Introduction of imatinib as first-line therapy for chronic myeloid leukemia in Cuba.

Introduction: Chronic myeloid leukemia is the first malignant disease to be associated with a genetic lesion and is the first leukemia to provide a genotype model conducive to targeted molecular therapy. It is a chronic clonal myeloproliferative disorder, originating in a pluripotent stem cell common to all three hematopoietic lineages, characterized by overproduction of myeloid cells in all stages of maturation. Approval of the use of imatinib in the United States in 2001 and its introduction in the treatment of chronic myeloid leukemia changed the evolution and prognosis of the disease and began the era of molecular therapy for malignancies.

[Minimally invasive surgery in pediatric patients within a general urology department].

Objectives: The advances of minimally invasive surgery in urology over the last years have enabled a progressive and constant implementation of endourology and laparoscopy in pediatric patients. We perform a review of our experience, as a general hospital, with minimally invasive surgery performed in pediatric patients over the last ten years.

Methods: We retrospectively analyzed the endourological and laparoscopic operations performed between 1997 and 2007 in children up to the age of 16 years, collecting data about patient's age and gender, type of disease, techniques, anesthesia, and perioperative events.

Experience in management of 51 non-functioning pituitary adenomas: indications for post-operative radiotherapy.

Object: The indications for additional radiotherapy (RT) after surgery for non-functioning pituitary adenoma are controversial. The goal of this retrospective study was to evaluate the outcome of surgically treated patients, with or without post- operative irradiation.

Methods: Review of cases treated for non-functioning pituitary adenoma.

Differential expression of three matrix metalloproteinases, MMP-19, MMP-26, and MMP-28, in normal and inflamed intestine and colon cancer.

Several matrix metalloproteinases (MMPs) have been implicated in intestinal inflammation, mucosal wound healing, and cancer progression. The purpose of this study was to examine the cellular location and putative function of MMP-19, MMP-26 (matrilysin-2), and MMP-28 (epilysin), in normal, inflammatory, and malignant conditions of the intestine. Peroperative tissue specimens from patients with ulcerative colitis (UC) (n = 16) and archival tissue samples of ischemic colitis (n = 9), Crohn's disease (n = 7), UC (n = 8), colon cancer (n = 20), and healthy intestine (n = 5) were examined using immunohistochemical analyses with polyclonal antibodies.

Human autophagins, a family of cysteine proteinases potentially implicated in cell degradation by autophagy.

We have cloned four human cDNAs encoding putative cysteine proteinases that have been tentatively called autophagins. These proteins are similar to Apg4/Aut2, a yeast enzyme involved in the activation of Apg8/Aut7 during the process of autophagy. The identified proteins ranging in length from 393 to 474 amino acids also contain several structural features characteristic of cysteine proteinases including a conserved cysteine residue that is essential for the catalytic properties of these enzymes.

Human macrophage metalloelastase (MMP-12) expression is induced in chondrocytes during fetal development and malignant transformation.

Fetal development and tumor progression both require a complex system of extracellular matrix (ECM) synthesis and breakdown, which is mediated by, for instance, the matrix metalloproteinases (MMPs). Human metalloelastase (MMP-12) is an MMP, the expression of which has so far been documented in macrophages associated with atherosclerosis, wound repair, and certain cancers. In this study we first examined the expression of MMP-12 during human fetal development.

Matrilysin-2, a new matrix metalloproteinase expressed in human tumors and showing the minimal domain organization required for secretion, latency, and activity.

We have identified a human placenta cDNA coding for a new member of the matrix metalloproteinase (MMP) family. The isolated cDNA encodes a polypeptide of 261 amino acids, the smallest MMP identified to date, which contains several structural features of MMPs including the signal sequence, the prodomain involved in enzyme latency, and the catalytic domain with the zinc-binding site. However, it lacks the hinge region and hemopexin-domain present in most MMPs.

