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1

Neoplasia: The Second Decade  

PubMed Central

This issue marks the end of the 10-year anniversary of Neoplasia where we have seen exciting growth in both number of submitted and published articles in Neoplasia. Neoplasia was first published in 1999. During the past 10 years, Neoplasia has dynamically adapted to the needs of the cancer research community as technologies have advanced. Neoplasia is currently providing access to articles through PubMed Central to continue to facilitate rapid broad-based dissemination of published findings to the scientific community through an Open Access model. This has in part helped Neoplasia to achieve an improved impact factor this past year, demonstrating that the manuscripts published by Neoplasia are of great interest to the overall cancer research community. This past year, Neoplasia received a record number of articles for review and has had a 21% increase in the number of published articles. PMID:19048110

Rehemtulla, Alnawaz

2008-01-01

2

Neoplasia: An Anniversary of Progress  

PubMed Central

This issue marks the 10th year anniversary of Neoplasia where we have seen exciting growth on the impact that Neoplasia has had on cancer research worldwide. Neoplasia was founded in 1999 at which time manuscripts were accepted through e-mail. In 2000, Neoplasia became the first journal to offer web-based online manuscript submission and peer-review using a custom-designed application JournalSoft. Now, the use of web-based manuscript processing has become an industry standard as it provides authors with a rapid and useful dialog exchange for improving the quality of the science and the overall speed of the review process. Moreover, during the past 10 years, the Internet has experienced a massive growth of a complex global grid of now over an estimated 1.2 billion Internet users which have resulted in a major shift in the medium of scientific communication for scholarly publishing. Neoplasia continues to evolve with the technology and has implemented a rapid time-to-publication schedule to continue dissemination of published cancer research findings quickly to the scientific community.

Rehemtulla, Alnawaz

2007-01-01

3

Men tend to be neoplasia prone and women neoplasia resistant  

Microsoft Academic Search

Background: Patients with a colorectal neoplasm are at risk for metachronous neoplasia. This risk usually is stratified according to\\u000a the number, size, and histology of the index lesion(s). This study was performed to search for factors contributing not only\\u000a to a very high risk of metachronous lesions but also to a very low risk.\\u000a \\u000a \\u000a \\u000a \\u000a Methods: An extensive neoplasia follow-up database

J. M. Church

2000-01-01

4

Pulmonary preinvasive neoplasia  

PubMed Central

Advances in molecular biology have increased our knowledge of the biology of preneoplastic lesions in the human lung. The recently published WHO lung tumour classification defines three separate lesions that are regarded as preinvasive neoplasia. These are (1) squamous dysplasia and carcinoma in situ (SD/CIS), (2) atypical adenomatous hyperplasia (AAH), and (3) diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). SD/CIS is graded in four stages (mild, moderate, severe, and CIS), based upon the distribution of atypical cells and mitotic figures. Most airways showing SD/CIS demonstrate a range of grades; many epithelia are hard to assess and the reproducibility of this complex system remains to be established. Detailed criteria are, however, welcome and provide an objective framework on which to compare various molecular changes. Alterations in gene expression and chromosome structure known to be associated with malignant transformation can be demonstrated in CIS, less so in dysplasias, but also in morphologically normal epithelium. The changes might be sequential, and their frequency and number increase with atypia. Less is known of the "risk of progression" of SD/CIS to invasive "central" bronchial carcinoma. It may take between one and 10 years for invasion to occur, yet the lesion(s) may be reversible if carcinogen exposure ceases. AAH may be an important precursor lesion for peripheral "parenchymal" adenocarcinoma of the lung: the "adenoma" in an adenoma–carcinoma sequence. There is good morphological evidence that AAH may progress from low to high grade to bronchioloalveolar carcinoma (BAC; a non-invasive lesion by definition). Invasion then develops within BAC and peripheral lung adenocarcinoma evolves. The molecular events associated with this progression are not well understood and studies are hampered by a lack of clear criteria to distinguish high grade AAH from BAC. Nonetheless, as with SD/CIS, the patterns of expression of tumour associated genes are consistent with neoplastic progression. We have little idea of the incidence of AAH in the normal or "smoking" populations. It is found more frequently in cancer bearing lungs, especially in those with adenocarcinoma, and is more common in women. No data are available on the risk of progression of AAH. DIPNECH is an exceptionally rare lesion associated with the development of multiple carcinoid tumours. Almost nothing is known of its biology. Knowledge of these lesions will be crucial in the design and understanding of lung cancer screening programmes, where it is likely that the morphological and, more importantly perhaps, the molecular characteristics of these lesions will provide useful targets for detection and possibly even treatment. Key Words: lung cancer • preneoplasia • carcinogenesis PMID:11304841

Kerr, K

2001-01-01

5

Lobular and ductal intraepithelial neoplasia.  

PubMed

Lobular and ductal intraepithelial neoplasias reflect proliferations of immunophenotypically variable, biologically and morphologically diverse cells with a potential, not always realized, for progression to carcinoma by breaking through the barriers of the myoepithelial cell layer and basement membrane, ultimately invading the stroma. Starting with the lobular and then the ductal proliferations, this review will address the evolution of our understanding of these lesions; the problems associated with the conventional terminology of ductal hyperplasia, atypical hyperplasia, and carcinoma in situ; and reasons for and advantages of the intraepithelial neoplasia terminology. PMID:18836725

Tavassoli, F A

2008-11-01

6

Multiple endocrine neoplasia type 1  

Microsoft Academic Search

The recent cloning of the gene responsible for multiple endocrine neoplasia type 1 (MEN 1) has opened new avenues for both clinical and basic science research in the field of endocrine oncology. A large amount of genetic information, particularly those in relation to germline and somatic mutations, has since been published during the last 2 years. This new knowledge has

Fung Ki Wong; John Burgess; Magnus Nordenskjöld; Catharina Larsson; Bin Tean Teh

2000-01-01

7

Canine histiocytic neoplasia: An overview  

PubMed Central

Canine histiocytic neoplasms include cutaneous histiocytoma, as well as localized and disseminated histiocytic sarcoma. These tumors have variable biologic behavior, although the malignant disorders often have a poor prognosis. Immunohistochemistry plays an essential role in differentiating histiocytic tumors from other neoplasias that may have similar histological appearances. This allows a definitive diagnosis to be established and provides a more accurate prediction of prognosis. This article reviews the biologic behavior, diagnosis, and treatment of histiocytic tumors in the dog. PMID:17987966

Fulmer, Amanda K.; Mauldin, Glenna E.

2007-01-01

8

Combinatorial chemoprevention of intestinal neoplasia  

Microsoft Academic Search

A combination of two drugs afforded remarkable protection from intestinal neoplasia in APCMin\\/+ mice, a murine model of human familial adenomatous polyposis (FAP). One of the drugs was sulindac, a prototypical non-steroidal anti-inflammatory drug with established chemopreventative activity. The second drug was EKI-569, a newly developed, irreversible inhibitor of the epidermal growth factor receptor kinase. Although 100% of the untreated

Christopher J. Torrance; Peta E. Jackson; Elizabeth Montgomery; Kenneth W. Kinzler; Bert Vogelstein; Allan Wissner; Maria Nunes; Carolyn M. Discafani; Philip Frost

2000-01-01

9

New concepts in neoplasia as applied to diagnostic pathology  

SciTech Connect

This book contains 13 selections. Some of the titles are: Cellular Aspects of Neoplasia; Oncogenes and Cancer; Chromosome and Oncogene Rearrangements in Leukemia and Lymphoma; Ionizing Radiation and Neoplasia; and Papillomaviruses and Neoplasia in Man.

Fenoglio-Preiser, C.M.; Weinstein, R.S.; Kaufman, N.

1986-01-01

10

Dietary fibre and colonic neoplasia.  

PubMed Central

Dietary plant fibre, or plantix, is thought to play a significant role in the pathogenesis of colon cancer in humans. It is a complex polymeric substance that has several distinct components resistant to hydrolysis by the digestive enzymes of humans. These components include cellulose, hemicelluloses, pectins, lignin, gums, mucilages and, in certain instances, algal polysaccharides. These polymers have different physicochemical properties, and recent evidence from experimental studies in animals treated with carcinogens suggests that some may exert protective effects in the intestine and others may enhance colon carcinogenesis. This review synthesizes information on the chemical composition, methods of analysis and physicochemical properties of dietary plant fibre and reviews available studies examining the role of fibre in colonic neoplasia in animals and humans. PMID:466603

Freeman, H J

1979-01-01

11

Fractal Analysis of Cervical Intraepithelial Neoplasia  

PubMed Central

Introduction Cervical intraepithelial neoplasias (CIN) represent precursor lesions of cervical cancer. These neoplastic lesions are traditionally subdivided into three categories CIN 1, CIN 2, and CIN 3, using microscopical criteria. The relation between grades of cervical intraepithelial neoplasia (CIN) and its fractal dimension was investigated to establish a basis for an objective diagnosis using the method proposed. Methods Classical evaluation of the tissue samples was performed by an experienced gynecologic pathologist. Tissue samples were scanned and saved as digital images using Aperio scanner and software. After image segmentation the box counting method as well as multifractal methods were applied to determine the relation between fractal dimension and grades of CIN. A total of 46 images were used to compare the pathologist's neoplasia grades with the predicted groups obtained by fractal methods. Results Significant or highly significant differences between all grades of CIN could be found. The confusion matrix, comparing between pathologist's grading and predicted group by fractal methods showed a match of 87.1%. Multifractal spectra were able to differentiate between normal epithelium and low grade as well as high grade neoplasia. Conclusion Fractal dimension can be considered to be an objective parameter to grade cervical intraepithelial neoplasia. PMID:25302712

Fabrizii, Markus; Moinfar, Farid; Jelinek, Herbert F.; Karperien, Audrey; Ahammer, Helmut

2014-01-01

12

Trophoblastic Neoplasia in an African Urban Population  

PubMed Central

A clinical study of trophoblastic neoplasia in a Nigerian population in Lagos over a four-year period is reported. A high incidence of one in 379 deliveries for benign trophoblastic tumor and one in 846 deliveries for malignant tumor was found. Seventeen percent of benign trophoblastic tumors in this series progressed to the malignant type, but malignant trophoblastic tumor was preceded by the benign type (hydatidiform mole) in 46 percent of cases. The anterior vaginal wall is a common site for metastases of malignant trophoblastic neoplasia and, in one patient, the lesion progressed further to form a vesicovaginal fistula. While the management of benign disease was conservative, all cases of malignant trophoblastic neoplasia received chemotherapy. PMID:231687

Agboola, Akin

1979-01-01

13

Genetics of Endocrine and Neuroendocrine Neoplasias (PDQ®)  

Cancer.gov

Expert-reviewed information summary about the genetics of endocrine and neuroendocrine neoplasias. This summary contains information about the MEN1 gene, the RET gene, genetic testing, and clinical interventions. Psychosocial issues associated with genetic testing and counseling of individuals who may have a hereditary medullary thyroid cancer syndrome are also discussed.

14

Suppression of intestinal neoplasia by DNA hypomethylation  

Microsoft Academic Search

We have used a combination of genetics and pharmacology to assess the effects of reduced DNA methyltransferase activity on ApcMin-induced intestinal neoplasia in mice. A reduction in the DNA methyltransferase activity in Min mice due to heterozygosity of the DNA methyltransferase gene, in conjunction with a weekly dose of the DNA methyltransferase inhibitor 5-azadeoxycytidine, reduced the average number of intestinal

Peter W Laird; Laurie Jackson-Grusby; Amin Fazeli; Stephanie L Dickinson; W Edward Jung; En Li; Robert A Weinberg; Rudolf Jaenisch

1995-01-01

15

Renal Neoplasia in Coypus ( Myocastor coypus)  

Microsoft Academic Search

Renal neoplasia is described in coypus (Myocastor coypus) from a feral population of the species in East Anglia. A population control campaign was started in 1962, and in 1981 this became an eradication scheme. From 1976 onwards, a research programme included the postmortem examination of 9400 wild caught and captive coypus. During the period 1980–91, 15 cases (0.16%) of renal

I. F KEYMER; G. A. H WELLS; H. L AINSWORTH

1999-01-01

16

Endoscopic therapies for Barrett’s neoplasia  

PubMed Central

The standard of care for treatment of Barrett’s esophagus (BE) with early esophageal neoplasia, including high-grade dysplasia (HGD) and intramucosal adenocarcinoma (IMC), has undergone a revolution over the past several years. With the introduction and popularization of endoscopic ablative technologies, along with the refinement of endoscopic mucosal resection (EMR) techniques, the majority of cases of early neoplasia in the setting of BE now are managed by endoscopic approaches. As a result, many patients who previously would have been referred for esophagectomy now may be spared from this major surgical procedure with its inherent morbidity, potential for mortality, and negative impact on long-term gastrointestinal function. The esophageal surgeon must be knowledgeable about the indications for such endoscopic therapies, as well as their limitations and potential pitfalls, so as to apply them in the appropriate clinical scenarios. PMID:24876934

2014-01-01

17

Sebaceous neoplasia and Torre–Muir syndrome  

PubMed Central

Summary Sebaceous tumours include hyperplasia, adenoma, sebaceoma and carcinoma. Importantly, the latter three are potential markers of Torre–Muir syndrome; the hereditary association of sebaceous neoplasia and internal malignancy, most commonly colorectal carcinoma. The diagnostic features, differential diagnosis, molecular diagnostics and recent advances in pathogenesis of this rare group of tumours are discussed along with Torre–Muir syndrome and recommendations for screening for this important association. PMID:18670585

Lazar, A.J.F.; Lyle, S.; Calonje, E.

2007-01-01

18

Multiple endocrine neoplasia type 1 : clinical and molecular characterization.  

E-print Network

??Multiple Endocrine Neoplasia Type 1 - Clinical and Molecular Characterization by Bin Tean Teh, Department of Molecular Medicine, Endocrine Tumor Unit, KarolinskaInstitute, Stockholm, Sweden This… (more)

Teh, Bin Tean

1997-01-01

19

Microparticles and exosomes in gynecologic neoplasias.  

PubMed

This review presents an overview of the functions of microparticles and exosomes in gynecologic neoplasias. Growing evidence suggests that vesicles released from cancer cells in gynecologic malignancies contribute to the hypercoagulable state of these patients and contribute to tumor progression by suppressing the immune system, facilitating extracellular matrix degradation and removal of cytostatics from the tumor cell. Exosomes from ovarian carcinoma cells were shown to be present in peripheral blood and to augment tumor growth, suggesting that these vesicles directly support growth of tumor cells. PMID:21049392

Nieuwland, Rienk; van der Post, Joris A M; Lok, Christianne A R; Gemma, Christianne A R Lok; Kenter, Gemma; Kenter, G; Sturk, Augueste

2010-11-01

20

Due anni di terapia con bosentan dell'ipertensione arteriosa polmonare associata a connettiviti sistemiche Two-years therapy with bosentan of pulmonary arterial hypertension related to connective tissue diseases  

Microsoft Academic Search

SUMMARY Objective: Pulmonary arterial hypertension (PAH) is a rare but severe complication of connective tissue diseases (CTD), with a negative impact on patients survival. Bosentan, a receptor antagonist of endothelin, has been proved effective for the treatment of PAH. The aim of this study was to evaluate the effects and the safety of bosentan administered for 2 years in a

H. Marotta; R. Montisci; F. Tiso; S. Pontarollo; M. Rizzo; F. Tona; S. Iliceto; F. Cozzi

21

Quantitative proteomics investigation of pancreatic intraepithelial neoplasia.  

PubMed

Patients with pancreatic cancer are usually diagnosed at late stages, when the disease is incurable. Pancreatic intraepithelial neoplasia (PanIN) 3 is believed to be the immediate precursor lesion of pancreatic adenocarcinoma, and would be an ideal stage to diagnose patients, when intervention and cure are possible and patients are curable. In this study, we used quantitative proteomics to identify dysregulated proteins in PanIN 3 lesions. Altogether, over 200 dysregulated proteins were identified in the PanIN 3 tissues, with a minimum of a 1.75-fold change compared with the proteins in normal pancreas. These dysregulated PanIN 3 proteins play roles in cell motility, the inflammatory response, the blood clotting cascade, the cell cycle and its regulation, and protein degradation. Further network analysis of the proteins identified c-MYC as an important regulatory protein in PanIN 3 lesions. Finally, three of the overexpressed proteins, laminin beta-1, galectin-1, and actinin-4 were validated by immunohistochemistry analysis. All three of these proteins were overexpressed in the stroma or ductal epithelial cells of advanced PanIN lesions as well as in pancreatic cancer tissue. Our findings suggest that these three proteins may be useful as biomarkers for advanced PanIN and pancreatic cancer if further validated. The dysregulated proteins identified in this study may assist in the selection of candidates for future development of biomarkers for detecting early and curable pancreatic neoplasia. PMID:19373808

Pan, Sheng; Chen, Ru; Reimel, Beth Ann; Crispin, David A; Mirzaei, Hamid; Cooke, Kelly; Coleman, Joshua F; Lane, Zhaoli; Bronner, Mary P; Goodlett, David R; McIntosh, Martin W; Traverso, William; Aebersold, Ruedi; Brentnall, Teresa A

2009-04-01

22

Renal neoplasia in coypus (Myocastor coypus).  

PubMed

Renal neoplasia is described in coypus (Myocastor coypus) from a feral population of the species in East Anglia. A population control campaign was started in 1962, and in 1981 this became an eradication scheme. From 1976 onwards, a research programme included the postmortem examination of 9400 wild caught and captive coypus. During the period 1980-91, 15 cases (0.16%) of renal neoplasia were detected. The tumours were found in both sexes between estimated ages of 25 months and 13 years with no significant sex prevalence. There was no clear evidence that renal tumours were more common in older animals. Tumours were most common in captive coypus and were bilateral in approximately half of the animals. In all cases, the tumours were of epithelial type resembling adenomata and adenocarcinomata of other animals. Most were clearly benign, and, although some showed evidence of malignancy, no unequivocal evidence of metastasis was established. The prevalence of renal tumours in this series is greater than that recorded in previous published surveys of coypus and other rodents. This may relate to the origin of the coypus population, differences in age structure in animals examined, and the varied conditions under which the rodents lived. Aetiological factors remain undetermined. PMID:10489271

Keymer, I F; Wells, G A; Ainsworth, H L

1999-09-01

23

Spontaneous neoplasia in four captive greater hedgehog tenrecs (Setifer setosus).  

PubMed

Little information is available about diseases and pathology of species within the family Tenrecidae, including the greater hedgehog tenrec (Setifer setosus), a Madagascan insectivore. This report summarizes necropsy and histopathologic findings of neoplasia in four captive greater hedgehog tenrecs. Although only four animals are included in this report, neoplasia seems to be a common and significant source of morbidity and mortality in greater hedgehog tenrecs. Types of neoplasia identified include a thyroid follicular-solid carcinoma, two urinary bladder transitional cell carcinomas, uterine endometrial polyps, and multicentric B-cell lymphoma. Due to small sample size, no etiology could be determined, but genetics, viral infection, pesticide treatment, nutrition, or other environmental factors might contribute to the development of neoplasia in this species. This is the first report of neoplasia in greater hedgehog tenrecs. PMID:18817002

Khoii, Mina K; Howerth, Elizabeth W; Burns, Roy B; Carmichael, K Paige; Gyimesi, Zoltan S

2008-09-01

24

Nucleolar organising regions in cervical intraepithelial neoplasia.  

PubMed Central

The variations in the numbers of nucleolar organising regions (NORs) among different grades of cervical intraepithelial neoplasia (CIN) were investigated using a silver staining technique. Twenty four biopsy specimens were studied (six normal and six of each of the three grades of CIN) by staining paraffin wax sections using a silver (AgNOR) method that stains the NORS as multiple black dots within nuclei (AgNORs). The number of AgNORs in the nuclei of cells in the basal half of the squamous epithelium was counted, and the average number of AgNORs in each cell calculated for each specimen (the AgNOR count). There was no difference in the number of AgNORs in the squamous epithelium of normal biopsy specimens and those showing CIN1 and CIN2, but there was a small but significant increase in the CIN3 group. Images Fig 2 Fig 3 PMID:2463271

Rowlands, D C

1988-01-01

25

Photodynamic therapy of cervical intraepithelial neoplasia  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors, especially in Gynecology. The photodynamic reaction is based on the production of reactive oxygen species after the activation of a photosensitizer. Advantages of the PDT in comparison to the surgical resection are: ambulatory treatment and tissue recovery highly satisfactory, through a non-invasive procedure. The cervical intraepithelial neoplasia (CIN) grades I and II presents potential indications for PDT. The aim of the proposed study is to evaluate the safety and efficacy of the PDT for the diagnostics and treatment of CIN I and II. The equipment and the photosensitizer are produced in Brazil with a representative low cost. It is possible to visualize the fluorescence of the cervix and to treat the lesions, without side effects. The proposed clinical protocol shows great potential to become a public health technique.

Inada, Natalia M.; Lombardi, Welington; Leite, Marieli F. M.; Trujillo, Jose R.; Kurachi, Cristina; Bagnato, Vanderlei S.

2014-03-01

26

Prostatic intraepithelial neoplasia and prostate cancer.  

PubMed

Prostatic intraepithelial neoplasia (PIN) is composed of dysplastic cells with a luminal cell phenotype, expressing the androgen receptor as well as prostate specific antigen. PIN is characterized by progressive abnormalities of phenotype which are intermediate between normal prostatic epithelium (NP) and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of carcinogenesis. High-grade PIN is considered the most likely precursor of prostatic carcinoma (PCa), according to virtually all available evidence. Androgen deprivation decreases the prevalence and extent of PIN and the degree of capillary vascularization (e.g., angiogenesis) in the surrounding stroma via the suppression of vascular endothelial growth factor (VEGF) production. It is likely that PCa might also arise from precursor lesions other than high-grade PIN (low-grade PIN, atypical adenomatous hyperplasia, malignancy-associated foci, and atrophy). PMID:12094135

Montironi, R; Santinelli, A; Mazzucchelli, R

2002-09-01

27

Molecular genetics of pancreatic intraepithelial neoplasia  

PubMed Central

Background Recent evidence suggests that noninvasive precursor lesions, classified as pancreatic intraepithelial neoplasia (PanIN), can progress to invasive pancreatic cancer. This review will discuss the major genetic alterations in PanIN lesions. Methods A comprehensive review of the literature was performed in order to find studies on the molecular profile of human PanIN lesions. In addition, recent publications on genetically engineered mouse models of preinvasive neoplasia and pancreatic cancers were reviewed. Results PanINs demonstrate abnormalities at the genomic (DNA), transcriptomic (RNA), and proteomic levels, and there is a progressive accumulation of molecular alterations that accompany the histological progression from low-grade PanIN-1A to high-grade PanIN-3 lesions. Molecular changes in PanINs can be classified as “early” (KRAS2 mutations, telomere shortening, p21WAF1/CIP1 up-regulation, etc.), “intermediate” (cyclin D1 up-regulation, expression of proliferation antigens, etc.), or “late” (BRCA2 and TP53 mutations, DPC4/SMAD4/MADH4 inactivation, etc.). All the genetic changes observed in PanINs are also found in invasive ductal adenocarcinomas, where they usually occur at a higher frequency. Genetically engineered mice expressing mutant Kras in the pancreas, with or without additional genetic alterations, provide a unique in vivo platform to study the pancreatic cancer progression model. Conclusions Molecular studies have been instrumental in establishing that PanIN lesions are the noninvasive precursors for invasive ductal adenocarcinomas. The availability of molecular date provides the basis for designing rational early detection strategies and therapeutic intervention trials before pancreatic neoplasms invade, with the intention of alleviating the dismal prognosis associated with this disease. PMID:17520196

Feldmann, Georg; Beaty, Robert; Hruban, Ralph H.; Maitra, Anirban

2009-01-01

28

Modeling human endothelial cell transformation in vascular neoplasias  

PubMed Central

Endothelial cell (EC)-derived neoplasias range from benign hemangioma to aggressive metastatic angiosarcoma, which responds poorly to current treatments and has a very high mortality rate. The development of treatments that are more effective for these disorders will be expedited by insight into the processes that promote abnormal proliferation and malignant transformation of human ECs. The study of primary endothelial malignancy has been limited by the rarity of the disease; however, there is potential for carefully characterized EC lines and animal models to play a central role in the discovery, development and testing of molecular targeted therapies for vascular neoplasias. This review describes molecular alterations that have been identified in EC-derived neoplasias, as well as the processes that underpin the immortalization and tumorigenic conversion of ECs. Human EC lines, established through the introduction of defined genetic elements or by culture of primary tumor tissue, are catalogued and discussed in relation to their relevance as models of vascular neoplasia. PMID:24046386

Wen, Victoria W.; MacKenzie, Karen L.

2013-01-01

29

Predictors of Proximal Neoplasia in Patients Without Distal Adenomatous Pathology  

Microsoft Academic Search

BACKGROUND:Previous colorectal cancer screening studies have observed that some patients may have advanced proximal neoplasia without distal findings. Since these studies have included only gender, age, and family history as risk factors, they are limited in their ability to identify predictors of isolated proximal neoplasia.METHODS:Data were collected from the charts of 1,988 patients who presented for colonoscopy. Information gathered included

Joseph C. Anderson; Zvi Alpern; Catherine R. Messina; Patricia Hubbard; Roger Grimson; Peter F. Ells; Douglas L. Brand

2004-01-01

30

Polyamines as biomarkers of cervical intraepithelial neoplasia.  

PubMed

Polyamines (putrescine, spermidine and spermine) play critical roles in cell growth and transformation. Ornithine decarboxylase (ODC), key enzyme in polyamine biosynthesis, is considered a putative protooncogene crucial to the regulation of cell growth and transformation. Cancer patients have elevated levels of polyamines in their physiological fluids compared to normal counterparts. alpha-Difluoromethylornithine (DFMO), a specific suicide inhibitor of ODC, exhibits antitumor and antimetastasis activities, and displays effectiveness in many carcinogen-induced animal chemoprevention models. Therefore, we are using DFMO in a chemoprevention trial for cervical intraepithelial neoplasia grade III (CIN III), and evaluating patients for changes in polyamine metabolism as an intermediate marker of DFMO effect. A preliminary study showed that several milligrams of abnormal cervical biopsy tissue contained detectable levels of ODC activity and polyamines. Additionally, the presence of cadaverine suggested bacterial contamination of these tissues. For this reason, normal and abnormal biopsies collected during colposcopy were rinsed prior to frozen storage. In most patients, abnormal tissue showed greater ODC activities and lower spermidine/spermine ratios than normal tissues. Patients are now being treated with de-escalating doses of DFMO (1-0.06 g/m2/day) for one month. To study the effect of DFMO in patients with CIN III, we are collecting blood and cervical tissue specimens to measure the following parameters: plasma DFMO, ornithine and arginine levels; plasma N1-acetylspermidine levels; erythrocyte (blood polyamine carrier) free polyamine levels; cervical tissue free polyamine levels; cervical tissue N1-acetylspermidine levels; and cervical tissue ODC activities. N1-acetylspermidine will be examined as this compound is known to exist primarily in tumor tissues, not in normal tissues. We therefore established a high-performance liquid chromatography method for N1-acetylspermidine. We expect to find that polyamines are effective markers in analyzing DFMO effects in this chemoprevention trial, thus functioning as pharmacodynamic parameters as well as biomarkers for transformation. PMID:8747382

Nishioka, K; Melgarejo, A B; Lyon, R R; Mitchell, M F

1995-01-01

31

Pathophysiology of ocular surface squamous neoplasia.  

PubMed

The incidence of ocular surface squamous neoplasia (OSSN) is strongly associated with solar ultraviolet (UV) radiation, HIV and human papilloma virus (HPV). Africa has the highest incidence rates in the world. Most lesions occur at the limbus within the interpalpebral fissure particularly the nasal sector. The nasal limbus receives the highest intensity of sunlight. Limbal epithelial crypts are concentrated nasally and contain niches of limbal epithelial stem cells in the basal layer. It is possible that these are the progenitor cells in OSSN. OSSN arises in the basal epithelial cells spreading towards the surface which resembles the movement of corneo-limbal stem cell progeny before it later invades through the basement membrane below. UV radiation damages DNA producing pyrimidine dimers in the DNA chain. Specific CC ? TT base pair dimer transformations of the p53 tumour-suppressor gene occur in OSSN allowing cells with damaged DNA past the G1-S cell cycle checkpoint. UV radiation also causes local and systemic photoimmunosuppression and reactivates latent viruses such as HPV. The E7 proteins of HPV promote proliferation of infected epithelial cells via the retinoblastoma gene while E6 proteins prevent the p53 tumour suppressor gene from effecting cell-cycle arrest of DNA-damaged and infected cells. Immunosuppression from UV radiation, HIV and vitamin A deficiency impairs tumour immune surveillance allowing survival of aberrant cells. Tumour growth and metastases are enhanced by; telomerase reactivation which increases the number of cell divisions a cell can undergo; vascular endothelial growth factor for angiogenesis and matrix metalloproteinases (MMPs) that destroy the intercellular matrix between cells. Despite these potential triggers, the disease is usually unilateral. It is unclear how HPV reaches the conjunctiva. PMID:25447808

Gichuhi, Stephen; Ohnuma, Shin-ichi; Sagoo, Mandeep S; Burton, Matthew J

2014-12-01

32

Radiogenic neoplasia in thyroid and mammary clonogens  

SciTech Connect

We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. Previous results indicated that these clonogens are the precursor cells of radiogenic cancer, and that initiation, is common event at the clonegenic cell level. Detailed information on the physiologic control of clonogen proliferation, differentiation, and total numbers is thus essential to an understanding of the carcinogenic process. We report here studies on investigations on the relationships between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamus-pituitary feedback axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH-(thyrotropin-) responsive sub- population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and a large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cell interactions during the neoplastic process.

Clifton, K.H.

1992-05-20

33

Radiogenic neoplasia in thyroid and mammary clonogens  

SciTech Connect

We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. During the end of the last grant year and the first half of the current grant year, we have completed analyses and summarized for publication: investigations on the relationship between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamicpituitary axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH- (thyrotropin-) responsive sub-population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and the results of the large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. We are testing new techniques for the culture, cytofluorescent analysis and characterization mammary epithelial cells and of clonogens in a parallel project, and plan to apply similar technology to the thyroid epithelial cells and clonogen population. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cells interactions during the neoplastic process.

Clifton, K.H.

1991-05-31

34

Factors associated with conjunctival intraepithelial neoplasia: A case control study  

SciTech Connect

Familial and environmental factors may play a role in the development of conjunctival intraepithelial neoplasia (CIN). Nineteen patients with biopsy-proven CIN completed a questionnaire to evaluate possible predisposing factors. Nineteen age-matched and sex-matched controls completed questionnaires and received slit-lamp examinations. Factors associated with a relatively increased risk of developing CIN included exposure to petroleum products, heavy cigarette smoking, light hair and ocular pigmentation, and family origin in the British Isles, Austria or Switzerland. Non-office and nonprofessional workers were more likely to develop conjunctival intraepithelial neoplasia (p = .05), as were those who were not college graduates (p = .07).

Napora, C.; Cohen, E.J.; Genvert, G.I.; Presson, A.C.; Arentsen, J.J.; Eagle, R.C.; Laibson, P.R. (Wills Eye Hospital, Philadelphia, PA (USA))

1990-01-01

35

HISTOLOGICAL PROGRESSION OF HEPATIC NEOPLASIA IN RAINBOW TROUT ('SALMO GAIRDNERI')  

EPA Science Inventory

The histological progression of hepatic neoplasia has not been as systematically studied in rainbow trout as it has been in rodents. Two putative preneoplastic lesions have been identified, the eosinophilic focus and the basophilic focus, but whether these correspond to similar l...

36

Colonoscopic Screening of Average-Risk Women for Colorectal Neoplasia  

Microsoft Academic Search

background Veterans Affairs (VA) Cooperative Study 380 showed that some advanced colorectal neoplasias (i.e., adenomas at least 1 cm in diameter, villous adenomas, adenomas with high-grade dysplasia, or cancer) in men would be missed with the use of flexible sig- moidoscopy but detected by colonoscopy. In a tandem study, we examined the yield of screening colonoscopy in women. methods To

Philip Schoenfeld; Brooks Cash; Andrew Flood; Richard Dobhan; John Eastone; Walter Coyle; James W. Kikendall; Hyungjin Myra Kim; David G. Weiss; Theresa Emory; Arthur Schatzkin; David Lieberman

2005-01-01

37

In vivo and in vitro hyperspectral imaging of cervical neoplasia  

NASA Astrophysics Data System (ADS)

Cervical cancer is a prevalent disease in many developing countries. Colposcopy is the most common approach for screening cervical intraepithelial neoplasia (CIN). However, its clinical efficacy heavily relies on the examiner's experience. Spectroscopy is a potentially effective method for noninvasive diagnosis of cervical neoplasia. In this paper, we introduce a hyperspectral imaging technique for noninvasive detection and quantitative analysis of cervical neoplasia. A hyperspectral camera is used to collect the reflectance images of the entire cervix under xenon lamp illumination, followed by standard colposcopy examination and cervical tissue biopsy at both normal and abnormal sites in different quadrants. The collected reflectance data are calibrated and the hyperspectral signals are extracted. Further spectral analysis and image processing works are carried out to classify tissue into different types based on the spectral characteristics at different stages of cervical intraepithelial neoplasia. The hyperspectral camera is also coupled with a lab microscope to acquire the hyperspectral transmittance images of the pathological slides. The in vivo and the in vitro imaging results are compared with clinical findings to assess the accuracy and efficacy of the method.

Wang, Chaojian; Zheng, Wenli; Bu, Yanggao; Chang, Shufang; Tong, Qingping; Zhang, Shiwu; Xu, Ronald X.

2014-02-01

38

Reptile neoplasia at the Philadelphia Zoological Garden, 1901-2002.  

PubMed

A retrospective study of neoplasia in reptiles held at the Philadelphia Zoological Garden was conducted. A total of 3,684 original necropsy reports for the period 1901-2002 were reviewed and revealed 86 cases of neoplasia. Original glass slides or re-cuts from paraffin-embedded tissue blocks were examined for confirmation of the original diagnosis. At necropsy, a total of six neoplasms were identified in six of 490 chelonians (1.2%), 22 neoplasms in 19 of 736 lizards (3.0%), and 58 neoplasms in 53 of 1,835 snakes (2.9%). An additional 12 neoplasms were found in biopsies of one turtle and 10 snakes. In the chelonians, all the neoplasms were seen in turtles, four of six tumors were malignant (66%) and no organ predilection was noted. For lizards, the liver was the most commonly affected organ, with 7 of 22 primary neoplasms (31%). Multiple tumor types were identified in three lizards (15%), metastasis occurred in five cases (25%), and malignant tumors were identified in 16 cases (73%). In snakes, the liver was most frequently affected by neoplasia at necropsy, with 13 of 58 primary neoplasms (22%); multiple types of neoplasm were identified in five cases (10%) and metastasis in six (9%); and 42 tumors (80%) were diagnosed as malignant. When biopsies were included for snakes, however, the skin was the most commonly affected organ, with 17 of 69 neoplasms (24%). One of five lizards (20%) and four of six snakes (66%) with metastasis also had a second primary neoplasm. Since 1967, the incidence of lizard neoplasia has increased from 0.7% to 5.9%, and snake neoplasia has increased from 2.6% to 9.3%. PMID:17312806

Sykes, John M; Trupkiewicz, John G

2006-03-01

39

Predictive factors of proximal advanced neoplasia in the large bowel  

PubMed Central

Introduction The aim of the study was to evaluate the impact of sex, age, family history and distal findings on the risk of proximal advanced neoplasia (cancer or advanced adenoma) in the large bowel. Material and methods Records for 10 111 asymptomatic participants of the Colonoscopy Screening Program (CSP), recruited from the Warsaw region between 2000 and 2004, were analyzed. A multivariate logistic regression model was used to estimate the impact of sex, age, family history and most advanced distal lesions on the occurrence of proximal advanced neoplasia. To enhance comparability of the study two definitions of the proximal colon were applied – either the splenic flexure (1st) or the bend between the descending and sigmoid colon (2nd definition) represented the boundary. Results One hundred and thirty-three (1st) and 167 patients (2nd definition) were found to have at least one advanced neoplastic lesion in the proximal part, respectively. Eleven and 14 patients were found to have carcinoma, while in 130 and 163 patients at least one proximal advanced adenoma appeared. Men were at twice as high risk of having advanced neoplasia in the proximal colon than women (OR = 1.94, 95% CI: 1.31–2.87, p = 0.001 or OR = 1.69, 95% CI: 1.20–2.40, p = 0.003, respectively). The presence of distal advanced neoplastic lesions was associated with 3.5 times higher risk of proximal advanced neoplasia (OR = 3.58, 95% CI: 2.00–6.43, p < 0.0001 or OR = 3.41, 95% CI: 1.95–5.96, p < 0.0001), respectively. Conclusions The results may confirm some limitation of flexible sigmoidoscopy in the screening settings in comparison with colonoscopy, at least in men and people with distal advanced neoplasia. PMID:25097578

Mroz, Andrzej; Kaminski, Michal F.; Kraszewska, Ewa; Orlowska, Janina; Regula, Jaroslaw

2014-01-01

40

Homozygotes for the autosomal dominant neoplasia syndrome (MEN1)  

SciTech Connect

Families in which both parents are heterozygotes for the same autosomal dominant neoplasia syndrome are extremely unusual. Recently, the authors had the unique opportunity to evaluate three symptomatic siblings from the union between two unrelated individuals affected by multiple endocrine neoplasia type 1 (MEN1). When the three siblings and their parents and relatives were genotyped for 12 markers tightly linked to the MEN1 locus, at 11q13, two of the siblings were found to be homozygotes, and one a heterozygote, for MEN1. With regard to the MEN1 syndrome, no phenotypic differences were observed between the two homozygotes and the heterozygotes. However, the two homozygotes showed unexplained infertility, which was not the case for any of the heterozygotes. Thus, MEN1 appears to be a disease with complete dominance, and the presence of two MEN1 alleles with mutations of the type that occur constitutionally may be insufficient for tumor development. 28 refs., 2 figs.

Brandi, M.L.; Falchetti, A.; Tonelli, F. (Univ. of Florence (Italy)); Weber, G.; Svensson, A.; Larsson, C. (Karolinska Hospital, Stockholm (Sweden)); Castello, R.; Furlani, L.; Scappaticci, S.; Fraccaro, M.

1993-12-01

41

Serrated neoplasia of the colon: what do we really know?  

PubMed

Colonoscopy offers incomplete protection from colorectal cancer, particularly in the right colon. Part of this inadequacy may be related to serrated neoplasia. Serrated polyps of the colorectum are now understood to be a heterogeneous group of polyps, some of which are cancer precursors, such as the sessile serrated adenoma (SSA) and the traditional serrated adenoma (TSA). In contrast to conventional adenomas, there is limited published literature on the epidemiology and natural history of these lesions. Furthermore, existing guidelines regarding screening and surveillance practices for these polyps are based largely on expert opinion without firm evidence. In this review, we describe the current understanding of the molecular biology, histopathology, and endoscopic features of serrated neoplasia of the colorectum, with an emphasis on aspects relevant to the practicing gastroenterologist. PMID:24595617

Haque, Tanvir; Greene, Kevin G; Crockett, Seth D

2014-04-01

42

Early Detection of and Screening for Colorectal Neoplasia  

PubMed Central

There are approximately one million new cases of colorectal cancer (CRC) per year worldwide, with substantial associated morbidity and mortality. The long natural history of colorectal neoplasia affords the opportunity to use preventive measures to improve survival in this disease. Currently screening for adenomatous polyps and early-stage cancers is the best methodology for improving survival. The increasing knowledge of CRC pathogenesis and its natural history is allowing the development of new tools to identify patients who will benefit most from colon cancer screening and the defining of appropriate surveillance intervals. The guidelines for screening for colorectal neoplasia have recently been substantially revised by several organizations based on developing technologies and a growing body of data on the efficacy of CRC screening. PMID:20431727

2009-01-01

43

Minimally Invasive Therapy of Cervical Intraepithelial Neoplasia for Fertility Preservation  

Microsoft Academic Search

The aim of this study was to determine the extension of cervical intraepithelial neoplasia grade III (CIN III) into endocervical\\u000a canal and depth of endocervical crypts involvement by CIN with the regard to patients’ age and parity. Correlation between\\u000a the area of CIN involvement and the extension into endocervical canal was estimated. A total of 218 cervical cone specimens\\u000a with

Darko Milinovic; Drzislav Kalafatic; Damir Babic; Lidija Beketic Oreskovic; Helena Lovric Grsic; Slavko Oreskovic

2009-01-01

44

Association of Large Serrated Polyps With Synchronous Advanced Colorectal Neoplasia  

Microsoft Academic Search

OBJECTIVES:Serrated polyps of the colorectum are a histologically and genetically heterogeneous group of lesions, which include classic hyperplasic polyps, sessile serrated adenomas (SSAs), and traditional serrated adenomas. Accumulating evidence suggests that they may have different malignancy potentials. This study sought to determine the association between the presence of large serrated colorectal polyps and synchronous advanced colorectal neoplasia.METHODS:Among 4,714 asymptomatic subjects

Dan Li; Chengshi Jin; Charles McCulloch; Sanjay Kakar; Barry M Berger; Thomas F Imperiale; Jonathan P Terdiman

2009-01-01

45

Piroxicam decreases postirradiation colonic neoplasia in the rat  

SciTech Connect

This study evaluated the effects of the nonsteroidal antiinflammatory agent piroxicam on chronic radiation proctitis in the rat. Forty female Wistar rats received a 2250-cGy dose of irradiation to the distal 2 cm of the colon. Twenty received piroxicam 8.0 mg/kg orally 30 minutes before exposure and 24 hours after exposure; 20 rats served as irradiated controls. All animals were evaluated by colonoscopy 1 and 3 weeks postexposure and every third week until death or killing at 1 year. At killing, colons were removed for light microscopic examination. One year postirradiation results showed no differences in mortality, vascular changes, acute inflammation, colitis cystica profunda, or rectal stricture between the control and piroxicam-treated groups. However, at 1 year postirradiation the control group demonstrated neoplasia in 15 of 19 animals compared with eight of 20 animals in the piroxicam-treated group. The first endoscopic appearance of colonic neoplasm occurred at 15 weeks postirradiation in one control irradiated rat whereas the first evidence of endoscopic neoplasm in the piroxicam-treated group did not occur until 36 weeks postirradiation. Histologic examination documented a tendency toward a greater presence of adenocarcinomas in the control group compared with the piroxicam-treated group. The authors conclude that piroxicam treatment significantly decreased the incidence of colonic neoplasia in general as well as delayed the endoscopic appearance of colonic neoplasia in rats after pelvic irradiation. 41 references.

Northway, M.G.; Scobey, M.W.; Cassidy, K.T.; Geisinger, K.R. (Wake Forest Univ., Winston Salem, NC (USA))

1990-12-01

46

CD44 is a marker of endocervical neoplasia.  

PubMed

The expression of CD44s, CD44v4, CD44v5, CD44v7-8, and CD44v10 was investigated immunohistochemically in a variety of neoplastic cervical lesions. Normal endocervical columnar cells exhibited no reactivity for any of the antibodies, whereas the subcolumnar reserve cells were strongly positive for CD44s, CD44v5, and CD44v7-8. In some cases, positive cells were identified in the stroma surrounding the endocervical glands and adjacent to reserve cells. Cervical glandular intraepithelial neoplasia and adenocarcinoma showed consistent immunoreactivity for CD44v5. There was no significant change in CD44 immunoreactivity in squamous cell carcinoma compared with normal epithelia and cervical intraepithelial neoplasia. These findings lend support to the origin of carcinoma of the cervix from a common progenitor reserve cell and suggest the origin of reserve cells from the stroma. CD44v5 may be useful as a diagnostic marker of endocervical neoplasia and could provide a target for therapeutic approaches directed against specific epitopes. PMID:10202665

Ibrahim, E M; Blackett, A D; Tidy, J A; Wells, M

1999-04-01

47

Activation of ras oncogenes preceding the onset of neoplasia  

SciTech Connect

The identification of ras oncogenes in human and animal cancers including precancerous lesions indicates that these genes participate in the early stages of neoplastic development. Yet, these observations do not define the timing of ras oncogene activation in the multistep process of carcinogenesis. To ascertain the timing of ras oncogene activation, an animal model system was devised that involves the induction of mammary carcinomas in rats exposed at birth to the carcinogen nitrosomethylurea. High-resolution restriction fragment length polymorphism analysis of polymerase chain reaction-amplified ras sequences revealed the presence of both H-ras and K-ras oncogenes in normal mammary glands 2 weeks after carcinogen treatment and at least 2 months before the onset of neoplasia. These ras oncogenes can remain latent within the mammary gland until exposure to estrogens, demonstrating that activation of ras oncogenes can precede the onset of neoplasia and suggesting that normal physiological proliferative processes such as estrogen-induced mammary gland development may lead to neoplasia if the targeted cells harbor latent ras oncogenes.

Kumar, R.; Barbacid, M. (Squibb Institute for Medical Research, Princeton, NJ (USA)); Sukumar, S. (Salk Institute, La Jolla, CA (USA))

1990-06-01

48

High frequency of gonadal neoplasia in a hard clam ( Mercenaria spp.) hybrid zone  

Microsoft Academic Search

The etiology of bivalve gonadal neoplasia has eluded invertebrate pathologists for over 20 yr. In a coastal Florida (USA) lagoon, where two species of hard clams (Mercenaria mercenaria and M. campechiensis) cooccur and hybridize, they exhibit a persistent, unusually high frequency of gonadal neoplasia. Hybridity, rather than environmental or other biological factors, appears to determine susceptibility, implicating a genetic mechanism

T. M. Bert; D. M. Hesselman; W. S. Arnold; W. S. Moore; H. Cruz-Lopez; D. C. Marelli

1993-01-01

49

Prospective evaluation of fecal calprotectin as a screening biomarker for colorectal neoplasia  

Microsoft Academic Search

OBJECTIVES:Stool testing is a well established method of screening for colorectal neoplasia. Emerging data suggest that novel biomarkers may offer performance advantages over fecal occult blood. In this large, prospective study, we assessed fecal calprotectin (a leukocyte-derived protein) as a screening biomarker for colorectal neoplasia. Fecal calprotectin was directly compared to fecal hemoglobin (Hb) and colonoscopy as the existing criterion

Paul J. Limburg; Mary E. Devens; Jonathan J. Harrington; Nancy N. Diehl; Douglas W. Mahoney; David A. Ahlquist

2003-01-01

50

Genetic testing for multiple endocrine neoplasia type 2.  

