0000000000033929
AUTHOR
David Ramos
WWOX, a Chromosomal Fragile Site Gene and its Role in Cancer
Allelic imbalances affecting the long arm of chromosome 16 have been extensively reported in the literature as common abnormalities observed in various carcinoma types, As a result of loss of heterozygosity (LOH) studies in breast cancer, we delimited a genomic area within chromosome 16 that demonstrated the highest frequency of abnormalities. This led us to the identification and cloning of WWOX, a candidate tumor suppressor gene (TSG) that spans a fragile region of DNA located at 16q23.3-24.1 (FRA16D: the second most active common chromosomal fragile site in the human genome). This gene encodes a protein that contains two WW domains responsible of protein-protein interactions and a short-…
The density and type of MECA-79-positive high endothelial venules correlate with lymphocytic infiltration and tumour regression in primary cutaneous melanoma
Aims Tumour-infiltrating lymphocytes have prognostic value in malignant melanoma. High endothelial venules (HEVs) are specialized vessels present in lymph nodes and tertiary lymphoid organs. CCL19, CCL21 and CCR7 regulate lymphocyte migration through HEVs. The aim of our study was to correlate HEV density in cutaneous primary and metastatic malignant melanomas with clinicopathological parameters, and with CCL19, CCL21 and CCR7 mRNA expression. Methods and results High endothelial venule density was evaluated by immunohistochemistry with a specific antibody, MECA-79, and chemokine expression was evaluated by real-time PCR. MECA-79-positive vessels, covered by cuboidal (C-HEV) or flat (F-HEV)…
Prognostic markers in low-grade papillary urothelial neoplasms of the urinary bladder
Summary Papillary urothelial neoplasms (PUNs) of the urinary bladder comprise a heterogeneous spectrum of ‘continuous' lesions in which the assessment of an accurate histological grade and tumor stage is necessary for an adequate clinical management of patients. Recently, the 1998 World Health Organization/International Society of Urologic Pathologists (WHO/ISUP) Consensus Classification and the 1999 WHO classification proposed a new malignancy grading scheme based mainly on morphometric studies. In accordance with these grading systems, two major categories of PUNs were distinguished: low-grade and high-grade. Concerning the specific subgroup of low-grade tumors two other entities were def…
Clear Cell Syringoid Carcinoma
Syringoid carcinoma (syringoid "eccrine" carcinoma or eccrine epithelioma) is a rare cutaneous tumor with some controversy regarding its correct definition. It may also be difficult to differentiate from its benign counterpart (syringoma), other adnexal carcinomas, and cutaneous metastasis from adenocarcinomas. We present a case of a syringoid carcinoma of the clear cell variant complemented with an immunohistochemical and ultrastructural study, the latter revealing cytoplasmic accumulation of glycogen and presence of intercellular and intracellular lumina in clear tumor cells, as well as diverse hallmarks of malignancy (i.e., perineural invasion, tumor necrosis, and deep invasion). Clear t…
Low levels of WWOX protein immunoexpression correlate with tumour grade and a less favourable outcome in patients with urinary bladder tumours
Aims: To correlate the immunohistochemical detection of WWOX with histological measures and disease progression within the whole spectrum of urothelial bladder neoplasms. Methods and results: One hundred and one patients with primary bladder tumours were retrospectively analysed. Immunohistochemically, a polyclonal antibody was utilized and the level of WWOX protein expression was analysed by using a combined score system based on intensity of the reaction and percentage of immunoreactive tumour cells. WWOX protein expression was consistently expressed in non-neoplastic urothelium, whereas a progressive loss of immunoreactivity was observed as tumour grade and stage increased (P < 0.05). …
Immunohistochemical Expression of Ki-67 Antigen, Cox-2 and Bax/Bcl-2 in Prostate Cancer; Prognostic Value in Biopsies and Radical Prostatectomy Specimens
Abstract Purposes: To elucidate the prognostic value of the immunohistochemical (IHC) expression of Bcl-2, Bax, Cox-2 and Ki-67 antigen in biopsy cores (C) and surgical specimens (SP) of prostate cancer (PC) and to determine the C to SP reproducibility. Material and methods: The IHC study was carried out in 91 patients operated by means of radical prostatectomy (RP) with available formalin-fixed paraffin-embedded material from both C and SP. Results: The IHC expression of Bcl-2 in C and SP was very low (5%). Bax was expressed in almost all the patients and did not show any prognostic value. We observed a good reproducibility between C and SP for all molecules except with Bax. In prostate C,…
Molecular and immunohistochemical analysis of the prognostic value of cell-cycle regulators in urothelial neoplasms of the bladder.
