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At least 1,765 records · Page 98Linked to original sources
PubMed1999

LOH at the sites of the DCC, APC, and TP53 tumor suppressor genes occurs in Barrett's metaplasia and dysplasia adjacent to adenocarcinoma of the esophagus.

Barrett's esophagus carries a 30- to 100-fold increased risk of adenocarcinoma, which is thought to develop via a metaplasia-dysplasia-carcinoma progression. A common genetic abnormality detected in Barrett's adenocarcinoma is loss of heterozygosity (LOH) at the sites of known or putative tumor suppressor genes, of which there are at least 9 associated with esophageal adenocarcinoma. The aim of this study was to identify at which histological stage of carcinogenesis LOH at these sites occur. Microdissection of multiple paraffin-embedded tissue blocks from 17 esophagogastrectomy specimens of adenocarcinoma arising in Barrett's esophagus yielded areas of metaplasia, low-, intermediate- and high-grade dysplasia, and carcinoma. LOH analysis of microdissected tissues was performed using a double polymerase chain reaction technique with 11 microsatellite primers shown previously to have LOH in at least 30% of esophageal adenocarcinomas. Identical LOH was detected in premalignant and malignant tissues in 4 of 17 patients, and was located at 5q21-q22 (D5S346 primer), 17p11.1-p12 (TCF2 primer), 17p13.1 (TP53 primer), 18q21.1 (detected in colon cancer tumor suppressor gene [DCC] primer), and 18q23-qter (D18S70 primer). These results suggest that LOH at the sites of the DCC, adenomatous polyposis coli (APC), and TP53 tumor suppressor genes occur before the development of adenocarcinoma in Barrett's esophagus, and so merit further study as potential biomarkers of neoplastic progression in patients with Barrett's esophagus undergoing endoscopic and histological surveillance.

Adenocarcinoma↗
PubMed2002

Assessment of clonal relationships in malignant lymphomas.

DNA sequencing of the antigen receptor genes remains the gold standard for the establishment of clonal relationships between samples. However, a variety of strategies may be employed as surrogates for the determination of the actual sequence of the clonally rearranged antigen receptor genes. The methods described in this chapter provide a framework for the rapid determination of clonal relationships between (microdissected) lymphoid populations. All of the methods described are PCR-based because of its versatility and ability to utilize very small amounts of DNA. For illustration purposes, the descriptions have been confined to B-cell populations. Although not described here, Ig kappa or Ig lambda PCR may also be utilized for determination of B-cell clonality and clonal relationships in the same manner. Similarly, the principles utilized may be extended to T-cell populations and T-cell receptor chain genes. Regardless of the methodology or targets involved, it is strongly recommended that all assays on microdissected material be run on parallel replicates of each sample to ensure reproducibility of results. The information about clonal relationships obtained by LCM has more than an academic significance and has utility in routine diagnostics for the establishment of minimal residual disease and the determination of microscopic disease recurrence vs the development of a secondary malignancy.

Cloning, Molecular↗
PubMed2005

Isolation of genes from plant Y chromosomes.

Few plant species are dioecious and only a small fraction of these species are known to have sex chromosomes. Considerable efforts to isolate sex-linked genes from dioecious Silene latifolia (Caryophillaceae) have resulted in the isolation of surprisingly few sex-linked genes, suggesting that the methods used previously were not efficient in plants. This chapter analyzes the methods that have been and can be used for isolation of genes from plant sex chromosomes. The most successful method used for the isolation of Y-linked genes included the screening of a male complementary DNA (cDNA) library with the probe obtained by degenerate oligonucleotide-primed polymerase chain reaction (PCR) of the microdissected Y chromosomes. However, chromosome microdissection requires sophisticated equipment and is difficult to apply to species with cytologically indistinguishable sex chromosomes. Genome and cDNA library subtraction methods were surprisingly unsuccessful, probably because of low divergence between the homologous X- and Y-linked genes in plants. Segregation testing and genomics-based methods are increasingly popular and are the most promising approaches for isolation of multiple genes from plant sex chromosomes.