PubMed

Multiple endocrine neoplasia type 2 (MEN 2) represents a complex autosomal dominant inherited syndrome characterized by occurrence of distinct proliferative disorders of endocrine tissues. The identification of RET proto-oncogene mutations in MEN 2 and FMCT has provided a precise method for identifying gene carriers. 30 subjects (9 males, 21 females, age range 11-63 years) with multiple endocrine neoplasia type 2 have been investigated from 1998 till 2006. 20 patients were considered as index cases and 10 patients were identified after a screening programme for MEN 2. Tumoral associations permitted the MEN 2A diagnosis in 21 cases, MEN 2A with cutaneous lichen amyloidosis in 6 cases and FMCT in 3 cases. We selected 22 patients from 14 families to investigate mutations in the RET proto-oncogene. In 7 subjects no mutations could be detected in the exons 10 and 11 of the RET proto-oncogene. Heterozygous missense mutations in exon 11 were found in 15 subjects consisting of three different mutations in codon 634 (TGC --> TGG, TGC --> GGC, TGC --> CGC). We conclude that our 15 patients have the most frequent mutations described in MEN 2A families. Because the testing for exons 10 and 11 is negative for other 7 patients, the remaining 13, 14, 15 and 16 exons should be sequenced in these cases. PMID:19284088

P?un, Diana Loreta; Mohora, Maria; Du??, Carmen; Dumitrache, C

2008-01-01

51

Microtopographic Inspection and Fractal Analysis of Skin Neoplasia  

NASA Astrophysics Data System (ADS)

Early detection of skin cancer is fundamental to a successful treatment. Changes in the shape, including the relief, of skin lesions are an indicator of a possible malignity. Optical microtopographic inspection of skin lesions can be used to identify diagnostic patterns of benign and malign skin' lesions. Statistical parameters like the mean roughness (Ra) may allow the discrimination between different types of lesions and degree of malignity. Fractal analysis of bi-dimensional and 3D images of skin lesions can validate or complement that assessment by calculation of its fractal dimensions (FD). On the study herein reported the microtopographic inspection of the skin lesions were performed using the optical triangulation based microtopographer developed at the Physics Department of the University of Minho, MICROTOP.03.MFC. The patients that participated in this research work were men and women older than 15 years with the clinical and histopathology diagnoses of: melanoma, basocellular carcinoma, epidermoide carcinoma, actinic keratosis, keratoacantosis and benign nevus. Latex impressions of the lesions were taken and microtopographically analyzed. Characteristic information for each type of studied lesion was obtained. For melanoma it was observed that on the average these tumors present an increased roughness of around 67 percent compared to the roughness of the healthy skin. This feature allows the distinction from other tumors as basocellular carcinoma (were the roughness increase was in the average of 49 percent) and benign lesions as the epidermoide cyst (37 percent) or the seborrhea keratosis (4 percent). Tumor size and roughness are directly proportional to the grade of malignality. The characterization of the fractal geometry of 2D (histological slides) and 3D images of skin lesions was performed by obtaining its FD evaluated by means of the Box counting method. Results obtained showed that the average fractal dimension of histological slide images (FDh) corresponding to some neoplasia is higher (1.334+/-0.072) than those for healthy skin (1.091+/-0.082). A significant difference between the fractal dimensions of neoplasia and healhty skin (>0.001) was registered. The FD of microtopography maps (FDm) can also distinguish between healthy and malignant tissue in general (2.277+/-0.070 to 2.309+/-0.040), but not discriminate the different types of skin neoplasias. The combination of the rugometric evaluation and fractal geometry characterization provides valuable information about the malignity of skin lesions and type of lesion.

Costa, Manuel F. M.; Hipolito, Alberto Valencia; Gutierrez, Gustavo Fidel; Chanona, Jorge; Gallegos, Eva Ramón

2008-04-01

52

Surgical interventions for high grade vulval intraepithelial neoplasia  

PubMed Central

Background Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin. This uncommon chronic skin condition of the vulva is associated with a high risk of recurrence and the potential to progress to vulval cancer. The condition is complicated by its’ multicentric and multifocal nature. The incidence of this condition appears to be rising particularly in the younger age group. There is a lack of consensus on the optimal surgical treatment method. However, the rationale for surgical treatment of VIN has been to treat symptoms and exclude underlying malignancy with the continued aim of preservation of vulval anatomy and function. Repeated treatments affect local cosmesis and cause psychosexual morbidity thus impacting on the patients’ quality of life. Objectives To evaluate the effectiveness and safety of surgical interventions for high grade VIN. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 3, 2010, Cochrane Gynaecological Cancer Group Trials Register, MEDLINE and EMBASE up to September 2010. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) that compared surgical interventions, in adult women diagnosed with high grade vulval intraepithelial neoplasia. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Main results We found only one RCT which included 30 women that met our inclusion criteria and this trial reported data on carbon dioxide laser (CO2 laser) versus ultrasonic surgical aspiration (USA). There was no statistically significant difference in the risk of disease recurrence after one year follow-up, pain, presence of scarring, dysuria or burning, adhesions, infection, abnormal discharge and eschar between women who received CO2 laser and those who received USA. The trial lacked statistical power due to the small number of women in each group and the low number of observed events, but was at low risk of bias. Authors’ conclusions The included trial lacked statistical power due to the small number of women in each group and the low number of observed events. Therefore in the absence of reliable evidence regarding the effectiveness and safety of the two surgical techniques for the management of vulval intraepithelial neoplasia precludes any definitive guidance or recommendations for clinical practice. PMID:21249698

Kaushik, Sonali; Pepas, Litha; Nordin, Andy; Bryant, Andrew; Dickinson, Heather O

2014-01-01

53

Gastroenteropancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1  

PubMed Central

We reviewed the literature about entero-pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia type 1 syndrome (MEN1) to clarify their demographic features, localization imaging, practice, and appropriate therapeutical strategies, analyzing the current approach to entero-pancreatic neuroendocrine tumors in MEN1. Despite the fact that hyperparathyroidism is usually the first manifestation of MEN1, the penetrance of these tumors is similar. They are characterized by multiplicity of lesions, variable expression of the tumors, and propensity for malignant degeneration. Both the histological type and the size of MEN1 neuroendocrine tumors correlate with malignancy. Monitoring of pancreatic peptides and use of imaging exams allow early diagnosis and prompt surgical treatment, resulting in prevention of metastatic disease and improvement of long-term survival. Surgery is often the treatment of choice for MEN1-neuroendocrine tumors. The rationale for surgical approach is to curtail malignant progression of the disease, and to cure the associated biochemical syndrome, should it be present. PMID:24213321

Tonelli, Francesco; Giudici, Francesco; Giusti, Francesca; Brandi, Maria Luisa

2012-01-01

54

ACOG Committee Opinion No. 509: Management of vulvar intraepithelial neoplasia.  

PubMed

Vulvar intraepithelial neoplasia (VIN) is an increasingly common problem, particularly among women in their 40s. The term VIN is used to denote high-grade squamous lesions and is subdivided into usual-type VIN (including warty, basaloid, and mixed VIN) and differentiated VIN. Usual-type VIN is commonly associated with carcinogenic genotypes of human papillomavirus (HPV) and other HPV persistence risk factors, such as cigarette smoking and immunocompromised status, whereas differentiated VIN usually is not associated with HPV and is more often associated with vulvar dermatologic conditions, such as lichen sclerosus. Biopsy is indicated for any pigmented vulvar lesion. Treatment is indicated for all cases of VIN. When occult invasion is not a concern, VIN can be treated with surgical therapy, laser ablation, or medical therapy. After resolution, women should be monitored at 6 and 12 months and annually thereafter. PMID:22015906

2011-11-01

55

Medical and surgical approaches to vulvar intraepithelial neoplasia.  

PubMed

Vulvar intraepithelial neoplasia (VIN) is a precursor to invasive vulvar carcinoma. The two major types of VIN, usual and differentiated, differ in epidemiology, pathogenesis, clinical manifestations, pathology, and malignant potential. Usual VIN commonly occurs in younger women. It is associated with human papillomavirus and tends to have multifocal and multicentric involvement. Differentiated VIN is frequently associated with benign vulvar dermatoses such as lichen sclerosus and lichen simplex chronicus. It occurs in older women and typically is unifocal and unicentric. Clinicians must have a high suspicion for VIN, which is diagnosed by biopsy. Surgical excision has been the standard treatment in order to prevent progression to invasive disease. The objectives of treatment have expanded to include preservation of normal vulvar function and anatomy. Therefore, management options are being investigated, including topical therapy, laser excision and vaporization, and photodynamic therapy. All can be effective in both eliminating disease and maintaining relatively normal-appearing and functioning anatomy. PMID:20868402

Lai, Kimberly W; Mercurio, Mary Gail

2010-01-01

56

[Thymic carcinoid associated with multiple endocrine neoplasia type 1].  

PubMed

We report a case of a thymic carcinoid associated with multiple endocrine neoplasia type 1( MEN-1). A 37-year-old man was referred to our hospital for further examination of an abnormal chest shadow. A chest computed tomography (CT) showed an anterior mediastinal mass measuring 6.5 cm in diameter. A pathological diagnosis of thymic carcinoid was made from a CT-guided needle biopsy specimen. Preoperative workup including endocrinological examination revealed a pituitary adenoma and hyperparathyroidism, and MEN-1 was clinically diagnosed. We performed total parathyroidectomy with autotransplantation and thymectomy with lymph node dissection through cervical collar incision and median sternotomy. The diagnosis of MEN-1 was confirmed by the genomic analysis postoperatively. Since 25% of thymic carcinoids are MEN-1 related and 95% of MEN-1 patients develop hyperparathyroidism, it should be kept in mind that this condition can be treated by thymectomy and concurrent parathyroidectomy. PMID:22647328

Ishida, Itaru; Oura, Hiroyuki; Niikawa, Hiromichi; Onodera, Ken; Handa, Masashi; Onuki, Koji; Kawamura, Minoru

2012-06-01

57

Ocular surface squamous neoplasia masquerading as superior limbic keratoconjunctivitis.  

PubMed

To report a case of ocular surface squamous neoplasia (OSSN) masquerading as superior limbic keratoconjunctivitis (SLK). A 62-year-old woman was referred with foreign body sensation, irritation, photophobia and decreased vision in the left eye. She was initially treated for 10 months with intermittent topical corticosteroids for a presumed diagnosis of SLK. She underwent excisional biopsy of the superior conjunctiva and was found, on histopathologic evaluation, to have OSSN with moderate to marked dysplasia. This is the first reported case of OSSN masquerading with signs and symptoms of SLK. Any ocular surface lesion refractory to standard medical treatment should raise suspicion for a malignant process and warrant further cytologic or histopathologic evaluation. PMID:21572741

Moshirfar, Majid; Khalifa, Yousuf M; Kuo, Annie; Davis, Don; Mamalis, Nick

2011-01-01

58

Ocular Surface Squamous Neoplasia Masquerading as Superior Limbic Keratoconjunctivitis  

PubMed Central

To report a case of ocular surface squamous neoplasia (OSSN) masquerading as superior limbic keratoconjunctivitis (SLK). A 62-year-old woman was referred with foreign body sensation, irritation, photophobia and decreased vision in the left eye. She was initially treated for 10 months with intermittent topical corticosteroids for a presumed diagnosis of SLK. She underwent excisional biopsy of the superior conjunctiva and was found, on histopathologic evaluation, to have OSSN with moderate to marked dysplasia. This is the first reported case of OSSN masquerading with signs and symptoms of SLK. Any ocular surface lesion refractory to standard medical treatment should raise suspicion for a malignant process and warrant further cytologic or histopathologic evaluation. PMID:21572741

Moshirfar, Majid; Khalifa, Yousuf M.; Kuo, Annie; Davis, Don; Mamalis, Nick

2011-01-01

59

Endoscopic versus surgical therapy for Barrett's esophagus neoplasia.  

PubMed

Esophagectomy has been the traditional therapy for high-grade dysplasia and intramucosal cancer. Though surgery can completely resect the cancer and the affected lymph nodes, it carries significant morbidity and mortality (often exceeds 2%). New developments in endoscopy have provided less-invasive therapies that can also be used to stage tissue invasion of cancer; they include esophageal mucosal resection (EMR) and endoscopic submucosal dissection. Additional endoscopic therapies include photodynamic therapy, radiofrequency ablation (RFA) and argon plasma coagulation. Combining EMR that targets the cancer and RFA that targets the surrounding Barrett's esophagus offers an alternative to the operative approach when there is no lymph node metastasis. Arguments for surgical esophagectomy include concern for missed lymph node metastasis and incomplete endoscopic resection. Based on EMR's high neoplasia eradication rate and its fewer and more manageable complications, EMR, especially when combined with RFA, appears to be a viable alternative to surgery in early submucosal cancers, that is, sm1. PMID:25160753

Smith, Ioana; Kahaleh, Michel

2015-01-01

60

Using the laser to treat vulvar condylomata acuminata and intraepidermal neoplasia.  

PubMed Central

The therapeutic effectiveness of the carbon dioxide laser was evaluated in 55 women with condylomata acuminata, particularly of the vulva but also of the urethral meatus and anal region, and in 11 women with multicentric vulvar intraepidermal neoplasia. The rates of persistence and recurrence were 13% and 5% respectively for condylomata and were both 9% for intraepidermal neoplasia. Perioperative and postoperative complications occurred in 6 of the 66 cases (9%) and all were managed on an outpatient basis. Laser beam therapy is recommended as an effective and safe means of treating extensive condylomata and intraepidermal neoplasia of the external urogenital region and anal mucous membrane. PMID:6848156

Ferenczy, A.

1983-01-01

61

Multiple Endocrine Neoplasia Type 1 and the Search for the Genetic Trigger  

Microsoft Academic Search

Multiple endocrine neoplasia type 1 (MEN-1) is characterized by primary hyperparathyroidism, endocrine pancreatic-duodenal and anterior pituitary tumors. The diagnosis is challenging and involves the exclusion of other endocrine neoplasia syndromes with overlapping features. The predisposing genetic defect was assigned to chromosomal region 11q13 based on linkage analysis. Combined tumor and pedigree genotype analysis showed that allele losses in pancreatic, parathyroid

Filip Farnebo; Johannes Järhult; Lars-Ove Farnebo; Olov Nilsson; Bin Tean Teh; Jacob Lagercrantz; Günther Weber; Kerstin Sandelin; Catharina Larsson

1997-01-01

62

High-resolution genomic profiling of human papillomavirus-associated vulval neoplasia  

PubMed Central

Background: The incidence of human papillomavirus-associated vulval neoplasia is increasing worldwide; yet the associated genetic changes remain poorly understood. Methods: We have used single-nucleotide polymorphism microarray analysis to perform the first high-resolution investigation of genome-wide allelic imbalance in vulval neoplasia. Our sample series comprised 21 high-grade vulval intraepithelial neoplasia and 6 vulval squamous cell carcinomas, with paired non-lesional samples used to adjust for normal copy number variation. Results: Overall the most common recurrent aberrations were gains at 1p and 20, with the most frequent deletions observed at 2q, 3p and 10. Copy-neutral loss of heterozygosity at 6p was a recurrent event in vulval intraepithelial neoplasia. The pattern of genetic alterations differed from the characteristic changes we previously identified in cutaneous squamous cell carcinomas. Vulval neoplasia samples did not exhibit gain at 5p, a frequent recurrent aberration in a series of cervical tumours analysed elsewhere using an identical protocol. Conclusion: This series of 27 vulval samples comprises the largest systematic genome-wide analysis of vulval neoplasia performed to date. Despite shared papillomavirus status and regional proximity, our data suggest that the frequency of certain genetic alterations may differ in vulval and cervical tumours. PMID:20234371

Purdie, K J; Harwood, C A; Gibbon, K; Chaplin, T; Young, B D; Cazier, J B; Singh, N; Leigh, I M; Proby, C M

2010-01-01

63

Expression of PBK/TOPK in cervical cancer and cervical intraepithelial neoplasia  

PubMed Central

objectives: To evaluate the expression of PBK/TOPK (PDZ-binding kinase/T-LAK cell-originated protein kinase) and its clinical significance in cervical cancer and cervical intraepithelial neoplasia. Methods: PBK/TOPK expression was detected in 28 cases of low-grade cervical intraepithelial neoplasia (CINI), 62 cases of high-grade intraepithelial neoplasia and 80 cases of cervical cancer by immunohistochemistry (IHC). Then, the correlation between PBK/TOPK expression and clinicopathological features was quantitatively analyzed by measuring the positive unit (PU). Results: PBK/TOPK expression was significantly greater in cervical cancer than that in high-grade intraepithelial neoplasia and CINI (P < 0.05). Meanwhile, PBK/TOPK expression in high-grade intraepithelial neoplasia was significantly higher compared with that in CINI (P < 0.05). In addition, PBK/TOPK expression in cervical cancer significantly correlated with histological type, differentiation, lymph node metastasis, vaginal and cervical invasion, TNM stage and tumor size (P < 0.05). Conclusion: PBK/TOPK expression is closely associated with cervical cancer and cervical intraepithelial neoplasia, which may be served as a useful target for tumor diagnosis and immunotherapy.

Luo, Qiong; Lei, Bin; Liu, Shuguang; Chen, Yaowen; Sheng, Wenjie; Lin, Peixin; Li, Wenxia; Zhu, Haili; Shen, Hong

2014-01-01

64

Pharmacological Intervention through Dietary Nutraceuticals in Gastrointestinal Neoplasia.  

PubMed

Abstract Neoplastic conditions associated with gastrointestinal (GI) tract are common worldwide with colorectal cancer alone accounting for the third leading rate of cancer incidence. Other GI malignancies such as esophageal carcinoma have shown an increasing trend in the last few years. The poor survival statistics of these fatal cancer diseases highlight the need for multiple alternative treatment options along with effective prophylactic strategies. Worldwide geographical variation in cancer incidence indicates a correlation between dietary habits and cancer risk. Epidemiological studies have suggested that populations with high intake of certain dietary agents in their regular meals have lower cancer rates. Thus an impressive embodiment of evidence supports the concept that dietary factors are key modulators of cancer including those of GI origin. Preclinical studies on animal models of carcinogenesis have reflected the pharmacological significance of certain dietary agents called as nutraceuticals in the chemoprevention of GI neoplasia. These include stilbenes (from red grapes and red wine), isoflavones (from soy), carotenoids (from tomatoes), curcuminoids (from spice turmeric), catechins (from green tea) and various other small plant metabolites (from fruits, vegetables and cereals). Pleiotropic action mechanisms have been reported for these diet-derived chemopreventive agents to retard, block or reverse carcinogenesis. This review presents a prophylactic approach to primary prevention of GI cancers by highlighting the translational potential of plant-derived nutraceuticals from epidemiological, laboratory and clinical studies, for the better management of these cancers through consumption of nutraceutical rich diets and their intervention in cancer therapeutics. PMID:25365584

Ullah, Mohammad F; Bhat, Showket H; Husain, Eram; Abu-Duhier, Faisel; Hadi, S M; Sarkar, Fazlul H; Ahmad, Aamir

2014-11-01

65

Microscopic features of colorectal neoplasia in inflammatory bowel diseases  

PubMed Central

The risk of developing dysplasia leading to colorectal cancer (CRC) is increased in both ulcerative colitis and Crohn’s disease. The prognosis of CRC may be poorer in patients with inflammatory bowel disease (IBD) than in those without IBD. Most CRCs, in general, develop from a dysplastic precursor lesion. The interpretation by the pathologist of the biopsy will guide decision making in clinical practice: colonoscopic surveillance or surgical management. This review summarizes features of dysplasia (or intraepithelial neoplasia) with macroscopic and microscopic characteristics. From an endoscopic (gross) point of view, dysplasia may be classified as flat or elevated (raised); from a histological point of view, dysplasia is separated into 3 distinct categories: negative for dysplasia, indefinite for dysplasia, and positive for dysplasia with low- or high-grade dysplasia. The morphologic criteria for dysplasia are based on a combination of cytologic (nuclear and cytoplasmic) and architectural aberrations of the crypt epithelium. Immunohistochemical and molecular markers for dysplasia are reviewed and may help with dysplasia diagnosis, although diagnosis is essentially based on morphological criteria. The clinical, epidemiologic, and pathologic characteristics of IBD-related cancers are, in many aspects, different from those that occur sporadically in the general population. Herein, we summarize macroscopic and microscopic features of IBD-related colorectal carcinoma. PMID:24696602

Bressenot, Aude; Cahn, Virginie; Danese, Silvio; Peyrin-Biroulet, Laurent

2014-01-01

66

Microscopic features of colorectal neoplasia in inflammatory bowel diseases.  

PubMed

The risk of developing dysplasia leading to colorectal cancer (CRC) is increased in both ulcerative colitis and Crohn's disease. The prognosis of CRC may be poorer in patients with inflammatory bowel disease (IBD) than in those without IBD. Most CRCs, in general, develop from a dysplastic precursor lesion. The interpretation by the pathologist of the biopsy will guide decision making in clinical practice: colonoscopic surveillance or surgical management. This review summarizes features of dysplasia (or intraepithelial neoplasia) with macroscopic and microscopic characteristics. From an endoscopic (gross) point of view, dysplasia may be classified as flat or elevated (raised); from a histological point of view, dysplasia is separated into 3 distinct categories: negative for dysplasia, indefinite for dysplasia, and positive for dysplasia with low- or high-grade dysplasia. The morphologic criteria for dysplasia are based on a combination of cytologic (nuclear and cytoplasmic) and architectural aberrations of the crypt epithelium. Immunohistochemical and molecular markers for dysplasia are reviewed and may help with dysplasia diagnosis, although diagnosis is essentially based on morphological criteria. The clinical, epidemiologic, and pathologic characteristics of IBD-related cancers are, in many aspects, different from those that occur sporadically in the general population. Herein, we summarize macroscopic and microscopic features of IBD-related colorectal carcinoma. PMID:24696602

Bressenot, Aude; Cahn, Virginie; Danese, Silvio; Peyrin-Biroulet, Laurent

2014-03-28

67

Minimally invasive therapy of cervical intraepithelial neoplasia for fertility preservation.  

PubMed

The aim of this study was to determine the extension of cervical intraepithelial neoplasia grade III (CIN III) into endocervical canal and depth of endocervical crypts involvement by CIN with the regard to patients' age and parity. Correlation between the area of CIN involvement and the extension into endocervical canal was estimated. A total of 218 cervical cone specimens with histologically proven CIN III were included in this study. Extension of CIN into the endocervical canal, depth of involved crypts and ectocervical area affected by CIN were histologically analyzed. The average endocervical crypt involvement was at 1.2 mm of depth. The excision of >4 mm (1.2 mm x 3S.D.) in depth removes >99% of CIN. With the cone length of 15 mm (nulliparous patients) and 18 mm (multiparous patients), no endocervical cone margins were affected with CIN. Since the cone length is the most important determining factor for fertility preservation, the measurement of cervical cone could be essential for future pregnancies. PMID:19148775

Milinovic, Darko; Kalafatic, Drzislav; Babic, Damir; Oreskovic, Lidija Beketic; Grsic, Helena Lovric; Oreskovic, Slavko

2009-09-01

68

Immunoperoxidase study of the secretory immunoglobulin system in colonic neoplasia.  

PubMed Central

The relation of the secretory immunoglobulin system in the colon to colorectal cancer and dysplasia has been examined by staining routine formalin-fixed, paraffin-embedded sections from cases of carcinoma, adenoma and ulcerative colitis for secretory component (SC), IgA and J chain. In carcinomas there was a close relation between SC synthesis and differentiation and a similar relation was apparent between SC synthesis and degrees of dysplasia in adenomas. In both morphological and functional (SC synthesis) terms degrees of dysplasia in adenomas resembled degrees of differentiation in carcinomas suggesting that the essential "switch" in the progression towards neoplasia may occur at the level of the adenoma and that invasive malignancy can arise from dysplastic mucosa of varying severity. Actively regenerating mucosa in ulcerative colitis (UC) showed intense staining for SC as opposed to foci of precancerous dysplasia where, with one exception, staining was markedly reduced or absent, suggesting staining for SC could be useful in identifying foci of precancerous dysplasia in UC. In the absence of severe chronic inflammation, as in UC, the number of IgA-containing plasma cells was closely related to SC staining of neoplastic mucosa suggesting that SC may be important in the mechanism by which IgA lymphocytes home to the lamina propria of the colon. Images PMID:6801094

Isaacson, P

1982-01-01

69

Pathways of vulvar intraepithelial neoplasia and squamous cell carcinoma.  

PubMed

Vulvar squamous cell carcinoma (VSCC) accounts for >90% of the malignant tumours of the vulva. Most VSCCs originate in intraepithelial lesions, named vulvar intraepithelial neoplasia (VIN), that precede the development of VSCC by a variable period of time. Strong evidence has accumulated showing that there are two different aetiopathogenic pathways for the development of VSCC and VIN, one associated with infection by human papillomavirus (HPV), and a second independent of HPV infection. These two different types of VSCC have different epidemiological, pathological and clinical characteristics, and should therefore be considered as two separate entities. Histologically, HPV-associated VSCCs are of the basaloid or warty type, and arise from VIN of the usual type. Inactivation of p53 and the retinoblastoma tumour suppressor gene product by the viral gene products E6 and E7 is involved in the process of malignant transformation. HPV-independent VSCCs are histologically keratinizing, are associated with differentiated VIN and lichen sclerosus, and frequently show mutations of p53. p16(INK4a) and p53 immunostaining can be useful for classifying VSCC into HPV-associated or HPV-independent. Although large, multicentre studies are needed to definitively assess the involvement of HPV in the prognosis of VSCC, most studies have not found clear differences in survival between HPV-associated and HPV-independent tumours. PMID:23190170

Del Pino, Marta; Rodriguez-Carunchio, Leonardo; Ordi, Jaume

2013-01-01

70

A shared transcriptional program in early breast neoplasias despite genetic and clinical distinctions  

PubMed Central

Background The earliest recognizable stages of breast neoplasia are lesions that represent a heterogeneous collection of epithelial proliferations currently classified based on morphology. Their role in the development of breast cancer is not well understood but insight into the critical events at this early stage will improve efforts in breast cancer detection and prevention. These microscopic lesions are technically difficult to study so very little is known about their molecular alterations. Results To characterize the transcriptional changes of early breast neoplasia, we sequenced 3?- end enriched RNAseq libraries from formalin-fixed paraffin-embedded tissue of early neoplasia samples and matched normal breast and carcinoma samples from 25 patients. We find that gene expression patterns within early neoplasias are distinct from both normal and breast cancer patterns and identify a pattern of pro-oncogenic changes, including elevated transcription of ERBB2, FOXA1, and GATA3 at this early stage. We validate these findings on a second independent gene expression profile data set generated by whole transcriptome sequencing. Measurements of protein expression by immunohistochemistry on an independent set of early neoplasias confirms that ER pathway regulators FOXA1 and GATA3, as well as ER itself, are consistently upregulated at this early stage. The early neoplasia samples also demonstrate coordinated changes in long non-coding RNA expression and microenvironment stromal gene expression patterns. Conclusions This study is the first examination of global gene expression in early breast neoplasia, and the genes identified here represent candidate participants in the earliest molecular events in the development of breast cancer. PMID:24887547

2014-01-01

71

Diagnosing early Barrett’s neoplasia and oesophageal squamous cell neoplasia by bioimpedance spectroscopy in human tissue  

PubMed Central

Background Detection of early oesophageal cancer in surrounding normal tissue can be challenging, but detection is essential to determine the subsequent treatment. Dysplastic tissue can be detected by using electrical impedance spectroscopy (EIS). Objective The aim of the present study was to evaluate the feasibility and value of EIS in the diagnosis of oesophageal neoplasia. Methods This prospective ex-vivo study included 23 patients with early oesophageal cancer (17 with Barrett’s cancer and six with early squamous cell cancer). Immediately after endoscopic resection, the electrical properties of the resected specimens were investigated using a pencil probe (5?mm in diameter, frequency range from 100 Hz to 1?MHz). Punch biopsies were taken from the measured site in order to compare the results of EIS with histology. Results EIS was able to detect dysplastic oesophageal mucosa with a high rate of accuracy (82% in Barrett’s oesophagus and 100% in squamous oesophagus) A total of 54 different sites in 26 tumours were evaluated. Conclusions EIS was able to differentiate reliably between non-neoplastic and neoplastic oesophageal mucosa. Using EIS, it might be possible to use it for targeted biopsies and to avoid unnecessary biopsies during cancer surveillance in future. PMID:24917967

Knabe, Mate; Kurz, Christian; Knoll, Thorsten; Velten, Thomas; Vieth, Michael; Manner, Hendrik; Ell, Christian

2013-01-01

72

Cyclooxygenase-1 and -2: Molecular Targets for Cervical Neoplasia  

PubMed Central

Cyclooxygenase (COX) is a key enzyme responsible for inflammation, converting arachidonic acid to prostaglandin and thromboxane. COX has at least two isoforms, COX-1 and COX-2. While COX-1 is constitutively expressed in most tissues for maintaining physiologic homeostasis, COX-2 is induced by inflammatory stimuli including cytokines and growth factors. Many studies have shown that COX-2 contributes to cancer development and progression in various types of malignancy including cervical cancer. Human papillomavirus, a necessary cause of cervical cancer, induces COX-2 expression via E5, E6 and E7 oncoproteins, which leads to prostaglandin E2 increase and the loss of E-cadherin, promotes cell proliferation and production of vascular endothelial growth factor. It is strongly suggested that COX-2 is associated with cancer development and progression such as lymph node metastasis. Many studies have suggested that non-selective COX-2 inhibitors such as non-steroidal anti-inflammatory drugs (NSAIDs), and selective COX-2 inhibitors might show anti-cancer activity in COX-2 -dependent and -independent manners. Two phase II trials for patients with locally advanced cervical cancer showed that celecoxib increased toxicities associated with radiotherapy. Contrary to these discouraging results, two phase II clinical trials, using rofecoxib and celecoxib, demonstrated the promising chemopreventive effect for patients with cervical intraepithelial neoplasia 2 or 3. However, these agents cause a rare, but serious, cardiovascular complication in spite of gastrointestinal protection in comparison with NSAIDs. Recent pharmacogenomic studies have showed that the new strategy for overcoming the limitation in clinical application of COX-2 inhibitors shed light on the use of them as a chemopreventive method. PMID:25337538

Kim, Hee Seung; Kim, Taehun; Kim, Mi-Kyung; Suh, Dong Hoon; Chung, Hyun Hoon; Song, Yong Sang

2013-01-01

73

Analysis of Fecal DNA Methylation to Detect Gastrointestinal Neoplasia  

PubMed Central

Background The development of noninvasive screening tests is important to reduce mortality from gastrointestinal neoplasia. We sought to develop such a test by analysis of DNA methylation from exfoliated cancer cells in feces. Methods We first analyzed methylation of the RASSF2 and SFRP2 gene promoters from 788 primary gastric and colorectal tissue specimens to determine whether methylation patterns could act as stage-dependent biomarkers of gastrointestinal tumorigenesis. Next, we developed a novel strategy that uses single-step modification of DNA with sodium bisulfite and fluorescence polymerase chain reaction methodology to measure aberrant methylation in fecal DNA. Methylation of the RASSF2 and SFRP2 promoters was analyzed in 296 fecal samples obtained from a variety of patients, including 21 with gastric tumors, 152 with colorectal tumors, and 10 with non-neoplastic or inflammatory lesions in the gastrointestinal lumen. Results Analysis of DNA from tissues showed presence of extensive methylation in both gene promoters exclusively in advanced gastric and colorectal tumors. The assay successfully identified one or more methylated markers in fecal DNA from 57.1% of patients with gastric cancer, 75.0% of patients with colorectal cancer, and 44.4% of patients with advanced colorectal adenomas, but only 10.6% of subjects without neoplastic or active diseases (difference, gastric cancer vs undiseased ?=? 46.5%, 95% confidence interval (CI) ?=? 24.6% to 68.4%, P < .001; difference, colorectal cancer vs undiseased = 64.4%, 95% CI = 53.5% to 75.2%, P < .001; difference, colorectal adenoma vs undiseased = 33.8%, 95% CI = 14.2% to 53.4%, P < .001). Conclusions Methylation of the RASSF2 and SFRP2 promoters in fecal DNA is associated with the presence of gastrointestinal tumors relative to non-neoplastic conditions. Our novel fecal DNA methylation assay provides a possible means to noninvasively screen not only for colorectal tumors but also for gastric tumors. PMID:19700653

Tanaka, Noriaki; Cullings, Harry M.; Sun, Dong-Sheng; Sasamoto, Hiromi; Uchida, Takuyuki; Koi, Minoru; Nishida, Naoshi; Naomoto, Yoshio; Boland, C. Richard; Matsubara, Nagahide; Goel, Ajay

2009-01-01

74

Current treatment options for management of anal intraepithelial neoplasia  

PubMed Central

Anal squamous cell cancer is an uncommon malignancy caused by infection with oncogenic strains of Human papilloma virus. Anal cancer is much more common in immunocompromised persons, including those infected with Human immunodeficiency virus. High-grade anal intraepithelial neoplasia (HGAIN), the precursor of anal cancer, is identified by clinicians providing care for patients with anorectal disease, and is increasingly being identified during screening of immunosuppressed patients for anal dysplasia. The traditional treatment for HGAIN has been excision of macroscopic disease with margins. This approach is effective for patients with small unifocal HGAIN lesions. Patients with extensive multifocal HGAIN frequently have recurrence of HGAIN after excision, and may have postoperative complications of anal stenosis or fecal incontinence. This led to the suggestion by some that treatment for HGAIN should be delayed until patients developed anal cancer. Alternative approaches in identification and treatment have been developed to treat patients with multifocal or extensive HGAIN lesions. High-resolution anoscopy combines magnification with anoscopy and is being used to identify HGAIN and determine treatment margins. HGAIN can then be ablated with a number of modalities, including infrared coagulation, CO2 laser, and electrocautery. These methods for HGAIN ablation can be performed with local anesthesia on outpatients and are relatively well tolerated. High-resolution anoscopy-directed HGAIN ablation is evolving into a standard approach for initial treatment and then subsequent monitoring of a disease which should be expected to be recurrent. Another treatment approach for HGAIN is topical treatment, principally with 5-fluorouracil or imiquimod. Topical therapies have the advantage of being nonsurgical and are well suited for treating widespread multifocal disease. Topical treatments have the disadvantage of requiring extended treatment courses and causing a symptomatic inflammatory response. Successful treatment requires adherence to a regime that is uncomfortable at best and at worst painful. Topical treatments can be successful in motivated adherent patients willing to accept these side effects. PMID:23788834

Weis, Stephen E

2013-01-01

75

How big is this neoplasia? Live colonoscopic size measurement using the Infocus-Breakpoint.  

PubMed

Colonoscopy is the reference medical examination for early diagnosis and treatment of colonic diseases. This minimally invasive technique allows endoscopists to explore the colon cavity and remove neoplasias - abnormal growths of tissue - which may develop into malignant tumors. The size, shape and appearance of a neoplasia are essential cues for diagnostic. However, the size is difficult to estimate because the absolute scale of the observed tissue is not directly conveyed in the 2D colonoscopic images. An erroneous size estimate may lead to inappropriate treatment. There currently exist no solutions to reproducible neoplasia size measurement adapted to colonoscopy. We propose a colonoscopic size measurement system for neoplasias. By using a simple planar geometry, the key technical problem is reduced to resolving scale. Our core contribution is introducing the Infocus-Breakpoint (IB) that allows us to resolve scale from a regular colonoscopic video. We define the IB as the lower limit of the colonoscope's depth of field. The IB corresponds to a precise colonoscope to tissue distance, called the reference depth, which we calibrate preoperatively. We detect the IB intraoperatively thanks to two novel modules: deformable Blur-Estimating Tracking (BET) and Blur-Model Fitting (BMF). With our system, the endoscopist may interactively measure the length and area of a neoplasia in a 2D colonoscopic image directly. Our system needs no hardware modification to standard monocular colonoscopes, yet reaching a size measurement accuracy of the order of a millimeter, as shown on several phantom and patient datasets. PMID:25277373

Chadebecq, F; Tilmant, C; Bartoli, A

2015-01-01

76

Infliximab and newly diagnosed neoplasia in Crohn's disease: a multicentre matched pair study  

PubMed Central

Background and aims The widespread use of anti?tumour necrosis factor ? antibody (Infliximab) in Crohn's disease (CD) raises concerns about a possible cancer risk in the long term. In a matched pair study, we assessed whether Infliximab is associated with an increased risk of neoplasia. Methods In a multicentre matched pair study, 404 CD patients treated with Infliximab (CD?IFX) were matched with 404 CD patients who had never received Infliximab (CD?C). Cases and controls were matched for sex, age (±5?years), site of CD, age at diagnosis (±5?years), immunosuppressant use, and follow up. New diagnoses of neoplasia from April 1999 to October 2004 were recorded. Results Among the 404 CD?IFX, neoplasia was diagnosed in nine patients (2.22%) while among the 404 CD?C, seven patients developed neoplasia (1.73%) (odds ratio 1.33 (95% confidence interval 0.46–3.84); p?=?0.40). The survival curve adjusted for patient year of follow up showed no differences between CD?IFX and CD?C (p?=?0.90; log rank test). In the CD?IFX group, there was one cholangiocarcinoma, three breast cancers, one skin cancer, one leukaemia, one laryngeal cancer, and two anal carcinomas. Among the 7/404 (1.73%) CD?C, there were three intestinal adenocarcinomas (two caecum, one rectum), one basalioma, one spinalioma, one non?Hodgkin's lymphoma, and one breast cancer. Age at diagnosis of neoplasia did not differ between groups (CD?IFX v CD?C: median 50 (range 40–70?years) v 45 (27–72); p?=?0.50). Conclusion In our multicentre matched pair study, the frequency of a new diagnosis of neoplasia in CD patients treated with Infliximab was comparable with CD patients who had never received Infliximab. PMID:16120759

Biancone, L; Orlando, A; Kohn, A; Colombo, E; Sostegni, R; Angelucci, E; Rizzello, F; Castiglione, F; Benazzato, L; Papi, C; Meucci, G; Riegler, G; Petruzziello, C; Mocciaro, F; Geremia, A; Calabrese, E; Cottone, M; Pallone, F

2006-01-01

77

[Immunohistochemical expression of PTEN antigen: a new tool for diagnosis of early endometrial neoplasia].  

PubMed

We examined immunohistochemical PTEN protein expression in endometrial samples obtained from perimenopausal women with uterine bleeding in order to diagnose early endometrial neoplasia. Paraffin sections of endometrial samples (biopsies, endometrium resection, hysterectomy) were reviewed and tested for immunocytochemical PTEN expression by epithelial cells. Immunohistochemical studies were performed with the Ventana Benchmark device and the immunoperoxidase technique with monoclonal anti-PTEN (6H2.1/Cascade Biosciences). We studied 45 samples of proliferative endometria, 42 samples of atypical hyperplasia (neoplasia), and 55 samples of endometrial carcinomas (30 endometrioid, 5 serous papillary, 10 clear cell, 5 adenosquamous, and 5 MMMT). A strong positive PTEN immunoreaction was observed in all 45 normal proliferative endometria, 2/30 endometrioid carcinomas, and 23/25 non endometrioid carcinomas. In contrast, PTEN immunoexpression was negative or weak in 40/42 atypical hyperplasia and 28/30 endometrioid carcinomas. Negative or weak PTEN expression correlated with endometrial neoplasia (atypical proliferation) (p < 0.001). Thus (i) PTEN immunoexpression in endometrial paraffin sections is a new diagnostic tool, distinguishing PTEN-positive cyclic abnormal monoclonal proliferative endometrium (anovulatory, non atypical, simple and complex hyperplasia) from PTEN-negative (or decreased) endometrial neoplasia, and especially early endometrial neoplasia (atypical simple and complex hyperplasia, in situ carcinoma, superficial carcinoma with focal invasion). (ii) Given the lack of reproducibility of histological identification of atypical (precancerous invasive) and non atypical (precancerous non invasive) endometrial hyperplasia, the new criteria (PTEN-negative crowded glands, gland/stroma ratio > 55%, nuclear pleomorphism, in areas > 1 mm) recently proposed to diagnose early endometrial neoplasia appear to be clinically relevant. PMID:15584653

Taranger-Charpin, Colette; Carpentier, Séverine; Dales, Jean-Philippe; Garcia, Stéphane; Djemli, Amina; Andrac, Lucile; Lavaut, Marie-Noëlle; Sferlazzo, Karine; Boubli, Léon

2004-01-01

78

Parathyroid mitogenic activity in plasma from patients with familial multiple endocrine neoplasia type 1  

SciTech Connect

Hyperplasia of the parathyroid glands is a central feature of familial multiple endocrine neoplasia type 1. We used cultured bovine parathyroid cells to test for mitogenic activity in plasma from patients with this disorder. Normal plasma stimulated (/sup 3/H)thymidine incorporation, on the average, to the same extent as it was stimulated in a plasma-free control culture. This contrasted with the results of the tests with plasma from patients with familial multiple endocrine neoplasia type 1, in which parathyroid mitogenic activity increased 2400 percent over the control value (P less than 0.001). Plasma from these patients also stimulated the proliferation of bovine parathyroid cells in culture, whereas plasma from normal subjects inhibited it. Parathyroid mitogenic activity in plasma from the patients with familial multiple endocrine neoplasia type 1 was greater than that in plasma from patients with various other disorders, including sporadic primary hyperparathyroidism (with adenoma, hyperplasia, or cancer of the parathyroid), sporadic primary hypergastrinemia, sporadic pituitary tumor, familial hypocalciuric hypercalcemia, and multiple endocrine neoplasia type 2 (P less than 0.05). Parathyroid mitogenic activity in the plasma of patients with familial multiple endocrine neoplasia type 1 persisted for up to four years after total parathyroidectomy. The plasma also had far more mitogenic activity in cultures of parathyroid cells than did optimal concentrations of known growth factors or of any parathyroid secretagogue. This mitogenic activity had an apparent molecular weight of 50,000 to 55,000. We conclude that primary hyperparathyroidism in familial multiple endocrine neoplasia type 1 may have a humoral cause.

Brandi, M.L.; Aurbach, G.D.; Fitzpatrick, L.A.; Quarto, R.; Spiegel, A.M.; Bliziotes, M.M.; Norton, J.A.; Doppman, J.L.; Marx, S.J.

1986-05-15

79

Am. J. Hum. Genet. 46:624-630, 1990 The Genetic Defect in Multiple Endocrine Neoplasia Type 2A  

E-print Network

Am. J. Hum. Genet. 46:624-630, 1990 The Genetic Defect in Multiple Endocrine Neoplasia Type 2A Maps of Medicine, Henry Ford Hospital, Detroit Summary Multiple endocrine neoplasia type 2A (MEN2A) is a rare and highly significant sex effect on recombination in the MEN2A region. Introduction The multiple endocrine

Kidd, Kenneth

80

Trends over time in the incidence of cervical neoplasia in comparison to trends over time in human papillomavirus infection  

Microsoft Academic Search

Introduction: The establishment of human papillomavirus (HPV) infection as a major cause of cervical neoplasia has resulted in major efforts to develop prophylactic HPV vaccines for prevention of cervical neoplasia. Cervical cancer and the other HPV-associated cancers constitute a major public health burden and eradication of the major causative infection is certainly the most appealing long-term preventive measure. Nevertheless, the

Joakim Dillner

2000-01-01

81

Clinical and Pathological Heterogeneity of Cervical Intraepithelial Neoplasia Grade 3  

PubMed Central

Objective Cervical intraepithelial neoplasia grade 3 (CIN3), the immediate cervical cancer precursor, is a target of cervical cancer prevention. However, less than half of CIN3s will progress to cancer. Routine treatment of all CIN3s and the majority of CIN2s may lead to overtreatment of many lesions that would not progress. To improve our understanding of CIN3 natural history, we performed a detailed characterization of CIN3 heterogeneity in a large referral population in the US. Methods We examined 309 CIN3 cases in the SUCCEED, a large population-based study of women with abnormal cervical cancer screening results. Histology information for 12 individual loop electrosurgical excision procedure (LEEP) segments was evaluated for each woman. We performed case-case comparisons of CIN3s to analyze determinants of heterogeneity and screening test performance. Results CIN3 cases varied substantially by size (1–10 LEEP segments) and by presentation with concomitant CIN2 and CIN1. All grades of CINs were equally distributed over the cervical surface. In half of the women, CIN3 lesions were found as multiple distinct lesions on the cervix. Women with large and solitary CIN3 lesions were more likely to be older, have longer sexual activity span, and have fewer multiple high risk HPV infections. Screening frequency, but not HPV16 positivity, was an important predictor of CIN3 size. Large CIN3 lesions were also characterized by high-grade clinical test results. Conclusions We demonstrate substantial heterogeneity in clinical and pathological presentation of CIN3 in a US population. Time since sexual debut and participation in screening were predictors of CIN3 size. We did not observe a preferential site of CIN3 on the cervical surface that could serve as a target for cervical biopsy. Cervical cancer screening procedures were more likely to detect larger CIN3s, suggesting that CIN3s detected by multiple independent diagnostic tests may represent cases with increased risk of invasion. PMID:22253702

Yang, Hannah P.; Zuna, Rosemary E.; Schiffman, Mark; Walker, Joan L.; Sherman, Mark E.; Landrum, Lisa M.; Moxley, Katherine; Gold, Michael A.; Dunn, S. Terence; Allen, Richard A.; Zhang, Roy; Long, Rodney; Wang, Sophia S.; Wentzensen, Nicolas

2012-01-01

82

Medical interventions for high grade vulval intraepithelial neoplasia  

PubMed Central

Background Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin; its incidence is increasing in women under 50 years. VIN is graded histologically as low grade or high grade. High grade VIN is associated with infection with human papilloma virus (HPV) infection and may progress to invasive disease. There is no consensus on the optimal management of high grade VIN. The high morbidity and high relapse rate associated with surgical interventions call for a formal appraisal of the evidence available for less invasive but effective interventions for high grade VIN. Objectives To evaluate the effectiveness and safety of medical interventions for high grade VIN. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE (up to September 2010). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) that assessed medical interventions, in adult women diagnosed with high grade VIN. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Where possible the data were synthesised in a meta-analysis. Main results Four trials met our inclusion criteria: three assessed the effectiveness of topical imiquimod versus placebo in women with high grade VIN; one examined low versus high dose indole-3-carbinol in similar women. Meta-analysis of three trials found that the proportion of women who responded to treatment at 5 to 6 months was much higher in the group who received topical imiquimod than in the group who received placebo (relative risk (RR) = 11.95, 95% confidence interval (CI) 3.21 to 44.51). A single trial showed similar results at 12 months in (RR = 9.10, 95% CI 2.38 to 34.77). Only one trial reported adverse events, which were more common in the imiquimod group. One trial found no significant differences in quality of life (QoL) or body image between the imiquimod and placebo groups. Authors’ conclusions Imiquimod appears to be effective, but its safety needs further examination. Its use is associated with side effects which are tolerable, but more extensive data on adverse effects are required. Long term follow-up should be mandatory in view of the known progression of high grade VIN to invasive disease. Alternative medical interventions, such as cidofovir, should be explored. PMID:21491403

Pepas, Litha; Kaushik, Sonali; Bryant, Andrew; Nordin, Andy; Dickinson, Heather O

2014-01-01

83

A Clinical and Pathological Overview of Vulvar Condyloma Acuminatum, Intraepithelial Neoplasia, and Squamous Cell Carcinoma  

PubMed Central

Condyloma acuminatum, intraepithelial neoplasia, and squamous cell carcinoma are three relatively frequent vulvar lesions. Condyloma acuminatum is induced by low risk genotypes of human papillomavirus (HPV). Vulvar intraepithelial neoplasia (VIN) and squamous cell carcinoma have different etiopathogenic pathways and are related or not with high risk HPV types. The goal of this paper is to review the main pathological and clinical features of these lesions. A special attention has been paid also to epidemiological data, pathological classification, and clinical implications of these diseases. PMID:24719870

Léonard, Boris; Kridelka, Frederic; Delbecque, Katty; Goffin, Frederic; Demoulin, Stéphanie; Doyen, Jean; Delvenne, Philippe

2014-01-01

84

Etiology, pathogenesis and epizootiology of hematopoietic neoplasia in the soft-shell clam, Mya arenaria  

SciTech Connect

Studies on the etiology of hematopoietic neoplasia (HN) in soft-shell clams, Mya arenaria, have been inconclusive. Petroleum-derived hydrocarbons, polychlorinated-biphenyls and a virus have all been implicated as causative agents. The isolation of 100 nm virus-like particles from neoplastic clams proved conclusively that the causative agent is a retrovirus. The virus can induce a neoplasia in non-neoplastic clams and similar virus particles can be re-isolated and induce neoplasia. The activities of the RT are temperature dependent, found at 6[degrees]C, but not at 25[degrees]C and 37[degrees]C. The incidence rate for neoplasia in Narragansett Bay, Rhode Island was 7.7% and for combined other locations, 3.7% (26/699). HN was present in clams throughout the year at varying levels. The highest incidence occurred in October (11.5%); the lowest incidence in April (1.2%) and June (2.5%). The outcome of the disease depends on the water temperature and degree of severity of neoplasia in the clams. Death rate was greatest when water temperature was at 15[degrees]C (100%). High severity clams had the highest death rate (100%). Chronicity of persistent neoplasia occurred more at 10[degrees]C (19%) than at 6[degrees]C (15%) or 15[degrees]C (0%). Remission occurred only in low severity juvenile clams at either 6[degrees]C or 10[degrees]C. Neoplasia causes metabolic alteration in clams. Remission occurred only in low severity juvenile clams at either 6[degrees]C or 10[degrees]C. The time to remission was longer at 6[degrees]C than 10[degrees]C. Neoplasia causes metabolic alteration in clams. This shown by a significant increase in uric acid, asparatate transminase and triglycerides and a decrease in urea in the hemolymph. The cell membrane of neoplastic hemocytes also shows differences in their binding pattern to lectin than the normal hemocytes, indicating a change in cell surface glycoprotein probably induced by the retrovirus.

