Transition Metal Complexes with Tridentate Schiff Bases (O N O and O N N) Derived from Salicylaldehyde: An Analysis of Their Potential Anticancer Activity.

Although it is known that the first case of cancer was recorded in ancient Egypt around 1600 BC, it was not until 1917 during the First World War and the development of mustard gas that chemotherapy against cancer became relevant; however, its properties were not recognised until 1946 to later be used in patients. In this sense, the use of metallopharmaceuticals in cancer therapy was extensively explored until the 1960s with the discovery of cisplatin and its anticancer activity. From that date to the present, the search for more effective, more selective metallodrugs with fewer side effects has been an area of continuous exploration. Efforts have led to considering a wide variety of metals from the periodic table, mainly from the d-block, as well as a wide variety of organic ligands, preferably with proven biological activity. In this sense, various research groups have found an ideal binder in Schiff bases, since their raw materials are easily accessible, their synthesis conditions are friendly and their denticity can be manipulated. Therefore, in this review, we have explored the anticancer and antitumor activity reported in the literature for coordination complexes of d-block metals coordinated with tridentate Schiff bases (O N O and O N N) derived from salicylaldehyde. For this work, we have used the main scientific databases CCDC® and SciFinder®.

Catecholamine levels and gene expression of their receptors in tissues of adults with osteosarcoma.

AIM: The purpose of this work was to identify and measure catecholamines, their metabolites, and the gene expression of catecholamine receptors in osteosarcoma tissue. MATERIALS AND METHODS: The levels of 3,4-dihydroxyphenylacetic acid, norepinephrine, serotonin, and 5-hydroxyindoleacetic acid in cancer tissue and in adjacent and non-oncological bone tissue were analysed by high-performance liquid chromatography, and the gene expression of catecholamine receptors and of dopamine ß-hydroxylase, monoaminoxidase, ki67, and Runx2 in the osteosarcoma tissue, tissue adjacent to the tumour, non-oncological bone, and human brain tissue was analysed by RT-PCR. RESULTS: We found significantly higher levels of 3,4-dihydroxyphenylacetic acid and norepinephrine in the cancer sample than in adjacent and non-oncological bone. We found that ß-adrenergic receptors and dopaminergic receptors, dopamine ß-hydroxylase, ki67, Runx2, and serotonergic receptor gene expression were significantly higher in tumour tissue than in adjacent and non-oncological bone. CONCLUSION: Catecholamines and their receptors could be potential molecular markers for osteosarcoma progression.

Fluorinated-NHC Transition Metal Complexes: Leading Characters as Potential Anticancer Metallodrugs.

In the last 20 years, N-Heterocyclic Carbene (NHC) ligands have been ubiquitous in biological and medicinal chemistry. Part of their success lies in the tremendous number of topologies that can be synthesized and thus finely tuned that have been described so far. This is particularly true in the case of those derivatives, including fluorine or fluorinated fragments on their NHC moieties, gaining much attention due to their enhanced biological properties and turning them into excellent candidates for the development of novel metallodrugs. Thus, this review summarizes the development that fluorinated-NHC transition metal complexes have had and their impact on cancer treatment.

Molecular alterations in non-functioning pituitary adenomas.

BACKGROUND: Clinically non-functioning Pituitary Adenomas (NFPA) are among the most common neoplasms of the sellar region. They usually present with compressive symptoms such as headache and visual field defects and not infrequently, are found incidentally. NFPA are classified as gonadotropinomas, null cell adenomas, according to their immunohistochemical phenotype. The molecular alterations responsible for the development of these lesions are incompletely understood, and there is scarce information regarding the molecular alterations and markers. OBJECTIVE: We carried out an in-silico analysis aimed at identifying the molecular alterations in NFPA and to discover new molecular markers. METHODS: Twenty-three microarray libraries were analyzed. Fourteen correspond to NFPA and 9 to control tissue gland. They were analyzed using Partek Genomic Suite to identify differentially expressed genes and WebGestalt and Metascape to understand the meaning behind the gene lists. RESULTS: Pituitary adenomas showed a markedly different transcriptome compared to the non-tumoral gland, regardless of their putative immunophenotype. Genes related to calcium metabolism such as CACNA2D4, immune-related CXCR4, and stem cell-related KLF8 and PITX2 were altered. CONCLUSIONS: Differentially expressed calcium metabolism and immune-related genes in NFPA represent attractive molecular markers and potential therapeutic targets.

