogen replacement therapy. High density lipoprotein (HDL) cholesterol significantly diminished in transdermal estradiol group, but it rose slightly in the oral estrogen group. Thus the fraction of HDL cholesterol over LDL cholesterol did not change in the transdermal group whereas it significantly rose in subjects treated with oral estrogens. It remains to be established to what extent these differences on lipid metabolism are relevant for the prevention of cardiovascular diseases.     

Expression and modulation of a mononuclear phagocyte differentiation antigen (PAM-1) during in vitro maturation of peripheral blood monocytes

Summary Human macrophages obtained by in vitro maturation of peripheral blood monocytes express a surface antigen, PAM-1, recognized by a monoclonal antibody and typical of pulmonary alveolar and tissue macrophages. PAM-1, undetectable in freshly isolated peripheral blood monocytes, was expressed in monocyte-derived macrophages after 3 days of in vitro adherent culture and was maximal after 14–15 days (50%–60% of positive cells). Similar levels of PAM-1 positivity were observed in non-adherent monocyte-derived macrophages suggesting that cell adhesion was not a critical requisite for the expression of this antigen. Bacterial lipolysaccharide and a monocyte chemotactic protein preparation respectively suppressed and upregulated PAM-1 expression in monocyte-derived macrophages. In contrast interferon-γ, although enhancing the levels of class II HLA-DR antigen in monocyte-derived macrophages, did not influence the kinetics of appearance and the levels of PAM-1 in these cells. Thus, expression of PAM-1, which is restricted to certain stages of the monocyte-macrophage differentiation pathway, is also differentially modulated by activation signals, which can be present in the microenvironment of inflammed tissues.     

The volumetric bone density and cortical thickness in adult patients affected by osteogenesis imperfecta.

In patients with osteogenesis imperfecta (OI), a disease characterized by abnormal bone fragility, bone mineral density (BMD) was found to be relatively preserved. Quantitative computed tomography (QCT) is the only available method for directly measuring in vivo both volumetric density and the cross-sectional area. Here we report the data from dual-energy X-ray absorptiometry DXA (spine and hip) and peripheral (pQCT) (ultradistal and proximal radius) measurement of 27 adult patients affected by OI, mostly of type I, compared with a group of healthy persons. In the patients with OI, areal BMD values at both femoral neck and lumbar spine were considerably lower than in control subjects (-32 and -36%, respectively; p<0.001 for body weight and height adjusted values). pQCT volumetric density at the ultradistal radius was 19% lower than in control subjects and this difference rose to 32% for purely cancellous bone tissue. The whole bone cross-sectional area of ultradistal radius, as measured by pQCT, was superimposable to normal. At the proximal radius, both cross-sectional area and cortical area, together with Bending Breaking Resistance Index (BBRI), were significantly lower in OI (-23; -22; -32% respectively; p<0.001 for body weight and height adjusted values), but cortical volumetric density was even slightly higher in the OI group than in control subjects. In conclusion, it appears that the most obvious defect in adults with OI is the inability to acquire an adequate thickness of the cortices of long bone and to achieve or maintain normal trabecular density.