Base Sequence↗
PubMed2003

Molecular assessment of depth of myometrial invasion in stage I endometrial cancer: a model based on K-ras mutation analysis.

INTRODUCTION: Overall nearly 20% of endometrial cancer (EC) patients die of the disease and over half of these had initially presented with clinical stage I disease. There is a strong correlation between disease mortality and depth of myometrial invasion. Current assessment of depth of invasion relies on light microscopy. Tumor cells can evade detection by light microscopy if they are vastly outnumbered by myometrial cells. Molecular techniques have a great potential in the detection of such isolated cells. OBJECTIVE: The objective was to develop a model for the application of molecular techniques to advance the assessment of risk status in patients with clinical stage I EC. METHODS: The study sample included 21 stage I ECs with a documented K-ras mutation from two series of 96 and 106 ECs from the United Kingdom and Norway, respectively. K-ras was documented using heteroduplex mobility analysis and amplified created restriction site, followed by sequencing to identify the specific base substitution at codon 12 and 13 of K-ras oncogene. For each case with a K-ras mutation, a modified mutant allele-specific amplification technique was carried out on a series of tissue strips microdissected at increasing depths from the myometrium underlying tumor. The microdissected myometrium had been previously examined histologically for absence of infiltrating tumor cells on light microscopy. Presence of K-ras mutations was used to identify the tumor cells within the histologically normal myometrium. Correlations between submicroscopic myometrial tumor cell infiltration and clinicopathological factors were studied. RESULTS: Of 21 cases with K-ras mutation, 6 cases (28%) showed molecular evidence of tumor cell infiltration beyond the histological boundary. The depth of submicroscopic myometrial infiltration was found to be variable. The staging of the tumors would have changed in 3 cases (14%) if tumor cells been detected histologically. A borderline significant correlation between presence of submicroscopic myometrial invasion and depth of myometrial invasion was noted (P = 0.053). The recurrence rate and survival of patients without submicroscopic invasion were better than those with, although it did not reach statistical significance (recurrence rate P = 0.13, recurrence free survival P = 0.14, cause-specific survival P = 0.12, and total survival P = 0.2). CONCLUSIONS: Molecular assessment of depth of myometrial invasion using K-ras mutation is feasible and may add information to conventional light microscopy. Further prospective studies are required to define the clinical significance of this technology.

Adult↗
PubMed1999

Homologous and heterologous induction of the human bradykinin B1-receptor and B1-receptor localisation along the rat nephron.

The kinin B1-receptor which is absent or expressed at very low levels under physiological conditions is strongly induced under inflammatory conditions. It has been shown that B1-receptor induction during inflammation involves interleukin-1beta (IL-1beta) production and activation of nuclear factor-kappaB (NF-kappaB). Since bradykinin (BK), the B2-receptor agonist induces IL-1beta expression and activates NF-kappaB, we have analysed the effect of B2-receptor activation in cultured human lung fibroblasts cells on B1-receptor expression by a semiquantitative RT-PCR analysis. Treatment with BK resulted in a significant increase in the expression of B1-receptor mRNA which was abolished by a specific B2-receptor antagonist. This result suggests that B2-receptor activation can prime the expression of B1-receptors. Although the renal localisation of the B2-receptor has been thoroughly studied, nothing is known about the distribution of the B1-receptor in the kidney. Using a combination of microdissection and a semiquantitative RT-PCR/Southern blot analysis we showed the absence of B1-receptors under physiological conditions in 10 microdissected rat nephron segments. However, 18 h LPS-treatment induced significant expression of the B1-receptor in all, but one segment. These studies provide the first molecular basis for the observed changes in renal haemodynamics after B1-agonist infusion in animal kidney models.

Animals↗
PubMed2001

Application of molecular cytogenetic techniques in a case study of human cutaneous metastatic melanoma.

