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Development. 2002 Jun;129(11):2773-83.
The meso-angioblast: a multipotent, self-renewing cell that originates from the dorsal aorta and differentiates into most mesodermal tissues.

Minasi MG, Riminucci M, De Angelis L, Borello U, Berarducci B, Innocenzi A, Caprioli A, Sirabella D, Baiocchi M, De Maria R, Boratto R, Jaffredo T, Broccoli V, Bianco P, Cossu G.

Stem Cell Research Institute, Dibit, H. S. Raffaele, Via Olgettina 58, 20132 Milano, Italy.

We have previously reported the origin of a class of skeletal myogenic cells from explants of dorsal aorta. This finding disagrees with the known origin of all skeletal muscle from somites and has therefore led us to investigate the in vivo origin of these cells and, moreover, whether their fate is restricted to skeletal muscle, as observed in vitro under the experimental conditions used. To address these issues, we grafted quail or mouse embryonic aorta into host chick embryos. Donor cells, initially incorporated into the host vessels, were later integrated into mesodermal tissues, including blood, cartilage, bone, smooth, skeletal and cardiac muscle. When expanded on a feeder layer of embryonic fibroblasts, the clonal progeny of a single cell from the mouse dorsal aorta acquired unlimited lifespan, expressed hemo-angioblastic markers (CD34, Flk1 and Kit) at both early and late passages, and maintained multipotency in culture or when transplanted into a chick embryo. We conclude that these newly identified vessel-associated stem cells, the meso-angioblasts, participate in postembryonic development of the mesoderm, and we speculate that postnatal mesodermal stem cells may be derived from a vascular developmental origin.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12015303&dopt=Abstract

Clin Infect Dis. 2002 Jun 1;34(11):1469-74. Epub 2002 May 07.
Bacteremia due to viridans group Streptococci with diminished susceptibility to Levofloxacin among neutropenic patients receiving levofloxacin prophylaxis.

Razonable RR, Litzow MR, Khaliq Y, Piper KE, Rouse MS, Patel R.

Division of Infectious Diseases, Mayo Clinic, Rochester, MN, 55905, USA.

Despite the use of levofloxacin prophylaxis during the neutropenic period after autologous peripheral blood stem cell transplantation, viridans group (VG) streptococcal bacteremia developed in 6 (16.2%) of 37 patients who underwent transplantation between 1 January and 25 February 2001 at the Mayo Clinic in Rochester, Minnesota. All 6 patients presented with fever and mucositis after a mean of 4.5 days of neutropenia, and 3 developed septic shock. All 6 VG streptococcal isolates from these patients exhibited distinct patterns on pulsed-field gel electrophoresis. All isolates had diminished susceptibility to levofloxacin, 5 to gatifloxacin, and 4 to moxifloxacin. Quinolone resistance was associated with mutations in the quinolone resistance-determining region of GyrA and (for 1 isolate) of ParC. The use of levofloxacin may select VG streptococci with diminished susceptibility to levofloxacin and other quinolones with enhanced activity against gram-positive organisms and, therefore, may not be optimal for preventing VG streptococcal bacteremia in neutropenic patients.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12015693&dopt=Abstract

Cancer. 2002 May 1;94(9):2353-62.
Prospective comparison of [18F]fluorodeoxyglucose positron emission tomography with conventional assessment by computed tomography scans and serum tumor markers for the evaluation of residual masses in patients with nonseminomatous germ cell carcinoma.

Kollmannsberger C, Oechsle K, Dohmen BM, Pfannenberg A, Bares R, Claussen CD, Kanz L, Bokemeyer C.

Department of Hematology/Oncology, University of Tuebingen, Tuebingen, Germany.

BACKGROUND: To assess the ability of [(18)F]fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET) to predict the viability of residual masses after chemotherapy in patients with metastatic nonseminomatous germ cell tumors (GCT), PET results were compared in a blinded analysis with computed tomography (CT) scans and serum tumor marker changes (TUM) as established methods of assessment. METHODS: Independent reviewers who were blinded to each other's results evaluated the PET results and corresponding CT scan and TUM results in 85 residual lesions from 45 patients. All patients were treated within prospective clinical trials and received primary/salvage, high-dose chemotherapy with autologous blood stem cell support for primary poor prognosis disease or recurrent disease. PET results were assessed both visually and by quantifying glucose uptake (standardized uptake values). Results were validated either by histologic examination of a resected mass and/or biopsy (n = 28 lesions) or by a 6-month clinical follow-up after evaluation (n = 57 lesions). RESULTS: F-18 FDG PET showed increased tracer uptake in 32 of 85 residual lesions, with 29 true positive (TP) lesions and three false positive (FP) lesions. Fifty-three lesions were classified by PET as negative (no viable GCT), 33 lesions were classified by PET as true negative (TN), and 20 lesions were classified by PET as false negative (FN). In the blinded reading of the corresponding CT scan and TUM results, 38 residual lesions were assessed correctly as containing viable carcinoma and/or teratoma. Forty-six lesions were classified as non-suspicious by CT scan/TUM (33 TN lesions and 14 falsely classified lesions). PET correctly predicted the presence of viable carcinoma in 5 of these 14 and the absence of viable carcinoma in 3 of these 14 lesions. Resulting sensitivities and specificities for the prediction of residual mass viability were as follows: PET, 59% sensitivity and 92% specificity; radiologic monitoring, 55% sensitivity and 86% specificity; and TUM, 42% sensitivity and 100% specificity. The positive and negative predictive values for PET were 91% and 62%, respectively. The diagnostic efficacy of PET did not improve when patients with teratomatous elements in the primary tumor were excluded from the analysis. In patients with multiple residual masses, a uniformly increased residual F-18 FDG uptake in all lesions was a strong predictor for the presence of viable carcinoma. CONCLUSIONS: F-18 FDG PET imaging performed in conjunction with conventional staging methods offers additional information for the prediction of residual mass histology in patients with nonseminomatous GCT. A positive PET is highly predictive for the presence of viable carcinoma. Other useful indications for a PET examination include patients with multiple residual masses and patients with marker negative disease. 2002 American Cancer Society.DOI 10.1002/cncr.10494