Revisiting the Genomic and Transcriptomic Landscapes from Female Malignancies Could Provide Molecular Markers and Targets for Precision Medicine.

AIMS: Gynaecological malignancies such as breast, ovarian and cervical cancers have become an important public health problem. Detection of molecular alterations in cancer research is fundamental since it can reveal specific pathogenic patterns and genes that could serve as markers. Our aim was to characterize common genomic and transcriptomic signatures for the three gynaecologic malignancies with the highest incidence and mortality to try to identify new molecular markers, therapeutic targets and molecular signatures. METHODS: Here we analysed a total of 723 microarray libraries corresponding to equal number of breast, ovary and cervical cancer and non-cancer patient samples. Copy number variation (CNV) was carried out using 428 libraries and transcriptomic analysis using the 295 remaining samples. RESULTS: Our results showed that breast, ovary and cervical malignancies are characterized by gain of 1q chromosome. At transcriptomic level, they share 351 coding and non-coding genes, which could represent core transcriptome of gynaecological malignancies. Pathway analysis from the resulting gene lists from CNV and expression showed participation in cell cycle, metabolism, and cell adhesion molecules among others. CONCLUSIONS: Chromosome 1q characterize the gynaecological malignancies, which could harbour a richness of genetic repertoire to mine for molecular markers and targets, particular gynaecologic expression profile, containing FANCI, FH and MIR155HG among others, could represent part of the transcriptomic core for diagnostic test and attractive therapeutic targets. It may not be long before every human cancer sample is profiled for a detections test to ascertain a molecular diagnosis and prognosis and to define an optimal and precise treatment strategy.

A Review on Viral Metagenomics in Extreme Environments.

Viruses are the most abundant biological entities in the biosphere, and have the ability to infect Bacteria, Archaea, and Eukaryotes. The virome is estimated to be at least ten times more abundant than the microbiome with 107 viruses per milliliter and 109 viral particles per gram in marine waters and sediments or soils, respectively. Viruses represent a largely unexplored genetic diversity, having an important role in the genomic plasticity of their hosts. Moreover, they also play a significant role in the dynamics of microbial populations. In recent years, metagenomic approaches have gained increasing popularity in the study of environmental viromes, offering the possibility of extending our knowledge related to both virus diversity and their functional characterization. Extreme environments represent an interesting source of both microbiota and their virome due to their particular physicochemical conditions, such as very high or very low temperatures and >1 atm hydrostatic pressures, among others. Despite the fact that some progress has been made in our understanding of the ecology of the microbiota in these habitats, few metagenomic studies have described the viromes present in extreme ecosystems. Thus, limited advances have been made in our understanding of the virus community structure in extremophilic ecosystems, as well as in their biotechnological potential. In this review, we critically analyze recent progress in metagenomic based approaches to explore the viromes in extreme environments and we discuss the potential for new discoveries, as well as methodological challenges and perspectives.

Complexes containing benzimidazolyl-phenol ligands and Ln(III) ions: Synthesis, spectroscopic studies and preliminary cytotoxicity evaluation.