Consistent structural chromosome rearrangements have rarely been identified in adult solid tumors. The introduction of advanced molecular cytogenetic techniques has provided new ways of analyzing highly complex karyotypes commonly encountered in these malignancies. This study describes a detailed molecular cytogenetic analysis of a sporadic human cutaneous melanoma biopsy, M92-047, using a combination of G-banding, fluorescence in situ hybridization (FISH), chromosome microdissection, and comparative genomic hybridization (CGH). G-banding revealed that this tumor was composed primarily of closely related near-diploid and near-tetraploid cell subpopulations containing several clonal numerical and structural chromosome alterations. Fluorescence in situ hybridization using whole chromosome painting probes and chromosome arm painting probes, was employed to verify the rearranged chromosomes; dic(1;4), der(8)t(1;8), and der(15)t(6;15), whereas marker chromosomes dic(8;1;16), der(12)t(9;12), and der(17)t(13;17) were discerned by chromosome microdissection and subsequent reverse in situ hybridization (rev ish) analysis. Comparative genomic hybridization illustrated DNA copy number changes in good agreement with the karyotypic analysis. Although this line exhibits recurrent alterations representative of melanoma, two unique breakpoints--1p13 and 8p21--were identified in two different rearranged chromosomes, suggesting potentially important regions for further dissection by molecular genetic techniques. This report demonstrates the advantages of combining multiple techniques in order to obtain a detailed description of cytogenetic changes in melanoma.

Aged↗
PubMed2003

Grade II astrocytomas are subgrouped by chromosome aberrations.

Grade II astrocytoma is defined as a low-grade tumor, yet patients have a wide range of survival and tumors can quickly progress to high-grade astrocytoma/glioblastoma. Previous studies using comparative genomic hybridization (CGH) failed to demonstrate frequent copy number aberrations (CNA) in these tumors. This may be related to technical difficulties because infiltrating astrocytic tumors are often intermixed with normal brain tissue. We developed methods to exclude most normal tissue and use small amounts of DNA for CGH by microdissecting small regions of tumor from paraffin sections and amplifying extracted DNA using degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR). Using this method, we examined 30 grade II astrocytoma cases. We found CNA in 25 cases (83%), with a mean of two CNA per case. The most frequent CNA were gains on 7q (12 cases), 5p (5 cases), 9 (5 cases), and 19p (3 cases), and losses on 19q (7 cases), 1p (6 cases), and Xp (3 cases). Gain on 7q and losses on 1p/19q were mutually exclusive. This is the first report on the genetic characterization of low-grade astrocytomas using CGH from microdissected and formalin-fixed tissue. The comparatively large number of cases in this study allows us to suggest that these tumors are genetically subgrouped.

Adolescent↗
PubMed1998

Epitympanic diaphragm in the new-born.

A series of 80 temporal bones included four specimens from infection-free new-born children. The microdissections showed that the epitympanic diaphragm in the new-born consists, in addition to the position fixed ligamental folds and ossicles, of only two position changing duplicate folds. These were the lateral incudomalleal fold, separating the upper and lower lateral attics, and the tensor fold, separating the anterior epitympanum from the supratubal recess. All other duplicate folds present during the fetal development had disappeared, a finding in accordance with the study on fetuses by Hammar in 1902 and with our own microdissection findings in normal adult temporal bones. Folds in other locations, even if until lately considered as participants of a normal epitympanic diaphragm, are of inflammatory origin.

Ear Ossicles↗
PubMed1999

Supratubal recess in neonates and infants.