Abstract Objective To evaluate the prognostic and predictive value of molecular and immunohistochemical markers related to cell-cycle control in terms of recurrence, progression, and survival in urothelial neoplasms of the bladder (UNB). Patients and Methods Clinical and pathological findings of 84 patients with UNB were assessed. Homozygous deletion (HD) and promoter methylation of p14 ARF , p15 INK4B , p16 INK4A , loss of heterozygosity of the locus 9p21, p53 mutations, and immunohistochemical expression of p53, p16, p14, p21, p27, pRb, Ki67, MDM2, and cyclin D1 proteins were evaluated in relation to overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS…
Prognostic markers in low-grade papillary urothelial neoplasms of the urinary bladder: an update
Abstract Papillary urothelial neoplasms of the urinary bladder comprise a heterogeneous spectrum of ‘continuous' lesions in which the assessment of an accurate histological grade and tumour stage is mandatory for the clinical management of patients. The 1998 World Health Organization/International Society of Urologic Pathologists (WHO/ISUP) consensus classification and the 1999 WHO classification proposed new malignancy grading schemes, mainly based on morphometric studies for the replacement of the 1973 WHO grading system. In accordance with these novel grading systems, two major categories of papillary urothelial neoplasms were distinguished: low-grade and high-grade papillary urothelial …
Cytokeratin expression patterns in low-grade papillary urothelial neoplasms of the urinary bladder.
BACKGROUND The differential expression patterns of cytokeratin 20 (CK20) and 34βE12 antigen in low-grade papillary urothelial tumors of the bladder are discussed. METHODS A retrospective study of 120 patients with low-grade papillary bladder tumors (45 neoplasms of low malignant potential and 75 low-grade WHO G1 carcinomas) was performed. All tumors were graded in accordance with the 1998 World Health Organization/International Society of Urological Pathology (WHO/ISUP) and 1999 WHO classifications. The mean follow-up was 76.6 months (range, 36–168 mos), considering for prognostic purposes the time to first recurrence, or relapse-free interval (RFI), and the total number of recurrent patien…
Electrochemical detection and screening of bladder cancer recurrence using direct electrochemical analysis of urine: A non-invasive tool for diagnosis
Although detection of urothelial cell carcinoma (or bladder cancer, BC) can be performed via cytological, molecular and genetic marker tests on urine, cystoscopy, an invasive technique, still remains as the gold methodology in clinical practice. It is presented a non-invasive method for detecting BC recurrence consisting of a direct electrochemical test in urine combining voltammetric data at gold and glassy carbon electrodes. The diagnosis is based on the ratio between characteristic voltammetric features recorded for tryptophan, serotonin and melatonin and other related metabolites. The method was tested by means of a clinical trial with 30 patients diagnosed of bladder cancer and a two c…
Papel de las quimiocinas en la progresión del melanoma
Resumen Las metastasis son la principal causa de mortalidad en el melanoma. Las quimiocinas son citocinas quimiotacticas de bajo peso molecular que permiten la migracion celular, atrayendo a celulas que expresan sus receptores. Como algunas quimiocinas son abundantes en organos que son asiento comun de metastasis, y sus receptores son expresados por las celulas tumorales, se planteo la hipotesis de que un gradiente de estas quimiocinas facilitaria selectivamente las metastasis a esos organos. El hallazgo posterior de la produccion de estas quimiocinas por las propias celulas tumorales, y su efecto autocrino, obliga a modular esta hipotesis. Ademas, muchas quimiocinas tienen efectos contrapu…
Asymptotic modeling of electrochemical signaling: Testing Zn in urine for non-invasive bladder cancer diagnosis
Abstract A theoretical model on chemical signaling for diagnosis based on the combination of signals for marker and inert and/or interfering metabolites is described. The model yields asymptotic relationships between the intensities of the signals representative of marker and accompanying metabolites compensating concentration fluctuations. The model fits well with voltammetric features associated to the oxidation of different urine metabolites and Zn(II) reduction in the same urine samples after alkaline digestion. As a result, a non-invasive electrochemical detection of urothelial carcinoma (bladder cancer, BC) is reported. Different diagnostic criteria are described all displaying high s…
Transmembrane electrochemistry of erythrocytes: Direct electrochemical test for detecting hemolysis in whole blood
A rapid method for detecting hemolysis in whole blood based on a direct electrochemical assay either in venous blood and finger blood, respectively at glassy carbon and screen-printed graphite electrodes is described. The presence of hemolysis is detected from characteristic voltammetric signatures associated to Fe-heme units in healthy and hemolyzed erythrocytes. The voltammetric response of blood was also investigated using scanning electrochemical microscopy (SECM) and scanning tunneling microscopy (STM) and involved transmembrane electrochemistry of erythrocytes superimposed to molecular electrochemistry of heme-containing proteins and heme fragments in the plasma. Voltammetric testing …
Role of Chemokines in Melanoma Progression
Metastasis is the main cause of death from melanoma. Chemokines are low molecular weight chemotactic cytokines that facilitate cellular migration. Thus, cells that express receptors for a given chemokine are attracted to the site of its production. As certain chemokines are found in abundance in organs that are common targets of metastasis and receptors for these chemokines are expressed by tumor cells, it was hypothesized that chemokine gradients might selectively facilitate metastasis to these organs. A later finding that these chemokines were produced by tumor cells, with evidence of autocrine effects, obliged the modification of that hypothesis. Many chemokines are also known to have op…