Fourteen new complexes were obtained from Ln(III)(NO3)3∙n-H2O and the chromophores 2-(1H-benzo[d]imidazol-2-yl)-phenol (Bzp1) or 2-(5-methyl-1H-benzo[d]imidazol-2-yl)-phenol (Bzp2). The complete characterization allowed us to assign unequivocally the structures of all the complexes. The techniques used for this purpose were Ultraviolet-Visible (UV-Vis) and Fourier-Transform Infrared (FT-IR) spectroscopies, High-Resolution Mass Spectrometry (HRMS), Magnetic Susceptibility (MS), Elemental Analysis (EA) and Molar Conductivity (MC). HRMS allowed us to find the molecular ion and its isotopic pattern. The FT-IR spectral data suggested that benzimidazolyl-phenol ligands coordinate with Ln(III) ions through iminic nitrogen and phenolic oxygen. Thermogravimetric Analysis (TGA) studies of NdBzp1 and GdBzp2 complexes indicate the presence of lattice water along with three nitrates and two benzimidazolyl-phenol ligands; the thermal decomposition was consistent with the minimal formula suggested by EA. The coordination type of the benzimidazolyl-phenol ligands, the geometry and the structural organization of these coordination complexes have been interpreted by Density Functional Theory (DFT) calculations, and they coincided with the physicochemical data suggesting a coordination number eight for the Ln(III) ions. The cytotoxicity of the chromophores and their coordination complexes was tested against a cancer cell line (HeLa), as compared with structure/support cells (NIH-3T3) and defense cells (J774A.1), revealing that three coordination complexes showed moderate cytotoxicity against the cell lines studied.

Extremophile deep-sea viral communities from hydrothermal vents: Structural and functional analysis.

Ten publicly available metagenomic data sets from hydrothermal vents were analyzed to determine the taxonomic structure of the viral communities present, as well as their potential metabolic functions. The type of natural selection on two auxiliary metabolic genes was also analyzed. The structure of the virome in the hydrothermal vents was quite different in comparison with the viruses present in sediments, with specific populations being present in greater abundance in the plume samples when compared with the sediment samples. ssDNA genomes such as Circoviridae and Microviridae were predominantly present in the sediment samples, with Caudovirales which are dsDNA being present in the vent samples. Genes potentially encoding enzymes that participate in carbon, nitrogen and sulfur metabolic pathways were found in greater abundance, than those involved in the oxygen cycle, in the hydrothermal vents. Functional profiling of the viromes, resulted in the discovery of genes encoding proteins involved in bacteriophage capsids, DNA synthesis, nucleotide synthesis, DNA repair, as well as viral auxiliary metabolic genes such as cytitidyltransferase and ribonucleotide reductase. These auxiliary metabolic genes participate in the synthesis of phospholipids and nucleotides respectively and are likely to contribute to enhancing the fitness of their bacterial hosts within the hydrothermal vent communities. Finally, evolutionary analysis suggested that these auxiliary metabolic genes are highly conserved and evolve under purifying selection, and are thus maintained in their genome.

HPV Could be a Potential Factor of Survival in Laryngeal Cancer: a Preliminary Study in Mexican Patients

Introduction: In Head and Neck (HN) cancer, the High-Risk Human Papillomavirus (hr HPV) infection has been associated in about 40% of these tumors. The hr HPV infection is one of the etiological factors of several epithelial tumors; however, its association with the prognosis has not yet been established for patients with Laryngeal Squamous Cell Carcinoma (LSCC). On the other hand, Epidermal Growth Factor Receptor (EGFR) is a molecular marker widely studied in cancer and its overexpression has been associated with poor prognosis in some types of cancer, including the HN cancer. In the present study, we analyzed EGFR expression and HPV detection in a cohort of Mexican patients with LSCC and define their association with clinical-pathological and survival parameters. Methods: EGFR expression analysis was performed by immunohistochemistry assay. A tissue array was constructed based on 30 paraffin-embedded tissue samples. HPV detection was performed by PCR. The results were then compared with the clinical-pathological variables and outcome measures (Kaplan Meier and Cox analysis). Results: High expression of EGFR was observed in 43% of the samples and 20% of HPV detection. The statistical analyses provided evidence of disassociation between clinical-pathological parameters and EGFR expression, but there was an association with poor prognosis. Interestingly, HPV detection is slightly associated with good prognosis. Conclusion: Both, EGFR overexpression and HPV presence could be associated with an unfavorable prognosis in patients with LSCC, independently of other clinical-pathological factors.