Paquette, G.E.

1992-01-01

85

Depressive Symptoms and Cervical Neoplasia in HIV+ Low-Income Minority Women with Human Papillomavirus Infection  

Microsoft Academic Search

Background  Prior work has related elevated life stress to greater risk of cervical neoplasia in women with human immunodeficiency virus\\u000a (HIV) and human papillomavirus (HPV).\\u000a \\u000a \\u000a \\u000a Purpose  This study investigated associations between depressive symptoms and cervical neoplasia in HIV+ HPV+ women. Participants were\\u000a 58 HIV+ HPV+ women.\\u000a \\u000a \\u000a \\u000a Method  Participants underwent colposcopy, including HPV screening, Papanicolaou smear, and cervical biopsy to determine study eligibility.\\u000a Eligible

Stacy M. Dodd; Deidre B. Pereira; Ilona Marion; Michele Andrasik; Rachel Rose; Trudi Simon; Mary Ann Fletcher; Joseph Lucci; Kevin Maher; Mary Jo O’Sullivan; JoNell Efantis-Potter; Michael H. Antoni

2009-01-01

86

Thymic carcinoids in multiple endocrine neoplasia type 1.  

PubMed Central

OBJECTIVE: To study the clinical, pathologic, and genetic features of thymic carcinoids in the setting of multiple endocrine neoplasia type 1 (MEN1) and to study means for detection and prevention of this tumor in patients with MEN1. SUMMARY BACKGROUND DATA: Thymic carcinoid is a rare malignancy, with approximately 150 cases reported to date. It may be associated with MEN1 and carries a poor prognosis, with no effective treatment. Its underlying etiology is unknown. METHODS: Ten patients with MEN1 from eight families with anterior mediastinal tumors were included in a case series study at tertiary referring hospitals. Clinicopathologic studies were done on these patients, with a review of the literature. Mutation analysis was performed on the MEN1 gene in families with clusterings of the tumor to look for genotype-phenotype correlation. Loss of heterozygosity was studied in seven cases to look for genetic abnormalities. RESULTS: Histologic studies of all tumors were consistent with the diagnosis of thymic carcinoid. Clustering of this tumor was found in some of the families-three pairs of brothers and three families with first- or second-degree relatives who had thymic carcinoid. All patients described here were men, with a mean age at detection of 44 years (range 31 to 66). Most of the patients had chest pain or were asymptomatic; none had Cushing's or carcinoid syndrome. All tumors were detected by computed tomography (CT) or magnetic resonance imaging (MRI) of the chest. The results of octreoscans performed in three patients were all positive. Histopathologic studies were consistent with the diagnosis of thymic carcinoid and did not stain for ACTH. Mutation analysis of the families with clustering revealed mutations in different exons/introns of the MEN1 gene. Loss of heterozygosity (LOH) studies of seven tumors did not show LOH in the MEN1 region, but two tumors showed LOH in the 1p region. CONCLUSIONS: MEN1-related thymic carcinoids constitute approximately 25% of all cases of thymic carcinoids. In patients with MEN1, this is an insidious tumor not associated with Cushing's or carcinoid syndrome. Local invasion, recurrence, and distant metastasis are common, with no known effective treatment. We propose that CT or MRI of the chest, as well as octreoscanning, should be considered as part of clinical screening in patients with MEN1. We also propose performing prophylactic thymectomy during subtotal or total parathyroidectomy on patients with MEN1 to reduce the risks of thymic carcinoid and recurrence of hyperparathyroidism. Its male predominance, the absence of LOH in the MEN1 region, clustering in close relatives, and the presence of different MEN1 mutations in these families suggest the involvement of modifying genes in addition to the MEN1 gene. A putative tumor suppressor gene in 1p may be involved. Images Figure 1. Figure 2. Figure 3. PMID:9671073

Teh, B T; Zedenius, J; Kytölä, S; Skogseid, B; Trotter, J; Choplin, H; Twigg, S; Farnebo, F; Giraud, S; Cameron, D; Robinson, B; Calender, A; Larsson, C; Salmela, P

1998-01-01

87

Predictive factors from cold knife conization for residual cervical intraepithelial neoplasia in subsequent hysterectomy  

Microsoft Academic Search

OBJECTIVE: The optimal management of cervical intraepithelial neoplasia after cold knife conization remains controversial. Reliable predictors of residual dysplasia in the cervix after cold knife conization have not been consistently identified. This study was initiated to examine the accuracy of the traditional factors used to predict residual dysplasia in hysterectomy specimens after cold knife conization.STUDY DESIGN: A retrospective 10-year chart

Barbara C. Moore; Robert V. Higgins; Sherry L. Laurent; Marie-Claire Marroum; Patricia Bellitt

1995-01-01

88

Trends in Squamous Cell Carcinoma of the Vulva: The Influence of Vulvar Intraepithelial Neoplasia  

Microsoft Academic Search

Objective: To determine trends in the clinicopathology of vulvar squamous cell carcinoma over the past 2 decades, with particular reference to the possible effects of the increasing incidence of vulvar intraepithelial neoplasia (VIN) during this time.Methods: Two cohorts of 56 and 57 women with squamous cell carcinoma of the vulva and separated by at least 2 decades were reviewed retrospectively.

R. W Jones; Judith Baranyai; S Stables

1997-01-01

89

Incidence and clinical significance of high-grade prostatic intraepithelial neoplasia in turp specimens  

Microsoft Academic Search

Objectives. To determine the incidence and clinical significance of high-grade prostatic intraepithelial neoplasia (PIN) in specimens obtained from transurethral resection of the prostate (TURP).Methods. All TURP specimens accessioned to the general surgical pathology service of the Johns Hopkins Hospital (JHH) from March 1984 through December 1987 that did not contain adenocarcinoma of the prostate were reviewed for the presence of

Paul B. Gaudin; Isabell A. Sesterhenn; Kirk J. Wojno; F. K. Mostofi; Jonathan I. Epstein

1997-01-01

90

Potential of Cervical Electrosurgical Excision Procedure for Diagnosis and Treatment of Cervical Intraepithelial Neoplasia  

Microsoft Academic Search

The aim of this study was to evaluate the diagnostic potential, treatment efficacy, specimen adequacy, and acute complication rate associated with electrosurgical excision procedure (EEP) of the cervix for the management of cervical intraepithelial neoplasia (CIN). Analysis was performed retrospectively on 153 consecutive patients who underwent EEP under colposcopic guidance. Patients with negative endocervical curettage (ECC), adequate colposcopy, and biopsy-proven

Thomas J. Herzog; Sybilann Williams; Lisa M. Adler; Janet S. Rader; Richard T. Kubiniec; H. Marvin Camel; David G. Mutch

1995-01-01

91

Cervical HPV infection and neoplasia in a large population-based prospective study: the Manchester cohort  

Microsoft Academic Search

Cytology and histology records and cervical samples for HPV assay were obtained from a prospective cohort of 49 655 women attending clinics for routine cervical cytology in or near Manchester between 1988 and 1993. The women were followed up for cytological abnormality and neoplasia through the cytology laboratory's records. HPV at entry was assayed in an age- and period-stratified random

J Peto; C Gilham; J Deacon; C Taylor; C Evans; W Binns; M Haywood; N Elanko; D Coleman; R Yule; M Desai

2004-01-01

92

Folate-genetics and colorectal neoplasia: What we know and need to know next  

Technology Transfer Automated Retrieval System (TEKTRAN)

The metabolism of folate involves a complex network of polymorphic enzymes that may explain a proportion of the risk associated with colorectal neoplasia. Over 60 observational studies primarily in non-Hispanic White populations have been conducted on selected genetic variants in specific genes, MTH...

93

Incidence of high-grade prostatic intraepithelial neoplasia in sextant needle biopsy specimens  

Microsoft Academic Search

ObjectivesThere is scant literature on the frequency of high-grade prostatic intraepithelial neoplasia (PIN) in needle biopsy specimens. These data have implications as to how often pathologists should be expected to diagnose these lesions on needle biopsy and impact on the feasibility of cancer chemoprevention trials for prostate cancer.

Marcia L. Wills; Ulrike M. Hamper; Alan W. Partin; Jonathan I. Epstein

1997-01-01

94

Pyrosequencing Technology as a Method for the Diagnosis of Multiple Endocrine Neoplasia Type 2  

Microsoft Academic Search

Background: Multiple endocrine neoplasia type 2 (MEN2) is a cancer syndrome with well-characterized causative mutations. Missense mutations in 15 codons of the RET gene have been linked to disease phenotypes in the vast majority of cases. These missense mutations range from very simple single nucleotide base changes to more numerous changes at a given codon; they therefore are often tested

Kent E. Kruckeberg; Stephen N. Thibodeau

95

USING THE INFOCUS-BREAKPOINT TO ESTIMATE THE SCALE OF NEOPLASIA IN COLONOSCOPY  

E-print Network

- blur breakpoint in a video sequence. We simultaneously track a neoplasia with a 2D affine. INTRODUCTION Colorectal cancer is the fourth leading cause of death by cancer according to the World Health). The polyp's scale is estimated from a gastroscope's video. This is achieved by finding the IB corresponding

Bartoli, Adrien

96

Post-surgical follow-up of primary hyperparathyroidism associated with multiple endocrine neoplasia type 1  

PubMed Central

The bone mineral density increments in patients with sporadic primary hyperparathyroidism after parathyroidectomy have been studied by several investigators, but few have investigated this topic in primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Further, as far as we know, only two studies have consistently evaluated bone mineral density values after parathyroidectomy in cases of primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Here we revised the impact of parathyroidectomy (particularly total parathyroidectomy followed by autologous parathyroid implant into the forearm) on bone mineral density values in patients with primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Significant increases in bone mineral density in the lumbar spine and femoral neck values were found, although no short-term (15 months) improvement in bone mineral density at the proximal third of the distal radius was observed. Additionally, short-term and medium-term calcium and parathyroid hormone values after parathyroidectomy in patients with primary hyperparathyroidism associated with multiple endocrine neoplasia type 1 are discussed. In most cases, this surgical approach was able to restore normal calcium/parathyroid hormone levels and ultimately lead to discontinuation of calcium and calcitriol supplementation. PMID:22584724

Coutinho, Flavia L.; Lourenco, Delmar M.; Toledo, Rodrigo A.; Montenegro, Fabio L. M.; Toledo, Sergio P. A.

2012-01-01

97

A linked genetic marker for multiple endocrine neoplasia type 2A on chromosome 10  

Microsoft Academic Search

Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominantly inherited cancer syndrome characterized by medullary carcinoma of the thyroid, phaeochromocytoma and hyperparathyroidism. Almost all gene carriers can be detected by screening tests before the age of 40 (ref. 1), but the nature and location of the predisposing gene are unknown. Simpson et al.2 recently reported preliminary evidence for linkage

C. G. P. Mathew; K. S. Chin; D. F. Easton; K. Thorpe; C. Carter; G. I. Liou; S.-L. Fong; C. D. B. Bridges; H. Haak; A. C. Nieuwenhuijzen Kruseman; S. Schifter; H. H. Hansen; H. Telenius; M. Telenius-Berg; B. A. J. Ponder

1987-01-01

98

Cortical-Sparing Laparoscopic Adrenalectomy in a Patient with Multiple Endocrine Neoplasia Type IIA  

Microsoft Academic Search

We describe the case of a patient affected by multiple endocrine neoplasia type IIA with a new diagnosis of an asymptomatic right pheochromocytoma. The patient underwent laparoscopic adrenalectomy with adrenal sparing. The removal of the tumor was successful with preservation of about one third of the adrenal gland. At the time of the last follow-up, the patient is well with

F. Porpiglia; P. Destefanis; S. Bovio; B. Allasino; F. Orlandi; D. Fontana; A. Angeli; M. Terzolo

2002-01-01

99

Multiple Intestinal Neoplasia Caused by a Mutation in the Murine Homolog of the APC Gene  

Microsoft Academic Search

Germ-line mutations of the APC gene are responsible for familial adenomatous polyposis (FAP), an autosomal dominantly inherited disease in humans. Patients with FAP develop multiple benign colorectal tumors. Recently, a mouse lineage that exhibits an autosomal dominantly inherited predisposition to multiple intestinal neoplasia (Min) was described. Linkage analysis showed that the murine homolog of the APC gene (mApc) was tightly

Li-Kuo Su; Kenneth W. Kinzler; Bert Vogelstein; Antonette C. Preisinger; Amy Rapaich Moser; Cindy Luongo; Karen A. Gould; William F. Dove

1992-01-01

100

Proceedings From the First Asia-Oceania Research Organisation on Genital Infections and Neoplasia (AOGIN) Meeting  

PubMed Central

The First Asia-Oceania Research Organisation on Genital Infections and Neoplasia (AOGIN) Meeting was held in Kota Kinabalu, Malaysia, in July 2005. The conference covered regional issues relating to infection with the human papillomavirus—epidemiology, virology, and immunology, testing, screening, and prevention strategies—as well as cervical cancer screening and its management.

Faro, Edited by Sebastian

2006-01-01

101

J Mammary Gland Biol Neoplasia . Author manuscript Snail family regulation and epithelial mesenchymal transitions in breast  

E-print Network

J Mammary Gland Biol Neoplasia . Author manuscript Page /1 12 Snail family regulation the mammary gland as cellular model. EMT: general characteristics, stages of EMT found and . Partial EMTin wound healing and mammary tubulogenesis ( ), and leads to an intermediate phenotype, retaining some2

Paris-Sud XI, Université de

102

Comparative genomic hybridization studies in tumours from a patient with multiple endocrine neoplasia type 1  

Microsoft Academic Search

Objective: To identify genetic changes, other than the MEN1 gene, that might be involved in the tumorigenesis and progression of multiple endocrine neoplasia type 1 (MEN1)-related tumours. Methods: We used comparative genomic hybridization (CGH) and loss of heterozygosity (LOH) to study tumours from various sites in a patient with MEN1. Results: Gain of genetic material was not found. Frequent losses

Soili Kytola; Markus J Makinen; Marketta Kahkonen; Bin Tean Teh; Jaakko Leisti; Pasi Salmela

1998-01-01

103

Expression of mutant protein p53 and Hsp70 and Hsp90 chaperones in cockles Cerastoderma edule affected by neoplasia.  

PubMed

High prevalence of disseminated neoplasia has been found in cockles Cerastoderma edule of Galicia (NW Spain). Disseminated neoplasia has been associated with high mortalities of various bivalve species. In vertebrates, proteins such as p53 and heat shock proteins (HSPs) play important roles in carcinogenesis. The protein p53 has been detected in neoplastic cells of bivalve molluscs such as Mytilus edulis, Mytilus trossulus, Mya arenaria, Spisula solidissima, Crassostrea rhizophorae and Crassostrea gigas. In this study, western blotting analyses were used to test the expression of Hsp70, Hsp90 and mutant p53 proteins in the cells and plasma of the haemolymph of cockles showing various intensities of neoplasia. Disseminated neoplasia was previously diagnosed by examination of stained haemolymph monolayers with light microscopy. In the present study, mutant p53 was detected in haemolymph cells of cockles diagnosed as affected by moderate and heavy neoplasia intensity, whereas it was not detected in cockles with either no or light neoplasia. The higher the neoplasia intensity, the higher the levels of Hsp70 and Hsp90. These proteins were not found in plasma. The results reveal the possible association between p53 and HSPs in neoplastic cells of cockles, which could prevent p53 from carrying out its functions, as occurs in human cancers. PMID:20815330

Díaz, S; Cao, A; Villalba, A; Carballal, M J

2010-07-01

104

Is Endoscopic Ultrasound (EUS) necessary in the pre-therapeutic assessment of Barrett’s esophagus with early neoplasia?  

PubMed Central

Endoscopic ultrasound (EUS) is considered the most accurate tool for the TNM staging of esophageal cancer, but its role in early Barrett’s neoplasia is still debatable. The aim was to evaluate the utility of EUS in Barrett’s patients prior to therapy. Retrospective review of 109 patients enrolled in a treatment protocol for Barrett’s neoplasia in our institution. EUS assessment was classified as suspicious for invasion in 19 patients; 84% of them had no evidence of invasion in final pathology. The assessment of depth of invasion of Barrett’s neoplasia based solely on EUS findings leads to overstaging in most patients. PMID:23205307

Fernández-Sordo, Jacobo Ortiz; Konda, Vani J.A.; Chennat, Jennifer; Madrigal-Hoyos, Erika; Posner, Mitchell C.; Ferguson, Mark K.

2012-01-01

105

Untypable human papillomavirus infection and risk of cervical intraepithelial neoplasia among women with abnormal cervical cytology.  

PubMed

The risk of cervical intraepithelial neoplasia and/or invasive cervical cancer associated with untypable human papillomavirus (HPV) infections has been not investigated fully. HPV infection caused by 18 high-risk and 7 low-risk genotypes as detected by the INNO-LIPA genotyping system, was investigated in 4,258 women with abnormal Pap smear referred to a colposcopic service. The prevalence of HPV infection was 76.1%. Rates of cervical intraepithelial neoplasia grade 3+ were 0.88% (9/1,017) in HPV-negative subjects, 1.8% (7/380) in subjects with untypable HPV infection, 3.2% (11/343) in subjects with single/multiple low-risk types, 28.3% (201/709) in subjects with multiple low and high-risk types, 15.2% (162/1,069) in subjects with single high-risk types, and 31.2% (229/733) in those with multiple high-risk types. Compared to women without any HPV infection, the odds ratios of cervical intraepithelial neoplasia grade 2+ or grade 3+ in subjects with untypable or low-risk HPV genotypes were 5.73 (95% CI?=?2.79-11.78) and 12.4 (95% CI?=?6.31-24.5, P?=?0.014 compared to untypable) and 3.1 (95% CI?=?1.11-8.16) and 7.1 (95% CI?=?2.9-17.2, P?=?0.07 compared to untypable), respectively. In the subgroup of subjects with cervical intraepithelial neoplasia grade 1 or negative colposcopy/biopsy, the progression to cervical intraepithelial neoplasia grade 2+ at follow-up (median 25 months, range 6-70) was 2% (14/684), 3.4% (7/205), and 5.6% (11/195, P?=?0.04 compared to negative) among negative, untypable, and low-risk HPV infection, respectively. The risk of cervical intraepithelial neoplasia associated with untypable HPV infection was higher than that recorded among uninfected women, but lower than the risk associated with low- or high-risk HPV genotypes. PMID:24692002

Spinillo, Arsenio; Gardella, Barbara; Roccio, Marianna; Alberizzi, Paola; Silini, Enrico Maria; Dal Bello, Barbara

2014-07-01

106

Genetics Home Reference: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia  

MedlinePLUS

... called a magnesium transporter, which moves charged atoms (ions) of magnesium (Mg2+) into certain T cells. Specifically, ... deficiency ; gene ; immune system ; immunodeficiency ; infection ; inheritance ; inherited ; ions ; lymphoma ; mutation ; neoplasia ; pneumonia ; population ; prevalence ; protein ; recessive ; ...

107

Endoscopic Mucosal Resection in the Management of Esophageal Neoplasia: Current Status and Future Directions  

PubMed Central

Endoscopic mucosal resection has expanded the role of the gastroenterologist in the management of esophageal neoplasia from screening and diagnosis to staging and endoscopic treatment. Its rise to prominence is a reflection of the long identified need to obtain histological information regarding depth of invasion and neoplastic margins during therapy that previously could not be achieved with ablative techniques. The resultant improvement in diagnosis and staging has allowed for better selection of patients for endoscopic therapy who may be spared invasive surgery. The clinical indications, endoscopic techniques, outcomes and complications in the management of esophageal neoplasia are reviewed in this manuscript. Training requirements to achieve proficiency in EMR as well as potential quality measures to assess competence are also proposed in this review. PMID:20541628

Namasivayam, Vikneswaran; Wang, Kenneth K.; Prasad, Ganapathy A

2010-01-01

108

A new association – multiple endocrine neoplasia type 1 and malignant peripheral nerve sheath tumor  

PubMed Central

Key Clinical Message We report a patient with multiple endocrine neoplasia type 1 (MEN-1) and an aggressive malignant peripheral nerve sheath tumor (MPNST) arising from a ganglioneuroma of the adrenal gland. Patients with MEN-1 require careful consideration of other tumor associations, including MPNST, as it can portend a poor prognosis. MEN-1 and MPNST have not been reported. We report a patient with multiple endocrine neoplasia type 1 (MEN-1) and an aggressive malignant peripheral nerve sheath tumor (MPNST) arising from a ganglioneuroma of the adrenal gland. Patients with MEN-1 require careful consideration of other tumor associations, including MPNST, as it can portend a poor prognosis. MEN-1 and MPNST have not been reported.

Preda, Veronica; Sywak, Mark; Learoyd, Diana

2015-01-01

109

The Cost-Effectiveness of CT Colonography in Screening for Colorectal Neoplasia  

Microsoft Academic Search

BACKGROUND:We examined the cost-effectiveness of 2- and 3-dimensional computerized tomography (CT) colonography as a screening test for colorectal neoplasia.METHODS:We created a Markov model of the natural history of colorectal cancer. Effectiveness of screening was based upon the diagnostic accuracy of tests in detecting polyps and cancer.RESULTS:CT colonography every 5 or 10 yr was effective and cost-effective relative to no screening.

Sandeep Vijan; Inku Hwang; John Inadomi; Roy K. H. Wong; J. Richard Choi; John Napierkowski; Jonathan M. Koff; Perry J. Pickhardt

2007-01-01

110

Laparoscopic management of benign serous neoplasia arising from persistent ovarian remnant.  

PubMed

Serous cystadenoma arising from ovarian remnant has not been reported in the literature. We report 3 cases with ovarian remnant syndrome that were treated with laparoscopic excision and were proven to be benign serous neoplasia with ovarian origin on final pathologic examination. We review the current evidence for malignant transformation potential of ovarian serous cystadenoma and discuss laparoscopic techniques for management of ovarian remnant syndrome. PMID:17848331

Mahdavi, Ali; Kumtepe, Yakup; Nezhat, Farr

2007-01-01

111

A hypothesis to relate salivary tumors with mammary and prostate neoplasias  

PubMed Central

Salivary, mammary and prostate glands are sex hormone-dependent organs sharing common aspects in structure, hormonal responsiveness and tumor histopathology. Salivary tumors (especially the malignant types) are not as frequent as mammary and prostate neoplasias. Hence, prognosis of some salivary tumors is not always efficient. Here, we review the oncology of salivary gland and its putative relation to breast/prostate tumors. PMID:17597843

Actis, Adriana B

2005-01-01

112

Nonpreserved human amniotic membrane transplantation for conjunctival reconstruction after excision of extensive ocular surface neoplasia  

Microsoft Academic Search

PurposeTo report our experience on the use of nonpreserved human amniotic membrane transplantation (AMT) in ocular surface reconstruction after excision of extensive ocular surface neoplasia (OSN).DesignProspective noncomparative interventional case series.ParticipantsIn all, 10 eyes of 10 consecutive patients with extensive OSN involving various areas of limbus, conjunctiva, and cornea (conjunctival carcinoma in situ, four eyes; squamous cell carcinoma, three eyes; malignant

K Gündüz; Ö Ö Uçakhan; A Kanpolat; I Günalp

2006-01-01

113

Acute renal failure as an initial manifestation of multiple endocrine neoplasia (MEN) type 1.  

PubMed

Multiple endocrine neoplasia (MEN) is a group of heritable syndromes characterized by aberrant growth of benign or malignant tumors in a subset of endocrine tissues. There are three major syndromes: MEN1, 2A and 2B. We describe a 60-year-old woman who initially manifested acute renal failure due to hypercalcemia and dehydration and, finally, was diagnosed as a sporadic MEN1 case. PMID:22237232

Afshar, Reza; Sanavi, Suzan; Taheri, Hamid-Reza

2012-01-01

114

The association between sexually transmitted pathogens and cervical intra-epithelial neoplasia in a developing community  

Microsoft Academic Search

OBJECTIVE--To determine the association of sexually transmitted pathogens in women with cervical intra-epithelial neoplasia (CIN). SETTING--An urban tertiary referral hospital serving a large indigent developing community. PARTICIPANTS--48 women attending a colposcopy clinic and 49 women attending a family planning clinic. METHODS--Vaginal, endocervical, rectal swab specimens and sera were collected for the detection of sexually transmitted pathogens. Cervical cytology was performed

A B Kharsany; A A Hoosen; J Moodley; J Bagaratee; E Gouws

1993-01-01

115

Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma  

Microsoft Academic Search

Multiple endocrine neoplasia type 1 (MEN-1) is a predisposition to hyperplasia of the parathyroid glands, and to hyperplasia or tumours of the anterior pituitary and the endocrine pancreas, and is inherited as an autosomal dominant trait1. Here we map the MEN-1 locus to chromosome 11 by family studies, and demon-strate tight linkage with the human muscle phosphorylase gene. By comparing

Catharina Larsson; Britt Skogseid; Kjell Öberg; Yusuke Nakamura; Magnus Nordenskjöld

1988-01-01

116

Where’s the High-Grade Cervical Neoplasia? The Importance of Minimally Abnormal Papanicolaou Diagnoses  

Microsoft Academic Search

%Objective: To characterize the relative contributions of the different abnormal Papanicolaou smear cytologic diagnoses in the Bethesda System to the subsequent histologic diagnosis of high-grade cervical neoplasia.Methods: A total of 46,009 nonpregnant female members of the Kaiser Permanente Health Plan, Northern California Region, were studied prospectively. The main outcome measures included routine Papanicolaou smear diagnoses and subsequent histologic diagnosis of

Walter K. Kinney; M. Michele Manos; Leo B. Hurley; Janice E. Ransley

1998-01-01

117

Neoplasia in felids at the Knoxville Zoological Gardens, 1979-2003.  

PubMed

A review of medical records and necropsy reports from 1979-2003 found 40 neoplasms in 26 zoo felids, including five lions (Panthera leo, two males and three females), three leopards (Panthera pardus, two males and one female), one jaguar (Panthera onca, female), 11 tigers (Panthera tigris, three males and eight females), two snow leopards (Panthera uncia, one male and one female), two cougars (Felis concolor, one male and one female), one bobcat (Felis rufus, male), and one cheetah (Acinonyx jubatus, female). Animals that had not reached 3 yr of age or had been housed in the collection less than 3 yrs were not included in the study. Neoplasia rate at necropsy was 51% (24/47), and overall incidence of felid neoplasia during the study period was 25% (26/103). Neoplasia was identified as the cause of death or reason for euthanasia in 28% (13/47) of those necropsied. Neoplasms were observed in the integumentary-mammary (n=11), endocrine (n=10), reproductive (n=8), hematopoietic-lymphoreticular (n=5), digestive (n=3), and hepatobiliary (n=2) systems. One neoplasm was unclassified by system. Multiple neoplasms were observed in 11 animals. Both benign and malignant neoplasms were observed in all systems except for the hematopoietic-lymphoreticular systems where all processes were malignant. Of the endocrine neoplasms, those involving the thyroid and parathyroid glands predominated (n=8) over other endocrine organs and included adenomas and carcinomas. In the integumentary system, 63% (7/11) of neoplasms involved the mammary gland, with mammary carcinoma representing 83% (6/7) of the neoplasms. The rates of neoplasia at this institution, during the given time period, appears to be greater than rates found in the one other published survey of captive felids. PMID:19110704

Owston, Michael A; Ramsay, Edward C; Rotstein, David S

2008-12-01

118

Laparoscopic colectomy for apparently benign colorectal neoplasia: A word of caution  

Microsoft Academic Search

Purpose  Endoscopically unresectable apparently benign colorectal polyps are considered by some surgeons as ideal for their early laparoscopic\\u000a colectomy experience. Our hypotheses were: (1) a substantial fraction of patients undergoing laparoscopic colectomy for apparently\\u000a benign colorectal neoplasia will have adenocarcinoma on final pathology; and (2) in our practice, we perform an adequate laparoscopic\\u000a oncological resection for apparently benign polyps as evidenced

Marc Brozovich; Thomas E. Read; Javier Salgado; Robert P. Akbari; James T. McCormick; Philip F. Caushaj

2008-01-01

119

Comparative analysis of the expression patterns of metalloproteinases and their inhibitors in breast neoplasia, sporadic colorectal neoplasia, pulmonary carcinomas and malignant non-Hodgkin's lymphomas in humans.  

PubMed Central

Matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases, TIMPs) play essential roles in the remodelling of the extracellular matrix (ECM). Results of in vivo and in vitro studies suggest that the balance between MMPs and TIMPs is altered in neoplasia, contributing to the invasive and metastatic properties of malignant tumours. In this study we have analysed the expression of five MMP genes and TIMP-1 and TIMP-2 in 37 benign and malignant lesions of human breast using Northern blot analysis. MMP-9 (92 kDa gelatinase) and MMP-11 (stromelysin 3) were most consistently expressed by carcinomas. Based on detection of either MMP-9 or MMP-11 mRNAs, we were able to distinguish between malignant and benign disease with a predictive accuracy of 90% with 94% sensitivity and 85% specificity. Subsequently, these results were compared with results for carcinomas of colon and lung and malignant non-Hodgkin's lymphomas (NHL). Elevated MMP-9 and TIMP-1 expression was observed in all four systems. MMP-11 characterised all carcinomas as well as carcinomas in situ but was not detectable in NHL. Our data therefore argue that there are remarkably similar patterns of specific functions involved in ECM remodelling that correlate with malignancy in different human tumours of different histogenesis. However, MMP-11 expression is a characteristic of tumours of epithelial origin that is not found in lymphoid neoplasia. Thus it suggests that MMP-11 may play a regulatory role in the invasion and metastasis of carcinomas. Images Figure 1 PMID:8645587

Kossakowska, A. E.; Huchcroft, S. A.; Urbanski, S. J.; Edwards, D. R.

1996-01-01

120

Detection of high-risk human papillomavirus subtypes in cervical glandular neoplasia by in situ hybridization  

PubMed Central

In situ hybridization (ISH) was performed on paraffin-embedded tissues to detect multiple high-risk human papillomavirus (HPV) subtypes in 27 cases of cervical adenocarcinoma in situ (AIS) and adenocarcinoma (CA) specimens. These results were compared with those of HPV detection by HPV-PCR genotyping and p16 immunohistochemistry in the same specimens. Of the 27 cases, 17 (63%) showed HPV-DNA by HPV-ISH, including 3 metastatic lesions. HPV-DNA was detected in 18 cases (67%) by PCR. The concordance rate between HPV-ISH and HPV-PCR genotyping was 74% with moderate agreement (Kappa value, 0.41). HPV-16 was identified in 5 cases, HPV-18 in 2 cases, and HPV-45 in 1 case. Combining the results of HPV-ISH and HPV-PCR/genotyping, 22 cases (81.5%) were considered HPV positive. Immunohistochemical staining of p16 indicated that 25 (93%) cases were positive; however, 4 of these cases were HPV-negative by both PCR and ISH. Combining HPV-ISH and HPV-PCR/genotyping techniques demonstrated a high sensitivity of HPV detection in FFPE tissues from cervical glandular neoplasias. In contrast, p16 immunohistochemistry seemed to have a low specificity for determining HPV status in cervical glandular neoplasia. HPV-ISH is useful for recognizing the distribution of HPV in AIS and CA tissues and visualizing signal patterns, and may be a useful tool to confirm the cervical origin of neoplasias and metastatic lesions. PMID:24133595

Sheng, Zhang; Minato, Hiroshi; Sasagawa, Toshiyuki; Nakada, Satoko; Kinoshita, Eriko; Kurose, Nozomu; Nojima, Takayuki; Makinoda, Satoru

2013-01-01

121

Detection of high-risk human papillomavirus subtypes in cervical glandular neoplasia by in situ hybridization.  

PubMed

In situ hybridization (ISH) was performed on paraffin-embedded tissues to detect multiple high-risk human papillomavirus (HPV) subtypes in 27 cases of cervical adenocarcinoma in situ (AIS) and adenocarcinoma (CA) specimens. These results were compared with those of HPV detection by HPV-PCR genotyping and p16 immunohistochemistry in the same specimens. Of the 27 cases, 17 (63%) showed HPV-DNA by HPV-ISH, including 3 metastatic lesions. HPV-DNA was detected in 18 cases (67%) by PCR. The concordance rate between HPV-ISH and HPV-PCR genotyping was 74% with moderate agreement (Kappa value, 0.41). HPV-16 was identified in 5 cases, HPV-18 in 2 cases, and HPV-45 in 1 case. Combining the results of HPV-ISH and HPV-PCR/genotyping, 22 cases (81.5%) were considered HPV positive. Immunohistochemical staining of p16 indicated that 25 (93%) cases were positive; however, 4 of these cases were HPV-negative by both PCR and ISH. Combining HPV-ISH and HPV-PCR/genotyping techniques demonstrated a high sensitivity of HPV detection in FFPE tissues from cervical glandular neoplasias. In contrast, p16 immunohistochemistry seemed to have a low specificity for determining HPV status in cervical glandular neoplasia. HPV-ISH is useful for recognizing the distribution of HPV in AIS and CA tissues and visualizing signal patterns, and may be a useful tool to confirm the cervical origin of neoplasias and metastatic lesions. PMID:24133595

Sheng, Zhang; Minato, Hiroshi; Sasagawa, Toshiyuki; Nakada, Satoko; Kinoshita, Eriko; Kurose, Nozomu; Nojima, Takayuki; Makinoda, Satoru

2013-01-01

122

Identifying constituent spectra sources in multispectral images to quantify and locate cervical neoplasia  

NASA Astrophysics Data System (ADS)

Optical spectroscopy has been shown to be an effective method for detecting neoplasia. Guided Therapeutics has developed LightTouch, a non invasive device that uses a combination of reflectance and fluorescence spectroscopy for identifying early cancer of the human cervix. The combination of the multispectral information from the two spectroscopic modalities has been shown to be an effective method to screen for cervical cancer. There has however been a relative paucity of work in identifying the individual spectral components that contribute to the measured fluorescence and reflectance spectra. This work aims to identify the constituent source spectra and their concentrations. We used non-negative matrix factorization (NNMF) numerical methods to decompose the mixed multispectral data into the constituent spectra and their corresponding concentrations. NNMF is an iterative approach that factorizes the measured data into non-negative factors. The factors are chosen to minimize the root-mean-squared residual error. NNMF has shown promise for feature extraction and identification in the fields of text mining and spectral data analysis. Since both the constituent source spectra and their corresponding concentrations are assumed to be non-negative by nature NNMF is a reasonable approach to deconvolve the measured multispectral data. Supervised learning methods were then used to determine which of the constituent spectra sources best predict the amount of neoplasia. The constituent spectra sources found to best predict neoplasia were then compared with spectra of known biological chromophores.

Baker, Kevin C.; Bambot, Shabbir

2011-02-01

123

Targeted imaging of esophageal neoplasia with a fluorescently labeled peptide: First in-human results  

PubMed Central

Esophageal adenocarcinoma is rising rapidly in incidence, and usually develops from Barrett’s esophagus, a precursor condition commonly found in patients with chronic acid reflux. Pre-malignant lesions are challenging to detect on conventional screening endoscopy because of their flat appearance. Molecular changes can be used to improve detection of early neoplasia. We have developed a peptide that binds specifically to high-grade dysplasia and adenocarcinoma. We first applied the peptide ex vivo to esophageal specimens from 17 patients to validate specific binding. Next, we performed confocal endomicroscopy in vivo in 25 human subjects after topical peptide administration and found 3.8-fold greater fluorescence intensity for esophageal neoplasia compared with Barrett’s esophagus and squamous epithelium with 75% sensitivity and 97% specificity. No toxicity was attributed to the peptide in either animal or patient studies. Therefore, our first-in-humans results show that this targeted imaging agent is safe, and may be useful for guiding tissue biopsy and for early detection of esophageal neoplasia and potentially other cancers of epithelial origin, such as bladder, colon, lung, pancreas, and stomach. PMID:23658246

Sturm, Matthew B.; Joshi, Bishnu P.; Lu, Shaoying; Piraka, Cyrus; Khondee, Supang; Elmunzer, B. Joseph; Kwon, Richard S.; Beer, David G.; Appelman, Henry; Turgeon, D. Kim; Wang, Thomas D.

2013-01-01

124

Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review.  

PubMed

Epidemiologic and mechanistic evidence suggests that folate is involved in colorectal neoplasia. Some polymorphic genes involved in folate metabolism--methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G), cystathionine beta-synthase (CBS exon 8, 68-base-pair insertion), and thymidylate synthase (TS enhancer region and 3' untranslated region)--have been investigated in colorectal neoplasia. For MTHFR C677T and A1298C, the variant allele is associated with reduced enzyme activity in vitro. For the other polymorphisms, functional data are limited and/or inconsistent. Genotype frequencies for all of the polymorphisms show marked ethnic and geographic variation. In most studies, MTHFR 677TT (10 studies, >4,000 cases) and 1298CC (four studies, >1,500 cases) are associated with moderately reduced colorectal cancer risk. In four of five genotype-diet interaction studies, 677TT subjects who had higher folate levels (or a "high-methyl diet") had the lowest cancer risk. In two studies, 677TT homozygote subjects with the highest alcohol intake had the highest cancer risk. Findings from six studies of MTHFR C677T and adenomatous polyps are inconsistent. There have been only one or two studies of the other polymorphisms; replication is needed. Overall, the roles of folate-pathway genes, folate, and related dietary factors in colorectal neoplasia are complex. Research priorities are suggested. PMID:14977639

Sharp, Linda; Little, Julian

2004-03-01

125

Modular video endoscopy for in vivo cross-polarized and vital-dye fluorescence imaging of Barrett's-associated neoplasia  

NASA Astrophysics Data System (ADS)

A modular video endoscope is developed and tested to allow imaging in different modalities. This system incorporates white light imaging (WLI), cross-polarized imaging (CPI), and vital-dye fluorescence imaging (VFI), using interchangeable filter modules. CPI and VFI are novel endoscopic modalities that probe mucosal features associated with Barrett's neoplasia. CPI enhances vasculature, while VFI enhances glandular architecture. In this pilot study, we demonstrate the integration of these modalities by imaging areas of Barrett's metaplasia and neoplasia in an esophagectomy specimen. We verify that those key image features are also observed during an in vivo surveillance procedure. CPI images demonstrate improved visualization of branching blood vessels associated with neoplasia. VFI images show glandular architecture with increased glandular effacement associated with neoplasia. Results suggests that important pathologic features seen in CPI and VFI are not visible during standard endoscopic white light imaging, and thus the modalities may be useful in future in vivo studies for discriminating neoplasia from Barrett's metaplasia. We further demonstrate that the integrated WLI/CPI/VFI endoscope is compatible with complementary high-resolution endomicroscopy techniques such as the high-resolution microendoscope, potentially enabling two-step ("red-flag" widefield plus confirmatory high-resolution imaging) protocols to be enhanced.

Thekkek, Nadhi; Pierce, Mark C.; Lee, Michelle H.; Polydorides, Alexandros D.; Flores, Raja M.; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca R.

2013-02-01

126

DNA Methylation Profiling across the Spectrum of HPV-Associated Anal Squamous Neoplasia  

PubMed Central

Background Changes in host tumor genome DNA methylation patterns are among the molecular alterations associated with HPV-related carcinogenesis. However, there is little known about the epigenetic changes associated specifically with the development of anal squamous cell cancer (SCC). We sought to characterize broad methylation profiles across the spectrum of anal squamous neoplasia. Methodology/Principal Findings Twenty-nine formalin-fixed paraffin embedded samples from 24 patients were evaluated and included adjacent histologically normal anal mucosa (NM; n?=?3), SCC-in situ (SCC-IS; n?=?11) and invasive SCC (n?=?15). Thirteen women and 11 men with a median age of 44 years (range 26–81) were included in the study. Using the SFP10 LiPA HPV-typing system, HPV was detected in at least one tissue from all patients with 93% (27/29) being positive for high-risk HPV types and 14 (93%) of 15 invasive SCC tissues testing positive for HPV 16. Bisulfite-modified DNA was interrogated for methylation at 1,505 CpG loci representing 807 genes using the Illumina GoldenGate Methylation Array. When comparing the progression from normal anal mucosa and SCC-IS to invasive SCC, 22 CpG loci representing 20 genes demonstrated significant differential methylation (p<0.01). The majority of differentially methylated gene targets occurred at or close to specific chromosomal locations such as previously described HPV methylation “hotspots” and viral integration sites. Conclusions We have identified a panel of differentially methlylated CpG loci across the spectrum of HPV-associated squamous neoplasia of the anus. To our knowledge, this is the first reported application of large-scale high throughput methylation analysis for the study of anal neoplasia. Our findings support further investigations into the role of host-genome methylation in HPV-associated anal carcinogenesis with implications towards enhanced diagnosis and screening strategies. PMID:23226306

Riggs, Bridget; Eschrich, Steven; Elahi, Abul; Qu, Xiaotao; Ajidahun, Abidemi; Berglund, Anders; Coppola, Domenico; Grady, William M.; Giuliano, Anna R.; Shibata, David

2012-01-01

127

Nucleolar organiser regions (AgNORS) in anal intraepithelial neoplasia and invasive anal squamous cell carcinoma.  

PubMed Central

AIM: To evaluate the usefulness of counting nucleolar organiser region associated proteins (AgNORs) in the management of anal squamous neoplasia. METHOD: Using a silver staining technique for NOR associated proteins, 32 routinely processed paraffin wax embedded sections of anal epithelium were assessed. These consisted of normal anal epithelium (n = 9), anal intraepithelial neoplasia (AIN) grades I (n = 5), and III (n = 13), and invasive squamous neoplasia of the anus (n = 5). RESULTS: The median AgNOR counts for every 100 cells are as follows: normal anal epithelium 2.15 (95% CI 1.89-3.94); AIN I 3.21 (95% CI 2.89-7.14); AIN III 4.32 (95% CI 4.00-8.10); and invasive squamous cell carcinoma of the anus 5.51 (95% CI 2.48-10.62). There were significant differences between AgNOR counts in anal cancer and normal epithelium (p < 0.05; Mann-Whitney U test)), AIN III and normal anal epithelium (p < 0.005), and AIN III and AIN I (p < 0.05). No significant differences were observed between AIN I and normal anal epithelium, anal cancer and AIN I, and anal cancer and AIN III. There was a considerable degree of overlap among the different groups. CONCLUSIONS: Despite the strong association between AgNOR values and degree of dysplasia, the variability within pathological grade may preclude the adoption of this technique on its own as a prognostic indicator. It may, however, be useful in conjunction with other markers of neoplastic growth such as c-myc oncogene amplification or overexpression as a marker of disease progression in AIN and invasive anal squamous cell cancer. Images PMID:1430259

Ogunbiyi, O A; Scholefield, J H; Sharp, F; Ginsberg, R; Rogers, K

1992-01-01

128

Clinical outcome in patients treated with endoscopic submucosal dissection for superficial Barrett's neoplasia.  

PubMed

Background and study aims: The role of endoscopic submucosal dissection (ESD) in Barrett's neoplasia is ill-defined, although it might provide a higher curative resection rate and better histologic assessment than endoscopic mucosal resection (EMR). We aimed to assess efficacy, safety, and long-term results of ESD. Patients and methods: A retrospective analysis was done of 75 consecutive patients with Barrett's esophagus who underwent ESD between January 2007 and February 2014.?ESD was performed for visible lesions that were multiple, larger than 15?mm, or poorly lifting, or suspected of submucosal infiltration. The primary end point was the rate of curative resection of carcinoma. Results: Median patient age was 68 years (interquartile range [IQR] 61?-?76), median follow-up was 20 months (IQR 8.5?-?37.5), and median maximum specimen diameter was 52.5?mm (IQR 43?-?71). En bloc resection rate was 90?% (66?/73), and rates of curative resection of carcinoma and high grade dysplasia/carcinoma were 85?% (47?/55) and 64?% (42?/66), respectively. G3 differentiation and invasion to greater than pT1m2 were observed in 25?% (14?/55) and 67?% (37?/55) of patients with adenocarcinoma, respectively. There were 5 early (?neoplasia and intestinal metaplasia was found in 92?% (54?/59) and 73?% (43?/59) of patients, respectively. Conclusion: ESD appears to be safe and effective, with a high rate of curative resection of carcinoma. ESD should be considered for patients with Barrett's neoplasia at risk of incomplete resection or poor pathologic assessment with conventional EMR. PMID:25412090

Chevaux, Jean Baptiste; Piessevaux, Hubert; Jouret-Mourin, Anne; Yeung, Ralph; Danse, Etienne; Deprez, Pierre H

2014-11-20

129

COMPARISON OF COMPUTED TOMOGRAPHIC AND PATHOLOGIC FINDINGS IN 17 DOGS WITH PRIMARY ADRENAL NEOPLASIA.  

PubMed

The CT appearance of canine adrenal masses has been reported, but associations between imaging features and pathologic features of these lesions have not been investigated in detail. The purpose of this study was to test associations between different types of adrenal neoplasia and their CT and pathologic features. A retrospective cross-sectional study was performed and inclusion criteria were histologic diagnosis of primary adrenal neoplasia, contrast-enhanced CT examination of the abdomen and surgical resection of the mass or necropsy examination. For all included dogs, CT images and histopathologic specimens were reviewed independently by two veterinary radiologists and a veterinary pathologist, respectively. Seventeen dogs met inclusion criteria. Diagnoses were adenocarcinoma in nine (53%) dogs, pheochromocytoma in five (29%) dogs, and adenoma in three (18%) dogs. Pheochromocytoma was associated with CT signs of vascular invasion (likelihood ratio = 4.8, 95% CI = 1.3-18.3, P = 0.03) and macroscopic vascular invasion (likelihood ratio = 9.6, 95% CI = 1.4-65.9, P = 0.02). There was excellent agreement between signs of vascular invasion in CT images and vascular invasion at surgery or necropsy (kappa = 0.86, P = 0.001). A peripheral contrast-enhancing rim in delayed postcontrast CT images was associated with fibrous encapsulation of the tumor (kappa = 0.53, P = 0.05), and a heterogeneous pattern of contrast distribution in delayed postcontrast CT images was associated with adrenal hemorrhage or infarction on histological examination (kappa = 0.45, P = 0.05). Findings indicated that CT enabled assessment of adrenal neoplasia features that reflected their biological behavior and pathological findings, however overlapping characteristics between tumor types limited the potential for reliably distinguishing them based on CT alone. PMID:25139015

Gregori, Tommaso; Mantis, Panagiotis; Benigni, Livia; Priestnall, Simon L; Lamb, Christopher R

2014-08-19

130

Human papilloma virus infection and cervical intraepithelial neoplasia in transplanted patients.  

