Nestin expression as a new marker in malignant peripheral nerve sheath tumors

Malignant peripheral nerve sheath tumor (MPNST) can be difficult to diagnose because it lacks specific immunohistochemical markers. S-100, which is a useful marker of MPNST, has limited diagnostic utility. Recent studies suggest that nestin, which is an intermediate filament protein, is expressed in neuroectodermal stem cells. The diagnostic utility of immunostains for nestin and three other neural markers (S-100, CD56 and protein gene product 9.5 (PGP 9.5)) were evaluated in 35 cases of MPNST and in other spindle cell tumors. All MPNST cases were strongly positive for nestin and had cytoplasmic staining. Stains for S-100, CD56, and PGP 9.5 were positive in fewer cases (17/35, 11/35, and 29/35 cases, respectively), and had less extensive staining. Nestin was negative in 10/10 leiomyomas, and weak nestin expression was seen in 10/10 schwannomas, 3/10 neurofibromas, 2/8 synovial sarcomas, 2/10 liposarcomas, 4/7 carcinosarcomas and 3/7 malignant fibrous histiocytomas. In contrast, strong nestin positivity was seen in 10/10 rhabdomyosarcomas, 15/19 leiomyosarcomas, and 9/9 desmoplastic melanomas. Nestin is more sensitive for MPNST than other neural markers and immunostains for nestin in combination with other markers could be useful in the diagnosis of MPNST.     

Development-dependent expression of cyclin D3 in precursor T-cell lymphoblastic leukemia/lymphoma

In contrast to the clear oncogenic role of cyclins D1 and D2, cyclin D3 is suggested to have a role in the initiation and/or maintenance of differentiation in a lineage-associated manner in addition to its basic role in proliferation. Recently, it has been reported that in cyclin D3-deficient mice, normal expansion of T lymphocytes is impaired because of maturation arrest at the double-negative thymocyte stage, suggesting a crucial role for cyclin D3 in early T-cell development. Therefore, cyclin D3 expression was examined in 36 human precursor T-lymphoblastic leukemia/lymphomas (T-LBLL), a neoplastic counterpart of T cells at the early developmental stages of differentiation. Using a standard panel of differentiation markers, all T-LBLL were categorized into four stages according to differentiation: progenitor, double-negative, double-positive, and single-positive stages. Cyclin D3 expression was initiated at the boundary between double-negative and double-positive stages, and was sustained in the single-positive stage. T-cell receptor was expressed simultaneously with cyclin D3, whereas CD79a expression was specific in the double-negative stage, and thus it was inversely correlated with that of cyclin D3. Taken together with the crucial and non-redundant role in T-cell development in mice, this molecule is suggested to play an important role in human T-cell development.     

RGD-albumin conjugate: expression of tissue regeneration activity.

Albumin conjugated with Arg-Gly-Asp (RGD) has cellular adhesive activity comparable to that of fibronectin in vitro. This study examined whether RGD-albumin conjugate (RGD-ALB) can promote soft tissue ingrowth into a porous matrix in vivo. Polyurethane sponges with 150-500 microns pore size adsorbed with RGD-ALB, fibronectin and albumin were implanted in the subcutaneous tissue of rats. The RGD-ALB-adsorbed sponge exhibited tissue ingrowth comparable to that of the fibronectin-adsorbed sponge at the early period of implantation. On the other hand, the tissue ingrowth was markedly retarded for non-adsorbed and albumin-adsorbed sponges. The enhanced tissue ingrowth found for RGD-ALB and fibronectin was deduced to be mainly a result of its cell-adhesion activity. It is concluded that RGD-ALB exhibits tissue ingrowth-promoting activity at the initial stage of wound healing as effectively as fibronectin.     

Synthesis and relationship between physicochemical properties and oral absorption of pivaloyloxymethyl esters of parenteral cephalosporins

To obtain fundamental information for designing orally active prodrugs of parenteral cephalosporins, the pivaloyloxymethyl esters of ten parenteral cephalosporins were prepared and their physicochemical properties and oral bioavailability in mice were measured. By esterification, lipophilicity was improved with a decrease in solubility, but all the esters were hydrolyzed to the parent cephalosporins rapidly in homogenates of mouse small intestine. These esters, except cefamandole, showed improved relative bioavailability (BA) when compared with the parent cephalosporins. Quantitative correlation of the partition coefficient (P), hydrolysis rate ($\text{t}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$) to the parent cephalosporin and water solubility (S) to the BA of the esters were attempted. A good linear relation between log S and log BA, but no significant relation between log P and log BA or between log $\text{t}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$ and log BA was observed. Among the prodrugs, the ester of Cefotiam, ‘1’, which has log P 1.57, and the highest water solubility, 2.71 mg/ml, showed the best BA, 41.8%. The results of this study indicate the importance of water solubility in designing an orally active ester prodrug of the parenteral cephalosporin, if the lipophilicity and hydrolysis rate are sufficiently high.