The KISS1 gene overexpression as a potential molecular marker for cervical cancer cells.

BACKGROUND: Similarities between the pathologic progression of cancer and the physiologic process of placentation have been recognized for many years proposing that both present similar mechanisms and processes. Cervical cancer (CC) is one of the most frequent neoplasia among Mexican women turning it into an important health problem. OBJECTIVE: The aim of this study was to determine the degree of the involvement of pregnancy related genes and in cancer progression by in-silico analysis and validated in CC samples. RESULTS: The data mining analysis resulted in the identification of genes expressed in term placenta, first trimester placenta and normal cervical tissues. Finally, we selected KISS1 for the involvement of pregnancy related gene and also in cancer process. In order to explore KISS1 in CC, we analyzed Copy Number Variation (CNV) and gene expression using microarray experiments. KISS1 showed 20% genomic gain in 1q32.1 on CC samples. Furthermore, microarray analysis showed KISS1 as up-regulated genes. Results were validated showing an overexpression of 85% of KISS1 in CC samples. CONCLUSIONS: Data suggest KISS1 as a great candidate for CC molecular markers or as a therapeutic target for CC. Also, HPV presence does not seem to alter the KISS1 expression in CC.

Abundancia y biomasa de chaetognatha (aphragmophora) en la zona pelágica del pacífico colombiano / Chaetognatha (aphragmophora) abundance and biomass in the epipelagic zone of the colombian pacific

RESUMEN Dada la importancia de los quetognatos por su alto impacto depredador y su rol en la transferencia energética desde el fitoplancton hasta niveles tróficos superiores, por primera vez, se evaluó en el Océano Pacífico Colombiano (OPC) su biomasa seca, además de su abundancia, en relación con la estructura termohalina y la influencia de la luz, durante septiembre de 2007. Se analizaron 23 muestras obtenidas con una red bongo, mediante arrastres oblicuos en el estrato epipelágico de sendas estaciones, distribuidas en toda el área. Las condiciones abióticas fueron características de una época normal, con posible beneficio para la comunidad de los quetognatos, en respuesta a la disponibilidad de alimento. Mientras que los adultos dominaron en las sub-áreas intermedia (x̅= 240 ind./100m3, 34,7g/100m3) y oceánica (x̅= 290 ind./100m3 39,2g/100m3), las aguas costeras, generalmente más productivas, pudieron promover el desove, el desarrollo y el mayor biomasa-abundancia de los juveniles (910ind./100m3, 26,2g/100m3), sugiriendo su mejor adaptación a aguas menos salinas, así como un impacto trófico más marcado y un papel más relevante, que los adultos en la estructura de la comunidad zooplanctónica. Es muy probable que la dinámica hidrológica haya influido en la distribución heterogénea de los organismos en la zona epipelágica, con biomasa-abundancia más alta en algunas estaciones costeras y oceánicas, debido a la mayor oferta trófica resultante de la conjunción de procesos de surgencia, migración vertical nocturna e influencia lunar, en especial, durante luna nueva y cuarto creciente. Se da una lista de verificación preliminar de los quetognatos.

SUMMARY Due to the importance of chaetognaths, their high predatory impact and their role in energy transfer from phytoplankton to higher trophic levels, their abundance and dry biomass were evaluated for the first time in relation to thermohaline structure and light influence in the Colombian Pacific Ocean (CPO) in September 2007. Twenty-three samples were obtained with a bongo net (294 μm mesh) by oblique trawls in the epipelagic stratum in equal number of stations distributed throughout the CPO. Abiotic conditions were characteristic of a normal period, with possible benefit to the chaetognath community as a result of food availability. While adults dominated in the intermediate (x̅= 240 ind/100 m3, 34.7 g/100 m3) and oceanic (x̅= 290 ind/100 m3 39.2 g/100 m3) subareas, coastal waters, generally more productive, promoted the spawning, development and higher abundance and biomass of juveniles (910 ind/100 m3, 26.2 g/100 m3), which indicates better adaptation to less saline waters, as well as a more pronounced trophic impact and relevant role to the structure of the zooplankton community when compared to the adult community. It is likely that hydrological dynamics have influenced heterogeneous organism distribution on the epipelagic zone, with a higher biomass-abundance in some coastal and oceanic stations, due to greater trophic supply resulting from upwelling processes, nocturnal vertical migration, and lunar influence, especially during the new moon and first quarter. A preliminary checklist of the chaetognaths is given.