PubMed

Progress in diagnosis and treatment has led to an increased number of transplantation patients who consequently have immunological depression and emergence of tumors. The incidence of cervical neoplasia, according to previous studies, is 11%; this tumor is the only one that can be investigated by screening before and after a graft. Our purpose was to evaluate whether transplanted patients showed an increased incidence of genital human papilloma virus (HPV) infection and whether this infection produced greater progression of disease in cases of low-risk HPV infections. Our study involved 151 transplant patients who underwent Papanicolaou (Pap) and HPV tests. Patients listed for grafts underwent Pap and HPV tests 6 months before and 6 months after transplantation. All patients had negative Pap tests before their grafts. After their grafts 16 patients (10.59%) had negative Pap tests, but positive viral typing. Eleven patients (7.28%) showed positive Pap tests, 6 of whom had low-grade squamous intraepithelial lesion (SIL) and 5 patients high-grade SIL. The final HPV infection incidence (15.23%) was consistent with the literature. The incidence of lower female genital tract intraepithelial lesions (7.28%) was higher than the healthy population or analogous studies (4.5%-8.5%). We showed a constant association between high-risk HPV infection and gynecologic intraepithelial neoplasia, whereas there was no association between low-risk broods HPV infection and neoplasia. In conclusion, screening should start at almost 6 months before grafting to avoid an irreversible situation that is difficult to treat. PMID:18675077

Paternoster, D M; Cester, M; Resente, C; Pascoli, I; Nanhorngue, K; Marchini, F; Boccagni, P; Cillo, U; Ribaldone, R; Amoruso, E; Cocca, N; Cuccolo, V; Bertolino, M; Surico, N; Stratta, P

2008-01-01

131

Neoplasia associated with feline immunodeficiency virus infection in cats of southern California.  

PubMed

Between 1988 and 1991, feline immunodeficiency virus (FIV) infection status was evaluated in 1,160 cats examined at an oncology referral and general practice in Los Angeles, California. Twenty-nine (2.5%) cats were FIV positive. Neoplasia was present in 18 of the 29 (62%) cats. Sampling for neoplasia was intentionally biased in the oncology referral group. However, 33% (6/18) of FIV-infected cats with neoplasia originated from the general practice. Three neoplastic processes were observed; myeloproliferative disease (MPD; 5/18), lymphoma (LSA; 5/18), and squamous cell carcinoma (SCC; 7/18). One cat had LSA and SCC. Extranodal sites of LSA were common (66%) in FIV-infected cats. Sites of LSA were submandibular and mesenteric lymph nodes, liver, kidneys, periorbital area, and diffuse (heart, pancreas, bladder). Sites of SCC were sublingual (n = 2), nasal planum (n = 3), nasal planum and eyelids (n = 1), and mandible (n = 2). Feline leukemia virus co-infection was observed in 17% (5/29) of FIV-infected cats. The FIV-infected cats with MPD were young (range, 8 months to 13 years; median, 4 years) and had short survival duration (2, 6, 21, 134, 249 days) even in response to aggressive treatment. The FIV-infected cats with LSA were older (median age, 8 years; range, 4 to 14 years) and survived 60 days if untreated. Cats administered chemotherapy survived 39, 45, 217, and 243 days; the latter 2 cats had partial remission of 2 months' duration. Older FIV-infected cats had SCC (median age, 12 years; remission range, 7 to 16 years) because of more frequent association of both diseases in older cats with outdoor environment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1666082

Hutson, C A; Rideout, B A; Pedersen, N C

1991-11-15

132

Tumour formation in multiple intestinal neoplasia (Apc Min/+) mice fed with filtered or unfiltered coffee  

PubMed Central

Background The aetiology of colorectal cancer has strong dietary links, and there may be an association between coffee and colorectal cancer risk. Objective To study the effects of filtered (low levels of kahweol/cafestol) and unfiltered (high levels of kahweol/cafestol) coffee on tumour formation in multiple intestinal neoplasia (Apc Min/+) mice. Design Apc Min/+ mice (n=11 per group) were fed for 9 weeks with 10% w/w of these two types of coffee. Coffee was served as a dietary ingredient mixed with a semi-synthetic AIN-93G-based diet. Plasma levels of caffeine and paraxanthine were used as compliance markers. At the end of the feeding period intestinal tumour number and size were determined. The levels of ?-catenin and cyclin D1, two cell-signalling proteins important to the progression of neoplasia, were also analysed in the tumour tissue. Results Plasma caffeine and paraxanthine concentrations were 3.2±1.4 and 1.7±0.4 µmol l?1 in the filtered coffee group and 3.6±2.3 and 1.6±0.6 µmol l?1 in the unfiltered coffee group. The level of plasma xanthines was below detection in the control group. The total number of tumours was equal between the dietary groups: 29 for the control, 30 (p =0.767) for the filtered coffee and 29 (p=0.430) for the unfiltered coffee groups. The levels of ?-catenin and cyclin D1 in the nuclear fraction of the tumour tissue were also the same between the groups. Conclusions Filtered or unfiltered coffee (10% w/w) does not exert antitumorigenic activity in Apc Min/+ mice or change ?-catenin and cyclin D1 signalling in the adenoma tissues. The results suggest that coffee does not change neoplasia progression in this animal model.

Oikarinen, Seija I; Erlund, Iris; Mutanen, Marja

2007-01-01

133

Disease progression and recurrence in women treated for vulvovaginal intraepithelial neoplasia  

PubMed Central

Objective The malignant potential of intraepithelial neoplasia of the vulva and vagina after treatment is not well defined. Our objective was to examine risk factors for recurrence and invasive disease. Methods Four hundred sixty-four women with biopsy proven high-grade intraepithelial neoplasia of the vulva and vagina were identified in the electronic databases of four colposcopy clinics. Inclusion criteria were a follow-up of more than one year, no history of invasive cancer and no invasive cancer within the first year after initial treatment. We investigated the potential factors associated with recurrence and progression using a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results Of the 411 eligible patients, 123 patients (29.9%) recurred later than one year after initial treatment and 24 patients (5.8%) progressed to invasive disease. According to multivariate analyses, the risk factors associated with recurrence were multifocality (OR, 3.33; 95% CI, 2.02 to 5.51), immunosuppression (OR, 2.51; 95% CI, 1.09 to 5.81), excision as initial treatment (vs. laser evaporation; OR, 1.79; 95% CI, 1.11 to 2.91) and smoking (OR, 1.61; 95% CI, 1.02 to 2.55). Risk factors for progression to invasive disease were immunosuppression (OR, 4.00; 95% CI, 1.30 to 12.25), multifocality (OR, 3.05; 95% CI, 1.25 to 7.43) and smoking (OR, 2.97; 95% CI, 1.16 to 7.60), but not treatment modality. Conclusion Laser evaporation combined with extensive biopsy is at least as efficacious as initial treatment of intraepithelial neoplasia with excision. Smoking is a risk factor for both recurrence and progression to invasive disease. Hence, smoking cessation should be advised and maintaining a long follow-up period due to late relapses is necessary. PMID:23875073

Baumann, Marc; Mueller, Michael; Fink, Daniel; Heinzl, Siegfried; Imesch, Patrick; Dedes, Konstantin

2013-01-01

134

The use of human papillomavirus typing in detection of cervical neoplasia in Recife (Brazil).  

PubMed

High risk types of human papillomavirus (HR-HPV) play a major role in cervical cancer oncogenesis. This study aims to evaluate the efficacy of HPV detection and typing as a means of identifying cervical neoplasia in a high risk population. A management algorithm for implementation of HPV detection in clinical practice is also proposed. A nested case-control within a cohort study was undertaken in Recife (Brazil). All 479 participants had cervical scrapes collected for HPV detection followed by colposcopy. Samples were blindly analyzed by polymerase chain reaction (PCR) and typed by restriction fragment length polymorphism (RFLP). HPV detection by PCR and typing with RFLP cost US$ 4.92 per woman screened in this study and is significantly better than cytology in identifying women at risk of developing cervical cancer (P = 0.0001). Women who tested positive for HR-HPV had over 35-fold increased risk of having high grade squamous intraepithelial lesion (HSIL) or cervical cancer, although this does not necessarily translate into the same risk rate for women with latent HPV infection developing major cervical neoplasia. HPV typing offers 90% sensitivity and 85% specificity for cervical cancer detection. In combination with cytology it provides a negative predictive value of 99.4% and a sensitivity of over 96% for detection of HSIL and cervical cancer. We conclude that HPV typing is an inexpensive and effective method for identification of cervical neoplasia and women at risk of developing it. It improves quality control for both false negative and false positive cytology results. Routine screening intervals could safely be increased to 3-5 years, decreasing anxiety and socio-economic inconveniences. PMID:11240666

Lorenzato, F.; Ho, L.; Terry, G.; Singer, A.; Santos, L. C.; De Lucena Batista, R.; Lubambo, T.

2000-03-01

135

Clinicopathological and patient characteristics of early gastric neoplasia endoscopically resected with loss of Mlh1 expression  

PubMed Central

Hypermethylation of the promoter region of the MLH1 gene leads to loss of Mlh1 protein expression and plays a key role in the development of gastric cancer. Little is known about the association between Mlh1 expression and the clinicopathological and patient characteristics in early gastric neoplasia, particularly in endoscopically resected tumors. Immunohistochemistry was used to examine Mlh1 expression in 140 early gastric neoplasias obtained by endoscopic resection and comprising 31 gastric adenomas (GAs) and 109 early gastric cancers (EGCs), and compared them to corresponding clinicopathological and patient data. P53 expression and phenotypic profiles were also analyzed. The rate of reduced Mlh1 expression and P53 overexpression was 9.6 and 6.5% in GAs, and 27.5 and 27.5% in EGCs, respectively. In elderly patients (?65 years of age), the aberrant expression of Mlh1 in EGCs was more significant in female than in male patients (59.9 vs. 29.8%; P=0.016). In addition, the frequency of aberrant Mlh1 expression in EGCs increased significantly in patients with oncological family histories and elevated gross type (P=0.033 and P=0.04, respectively). Moreover, a significant correlation was observed among aberrant Mlh1, P53-negative and HGM expression. The present findings suggest that loss of Mlh1 expression is associated with age, gender, oncological family history and tumor growth pattern in EGC. Patient and tumor characteristics are key factors in the screening, surveillance and diagnosis of early gastric neoplasia, particularly in elderly individuals. PMID:22866067

SASAKI, SHUJI; YASHIMA, KAZUO; HAYASHI, AKIHIRO; TAKEDA, YOHEI; YASUGI, AKIKO; KODA, MASAHARU; KAWAGUCHI, KOICHIRO; HARADA, KENICHI; ITO, HISAO; MURAWAKI, YOSHIKAZU

2011-01-01

136

Recurrent Respiratory Papillomatosis: HPV Genotypes and Risk of High-Grade Laryngeal Neoplasia  

PubMed Central

Patients with recurrent respiratory papillomatosis (RRP) in Norway treated between 1987 and 2009 were recruited to this cohort study. They were followed from disease onset and data recorded until January 2012. Here, we describe the distribution of human papillomavirus (HPV) genotypes, the prevalence of multiple HPV infections, and the risk of high-grade laryngeal neoplasia and respiratory tract invasive carcinoma in a large cohort of patients with RRP. We also examined whether HPV genotype, gender, age or clinical course are risk factors for this development. Clinical records and histological specimens were reviewed. Using formalin-fixed paraffin-embedded biopsies, HPV genotyping were performed by quantitative polymerase chain reaction assays identifying 15 HPV types. HPV-negative specimens were analyzed by metagenomic sequencing. Paraffin blocks were available in 224/238 patients. The DNA quality was approved in 221/224 cases. HPV DNA was detected in 207/221 patients and all were HPV 6 or HPV 11 positive, comprising HPV 6 in 133/207, HPV 11 in 40/207 cases and HPV 6/11 in 15/207 cases. Co-infection with one or two high-risk HPV types together with HPV 6 or HPV 11 was present in 19/207 patients. Metagenomic sequencing of 14 HPV-negative specimens revealed HPV 8 in one case. In total, 39/221 patients developed high-grade laryngeal neoplasia. 8/221 patients developed carcinoma of the respiratory tract (six patients with laryngeal carcinoma and two patients with lung carcinoma). High-grade laryngeal neoplasias were found more frequently in HPV-negative versus HPV-positive patients, (RR?=?2.35, 95% CI 1.1, 4.99), as well as respiratory tract carcinomas (RR?=?48, 95% CI 10.72, 214.91). In summary, the majority of RRP were associated with HPV 6 and/or 11. HPV-negative RRP biopsies occurred more frequently in adult-onset patients, and were associated with an increased risk of laryngeal neoplasia and carcinoma in the respiratory tract. PMID:24918765

Omland, Turid; Lie, Kathrine A.; Akre, Harriet; Sandlie, Lars Erik; Jebsen, Peter; Sandvik, Leiv; Nymoen, Dag Andre; Bzhalava, Davit; Dillner, Joakim; Brøndbo, Kjell

2014-01-01

137

Laparoscopic resection of periadrenal paraganglioma in a patient with multiple endocrine neoplasia type 2A.  

PubMed

We report here a case of recurrent pheochromocytoma successfully managed by laparoscopic surgery in a patient with multiple endocrine neoplasia type 2A. A 25-year-old man presented with the contralateral adrenal mass after earlier right adrenalectomy. For the preoperative diagnosis of left adrenal pheochromocytoma, adrenal sparing surgery was considered. From the intraoperative laparoscopic view, we found that the tumor originated in periadrenal sympathetic ganglia, and laparoscopic excision of paraganglioma was successfully performed that preserved the integrity of normal adrenal gland. Extra-adrenal pheochromocytoma is rather rare in MEN 2A and it is important to identify precise intraoperative localization of pheochromocytoma with laparoscopic surgery. PMID:21304370

Nomura, Takeo; Takahashi, Mika; Ando, Tadasuke; Sato, Fuminori; Fujii, Sumie; Mimata, Hiromitsu

2011-02-01

138

A historical appreciation of bronchopulmonary neuroendocrine neoplasia: resolution of a carcinoid conundrum.  

PubMed

In the three-quarters of a century that have elapsed since the first description of a bronchial carcinoid, the field has progressed from serendipitous radiological or bronchoscopic diagnosis to computed tomography, magnetic resonance imaging, and somatostatin receptor imaging identification. Similarly, pathologic techniques have advanced from a naïve assessment of neoplasia to a delineation of several tumor subtypes and an understanding of the neuroendocrine basis of the disease process. A key unresolved question is the identification of the genetic and environmental activators that are responsible for the initiation of pulmonary neuroendocrine cell proliferation and neoplastic transformation. PMID:25065925

Modlin, Irvin M; Bodei, Lisa; Kidd, Mark

2014-08-01

139

Influence of disseminated neoplasia, trematode infections and gametogenesis on surfacing and mortality in the cockle Cerastoderma edule.  

PubMed

Cerastoderma edule is a widely distributed bivalve mollusc, commercially exploited throughout Europe and is also an important food source for birds and crustaceans. Recently, mass surfacing and mortalities of cockles have been observed and reported at sites in Ireland and elsewhere, particularly in the summer months. One such site is Flaxfort Strand, Courtmacsherry Bay, County Cork, Ireland, an important feeding area used by many seabirds during the summer months. For the past few years large numbers of surfaced cockles have been observed at the site in a moribund condition. Samples of cockles from this area were collected over the summer months and their health status assessed. Cockles that had surfaced (moribund) and those still buried in the sediment were quantified and screened: sex, gonadal maturity and size class of cockles were also determined. Disseminated neoplasia and trematodes were observed in screened cockles. The most significant finding during the study was that mortalities and surfacing of cockles was related to a greater incidence of disseminated neoplasia. No neoplasia was observed in the smallest and largest size classes. There was a significantly higher prevalence of neoplasia in moribund cockles than in buried cockles, whereas in both groups a similar concentration of trematode metacercariae was observed in the screened tissues. Also, most of the cockles that had surfaced were either in the process of spawning or were spent. Overall a much larger percentage of moribund cockles exhibited both trematode infections plus neoplasia compared with buried cockles. A combination of the presence of neoplasia and trematodes, along with stress related to spawning, may immunocompromise the cockless, causing the animals to surface and become moribund. PMID:22422131

Morgan, E; O'Riordan, R M; Kelly, T C; Culloty, S C

2012-02-17

140

POLYMORPHIC VARIATION IN THE GC AND CASR GENES AND ASSOCIATIONS WITH VITAMIN D METABOLITE CONCENTRATION AND METACHRONOUS COLORECTAL NEOPLASIA  

PubMed Central

Background Vitamin D levels and calcium intake have been associated with risk of colorectal neoplasia, and genetic variation in vitamin D-pathway genes may affect circulating vitamin D metabolite concentrations and/or risk for colorectal lesions. This study evaluated associations between polymorphic variation in the Gc-globulin (GC) and Calcium-sensing receptor (CASR) and odds for metachronous colorectal neoplasia and vitamin D metabolite concentrations. Methods Participants from the Ursodeoxycholic Acid (UDCA) and Wheat Bran Fiber (WBF) trials (n=1439) were analyzed using a single nucleotide polymorphism (SNP) tagging approach, with a subset (n=404) of UDCA trial participants for whom vitamin D metabolite concentrations were also available. A total of 25 GC and 35 CASR tagSNPs were evaluated using multiple statistical methods. Results Principal components analyses did not reveal gene-level associations between GC or CASR and colorectal neoplasia, however, a significant gene-level association between GC and 25(OH)D concentrations (p < 0.01) was observed. At the individual SNP-level and following multiple comparisons adjustments, significant associations were observed between seven GC (rs7041, rs222035, rs842999, rs1155563, rs12512631, rs16846876, rs1746825) polymorphisms and circulating measures of 25(OH)D (adjusted p < 0.01), and CASR SNP rs1042636 and proximal colorectal neoplasia (adjusted p = 0.01). Conclusions These results demonstrate a possible association between variation in CASR and odds of colorectal neoplasia as well as the potential role of variation in GC with circulating 25(OH)D concentrations. Impact Additional research is warranted to determine the mechanism of GC genotype in influencing 25(OH)D concentrations and to further elucidate the role of CASR in colorectal neoplasia. PMID:22144504

Hibler, Elizabeth A.; Hu, Chengcheng; Jurutka, Peter W.; Martinez, Maria E.; Jacobs, Elizabeth T.

2011-01-01

141

High prevalence of HPV 16 in South African women with cancer of the cervix and cervical intraepithelial neoplasia.  

PubMed

Despite the high prevalence of cervical cancer and cervical neoplasias in South Africa, few studies have been performed in this region to establish which human papillomavirus (HPV) types are associated with the development of high-grade cervical intraepithelial neoplasia lesions and cervical cancer. To investigate these prevalence rates, punch biopsies were obtained from 56 women with cervical cancer and 141 women with histologically diagnosed cervical intraepithelial neoplasia 2 or 3 lesions. Nested polymerase chain reaction (PCR) using consensus degenerate PCR primers was performed for the detection of HPV DNA and HPV typing was done by restriction fragment length polymorphism. Forty-seven (94%) of the cervical cancer and 114 (88%) of the cervical intraepithelial neoplasia 2/3 biopsies were positive for HPV DNA. The prevalence rates of the HPV types detected in the cervical cancer biopsies were HPV 16 (82%), HPV 18, (10%), HPV 33 (10%), HPV 31 (2%), HPV 58 (2%), HPV 35 (2%), and HPV 59 (2%). The cervical intraepithelial neoplasia lesions contained HPV 16 (56.6%), HPV 33 (14%), HPV 31 (10.9%), HPV X (7%), HPV 52 (3.9), HPV 58 (3.1%), HPV 35 (2.3%), HPV 18 (1.6%), HPV 11 (0.8%). Five of the nine fragments that were not typed by the RFLP, designated HPV-X, were sequenced to give HPV6 (1/5), HPV 26 (2/5), HPV 68 (1/5), and candHPV 87 (1/5). HPV 58 was detected in one cervical cancer biopsy and four biopsies from cervical intraepithelial neoplasia grade 3 lesions and was shown to be a previously described variant [Williamson and Rybicki (1991) J. Med. Virol. 33:165-171]. In addition, a cervical intraepithelial neoplasia grade 2 lesion was shown to harbour HPV type HAN2294 (cand HPV 87). The results of this study indicate that cervical cancer and cervical intraepithelial neoplasia 2/3 are largely associated with HPV 16 infection in this group of South African women and, therefore, an effective HPV 16 based vaccine should prevent the development of cervical cancer in a large proportion of women from this region of South Africa. PMID:12938202

Kay, Patti; Soeters, Robbert; Nevin, James; Denny, Lynette; Dehaeck, Catherine M C; Williamson, Anna-Lise

2003-10-01

142

Multispectral optical imaging device for in vivo detection of oral neoplasia  

PubMed Central

A multispectral digital microscope (MDM) is designed and constructed as a tool to improve detection of oral neoplasia. The MDM acquires in vivo images of oral tissue in fluorescence, narrowband (NB) reflectance, and orthogonal polarized reflectance (OPR) modes, to enable evaluation of lesions that may not exhibit high contrast under standard white light illumination. The device rapidly captures image sequences so that the diagnostic value of each modality can be qualitatively and quantitatively evaluated alone and in combination. As part of a pilot clinical trial, images are acquired from normal volunteers and patients with precancerous and cancerous lesions. In normal subjects, the visibility of vasculature can be enhanced by tuning the reflectance illumination wavelength and polarization. In patients with histologically confirmed neoplasia, we observe decreased blue/green autofluorescence and increased red autofluorescence in lesions, and increased visibility of vasculature using NB and OPR imaging. The perceived lesion borders change with imaging modality, suggesting that multimodal imaging has the potential to provide additional diagnostic information not available using standard white light illumination or by using a single imaging mode alone. PMID:18465982

Roblyer, Darren; Richards-Kortum, Rebecca; Sokolov, Konstantin; El-Naggar, Adel K.; Williams, Michelle D.; Kurachi, Cristina; Gillenwater, Ann M.

2014-01-01

143

C-C Chemokine Receptor 1 Expression in Human Hematolymphoid Neoplasia  

PubMed Central

Chemokine receptor 1 (CCR1) is a G protein–coupled receptor that binds to members of the C-C chemokine family. Recently, CCL3 (MIP-1?), a high-affinity CCR1 ligand, was identified as part of a model that independently predicts survival in patients with diffuse large B-cell lymphoma (DLBCL). However, the role of chemokine signaling in the pathogenesis of human lymphomas is unclear. In normal human hematopoietic tissues, we found CCR1 expression in intraepithelial B cells of human tonsil and granulocytic/monocytic cells in the bone marrow. Immunohistochemical analysis of 944 cases of hematolymphoid neoplasia identified CCR1 expression in a subset of B- and T-cell lymphomas, plasma cell myeloma, acute myeloid leukemia, and classical Hodgkin lymphoma. CCR1 expression correlated with the non–germinal center subtype of DLBCL but did not predict overall survival in follicular lymphoma. These data suggest that CCR1 may be useful for lymphoma classification and support a role for chemokine signaling in the pathogenesis of hematolymphoid neoplasia. PMID:20154287

Anderson, Matthew W.; Zhao, Shuchun; Ai, Weiyun Z.; Tibshirani, Robert; Levy, Ronald; Lossos, Izidore S.; Natkunam, Yasodha

2015-01-01

144

www.neoplasia.com Individual Telomere Lengths in Chronic Myeloid Leukemia 1,2  

E-print Network

Chronic myeloid leukemia (CML) is a neoplasia characterized by proliferation of a myeloid cell lineage and chromosome translocation t(9;22) (q34;q11.2). As in the case of most cancers, the average telomere length in CML cells is shorter than that in normal blood cells. However, there are currently no data available concerning specific individual telomere length in CML. Here, we studied telomere length on each chromosome arm of CML cells. In situ hybridization with peptide nucleic acid probes was performed on CML cells in metaphase. The fluorescence intensity of each specific telomere was converted into kilobases according to the telomere restriction fragment results for each sample. We found differences in telomere length between short arm ends and long arm ends. We observed recurrent telomere length changes as well as telomere length maintenance and elongation in some individual telomeres. We propose a possible involvement of individual telomere length changes to some chromosomal abnormalities in CML. We suggest that individual telomere length maintenance is chromosome arm–specific associated with leukemia cells. Neoplasia (2009) 11, 1146–1154

Oumar Samassekou; Aimé Ntwari; Josée Hébert; Ju Yan; Cell Bank Of Quebec; Division Of Hematology

2009-01-01

145

Targeted therapy of colorectal neoplasia with rapamycin in peptide-labeled pegylated octadecyl lithocholate micelles.  

PubMed

Many powerful drugs have limited clinical utility because of poor water solubility and high systemic toxicity. Here, we formulated a targeted nanomedicine, rapamycin encapsulated in pegylated octadecyl lithocholate micelles labeled with a new ligand for colorectal neoplasia, LTTHYKL peptide. CPC;Apc mice that spontaneously develop colonic adenomas were treated with free rapamycin, plain rapamycin micelles, and peptide-labeled rapamycin micelles via intraperitoneal injection for 35days. Endoscopy was performed to monitor adenoma regression in vivo. We observed complete adenoma regression at the end of therapy. The mean regression rate for peptide-labeled rapamycin micelles was significantly greater than that for plain rapamycin micelles, P<0.01. On immunohistochemistry, we observed a significant reduction in phospho-S6 but not ?-catenin expression and reduced tumor cell proliferation, suggesting greater inhibition of downstream mTOR signaling. We observed significantly reduced renal toxicity for peptide-labeled rapamycin micelles compared to that of free drug, and no other toxicities were found on chemistries. Together, this unique targeted micelle represents a potential therapeutic for colorectal neoplasia with comparable therapeutic efficacy to rapamycin free drug and significantly less systemic toxicity. PMID:25483425

Khondee, Supang; Rabinsky, Emily F; Owens, Scott R; Joshi, Bishnu P; Qiu, Zhen; Duan, Xiyu; Zhao, Lili; Wang, Thomas D

2015-02-10

146

Surgical management of pancreatico-duodenal tumors in multiple endocrine neoplasia syndrome type 1  

PubMed Central

Pancreatico-duodenal tumors are the second most common endocrinopathy in multiple endocrine neoplasia syndrome type 1, and have a pronounced effect on life expectancy as the principal cause of disease-related death. Previous discussions about surgical management have focused mainly on syndromes of hormone excess and, in particular, the management of multiple endocrine neoplasia syndrome type 1-related Zollinger–Ellison syndrome. Since hormonal syndromes tend to occur late and indicate the presence of metastases, screening with biochemical markers and endoscopic ultrasound is recommended for early detection of pancreatico-duodenal tumors, and with early surgery before metastases have developed. Surgery is recommended in patients with or without hormonal syndromes in the absence of disseminated liver metastases. The suggested operation includes distal 80% subtotal pancreatic resection together with enucleation of tumors in the head of the pancreas, and in cases with Zollinger–Ellison syndrome, excision of duodenal gastrinomas together with clearance of regional lymph node metastases. This strategy, with early and aggressive surgery before metastases have developed, is believed to reduce the risks for tumor recurrence and malignant progression. PMID:22584725

Åkerström, Göran; Stålberg, Peter; Hellman, Per

2012-01-01

147

Multispectral optical imaging device for in vivo detection of oral neoplasia.  

PubMed

A multispectral digital microscope (MDM) is designed and constructed as a tool to improve detection of oral neoplasia. The MDM acquires in vivo images of oral tissue in fluorescence, narrow-band (NB) reflectance, and orthogonal polarized reflectance (OPR) modes, to enable evaluation of lesions that may not exhibit high contrast under standard white light illumination. The device rapidly captures image sequences so that the diagnostic value of each modality can be qualitatively and quantitatively evaluated alone and in combination. As part of a pilot clinical trial, images are acquired from normal volunteers and patients with precancerous and cancerous lesions. In normal subjects, the visibility of vasculature can be enhanced by tuning the reflectance illumination wavelength and polarization. In patients with histologically confirmed neoplasia, we observe decreased blue/green autofluorescence and increased red autofluorescence in lesions, and increased visibility of vasculature using NB and OPR imaging. The perceived lesion borders change with imaging modality, suggesting that multimodal imaging has the potential to provide additional diagnostic information not available using standard white light illumination or by using a single imaging mode alone. PMID:18465982

Roblyer, Darren; Richards-Kortum, Rebecca; Sokolov, Konstantin; El-Naggar, Adel K; Williams, Michelle D; Kurachi, Cristina; Gillenwater, Ann M

2008-01-01

148

Clonal BRAF Mutations in Melanocytic Nevi and Initiating Role of BRAF in Melanocytic Neoplasia  

PubMed Central

BRAFV600E mutations are frequent in melanomas originating from intermittently sun-exposed skin and also in common acquired melanocytic nevi, suggesting that BRAF mutation is an early event in melanocytic neoplasia. All neoplastic melanocytes within such a nevus would be expected to carry the BRAF mutation, and thus we evaluated the frequency of cells with BRAFV600E mutations within acquired nevi by droplet digital polymerase chain reaction. In BRAF-mutant nevi the number of BRAF mutant alleles equaled the number of wild-type (WT) alleles in the neoplastic cell population, consistent with a fully clonal heterozygous BRAF mutation. The allelic ratio of BRAFV600E to BRAFWT in the eight VE1-positive nevi, adjusted for degree of stromal contamination, ranged from 0.84 to 1.12 with an average ratio of 1.01. This was confirmed by immunohistochemistry with an antibody specific for BRAFV600E, which uniformly labeled the neoplastic cells without any evidence of heterogeneity. We found BRAFV600E mutations in the melanocytic nevi to be fully clonal, strongly suggesting that BRAF-activating mutations typically are early initiating events in melanocytic neoplasia. PMID:23690527

2013-01-01

149

Induction of Chromosomal Instability via Telomere Dysfunction and Epigenetic Alterations in Myeloid Neoplasia  

PubMed Central

Chromosomal instability (CIN) is a characteristic feature of cancer. In this review, we concentrate on mechanisms leading to CIN in myeloid neoplasia, i.e., myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The pathogenesis of myeloid neoplasia is complex and involves genetic and epigenetic alterations. Chromosome aberrations define specific subgroups and guide clinical decisions. Genomic instability may play an essential role in leukemogenesis by promoting the accumulation of genetic lesions responsible for clonal evolution. Indeed, disease progression is often driven by clonal evolution into complex karyotypes. Earlier studies have shown an association between telomere shortening and advanced MDS and underlined the important role of dysfunctional telomeres in the development of genetic instability and cancer. Several studies link chromosome rearrangements and aberrant DNA and histone methylation. Genes implicated in epigenetic control, like DNMT3A, ASXL1, EZH2 and TET2, have been discovered to be mutated in MDS. Moreover, gene-specific hypermethylation correlates highly significantly with the risk score according to the International Prognostic Scoring System. In AML, methylation profiling also revealed clustering dependent on the genetic status. Clearly, genetic instability and clonal evolution are driving forces for leukemic transformation. Understanding the mechanisms inducing CIN will be important for prevention and for novel approaches towards therapeutic interventions. PMID:24202323

Vajen, Beate; Thomay, Kathrin; Schlegelberger, Brigitte

2013-01-01

150

A Kindred with a Variant of Multiple Endocrine Neoplasia Type 1 Demonstrating Frequent Expression of Pituitary Tumors but Not Linked to the Multiple Endocrine Neoplasia Type 1 Locus at Chromosome Region 11q13  

Microsoft Academic Search

Acromegaly is uncommon in kindreds with multiple endocrine neoplasia type 1 (MEN1), whereas primary hyperparathyroidism (PHP) has the highest penetrance of any endocrinopathy. We report an unusual MEN1 kindred with frequent expression of pituitary tu- mors and a low penetrance of PHP. Four members were found to have disease: PHP in generation I, acromegaly (2 cases) in generation II, and

JOHN L. STOCK; MARIA R. WARTH; BIN TEAN TEH; JAMES A. CODERRE; JUDITH H. OVERDORF; GERHARD BAUMANN; RAYMOND L. HINTZ; MARK L. HARTMAN; BERND R. SEIZINGER; CATHARINA LARSSON; NEIL ARONIN

151

Three Nordic berries inhibit intestinal tumorigenesis in multiple intestinal neoplasia/+ mice by modulating beta-catenin signaling in the tumor and transcription in the mucosa.  

PubMed

Berries contain a number of compounds that are proposed to have anticarcinogenic properties. We studied the effects and molecular mechanisms of wild berries with different phenolic profiles on intestinal tumorigenesis in multiple intestinal neoplasia/+ mice. The mice were fed a high-fat AIN93-G diet (Con) or AIN93-G diets containing 10% (w:w) freeze-dried bilberry, lingonberry (LB), or cloudberry (CB) for 10 wk. All 3 berries significantly inhibited the formation of intestinal adenomas as indicated by a 15-30% reduction in tumor number (P < 0.05). CB and LB also reduced tumor burden by over 60% (P < 0.05). Compared to Con, CB and LB resulted in a larger (P < 0.05) proportion of small adenomas (43, 69, and 64%, respectively) and a smaller proportion of large adenomas (56, 29, and 33%, respectively). Beta-catenin and cyclin D1 in the small and large adenomas and in the normal-appearing mucosa were measured by Western blotting and immunohistochemistry. CB resulted in decreased levels of nuclear beta-catenin and cyclin D1 and LB in the level of cyclin D1 in the large adenomas (P < 0.05). Early changes in gene expression in the normal-appearing mucosa were analyzed by Affymetrix microarrays, which revealed changes in genes implicated in colon carcinogenesis, including the decreased expression of the adenosine deaminase, ecto-5'-nucleotidase, and prostaglandin E2 receptor subtype EP4. Our results indicate that berries are potentially a rich source of chemopreventive components. PMID:17885012

Misikangas, Marjo; Pajari, Anne-Maria; Päivärinta, Essi; Oikarinen, Seija I; Rajakangas, Johanna; Marttinen, Maija; Tanayama, Heidi; Törrönen, Riitta; Mutanen, Marja

2007-10-01

152

Vitamin and calcium supplement use is associated with decreased adenoma recurrence in patients with a previous history of neoplasia  

Microsoft Academic Search

INTRODUCTION: Although some have suggested that certain vitamins or calcium supplements may reduce adenoma recurrence, our own prior retrospective study found no such effects. The purpose of this case-control study was to further investigate whether regular vitamin or calcium supplement intake influenced the incidence of recurrent adenomatous polyps in patients with previous neoplasia who were undergoing follow-up colonoscopy. METHODS: This

Richard L. Whelan; Karen D. Horvath; Neil R. Gleason; Kenneth A. Forde; Michael D. Treat; Susan L. Teitelbaum; Andrea Bertram; Alfred I. Neugut

1999-01-01

153

Evaluation of quantitative image analysis criteria for the high-resolution microendoscopic detection of neoplasia in Barrett's esophagus  

Microsoft Academic Search

Early detection of neoplasia in patients with Barrett's esophagus is essential to improve outcomes. The aim of this ex vivo study was to evaluate the ability of high-resolution microendoscopic imaging and quantitative image analysis to identify neoplastic lesions in patients with Barrett's esophagus. Nine patients with pathologically confirmed Barrett's esophagus underwent endoscopic examination with biopsies or endoscopic mucosal resection. Resected

Timothy J. Muldoon; Nadhi Thekkek; Darren Roblyer; Dipen Maru; Noam Harpaz; Jonathan Potack; Sharmila Anandasabapathy; Rebecca Richards-Kortum

2010-01-01

154

Prolonged hypergastrinemia does not increase the frequency of colonic neoplasia in patients with Zollinger-Ellison syndrome  

Microsoft Academic Search

Whereas considerable experimental evidence suggests chronic hypergastrinemia can increase the occurrence of colonic neoplasia, the risks in man remain unclear. Zollinger-Ellison syndrome (ZES) is associated with marked plasma elevation of all forms of gastrin and, because of its prolonged course, has been shown to be an excellent model disease to study the effects of chronic hypergastrinemia in man. To determine

Murray Orbuch; David J. Venzon; Irina A. Lubensky; Horst C. Weber; Fathia Gibril; Robert T. Jensen

1996-01-01

155

Prevalence and risk factors of sexually transmitted infections and cervical neoplasia in women from a rural area of southern Mozambique.  

PubMed

There is limited information on the prevalence of sexually transmitted infections and the prevalence of cervical neoplasia in rural sub-Saharan Africa. This study describes the prevalence and the etiology of STIs and the prevalence of cervical neoplasia among women in southern Mozambique. An age-stratified cross-sectional study was performed where 262 women aged 14 to 61 years were recruited at the antenatal clinic (59%), the family-planning clinic (7%), and from the community (34%). At least one active STI was diagnosed in 79% of women. Trichomonas vaginalis was present in 31% of all study participants. The prevalence of Neisseria gonorrhea and Chlamydia trachomatis were 14% and 8%, respectively, and Syphilis was diagnosed in 12% of women. HPV DNA was detected in 40% of women and cervical neoplasia was diagnosed in 12% of all women. Risk factors associated with the presence of some of the STIs were being divorced or widowed, having more than one sexual partner and having the partner living in another area. A higher prevalence was observed in the reproductive age group and some of the STIs were more frequently diagnosed in pregnant women. STI control programs are a priority to reduce the STIs burden, including HIV and cervical neoplasia. PMID:20706691

Menéndez, Clara; Castellsagué, Xavier; Renom, Montse; Sacarlal, Jahit; Quintó, Llorenç; Lloveras, Belen; Klaustermeier, Joellen; Kornegay, Janet R; Sigauque, Betuel; Bosch, F Xavier; Alonso, Pedro L

2010-01-01

156

Journal of Mammary Gland Biology and Neoplasia, Vol. 3, No. 3, 1998 Origin and Secretion of Milk Lipids  

E-print Network

Journal of Mammary Gland Biology and Neoplasia, Vol. 3, No. 3, 1998 Origin and Secretion of Milk Lipids Ian H. Mather1,3 and Thomas W. Keenan2 The cream fraction of milk comprises droplets-bounded compartments of the secretory pathway. Milk lipids originate as small droplets of triacylglycerol, synthesized

Mather, Ian

157

Chemotherapy Is of Limited Efficacy in the Control of Contralateral Testicular Intraepithelial Neoplasia in Patients with Testicular Germ Cell Cancer  

Microsoft Academic Search

Introduction: Testicular intraepithelial neoplasia (TIN, also called carcinoma in situ of the testis), the precursor of testicular germ cell tumors, will progress to invasive cancer unless appropriate treatment is instituted. Orchiectomy and local radiotherapy have been shown to eradicate TIN safely. The efficacy of chemotherapy is equivocal to date. Patients and Methods: Eleven patients with unilateral testicular cancer (5 pure

Klaus Kleinschmidt; Klaus-Peter Dieckmann; Alexander Georgiew; Volker Loy; Lothar Weissbach

2009-01-01

158

Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis  

Microsoft Academic Search

Background & Aims: Timely diagnosis of intraepithelial neoplasias (IN) and colitis-associated colon carcinomas (CRC) is crucially important for the treatment of ulcerative colitis (UC). We performed a randomized, controlled trial to test whether chromoendoscopy (CE) might facilitate early detection of IN and CRC in UC. Methods: A total of 263 patients with long-standing UC (?8 years) were screened for potential

Ralf Kiesslich; Johannes Fritsch; Martin Holtmann; Heinz H. Koehler; Manfred Stolte; Stephan Kanzler; Bernhard Nafe; Michael Jung; Peter R. Galle; Markus F. Neurath

2003-01-01

159

Comparing Benign and Malignant Neoplasia and DSB Induction for Low-and High-LET Radiation  

NASA Astrophysics Data System (ADS)

One-and 2-stage models based on DNA double strand breaks (DSBs) have been developed to describe the dose and LET dependence of cancer induction in rat skin exposed to the Bragg plateau of several ion beams or electron radiation. Data are presented showing that carcinomas (malignant) and fibromas (benign) are induced differently by low and high LET radiation. DSBs are subject to complex repair processes, including homologous and non-homologous end joining, that slowly eliminate broken chromosome ends but at the expense of elevating genomic instability that increases the risk of neoplasia. In this formulation the initial molecular lesion in radiation carcinogenesis is assumed to be a DNA double strand break (DSB). The 2-event model assumes that pairs of DSBs join to create cellular genomic instability that eventually progresses to malignancy. The 1-event model assumes that joining is insignificant but that unrepaired DSBs remain and are sufficiently destabilizing to produce low-grade neoplasias. The respective expected relationships between neoplasia yield (Y), radiation dose (D) and LET (L) are: Y(D) = CLD + BD2 (A) for 2-events and Y(D) = CLD (B) for 1-event. Respective B and C values have been evaluated empirically for carcinomas, fibromas and DSBs, the latter via the -H2Ax technique in surrogate keratinocytes, for several types of radiations, including, 40Ar ions, 56Fe ions, 20Ne ions, protons, electrons and x-rays. Fibromas outnumber carcinomas by about 6:1 but are more sensitive than carcinomas to the cytolethal effect of the radiations. The 2-event model agrees well with carcinoma yields in rat skin but fails to model fibromas correctly. Instead the fibroma yields best fitted with the 1-event model for the high LET ion radiations, but at very low LET (electron radiation), an empirical D3 component becomes apparent which is not currently incorporated into the theoretical model. At higher LET values, the D3 component was not detected. The overall results are summarized as follows: 1) DSBs predict carcinoma yields in regard to dose and LET in conformity to Equation A, 2) fibroma yields for 40Ar and 20Ne ions conform to Equation B, i.e. yield proportionality to D and L and 3) the positive slope of the fibroma yield to electron radiation is a third order discrepancy suggesting a more complicated response that has yet to be incorporated into the model. The results provide encouragement that once calibrated for humans, a short-term test of DSB yield might be capable of predicting cancer risks for a variety of space radiation exposure scenarios.

Burns, Fredric; (Eric) Tang, Moon-Shong; Wu, Feng

160

Fluorescence spectroscopy incorporated in an Optical Biopsy System for the detection of early neoplasia in Barrett's esophagus.  

PubMed

Endoscopic surveillance is recommended for patients with Barrett's esophagus (BE) to detect high-grade intraepithelial neoplasia (HGIN) or early cancer (EC). Early neoplasia is difficult to detect with white light endoscopy and random biopsies are associated with sampling error. Fluorescence spectroscopy has been studied to distinguish non-dysplastic Barrett's epithelium (NDBE) from early neoplasia. The Optical Biopsy System (OBS) uses an optical fiber integrated in a regular biopsy forceps. This allows real-time spectroscopy and ensures spot-on correlation between the spectral signature and corresponding physical biopsy. The OBS may provide an easy-to-use endoscopic tool during BE surveillance. We aimed to develop a tissue-differentiating algorithm and correlate the discriminating properties of the OBS with the constructed algorithm to the endoscopist's assessment of the Barrett's esophagus. In BE patients undergoing endoscopy, areas suspicious for neoplasia and endoscopically non-suspicious areas were investigated with the OBS, followed by a correlating physical biopsy with the optical biopsy forceps. Spectra were correlated to histology and an algorithm was constructed to discriminate between HGIN/EC and NDBE using smoothed linear dicriminant analysis. The constructed classifier was internally cross-validated and correlated to the endoscopist's assessment of the BE segment. A total of 47 patients were included (39 males, age 66 years): 35 BE patients were referred with early neoplasia and 12 patients with NDBE. A total of 245 areas were investigated with following histology: 43 HGIN/EC, 66 low-grade intraepithelial neoplasia, 108 NDBE, 28 gastric or squamous mucosa. Areas with low-grade intraepithelial neoplasia and gastric/squamous mucosa were excluded. The area under the receiver operating characteristic curve of the constructed classifier was 0.78. Sensitivity and specificity for the discrimination between NDBE and HGIN/EC of OBS alone were 81% and 58% respectively. When OBS was combined with the endoscopist's assesssment, sensitivity was 91% and specificity 50%. If this protocol would have guided the decision to obtain biopsies, half of the biopsies would have been avoided, yet 4/43 areas containing HGIN/EC (9%) would have been inadvertently classified as unsuspicious. In this study, the OBS was used to construct an algorithm to discriminate neoplastic from non-neoplastic BE. Moreover, the feasibility of OBS with the constructed algorithm as an adjunctive tool to the endoscopist's assessment during endoscopic BE surveillance was demonstrated. These results should be validated in future studies. In addition, other probe-based spectroscopy techniques may be integrated in this optical biopsy forceps system. PMID:24602242

Boerwinkel, D F; Holz, J A; Hawkins, D M; Curvers, W L; Aalders, M C; Weusten, B L; Visser, M; Meijer, S L; Bergman, J J

2014-03-01

161

Mortality by neoplasia and cellular telephone base stations in the Belo Horizonte municipality, Minas Gerais state, Brazil.  

PubMed

Pollution caused by the electromagnetic fields (EMFs) of radio frequencies (RF) generated by the telecommunication system is one of the greatest environmental problems of the twentieth century. The purpose of this research was to verify the existence of a spatial correlation between base station (BS) clusters and cases of deaths by neoplasia in the Belo Horizonte municipality, Minas Gerais state, Brazil, from 1996 to 2006 and to measure the human exposure levels to EMF where there is a major concentration of cellular telephone transmitter antennas. A descriptive spatial analysis of the BSs and the cases of death by neoplasia identified in the municipality was performed through an ecological-epidemiological approach, using georeferencing. The database employed in the survey was composed of three data banks: 1. death by neoplasia documented by the Health Municipal Department; 2. BSs documented in ANATEL ("Agência Nacional de Telecomunicações": 'Telecommunications National Agency'); and 3. census and demographic city population data obtained from official archives provided by IBGE ("Instituto Brasileiro de Geografia e Estatística": 'Brazilian Institute of Geography and Statistics'). The results show that approximately 856 BSs were installed through December 2006. Most (39.60%) of the BSs were located in the "Centro-Sul" ('Central-Southern') region of the municipality. Between 1996 and 2006, 7191 deaths by neoplasia occurred and within an area of 500 m from the BS, the mortality rate was 34.76 per 10,000 inhabitants. Outside of this area, a decrease in the number of deaths by neoplasia occurred. The greatest accumulated incidence was 5.83 per 1000 in the Central-Southern region and the lowest incidence was 2.05 per 1000 in the Barreiro region. During the environmental monitoring, the largest accumulated electric field measured was 12.4 V/m and the smallest was 0.4 V/m. The largest density power was 40.78 ?W/cm(2), and the smallest was 0.04 ?W/cm(2). PMID:21741680

Dode, Adilza C; Leão, Mônica M D; Tejo, Francisco de A F; Gomes, Antônio C R; Dode, Daiana C; Dode, Michael C; Moreira, Cristina W; Condessa, Vânia A; Albinatti, Cláudia; Caiaffa, Waleska T

2011-09-01

162

Fine-scale mapping of the gene responsible for multiple endocrine neoplasia type 1 (MEN 1).  