OBJECTIVE: The fetal development of the supratubal recess and of the tensor fold was described by Hammar in 1902. Recent studies claim that neither structure is regularly present in neonates and controversial views have been presented of the separation of the anterior attic and supratubal recess. The objective of this study is to clarify these issues. METHODS: Twenty temporal bones, 13 neonate and seven infant, were studied either by microdissection of fresh (five bones) or formalin stored (two) specimens, or by serial sectioning after formalin fixation and decalcification (13 bones). The serial sections were cut to 20 microm, every tenth section saved and stained by hematoxylin eosin. RESULTS: In all specimens the separating structure between the anterior attic and supratubal recess was the tensor fold. It was intact in 15 bones while five showed a membrane defect. In vertically oriented folds the recess was deep and in horizontally oriented folds shallow. In 19 bones the tensor fold inserted superiorly to a soft tissue insertion ring of varying thickness and only once directly to a shallow transverse crest. The breadth of the tensor fold near the tensor tendon showed only little variation, whereas its height, and the distance from the tensor tendon to the supratubal tegmen varied in larger limits. CONCLUSIONS: The tensor fold and the supratubal recess are present already in the neonate and thus develop during the fetal period. The shape of the recess is determined by the fold direction and its size grows in conjunction with the other middle ear spaces. The transverse crest has no apparent influence on the position of the tensor fold. The easiest method to study the integrated whole of the anterior attic and supratubal recess is to view them alternatively from the anterior and superior microdissection approaches. Clinically, removal of the tensor fold creates an efficient additional aeration route from the supratubal recess to the anterior attic.

Culture Techniques↗
PubMed2000

p53 gene mutations in Bowen's disease in Koreans: clustering in exon 5 and multiple mutations.

We analyzed the p53 protein expression and gene mutations to evaluate the role of ultraviolet radiation or other carcinogens, and possible racial differences in 17 samples from 12 Korean patients with Bowen's disease. A simple microdissection technique was used to collect the tumor cells selectively. p53 protein expression was found in eight of 17 (47%) samples. Abnormalities in polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis were observed in 16 (94%) samples. A total of 14 missense mutations were detected in eight (47%) samples; 11 were clustered in exon 5 and the remaining three were located in exon 8. UV-like mutations were seen in five of 14 (36%) mutations, but no CC to TT transitions, UV-fingerprint mutations were observed. Multiple mutations were present in two cases and double mutation in a single case. Each lesion in multiple Bowen's disease showed different mutations and was suggested to be of different clonal origins. TP53-loss of heterozygosity (LOH) was detected in four out of 15 (27%) informative samples. Clustering of mutations in exon 5 suggests the role of another carcinogen in Koreans or Asians other than the UVR. Microdissection would increase the detection rate of the p53 gene mutations and LOH not only in skin cancer but also in precancerous lesions.

Adult↗
PubMed1996

LOH at the APC/MCC gene (5Q21) in gastric cancer and preneoplastic lesions. Prognostic implications.

The APC/MCC gene (Familial Adenomatous Polyposis) at 5q21 plays a role in colon cancer carcinogenesis. LOH at this locus has also been described in gastric cancer and preneoplastic lesions. The APC locus has been recently related to a cell surface adhesion molecule and its alteration may favour metastatic dissemination. LOH at 5q21 has been associated with poor prognosis in other tumors such as lung cancer. Thirty-six gastric cancers were evaluated for LOH at 5q21 with 2 polymorphic markers from microdissected paraffin-embedded material. All tumors were classified by stage, histologic type, degree of differentiation and survival rates. In 4 cases, intestinal metaplasia cells in the adjacent mucosae were also microdissected. Six cases of moderate-severe gastric dysplasia were also added to the study. LOH was determined in 84% of the informative cases of GC, affecting both early and advanced stages of disease. Genomic instability was assessed in 5 cases, 3 of them associated with LOH. The only case of gastric cancer that did not show LOH or instability at 5q21 was a stage II, poorly differentiated intestinal carcinoma without evidence of recurrence after a 36 month follow-up period (the mean survival rate in our series was 28.3% at 36 months). We also found LOH in 2/6 dysplastic lesions and 1/4 intestinal metaplasias. Our data show that LOH at 5q21 is frequent in gastric cancer and is also present in intestinal metaplasia and dysplastic lesions. LOH at this locus is not a prognostic factor in GC in our study, due to the high incidence of LOH that we found.