Modeling the dynamics of chromosomal alteration progression in cervical cancer: A computational model.

Computational modeling has been applied to simulate the heterogeneity of cancer behavior. The development of Cervical Cancer (CC) is a process in which the cell acquires dynamic behavior from non-deleterious and deleterious mutations, exhibiting chromosomal alterations as a manifestation of this dynamic. To further determine the progression of chromosomal alterations in precursor lesions and CC, we introduce a computational model to study the dynamics of deleterious and non-deleterious mutations as an outcome of tumor progression. The analysis of chromosomal alterations mediated by our model reveals that multiple deleterious mutations are more frequent in precursor lesions than in CC. Cells with lethal deleterious mutations would be eliminated, which would mitigate cancer progression; on the other hand, cells with non-deleterious mutations would become dominant, which could predispose them to cancer progression. The study of somatic alterations through computer simulations of cancer progression provides a feasible pathway for insights into the transformation of cell mechanisms in humans. During cancer progression, tumors may acquire new phenotype traits, such as the ability to invade and metastasize or to become clinically important when they develop drug resistance. Non-deleterious chromosomal alterations contribute to this progression.

Crystal structure of catena-poly[[[tri-aqua-(4-cyano-benzoato-κO)nickel(II)]-µ-4,4'-bi-pyridine-κ(2) N:N'] 4-cyano-benzoate].

In the title polymeric complex salt, {[Ni(C8H4NO2)(C10H8N2)(H2O)3](C8H4NO2)} n , the Ni(II) cation is coordinated by a 4-cyano-benzoate anion, two 4,4'-bi-pyridine ligands and three water mol-ecules in a distorted N2O4 octa-hedral geometry. The 4,4'-bi-pyridine ligands bridge the Ni(II) cations to form polymeric chains of the title complex cations, propagating along the c-axis direction. The dihedral angle between the pyridine rings of the 4,4'-bi-pyridine ligand is 24.9 (6)°. In the crystal, the uncoordinating 4-cyano-benzoate anions link with the complex cations via O-H⋯O hydrogen bonds into a three-dimensional supra-molecular architecture. Weak C-H⋯O, C-H⋯N inter-actions and π-π stacking [centroid-to-centroid distances = 3.566 (4) and 3.885 (4) Å] are also observed in the crystal.

Dynamics of high-risk nonvaccine human papillomavirus types after actual vaccination scheme.

Human papillomavirus (HPV) has been identified as the main etiological factor in the developing of cervical cancer (CC). This finding has propitiated the development of vaccines that help to prevent the HPVs 16 and 18 infection. Both genotypes are associated with 70% of CC worldwide. In the present study, we aimed to determine the emergence of high-risk nonvaccine HPV after actual vaccination scheme to estimate the impact of the current HPV vaccines. A SIR-type model was used to study the HPV dynamics after vaccination. According to the results, our model indicates that the application of the vaccine reduces infection by target or vaccine genotypes as expected. However, numerical simulations of the model suggest the presence of the phenomenon called vaccine-induced pathogen strain replacement. Here, we report the following replacement mechanism: if the effectiveness of cross-protective immunity is not larger than the effectiveness of the vaccine, then the high-risk nonvaccine genotypes emerge. In this scenario, further studies of infection dispersion by HPV are necessary to ascertain the real impact of the current vaccines, primarily because of the different high-risk HPV types that are found in CC.