PubMed Central

We have constructed a high-resolution genetic linkage map in the vicinity of the gene responsible for multiple endocrine neoplasia type 1 (MEN1). The mutation causing this disease, inherited as an autosomal dominant, predisposes carriers to development of neoplastic tumors in the parathyroid, the endocrine pancreas, and the anterior lobe of the pituitary. The 12 markers on the genetic linkage map reported here span nearly 20 cM, and linkage analysis of MEN1 pedigrees has placed the MEN1 locus within the 8-cM region between D11S480 and D11S546. The markers on this map will be useful for prenatal or presymptomatic diagnosis of individuals in families that segregate a mutant allele of the MEN1 gene. PMID:1734719

Fujimori, M; Wells, S A; Nakamura, Y

1992-01-01

163

High incidence of lymphoid neoplasia in a colony of Egyptian spiny-tailed lizards (Uromastyx aegyptius).  

PubMed

Hematopoietic malignancies are the most commonly reported neoplasms in lizards, occurring sporadically as in other reptiles. An unusually high incidence of lymphoid neoplasia occurred in a collection of Egyptian spiny-tailed lizards (Uromastyx aegyptius) from 1993-2001. Eight of 15 lizards necropsied at the Louisville Zoological Garden (53%) had multicentric lymphoma. Immunohistochemistry was not useful in characterizing the lineage of normal or neoplastic lymphocytes. By light and electron microscopy (EM), the neoplasms had plasmacytoid morphologic features suggesting B-cell origin, although some tumors also had a primitive lymphoblast component. A concurrent leukemic blood profile was identified in seven of the cases (88%). All were adult animals and no sex predilection was observed. No exposure to exogenous carcinogens was observed. Some of the lizards were unrelated, so hereditary factors were unlikely. Although examination by EM and viral isolation performed on archived tissues and plasma failed to detect viruses, an infectious etiology still warrants consideration. PMID:17315465

Gyimesi, Zoltan S; Garner, Michael M; Burns, Roy B; Nichols, Donald K; Brannian, Roger E; Raymond, James T; Poonacha, Kockanda B; Kennedy, Melissa; Wojcieszyn, John W; Nordhausen, Robert

2005-03-01

164

Primary localized amyloidosis of the urinary tract frequently mimics neoplasia: a clinicopathologic analysis of 11 cases  

PubMed Central

Localized urinary tract amyloidosis (UTA) is a rare disease that mimics neoplasia clinically, cystoscopically, and radiologically. We report eleven cases of isolated UTA from the urinary bladder (n=7) and upper urinary tract including the ureter (n=2) and renal pelvis (n=2). All cases clinically presented as mass lesions prior to histologic examination and clinically suggested a neoplastic process. The amyloid composition in most cases was mixed Kappa and Lambda light chains. All cases were cured after surgical excision except one case which was diagnosed as plasmacytosis/plasmacytoma six months later. Localized amyloidosis of the urinary tract usually has a benign clinical course and simple resection is recommended after systemic disease is ruled out. PMID:25374907

Zhou, Fang; Lee, Peng; Zhou, Ming; Melamed, Jonathan; Deng, Fang-Ming

2014-01-01

165

Primary localized amyloidosis of the urinary tract frequently mimics neoplasia: a clinicopathologic analysis of 11 cases.  

PubMed

Localized urinary tract amyloidosis (UTA) is a rare disease that mimics neoplasia clinically, cystoscopically, and radiologically. We report eleven cases of isolated UTA from the urinary bladder (n=7) and upper urinary tract including the ureter (n=2) and renal pelvis (n=2). All cases clinically presented as mass lesions prior to histologic examination and clinically suggested a neoplastic process. The amyloid composition in most cases was mixed Kappa and Lambda light chains. All cases were cured after surgical excision except one case which was diagnosed as plasmacytosis/plasmacytoma six months later. Localized amyloidosis of the urinary tract usually has a benign clinical course and simple resection is recommended after systemic disease is ruled out. PMID:25374907

Zhou, Fang; Lee, Peng; Zhou, Ming; Melamed, Jonathan; Deng, Fang-Ming

2014-01-01

166

Differential gene expression profiling of gastric intraepithelial neoplasia and early-stage adenocarcinoma  

PubMed Central

AIM: To investigate the differentiated whole genome expression profiling of gastric high- and low-grade intraepithelial neoplasia and early-stage adenocarcinoma. METHODS: Gastric specimens from an upper magnifying chromoendoscopic targeted biopsy were collected from March 2010 to May 2013. Whole genome expression profiling was performed on 19 low-grade intraepithelial neoplasia (LGIN), 20 high-grade intraepithelial neoplasia (HGIN), 19 early-stage adenocarcinoma (EGC), and 19 chronic gastritis tissue samples using Agilent 4 × 44K Whole Human Genome microarrays. Differentially expressed genes between different types of lesions were identified using an unpaired t-test and corrected with the Benjamini and Hochberg false discovery rate algorithm. A gene ontology (GO) enrichment analysis was performed using the GeneSpring software GX 12.6. The differentially expressed gene was verified using a real-time TaqMan® PCR assay with independent tissue samples, including 26 LGIN, 15 HGIN, 14 EGC, and 20 chronic gastritis. The expression of G0S2 were further validated by immunohistochemical staining (IHC) in 24 LGIN, 40 HGIN, 30 EGC and 61 chronic gastritis specimens. RESULTS: The gene expression patterns of LGIN and HGIN tissues were distinct. There were 2521 significantly differentially expressed transcripts in HGIN, with 951 upregulated and 1570 downregulated. A GO enrichment analysis demonstrated that the most striking overexpressed transcripts in HGIN compared with LGIN were in the category of metabolism, defense response, and nuclear factor ?B (NF-?B) cascade. While the vast majority of transcripts had barely altered expression in HGIN and EGC tissues, only 38 transcripts were upregulated in EGC. A GO enrichment analysis revealed that the alterations of the immune response were most prominent in the progression from HGIN to EGC. It is worth noting that, compared with LGIN, 289 transcripts were expressed at higher levels both in HGIN and EGC. A characteristic gene, G0/G1 switch 2 (G0S2) was one of the 289 transcripts and related to metabolism, the immune response, and the NF-?B cascade, and its expression was validated in independent samples through real-time TaqMan® PCR and immunohistochemical staining. In real-time PCR analysis, the expression of G0S2 was elevated both in HGIN and EGC compared with that in LGIN (P < 0.01 and P < 0.001, respectively). In IHC analysis, G0S2 immunoreactivity was detected in the cytoplasmic of neoplastic cells, but was undetectable in chronic gastritis cells. The G0S2 expression in HGIN was higher than that of LGIN (P = 0.012, ?2 = 6.28) and EGC (P = 0.008, ?2 = 6.94). CONCLUSION: A clear biological distinction between gastric high- and low-grade intraepithelial neoplasia was identified, and provides molecular evidence for clinical application. PMID:25548486

Xu, Xue; Feng, Lin; Liu, Yu; Zhou, Wei-Xun; Ma, Ying-Cai; Fei, Gui-Jun; An, Ning; Li, Yuan; Wu, Xi; Yao, Fang; Cheng, Shu-Jun; Lu, Xing-Hua

2014-01-01

167

Faecal occult blood screening for colorectal neoplasia in a targeted high-risk population.  

PubMed

A general practice-based programme was initiated in 1987 to identify individuals at high risk of developing large bowel cancer and offer them screening of faecal occult blood. In all, 5298 people from 21 general practices in the Guildford area were offered 7510 screening tests. In total, 5934 tests were completed (compliance rate 79.0 per cent) with 287 positive results (4.8 per cent). Of the patients with positive results, 44 had cancer and 38 polyps. The sensitivity of the test for cancer was 63 per cent, the specificity 96 per cent and the positive predictive value for all neoplasia 29 per cent. The detection rate of 44 cancers per 5934 people screened compares favourably with data from the Nottingham-based screening of an unselected population (0.74 versus 0.23 per cent). PMID:8252347

Caffarey, S M; Broughton, C I; Marks, C G

1993-11-01

168

Myeloproliferative neoplasia remodels the endosteal bone marrow niche into a self-reinforcing leukemic niche.  

PubMed

Multipotent stromal cells (MSCs) and their osteoblastic lineage cell (OBC) derivatives are part of the bone marrow (BM) niche and contribute to hematopoietic stem cell (HSC) maintenance. Here, we show that myeloproliferative neoplasia (MPN) progressively remodels the endosteal BM niche into a self-reinforcing leukemic niche that impairs normal hematopoiesis, favors leukemic stem cell (LSC) function, and contributes to BM fibrosis. We show that leukemic myeloid cells stimulate MSCs to overproduce functionally altered OBCs, which accumulate in the BM cavity as inflammatory myelofibrotic cells. We identify roles for thrombopoietin, CCL3, and direct cell-cell interactions in driving OBC expansion, and for changes in TGF-?, Notch, and inflammatory signaling in OBC remodeling. MPN-expanded OBCs, in turn, exhibit decreased expression of many HSC retention factors and severely compromised ability to maintain normal HSCs, but effectively support LSCs. Targeting this pathological interplay could represent a novel avenue for treatment of MPN-affected patients and prevention of myelofibrosis. PMID:23850243

Schepers, Koen; Pietras, Eric M; Reynaud, Damien; Flach, Johanna; Binnewies, Mikhail; Garg, Trit; Wagers, Amy J; Hsiao, Edward C; Passegué, Emmanuelle

2013-09-01

169

Differentiated (simplex) vulvar intraepithelial neoplasia: a case report and review of the literature.  

PubMed

Differentiated (simplex) vulvar intraepithelial neoplasia (VIN) is an uncommon variant of VIN characterized by highly differentiated morphology, making it a potential diagnostic pitfall. It may arise in the background of lichen sclerosus, and unlike most VIN, is not causally associated with human papilloma virus infection. It occurs in an older demographic and is thought to be the precursor of aggressive, invasive vulvar squamous cell carcinoma. For this reason, the timely and accurate diagnosis of this unusual lesion is crucial. The clinical and histologic features of a case of a 70-year-old woman with newly diagnosed differentiated (simplex) VIN arising in a background of long-standing lichen sclerosus is reported, and the historic aspects, current terminology, and diagnostic criteria of differentiated (simplex) VIN are reviewed. PMID:21522046

Taube, Janis M; Badger, Joanna; Kong, Christina S; Dadras, Soheil S

2011-05-01

170

Primary hyperparathyroidism in patients with multiple endocrine neoplasia syndromes. Surgical experience.  

PubMed

Forty-five patients with biochemically documented primary hyperparathyroidism as part of multiple endocrine neoplasia syndrome types 1 or 2 were surgically treated from 1960 through 1980. Hyperplasia occurred in 69% of the patients, single adenoma in 27%, and double adenomas in 4%. All but two patients with hyperplasia underwent subtotal parathyroidectomy. In this group, the cure rate was 93% and the incidence of permanent postoperative hypoparathyroidism 23%. In the adenoma group, treatment included excision of the adenoma and biopsy of at least one other gland. The cure rate was 76%, with no postoperative hypoparathyroidism. Analysis of patients with persistent hyperparathyroidism suggested that failure to recognize multiple gland disease was the principal cause of postoperative hypercalcemia. In view of the high incidence of hypocalcemia after subtotal parathyroidectomy, approximately 500 mg of tissue should be cryopreserved to allow transplantation should hypocalcemia ensue postoperatively. PMID:6132593

van Heerden, J A; Kent, R B; Sizemore, G W; Grant, C S; ReMine, W H

1983-05-01

171

Fine-scaling mapping of the gene responsible for multiple endocrine neoplasia type I (MEN1)  

SciTech Connect

The authors have constructed a high-resolution genetic linkage map in the vicinity of the gene responsible for multiple endocrine neoplasia type 1 (MEN1). The mutation causing this disease, inherited as an autosomal dominant, predisposes carriers to development of neoplastic tumors in the parathyroid, the endocrine pancreas, and the anterior lobe of the pituitary. The 12 markers on the genetic linkage map reported here span nearly 20 cM, and linkage analysis of MEN1 pedigrees has placed the MEN1 locus within the 8-cM region between D11S480 and D11S546. The markers on this map will be useful for prenatal or presymptomatic diagnosis of individuals in families that segregate a mutant allele of the MEN1 gene.

Fujimori, Minoru; Nakamura, Yusuke (Cancer Institute, Tokyo (Japan)); Wells, S.A. (Washington University School of Medicine, St. Louis (United States))

1992-02-01

172

Myeloproliferative Neoplasia Remodels the Endosteal Bone Marrow Niche into a Self-Reinforcing Leukemic Niche  

PubMed Central

SUMMARY Multipotent stromal cells (MSC) and their osteoblastic lineage cell (OBC) derivatives are part of the BM niche and contribute to hematopoietic stem cells (HSC) maintenance. Here, we show that myeloproliferative neoplasia (MPN) progressively remodels the endosteal BM niche into a self-reinforcing leukemic niche that impairs normal hematopoiesis, favors leukemic stem cell (LSC) function and contributes to BM fibrosis. We show that leukemic myeloid cells stimulate MSCs to overproduce functionally altered OBCs, which accumulate in the BM cavity as inflammatory myelofibrotic cells. We identify roles for TPO, CCL3 and direct cell-cell interactions in driving OBC expansion, and for changes in TGF?, Notch and inflammatory signaling in OBC remodeling. MPN-expanded OBCs, in turn, exhibit decreased expression of many HSC retention factors and severely compromised ability to maintain normal HSCs, but effectively support LSCs. Targeting this pathological interplay could represent a novel avenue to treat MPN patients and prevent myelofibrosis. PMID:23850243

Schepers, Koen; Pietras, Eric M.; Reynaud, Damien; Flach, Johanna; Binnewies, Mikhail; Garg, Trit; Wagers, Amy J.; Hsiao, Edward C.; Passegué, Emmanuelle

2013-01-01

173

Hidden diagnosis of multiple endocrine neoplasia-1 unraveled during workup of virilization caused by adrenocortical carcinoma  

PubMed Central

Multiple endocrine neoplasia-1 (MEN1) is an autosomal dominant syndrome with classic triad of parathyroid hyperplasia, pancreatic neuroendocrine tumors, and pituitary adenomas. Other recognized manifestations include carcinoid, cutaneous or adrenocortical tumors. It is commonly presented with clinical features related to parathyroid, pancreas or pituitary lesions. Here, we have presented a case that had virilization and biochemical Cushing's syndrome due to adrenocortical carcinoma as presenting feature of MEN1. Cushing's syndrome in MEN1 is an extremely rare and usually late manifestation and most cases are due to corticotropin-producing pituitary adenomas. Although Cushing's syndrome generally develops years after the more typical manifestations of MEN1 appear, it may be the primary manifestation of MEN1 syndrome particularly when related to adrenal adenoma or carcinoma. PMID:23869313

Kharb, Sandeep; Pandit, Aditi; Gundgurthi, Abhay; Garg, M. K.; Brar, K. S.; Kannan, N.; Bharwaj, Reena

2013-01-01

174

Neoplasia associated with atypical glandular cells of undetermined significance on cervical cytology.  

PubMed

The clinical importance of atypical glandular cells of undetermined significance (AGUS) on cervicovaginal smear has not been well defined. Between January 1990 and April 1996, 127 smears were reported as showing AGUS changes by the cytopathology division at the University of Massachusetts Medical Center. The medical records of these women were reviewed: 17 women were excluded because of previous hysterectomy or gynecologic cancer, 85 were biopsied, 16 were followed by repeat smears, and 9 were lost to follow-up. Forty-four women had negative biopsies or cervicitis. There were 15 endometrial lesions: 10 hyperplasias (2 with atypia) and 5 adenocarcinomas. Twenty-five women had cervix lesions including 3 endocervical atypias, 12 low-grade cervical intraepithelial neoplasia (CIN), 6 high-grade CIN, one adenocarcinoma in situ, and 3 invasive adenocarcinomas. One patient had ovarian cancer. Two of the 16 women followed by repeat pap smear eventually had a cancer diagnosis: one with cervix cancer and one with colon cancer. We were unable to identify a subgroup of women with AGUS who were at increased risk for serious pathology when we compared multiple demographic variables, symptoms, or the presence of coexistent squamous abnormalities on cervical cytology. The mean age of the 15 women with endometrial lesions was 59.9 years, which was significantly older than those patients with cervix lesions who had a mean age of 38.9 years. The presence of AGUS on cervical cytology is a marker for significant gynecologic neoplasia and should be investigated with colposcopically directed biopsies, endocervical curettage, and, in older women, endometrial biopsy. PMID:9159344

Zweizig, S; Noller, K; Reale, F; Collis, S; Resseguie, L

1997-05-01

175

Single visit approach for management of cervical intraepithelial neoplasia by visual inspection & loop electrosurgical excision procedure  

PubMed Central

Background & objectives: Developing a feasible and sustainable model of cervical cancer screening in developing countries continues to be a challenge because of lack of facilities and awareness in the population and poor compliance with screening and treatment. This study was aimed to evaluate a single visit approach (SVA) for the management of cervical intraepithelial neoplasia (CIN) using visual inspection with acetic acid (VIA) and Lugol's iodine (VILI) along with loop electrosurgical excision procedure (LEEP) in women attending Gynaecology OPD in a tertiary care hospital in north India. Methods: In this hospital-based study, 450 women receiving opportunistic screening by conventional Pap cytology were also screened by VIA and VILI. VIA/VILI positive cases underwent same-day colposcopy and biopsy of all lesions. If the modified Reid score was >3, the patient underwent LEEP at the same visit. Results: Of the 450 women screened, 86 (19.1%) and 92 (20.5%) women were VIA and VILI positive, respectively. Detection rates of VIA, VILI and cytology findings at ASCUS threshold were 33.3, 35.5 and 24.4 per 1000, women, respectively to detect a lesion >CIN1. For detection of CIN2+ lesion, detection rates of VIA, VILI and cytology were 20, 22.2 and 22.2 per 1000 women, respectively. Sixteen patients with Reid score >3 underwent the See-and-treat protocol. The overtreatment rate was 12.5 per cent and the efficacy of LEEP was 81.3 per cent. There were no major complications. Interpretation & conclusions: The sensitivity of VIA/VILI was comparable to cytology. A single visit approach using visual screening methods at community level by trained paramedical personnel followed by a combination of ablative and excisional therapy can help to decrease the incidence of cervical neoplasia. PMID:22771589

Singla, Shilpa; Mathur, Sandeep; Kriplani, Alka; Agarwal, Nutan; Garg, Pradeep; Bhatla, Neerja

2012-01-01

176

Endoscopic features suggesting gastric cancer in biopsy-proven gastric adenoma with high-grade neoplasia  

PubMed Central

AIM: To elucidate the endoscopic features that predict the cancer following endoscopic submucosal dissection (ESD) in patients with high-grade neoplasia (HGN). METHODS: We retrospectively analyzed the medical records of patients who underwent ESD of gastric neoplasms from January 2007 to September 2010. ESD was performed in 555 cases involving 550 patients. A total of 112 lesions from 110 consecutive patients were initially diagnosed as HGN without cancer by forceps biopsy, and later underwent ESD. We classified lesions into two groups according to histologic discrepancies between the biopsy and ESD diagnosis. Gastric adenoma in the final diagnosis by ESD specimens were defined as adenoma group. Lesions with coexisting cancer after ESD were defined as cancer group. RESULTS: The mean age was 65.3 years, and 81 patients were male. There was no significant difference in the age or gender distribution between the adenoma (n = 52) and cancer (n = 60) groups. Thirty-six of these lesions (32.1%) showed histologic concordance between the forceps biopsy and ESD specimens, 16 (14.3%) showed a downgraded histology (low-grade neoplasia), and 60 (53.6%) showed an upgraded histology (cancer). A red color change of the mucosal surface on endoscopy was found in 27/52 (51.9%) of cases in the adenoma group and in 46/60 (76.7%) of cases in the cancer group (P = 0.006). Ulceration of the mucosal surface on endoscopy was found in 5 (9.6%) of 52 lesions in the adenoma group and in 17 (28.3%) of 60 lesions in the cancer group (P = 0.013). In the multivariate analysis, a reddish surface color change and mucosal ulceration were significant predictive factors correlated with cancer after ESD of the HGN by forceps biopsy. CONCLUSION: HGN with a red color change or mucosal ulceration correlated with the presence of gastric cancer. These finding may help to guide the diagnosis and treatment. PMID:25232257

Kim, Jung Ho; Kim, Yoon Jae; An, Jungsuk; Lee, Jong Joon; Cho, Jae Hee; Kim, Kyoung Oh; Chung, Jun-Won; Kwon, Kwang An; Park, Dong Kyun; Kim, Ju Hyun

2014-01-01

177

Immune concept of human papillomaviruses and related antigens in local cancer milieu of human cervical neoplasia.  

PubMed

It is presently the right time for clarifying human papillomavirus (HPV)-associated cellular immunity and clinical implications before global HPV vaccination programs begin. Infection with oncogenic HPV associates with the progression of cervical neoplasia. Both cellular and humoral immune responses are essential for the clearance of HPV-associated cervical lesions. There is increasing evidence that the immune system plays a pivotal role in determining the outcome of HPV infection. Viruses and associated neoplastic cells are proposed to have evolved mechanisms to avoid immune attack. T-cell-mediated immune responses against oncogenic HPV are believed to play a central role in cervical carcinogenesis. The presence of HPV-specific cytotoxic T lymphocytes (CTL) in a majority of human cervical cancer patients provides an approach for further study of their functional role in modulating this malignancy. Tumor-infiltrating lymphocytes (TIL) develop as manifestations of the recognition and defense against malignant cells by the host immune system. Cancer cells may overcome immune surveillance, either by downregulating the proliferation of HPV-specific CTL, or altering the effector compositions of immune cells against HPV infections. TIL in the tumor microenvironment can be functionally inhibited and lose the ability of clonal proliferation as a result of depressed expression of IL-2Ralpha. The upregulation of inhibitory signaling relates to the modulation of the virus- and/or tumor-specific immune responses. Alteration of host genetic susceptibility may also lead to abnormal immune response as a general genomic instability resulting from virus persistence. Induction of HPV-specific immune responses is anticipated as an intimate point for the treatment of cervical neoplasia. PMID:17441881

Sheu, Bor-Ching; Chang, Wen-Chun; Lin, Ho-Hsiung; Chow, Song-Nan; Huang, Su-Cheng

2007-04-01

178

Immunohistochemical expression of SOX2 in vulvar intraepithelial neoplasia and squamous cell carcinoma.  

PubMed

SOX2 is a transcription factor controlling pluripotency in both embryonic stem cells and adult tissue-specific stem cells. SOX2 has been reported as an important factor in squamous cell carcinomas (SCC) of different locations and is involved in tumorigenesis. We evaluated the expression of SOX2 in vulvar non-neoplastic and neoplastic epithelia to test whether it is related to neoplastic progression. SOX2 immunoexpression was evaluated in 101 formalin-fixed, paraffin-embedded archival vulvar epithelia consisting of normal squamous vulvar epithelia (n=25), lichen sclerosus (n=9), high-grade classic vulvar intraepithelial neoplasia (HG-VIN, n=16), differentiated vulvar intraepithelial neoplasia (d-VIN, n=18), and vulvar invasive keratinizing SCC (n=33). Immunoexpression of SOX2 was nuclear and increased stepwise from normal vulvar epithelia/lichen sclerosus to HG-VIN and d-VIN (P<0.0001), from HG-VIN and d-VIN to invasive SCC (P=0.0029), and followed the morphologic distribution of atypical squamous epithelial cells. Scores for normal vulvar epithelia versus lichen sclerosus and HG-VIN versus d-VIN, respectively, did not differ significantly. SOX2 expression increased from tumor Grade 1 to 3 (P=0.0124); there was no relation to recurrence and survival. This is the first study presenting SOX2 as overexpressed in vulvar intraepithelial and invasive squamous lesions. This overexpression apparently reflects an early event in the neoplastic transformation of vulvar squamous epithelia. However, SOX2 seems to play a role in histologic dedifferentiation to Grade 3 invasive SCC too, and may be relevant to vulvar carcinogenesis. PMID:23518916

Brustmann, Hermann; Brunner, Andreas

2013-05-01

179

Localized amyloidosis of the vulva with and without vulvar intraepithelial neoplasia: report of a series.  

PubMed

Localized primary cutaneous amyloidosis is uncommon in Europe and North America and is infrequently reported in the English literature. The constituents of such deposits have not been previously examined; this series characterizes amyloid deposits in localized vulvar amyloidosis and their association with vulvar intraepithelial neoplasia. All biopsies and excisions of vulva over 18 months were reviewed. Cases with suspected amyloidosis were retrieved after institutional review board approval. Twenty cases mimicking amyloidosis were selected as controls. All study and control cases were stained with Congo red. Four Congo red-positive study cases were studied by liquid chromatography-tandem mass spectrometry. Of 27 Congo red-positive study cases, 25 were then examined by immunohistochemical stains with antibodies to cytokeratin 5 (CK5) and cytokeratin 14 (CK14). Of 149 cases reviewed, 26 localized and 1 systemic vulvar amyloidosis were identified. Liquid chromatography-tandem mass spectrometry analysis of the deposits revealed unique peptide profile consistent with CK5 and CK14. Immunohistochemical staining with antibodies to CK5 and CK14 also detected these components in the deposits. The vulvar deposit of systemic amyloidosis consisted of amyloid light chain (?)-type amyloid deposit. All control cases were negative for Congo red. Keratin-associated amyloid materials (CK5 and CK14) were found to be unique in localized vulvar amyloidosis. Leakage of keratins from the basal layer of the epithelium into the superficial dermis may have been the possible source of the deposits. It appears to be associated with both high-grade and low-grade vulvar intraepithelial neoplasias and, rarely, lichen sclerosus, seborrheic keratosis, and benign vulvar skin. PMID:25149547

Quddus, M Ruhul; Sung, C James; Simon, Rochelle A; Lawrence, W Dwayne

2014-10-01

180

Genome-wide methylation profiling identifies hypermethylated biomarkers in high-grade cervical intraepithelial neoplasia.  

PubMed

Epigenetic modifications, such as aberrant DNA promoter methylation, are frequently observed in cervical cancer. Identification of hypermethylated regions allowing discrimination between normal cervical epithelium and high-grade cervical intraepithelial neoplasia (CIN2/3), or worse, may improve current cervical cancer population-based screening programs. In this study, the DNA methylome of high-grade CIN lesions was studied using genome-wide DNA methylation screening to identify potential biomarkers for early diagnosis of cervical neoplasia. Methylated DNA Immunoprecipitation (MeDIP) combined with DNA microarray was used to compare DNA methylation profiles of epithelial cells derived from high-grade CIN lesions with normal cervical epithelium. Hypermethylated differentially methylated regions (DMRs) were identified. Validation of nine selected DMRs using BSP and MSP in cervical tissue revealed methylation in 63.2-94.7% high-grade CIN and in 59.3-100% cervical carcinomas. QMSP for the two most significant high-grade CIN-specific methylation markers was conducted exploring test performance in a large series of cervical scrapings. Frequency and relative level of methylation were significantly different between normal and cancer samples. Clinical validation of both markers in cervical scrapings from patients with an abnormal cervical smear confirmed that frequency and relative level of methylation were related with increasing severity of the underlying CIN lesion and that ROC analysis was discriminative. These markers represent the COL25A1 and KATNAL2 and their observed increased methylation upon progression could intimate the regulatory role in carcinogenesis. In conclusion, our newly identified hypermethylated DMRs represent specific DNA methylation patterns in high-grade CIN lesions and are candidate biomarkers for early detection. PMID:23018867

Lendvai, Ágnes; Johannes, Frank; Grimm, Christina; Eijsink, Jasper J H; Wardenaar, René; Volders, Haukeline H; Klip, Harry G; Hollema, Harry; Jansen, Ritsert C; Schuuring, Ed; Wisman, G Bea A; van der Zee, Ate G J

2012-11-01

181

Genome-wide methylation profiling identifies hypermethylated biomarkers in high-grade cervical intraepithelial neoplasia  

PubMed Central

Epigenetic modifications, such as aberrant DNA promoter methylation, are frequently observed in cervical cancer. Identification of hypermethylated regions allowing discrimination between normal cervical epithelium and high-grade cervical intraepithelial neoplasia (CIN2/3), or worse, may improve current cervical cancer population-based screening programs. In this study, the DNA methylome of high-grade CIN lesions was studied using genome-wide DNA methylation screening to identify potential biomarkers for early diagnosis of cervical neoplasia. Methylated DNA Immunoprecipitation (MeDIP) combined with DNA microarray was used to compare DNA methylation profiles of epithelial cells derived from high-grade CIN lesions with normal cervical epithelium. Hypermethylated differentially methylated regions (DMRs) were identified. Validation of nine selected DMRs using BSP and MSP in cervical tissue revealed methylation in 63.2–94.7% high-grade CIN and in 59.3–100% cervical carcinomas. QMSP for the two most significant high-grade CIN-specific methylation markers was conducted exploring test performance in a large series of cervical scrapings. Frequency and relative level of methylation were significantly different between normal and cancer samples. Clinical validation of both markers in cervical scrapings from patients with an abnormal cervical smear confirmed that frequency and relative level of methylation were related with increasing severity of the underlying CIN lesion and that ROC analysis was discriminative. These markers represent the COL25A1 and KATNAL2 and their observed increased methylation upon progression could intimate the regulatory role in carcinogenesis. In conclusion, our newly identified hypermethylated DMRs represent specific DNA methylation patterns in high-grade CIN lesions and are candidate biomarkers for early detection. PMID:23018867

Lendvai, Ágnes; Johannes, Frank; Grimm, Christina; Eijsink, Jasper J.H.; Wardenaar, René; Volders, Haukeline H.; Klip, Harry G.; Hollema, Harry; Jansen, Ritsert C.; Schuuring, Ed; Wisman, G. Bea A.; van der Zee, Ate G.J.

2012-01-01

182

Identification of subjects at risk of proximal advanced neoplasia for colorectal cancer screening.  

PubMed

Flexible sigmoidoscopy (FS) and colonoscopy are two commonly used screening tools for colorectal cancer (CRC), and FS mainly detects distal lesions. Colonoscopy resource is limited, yet there is no definite evidence on when flexible sigmoidoscopy is suitable as a screening alternative. This study evaluated the optimal cut-off score from a validated risk stratification system which best predicts proximal advanced neoplasia (PAN) by comparing the sensitivity, specificity and relative risk of PAN according to various cut-off scores. 5819 asymptomatic subjects aged between 50 and 70years (average age 57.7years, standard deviation (SD) 4.9) received colonoscopy between 2008 and 2014 in Hong Kong. Their prevalence of PAN was evaluated according to a prediction tool for colorectal neoplasia based on age, gender, smoking status, family history of CRC, body mass index (BMI) and diabetes (ranging from 0 to 6). One binary logistic regression model was performed with PAN as the outcome variable and the risk score as the variable tested for association. In multivariate regression analysis, risk score ?3 was associated with significantly higher risk of PAN (3.4-9.1%; AOR=3.18-8.09, p<0.001) when compared with those scoring 0. Risk scores 0-2 were associated with either insignificant or lower risks of PAN compared to the overall risk. Applying FS for screening those who scored 0-2 and colonoscopy for those who scored ?3 led to a very small proportion of PAN being missed (1.60%), whilst maintaining a high level of specificity (81.9%). Clinicians may use this scoring system to inform subjects and facilitate their choice between colonoscopy and FS. PMID:25459390

Wong, Martin C S; Ching, Jessica Y L; Chan, Victor C W; Lam, Thomas Y T; Luk, Arthur K C; Wong, Sunny H; Ng, Siew C; Ng, Simon S M; Wu, Justin C Y; Chan, Francis K L; Sung, Joseph J Y

2015-01-01

183

Conversación con Ricardo Monti  

E-print Network

las carreras sucedía lo siguiente: yo quería ser e iba a ser escritor. Empecé filosofía y cursé seis o siete materias. Luego inicié la carrera de psi cología, pero mis estudios de psicología se interrumpieron cuando estrené mi primera obra de teatro... caos, organizar una serie de sensaciones e ideas, que impliquen cierta forma, cierta organización. Además, cada obra mía se empalma con la otra, como si yo buscara obscuramente no solamente organizar ese caos en cada obra, sino ir organizándolo con...

Driskell, Charles B.

1979-04-01

184

Risk Association between Human Leukocyte Antigen-A Allele and High-Risk Human Papillomavirus Infection for Cervical Neoplasia in Chinese Women  

Microsoft Academic Search

To examine the association between human leukocyte antigen-A (HLA-A) allele polymorphism, human papillomavirus (HPV) infection, and risk for cervical neoplasia in Chinese women, 263 patients (155 with cervical intraepithelial neoplasia [CIN] II\\/III and 108 with invasive cervical cancer [ICC]) were compared with 572 controls. Overall, regardless of HPV status, a decreased risk for ICC was observed for patients with A*0207\\/0215N

2005-01-01

185

Transgenic mouse models that explore the multistep hypothesis of intestinal neoplasia.  

PubMed

SV-40 T antigen (TAg), human K-rasVal12, and a dominant negative mutant of human p53 (p53Ala143) have been expressed singly and in all possible combinations in postmitotic enterocytes distributed throughout the duodenal-colonic axis of 1-12-mo-old FVB/N transgenic mice to assess the susceptibility of this lineage to gene products implicated in the pathogenesis of human gut neoplasia. SV-40 TAg produces re-entry into the cell cycle. Transgenic pedigrees that produce K-rasVal12 alone, p53Ala143 alone, or K-rasVal12 and p53Ala143 have no detectable phenotypic abnormalities. However, K-rasVal12 cooperates with SV-40 TAg to generate marked proliferative and dysplastic changes in the intestinal epithelium. These abnormalities do not progress to form adenomas or adenocarcinomas over a 9-12-mo period despite sustained expression of the transgenes. Addition of p53Ala143 to enterocytes that synthesize SV-40 TAg and K-rasVal12 does not produce any further changes in proliferation or differentiation. Mice that carry one, two, or three of these transgenes were crossed to animals that carry Min, a fully penetrant, dominant mutation of the Apc gene associated with the development of multiple small intestinal and colonic adenomas. A modest (2-5-fold) increase in tumor number was noted in animals which express SV-40 TAg alone, SV-40 TAg and K-rasVal12, or SV-40 TAg, K-rasVal12 and p53Ala143. However, the histopathologic features of the adenomas were not altered and the gut epithelium located between tumors appeared similar to the epithelium of their single transgenic, bi-transgenic, or tri-transgenic parents without Min. These results suggest that (a) the failure of the dysplastic gut epithelium of SV-40 TAg X K-rasVal12 mice to undergo further progression to adenomas or adenocarcinomas is due to the remarkable protective effect of a continuously and rapidly renewing epithelium, (b) initiation of tumorigenesis in Min mice typically occurs in crypts rather than in villus-associated epithelial cell populations, and (c) transgenic mouse models of neoplasia involving members of the enterocytic lineage may require that gene products implicated in tumorigenesis be directed to crypt stem cells or their immediate descendants. Nonetheless, directing K-rasVal12 production to proliferating and nonproliferating cells in the lower and upper half of small intestinal and colonic crypts does not result in any detectable abnormalities. PMID:8227147

Kim, S H; Roth, K A; Moser, A R; Gordon, J I

1993-11-01

186

Genetic and Clinical Features of Multiple Endocrine Neoplasia Types 1 and 2  

PubMed Central

Multiple endocrine neoplasia (MEN) are clinical inherited syndromes affecting different endocrine glands. Three different patterns of MEN syndromes can occur (MEN 1, MEN 2A, and MEN 2B). MEN syndromes are very rare, affect all ages and both sexes are equally affected. MEN 1 is characterized by the neoplastic transformation of the parathyroid glands, pancreatic islets, anterior pituitary, and gastrointestinal tract. Heterozygous MEN 1 germline mutations have been detected in about 70–80% of patients with MEN 1. The mutations are scattered throughout the entire genomic sequence of the gene. MEN 1 patients are characterized by variable clinical features, thus suggesting the lack of a genotype-phenotype correlation. Therapeutical approaches are different according to the different endocrinopathies. The prognosis is generally good if adequate treatment is provided. In MEN 2 syndromes, the medullary thyroid cancer (MTC) is almost invariably present and can be associated with pheochromocytoma (PHEO) and/or multiple adenomatosis of parathyroid glands with hyperparathyroidism (PHPT). The different combination of the endocrine neoplasia gives origin to 3 syndromes: MEN 2A, MEN 2B, and FMTC. The clinical course of MTC varies considerably in the three syndromes. It is very aggressive in MEN 2B, almost indolent in the majority of patients with FMTC and with variable degrees of aggressiveness in patients with MEN 2A. Activating germline point mutations of the RET protooncogene are present in 98% of MEN 2 families. A strong genotype-phenotype correlation has been observed and a specific RET mutation may be responsible for a more or less aggressive clinical course. The treatment of choice for primary MTC is total thyroidectomy with central neck lymph nodes dissection. Nevertheless, 30% of MTC patients, especially in MEN 2B and 2A, are not cured by surgery. Recently, developed molecular therapeutics that target the RET pathway have shown very promising activity in clinical trials of patients with advanced MTC. MEN 2 prognosis is strictly dependent on the MTC aggressiveness and thus on the success of the initial treatment. PMID:23209466

Romei, C.; Pardi, E.; Cetani, F.; Elisei, R.

2012-01-01

187

Development of a reactive stroma associated with prostatic intraepithelial neoplasia in EAF2 deficient mice.  

PubMed

ELL-associated factor 2 (EAF2) is an androgen-responsive tumor suppressor frequently deleted in advanced prostate cancer that functions as a transcription elongation factor of RNA Pol II through interaction with the ELL family proteins. EAF2 knockout mice on a 129P2/OLA-C57BL/6J background developed late-onset lung adenocarcinoma, hepatocellular carcinoma, B-cell lymphoma and high-grade prostatic intraepithelial neoplasia. In order to further characterize the role of EAF2 in the development of prostatic defects, the effects of EAF2 loss were compared in different murine strains. In the current study, aged EAF2(-/-) mice on both the C57BL/6J and FVB/NJ backgrounds exhibited mPIN lesions as previously reported on a 129P2/OLA-C57BL/6J background. In contrast to the 129P2/OLA-C57BL/6J mixed genetic background, the mPIN lesions in C57BL/6J and FVB/NJ EAF2(-/-) mice were associated with stromal defects characteristic of a reactive stroma and a statistically significant increase in prostate microvessel density. Stromal inflammation and increased microvessel density was evident in EAF2-deficient mice on a pure C57BL/6J background at an early age and preceded the development of the histologic epithelial hyperplasia and neoplasia found in the prostates of older EAF2(-/-) animals. Mice deficient in EAF2 had an increased recovery rate and a decreased overall response to the effects of androgen deprivation. EAF2 expression in human cancer was significantly down-regulated and microvessel density was significantly increased compared to matched normal prostate tissue; furthermore EAF2 expression was negatively correlated with microvessel density. These results suggest that the EAF2 knockout mouse on the C57BL/6J and FVB/NJ genetic backgrounds provides a model of PIN lesions associated with an altered prostate microvasculature and reactive stromal compartment corresponding to that reported in human prostate tumors. PMID:24260246

Pascal, Laura E; Ai, Junkui; Masoodi, Khalid Z; Wang, Yujuan; Wang, Dan; Eisermann, Kurtis; Rigatti, Lora H; O'Malley, Katherine J; Ma, Hei M; Wang, Xinhui; Dar, Javid A; Parwani, Anil V; Simons, Brian W; Ittman, Michael M; Li, Luyuan; Davies, Benjamin J; Wang, Zhou

2013-01-01

188

Cervical intraepithelial neoplasia III: long-term follow-up after cold-knife conization with involved margins  

Microsoft Academic Search

OBJECTIVE:To evaluate the long-term outcome of patients with severe cervical intraepithelial neoplasia (CIN) III or squamous carcinoma in situ after cold-knife conization with involved margins.METHODS:A total of 390 patients (median age 39 years, range 20–69) with positive margins after cold-knife conization for CIN III were followed expectantly for a mean of 19 (range 6–30) years. Follow-up consisted of colposcopy, cytology,

Olaf Reich; Manfred Lahousen; Hellmuth Pickel; Karl Tamussino; Raimund Winter

2002-01-01

189

Prevalence of advanced neoplasia at screening colonoscopy in men in private practice versus academic and Veterans Affairs medical centers  

Microsoft Academic Search

OBJECTIVES:Several large population studies assessing the yield of average risk screening colonoscopy have evaluated Veterans Affairs (VA) populations. It remains uncertain how generalizable these findings are to men in the general population. The aim of this study was to define the prevalence of advanced neoplasia in male patients undergoing screening colonoscopy in diverse practice settings.METHODS:The Clinical Outcomes Research Initiative (CORI)

Gavin C. Harewood; David A. Lieberman

2003-01-01

190

Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A  

Microsoft Academic Search

MULTIPLE endocrine neoplasia type 2A (MEN 2A) is a dominantly inherited cancer syndrome that affects tissues derived from neural ectoderm. It is characterized by medullary thyroid carcinoma (MTC) and phaeochromocytomal. The MEN2A gene has recently been localized by a combination of genetic and physical mapping techniques to a 480-kilobase region in chromosome 10qll.2 (refs 2,3). The DNA segment encompasses the

Lois M. Mulligan; John B. J. Kwok; Catherine S. Healey; Mark J. Elsdon; Charis Eng; Emily Gardner; Donald R. Love; Sara E. Mole; Julie K. Moore; Laura Papi; Margaret A. Ponder; Hakan Telenius; Alan Tunnacliffe; Bruce A. J. Ponder

1993-01-01

191

immunohistochemical expression of survivin and ?-H2AX in vulvar intraepithelial neoplasia and low-stage squamous cell carcinoma.  

PubMed

Survivin inhibits apoptosis and is involved in the regulation of cell cycle progression and in the mitotic spindle formation. It is overexpressed in many cancers. The histone ?-H2AX is a marker of activated DNA damage and is overexpressed in different cancers and their precursor lesions. It also forms early during apoptosis. Eighty-seven formalin-fixed, paraffin-embedded archival vulvar tissues originating from 55 preoperatively untreated patients were immunostained with antibodies to survivin and ?-H2AX to determine their expression in normal squamous vulvar epithelia (NE, n=25), lichen sclerosus (n=10), high-grade classic vulvar intraepithelial neoplasia (n=16), differentiated vulvar intraepithelial neoplasia (n=16), and vulvar invasive keratinizing squamous cell carcinoma (ISCC, n=20; FIGO Ib). Immunostaining for both factors was scored for moderate and strong intensities with regard to quantity. Statistical analysis was performed by the ? test and Fisher exact test. Nuclear surviving expression increased from NE and lichen scleros to high-grade classic vulvar intraepithelial neoplasia, differentiated vulvar intraepithelial neoplasia, and ISCC significantly (P=0.0001) and followed the distribution of immature squamous epithelial cells. Positive scores for ?-H2AX were found in nuclei of cells in all diagnostic cohorts, in any epithelial level with some accentuation in the upper layers, was seen in pycnotic nuclei in horn pearls of ISCC and apoptotic bodies, without relevant statistical distributions. Immunoscores did not differ between grade 1 and grades 2/3. Expression patterns were different for both factors, suggesting their involvement in different biologic mechanisms as an early event leading to resistance to apoptosis in vulvar carcinogenesis. PMID:21979596

Brustmann, Hermann; Hinterholzer, Susanne; Brunner, Andreas

2011-11-01

192

Predictive DNA Testing and Prophylactic Thyroidectomy in Patients at Risk for Multiple Endocrine Neoplasia Type 2A  

Microsoft Academic Search

Background: Missense germ-line mutations in the RET protooncogene are associated with multiple endocrine neoplasia type 2A (MEN 2A). Detection of these mutant alleles in kindred members predicts disease inheritance and provides the basis for preventative thyroidectomy. Methods: A polymerase chain reaction (PCR)-based genetic test for the 19 known RET mutations was designed to study 132 members of 7 kindreds with

Samuel A. Wells; David D. Chi; Koji Toshima; Louis P. Dehner; Cheryl M. Coffin; S. Bruce Dowton; Jennifer L. Ivanovich; Mary K. DeBenedettl; William G. Dilley; Jeffrey F. Moley; Jeffrey A. Norton; Helen Donis-Keller

1994-01-01

193

Prevalence of high-risk human papillomavirus types in Mexican women with cervical intraepithelial neoplasia and invasive carcinoma  

Microsoft Academic Search

BACKGROUND: Prevalence of high risk (HR) human papillomavirus (HPV) types in the states of San Luis Potosí (SLP) and Guanajuato (Gto), Mexico, was determined by restriction fragment length-polymorphism (RFLP) analysis on the E6 ~250 bp (E6-250) HR-HPV products amplified from cervical scrapings of 442 women with cervical intraepithelial neoplasia and invasive carcinoma (280 from SLP and 192 from Gto). Fresh

Rubén López-Revilla; Luz A Martínez-Contreras; Mireya Sánchez-Garza

2008-01-01

194

Flexible sigmoidoscopy screening for colorectal neoplasia in average- risk people: evaluation of a five-year rescreening interval  

Microsoft Academic Search

Objective: To determine the prevalence of colorectal neoplasia detected by rescreening people with average risk five years after initial screening by flexible sigmoidoscopy. recorded address, and 361 of the remaining 665 (54%) were rescreened. Rescreening found a significantly lower prevalence of colorectal adenomas than initial screening (8% (95% CI, 5%-11%) versus 14% (95% CI, 13%-15%); P < 0.05) and also

Cameron F E Platell; Gillian Philpott; John K Olynyk

195

Feasibility of confocal fluorescence microscopy for real-time evaluation of neoplasia in fresh human breast tissue.  