Adult↗
PubMed2003

Microsatellite dinucleotide (T-G) repeat: a candidate DNA marker for breast metastasis.

A dinucleotide (T-G) repeat sequence was isolated by comparing DNA from metastatic lymph node and matched normal breast samples from a ductal mammary carcinoma patient using representational difference analysis (RDA) method. Our present study used this metastasis associated DNA sequence (MADS) as a diagnostic probe to screen five patient samples by slot blot method. A new approach to isolate single cells by microdissection, namely single cell microdissection (SCM) was developed to obtain homogeneous population of tumor cells (approximately 1000) from matched primary tumors and corresponding positive lymph nodes of five patients. We isolated DNA from these homogeneous tumor cells and used for the RDA and DNA slot blot experiments. The screening of patient samples showed loss of this MADS in the transition from primary to metastasis in four out of five cases (80%) suggesting its possible role in breast metastasis.

Biomarkers, Tumor↗
PubMed1998

Alpha1A-adrenergic receptors mediate vasoconstriction of the isolated spiral modiolar artery in vitro.

Several lines of evidence suggest that cochlear blood flow is under the control of the sympathetic nervous system and that this control is mediated via alpha-adrenergic receptors. The goal of the present study was to determine whether alpha-adrenergic receptors mediate vasoconstriction of the spiral modiolar artery and, if so, to determine which subtype dominates this response. Vascular diameter was measured with video microscopy in the isolated superfused spiral modiolar artery in vitro. The diameter of the spiral modiolar artery under control conditions was 61 +/- 2 microm (n = 60). Spontaneous vasomotion was observed in most specimens. Addition of norepinephrine to the superfusate caused a phasic vasoconstriction and an increase in the amplitude of vasomotion. These effects were limited to the vicinity of arteriolar branch points of the spiral modiolar artery. Norepinephrine-induced vasoconstriction occurred with EC50 of (1.9 +/- 0.4) x 10(-5) M (n = 44) and the vascular diameter was maximally reduced by a factor of 0.87 +/- 0.01 (n = 29). Neither the phasic nature nor the EC50 of the norepinephrine-induced vasoconstrictions was altered in the presence of the beta2-adrenergic receptor antagonist 10(-5) M ICI118551 or the nitric oxide synthase inhibitor 10(-4) M NOARG. In contrast, the alpha2-adrenergic receptor antagonist 10(-7) M yohimbine and the alpha1-adrenergic receptor antagonist 10(-9) and 10(-8) M prazosin caused a significant shift in the dose-response curve. The affinity constants (K(DB)) for yohimbine and prazosin were (5+/-2) x 10(-8) M (n=4) and (2.0+/-0.7) x 10(-10) M (n=18), respectively. The alpha1A-adrenergic receptor antagonist 10(-8) M 5-methyl urapidil and the alpha1D-adrenergic receptors antagonist 5 x 10(-6) M BMY7378 caused a significant shift in the dose-response curve. The K(DB) values for 5-methyl urapidil and for BMY7378 were (2.7 +/- 0.7) x 10(-10) M (n = 8) and (4.4 +/- 2.7) x 10(-7) M (n = 8), respectively. Further, total RNA was isolated from microdissected spiral modiolar arteries and the presence of transcripts for alpha1-adrenergic receptor subtypes was determined by reverse transcription polymerase chain reaction (RT-PCR). Primers specific for gerbil alpha1-adrenergic receptor subtypes were developed using RNA from rat and gerbil brain. Analysis of RNA extracted from the spiral modiolar artery revealed RT-PCR products of the appropriate size for the alpha1A-adrenergic receptor, however, no evidence for the alpha1B- and alpha1D-adrenergic receptor was found. Further, analysis of RNA extracted from blood, which was a contaminant of the microdissected spiral modiolar arteries, revealed no RT-PCR products. Sequence analysis of the RT-PCR product of the alpha1A-adrenergic receptor from the spiral modiolar artery confirmed its identity. Identity between the 175 nt gerbil sequence fragment and the known rat, mouse and human alpha1A-adrenergic receptor sequences was 90.9, 92.0 and 85.2%, respectively. These observations demonstrate that the spiral modiolar artery contains alpha1A-adrenergic receptors which mediate vasoconstriction at branch points.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2001

Gene expression profiling in the post-mortem human brain--no cause for dismay.