Bis(µ2-benzoato-κ(2) O:O')bis-[(benzoato-κ(2) O,O')bis(4,4'-bi-pyridine-κN)cobalt(II)]-benzoic acid (1/6).

In the title compound, [Co2(C7H5O2)4(C10H8N2)4]·6C6H5COOH, the centrosymmetric cobalt dimer co-crystallizes with six mol-ecules of benzoic acid. Each Co(II) atom is coordinated by four O atoms in a distorted square-planar arrangement while the N atoms are located in apical positions. The dihedral angles between the rings comprising each of the 4,4'-bipyridyl ligands are 25.2 (2) and 22.8 (2)°. In the crystal, the three-dimensional network is assembled by O-H⋯O and C-H⋯O hydrogen bonds.

Human papillomavirus genotypes among females in Mexico: a study from the Mexican institute for social security.

BACKGROUND: The aetiological relationship between human papillomavirus (HPV) infection and cervical cancer (CC) is widely accepted. Our goal was to determine the prevalence of HPV types in Mexican women attending at the Mexican Institute for Social Security from different areas of Mexico. MATERIALS AND METHODS: DNAs from 2,956 cervical samples were subjected to HPV genotyping: 1,020 samples with normal cytology, 931 with low-grade squamous intraepithelial lesions (LGSIL), 481 with high grade HGSIL and 524 CC. RESULTS: Overall HPV prevalence was 67.1%. A total of 40 HPV types were found; HPV16 was detected in 39.4% of the HPV-positive samples followed by HPV18 at 7.5%, HPV31 at 7.1%, HPV59 at 4.9%, and HPV58 at 3.2%. HPV16 presented the highest prevalence both in women with altered or normal cytology and HPV 18 presented a minor prevalence as reported worldwide. The prevalence ratio (PR) was calculated for the HPV types. The analysis of PR showed that HPV16 presents the highest association with CC, HPV 31, -33, -45, -52 and -58 also demonstrating a high association. CONCLUSIONS: The most prevalent HPV types in cervical cancer samples were -16, -18, -31, but it is important to note that we obtained a minor prevalence of HPV18 as reported worldwide, and that HPV58 and -52 also were genotypes with an important prevalence in CC samples. Determination of HPV genotypes is very important in order to evaluate the impact of vaccine introduction and future cervical cancer prevention strategies.

Cellular retinol binding protein 1 could be a tumor suppressor gene in cervical cancer.

AIMS: Cervical Cancer (CC) is one of the most important health problems in women. It frequently presents genetic changes at chromosome region 3q21. This region contains the Cellular Retinol Binding Protein 1 gene (CRBP1) which has been implicated as an important element in the development of other types of cancer. The main goal of the present work was to determine the molecular alterations of CRBP1 and its relationship to CC. METHODS: To determine the molecular alterations of CRBP1 gene in CC; twenty-six CC and twenty-six healthy cervix samples were evaluated for: 1) Copy number gain by real-time PCR analysis, 2) expression levels by an immunohistochemistry assay on tissue microarray, and 3) the methylation status of the CRBP1 promoter region. RESULTS: The increase in CRBP1 copy number was observed in 10 out of the 26 CC samples analyzed, while healthy cervices samples showed no changes in the copy number. In addition, there was a lack of expression of the CRBP1 gene in an important number of the CC samples (17/26), and the CRBP1 gene promoter was methylated in 15/26 of the CC samples. Interestingly, there was a significant association between the lack of expression of the CRBP1 gene and its methylation status. CONCLUSIONS: The data indicates that, both activating and inactivating changes in the CRBP1 gene could be significant events in the development and progression of CC, and the lack of expression of the CRBP1 protein could be related with to the development of CC. We believe that there is enough evidence to consider to CRBP1 gene as a tumor suppressor gene for CC.

HPV frequency in penile carcinoma of Mexican patients: important contribution of HPV16 European variant.