PubMed

Breast cancer management could be improved by developing real-time imaging tools to assess tissue architecture without extensive processing. We sought to determine whether confocal fluorescence microscopy (CFM) provides sufficient information to identify neoplasia in breast tissue. Breast tissue specimens were imaged following proflavine application. Regions of interest (ROIs) were selected in histologic slides and in the corresponding region on confocal images, and then divided into sets for training and validation. Readers reviewed images in the training set and evaluated images in the validation set for the presence of neoplasia. Accuracy was assessed using histologic diagnosis as the gold standard. Seventy tissue specimens from 31 patients were imaged; 235 ROIs were identified and diagnosed as neoplastic or non-neoplastic. A training set was assembled using 23 matched ROIs; 49 matched ROIs were assembled into a validation set. Neoplasia was identified in histologic images: 93% sensitivity, 97% specificity [area under the curve (AUC=0.987)] and in confocal images: 93% sensitivity 93% specificity (AUC=0.957). CFM produced images of architectural features in breast tissue comparable with conventional histology, while requiring little processing. Potential applications include assessment of excised tissue margins and evaluation of tissue adequacy for bio-banking and genomic studies. PMID:24165742

Dobbs, Jessica L; Ding, Hao; Benveniste, Ana Paula; Kuerer, Henry M; Krishnamurthy, Savitri; Yang, Wei; Richards-Kortum, Rebecca

2013-10-01

196

Morphologically and immunohistochemically undifferentiated gastric neoplasia in a patient with multiple metastatic malignant melanomas: a case report  

PubMed Central

Introduction Malignant melanoma is a neoplasia which frequently involves the gastrointestinal tract (GIT). GIT metastases are difficult to diagnose because they often recur many years after treatment of the primary cutaneous lesion and also manifest clinically at an advanced stage of the neoplasia. Furthermore, GIT metastases can appear in various morphological forms, and therefore immunohistochemistry is often useful in distinguishing between a malignant melanoma and other malignancies. Case presentation We report the case of a 60-year-old man with a multiple metastatic melanoma who underwent an upper endoscopy to clarify the possible involvement of the gastric wall with a mass localized in the upper abdomen involving the pancreas and various lymph nodes, which was previously described with computed tomography. Clinically, the patient reported a progressive loss of appetite, nausea and vomiting. The upper endoscopy and histological examination revealed a gastric location of an undifferentiated neoplasm with an absence of immunohistochemical characteristics referable to the skin malignant melanoma that was removed previously. Conclusion The present case report shows the difficulty in diagnosing a metastatic melanoma in the GIT and therefore, it seems worthwhile to consider metastatic malignant melanoma in the differential diagnosis of undifferentiated neoplasia. PMID:18445301

Alghisi, Federico; Crispino, Pietro; Cocco, Andrea; Richetta, Antonio G; Nardi, Francesco; Paoluzi, Paolo; Badiali, Danilo

2008-01-01

197

MicroRNAs Involved in Tumor Suppressor and Oncogene Pathways; Implications for Hepatobiliary Neoplasia  

PubMed Central

MicroRNAs are a class of small regulatory RNAs that function to modulate protein expression. This control allows for fine-tuning of the cellular phenotype, including regulation of proliferation, cell signaling, and apoptosis; not surprisingly, microRNAs contribute to liver cancer biology. Recent investigations in human liver cancers and tumor-derived cell lines have demonstrated decreased or increased expression of particular microRNAs in hepatobiliary cancer cells. Based on predicted and validated protein targets as well as functional consequences of altered expression, microRNAs with decreased expression in liver tumor cells may normally aid in limiting neoplastic transformation. Conversely, selected microRNAs that are upregulated in liver tumor cells can promote malignant features, contributing to carcinogenesis. In addition, microRNAs themselves are subject to regulated expression, including regulation by tumor suppressor and oncogene pathways. This review will focus on the expression and function of cancer-related microRNAs, including their intimate involvement in tumor suppressor and oncogene signaling networks relevant to hepatobiliary neoplasia. PMID:19585622

Mott, Justin L.

2009-01-01

198

An update on vulvar intraepithelial neoplasia: terminology and a practical approach to diagnosis.  

PubMed

There are two distinct types of vulvar intraepithelial neoplasia (VIN), which differ in their clinical presentation, aetiology, pathogenesis and histological/immunophenotypical features. One form driven by high-risk human papilloma virus infection usually occurs in young women and has been termed classic or usual VIN (uVIN). The other, not related to viral infection, occurs in postmenopausal women with chronic skin conditions such as lichen sclerosus and lichen simplex chronicus and is termed differentiated or simplex-type VIN. The latter is the precursor lesion of the most common type of squamous cell carcinoma (SCC) in the vulva, namely keratinizing SCC (representing 60% of cases). In contrast, uVIN usually gives rise to basaloid or warty SCC (40% of cases). The histological features of uVIN are similar to those of high grade lesions encountered in other lower anogenital tract sites (hyperchomatic nuclei with high nuclear to cytoplasmic ratios and increased mitotic activity). However, differentiated VIN has very subtle histopathological changes and often escapes diagnosis. Since uVIN is driven by high-risk human papilloma virus infections, p16 immunohistochemistry is diffusely positive in these lesions and is characterized with a high Ki-67 proliferation index. In contrast, differentiated or simplex-type VIN is consistently negative for p16 and the majority of the cases harbour TP53 mutations, correlating with p53 positivity by immunohistochemistry. PMID:24399036

Reyes, M Carolina; Cooper, Kumarasen

2014-04-01

199

Role of human papillomavirus in penile cancer, penile intraepithelial squamous cell neoplasias and in genital warts.  

PubMed

Using PCR, the overall prevalence of human papillomavirus (HPV) DNA in penile carcinoma is about 40-45%, which is similar to the detection rate of HPV-DNA in vulvar carcinoma (50%). In analogy to vulvar cancer two different pathways of penile carcinogenesis seem to exist. In contrast to basaloid and warty penile cancers which are regularly HPV-associated (about 80-100%), only a part of keratinizing and verrucous penile carcinomas appear to be related with HPV (33-35%). Penile intraepithelial neoplasias comprising Bowen's disease, erythroplasia of Queyrat and bowenoid papulosis are precursor lesions of basaloid and warty carcinomas of the penis. Precursors of keratinizing carcinomas and verrucous carcinomas are not established. Whether lichen sclerosus and squamous-cell hyperplasia precede penile keratinizing carcinoma is a matter of discussion. Giant condylomata acuminata may precede the development of verrucous carcinomas in some cases. Since high risk HPVs are more frequently found in verrucous carcinomas than in giant condylomas, HPV typing may be a helpful diagnostic step to differentiate giant condyloma from verrucous carcinoma. PMID:12838415

Gross, G; Pfister, H

2004-02-01

200

Thyroid dysfunction and neoplasia in children receiving neck irradiation for cancer  

SciTech Connect

The reported relationship of radiation exposure and thyroid carcinoma stimulated this retrospective study of 298 patients treated at St. Jude Children's Hospital with radiation therapy to the neck for childhood cancer to identify patients who developed subsequent thyroid abnormalities. This series includes 153 patients with Hodgkin's disease, 95 with acute lymphocytic leukemia, 28 with lymphoepithelioma, and 22 with miscellaneous tumors. Inclusion in the study required 5 years of disease-free survival following therapy for their original tumor, which included thyroid irradiation. Follow-up has been 100%. Most patients also received chemotherapy. Seventeen patients were found to have decreased thyroid reserve with normal levels of free triiodothyroxine (T3) or free thyroxin, (T4) and an elevated level of thyroid-stimulating hormone (TSH). In nine patients hypothyroidism developed, with decreased T3 or T4 levels and an elevated level of TSH. One hyperthyroid patient was identified. Two patients had thyroiditis, and seven had thyroid neoplasms: (carcinoma in two, adenoma in two, colloid nodule in one, and undiagnosed nodules in two). This survey has demonstrated an increased incidence of thyroid dysfunction and thyroid neoplasia when compared to the general population. The importance of long-term follow-up for thyroid disease is emphasized in patients who have received thyroid irradiation. The possible role of subclinical hypothyroidism with TSH elevation coupled with radiation damage to the thyroid gland as a model for the development of neoplastic disease is discussed.

Fleming, I.D.; Black, T.L.; Thompson, E.I.; Pratt, C.; Rao, B.; Hustu, O.

1985-03-15

201

Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion.  

PubMed

Nodular fasciitis (NF) is a relatively common mass-forming and self-limited subcutaneous pseudosarcomatous myofibroblastic proliferation of unknown pathogenesis. Due to its rapid growth and high mitotic activity, NF is often misdiagnosed as a sarcoma. While studying the USP6 biology in aneurysmal bone cyst and other mesenchymal tumors, we identified high expression levels of USP6 mRNA in two examples of NF. This finding led us to further examine the mechanisms underlying USP6 overexpression in these lesions. Upon subsequent investigation, genomic rearrangements of the USP6 locus were found in 92% (44 of 48) of NF. Rapid amplification of 5'-cDNA ends identified MYH9 as the translocation partner. RT-PCR and direct sequencing revealed the fusion of the MYH9 promoter region to the entire coding region of USP6. Control tumors and tissues were negative for this fusion. Xenografts of cells overexpressing USP6 in nude mice exhibited clinical and histological features similar to human NF. The identification of a sensitive and specific abnormality in NF holds the potential to be used diagnostically. Considering the self-limited nature of the lesion, NF may represent a model of 'transient neoplasia', as it is, to our knowledge, the first example of a self-limited human disease characterized by a recurrent somatic gene fusion event. PMID:21826056

Erickson-Johnson, Michele R; Chou, Margaret M; Evers, Barbara R; Roth, Christopher W; Seys, Amber R; Jin, Long; Ye, Ying; Lau, Alan W; Wang, Xiaoke; Oliveira, Andre M

2011-10-01

202

Thymic carcinoid in a patient with multiple endocrine neoplasia type 1: report of a case.  

PubMed

We report herein the rare case of a 33-year-old man found to have a multiple endocrine neoplasia type 1 (MEN1)-associated carcinoid tumor in the thymus. A chest roentgenogram demonstrated an asymptomatic anterior mediastinal mass, 7 cm in diameter, and ultrasound-guided percutaneous Tru-Cut biopsy revealed a carcinoid tumor of the thymus. An extended thymectomy was performed through a median sternotomy and pathological examination confirmed the diagnosis of a thymic carcinoid tumor, which was mainly encapsulated with locally invasive growth into the pleura. Despite the absence of a family history of MEN1, he was treated for two pancreatic islet cell tumors, hyperparathyroidism, an adrenal tumor, and a retroperitoneal lipoma. MEN1 mutations were detected both in blood samples and pancreatic tumor tissues. He is now well without any evidence of tumor recurrence 27 months after the operation for the thymic carcinoid. MEN1 mutations were screened by direct nucleotide sequencing of all protein-coding regions of exons 2-10 of the MEN1 gene. Heterozygous germline mutation was detected in the blood sample analyses. Moreover, fresh-frozen pancreatic tumor tissues showed a loss of heterozygosity in the MEN1 region. PMID:11381507

Sugiura, H; Morikawa, T; Itoh, K; Ono, K; Okushiba, S; Kondo, S; Kato, H

2001-01-01

203

Epidemiology of neoplasia in captive black-footed ferrets (Mustela nigripes), 1986-1996.  

PubMed

The epidemiology of neoplastic disease was studied retrospectively in the captive population of black-footed ferrets (Mustela nigripes). Postmortem reports were reviewed and archived tissues examined from 184 of the 227 adult (>1 yr old) black-footed ferrets that died from the beginning of the current captive propagation program in late 1985 to the end of 1996. A total of 185 neoplasms, of 28 distinct phenotypes, were seen in 102 (55.4%) of these ferrets. There was more than one tumor type present in 51 ferrets. Tumors of the apocrine glands (28.3%), renal tubular neoplasms (20.7%), and biliary cystadenoma or carcinoma (20.1%) were the most common neoplasms. The probability of developing most types of neoplasms increased with age. Neoplasms of the apocrine glands were more common in males and may be hormonally influenced. The unusually high prevalence of biliary cystadenocarcinoma may be secondary to the common occurrence of intrahepatic biliary cysts in this population. Although neoplasia is an important cause of mortality in captive adult black-footed ferrets, its impact on captive propagation of the species, and on the wild population, is probably limited because clinically significant tumors are encountered almost exclusively in postreproductive ferrets (>3 yr old) and because ferrets released into their natural habitat rarely reach susceptible age. PMID:12462486

Lair, Stéphane; Barker, Ian K; Mehren, Kay G; Williams, Elizabeth S

2002-09-01

204

Malignant neoplasia arising from ovarian remnants following bilateral salpingo-oophorectomy (Review)  

PubMed Central

Ovarian remnant syndrome (ORS) is a rare, but well-known gynecological complication, most often induced by difficult bilateral salpingo-oophorectomy (BSO) procedures that leave residual ovarian tissue on the pelvic wall. The most common preexisting conditions for this complication include endometriosis, pelvic inflammatory disease and prior abdominal surgery. The residual ovarian tissue may eventually cause malignant development. A total of 12 cases of malignant and benign tumors (clear cell adenocarcinoma in 1 case, mucinous-type tumors in 2, endometrioid-type tumors in 5, adenocarcinoma in 3 and border serous neoplasia in 1) and 21 benign cysts developing from an ovarian remnant have been described in the literature to date. Endometriosis, known to increase the risk of ovarian cancer, predisposes patients to ORS, with an incidence rate of 30 to 50% in ORS patients with ovarian carcinoma. Although the true incidence of ORS remains unknown, when endometriotic adhesions are diagnosed during BSO, the possibility of ORS and subsequent ovarian malignant transformation may mandate complete surgical resection. PMID:24959210

IMAI, ATSUSHI; MATSUNAMI, KAZUTOSHI; TAKAGI, HIROSHI; ICHIGO, SATOSHI

2014-01-01

205

Malignant neoplasia arising from ovarian remnants following bilateral salpingo-oophorectomy (Review).  

PubMed

Ovarian remnant syndrome (ORS) is a rare, but well-known gynecological complication, most often induced by difficult bilateral salpingo-oophorectomy (BSO) procedures that leave residual ovarian tissue on the pelvic wall. The most common preexisting conditions for this complication include endometriosis, pelvic inflammatory disease and prior abdominal surgery. The residual ovarian tissue may eventually cause malignant development. A total of 12 cases of malignant and benign tumors (clear cell adenocarcinoma in 1 case, mucinous-type tumors in 2, endometrioid-type tumors in 5, adenocarcinoma in 3 and border serous neoplasia in 1) and 21 benign cysts developing from an ovarian remnant have been described in the literature to date. Endometriosis, known to increase the risk of ovarian cancer, predisposes patients to ORS, with an incidence rate of 30 to 50% in ORS patients with ovarian carcinoma. Although the true incidence of ORS remains unknown, when endometriotic adhesions are diagnosed during BSO, the possibility of ORS and subsequent ovarian malignant transformation may mandate complete surgical resection. PMID:24959210

Imai, Atsushi; Matsunami, Kazutoshi; Takagi, Hiroshi; Ichigo, Satoshi

2014-07-01

206

Multiple endocrine neoplasia type 2A in an Iranian family: clinical and genetic studies.  

PubMed

Multiple endocrine neoplasia (MEN) type 2A, a dominant inherited syndrome caused by germline activating mutations in the RET protooncogene, is characterized by association of medullary thyroid carcinoma, pheochromocytoma and primary hyperparathyroidism. There is limited data on this disease in the Middle East region. In this paper, we present clinical and genetic studies of an Iranian patient and her family members. The patient was a 49-year old Iranian woman who presented with hypertension due to bilateral pheochromocytoma. She had history of a medullary carcinoma of thyroid which had been operated 28 years ago. Analysis of the RET gene in the family revealed a C634R mutation in codon 11 and 3 polymorphisms, G691S, S836S and S904S in codons 11, 14 and 15, respectively, that might have been important in modifying the clinical picture. Due to paucity of information on MEN type 2 in the area, this study can be helpful in portraying the clinical and cytogenetic characteristics of the disease in the region. PMID:24784869

Ghazi, Ali Asghar; Bagheri, Mahmoud; Tabibi, Ali; Sarvghadi, Farzaneh; Abdi, Hengameh; Hedayati, Mehdi; Pourafkari, Marina; Tirgari, Farrokh; Yu, Run

2014-05-01

207

Induction of Cervical Neoplasia in the Mouse by Herpes Simplex Virus Type 2 DNA  

NASA Astrophysics Data System (ADS)

Induction of cervical neoplasia in the mouse cervix by herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) has been reported. The present study was done to determine if transfection with DNA of HSV-2 can induce carcinogenesis in this animal model. Genomic HSV-2 DNA was isolated from infected HEp-2 cells and separated from host cell DNA by cesium chloride density gradient centrifugation. The DNA was applied to mouse cervix for periods of 80-100 weeks. Experimental controls were treated with uninfected genomic HEp-2 cell DNA or with calf thymus DNA. Vaginal cytological preparations from all animals were examined monthly to detect epithelial abnormalities. Animals were sacrificed and histopathology studies were done when cellular changes indicative of premalignant or malignant lesions were seen on vaginal smears. Cytologic and histologic materials were coded and evaluated without knowledge of whether they were from animals treated with virus or control DNA. Premalignant and malignant cervical lesions similar to those that occur in women were detected in 61% of the histologic specimens obtained from animals exposed to HSV-2 DNA. The yield of invasive cancers was 21% in animals treated with HSV-2 DNA. No cancers were detected in mice treated with either HEp-2 or calf thymus DNA. Dysplasia was detected in only one of these control animals.

Anthony, Donald D.; Budd Wentz, W.; Reagan, James W.; Heggie, Alfred D.

1989-06-01

208

HIRA orchestrates a dynamic chromatin landscape in senescence and is required for suppression of neoplasia.  

PubMed

Cellular senescence is a stable proliferation arrest that suppresses tumorigenesis. Cellular senescence and associated tumor suppression depend on control of chromatin. Histone chaperone HIRA deposits variant histone H3.3 and histone H4 into chromatin in a DNA replication-independent manner. Appropriately for a DNA replication-independent chaperone, HIRA is involved in control of chromatin in nonproliferating senescent cells, although its role is poorly defined. Here, we show that nonproliferating senescent cells express and incorporate histone H3.3 and other canonical core histones into a dynamic chromatin landscape. Expression of canonical histones is linked to alternative mRNA splicing to eliminate signals that confer mRNA instability in nonproliferating cells. Deposition of newly synthesized histones H3.3 and H4 into chromatin of senescent cells depends on HIRA. HIRA and newly deposited H3.3 colocalize at promoters of expressed genes, partially redistributing between proliferating and senescent cells to parallel changes in expression. In senescent cells, but not proliferating cells, promoters of active genes are exceptionally enriched in H4K16ac, and HIRA is required for retention of H4K16ac. HIRA is also required for retention of H4K16ac in vivo and suppression of oncogene-induced neoplasia. These results show that HIRA controls a specialized, dynamic H4K16ac-decorated chromatin landscape in senescent cells and enforces tumor suppression. PMID:25512559

Rai, Taranjit Singh; Cole, John J; Nelson, David M; Dikovskaya, Dina; Faller, William J; Vizioli, Maria Grazia; Hewitt, Rachael N; Anannya, Orchi; McBryan, Tony; Manoharan, Indrani; van Tuyn, John; Morrice, Nicholas; Pchelintsev, Nikolay A; Ivanov, Andre; Brock, Claire; Drotar, Mark E; Nixon, Colin; Clark, William; Sansom, Owen J; Anderson, Kurt I; King, Ayala; Blyth, Karen; Adams, Peter D

2014-12-15

209

Identification of interstitial deletions in human neoplasia by FISH-technique  

SciTech Connect

Undoubtedly, the discovery of the minute chromosome in chronic myelogenous leukemia (CML), termed the Philadelphia chromosome, has revolutionized cancer cytogenetics. Rowely`s seminal findings of a balanced translocation between chromosomes 9 and 22 opened new avenues where a simple deletion was clearly refuted. Even today, thousands of cases are being identified as simple terminal deletions by routine banding techniques in various human neoplasias. If these deletions are terminal, then how is the instability of the chromosome retained? Apparently, the precise characterization of telomeric ends has gone undetected in the past by conventional methods. It is evident that telomeres of chromosomes consist of short tandemly repeated DNA sequences (TTAGGG){sub n} which are conserved on both ends. The recent availability of chromosome-specific telomeric probes has become a cytogenetic icon for many perplexing questions. For example, we were referred a patient with acute myelogenous leukemia evolving from agnogenic myloid metaplasia. Routine cytogenetic techniques revealed a terminal deletion of one of the chromosomes 7 [del(7)(q21)]. When we hybridized the metaphases with chromosome 7q-specific telomeric probe [Oncor, Gaithersburg, MD], signal was detected at the distal q arms of the deleted chromosomes, apparently suggesting an interstial deletion. The cytogenetic diagnosis was changed to 46,SY,del(7)(q21.lq36.2). All deletions must be identified by FISH.

Gogineni, S.K.; Sanchez, M.A.; Elizalde, S.A. [Long Island College Hospital, Brooklyn, NY (United States)]|[New York Methodist Hospital, Brooklyn, NY (United States)] [and others

1994-09-01

210

Experimental pancreatic hyperplasia and neoplasia: effects of dietary and surgical manipulation.  

PubMed Central

Several studies carried out during the past two decades have investigated the effect of dietary and surgical manipulation on pancreatic growth and carcinogenesis. Diets high in trypsin inhibitor stimulate pancreatic growth and increase the formation of preneoplastic lesions and carcinomas in the rat pancreas. Cholecystokinin (CCK) is the key intermediary in this response, since both natural and synthetic trypsin inhibitors increase circulating levels of the hormone and CCK antagonists largely prevent these changes. Fatty acids enhance pancreatic carcinogenesis in both rats and hamsters, whereas protein appears to have a protective role in the rat, but to increase tumour yields in the hamster. Several surgical operations affect the pancreas. Pancreatobiliary diversion and partial gastrectomy stimulate pancreatic growth and enhance carcinogenesis, probably by means of increased CCK release. Complete duodenogastric reflux has similar effects on the pancreas but the gut peptide involved is gastrin. Although massive small bowel resection increases pancreatic growth, the marked reduction in caloric absorption probably explains its failure to enhance carcinogenesis. CCK and enteroglucagon might work in concert to modulate the tropic response of the pancreas to small bowel resection. In the pancreas, as in the large intestine, hyperplasia appears to precede and predispose to neoplasia. PMID:8494719

Watanapa, P.; Williamson, R. C.

1993-01-01

211

Disseminated neoplasia causes changes in ploidy and apoptosis frequency in cockles Cerastoderma edule.  

PubMed

A proliferative disease, usually referred as disseminated neoplasia (DN), shows high prevalence in some cockle Cerastoderma edule beds of Galicia (NW Spain). Chromosome counts, examination of chromosome morphology, DNA quantification by flow cytometry and estimation of apoptosis frequency by TUNEL assay and flow cytometry were performed in cockles with different DN severity. Metaphases obtained from gills of DN-affected cockles displayed a chromosome number ranging from 41 to 145, while normal number is 38; changes in chromosome morphology were also evident, with numerous microchromosomes occurring. Haemolymph flow cytometry analysis revealed difference in DNA content between healthy and DN-affected cockles. Aneuploid peaks ranged from 1.3n to 8.9n. Apoptosis frequency was determined on histological sections (TUNEL assay) and haemolymph samples (flow cytometry). Both techniques revealed neoplastic cells in apoptosis. The higher DN severity, the lower the percentage of apoptotic cells. According to flow cytometry results, the negative association between DN severity and apoptosis frequency only affected the neoplastic cells, whereas DN did not significantly affect the percentage of apoptotic hyalinocytes or apoptotic granulocytes. PMID:23583807

Díaz, S; Villalba, A; Insua, A; Soudant, P; Fernández-Tajes, J; Méndez, J; Carballal, M J

2013-07-01

212

Cytomorphology and PCNA expression pattern in bivalves Mytilus galloprovincialis and Cerastoderma edule with haemic neoplasia.  

PubMed

Haemic neoplasia (HN) is a pathologic condition reported in several bivalve species in different geographic areas. In this study we describe the cytomorphological features and the proliferative behaviour, assessed by the proliferating cell nuclear antigen (PCNA), of HN in common cockle Cerastoderma edule and Mediterranean mussel Mytilus galloprovicialis. In mussels the presence of at least 5 types of atypical haemocytes was detected, including A- and B-type cells, previously described in M. edulis and Mytilus sp., with predominance of A-type cells in early phases of the disease and B-type cells in more advanced stages. PCNA immunostaining was positive for 97 to 100% of the neoplastic cells, with both cytoplasmic (A cells) and nuclear patterns (B cells). Conversely, in C. edule there was no distinctive morphological cell sub-population, and staining atypical haemocytes with PCNA (range 93 to 100%) showed nuclear expression in early phases of disease and cytoplasmic expression in more advanced stages. The above findings suggest distinct histo-pathogenetic pathways for HN in mussels and common cockles. PMID:23836773

Carella, Francesca; Figueras, Antonio; Novoa, Beatriz; De Vico, Gionata

2013-07-01

213

Disseminated neoplasia in cockles Cerastoderma edule: ultrastructural characterisation and effects on haemolymph cell parameters.  

PubMed

Disseminated neoplasia (DN) has been detected in cockles from various beds in Galicia (NW Spain). A study was performed to characterise cockle neoplastic cell ultrastructure and to evaluate the effect of this disease at different severity stages on various haemolymph cell parameters. Examination of cockle neoplastic cells with transmission electron microscopy (TEM) showed round shapes and a lack of pseudopods, a high nucleus:cytoplasm diameter ratio, Golgi complexes, abundant mitochondria, ribosomes, and numerous endoplasmic reticulum tubes and electron-lucent vesicles. Various haemolymph cell parameters (cell mortality, non-specific esterase and lysosome biovolume, reactive oxygen intermediates [ROI] production, phagocytosis ability, intracellular Ca2+ and actin levels) were compared between DN severity categories by flow cytometry; haemocyte mortality, non-specific esterase activities and lysosome biovolume were found to be higher with increasing DN severity. The phagocytic ability of neoplastic cells was sharply reduced with regard to haemocytes. The cytoplasmic-free Ca2+ level was higher and actin content lower in haemolymph cells of diseased cockles compared to unaffected ones. A significant increase in ROI production was detected in later stages of disease progression. PMID:22013755

Díaz, Seila; Renault, Tristan; Villalba, Antonio; Carballal, María Jesús

2011-09-01

214

Morphological and morphometric measurements in colorectal mucosa of subjects at increased risk for colonic neoplasia.  

PubMed

Measurements of intermediate biomarkers have recently increased, attempting to provide useful information about cancer risk. We report morphological findings in rectal mucosal biopsies from patients at low risk and at high risk for colorectal cancer. Rectal biopsies were analyzed from fourteen Seventh-Day Adventist (SDA) subjects at low risk and from twenty-seven members of families with hereditary nonpolyposis colonic cancer (HNPCC) at higher risk. The following measurements were made on rectal crypts: length of crypts, numbers of cells, diameter of the surface, middle and base of the crypts and infiltration of inflammatory cells into the lamina propria. Findings indicated morphological differences in normal-appearing rectal mucosa of individuals in the HNPCC group compared with SDA subjects (P < 0.05). They included shorter crypts with fewer epithelial cells and increased cellular infiltration in the mucosa of HNPCC subjects compared with SDA subjects, suggesting minimal inflammation, and an early stage of crypt atrophy in the rectal mucosa of subjects at higher risk for colonic neoplasia. PMID:8287373

Richter, A; Yang, K; Richter, F; Lynch, H T; Lipkin, M

1993-10-15

215

An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms.  

PubMed

Invasive pancreatic ductal adenocarcinoma is an almost uniformly fatal disease. Several distinct noninvasive precursor lesions can give rise to invasive adenocarcinoma of the pancreas, and the prevention, detection, and treatment of these noninvasive lesions offers the potential to cure early pancreatic cancers. Noninvasive precursors of invasive ductal adenocarcinoma of the pancreas include pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms. Diagnostic criteria, including a distinct ovarian-type stroma, and a consistent nomenclature are well established for mucinous cystic neoplasms. By contrast, consistent nomenclatures and diagnostic criteria have been more difficult to establish for PanINs and IPMNs. Because both PanINs and IPMNs consist of intraductal neoplastic proliferations of columnar, mucin-containing cells with a variable degree of papilla formation, the distinction between these two classes of precursor lesions remains problematic. Thus, considerable ambiguities still exist in the classification of noninvasive neoplasms in the pancreatic ducts. A meeting of international experts on precursor lesions of pancreatic cancer was held at The Johns Hopkins Hospital from August 18 to 19, 2003. The purpose of this meeting was to define an international acceptable set of diagnostic criteria for PanINs and IPMNs and to address a number of ambiguities that exist in the previously reported classification systems for these neoplasms. We present a consensus classification of the precursor lesions in the pancreatic ducts, PanINs and IPMNs. PMID:15252303

Hruban, Ralph H; Takaori, Kyoichi; Klimstra, David S; Adsay, N Volkan; Albores-Saavedra, Jorge; Biankin, Andrew V; Biankin, Sandra A; Compton, Carolyn; Fukushima, Noriyoshi; Furukawa, Toru; Goggins, Michael; Kato, Yo; Klöppel, Gunter; Longnecker, Daniel S; Lüttges, Jutta; Maitra, Anirban; Offerhaus, G Johan A; Shimizu, Michio; Yonezawa, Suguru

2004-08-01

216

Serrated adenoma: a distinct form of non-polypoid colorectal neoplasia?  

PubMed

Until recently, 2 major forms of colorectal polyp were recognized: the adenoma and the hyperplastic polyp. Adenomas were known to represent a precursor to colorectal cancer, whereas hyperplastic polyps were viewed as nonneoplastic, having no potential for progression to malignancy. We now recognize, however, that the lesions diagnosed as hyperplastic polyps in the past represent a heterogeneous group of polyps, some of which truly are hyperplastic, and others that truly have a significant risk for transformation to colorectal cancer. These polyps have a characteristic serrated architecture, and include not only hyperplastic polyps but also the recently recognized serrated adenomas. Serrated adenomas occur in 2 forms: the traditional serrated adenoma, which is usually a polypoid lesion endoscopically, and the sessile serrated adenoma, a flat or slightly raised, usually right-sided lesion. Serrated adenomas of both types show characteristic molecular alterations not commonly seen in traditional colorectal adenomas, and probably progress to colorectal cancer by means of a different pathway, the so-called serrated neoplasia pathway. The morphologic features of serrated colorectal lesions, the molecular alterations that characterize them, and their role in colorectal cancer development are discussed. PMID:20656251

Noffsinger, Amy E; Hart, John

2010-07-01

217

A panel of regulated proteins in serum from patients with cervical intraepithelial neoplasia and cervical cancer.  

PubMed

We developed a discovery-validation mass-spectrometry-based pipeline to identify a set of proteins that are regulated in serum of patients with cervical intraepithelial neoplasia (CIN) and squamous cell cervical cancer using iTRAQ, label-free shotgun, and targeted mass-spectrometric quantification. In the discovery stage we used a "pooling" strategy for the comparative analysis of immunodepleted serum and revealed 15 up- and 26 down-regulated proteins in patients with early- (CES) and late-stage (CLS) cervical cancer. The analysis of nondepleted serum samples from patients with CIN, CES, an CLS and healthy controls showed significant changes in abundance of alpha-1-acid glycoprotein 1, alpha-1-antitrypsin, serotransferrin, haptoglobin, alpha-2-HS-glycoprotein, and vitamin D-binding protein. We validated our findings using a fast UHPLC/MRM method in an independent set of serum samples from patients with cervical cancer or CIN and healthy controls as well as serum samples from patients with ovarian cancer (more than 400 samples in total). The panel of six proteins showed 67% sensitivity and 88% specificity for discrimination of patients with CIN from healthy controls, a stage of the disease where current protein-based biomarkers, for example, squamous cell carcinoma antigen (SCCA), fail to show any discrimination. Additionally, combining the six-protein panel with SCCA improves the discrimination of patients with CES and CLS from healthy controls. PMID:25232869

Boichenko, Alexander P; Govorukhina, Natalia; Klip, Harry G; van der Zee, A G J; Güzel, Co?kun; Luider, Theo M; Bischoff, Rainer

2014-11-01

218

Radiogenic neoplasia in thyroid and mammary clonogens. Progress report, January 1, 1993--December 31, 1993  

SciTech Connect

The induction of cancer by ionizing radiation is a matter of great practical importance to the nuclear industry, to national defense, to radiological medicine and to the general public. It is increasingly apparent that carcinogenesis is one of the leading dose-limiting effects of radiation exposure (Co90). Quantitative information at the cellular level is essential to an understanding of the mechanisms of radiogenic neoplastic initiation and the stages of promotion and progression to overt neoplasia. We have developed two experimental models, the rat thyroid and rat mammary clonogen transplant systems, for the quantitative study of radiation carcinogenesis at the cellular level in vivo (C185). The most important steps taken or completed during the current grant year include: (a) demonstration of the high age-dependent radiosensitivity of prepubertal rat mammary clonogens to radiogenic damage which may influence their susceptibility to neoplastic initiation, and (b) demonstration of the feasibility of using a molecular test for clonogenicity in which Simple Sequence Repeats in the DNA serve as identifying signals of the genotypic origin of the cells. We have also (c) set up a large carcinogenesis experiment to test the effect of close intercellular contact in thyroid glands in situ on promotion-progression of radiogenically initiated clonogens, (d) achieved considerable further concentration of thyroid clonogens, and (e) begun to explore whether thyroid cells can be induced to give rise to three dimensional multicellular structures in culture in reconstituted basement membrane. These are discussed in this report.

Clifton, K.H.

1993-07-30

219

Grading of cervical intraepithelial neoplasia using spatial frequency for optical histology  

NASA Astrophysics Data System (ADS)

It is important to detect cervical dysplasia, Cervical Intraepithelial Neoplasia (CIN). CIN is the potentially premalignant and abnormal squamous cells on surface of cervix. In this study, the spatial frequency spectra of pre-cancer cervical tissues are used to detect differences among different grades of human cervical tissues. Seven sets of thick tissue sections of human cervix of normal, CIN 1, CIN 2, and CIN 3 tissues are studied. The confocal microscope images of the stromal region of normal and CIN human tissues were analyzed using Fast Fourier Transform (FFT) to generate the spatial spectra. It is observed that higher frequency components exist in CIN tissues than those in normal tissue, as well as those in higher grade CIN tissue than those in lower grade CIN tissue. The width of the spatial frequency of different types of tissues is used to create a criterion for CIN grading by training a support vector machine (SVM) classifier. The results show that the randomness of tissue structures from normal to different stages of precancer in cervical tissue can be recognized by fingerprints of the spatial frequency. The efficacy of spatial frequency analysis for CIN grading is evaluated as excellent since high AUC (area under the ROC curve), sensitivity and specificity are obtained by the statistics study. This works lays the foundation of using spatial frequency spectra for a histology evaluation.

Pu, Yang; Jagtap, Jaidip; Pradhan, Asima; Alfano, Robert R.

2014-03-01

220

PLASMA CELL NEOPLASIA IN A SINGLE HOST: A MOSAIC OF DIFFERENT PROTEIN-PRODUCING CELL TYPES  

PubMed Central

The peritoneal plasma cell neoplasias that develop in strain BALB/c mice after the injection of adjuvant-staphylococcus mixtures or mineral oil alone appear in the form of multiple nodules in the mesentery and on peritoneal surfaces. Experiments were done to determine if these nodules were metastases or multiple primary neoplasms. Nodules or pieces of masses were transplanted subcutaneously by the trochar method or by insertion of tissue under the kidney capsule from 6 primary cases and parallel transplant lines were established. The serum and urinary protein abnormality (a stable heritable characteristic) of each of the various transplant lines was characterized by agar gel electrophoresis and immunoelectrophoresis. Different protein-producing lines were found in 3 cases; in one case 5 different protein-producing lines were isolated. Two different lines were found for each of the other 2 cases. When transplantation studies were begun early, it was demonstrated that the nodules were multiple primary plasma cell neoplasms; when delayed, only one protein-producing plasma cell neoplasm was found. PMID:14488298

Potter, Michael

1962-01-01

221

Neoplasia of captive yellow sea horses (Hippocampus kuda) and weedy sea dragons (Phyllopteryx taeniolatus).  

PubMed

Syngnathidae is the family of fish that includes sea horses, pipefish, and sea dragons. To date, only a single publication has described neoplasia in syngnathids, a fibrosarcoma of the brood pouch in an aquarium-reared lined sea horse (Hippocampus erectus). From 1998 until 2010, the Toronto Zoo submitted 172 syngnathids for postmortem; species included the spotted or yellow sea horse (Hippocampus kuda), the pot-bellied sea horse (Hippocampus abdominalis) and the weedy sea dragon (Phyllopteryx taeniolatus). Seven neoplasms and two neoplastic-like lesions were identified from these cases. Under light microscopy, the neoplasms had morphological characteristics of a cardiac rhabdomyosarcoma, renal adenocarcinoma, renal adenoma, renal round cell tumors, which were likely lymphomas, exocrine pancreatic carcinoma, and intestinal carcinoma. Of these neoplasms, four had clear evidence of metastasis: the pancreatic and intestinal carcinomas and both round cell tumors. As syngnathids are highly fastidious animals, they can be difficult to maintain in captivity. In order to improve their husbandry, preventative and palliative care, as well as treatment, it is important to investigate and document the types of diseases affecting syngnathids. PMID:22448509

LePage, Véronique; Dutton, Christopher J; Kummrow, Maya; McLelland, David J; Young, Karrie; Lumsden, John S

2012-03-01

222

Soft shell clams Mya arenaria with disseminated neoplasia demonstrate reverse transcriptase activity  

USGS Publications Warehouse

Disseminated neoplasia (DN), a proliferative cell disorder of the circulatory system of bivalves, was first reported in oysters in 1969. Since that time, the disease has been determined to be transmissible through water-borne exposure, but the etiological agent has not been unequivocally identified. In order to determine if a viral agent, possibly a retrovirus, could be the causative agent of DN, transmission experiments were performed, using both a cell-free filtrate and a sucrose gradient-purified preparation of a cell-free filtrate of DN positive materials. Additionally, a PCR-enhanced reverse transcriptase assay was used to determine if reverse transcriptase was present in tissues or hemolymph from DN positive soft shell clams Mya arenaria. DN was transmitted to healthy clams by injection with whole DN cells, but not with cell-free flitrates prepared from either tissues from DN positive clams, or DN cells. The cell-free preparations from DN-positive tissues and hemolymph having high levels of DN cells in circulation exhibited positive reactions in the PCR-enhanced reverse transcriptase assay. Cell-free preparations of hemolymph from clams having low levels of DN (<0.1% of cells abnormal), hemocytes from normal soft shell clams, and normal soft shell clam tissues did not produce a positive reaction in the PCR enhanced reverse transcriptase assay.

House, M.L.; Kim, C.H.; Reno, P.W.

1998-01-01

223

Genetic mapping and predictive testing for multiple endocrine neoplasia type 1 (MEN1)  

SciTech Connect

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder with an estimated prevalance of 20-200 per million persons. It is characterized by the combined occurence of tumors involving two or more endocrine glands, namely the parathyroid glands, the endocrine pancreas and the anterior pituitary. This disorder affects virtually all age groups with an average range of 20-60 years. Linkage analysis mapped the MEN1 locus to 11q13 near the human muscle glycogen phosphorylase (PYGM) locus. Additional genetic mapping and deletion analysis studies have refined the region containing the MEN1 locus to a 3 cM interval flanked by markers PYGM and D11S146/D11S97, a physical distance of approximately 1.5 Mb. We have identified 8 large families segregating MEN1 (71 affected from a population of 389 individuals). A high resolution reference map for the 11q13 region has been constructed using four new microsatellite markers, the CEPH reference (40 family) pedigree resource, and the CRI-MAP program package. Subsequent analyses using the LINKAGE program package and 8 MEN 1 families placed the MEN1 locus within the context of the microsatellite map. This map was used to develop a linkage-based predictive test. These markers have also been used to further refine the interval containing the MEN1 locus from the study of chromosome deletions (loss of heterozygosity, LOH studies) in paired sets of tumor and germline DNA from 87 MEN 1 affected individuals.

Pandit, S.D.; Read, C.; Liu, L. [Washington Univ. School of Medicine, St Louis, MO (United States)] [and others

1994-09-01

224

One-year Risk of Advanced Colorectal Neoplasia: United States vs. United Kingdom Risk-stratification Guidelines  

PubMed Central

Background United Kingdom (U.K.) and United States (U.S.) guidelines for risk stratification after polypectomy differ, as do recommended surveillance intervals. Objective To compare risk of advanced colorectal neoplasia at one-year colonoscopy among patients cross-classified by U.S. and U.K. surveillance guidelines. Design Pooled analysis of four prospective studies, 1984-1998. Setting Academic and private clinics in the U.S. Patients 3226 post-polypectomy patients with 6-18 month follow-up colonoscopy. Measurements Rates of advanced neoplasia (adenoma ? 1cm, high-grade dysplasia, >25% villous histology, or invasive cancer) at one year, compared across U.S. and U.K. risk categories. Results Advanced neoplasia (95% CI) was detected one year post-polypectomy in 3.8% (2.7%-4.9%) of lower-risk and 11.2% (9.8%-12.6%) of higher-risk patients, by U.S. criteria. Using U.K. criteria, 4.4% (3.3%-5.4%), 9.9% (8.3%-11.5%), and 18.7% (14.8%-22.5%) of low-, intermediate-, and high-risk patients, respectively, presented with advanced neoplasia; U.K. high-risk patients comprised 12% of all patients. All U.S. lower-risk patients were low-risk by U.K. criteria; however, since the U.K. guidelines do not consider histological features, more patients are classified as low-risk. U.S. higher-risk patients distributed across the three U.K. categories. Considering all patients with advanced neoplasia, 26.3% were reclassified by the U.K criteria to a higher and 7.0% to a lower risk category, with a net 19% benefiting from two-year earlier detection. Overall, substitution of U.K. for U.S. guidelines resulted in an estimated 0.03 additional colonoscopies per five years per patient. Limitations Patients were enrolled 15-20 years ago; colonoscopy quality measures were unavailable. Patients lacking follow-up colonoscopy or with surveillance colonoscopy after 6-18 months, and those with cancer or insufficient baseline adenoma characteristics were excluded (2076/5302). Conclusions Application of the U.K. guidelines in the U.S. could identify a subset of patients whose high risk may warrant a one-year clearing colonoscopy, without substantially increasing colonoscopy rates. PMID:23247939

Martínez, María Elena; Thompson, Patricia; Messer, Karen; Ashbeck, Erin L.; Lieberman, David A.; Baron, John A.; Ahnen, Dennis J.; Robertson, Douglas J.; Jacobs, Elizabeth T.; Greenberg, E. Robert; Cross, Amanda J.; Atkin, Wendy

2013-01-01

225

Entrevista con Enrique Buenaventura  

E-print Network

, era muy terrible ya, realmente muy feroz, esta escalada somocista. En tonces, la respuesta también fue tan firme que empezó a desmoralizar a la Guardia. Te contaré un caso. En Masalla, en el mercado, las vendedoras nos contaron cómo se había... refugiado allí la Guardia, muy bien armada, con mucho parque y resultaba muy difícil sacarla de allí. Entonces las mismas mujeres del mercado, que había sido anteriormente bombardeado, salieron en grupo y fueron a tocar a la puerta donde estaba metida la...

Dí ez, Luys A.

1981-04-01

226

Coexistence of multiple endocrine neoplasia type 1 and type 2 in a large Italian family.  

PubMed

To describe the coexistence of mutations of both the multiple endocrine neoplasia type 1 (MEN1) and type 2 (MEN2) genes in a large Italian family and evaluate if it could be associated with more aggressive clinical manifestations of the two syndromes. Blood samples were obtained for genetic and biochemical analyses. The RET gene exons (8, 10, 11, 13, 14, 15, 16, 18) and the MEN1 coding regions, including the exon-intron boundaries, were amplified by PCR and directly sequenced. We identified two germline mutations in the proband: the first one, K666M, located at the exon 11 of RET proto-oncogene and the second one, IVS4+1G>T, located in the MEN1 gene. The functional characterization of IVS4+1G>T variation, located in the splicing donor site of exon 4 of MEN1 gene, caused the in-frame junction of exon 3 to exon 5, thus obtaining a shorter protein. The same proband's germline mutations were found in 16 relatives out of 21 screened subjects: 8 carried IVS4+1G>T, 4 RET K666M, and 4 both the mutations. This is the second report in literature of coexistence in the same family of germline mutations of both RET proto-oncogene and MEN1 gene. The simultaneous presence of the two mutations was not apparently associated with more aggressive diseases, since at last follow-up all patients appeared to be disease-free or well compensated by medical therapy; finally, no one exhibited metastatic diseases. PMID:21678021

Mastroianno, Sandra; Torlontano, Massimo; Scillitani, Alfredo; D'Aloiso, Leonardo; Verrienti, Antonella; Bonfitto, Nazario; De Bonis, Antonio; D'Agruma, Leonardo; Muscarella, Lucia Anna; Guarnieri, Vito; Dicembrino, Franca; Maranghi, Marianna; Durante, Cosimo; Filetti, Sebastiano

2011-12-01

227

Association of Chlamydia trachomatis infection with human papillomavirus (HPV) & cervical intraepithelial neoplasia - A pilot study  

PubMed Central

Background & objectives: Human papillomavirus (HPV) is the necessary cause of cervical cancer and Chlamydia trachomatis (CT) is considered a potential cofactor in the development of cervical intraepithelial neoplasia (CIN). The objective of this pilot study was to determine the association of CT infection with HPV, other risk factors for cervical cancer, and CIN in symptomatic women. Methods: A total of 600 consecutively selected women aged 30-74 yr with persistent vaginal discharge, intermenstrual/postcoital bleeding or unhealthy cervix underwent conventional Pap smear, Hybrid Capture 2® (HC2) testing for HPV and CT DNA and colposcopy, with directed biopsy of all lesions. Results: HPV DNA was positive in 108 (18.0%) women, CT DNA in 29 (4.8%) women. HPV/CT co-infection was observed in only four (0.7%) women. Of the 127 (21.2%) women with Pap >ASCUS, 60 (47.2%) were HPV positive and four (3.1%) were CT positive. Of the 41 women with CIN1 lesions, 11 (26.8%) were HPV positive, while two were CT positive. Of the 46 women with CIN2+ on histopathology, 41 (89.1%) were HPV positive, two (4.3%) were CT positive and one was positive for both. The risk of CIN2+ disease was significantly increased (P<0.05) by the following factors: age <18 yr at first coitus, HPV infection and a positive Pap smear. Older age (>35 yr), higher parity, use of oral contraceptives or smoking did not show any significant association with HPV or abnormal histopathology. Parity >5 was the only risk factor positivity associated with CT infection (P<0.05). Interpretation & conclusions: Our findings showed that CT infection was not significantly associated with CIN, and most of its risk factors, including HPV infection, in symptomatic women. Longitudinal studies with carefully selected study sample would be able to answer these questions. PMID:23640561

Bhatla, Neerja; Puri, Kriti; Joseph, Elizabeth; Kriplani, Alka; Iyer, Venkateswaran K.; Sreenivas, V.

2013-01-01

228

A comparative evaluation of Raman and fluorescence spectroscopy for optical diagnosis of oral neoplasia  

NASA Astrophysics Data System (ADS)

We report the results of a comparative evaluation of in vivo fluorescence and Raman spectroscopy for diagnosis of oral neoplasia. The study carried out at Tata Memorial Hospital, Mumbai, involved 26 healthy volunteers and 138 patients being screened for neoplasm of oral cavity. Spectral measurements were taken from multiple sites of abnormal as well as apparently uninvolved contra-lateral regions of the oral cavity in each patient. The different tissue sites investigated belonged to one of the four histopathology categories: 1) squamous cell carcinoma (SCC), 2) oral sub-mucous fibrosis (OSMF), 3) leukoplakia (LP) and 4) normal squamous tissue. A probability based multivariate statistical algorithm utilizing nonlinear Maximum Representation and Discrimination Feature for feature extraction and Sparse Multinomial Logistic Regression for classification was developed for direct multi-class classification in a leave-one-patient-out cross validation mode. The results reveal that the performance of Raman spectroscopy is considerably superior to that of fluorescence in stratifying the oral tissues into respective histopathologic categories. The best classification accuracy was observed to be 90%, 93%, 94%, and 89% for SCC, SMF, leukoplakia, and normal oral tissues, respectively, on the basis of leave-one-patient-out cross-validation, with an overall accuracy of 91%. However, when a binary classification was employed to distinguish spectra from all the SCC, SMF and leukoplakik tissue sites together from normal, fluorescence and Raman spectroscopy were seen to have almost comparable performances with Raman yielding marginally better classification accuracy of 98.5% as compared to 94% of fluorescence.

Majumder, S. K.; Krishna, H.; Sidramesh, M.; Chaturvedi, P.; Gupta, P. K.