Global expression profiling techniques such as microarray technology promise to revolutionize biology. Soon it will be possible to investigate alterations at the transcript level of the entire human genome. There is great hope that these techniques will at last shed light on the pathological processes involved in complex neuropsychiatric disorders such as schizophrenia. These scientific advances in turn have re-kindled a great interest and demand for post-mortem brain tissue. Good quality post-mortem tissue undoubtedly is the fundamental prerequisite to investigate complex brain disorders with molecular profiling techniques. In this review we show that post-mortem brain tissue can yield good quality mRNA and intact protein antigens which allow the successful application of traditional molecular biology methods as well as novel profiling techniques. We also consider the use of laser-capture microdissection on post-mortem tissue. This recently developed technique allows the experimenter to explore the molecular basis of cellular function at the single cell level. The combination of laser-capture microdissection with high throughput profiling techniques offers opportunities to obtain precise genetic fingerprints of individual neurons allowing comparisons of normal and pathological states.

Autopsy↗
PubMed1990

Production of collagenase and tissue inhibitor of metalloproteinases (TIMP) by rat growth plates in culture.

Growth plate cartilage from normal and vitamin D-phosphate deficient (-VDP) rats was cultured to study the production of collagenase and tissue inhibitor of metalloproteinases (TIMP) in vitro. All tissues secreted latent collagenase into the medium at a constant rate during the 5 days in culture. Microdissected-VDP growth plates, containing predominatly hypertrophic cells, released up to 8-fold more collagenase into the medium than either intact-VDP or normal growth plates. TIMP was also secreted during the culture, but its rate of production was not as dependent on tissue type as collagenase. The tissue level of collagenase and TIMP before culture was compared with that found in conditioned medium and remnant tissue after culture. During the 5 day culture period microdissected-VDP growth plates, containing predominatly hypertrophic cells, produced 3-times more collagenase/microgram DNA over the starting level than either intact-VDP or normal growth plates. TIMP was never found in tissues after they had been cultured, but was present in all tissues before culture except those containing predominatly hypertrophic cells. The amount of TIMP required to block collagenase was calculated. Growth plates in culture produced enough TIMP to block all collagenase found in the medium and remnant tissue, while extracts of uncultured intact -VDP growth plates, and those divided to contain hypertrophic cells, had an excess of collagenase over TIMP. The results suggest that hypertrophic cells produce far more collagenase than other cells in the growth plate, but all cell types have about the same capacity to synthesize TIMP. As a result, increased collagenase synthesis by hypertrophic cells may surpass increases in TIMP synthesis and lead to collagen removal. This would allow for thinning of the longitudinal septa and expansion of the hypertrophic cells.

Animals↗
PubMed1999

The subarcuate canaliculus and its artery--a radioanatomical study.

The anatomy of the subarcuate canaliculus (SAC), subarcuate fossa (SAF) and subarcuate artery (SAA) was studied in 12 cadavers and 35 dry temporal bones. Each cadaver was scanned with high resolution CT (HRCT) prior to microdissection. The SAC was always found to be a single canal located between the two arcs of the anterior semicircular canal in both microdissections and HRCT scans and the internal acoustic meatus was observed to be located just inferior to the SAC. The SAC was on average of 9.2 mm in length and 1 mm in width. The SAF was situated at a distance of 4.2 mm from the internal acoustic meatus, 3.5 mm from the groove for the superior petrosal sinus, 6.7 mm from the opening of the vestibular canaliculus and 11.5 mm from the most superior part of the jugular foramen. The SAA was found to originate from the anterior inferior cerebellar artery in 9 cadavers and from the internal auditory artery in 3 cadavers. The SAA always emerged from the main artery outside the internal acoustic meatus. It ran through the SAC as a single artery. This study investigated CT correlated anatomical aspects of the subarcuate canaliculus and its artery which is claimed to be responsible for the blood supply of the mastoid antrum, facial canal and bony labyrinth.