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12015760&dopt=Abstract

Cancer. 2002 May 1;94(9):2409-15.
Allogeneic blood stem cell transplantation after a reduced-intensity, preparative regimen: a pilot study in patients with refractory malignancies.

Pedrazzoli P, Da Prada GA, Giorgiani G, Schiavo R, Zambelli A, Giraldi E, Landonio G, Locatelli F, Siena S, Della Cuna GR.

Divisione di Oncologia Medica Falck, Ospedale Niguarda Ca' Granda, Milano, Italy. pedrain.it

BACKGROUND: The immune-mediated graft-versus-tumor (GVT) effect plays a therapeutic role in the treatment of patients with hematologic malignancies who undergo allogeneic hematopoietic stem cell transplantation (HSCT). More recently, it was reported that a GVT effect also occurred in patients who underwent transplantation for metastatic renal carcinoma. The authors carried out a pilot trial of allogeneic transplantation after a reduced-intensity, preparative regimen in patients with refractory malignancies, including solid tumors. The objectives of the current study were to evaluate the feasibility of this approach in terms of toxicity and engraftment and to document evidence of GVT effects. METHODS: Seventeen patients with Stage IV malignancies (7 patients with renal cell carcinoma, 3 patients with sarcoma, 2 patients with breast carcinoma, 2 patients with Hodgkin disease, 1 patient with ovarian carcinoma, 1 patient with melanoma, and 1 patient with both melanoma and renal cell carcinoma) that were not amenable to further conventional treatment were enrolled. The median patient age was 43 years (range, 10-60 years). The Eastern Cooperative Oncology Group performance status (PS) was 0-1 in 11 patients and 2-3 in 6 patients. Preparative treatment consisted of reduced-intensity chemotherapy with fludarabine (30 mg/m(2) per day for 4 consecutive days) and cyclophosphamide (30 mg/Kg per day for 2 consecutive days) prior to allogeneic HSCT from a human leukocyte antigen-identical sibling. The median number of CD34+ cells infused was 6.06 x 10(6)/kg (range, 1.5-14.0 x 10(6)/kg). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin-A and short-term methotrexate. RESULTS: Patients who had a PS of 2-3 prior to undergoing HSCT experienced Grade 4 hematologic toxicities and Grade > or = 3 organ toxicities and died of either treatment-related complications or disease progression within 100 days from transplantation. By contrast, 10 of 11 patients who had a PS of 0-1 prior to undergoing HSCT experienced only short-lasting, Grade < or = 3 neutropenia and thrombocytopenia and no organ toxicity; 1 of 10 patients died of graft failure on Day +29 after undergoing HSCT. By Day +90, 100% donor chimerism was documented in all patients with a past history of heavy chemotherapy, whereas mixed donor chimerism was observed in the 4 patients with a past history of only 1 line of chemotherapy and/or immunotherapy prior to entering the HSCT program. Grade 2-3 acute GVHD occurred in 5 patients. Among patients with a follow-up > 100 days, 2 complete responses and 3 transitory partial responses were recorded. CONCLUSIONS: With this conditioning regimen, full donor chimerism was achieved rapidly only in patients who had received previous intensive chemotherapy. In a proportion of patients with refractory malignancies, allogeneic transplantation resulted in tumor regression. This novel therapeutic strategy may provide little benefit in patients with poor PS and rapidly progressing disease. 2002 American Cancer Society.DOI 10.1002/cncr.10491

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12015766&dopt=Abstract

Dev Cell. 2002 May;2(5):607-16.
A dominant-negative form of p63 is required for epidermal proliferation in zebrafish.

Lee H, Kimelman D.

Department of Biochemistry, University of Washington, Box 357350, Seattle, WA 98195, USA.

Epidermal stem cells play a critical role in producing the multilayered vertebrate skin. Products of the p63 gene not only mark the epidermal stem cells, but also are absolutely required for the formation of mammalian epidermis. We find that early zebrafish embryos express a dominant-negative form of p63 (DeltaNp63), which accumulates in the nucleus just as epidermal growth begins. Using antisense morpholino oligonucleotides, we show that DeltaNp63 is needed for epidermal growth and limb development and is specifically required for the proliferation of epidermal cells by inhibiting p53 activity. While the structure of fish epidermis is very different from that of higher vertebrates, our study shows that DeltaNp63 has essential and ancient role in the development of skin.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12015968&dopt=Abstract

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