An overview of collagenase-3 expression in malignant tumors and analysis of its potential value as a target in antitumor therapies.

Collagenase-3 (MMP-13) is a member of the matrix metalloproteinase family of endopeptidases that is characterized by a potent degrading activity against a wide spectrum of substrates. This enzyme was first detected in breast carcinomas but it is also overexpressed in a variety of malignant tumors including head and neck carcinomas, chondrosarcomas, skin carcinomas, and carcinomas of the female genital tract. Clinical studies have revealed that in all these tumors collagenase-3 expression is associated with invasive and metastatic tumors.

Phenotypic switching in Candida albicans is controlled by a SIR2 gene.

We report the cloning of a gene from the human fungal pathogen Candida albicans with sequence and functional similarity to the Saccharomyces cerevisiae SIR2 gene. Deletion of the gene in C. albicans produces a dramatic phenotype: variant colony morphologies arise at frequencies as high as 1 in 10.

Expression and regulation of collagenase-3 (MMP-13) in human malignant tumors.

Human collagenase-3 (MMP-13) is a matrix metalloproteinase originally identified in breast carcinomas. Recent studies have revealed that this enzyme is also produced by a variety of malignant tumors including head and neck carcinomas, chondrosarcomas and basal cell carcinomas of the skin. In all cases, the expression of collagenase-3 is associated with aggressive tumors.

Matrix metalloproteinases and their expression in mammary gland.

The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that play a key role in both normal and pathological processes involving tissue remodeling events. The expression of these proteolytic enzymes is highly regulated by a balance between extracellular matrix (ECM) deposition and its degradation, and is controlled by growth factors, cytokines, hormones, as well as interactions with the ECM macromolecules. Furthermore, the activity of the MMPs is regulated by their natural endogenous inhibitors, which are members of the tissue inhibitor of metalloproteinases (TIMP) family.

Collagenase-3 (MMP-13) expression in chondrosarcoma cells and its regulation by basic fibroblast growth factor.

Human collagenase-3 (MMP-13) is a member of the matrix metalloproteinase family of enzymes that was originally identified in breast carcinomas and subsequently detected during fetal ossification and in arthritic processes. In this work, we have found that collagenase-3 is produced by HCS-2/8 human chondrosarcoma cells. An analysis of the ability of different cytokines and growth factors to induce the expression of collagenase-3 in these cells revealed that basic fibroblast growth factor (bFGF or FGF-2) strongly up-regulated the expression of this gene.

Differential effects of transforming growth factor-beta on the expression of collagenase-1 and collagenase-3 in human fibroblasts.

Collagenase-3 (MMP-13) is a matrix metalloproteinase (MMP) originally identified in breast carcinomas which is also produced at significant levels during fetal ossification and in arthritic processes. In this work, we have found that transforming growth factor beta1 (TGF-beta1), a growth factor widely assumed to be inhibitory for MMPs, strongly induces collagenase-3 expression in human KMST fibroblasts. In contrast, this growth factor down-regulated the expression in these cells of collagenase-1 (MMP-1), an enzyme highly related to collagenase-3 in terms of structure and enzymatic properties.

Regulation of collagenase-3 expression in human breast carcinomas is mediated by stromal-epithelial cell interactions.

Collagenase-3 (MMP-13) is a recently identified member of the human matrix metalloproteinase gene family that is expressed in breast carcinomas and in articular cartilage from arthritic patients. Here, we have studied the cellular origin of this enzyme in breast carcinomas by in situ RNA hybridization, and we found that collagenase-3 is expressed by stromal cells immediately adjacent to epithelial tumor cells but not by the tumor cells themselves; nor is it expressed by the normal breast glandular epithelium. Consistent with this observation, coculture experiments using human fibroblasts and MCF-7 breast cancer cells revealed that conditioned medium from breast cancer cells stimulated the fibroblastic expression of collagenase-3 mRNA.