Cadaver↗
PubMed2000

Recipient origin of neointimal vascular smooth muscle cells in cardiac allografts with transplant arteriosclerosis.

BACKGROUND: Coronary artery disease is today's most important post-heart transplantation problem after the first perioperative year. Histologically, coronary artery disease is characterized by transplant arteriosclerosis. The current view on this vasculopathy is that vascular smooth muscle (VSM) cells from the media of affected arteries proliferate and migrate into the sub-endothelial space (intima) in response to signals from inflammatory cells and damaged graft endothelium. According to this model, the intimal VSM cells in transplant arteriosclerotic lesions should originate from donor tissue. Using recipient-specific polymerase chain reaction (PCR) analysis of microdissected, single, neointimal VSM nuclei, we recently showed that after allogeneic aorta transplantation the neointimal VSM cells are of recipient and not of donor origin. In this study, we analyzed whether VSM-cell replacement with recipient-derived cells also takes place after allogeneic heart transplantation. METHODS: Cardiac allografts, when transplanted from female donors to male immune-modulated recipient rats, eventually developed transplant arteriosclerosis. We microdissected alpha-actin positive neointimal VSM cells from tissue sections and determined the origin (donor or recipient) using recipient-specific (male), single-cell, PCR analysis. RESULTS: In total, we analyzed 35 VSM-cell nuclei from 3 allografts, and PCR analysis revealed that 30/35 (86%) of the samples displayed the male-specific 128 base pair DNA fragment. These results indicate that after allogeneic cardiac transplantation, at least 86% of VSM cells in transplant arteriosclerotic lesions are of recipient origin. CONCLUSIONS: In contrast to current thought, the neointimal VSM cells in cardiac allografts that show transplant arteriosclerosis are of recipient and not of donor origin.

Actins↗
PubMed2004

The role of genomic instability in the pathogenesis of squamous cell carcinoma of the head and neck.

Measurements of genomic instability, or identification of genes responsible for instability, may potentially be used as molecular markers to predict disease course and response to therapy. Other possible applications include use of genomic instability measurements, or genes, as tools to screen for primary or recurrent disease. Methodologies for detection of genetic mutations in saliva, blood, and sputum have already been described[61,62]. Brennan et al [63] have described a molecular technique for analyzing histopathologically negative margins and lymph nodes for the presence of p53 gene mutation. This study showed that a positive molecular margin significantly predicted disease recurrence. The recognition that HNSCC is a genetically heterogeneous disease represents a major step toward developing an understanding of its underlying genetic basis. To develop an insight into this genetically heterogeneous disease, investigators must not only focus their efforts on specific head and neck disease sites. Laser-capture microdissection represents a powerful tool for isolating very specific cell populations from tumors [64]. Leethanakul et al[65] performed laser-capture microdissection on oral cavity SCC to construct stage-specific cDNA libraries. Sequencing of 96 clones from each of the six libraries constructed suggested the existence of 132 novel genes, which may play a role in the pathogenesis of HNSCC. The current literature suggests that many individuals diagnosed withHNSCC are genetically predisposed to developing malignancy because of some inherent deficiency of their capacity to maintain their genome in the presence of environmental stressors. Head and neck cancers are highly heterogeneous tumors and exhibit a wide variety of forms of genomic instability. Thus, genomic instability may be viewed as a fundamental force driving head and neck tumorigenesis and evolution. Future study of the specific genetic mechanisms that underlie genomic instability in the HNSCCpatient population is needed. It is only through study of this fundamental force that drives the development of these tumors that clinicians may gain the insight required to develop new diagnostic and therapeutic modalities to benefit the HNSCC patient population as a whole.

Carcinoma, Squamous Cell↗