The role of human papillomavirus (HPV) infection in penile carcinoma (PeC) is currently reported and about half of the PeC is associated with HPV16 and 18. We used a PCR-based strategy by using HPV general primers to analyze 86 penile carcinomas paraffin-embedded tissues. Some clinical data, the histological subtype, growth pattern, and differentiation degree were also collected. The amplified fragments were then sequenced to confirm the HPV type and for HPV16/18 variants. DNA samples were also subjected to relative real time PCR for hTERC gene copy number. Some clinical data were also collected. Global HPV frequency was 77.9%. Relative contributions was for HPV16 (85%), 31 (4.4%), 11 (4.4%), 58, 33, 18, and 59 (1.4% each one). Sequence analysis of HPV16 identified European variants and Asian-American (AAb-c) variants in 92% and in 8% of the samples, respectively. Furthermore hTERC gene amplification was observed in only 17% of the cases. Our results suggest that some members of HPV A9 group (represented by HPV16, 58, and 31) are the most frequent among PeC patients studied with an important contribution from HPV16 European variant. The hTERC gene amplification could be poorly related to penile epithelial tissue.

Genetic alterations in a primary medullary thyroid carcinoma and its lymph node metastasis in a patient with 15 years follow-up.

BACKGROUND: Association between DNA alterations and clinical parameters as recurrence, survival or prognosis has been found in a variety of tumors. A clear association between Medullary Thyroid Carcinoma (MTC) and RET oncogene mutation has been accepted. Specifically M918T RET mutation represents the main genetic event in most cases of sporadic MTC (SMTC) and limited chromosomal alterations analyses have been performed. METHODS: In the present work, a comparative genomic hybridization (CGH) study was performed using DNA from a primary tumor in a M918T RET mutation-positive SMTC patient and from its lymph node metastasis to investigate additional genetic alterations. We studied a patient with 15 years of follow-up and persistence of disease, confirmed by periodical elevated serum calcitonin (CT) levels. RESULTS: Only 3 chromosomal imbalances were identified in the primary tumor, gain of 18p, and loss of 6p and 16p region, whereas 25 chromosomal imbalances were identified in the metastasis (9 gains and 16 losses). CONCLUSION: The chromosomal changes 6p-, 16p-, 18p + could determine in part the oncogenic phenotype in the primary M918T RET positive tumor and probably related to persistence of high serum CT levels in this patient. The additional chromosomal changes observed could be related to the metastasis phenotype. We suggest that some genes mapped at 6p, 16p and 18p chromosomal regions, could act as genes associated to cancer and could be related to persistent SMTC and good prognosis. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1720753793691097.

The neurofibromin 1 type I isoform predominance characterises female population affected by sporadic breast cancer: preliminary data.

AIMS: Neurofibromin 1 (NF1) as a tumour suppressor gene can give rise to several transcripts by an alternative splicing event, generated at least for CELF cofactors. At present, the NF1 isoforms and CELF splicing transcripts in sporadic breast cancer are unknown. The aim of the authors was to detect NF1 gene expression, the NF1 isoform ratio and the CELF transcripts present in sporadic breast cancer. METHODS: Neurofibromin and RAS expression were analysed on tissue microarrays containing sporadic breast cancer (n=22), benign lesions (n=18, including six fibroadenomas, six fibrocystic changes and six ductal hyperplasias) and normal breast tissue (n=6) by immunohistochemistry assay. NF1 and CELF 3-6 RNA expression was performed by end point reverse transcription-PCR in the breast samples. RESULTS: NF1 and RAS expression in breast tissues showed no differential expression by immunohistochemistry results. Interestingly, the authors observed a shift transition in the isoform transcripts, from type II in normal breast tissue to type I isoform in breast carcinomas. CELF cofactor expression failed to be related with the shift transition of NF1 in breast tissues. CONCLUSIONS: These data suggest that there is a tendency for an NF1 expression shift transition from type II to type I isoform, which could comprise a significant event in the development and progression of sporadic breast cancer. This shift transition may not be related with CELF cofactors.