Long-term improvement in patients with severe Parkinson's disease after implantation of fetal ventral mesencephalic tissue in a cavity of the caudate nucleus: 5-year follow up in 10 patients. Clinica Puerta de Hierro Neural Transplantation Group.

Different groups worldwide have observed in recent years that stereotactic implantation of fetal tissue can ameliorate the clinical symptoms of Parkinson's disease. The authors therefore investigated whether implantation of fetal ventral mesencephalic (FVM) tissue via open surgery is also capable of producing an improvement and whether this improvement is transient or long lasting. The authors report their findings in a 5-year follow-up study in 10 patients with Hoehn and Yahr Grade IV or V Parkinson's disease in whom a single FVM graft was implanted in a cavity created in the right caudate nucleus.

Alternative splicing gives rise to two novel long isoforms of Zn-alpha 2-glycoprotein, a member of the immunoglobulin superfamily.

We have isolated, from a rat liver cDNA library, two cDNAs encoding novel long isoforms of Zn-alpha2-glycoprotein (Zn-alpha2-gp), a member of the immunoglobulin superfamily with a high degree of sequence similarity to class-I major histocompatibility complex (MHC) antigens. Nucleotide (nt) sequence analysis of these two novel cDNAs has revealed that they contain insertions of 138 and 123 nt between the second and third exons of Zn-alpha2-gp, resulting in in-frame insertions of 46 and 41 amino acids (aa), respectively. Analysis of the mechanism of generation of both isoforms, named Zn-alpha2-gpA and Zn-alpha2-gpB, has shown that they result from a series of alternative splicing events, including alternative use of two additional exons, and of two different 3'-splice sites present in the first of these novel exons.

Sb(III) and Sb(V) separation and analytical speciation by a continuous tandem on-line separation device in connection with inductively coupled plasma atomic emission spectrometry.

A sensitive, precise and automated non-chromatographic method for Sb(III) and Sb(V) analytical speciation based on a continuous tandem on-line separation device in connection with inductively coupled plasma-atomic emission (ICP-AES) detection is proposed. Two on-line successive separation steps are included into this method: a continuous liquid-liquid extraction of Sb(III) with ammonium pyrrolidine dithiocarbamate (APDC) into methylisobuthylketone (MIBK), followed by direct stibine generation from the organic phase. Both separation steps are carried out in a continuous mode and on-line with the ICP-AES detector.

Cloning and expression analysis of the cDNA encoding rat Zn-alpha 2-glycoprotein.

We report here the nucleotide (nt) sequence of a rat liver cDNA encoding Zn-alpha 2-glycoprotein (Zn-alpha 2-gp), a plasma protein with a high degree of sequence similarity to class-I major histocompatibility complex (MHC) antigens. The deduced amino acid (aa) sequence contains the coding information for 293 aa residues and shows 60% identity with the aa sequence of human Zn-alpha 2-gp and 35% identity with that corresponding to the extracellular domains of RT1, a rat class-I MHC antigen. Northern blot analysis showed that rat Zn-alpha 2-gp is expressed in liver, but not in a wide number of tissues, including prostate, mammary gland, kidney, intestine, lung, pancreas, ovary, uterus, thyroid, placenta, spleen, brain and heart.

Structure and expression in breast tumors of human TIMP-3, a new member of the metalloproteinase inhibitor family.

A new member of the metalloproteinase inhibitor family of proteins has been cloned from a complementary DNA library derived from a human breast tumor. The isolated complementary DNA contains an open reading frame 633 base pairs long, encoding a polypeptide of 211 amino acids, which has been called tissue inhibitor of metalloproteinase 3 (TIMP-3). This protein displays low sequence similarity to the previously known human TIMPs but shows a high degree of similarity with chicken inhibitor of metalloproteinase 3, a recently described metalloproteinase inhibitor stimulated during oncogenic transformation of chicken fibroblasts and with the ability to promote some phenotypic properties of transformed cells.