2010-12-01

229

A comparative evaluation of Raman and fluorescence spectroscopy for optical diagnosis of oral neoplasia  

NASA Astrophysics Data System (ADS)

We report the results of a comparative evaluation of in vivo fluorescence and Raman spectroscopy for diagnosis of oral neoplasia. The study carried out at Tata Memorial Hospital, Mumbai, involved 26 healthy volunteers and 138 patients being screened for neoplasm of oral cavity. Spectral measurements were taken from multiple sites of abnormal as well as apparently uninvolved contra-lateral regions of the oral cavity in each patient. The different tissue sites investigated belonged to one of the four histopathology categories: 1) squamous cell carcinoma (SCC), 2) oral sub-mucous fibrosis (OSMF), 3) leukoplakia (LP) and 4) normal squamous tissue. A probability based multivariate statistical algorithm utilizing nonlinear Maximum Representation and Discrimination Feature for feature extraction and Sparse Multinomial Logistic Regression for classification was developed for direct multi-class classification in a leave-one-patient-out cross validation mode. The results reveal that the performance of Raman spectroscopy is considerably superior to that of fluorescence in stratifying the oral tissues into respective histopathologic categories. The best classification accuracy was observed to be 90%, 93%, 94%, and 89% for SCC, SMF, leukoplakia, and normal oral tissues, respectively, on the basis of leave-one-patient-out cross-validation, with an overall accuracy of 91%. However, when a binary classification was employed to distinguish spectra from all the SCC, SMF and leukoplakik tissue sites together from normal, fluorescence and Raman spectroscopy were seen to have almost comparable performances with Raman yielding marginally better classification accuracy of 98.5% as compared to 94% of fluorescence.

Majumder, S. K.; Krishna, H.; Sidramesh, M.; Chaturvedi, P.; Gupta, P. K.

2011-08-01

230

Pheochromocytoma in rats with multiple endocrine neoplasia (MENX) shares gene expression patterns with human pheochromocytoma.  

PubMed

Pheochromocytomas are rare neoplasias of neural crest origin arising from chromaffin cells of the adrenal medulla and sympathetic ganglia (extra-adrenal pheochromocytoma). Pheochromocytoma that develop in rats homozygous for a loss-of-function mutation in p27Kip1 (MENX syndrome) show a clear progression from hyperplasia to tumor, offering the possibility to gain insight into tumor pathobiology. We compared the gene-expression signatures of both adrenomedullary hyperplasia and pheochromocytoma with normal rat adrenal medulla. Hyperplasia and tumor show very similar transcriptome profiles, indicating early determination of the tumorigenic signature. Overrepresentation of developmentally regulated neural genes was a feature of the rat lesions. Quantitative RT-PCR validated the up-regulation of 11 genes, including some involved in neural development: Cdkn2a, Cdkn2c, Neurod1, Gal, Bmp7, and Phox2a. Overexpression of these genes precedes histological changes in affected adrenal glands. Their presence at early stages of tumorigenesis indicates they are not acquired during progression and may be a result of the lack of functional p27Kip1. Adrenal and extra-adrenal pheochromocytoma development clearly follows diverged molecular pathways in MENX rats. To correlate these findings to human pheochromocytoma, we studied nine genes overexpressed in the rat lesions in 46 sporadic and familial human pheochromocytomas. The expression of GAL, DGKH, BMP7, PHOX2A, L1CAM, TCTE1, EBF3, SOX4, and HASH1 was up-regulated, although with different frequencies. Immunohistochemical staining detected high L1CAM expression selectively in 27 human pheochromocytomas but not in 140 nonchromaffin neuroendocrine tumors. These studies reveal clues to the molecular pathways involved in rat and human pheochromocytoma and identify previously unexplored biomarkers for clinical use. PMID:20937862

Molatore, Sara; Liyanarachchi, Sandya; Irmler, Martin; Perren, Aurel; Mannelli, Massimo; Ercolino, Tonino; Beuschlein, Felix; Jarzab, Barbara; Wloch, Jan; Ziaja, Jacek; Zoubaa, Saida; Neff, Frauke; Beckers, Johannes; Höfler, Heinz; Atkinson, Michael J; Pellegata, Natalia S

2010-10-26

231

Autophagy may occur at an early stage of cholangiocarcinogenesis via biliary intraepithelial neoplasia.  

PubMed

Similar to the pancreatic carcinoma sequence model, cholangiocarcinoma reportedly follows a stepwise carcinogenesis process via the precursor lesion biliary intraepithelial neoplasia (BilIN). Given that autophagy plays an important role in the occurrence and development of carcinomas, we examined the involvement of autophagy in multistep cholangiocarcinogenesis. Thirty-six patients with hepatolithiasis associated with BilIN and/or cholangiocarcinoma, 7 with intrahepatic cholangiocarcinoma, 8 with intraductal papillary neoplasm of the bile duct (IPNB), and 6 with control livers were surveyed. Their lesions were categorized as follows: invasive carcinoma (n = 16), IPNB (n = 8), BIlN-3 (n = 16), BilIN-1/2 (n = 40), nonneoplastic large bile duct (n = 55), and peribiliary gland (n = 55). We examined the immunohistochemical expression of autophagy-related proteins, microtubule-associated proteins light chain 3? (LC3), beclin-1, and p62/sequestosome-1 (p62), as well as tumor suppressor gene product p53. The extent of expression was semiquantitatively assessed. The status of KRAS mutations at codons 12 and 13 was examined in selected cases of BilIN-1/2. The expression of LC3 (cytoplasmic), beclin-1 (cytoplasmic), and p62 (cytoplasmic and nuclear) was significantly higher in BilIN-1/2, BilIN-3, IPNB, and invasive carcinoma than in large bile duct and peribiliary gland (P < .01). KRAS mutation was detected in 6 (40%) of 15 BilIN-1/2 lesions, and there was no correlation between the status of KRAS mutation and the expression of autophagy-related proteins. In conclusion, this study is the first to disclose that the expression of autophagy-related proteins, LC3, beclin-1, and p62, was increased at an early stage of multistep cholangiocarcinogenesis in hepatolithiasis. Autophagy, probably deregulated autophagy, may be related to the occurrence and development of cholangiocarcinoma. PMID:25466963

Sasaki, Motoko; Nitta, Takeo; Sato, Yasunori; Nakanuma, Yasuni

2015-02-01

232

Pregnancy incidence and outcome before and after cervical intraepithelial neoplasia: a retrospective cohort study.  

PubMed

We performed a retrospective cohort study of 3530 women treated for cervical intraepithelial neoplasia (CIN) in Helsinki University Central Hospital, Finland, to investigate whether CIN treatment itself affects pregnancy incidence and outcome. We estimated the incidence of live births, miscarriages, extrauterine pregnancies, molar pregnancies, and termination of pregnancies (TOPs) before and after CIN treatment using nationwide registers. Women were followed up until death, emigration, sterilization, or the end of 2004. The comparison of incidence of pregnancy outcomes before and after the treatment was estimated by calculating hazard ratios (HRs) with conditional Poisson regression. After 76,162 woman-years of follow-up, the incidence of any pregnancy remained constant over CIN-treatment, HR 1.02 and 95% confidence interval (CI) 0.97-1.08, but the incidence of the first pregnancy was significantly elevated after treatment, HR 1.13, and 95% CI 1.03-1.23. The incidence of live births was significantly elevated after treatment, HR 1.08 and 95% CI 1.01-1.15. Incidence of miscarriages, TOPs, extrauterine pregnancies, and molar pregnancies was not elevated. TOPs was significantly increased in the first pregnancy, HR 1.40, 95% CI 1.15-1.72 and after treatment by the loop electrosurgical excision procedure (LEEP), HR 1.36, 95% CI 1.15-1.60. CIN treatment did not reduce pregnancy incidence and women had more live births after than before CIN treatment. TOPs was more common in the first pregnancy or after treatment by LEEP. We encourage research on the psychosocial consequences of CIN treatment also in other countries and settings. PMID:25146172

Kalliala, Ilkka; Anttila, Ahti; Nieminen, Pekka; Halttunen, Mervi; Dyba, Tadeusz

2014-12-01

233

Efficacy of 5% Imiquimod Cream on Vulvar Intraepithelial Neoplasia in Korea: Pilot Study  

PubMed Central

Background Various therapeutic options, including surgery, electrocautery, cryotherapy, 5-fluorouracil treatment, laser therapy, radiotherapy, photodynamic therapy, and interferon-?/? injection, have been employed to treat vulvar intraepithelial neoplasia (VIN) with varying degrees of success. To truly cure VIN, human papillomavirus elimination is considered important. Objective To investigate the efficacy of 5% imiquimod cream used to treat VIN in Korean patients Methods We performed a prospective, uncontrolled, observational study. Nine patients with histologically confirmed VIN applied 5% imiquimod cream to their vulvar lesions three to five times a week until a clinical response was apparent. All lesions were photo-documented, and therapeutic efficacy was assessed in terms of local adverse effects lesion number, size, and hyperpigmentation. Results The mean treatment duration was 30.2 months, and the median follow-up period after therapy completion was 30 months. Of the nine patients recruited, six (66.6%) experienced complete responses (CR) or partial responses (PR). Hyperpigmented patches in the VIN lesions were evident in five subjects (55.6%), and all experienced either CR or PR. Only three patients (33.3%) suffered from local adverse effects, which were relieved after temporary suspension of therapy, and better outcomes were attained ultimately. Conclusion The imiquimod cream was more efficacious when used to treat VIN of the hyperpigmented type compared with lesions lacking pigmentation. The unifocal nature of a lesion and the development of local adverse effects are useful factors when imiquimod cream is prescribed. However, although the cream is convenient and effective, regional resistance may develop, and close follow-up is essential because VIN may become malignant.

Kim, Jeong-Min; Lee, Hyun-Joo; Kim, Su-Han; Kim, Hoon-Soo; Ko, Hyun-Chang; Kim, Byung-Soo; Kim, Moon-Bum

2015-01-01

234

Prediction of high-grade cervical intraepithelial neoplasia in cytologically normal women by human papillomavirusesting  

PubMed Central

Human papillomavirus (HPV) testing has been suggested for primary screening of cervical cancer. Prediction of future high-grade cervical lesions is crucial for effectiveness and cost. We performed a case control study in a retrospective cohort of women with at least two cervical smears, all but the last one being negative, from the organized cervical screening programme in Florence, Italy. We searched for high-risk HPV in all previous, archival, smears from cases (new histologically confirmed cervical intraepithelial neoplasia (CIN) grade II or worse) and in one previous smear from each control (last smear cytologically normal, matched by age and interval (latency) from last smear). We applied polymerase chain reaction (PCR), and the b-globin gene was used as a DNA preservation marker. High-risk HPV was identified in 71/92 (77.17%) previous smears from 79 cases and 17/332 controls (5.12%). The odds ratio (OR) was 63.76 (95% CI 30.57–132.96). Among cases the proportion of HPV-positive smears declined slightly with increasing latency. Among cases, HPV was found in 81.24% (95% CI 69.93–88.96%) of smears with latency < 4 years and in 67.80% (95% CI 47.72–82.93%) of those taken at longer intervals, up to 6 years. These findings suggest that testing for high-risk HPV allows predicting 80% of CINII/III 3 years before the cytological diagnosis and two thirds 6 years before. They also suggest that testing women negative for high-risk HPV at longer interval and strictly following-up women who are HPV positive could be an effective strategy for cervical cancer screening. © 2000 Cancer Research Campaign http://www.bjcancer.com PMID:11076654

Carozzi, F; Ronco, G; Confortini, M; Noferini, D; Maddau, C; Ciatto, S; Segnan, N

2000-01-01

235

Germ-line mutation analysis in patients with multiple endocrine neoplasia type 1 and related disorders.  

PubMed Central

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome predisposing to tumors of the parathyroid, endocrine pancreas, anterior pituitary, adrenal glands, and diffuse neuroendocrine tissues. The MEN1 gene has been assigned, by linkage analysis and loss of heterozygosity, to chromosome 11q13 and recently has been identified by positional cloning. In this study, a total of 84 families and/or isolated patients with either MEN1 or MEN1-related inherited endocrine tumors were screened for MEN1 germ-line mutations, by heteroduplex and sequence analysis of the MEN1 gene-coding region and untranslated exon 1. Germ-line MEN1 alterations were identified in 47/54 (87%) MEN1 families, in 9/11 (82%) isolated MEN1 patients, and in only 6/19 (31.5%) atypical MEN1-related inherited cases. We characterized 52 distinct mutations in a total of 62 MEN1 germ-line alterations. Thirty-five of the 52 mutations were frameshifts and nonsense mutations predicted to encode for a truncated MEN1 protein. We identified eight missense mutations and five in-frame deletions over the entire coding sequence. Six mutations were observed more than once in familial MEN1. Haplotype analysis in families with identical mutations indicate that these occurrences reflected mainly independent mutational events. No MEN1 germ-line mutations were found in 7/54 (13%) MEN1 families, in 2/11 (18%) isolated MEN1 cases, in 13/19 (68. 5%) MEN1-related cases, and in a kindred with familial isolated hyperparathyroidism. Two hundred twenty gene carriers (167 affected and 53 unaffected) were identified. No evidence of genotype-phenotype correlation was found. Age-related penetrance was estimated to be >95% at age >30 years. Our results add to the diversity of MEN1 germ-line mutations and provide new tools in genetic screening of MEN1 and clinically related cases. PMID:9683585

Giraud, S; Zhang, C X; Serova-Sinilnikova, O; Wautot, V; Salandre, J; Buisson, N; Waterlot, C; Bauters, C; Porchet, N; Aubert, J P; Emy, P; Cadiot, G; Delemer, B; Chabre, O; Niccoli, P; Leprat, F; Duron, F; Emperauger, B; Cougard, P; Goudet, P; Sarfati, E; Riou, J P; Guichard, S; Rodier, M; Meyrier, A; Caron, P; Vantyghem, M C; Assayag, M; Peix, J L; Pugeat, M; Rohmer, V; Vallotton, M; Lenoir, G; Gaudray, P; Proye, C; Conte-Devolx, B; Chanson, P; Shugart, Y Y; Goldgar, D; Murat, A; Calender, A

1998-01-01

236

Parenchymal Signal Intensity in 3-T Body MRI of Dogs with Hematopoietic Neoplasia  

PubMed Central

We performed a preliminary study involving 10 dogs to assess the applicability of body MRI for staging of canine diffuse hematopoietic neoplasia. T1-weighted (before and after intravenous gadolinium), T2-weighted, in-phase, out-of-phase, and short tau inversion recovery pulse sequences were used. By using digital region of interest (ROI) and visual comparison techniques, relative parenchymal organ (medial iliac lymph nodes, liver, spleen, kidney cortex, and kidney medulla) signal intensity was quantified as less than, equal to, or greater than that of skeletal muscle in 2 clinically normal young adult dogs and 10 dogs affected with either B-cell lymphoma (n = 7) or myelodysplastic syndrome (n = 3). Falciform fat and urinary bladder were evaluated to provide additional perspective regarding signal intensity from the pulse sequences. Dogs with nonfocal disease could be distinguished from normal dogs according to both the visual and ROI signal-intensity relationships. In normal dogs, liver signal intensity on the T2-weighted sequence was greater than that of skeletal muscle by using either the visual or ROI approach. However in affected dogs, T2-weighted liver signal intensity was less than that of skeletal muscle by using either the ROI approach (10 of 10 dogs) or the visual approach (9 of 10 dogs). These findings suggest that the comparison of relative signal intensity among organs may have merit as a research model for infiltrative parenchymal disease (ROI approach) or metabolic effects of disease; this comparison may have practical clinical applicability (visual comparison approach) as well. PMID:23582424

Feeney, Daniel A; Sharkey, Leslie C; Steward, Susan M; Bahr, Katherine L; Henson, Michael S; Ito, Daisuke; O'Brien, Timothy D; Jessen, Carl R; Husbands, Brian D; Borgatti, Antonella; Modiano, Jaime F

2013-01-01

237

Whole Genome Expression Profiling of Gastric High-grade Intraepithelial Neoplasia with or without Cancer.  

PubMed

Objective To investigate the whole genome expression profiles between gastric high-grade intraepithelial neoplasia(HGIN)tissues with cancer and HGIN tissues without cancer. Methods Gastric specimens from an upper magnifying chromoendoscopic targeted biopsy were collected at Peking Union Medical College Hospital from March 2010 to May 2013. Each of the forceps biopsies from the 21 patients was HGIN,but there were 10 HGIN and 11 HGIN with cancer after the endoscopic submucosal dissection. The whole genome expression profiling was performed on 10 HGIN samples and 11 HGIN with cancer samples using Agilent 4 × 44K Whole Human Genome microarrays. Differentially expressed genes between different types of lesions were identified using an unpaired t-test and corrected with the Benjamini and Hochberg false discovery rate algorithm. A gene ontology(GO)enrichment analysis was performed using the GeneSpring software GX 12.6. Results The gene expression patterns were different between HGIN tissues with cancer and HGIN tissues without cancer. There were 470 significantly differentially expressed transcripts between them(P<0.05,Fold Change>2),with 180 up-regulated genes and 290 down-regulated genes in HGIN tissues with cancer. A GO enrichment analysis demonstrated that the most striking over-expressed transcripts in HGIN with cancer were in the category of triglyceride biosynthetic process,acylglycerol biosynthetic process,neutral lipid biosynthetic process,glycerol ether metabolic process,organic ether metabolic process,and glycerolipid metabolic process. Conclusion The change of lipid metabolism may contribute to the pathogenesis of gastric cancer at an early stage. PMID:25676266

Zu, Ming; Xu, Xue; Zhou, Wei-Xun; Fei, Gui-Jun; Wu, Xi; Yao, Fang; Li, Yuan; Cheng, Shu-Jun; Lu, Xing-Hua

2015-02-12

238

High-Dose-Rate Brachytherapy for the Treatment of Vaginal Intraepithelial Neoplasia  

PubMed Central

Purpose Vaginal intraepithelial neoplasia (VAIN), a rare premalignant condition, is difficult to eradicate. We assess the effectiveness of high-dose rate intracavitary brachytherapy (HDR-ICR) in patients with VAIN or carcinoma in situ (CIS) of the vagina after hysterectomy. Materials and Methods We reviewed 34 patients treated for posthysterectomy VAIN or CIS of the vagina by brachytherapy as the sole treatment. All patients underwent a coloposcopic-directed punch biopsy or had abnormal cytology, at least 3 consecutive times. All patients were treated with a vaginal cylinder applicator. The total radiation dose was mainly 40 Gy in 8 fractions during the periods of 4 weeks at a prescription point of the median 0.2 cm (range, 0 to 0.5 cm) depth from the surface of the vaginal mucosa. Results Acute toxicity was minimal. Seven patients had grade 1/2 acute urinary and rectal complications. There were 15 cases of late toxicity, predominantly vaginal mucosal reaction in 12 patients. Of these patients, two patients suffered from grade 3 vaginal stricture and dyspareunia continuously. After a median follow-up time of 48 months (range, 4 to 122 months), there were 2 recurrences and 2 persistent diseases, in which a second-line therapy was needed. The success rate was 88.2%. The average prescription point in failure patients was 1.1 mm from the surface of the vagina compared to an average of 2.6 mm in non-recurrent patients (p=0.097). Conclusion HDR-ICR is an effective treatment method in VAIN patients. In spite of high cure rates, we should consider issues regarding vaginal toxicity and radiation techniques to reduce the occurrence of failure and toxicity. PMID:24520226

Song, Jin Ho; Lee, Joo Hwan; Lee, Jong Hoon; Park, Jong Sup; Hong, Sook Hee; Jang, Hong Seok; Kim, Yeon Sil; Choi, Byung Ock

2014-01-01

239

Pregnancy incidence and outcome before and after cervical intraepithelial neoplasia: a retrospective cohort study  

PubMed Central

We performed a retrospective cohort study of 3530 women treated for cervical intraepithelial neoplasia (CIN) in Helsinki University Central Hospital, Finland, to investigate whether CIN treatment itself affects pregnancy incidence and outcome. We estimated the incidence of live births, miscarriages, extrauterine pregnancies, molar pregnancies, and termination of pregnancies (TOPs) before and after CIN treatment using nationwide registers. Women were followed up until death, emigration, sterilization, or the end of 2004. The comparison of incidence of pregnancy outcomes before and after the treatment was estimated by calculating hazard ratios (HRs) with conditional Poisson regression. After 76,162 woman-years of follow-up, the incidence of any pregnancy remained constant over CIN-treatment, HR 1.02 and 95% confidence interval (CI) 0.97–1.08, but the incidence of the first pregnancy was significantly elevated after treatment, HR 1.13, and 95% CI 1.03–1.23. The incidence of live births was significantly elevated after treatment, HR 1.08 and 95% CI 1.01–1.15. Incidence of miscarriages, TOPs, extrauterine pregnancies, and molar pregnancies was not elevated. TOPs was significantly increased in the first pregnancy, HR 1.40, 95% CI 1.15–1.72 and after treatment by the loop electrosurgical excision procedure (LEEP), HR 1.36, 95% CI 1.15–1.60. CIN treatment did not reduce pregnancy incidence and women had more live births after than before CIN treatment. TOPs was more common in the first pregnancy or after treatment by LEEP. We encourage research on the psychosocial consequences of CIN treatment also in other countries and settings. PMID:25146172

Kalliala, Ilkka; Anttila, Ahti; Nieminen, Pekka; Halttunen, Mervi; Dyba, Tadeusz

2014-01-01

240

Significance of Atypical Small Acinar Proliferation and High-Grade Prostatic Intraepithelial Neoplasia in Prostate Biopsy  

PubMed Central

Purpose In clinical practice, atypical small acinar proliferation (ASAP) and high-grade prostatic intraepithelial neoplasia (HGPIN) are two common findings on prostate biopsies. Knowing the frequency of a prostate cancer diagnosis on repeat biopsies would aid primary treating physicians regarding their decisions in suspicious cases. Materials and Methods One hundred forty-three patients in whom biopsies revealed ASAP or HGPIN or both were enrolled in the present study; prostate cancer was not reported in the biopsy specimens and at least one repeat biopsy was performed. Age, digital rectal examination findings, prostate volumes, and free and total prostate-specific antigen (PSA) levels and the biopsy results of the patients were recorded. Results Of the 97 patients with ASAP on the first set of biopsies, prostate cancer was diagnosed in the second and third biopsies of 32 and 6 patients, respectively. Prostate cancer was not detected in the second or third biopsies of the 40 patients with HGPIN in the first biopsy. Of the 6 patients with ASAP+HGPIN in the first biopsy, prostate cancer was detected in 3 patients in the second biopsy and in 1 patient in the third biopsy. Conclusions The diagnosis of ASAP is a strong risk factor for prostate cancer. A repeat biopsy should be performed for the entire prostate subsequent to the diagnosis of ASAP. In patients with HGPIN according to the biopsy result, the clinical decision should be based on other parameters, such as PSA values and rectal examination, and a repeat biopsy should be avoided if the initial biopsy was performed with multiple sampling. PMID:22195261

Çal??kan, Selahattin; Öztürk, Metin ?shak; Güne?, Mustafa; Karaman, M. Ihsan

2011-01-01

241

Phase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia  

PubMed Central

Background: Vulval intraepithelial neoplasia (VIN) is a premalignant condition, which is frequently associated with type HPV16 infection, and multifocal disease has high rates of surgical treatment failure. Methods: We report a phase II clinical trial of the topical immunomodulator, imiquimod, for 8 weeks, followed by 3 doses (weeks 10, 14 and 18) of therapeutic human papillomavirus (HPV) vaccination (TA-CIN, fusion protein HPV16 E6E7L2) in 19 women with VIN grades 2 and 3. Histology and HPV testing of biopsies were performed at weeks 0, 10, 20 and 52. Intralesional infiltration of T-cell subsets and lymphocyte proliferation for HPV systemic immune responses were also assessed. Results: Lesion response (complete regression of VIN on histology) was observed in 32% (6 out of 19) of women at week 10, increasing to 58% (11 out of 19) at week 20 and 63% (12 out of 19) at week 52. At this time, 36% (5 out of 14) of lesions showed HPV16 clearance and 79% (15 out of 19) of women were symptom free. At week 20, after treatment with imiquimod and vaccination, there was significantly increased local infiltration of CD8 and CD4 T cells in lesion responders; in contrast, non-responders (persistent VIN by histology) showed an increased density of T regulatory cells. After vaccination, only lesion responders had significantly increased lympho-proliferation to the HPV vaccine antigens. Conclusion: The therapeutic effect of treatment depends on the differential immune response of responders and non-responders with affect locally and systemically. PMID:20234368

Daayana, S; Elkord, E; Winters, U; Pawlita, M; Roden, R; Stern, P L; Kitchener, H C

2010-01-01

242

Mortality in beagles irradiated during prenatal and postnatal development. II. Contribution of benign and malignant neoplasia.  

PubMed

To evaluate the lifetime carcinogenic hazards of exposure to ionizing radiation during development, 1,680 beagles received whole-body exposures to 60Co gamma rays or sham exposures. Eight groups of 120 dogs each received mean doses of 15.6-17.5 or 80.8-88.3 cGy in early, mid- or late gestation, at 8, 28 or 55 days postcoitus or at 2 days after birth. Another group of 120 dogs received a mean dose of 82.6 cGy as 70-day-old juveniles and one group of 240 dogs received a mean dose of 81.2 cGy as 365-day-old young adults. Sham irradiations were given to 360 controls. Sexes were equally represented. In 1,343 dogs allowed to live out their life span, neoplasia was a major disease, contributing to mortality in 40% of the dogs. There was a significant increase in benign and malignant neoplasms occurring in young dogs (<4 years old), including fatal malignancies, after irradiation in the perinatal (late fetal and neonatal) periods. The lifetime incidence of fatal neoplasms was also increased in dogs irradiated perinatally. Three malignancies-lymphomas, hemangiosarcomas and mammary carcinomas-accounted for 51% of all fatal tumors. There was an apparent lifetime increase and earlier onset of lymphomas in dogs exposed as fetuses. Fatal hemangiosarcomas were increased in dogs irradiated early and late in gestation. Fatal mammary carcinomas were not increased by irradiation, although non-fatal carcinomas were increased after perinatal exposure. Myeloproliferative disorders and central nervous system astrocytomas appeared to be increased in perinatally irradiated dogs. These data suggest that irradiation in both the fetal and neonatal periods is associated with increased early onset and lifetime cancer risk. PMID:9728662

Benjamin, S A; Lee, A C; Angleton, G M; Saunders, W J; Keefe, T J; Mallinckrodt, C H

1998-09-01

243

Functional attributes of mucosal immunity in cervical intraepithelial neoplasia and effects of HIV infection.  

PubMed

The role of mucosal immunity in human papillomavirus (HPV)-related cervical diseases is poorly understood. To characterize the local immune microenvironment in cervical intraepithelial neoplasia (CIN) 2/3 and determine the effects of HIV infection, we compared samples from three groups: normal cervix, CIN 2/3 from immunocompetent women (HIV- CIN 2/3), and CIN 2/3 from HIV seropositive women (HIV+ CIN 2/3). CIN 2/3 lesions contained increased numbers of immune cells from both the acquired and innate arms of the immune response in stroma [CD4+ and CD8+ T cells, macrophages, mast cells, B cells, neutrophils, and natural killer (NK) cells] and dysplastic epithelium (CD4+ T cells, macrophages, and NK cells). Immune cells in CIN 2/3 expressed activation markers, as measured by interleukin-2 receptor (IL-2R) and transcription factor T bet. Interferon-gamma production was significantly up-regulated in CIN lesions and was expressed by CD4+ and CD8+ T cells and NK cells, indicating the activation of immune cells. Abundant presence of transforming growth factor-beta+ CD25+ cells in the infiltrates associated with CIN lesions, and of immature CD1a+ dendritic cells expressing IL-10 and transforming growth factor-beta, indicate that CIN is associated with an influx of immune cells that produce a mixture of proinflammatory and regulatory cytokines. In HIV+ CIN, immune cell densities (CD4+ T cells, macrophages, neutrophils, and NK cells) and expression of interferon-gamma were significantly decreased compared with HIV- CIN. Regulatory cytokines were also down-regulated in this group. Therefore, both pro- and anti-inflammatory responses present in CIN 2/3 lesions are suppressed in HIV-seropositive women. PMID:15374995

Kobayashi, Akiko; Greenblatt, Ruth M; Anastos, Kathryn; Minkoff, Howard; Massad, Leslie S; Young, Mary; Levine, Alexandra M; Darragh, Teresa M; Weinberg, Vivian; Smith-McCune, Karen K

2004-09-15

244

AKT1 Loss Correlates with Episomal HPV16 in Vulval Intraepithelial Neoplasia  

PubMed Central

Anogenital malignancy has a significant association with high-risk mucosal alpha-human papillomaviruses (alpha-PV), particularly HPV 16 and 18 whereas extragenital SCC has been linked to the presence of cutaneous beta and gamma–HPV types. Vulval skin may be colonised by both mucosal and cutaneous (beta-, mu-, nu- and gamma-) PV types, but there are few systematic studies investigating their presence and their relative contributions to vulval malignancy. Dysregulation of AKT, a serine/threonine kinase, plays a significant role in several cancers. Mucosal HPV types can increase AKT phosphorylation and activity whereas cutaneous HPV types down-regulate AKT1 expression, probably to weaken the cornified envelope to promote viral release. We assessed the presence of mucosal and cutaneous HPV in vulval malignancy and its relationship to AKT1 expression in order to establish the corresponding HPV and AKT1 profile of normal vulval skin, vulval intraepithelial neoplasia (VIN) and vulval squamous cell carcinoma (vSCC). We show that HPV16 is the principle HPV type present in VIN, there were few detectable beta types present and AKT1 loss was not associated with the presence of these cutaneous HPV. We show that HPV16 early gene expression reduced AKT1 expression in transgenic mouse epidermis. AKT1 loss in our VIN cohort correlated with presence of high copy number, episomal HPV16. Maintained AKT1 expression correlated with low copy number, an increased frequency of integration and increased HPV16E7 expression, a finding we replicated in another untyped cohort of vSCC. Since expression of E7 reflects tumour progression, these findings suggest that AKT1 loss associated with episomal HPV16 may have positive prognostic implications in vulval malignancy. PMID:22685591

Gibbon, Karen; Byrne, Carolyn R.; Arbeit, Jeffrey M.; Harwood, Catherine A.; O'Shaughnessy, Ryan F. L.

2012-01-01

245

Phosphorylated S6 as an immunohistochemical biomarker of vulvar intraepithelial neoplasia.  

PubMed

As life expectancy lengthens, cases of non-viral-associated vulvar squamous cell carcinoma and its precursor lesion, so-called differentiated vulvar intraepithelial neoplasia (VIN), continue to increase in frequency. Differentiated VIN often is difficult to recognize and failure to detect it before invasion results in morbidity and mortality. Thus, identification of a reliable biomarker for this type of lesion would be of great clinical benefit. Our recent studies have identified activation (ser235/236 phosphorylation) of ribosomal protein S6 (p-S6) in basal epithelial cells as an event that precedes and accompanies laminin ?(2) overexpression in most preinvasive oral dysplasias. To test this as a potential biomarker of vulvar dysplasia, we immunostained seven differentiated VINs and nine papillomavirus-related 'classic' VINs, most of which were associated with carcinoma, for p-S6. All carcinomas, all differentiated VINs, and most classic VINs contained regions of p-S6 staining in the basal layer, whereas basal and parabasal cells of normal vulvar epithelium and hyperplastic and inflamed lesions lacking cellular atypia were p-S6 negative. Laminin ?(2) was expressed in a subset of VINs, always occurring within basal p-S6 positive regions, as we had found previously for oral dysplasias. Lichen sclerosus is considered a potential precursor of vulvar carcinoma. Two lichen sclerosus lesions of patients with a concurrent carcinoma and one of six lichen sclerosus lesions without atypia or known concurrent carcinoma were basal p-S6 positive. In summary, there is a distinct difference in p-S6 basal cell layer staining between benign and neoplastic vulvar squamous epithelium, with consistent staining of differentiated VIN and of some lichen sclerosus lesions. These results support further studies to assess the potential of p-S6 as a biomarker to identify vulvar lesions at risk of progressing to invasive cancer. PMID:23765247

Pinto, Alvaro P; Degen, Martin; Barron, Patricia; Crum, Christopher P; Rheinwald, James G

2013-11-01

246

Unique recurrence patterns of cervical intraepithelial neoplasia after excision of the squamocolumnar junction.  

PubMed

Recent studies have identified a putative cell of origin for cervical intraepithelial neoplasia (CIN) and cervical cancer at the squamocolumnar junction (SCJ) and suggest that these cells may not regenerate after excision (loop electrosurgical excision procedure). Our study addressed the impact of SCJ excision on the temporal dynamics, histologic and viral (human papillomavirus, HPV) characteristics of recurrent CIN. One hundred and thirty-one consecutive patients treated by excision and attending follow-up visits were enrolled. We compared recurrent and initial CIN with attention to excision margins, timing of recurrence, CIN grade, HPV types, p16 immunophenotype and SCJ immunophenotype. During the follow-up period (up to 4 years), 16 (12.2%) recurrences were identified. Four (25%) were identified at the first follow-up visit, closely resembled the initial CIN 2/3 in grade and HPV type and were typically SCJ marker positive [SCJ(+)], suggesting nonexcised (residual) disease. Twelve (75%) manifested after the first postoperative visit and all were in the ectocervix or in mature metaplastic epithelium. All of the 12 delayed recurrences were classified as CIN 1 and were SCJ (-). In total, 9 out of 11 SCJ (-) recurrences (82%) followed regressed spontaneously. Taken together, these results show that new lesions developing from any HPV infection are delayed and occur within the ectocervix or metaplastic epithelium. This markedly lower risk of CIN 2/3 after successful SCJ excision suggests that the removal of the SCJ could be a critical variable in reducing the risk of subsequent CIN 2/3 and cervical cancer. PMID:24839092

Herfs, Michael; Somja, Joan; Howitt, Brooke E; Suarez-Carmona, Meggy; Kustermans, Gaelle; Hubert, Pascale; Doyen, Jean; Goffin, Frederic; Kridelka, Frederic; Crum, Christopher P; Delvenne, Philippe

2015-03-01

247

Immune response to JC virus T antigen in patients with and without colorectal neoplasia.  

PubMed

JC virus (JCV) is a polyomavirus that infects approximately 75% of the population and encodes a T antigen (T-Ag) gene, which is oncogenic and inactivates the p53 and pRb/p107/p130 protein families. Previous work in our lab has identified the presence of T-Ag in colorectal neoplasms. While JCV remains in a latent state for the majority of those infected, we hypothesized that a disturbance in immunological control may permit JCV to reactivate, which may be involved in the development of colorectal neoplasia. Our aim was to determine the cell mediated immune response to JCV T-Ag, and determine if it is altered in patients with colorectal adenomatous polyps (AP) or cancers (CRC). Peripheral blood mononuclear cells (PBMCs) isolated from the blood of patients undergoing colonoscopy or colorectal surgery were stimulated by a peptide library covering the entire T-Ag protein of JCV. Cytokine production and T cell proliferation were evaluated following T-Ag stimulation using Luminex and flow cytometry assays. JCV T-Ag peptides stimulated secretion of IL-2, which induced T cell expansion in all three groups. However, stronger IL-10 and IL-13 production was seen in patients without colorectal neoplasms. IP-10 was produced at very high levels in all groups, but not significantly differently between groups. Most patients exhibited CD4(+) and CD8(+) T cells in response to stimulation by the T-Ag clusters. The combination of IL-2 and IP-10 secretion indicates the presence of T-Ag-specific Th1 cells in all patients, which is higher in patients without carcinoma. PMID:25007286

Butcher, Lindsay D; Garcia, Melissa; Arnold, Mildred; Ueno, Hideki; Goel, Ajay; Boland, C Richard

2014-07-01

248

Prediction of Spontaneous Regression of Cervical Intraepithelial Neoplasia Lesions Grades 2 and 3 by Proteomic Analysis  

PubMed Central

Regression of cervical intraepithelial neoplasia (CIN) 2-3 to CIN 1 or less is associated with immune response as demonstrated by immunohistochemistry in formaldehyde-fixed paraffin-embedded (FFPE) biopsies. Proteomic analysis of water-soluble proteins in supernatants of biopsy samples with LC-MS (LTQ-Orbitrap) was used to identify proteins predictive of CIN2-3 lesions regression. CIN2-3 in the biopsies and persistence (CIN2-3) or regression (?CIN1) in follow-up cone biopsies was validated histologically by two experienced pathologists. In a learning set of 20 CIN2-3 (10 regressions and 10 persistence cases), supernatants were depleted of seven high abundance proteins prior to unidimensional LC-MS/MS protein analysis. Mean protein concentration was 0.81?mg/mL (range: 0.55–1.14). Multivariate statistical methods were used to identify proteins that were able to discriminate between regressive and persistent CIN2-3. The findings were validated in an independent test set of 20 CIN2-3 (10 regressions and 10 persistence cases). Multistep identification criteria identified 165 proteins. In the learning set, zinc finger protein 441 and phospholipase D6 independently discriminated between regressive and persistent CIN2-3 lesions and correctly classified all 20 patients. Nine regression and all persistence cases were correctly classified in the validation set. Zinc finger protein 441 and phospholipase D6 in supernatant samples detected by LTQ-Orbitrap can predict regression of CIN2-3. PMID:25018881

Uleberg, Kai-Erik; Øvestad, Irene Tveiterås; Munk, Ane Cecilie; van Diermen, Bianca; Gudlaugsson, Einar; Janssen, Emiel A. M.; Hjelle, Anne; Baak, Jan P. A.

2014-01-01

249

Radiogenic neoplasia in thyroid and mammary clonogens. Progress report, January 1, 1990--December 31, 1992  

SciTech Connect

We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. Previous results indicated that these clonogens are the precursor cells of radiogenic cancer, and that initiation, is common event at the clonegenic cell level. Detailed information on the physiologic control of clonogen proliferation, differentiation, and total numbers is thus essential to an understanding of the carcinogenic process. We report here studies on investigations on the relationships between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamus-pituitary feedback axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH-(thyrotropin-) responsive sub- population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and a large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cell interactions during the neoplastic process.

Clifton, K.H.

1992-05-20

250

Canine hyperadrenocorticism due to adrenocortical neoplasia. Pretreatment evaluation of 41 dogs.  

PubMed

This retrospective study identifies parameters that might separate dogs with hyperadrenocorticism caused by adrenocortical tumors from dogs with pituitary-dependent hyperadrenocorticism. Further, an attempt was made to identify factors that could separate dogs with adrenocortical adenomas from dogs with carcinomas. The records of 41 dogs with hyperadrenocorticism caused by adrenocortical neoplasia were reviewed. The history, physical examination, urinalysis, hemogram (CBC), chemistry profile adrenocorticotrophic hormone (ACTH) stimulation and low dose dexamethasone test results were typical of the nonspecific diagnosis of hyperadrenocorticism. The preceding information on the 41 dogs with adrenocortical tumors was compared with that from 44 previously diagnosed pituitary-dependent hyperadrenocorticoid dogs. There was no parameter which aided in separating these two groups of dogs. Thirty dogs with adrenocortical tumors were tested with a high-dose dexamethasone test and none had suppressed plasma cortisol concentrations 8 hours after IV administration of 0.1 mg/kg of dexamethasone. In 29 of the 41 adrenal tumor dogs, plasma endogenous ACTH was not detectable on at least one measurement (less than 20 pg/ml). The remaining 12 dogs from this group had nondiagnostic concentrations (20-45 pg/ml). Thirteen of 22 dogs (59%) with adrenocortical carcinomas had adrenal masses identified on abdominal radiographs and seven of 13 dogs (54%) with adrenocortical adenomas had radiographically visible adrenal masses. Thirteen of 17 adrenocortical carcinomas (76%) and five of eight adenomas (62%) were identified with ultrasonography. Radiographs of the thorax and ultrasonography of the abdomen identified most of the dogs (8 of 11) with metastatic lesions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1850483

Reusch, C E; Feldman, E C

1991-01-01

251

A1BG and C3 are overexpressed in patients with cervical intraepithelial neoplasia III  

PubMed Central

The present study aimed to analyze sera proteins in females with cervical intraepithelial neoplasia, grade III (CIN III) and in healthy control females, in order to identify a potential biomarker which detects lesions that have a greater probability of cervical transformation. The present study investigated five sera samples from females who were Human Papilloma Virus (HPV) 16+ and who had been histopathologically diagnosed with CIN III, as well as five sera samples from healthy control females who were HPV-negative. Protein separation was performed using two-dimensional (2D) gel electrophoresis and the proteins were stained with Colloidal Coommassie Blue. Quantitative analysis was performed using ImageMaster 2D Platinum 6.0 software. Peptide sequence identification was performed using a nano-LC ESIMS/MS system. The proteins with the highest Mascot score were validated using western blot analysis in an additional 55 sera samples from the control and CIN III groups. The eight highest score spots that were found to be overexpressed in the CIN III sera group were identified as ?-1-B glycoprotein (A1BG), complement component 3 (C3), a pro-apolipoprotein, two apolipoproteins and three haptoglobins. Only A1BG and C3 were validated using western blot analysis, and the bands were compared between the two groups using densitometry analysis. The relative density of the bands of A1BG and C3 was found to be greater in all of the serum samples from the females with CIN III, compared with those of the individuals in the control group. In summary, the present study identified two proteins whose expression was elevated in females with CIN III, suggesting that they could be used as biomarkers for CIN III. However, further investigations are required in order to assess the expression of A1BG and C3 in different pre-malignant lesions. PMID:25009667

CANALES, NORMA ANGÉLICA GALICIA; MARINA, VICENTE MADRID; CASTRO, JORGE SALMERÓN; JIMÉNEZ, ALFREDO ANTÚNEZ; MENDOZA-HERNÁNDEZ, GUILLERMO; McCARRON, ELIZABETH LANGLEY; ROMAN, MARGARITA BAHENA; CASTRO-ROMERO, JULIETA IVONE

2014-01-01

252

An exogenous retrovirus isolated from koalas with malignant neoplasias in a US zoo.  

PubMed

Leukemia and lymphoma account for more than 60% of deaths in captive koalas (Phascolarctos cinereus) in northeastern Australia. Although the endogenizing gammaretrovirus koala endogenous retrovirus (KoRV) was isolated from these koalas, KoRV has not been definitively associated with leukemogenesis. We performed KoRV screening in koalas from the San Diego Zoo, maintained for more than 45 y with very limited outbreeding, and the Los Angeles Zoo, maintained by continuously assimilating captive-born Australian koalas. San Diego Zoo koalas are currently free of malignant neoplasias and were infected with only endogenous KoRV, which we now term subtype "KoRV-A," whereas Los Angeles Zoo koalas with lymphomas/leukemias are infected in addition to KoRV-A by a unique KoRV we term subtype "KoRV-B." KoRV-B is most divergent in the envelope protein and uses a host receptor distinct from KoRV-A. KoRV-B also has duplicated enhancer regions in the LTR associated with increased pathology in gammaretroviruses. Whereas KoRV-A uses the sodium-dependent phosphate transporter 1 (PiT1) as a receptor, KoRV-B employs a different receptor, the thiamine transporter 1 (THTR1), to infect cells. KoRV-B is transmitted from dam to offspring through de novo infection, rather than via genetic inheritance like KoRV-A. Detection of KoRV-B in native Australian koalas should provide a history, and a mode for remediation, of leukemia/lymphoma currently endemic in this population. PMID:23798387

Xu, Wenqin; Stadler, Cynthia K; Gorman, Kristen; Jensen, Nathaniel; Kim, David; Zheng, HaoQiang; Tang, Shaohua; Switzer, William M; Pye, Geoffrey W; Eiden, Maribeth V

2013-07-01

253

Radiogenic neoplasia in thyroid and mammary clonogens. Progress report, January 1, 1991--December 31, 1991  

SciTech Connect

We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. During the end of the last grant year and the first half of the current grant year, we have completed analyses and summarized for publication: investigations on the relationship between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamicpituitary axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH- (thyrotropin-) responsive sub-population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and the results of the large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. We are testing new techniques for the culture, cytofluorescent analysis and characterization mammary epithelial cells and of clonogens in a parallel project, and plan to apply similar technology to the thyroid epithelial cells and clonogen population. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cells interactions during the neoplastic process.

Clifton, K.H.

1991-05-31

254

Dietary Supplementation with Fresh Pineapple Juice Decreases Inflammation and Colonic Neoplasia in IL-10-deficient Mice with Colitis  

PubMed Central

Background Bromelain, a mixture of proteolytic enzymes typically derived from pineapple stem, decreases production of pro-inflammatory cytokines and leukocyte homing to sites of inflammation. We previously showed that short-term oral treatment with bromelain purified from pineapple stem decreased the severity of colonic inflammation in C57BL/6 Il10?/? mice with chronic colitis. Since fresh pineapple fruit contains similar bromelain enzymes but at different proportions, this study aimed to determine whether long-term dietary supplementation with pineapple (supplied as juice) could decrease colon inflammation and neoplasia in Il10?/? mice with chronic colitis as compared with bromelain derived from stem. Results Experimental mice readily consumed fresh pineapple juice at a level that generated mean stool proteolytic activities equivalent to 16 mg bromelain purified from stem, while control mice received boiled juice with inactive enzymes. Survival was increased in the group supplemented with fresh rather than boiled juice (p = 0.01). Mice that received fresh juice also had decreased histologic colon inflammation scores and a lower incidence of inflammation-associated colonic neoplasia (35% vs. 66%; p< 0.02), with fewer neoplastic lesions/colon (p = 0.05). Flow cytometric analysis of murine splenocytes exposed to fresh pineapple juice in vitro demonstrated proteolytic removal of cell surface molecules that can affect leukocyte trafficking and activation. Conclusions These results demonstrate that long-term dietary supplementation with fresh or unpasteurized frozen pineapple juice with proteolytically active bromelain enzymes is safe and decreases inflammation severity and the incidence and multiplicity of inflammation-associated colonic neoplasia in this commonly used murine model of inflammatory bowel disease. PMID:20848493

Hale, Laura P.; Chichlowski, Maciej; Trinh, Chau T.; Greer, Paula K.

2010-01-01

255

Disseminated neoplasia in the soft-shell clam Mya arenaria: membrane lipid composition and functional parameters of circulating cells.  

PubMed

In a previous study we compared lipid composition and functional parameters of circulating cells from Cerastoderma edule affected or not by disseminated neoplasia (neoplastic cells vs hemocytes) (Le Grand et al. Chem Phys Lipids 167:9-20 2013). Neoplastic cells presented morpho-functional modifications concomitant to striking membrane lipid alterations: the proportion of particular plasmalogen molecular species was drastically decreased. We wanted to test whether this pattern was representative of bivalve neoplastic cells. For the purpose, a similar study was conducted on another bivalve species affected by disseminated neoplasia, the soft-shell clam (Mya arenaria). Although total reactive oxygen species production was unaffected, M. arenaria neoplastic cells presented some functional alterations: phagocytosis activity was reduced by 33 %. However, lipid compositions were not drastically altered. Particularly, sterol and plasmalogen levels did not differ between both cell types (about 43 % of membrane lipids and 35 % of phospholipids, respectively in hemocytes and neoplastic cells). This could be related to the fact that disseminated neoplasia was not related to hemolymph cell proliferation in M. arenaria (0.9 ± 0.2 10(6)cell mL(-1), considering both healthy and neoplastic clams, n = 6). Nevertheless this study highlighted minor but specific alterations of membrane lipid composition in M. arenaria neoplastic cells. The only phospholipid subclass in which the fatty acid profile strongly differed between both cell types was serine plasmalogen (PlsSer), with neoplastic cells presenting lower specific enrichment of 20:1n-11 in PlsSer. Such specific alteration of membrane lipid composition strengthened the assumption of an implication of key plasmalogen molecular species in this leukemia-like disease in bivalves. PMID:24934587

Le Grand, Fabienne; Soudant, Philippe; Siah, Ahmed; Tremblay, Réjean; Marty, Yanic; Kraffe, Edouard

2014-08-01

256

Fertility and early pregnancy outcomes after treatment for cervical intraepithelial neoplasia: systematic review and meta-analysis  

PubMed Central

Objective To determine the impact of cervical excision for cervical intraepithelial neoplasia on fertility and early pregnancy outcomes. Design Systematic review and meta-analysis of cohort studies. Data sources Medline and Embase. Eligibility criteria Studies assessing fertility and early pregnancy outcomes in women with a history of treatment for cervical intraepithelial neoplasia versus untreated women. We classified the included studies according to treatment type and fertility or early pregnancy endpoint. Analysis Pooled relative risks and 95% confidence intervals using a random effect model, and interstudy heterogeneity with I2 statistics. Results 15 studies fulfilled the inclusion criteria and were included. The meta-analysis did not provide any evidence that treatment for cervical intraepithelial neoplasia adversely affected the chances of conception. The overall pregnancy rate was higher for treated women than for untreated women (four studies; 43% v 38%, pooled relative risk 1.29, 95% confidence interval 1.02 to 1.64), although the heterogeneity between studies was high (P<0.0001). Pregnancy rates did not differ between women with an intention to conceive (two studies; 88% v 95%, 0.93, 0.80 to 1.08) and the number requiring more than 12 months to conceive (three studies, 15% v 9%, 1.45, 0.89 to 2.37). Although the rates for total miscarriages (10 studies; 4.6% v 2.8%, 1.04, 0.90 to 1.21) and miscarriage in the first trimester (four studies; 9.8% v 8.4%, 1.16, 0.80 to 1.69) was similar for treated and untreated women, cervical treatment was associated with a significantly increased risk of miscarriage in the second trimester. The rate was higher for treated women than for untreated women (eight studies; 1.6% v 0.4%, 16?558 women; 2.60, 1.45 to 4.67). The number of ectopic pregnancies (1.6% v 0.8%; 1.89, 1.50 to 2.39) and terminations (12.2% v 7.4%; 1.71, 1.31 to 2.22) was also higher for treated women. Conclusion There is no evidence suggesting that treatment for cervical intraepithelial neoplasia adversely affects fertility, although treatment was associated with a significantly increased risk of miscarriages in the second trimester. Research should explore mechanisms that may explain this increase in risk and stratify the impact that treatment may have on fertility and early pregnancy outcomes by the size of excision and treatment method used. PMID:25352501

Mitra, Anita; Arbyn, Marc; Stasinou, Sofia Melina; Martin-Hirsch, Pierre; Bennett, Phillip; Paraskevaidis, Evangelos

2014-01-01

257

Entrevista con José Triana  

E-print Network

cenagoso. ¿Tú has visto a esos equilibristas que atraviesan de un lado a otro en un circo, en una cuerda floja? Y tú los ves que van pasando. . . . Pues eso yo creo que es una de las definiciones que podría plantearme o replantearme con la escritura... es su teoría del distanciamiento . . . Eso me interesa mucho, y sobre todo distanciamiento en el sentido de la representación. La obra de Ramón del Valle-lnclán es totalmente distinta de la obra de Bertolt Brecht, y sin embargo tienen un punto...

Vasserot, Christilla

1995-10-01

258

Depth-sensitive optical spectroscopy for noninvasive diagnosis of oral neoplasia  

NASA Astrophysics Data System (ADS)

Oral cancer is the 11th most common cancer in the world. Cancers of the oral cavity and oropharynx account for more than 7,500 deaths each year in the United States alone. Major advances have been made in the management of oral cancer through the combined use of surgery, radiotherapy and chemotherapy, improving the quality of life for many patients; however, these advances have not led to a significant increase in survival rates, primarily because diagnosis often occurs at a late stage when treatment is more difficult and less successful. Accurate, objective, noninvasive methods for early diagnosis of oral neoplasia are needed. Here a method is presented to noninvasively evaluate oral lesions using depth-sensitive optical spectroscopy (DSOS). A ball lens coupled fiber-optic probe was developed to enable preferential targeting of different depth regions in the oral mucosa. Clinical studies of the diagnostic performance of DSOS in 157 subjects were carried out in collaboration with the University of Texas M. D. Anderson Cancer Center. An overall sensitivity of 90% and specificity of 89% were obtained for nonkeratinized oral tissue relative to histopathology. Based on these results a compact, portable version of the clinical DSOS device with real-time automated diagnostic capability was developed. The portable device was tested in 47 subjects and a sensitivity of 82% and specificity of 83% were obtained for nonkeratinized oral tissue. The diagnostic potential of multimodal platforms incorporating DSOS was explored through two pilot studies. A pilot study of DSOS in combination with widefield imaging was carried out in 29 oral cancer patients, resulting in a combined sensitivity of 94% and specificity of 69%. Widefield imaging and spectroscopy performed slightly better in combination than each method performed independently. A pilot study of DSOS in combination with the optical contrast agents 2-NBDG, EGF-Alexa 647, and proflavine was carried out in resected tissue specimens from 15 oral cancer patients. Improved contrast between neoplastic and healthy tissue was observed using 2-NBDG and EGF-Alexa 647.

Schwarz, Richard Alan

259

Quantitative histopathological assessment of ocular surface squamous neoplasia using digital image analysis  

PubMed Central

The aim of this retrospective pilot study was to evaluate the Aperio nuclear V9 algorithm as an image analysis tool to observe the histopathological changes of ocular surface squamous neoplasia (OSSN). A histopathological assessment, including the Ki-67 proliferative index (PI) of immunohistochemically-stained tumor conjunctiva (TC) and healthy conjunctiva (HC) tissues, was performed in six cases of OSSN. The Aperio V9 algorithm was applied to digital images of the tissue specimens to count the Ki-67 PI and to measure the nuclear area indices. This digital algorithm was validated using stereological and visual analysis methods. The visual scoring of Ki-67 PI ranged from 22 to 60% (mean, 38.5%), and from 5 to 20% (mean 9.5%) in TC and HC tissue, respectively. The computer-aided analysis, using the Aperio nuclear V9 algorithm, revealed that the Ki-67 PI ranged from 21.5 to 43.5% (mean, 33.6%), and from 1.9 to 21.0% (mean, 11.8%) in the TC and HC tissue, respectively. The stereological method demonstrated that the Ki-67 PI ranged from 30.1 to 51.5% (mean, 41.0%), and from 3.2 to 30.1% (mean, 15.1%) in the TC and HC tissues, respectively. The strongest association in the collinearity of regression analysis was observed between the Aperio nuclear V9 algorithm/stereological models in the TC tissue (r2=0.7; P=0.04) and the HC tissue (r2=0.7; P=0.03), and the visual/stereological models in the TC tissue (r2=0.7; P=0.04) and the visual/Aperio nuclear V9 algorithm models in the HC tissue (r2=0.7; P=0.04). A weak and statistically insignificant association was identified between the visual/Aperio nuclear V9 algorithm analysis in the TC tissue (r2=0.4; P=0.2) and the visual/stereological models in the HC tissue (r2=0.5; P=0.13). No significant difference was observed between the nuclear area of the TC (mean, 36.5 ?m2) and HC (mean, 35.7 ?m2; P=0.88) tissues. It was concluded that the Aperio nuclear V9 algorithm is a useful tool for the reliable analysis of histopathological changes of OSSN. The results of this computer-aided algorithm correlate strongly with the stereological method when assessing the Ki-67 PI. PMID:25202353

AŠOKLIS, RIMVYDAS; KADZIAUSKIEN?, AIST?; PAULAVI?IEN?, RASA; PETROŠKA, DONATAS; LAURINAVI?IUS, ARVYDAS

2014-01-01

260

Multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4)  

PubMed Central

Multiple endocrine neoplasia (MEN) is characterized by the occurrence of tumors involving two or more endocrine glands within a single patient. Four major forms of MEN, which are autosomal dominant disorders, are recognized and referred to as: MEN type 1 (MEN1), due to menin mutations; MEN2 (previously MEN2A) due to mutations of a tyrosine kinase receptor encoded by the rearranged during transfection (RET) protoncogene; MEN3 (previously MEN2B) due to RET mutations; and MEN4 due to cyclin-dependent kinase inhibitor (CDNK1B) mutations. Each MEN type is associated with the occurrence of specific tumors. Thus, MEN1 is characterized by the occurrence of parathyroid, pancreatic islet and anterior pituitary tumors; MEN2 is characterized by the occurrence of medullary thyroid carcinoma (MTC) in association with phaeochromocytoma and parathyroid tumors; MEN3 is characterized by the occurrence of MTC and phaeochromocytoma in association with a marfanoid habitus, mucosal neuromas, medullated corneal fibers and intestinal autonomic ganglion dysfunction, leading to megacolon; and MEN4, which is also referred to as MENX, is characterized by the occurrence of parathyroid and anterior pituitary tumors in possible association with tumors of the adrenals, kidneys, and reproductive organs. This review will focus on the clinical and molecular details of the MEN1 and MEN4 syndromes. The gene causing MEN1 is located on chromosome 11q13, and encodes a 610 amino-acid protein, menin, which has functions in cell division, genome stability, and transcription regulation. Menin, which acts as scaffold protein, may increase or decrease gene expression by epigenetic regulation of gene expression via histone methylation. Thus, menin by forming a subunit of the mixed lineage leukemia (MLL) complexes that trimethylate histone H3 at lysine 4 (H3K4), facilitates activation of transcriptional activity in target genes such as cyclin-dependent kinase (CDK) inhibitors; and by interacting with the suppressor of variegation 3–9 homolog family protein (SUV39H1) to mediate H3K methylation, thereby silencing transcriptional activity of target genes. MEN1-associated tumors harbor germline and somatic mutations, consistent with Knudson’s two-hit hypothesis. Genetic diagnosis to identify individuals with germline MEN1 mutations has facilitated appropriate targeting of clinical, biochemical and radiological screening for this high risk group of patients for whom earlier implementation of treatments can then be considered. MEN4 is caused by heterozygous mutations of CDNK1B which encodes the 196 amino-acid CDK1 p27Kip1, which is activated by H3K4 methylation. PMID:23933118

Thakker, Rajesh V.

2014-01-01

261

Genotype/phenotype correlation of multiple endocrine neoplasia type 1 gene mutations in sporadic gastrinomas.  

PubMed

Multiple endocrine neoplasia type 1 (MEN1) gene mutations are reported in some gastrinomas occurring in patients without MEN1 as well as in some other pancreatic endocrine tumors (PETs). In some inherited syndromes phenotype-genotype correlations exist for disease severity, location, or other manifestations. The purpose of the present study was to correlate mutations of the MEN1 gene in a large cohort of patients with sporadic gastrinomas to disease activity, tumor location, extent, and growth pattern. DNA was extracted from frozen gastrinomas from 51 patients and screened by dideoxyfinger-printing (ddF) for abnormalities in the 9 coding exons and adjacent splice junctions of the MEN1 gene. Tumor DNA exhibiting abnormal ddF patterns was sequenced for mutations. The findings were correlated with clinical manifestations of the disease, primary tumor site, disease extent, and tumor growth postoperatively. Tumor growth was determined by serial imaging studies. Sixteen different MEN1 gene mutations in the 51 sporadic gastrinomas (31%) were identified (11 truncating, 4 missense, and 1 in-frame deletion). Nine of the 16 mutations were located in exon 2 compared to 7 of 16 in the remaining 8 coding exons (P = 0.005 on a per nucleotide basis). Primary pancreatic or lymph node gastrinomas with a mutation had only exon 2 mutations, whereas duodenal tumors uncommonly harbored exon 2 mutations (P = 0.011). Similarly, small primary tumors (<1 cm) more frequently contained a nonexon 2 mutation (P = 0.02). There was no difference between patients with or without a mutation with respect to clinical characteristics, primary tumor site, disease extent, or proportion of patients disease free after surgery. Postoperative tumor growth tended to be more aggressive in patients with a mutation (P = 0.09). No correlation in the rate of disease-free status or postoperative tumor growth in patients with active disease to the location of the mutation was seen. These results demonstrate that the MEN1 gene is mutated in 31% of sporadic gastrinomas, and mutations are clustered between amino acids 66-166, which differs from patients with familial MEN1, in whom mutations occur throughout the gene. The presence of an MEN1 gene mutation does not correlate with clinical characteristics of patients with gastrinomas, gastrinoma extent, or growth pattern; however, the location of the mutation differed with gastrinoma location. These data suggest that mutations in the MEN1 gene are important in a proportion of sporadic gastrinomas, but the presence or absence of these mutations will not identify the clinically important subgroups with different growth patterns. PMID:10634374

Goebel, S U; Heppner, C; Burns, A L; Marx, S J; Spiegel, A M; Zhuang, Z; Lubensky, I A; Gibril, F; Jensen, R T; Serrano, J

2000-01-01

262

Comparison of /sup 125/I-fibrinogen kinetics and fibrinopeptide A in patients with disseminated neoplasias  

SciTech Connect

To provide more information on the pathways of fibrinogen catabolism in generalized cancer, the effect of heparin on fibrinopeptide A (fpA) and on /sup 125/I-fibrinogen kinetics was studied in 15 patients with disseminated neoplasia. Three patients had evidence of venous thrombosis and in 2 additional patients a low fibrinogen level together with increased amounts of FDP/fdp and a positive ethanol test indicated disseminated intravascular coagulation (DIC). The plasma levels of fpA were grossly elevated (4.6--20, mean 11.4 ng/ml, normal values 1.01 +/- 0.45 ng/ml) in patients with thrombosis or DIC, and normal to grossly elevated (0.4--10.4, mean 6.1 ng/ml) in the other patients. Intravenous heparin bolus lowered the fpA level in 11/11 patients, and continuous heparin treatment led to an impressive suppression or complete normalization of the plasma fpA in 5/6 patients. This finding is thought to reflect heparin suppression of thrombin activity on fibrinogen. In some cases, the fpA fall after heparin bolus was slow and/or incomplete, suggesting fpA generation at sites not easily accessible to heparin or insufficient heparin dosage. The /sup 125/I-fibrinogen kinetics were characterized by a significantly shorter half-life (t1/2: 2.5 days), increased catabolic rate constant (j: 0.44 days-1), and increased absolute turnover (68.9 mg fibrinogen/kg/day) as compared to 4 normal subjects (t1/2: 4.2 days; j: 0.26 days-1; turnover 21.7 mg fibrinogen/kg/day). As estimated from the fpA generation rates, intravascular thrombin action on fibrinogen contributed only in minor part to increase the turnover of /sup 125/I-fibrinogen. In particular, the turnover was greatly accelerated in heparin-treated patients despite impressive suppression or normalization of the fpA levels in 5/6 cases.

Mombelli, G.; Roux, A.; Haeberli, A.; Straub, P.W.

1982-08-01

263

Tumour-associated fibroblasts contribute to neoangiogenesis in human parathyroid neoplasia.  

PubMed

Components of the tumour microenvironment initiate and promote cancer development. In this study, we investigated the stromal component of parathyroid neoplasia. Immunohistochemistry for alpha-smooth muscle actin (?-SMA) showed an abundant periacinar distribution of ?-SMA(+) cells in normal parathyroid glands (n=3). This pattern was progressively lost in parathyroid adenomas (PAds; n=6) where ?-SMA(+)cells were found to surround new microvessels, as observed in foetal parathyroid glands (n=2). Moreover, in atypical adenomas (n=5) and carcinomas (n=4), ?-SMA(+) cells disappeared from the parenchyma and accumulated in the capsula and fibrous bands. At variance with normal glands, parathyroid tumours (n=37) expressed high levels of fibroblast-activation protein (FAP) transcripts, a marker of tumour-associated fibroblasts. We analysed the ability of PAd-derived cells to activate fibroblasts using human bone-marrow mesenchymal stem cells (hBM-MSCs). PAd-derived cells induced a significant increase in FAP and vascular endothelial growth factor A (VEGFA) mRNA levels in co-cultured hBM-MSCs. Furthermore, the role of the calcium-sensing receptor (CASR) and of the CXCL12/CXCR4 pathway in the PAd-induced activation of hBM-MSCs was investigated. Treatment of co-cultures of hBM-MSCs and PAd-derived cells with the CXCR4 inhibitor AMD3100 reduced the stimulated VEGFA levels, while CASR activation by the R568 agonist was ineffective. PAd-derived cells co-expressing parathyroid hormone (PTH)/CXCR4 and PTH/CXCL12 were identified by FACS, suggesting a paracrine/autocrine signalling. Finally, CXCR4 blockade by AMD3100 reduced PTH gene expression levels in PAd-derived cells. In conclusion, i) PAd-derived cells activated cells of mesenchymal origin; ii) PAd-associated fibroblasts were involved in tumuor neoangiogenesis and iii) CXCL12/CXCR4 pathway was expressed and active in PAd cells, likely contributing to parathyroid tumour neoangiogenesis and PTH synthesis modulation. PMID:25515730

Verdelli, C; Avagliano, L; Creo, P; Guarnieri, V; Scillitani, A; Vicentini, L; Steffano, G B; Beretta, E; Soldati, L; Costa, E; Spada, A; Bulfamante, G P; Corbetta, S

2015-02-01

264

Alterations in Nucleolar Structure and Gene Expression Programs in Prostatic Neoplasia Are Driven by the MYC Oncogene  

PubMed Central

Increased nucleolar size and number are hallmark features of many cancers. In prostate cancer, nucleolar enlargement and increased numbers are some of the earliest morphological changes associated with development of premalignant prostate intraepithelial neoplasia (PIN) lesions and invasive adenocarcinomas. However, the molecular mechanisms that induce nucleolar alterations in PIN and prostate cancer remain largely unknown. We verify that activation of the MYC oncogene, which is overexpressed in most human PIN and prostatic adenocarcinomas, leads to formation of enlarged nucleoli and increased nucleolar number in prostate luminal epithelial cells in vivo. In prostate cancer cells in vitro, MYC expression is needed for maintenance of nucleolar number, and a nucleolar program of gene expression. To begin to decipher the functional relevance of this transcriptional program in prostate cancer, we examined FBL (encoding fibrillarin), a MYC target gene, and report that fibrillarin is required for proliferation, clonogenic survival, and proper ribosomal RNA accumulation/processing in human prostate cancer cells. Further, fibrillarin is overexpressed in PIN lesions induced by MYC overexpression in the mouse prostate, and in human clinical prostate adenocarcinoma and PIN lesions, where its expression correlates with MYC levels. These studies demonstrate that overexpression of the MYC oncogene increases nucleolar number and size and a nucleolar program of gene expression in prostate epithelial cells, thus providing a molecular mechanism responsible for hallmark nucleolar alterations in prostatic neoplasia. PMID:21435462

Koh, Cheryl M.; Gurel, Bora; Sutcliffe, Siobhan; Aryee, Martin J.; Schultz, Denise; Iwata, Tsuyoshi; Uemura, Motohide; Zeller, Karen I.; Anele, Uzoma; Zheng, Qizhi; Hicks, Jessica L.; Nelson, William G.; Dang, Chi V.; Yegnasubramanian, Srinivasan; De Marzo, Angelo M.

2011-01-01

265

Loss of sirt1 promotes prostatic intraepithelial neoplasia, reduces mitophagy, and delays park2 translocation to mitochondria.  

PubMed

Prostatic intraepithelial neoplasia is a precursor to prostate cancer. Herein, deletion of the NAD(+)-dependent histone deacetylase Sirt1 induced histological features of prostatic intraepithelial neoplasia at 7 months of age; these features were associated with increased cell proliferation and enhanced mitophagy. In human prostate cancer, lower Sirt1 expression in the luminal epithelium was associated with poor prognosis. Genetic deletion of Sirt1 increased mitochondrial superoxide dismutase 2 (Sod2) acetylation of lysine residue 68, thereby enhancing reactive oxygen species (ROS) production and reducing SOD2 activity. The PARK2 gene, which has several features of a tumor suppressor, encodes an E3 ubiquitin ligase that participates in removal of damaged mitochondria via mitophagy. Increased ROS in Sirt1(-/-) cells enhanced the recruitment of Park2 to the mitochondria, inducing mitophagy. Sirt1 restoration inhibited PARK2 translocation and ROS production requiring the Sirt1 catalytic domain. Thus, the NAD(+)-dependent inhibition of SOD2 activity and ROS by SIRT1 provides a gatekeeper function to reduce PARK2-mediated mitophagy and aberrant cell survival. PMID:25529796

Di Sante, Gabriele; Pestell, Timothy G; Casimiro, Mathew C; Bisetto, Sara; Powell, Michael J; Lisanti, Michael P; Cordon-Cardo, Carlos; Castillo-Martin, Mireia; Bonal, Dennis M; Debattisti, Valentina; Chen, Ke; Wang, Liping; He, Xiaohong; McBurney, Michael W; Pestell, Richard G

2015-01-01

266

Ocular surface squamous neoplasia – Review of etio-pathogenesis and an update on clinico-pathological diagnosis  

PubMed Central

Ocular surface squamous neoplasia (OSSN) has a varied clinical presentation, the diagnosis of which rests on the histopathological examination of the excised lesion. The term OSSN includes mild dysplasia on one end of the spectrum and invasive squamous cell carcinoma on the other end. This lesion has a multi factorial aetiology with interplay of several factors like exposure to ultraviolet radiation, various chemical carcinogens and viral infections, however role of individual agents is not well understood. With the upsurge of infection with human immunodeficiency virus, a changing trend is seen in the clinical presentation and prognosis of patients of OSSN even in developed countries. Anterior segment optical coherence tomography (OCT) and confocal microscopy, hold promise in in-vivo differentiation of intraepithelial neoplasia from invasive squamous cell carcinoma. Variants of squamous cell carcinoma like Mucoepidermoid carcinoma, spindle cell carcinoma and OSSN associated with HIV infection should be suspected in a case of aggressive clinical presentation of OSSN or with massive and recurrent tumours. Surgery, chemotherapy and immunotherapy are the various treatment modalities which in combination show promising results in aggressive, recurrent and larger tumours. PMID:24227983

Mittal, Ruchi; Rath, Suryasnata; Vemuganti, Geeta Kashyap

2013-01-01

267

A case of esophageal squamous cell intraepithelial neoplasia with positivity for type 16 human papillomavirus successfully treated with radiofrequency ablation  

PubMed Central

Esophageal cancer is the eight most common cancer worldwide and the sixth cause of cancer related death with squamous cell carcinoma (SCC) accounting for almost half of all esophageal cancers. Persistent human papilloma virus (HPV) infection has been suspected to play an active role in esophageal carcinogenesis but a clear association has not still been proven and no specific indications or guidelines for possible endoscopic and surgical therapeutic approaches to this clinical scenario are available. We report a case of a 62-year-old woman with histological diagnosis of high-grade intraepithelial squamous neoplasia of distal esophagus associated with cytological modifications resembling cervical HPV infection and with a positive INNO-LiPA assay for genotype 16 HPV. A single session of radiofrequency ablation (RFA) was performed on the dysplastic esophageal area with complete endoscopic eradication as confirmed by the following endoscopic, histologic and microbiologic examinations. Our report might give further strength to the hypothesis of an etiological role of HPV in selected cases of esophageal carcinogenesis and opens a discussion on the possible use of Radio Frequency Ablation as an effective and safe endoscopic treatment for both early squamous cell neoplasia and HPV esophageal colonization. PMID:24772344

Genco, Chiara; Anderloni, Andrea; Spaggiari, Paola; Minieri, Rosanna; Carlino, Alessandra; Jovani, Manol; Villanacci, Vincenzo; Sharma, Prateek; Malesci, Alberto

2014-01-01

268

THE FAILURE OF CHLOROFORM ADMINISTERED IN THE DRINKING WATER TO INDUCE RENAL TUBULAR CELL NEOPLASIA IN MALE F344/N RATS  

EPA Science Inventory

The failure of chloroform administered in drinking water to induce renal tubular cell neoplasia in male F344/N rats Chloroform (TCM) has been demonstrated to be a renal carcinogen in the male Osborne- Mendel rat when administered either by corn oil gavage or in drin...

269

Vol. 7, 1361-1368, October 1996 Cell Growth & Differentiation 1361 Action of Mm and Momi on Neoplasia in Ectopic Intestinal  

E-print Network

on Neoplasia in Ectopic Intestinal Grafts' Karen A. Gould2 and William F. Dove3 McArdle Laboratory for Cancer.] Abstract Mice heterozygous for Mm, a mutant allele of Apc, develop adenomas throughout the intestinal tract using ectopic intestinal isografts. Within the small intestinal grafts, both Mm and Momi act in a tissue

Dove, William

270

Off-pump coronary artery bypass surgery in patients with coronary artery disease and malign neoplasia: results of ten patients and review of the literature.  

PubMed

Cardiopulmonary bypass has been reported to have many effects on the immune system. The aim of this study was to investigate the efficiency and usefulness of off-pump coronary artery bypass (OPCAB) surgery on patients who had coronary artery disease besides malign neoplasia. We applied OPCAB operations to 217 patients between March 2001 and April 2004, ten of whom had malign neoplasia. These patients were diagnosed to have coronary artery disease on their routine examination for their oncologic operation. The malignancies were stomach cancer (2 patients), colon-rectum carcinoma (3 patients), breast carcinoma (2 patients), surrenal carcinoma (1 patient), larynx carcinoma (1 patient), and meningioma (1 patient). The patients were operated on for their neoplasia by the related clinics at a mean of 42 days after the OPCAB surgery. The patients were discharged with surgical success and without any cardiac complications. Coronary artery bypass surgery before a noncardiac major operation may effectively decrease the long-term mortality due to myocardial ischemia. Severe coronary artery disease should be surgically treated in those patients who are scheduled to undergo an operation for malign neoplasia. Extracorporeal circulation impairs the immune system and negatively affects the defense of host against malignancy. Therefore, patients with severe coronary artery disease who are candidates for oncologic operation should be treated with OPCAB. PMID:17143712

Ozsöyler, Ibrahim; Yilik, Levent; Bozok, Sahin; Emrecan, Bilgin; Kestelli, Mert; Karahan, Nagihan; Gürbüz, Ali

2006-11-01

271

Journal of Mammary Gland Biology and Neoplasia, Vol. 9, No. 4, October 2004 ( C 2004) DOI: 10.1007/s10911-004-1410-z  

E-print Network

Journal of Mammary Gland Biology and Neoplasia, Vol. 9, No. 4, October 2004 ( C 2004) DOI: 10 plays a crucial role in driving both normal mammary gland development as well tu- mor initiation associated with cell-ECM interactions. When applied to questions in mammary gland development and neo- plasia

Chen, Christopher S.

272

Journal of Mammary Gland Biology and Neoplasia, Vol. 9, No. 4, October 2004 ( C 2004) DOI: 10.1007/s10911-004-1406-8  

E-print Network

Journal of Mammary Gland Biology and Neoplasia, Vol. 9, No. 4, October 2004 ( C 2004) DOI: 10-function; cell shape; cell biome- chanics; 3D cultures. INTRODUCTION The mammary gland is a highly organized or in Mammary Epithelia Jordi Alcaraz,1,2 Celeste M. Nelson,1 and Mina J. Bissell1,2 The structure and function

Nelson, Celeste M.

273

Journal of Mammary Gland Biology and Neoplasia, Vol. 8, No. 2, April 2003 ( C 2003) The Nuclear Factor I (NFI) Gene Family in Mammary  

E-print Network

Journal of Mammary Gland Biology and Neoplasia, Vol. 8, No. 2, April 2003 ( C 2003) The Nuclear Factor I (NFI) Gene Family in Mammary Gland Development and Function Janice Murtagh,1 Finian Martin,1,3 and Richard M. Gronostajski2,3 Mammary gland development and function require the coordinated spatial

Gronostajski, Richard M.

274

Genetic Variants on Chromosome 8q24 and Colorectal Neoplasia Risk: A Case-Control Study in China and a Meta-Analysis of the Published Literature  

PubMed Central

Previous studies have found that common genetic variants on chromosome 8q24 are associated with the risk of developing colorectal neoplasia. We conducted a hospital-based case-control study, including 435 cases and 788 unrelated controls to investigate the associations between common variants on 8q24 and the risk of colorectal cancer in a Chinese population. We also evaluated the association of rs6983267 with colorectal neoplasia in the published literature via a meta-analysis study. We found that rs6983267 was significantly associated with the risk of colorectal cancer in the Chinese population, with an adjusted odds-ratio (OR) for the GT heterozygotes and GG homozygotes of 1.30 (95% CI ?=?0.98–1.71, P?=?0.069) and 1.66 (95% CI ?=?1.18–2.34, P?=?0.004), respectively, compared to the TT homozygotes, with a P-trend value of 0.003. No association was found for the other three loci (rs16901979, rs1447295 and rs7837688). In the meta-analysis of the published genetic association studies, the rs6983267 variant was found to be associated with an increased risk of colorectal neoplasia. The heterozygous GT carriers showed a 20% increased risk of colorectal neoplasia (OR ?=?1.20, 95% CI ?=?1.16–1.25; random effects model) with a summary OR for homozygous GG carriers of 1.39 (95% CI ?=?1.32–1.48; random effects model) compared to the TT genotype carriers. We found no significant differences between the association of rs6983267 and colorectal cancer and colorectal adenomas. In summary, our study confirms that the variant rs6983267 is a risk factor for colorectal neoplasia in various populations, including the Chinese population. PMID:21455501

Chen, Peizhan; Yang, Huan; Yuan, Xiaoyan; Tajima, Kazuo; Cao, Jia; Wang, Hui

2011-01-01

275

Planificación Neuroquirúrgica con Software Osirix  

PubMed Central

Introducción: La individualidad anatómica es clave para reducir el trauma quirúrgico y obtener un mejor resultado. Actualmente, el avance en las neuroimágenes ha permitido objetivar esa individualidad anatómica, permitiendo planificar la intervención quirúrgica. Con este objetivo, presentamos nuestra experiencia con el software Osirix. Descripción de la técnica: Se presentan 3 casos ejemplificadores de 40 realizados. Caso 1: Paciente con meningioma de la convexidad parasagital izquierda en área premotora; Caso 2: Paciente con macroadenoma hipofisario, operada previamente por vía transeptoesfenoidal en otra institución con una resección parcial; Caso 3: Paciente con lesiones en pedúnculo cerebeloso medio bilateral. Se realizó la planificación prequirúrgica con el software OsiriX, fusionando y reconstruyendo en 3D las imágenes de TC e IRM, para analizar relaciones anatómicas, medir distancias, coordenadas y trayectorias, entre otras funciones. Discusión: El software OsiriX de acceso libre y gratuito permite al cirujano, mediante la fusión y reconstrucción en 3D de imágenes, analizar la anatomía individual del paciente y planificar de forma rápida, simple, segura y económica cirugías de alta complejidad. En el Caso 1 se pudo analizar las relaciones del tumor con las estructuras adyacentes para minimizar el abordaje. En el Caso 2 permitió comprender la anatomía post-operatoria previa del paciente, para determinar la trayectoria del abordaje transnasal endoscópico y la necesidad de ampliar su exposición, logrando la resección tumoral completa. En el Caso 3 permitió obtener las coordenadas estereotáxicas y trayectoria de una lesión sin representación tomográfica. Conclusión: En casos de no contar con costosos sistemas de neuronavegación o estereotáxia el software OsiriX es una alternativa a la hora de planificar la cirugía, con el objetivo de disminuir el trauma y la morbilidad operatoria. PMID:25165617

Jaimovich, Sebastián Gastón; Guevara, Martin; Pampin, Sergio; Jaimovich, Roberto; Gardella, Javier Luis

2014-01-01

276

A prostatic intraepithelial neoplasia-dependent p27kip1 checkpoint induces senescence, inhibits cell proliferation and cancer progression  

PubMed Central

SUMMARY Transgenic expression of activated AKT1 in the murine prostate induces Prostatic Intraepithelial Neoplasia (PIN) that does not progress to invasive prostate cancer (CaP). In luminal epithelial cells of Akt-driven PIN we show the concomitant induction of p27kip1 and senescence. Genetic ablation of p27Kip1 led to down regulation of senescence markers and progression to cancer. In humans, p27Kip1 and senescence markers were elevated in PIN not associated with CaP, but were decreased and absent, respectively in cancer-associated PIN and in CaP. Importantly, p27Kip1 up-regulation in mouse and human in situ lesions did not depend upon mTOR or Akt activation but was instead specifically associated with alterations in cellular polarity, architecture and adhesion molecules. These data suggest that a p27Kip1-driven checkpoint limits progression of PIN to CaP. PMID:18691549

Majumder, Pradip K.; Grisanzio, Chiara; O’Connell, Fionnuala; Barry, Marc; Brito, Joseph M.; Xu, Qing; Guney, Isil; Berger, Raanan; Herman, Paula; Bikoff, Rachel; Fedele, Giuseppe; Baek, Won-Ki; Wang, Shunyou; Ellwood-Yen, Katharine; Wu, Hong; Sawyers, Charles L.; Signoretti, Sabina; Hahn, William C.; Loda, Massimo; Sellers, William R.

2008-01-01

277

Embolization as an Alternative Treatment of Insulinoma in a Patient with Multiple Endocrine Neoplasia Type 1 Syndrome  

SciTech Connect

Insulinoma is a rare neuroendocrine tumor, most commonly originating from the pancreas, which is either sporadic or familial as a component of multiple endocrine neoplasia type 1 syndrome (MEN1). It is characterized by increased insulin secretion leading to hypoglycemia. Surgical removal is considered the treatment of choice, with limited side effects and relatively low morbidity and mortality, both being improved by the laparoscopic procedure. We present the case of a 30-year-old patient with MEN1 and recurrent insulinoma with severe hypoglycemic episodes who could not be surgically treated due to the adherence of the tumor to large blood vessels and to prior multiple surgical operations. He was treated by repeated embolization using spherical polyvinyl alcohol particles, resulting in shrinkage of the tumor, improvement of the frequency and severity of the hypoglycemic episodes, and better quality of life.

Peppa, Melpomeni, E-mail: molypepa@otenet.g ['Attikon' University Hospital, Endocrine Unit, Second Department of Internal Medicine-Propaedeutic, Research Institute and Diabetes Center, Athens University Medical School (Greece); Brountzos, Elias; Economopoulos, Nicolaos ['Attikon' University Hospital, Second Radiology Department, Athens University Medical School (Greece); Boutati, Eleni ['Attikon' University Hospital, Second Department of Internal Medicine-Propaedeutic, Research Institute and Diabetes Center, Athens University Medical School (Greece); Pikounis, Vasilios ['Attikon' University Hospital, Endocrine Unit, Second Department of Internal Medicine-Propaedeutic, Research Institute and Diabetes Center, Athens University Medical School (Greece); Patapis, Paul ['Attikon' University Hospital, Third Surgery Department, Athens University Medical School (Greece); Economopoulos, Theofanis; Raptis, Sotirios A. ['Attikon' University Hospital, Second Department of Internal Medicine-Propaedeutic, Research Institute and Diabetes Center, Athens University Medical School (Greece); Hadjidakis, Dimitrios ['Attikon' University Hospital, Endocrine Unit, Second Department of Internal Medicine-Propaedeutic, Research Institute and Diabetes Center, Athens University Medical School (Greece)

2009-07-15

278

Rapid development of thymic neuroendocrine carcinoma despite transcervical thymectomy in a patient with multiple endocrine neoplasia type 1  

PubMed Central

Thymic neuroendocrine (NE) tumors are a rare manifestation of multiple endocrine neoplasia syndrome type 1 (MEN-1). They are malignant and aggressive tumors and form a major cause of mortality in MEN-1. Transcervical thymectomy (TCT) at the time of parathyroid surgery for primary hyperparathyroidism (PHPT) in MEN-1 usually prevents thymic NE tumors. We report a 56-year-old nonsmoker male with sporadic MEN-1 who presented with thymic NE carcinoma developing rapidly within a span of 8 months after subtotal parathyroidectomy and TCT for PHPT. We present a brief review of literature on this rare NE malignancy, focusing on its occurrence despite TCT. This case highlights the fact that thymic NE carcinoma may develop even after TCT in MEN-1. Regular surveillance for these aggressive thymic NE tumors is mandatory even after TCT in MEN-1 setting. PMID:23961499

Sadacharan, Dhalapathy; Reddy, Sagili Vijaya Bhaskar; Agrawal, Vinita; Agarwal, Gaurav

2013-01-01

279

In vivo three-dimensional optical coherence tomography and multiphoton microscopy in a mouse model of ovarian neoplasia  

NASA Astrophysics Data System (ADS)

Our goal is to use optical coherence tomography (OCT) and multiphoton microscopy (MPM) to detect early tumor development in a mouse model of ovarian neoplasia. We hope to use information regarding early tumor development to create a diagnostic test for high-risk patients. In this study we collect in vivo images using OCT, second harmonic generation and two-photon excited fluorescence from non-vinylcyclohexene diepoxide (VCD)-dosed and VCD-dosed mice. VCD causes follicular apoptosis (simulating menopause) and leads to tumor development. Using OCT and MPM we visualized the ovarian microstructure and were able to see differences between non-VCD-dosed and VCD-dosed animals. This leads us to believe that OCT and MPM may be useful for detecting changes due to early tumor development.

Watson, Jennifer M.; Marion, Samuel L.; Rice, Photini Faith; Bentley, David L.; Besselsen, David; Utzinger, Urs; Hoyer, Patricia B.; Barton, Jennifer K.

2013-03-01

280

Is differentiated vulval intraepithelial neoplasia the precursor lesion of human papillomavirus-negative vulval squamous cell carcinoma?  

PubMed

Vulval squamous cell carcinoma appears to arise via 2 distinct pathways. A significant minority are associated with oncogenic human papillomavirus (HPV) infection and undifferentiated vulval intraepithelial neoplasia (VIN). However, the majority arises in the absence of HPV, on a background of chronic inflammation. Until recently, it was assumed that lichen sclerosus was the underlying inflammatory condition in the majority of HPV-negative cancers. This pathway of carcinogenesis has been less well studied than the HPV pathway. Emerging evidence implicates differentiated VIN (DVIN), rather than lichen sclerosus, as the most likely precursor lesion in HPV-negative vulval squamous cell carcinoma. Here we discuss the clinical and molecular evidence that implicates DVIN as a lesion with a high malignant potential. This lesion is probably underdiagnosed and may be undertreated. Better recognition of DVIN by gynecologists and pathologists may therefore offer an opportunity to prevent some vulval cancers. PMID:21946295

Kokka, Fani; Singh, Naveena; Faruqi, Asma; Gibbon, Karen; Rosenthal, Adam N

2011-10-01

281

Premalignant epithelial disorders of the vulva: squamous vulvar intraepithelial neoplasia, vulvar Paget's disease and melanoma in situ.  

PubMed

No standard screening programs exist to detect vulvar carcinoma or its precursor lesions, and therefore gynecologists, dermatologists and other healthcare providers in this field should be aware of the clinical features, behavior and management of the different existing premalignant vulvar lesions, squamous vulvar intraepithelial neoplasia (VIN), vulvar Paget's disease and melanoma in situ. In 2004, a new classification for squamous VIN was introduced by the International Society for the Study of Vulvar Disease, subdividing squamous VIN into the HPV-related usual type, and into differentiated type, which is associated with lichen sclerosus. This review describes the relevant aspects of squamous VIN, vulvar Paget's disease and melanoma in situ, its epidemiological characteristics, diagnosis, management and malignant potential. PMID:20504079

Terlou, Annelinde; Blok, Leen J; Helmerhorst, Theo J M; van Beurden, Marc

2010-06-01

282

Neoplasia in Chronic Pancreatitis: How to Maximize the Yield of Endoscopic Ultrasound-Guided Fine Needle Aspiration  

PubMed Central

When performing endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), identifying neoplasia in the setting of chronic pancreatitis can be technically challenging. The morphology of an ill-defined mass on sonography, presence of calcifications or intervening collaterals, reverberation from a biliary stent, low yield of tissue procurement, and interpretative errors in cytopathology can result in both false-negative and false-positive results. Although these challenges cannot be completely eliminated, elastography or contrast-enhanced imaging can aid in differentiating an inflammatory mass from a neoplasm. Also, performing more passes of FNA, procuring core biopsy material, performing rapid onsite evaluation, conducting ancillary pathology studies, and even repeating the procedure on a different day can aid in improving the diagnostic performance of EUS-FNA. This review provides a concise update and offers practical tips to improving the diagnostic yield of EUS-FNA when sampling solid pancreatic mass lesions in the setting of chronic pancreatitis. PMID:25325001

Bang, Ji Young

2014-01-01

283

Meta-Analysis on Prevalence and Attribution of Human Papillomavirus Types 52 and 58 in Cervical Neoplasia Worldwide  

PubMed Central

Objective To estimate the prevalence and attribution of two non-vaccine-covered HPV types (HPV52 and HPV58) across the world. Methods Meta-analysis on studies reported in English and Chinese between 1994 and 2012. Results The pooled prevalence and attribution rates of HPV52 and HPV58 in invasive cervical cancers were significantly higher in Eastern Asia compared to other regions (HPV52 prevalence: 5.7% vs. 1.8–3.6%, P<0.001; HPV52 attribution: 3.7% vs. 0.2–2.0%; HPV58 prevalence: 9.8% vs. 1.1–2.5%, P<0.001; HPV58 attribution: 6.4% vs. 0.7–2.2%, P<0.001). Oceania has an insufficient number of studies to ascertain the prevalence of HPV52. Within Eastern Asia, the attribution of HPV58 to invasive cervical cancer was 1.8-fold higher than that of HPV52. Similarly, HPV52 and HPV58 shared a higher prevalence and attribution among cervical intraepithelial neoplasia in Eastern Asia. In contrast to the classical high-risk type, HPV16, the prevalence and attribution of HPV52 and HPV58 decreased with increasing lesion severity. Thus, HPV52 and HPV58 behave as an “intermediate-risk” type. Conclusion The attribution of HPV52 and HPV58 to cervical intraepithelial neoplasia and invasive cancer in Eastern Asia were respectively 2.5–2.8 and 3.7–4.9 folds higher than elsewhere. Changes in the attributed disease fraction can serve as a surrogate marker for cross-protection or type replacement following widespread use of HPV16/18-based vaccines. This unique epidemiology should be considered when designing HPV screening assays and vaccines for Eastern Asia. PMID:25229350

Chan, Paul K. S.; Ho, Wendy C. S.; Chan, Martin C. W.; Wong, Martin C. S.; Yeung, Apple C. M.; Chor, Josette S. Y.; Hui, Mamie

2014-01-01

284

Biomarkers and transcription levels of cancer-related genes in cockles Cerastoderma edule from Galicia (NW Spain) with disseminated neoplasia.  

PubMed

Disseminated neoplasia (DN) is a pathological condition reported for several species of marine bivalves throughout the world, but its aetiology has not yet been satisfactorily explained. It has been suggested that chemical contamination could be a factor contributing to neoplasia. The aim of the present study was to compare cell and tissue biomarkers and the transcription level of cancer-related genes in cockles (Cerastoderma edule) affected by DN with those of healthy cockles in relation to chemical contaminant burdens. For this, cockles were collected from a natural bed in Cambados (Ria de Arousa, Galicia) in May 2009. The prevalence of DN was 12.36% and 3 degrees of DN severity were distinguished. No significant differences in metal accumulation, non-specific inflammatory responses and parasites were observed between healthy and DN-affected cockles. Lysosomal membrane stability was significantly reduced in cockles affected by DN, which indicates a poorer health condition. Very low frequencies of micronuclei were recorded and no significant differences were detected between DN severity groups. Haemolymph analyses showed a higher frequency of mitotic figures and binucleated cells in cockles affected by moderate and heavy DN than in healthy ones. Neoplastic animals showed significantly higher transcription levels of p53 and ras than healthy cockles and mutational alterations in ras gene sequence were detected. Low concentrations of metals, polycyclic aromatic hydrocarbons, polychlorinated biphenyls and phthalate esters were measured in cockles from Cambados. In conclusion, cockles affected by DN suffer a general stress situation and have altered patterns of cancer-related gene transcription. Further studies are in progress to elucidate mechanisms of carcinogenesis in this species. PMID:23665240

Ruiz, Pamela; Díaz, Seila; Orbea, Amaia; Carballal, Maria J; Villalba, Antonio; Cajaraville, Miren P

2013-07-15

285

The expanding family of SMARCB1(INI1)-deficient neoplasia: implications of phenotypic, biological, and molecular heterogeneity.  

PubMed

Since the description of atypical teratoid/rhabdoid tumors of the central nervous system and renal/extrarenal malignant rhabdoid tumors in children, the clinicopathologic spectrum of neoplasms having in common a highly variable rhabdoid cell component (0% to 100%) and consistent loss of nuclear SMARCB1 (INI1) expression has been steadily expanding to include cribriform neuroepithelial tumor of the ventricle, renal medullary carcinoma and a subset of collecting duct carcinoma, epithelioid sarcoma, subsets of miscellaneous benign and malignant soft tissue tumors, and rare rhabdoid carcinoma variants of gastroenteropancreatic, sinonasal, and genitourinary tract origin. Although a majority of SMARCB1-deficient neoplasms arise de novo, the origin of SMARCB1-deficient neoplasia in the background of a phenotypically or genetically definable differentiated SMARCB1-intact "parent neoplasm" has been convincingly demonstrated, highlighting the rare occurrence of rhabdoid tumors as "double-hit neoplasia." As a group, SMARCB1-deficient neoplasms occur over a wide age range (0 to 80 y), may be devoid of rhabdoid cells or display uniform rhabdoid morphology, and follow a clinical course that varies from benign to highly aggressive causing death within a few months irrespective of aggressive multimodality therapy. Generally applicable criteria that would permit easy recognition of these uncommon neoplasms do not exist. Diagnosis is based on site-specific and entity-specific sets of clinicopathologic, immunophenotypic, and/or molecular criteria. SMARCB1 immunohistochemistry has emerged as a valuable tool in confirming or screening for SMARCB1-deficient neoplasms. This review summarizes the different phenotypic and topographic subgroups of SMARCB1-deficient neoplasms including sporadic and familial, benign and malignant, and rhabdoid and nonrhabdoid variants, highlighting their phenotypic heterogeneity and molecular complexity. PMID:25299309

Agaimy, Abbas

2014-11-01

286

Associations of dietary dark-green and deep-yellow vegetables and fruits with cervical intraepithelial neoplasia: modification by smoking.  

PubMed

Smoking has been positively and fruit and vegetable intake has been negatively associated with cervical cancer, the second most common cancer among women worldwide. However, a lower consumption of fruits and reduced serum carotenoids have been observed among smokers. It is not known whether the smoking effect on the risk of cervical neoplasia is modified by a low intake of fruits and vegetables. The present study examined the combined effects of tobacco smoking and diet using a validated FFQ and serum carotenoid and tocopherol levels on cervical intraepithelial neoplasia grade 3 (CIN3) risk in a hospital-based case-control study conducted in São Paulo, Brazil, between 2003 and 2005. The sample comprised 231 incident, histologically confirmed cases of CIN3 and 453 controls. A low intake ( ? 39 g) of dark-green and deep-yellow vegetables and fruits without tobacco smoking had a lesser effect on CIN3 (OR 1·14; 95 % CI 0·49, 2·65) than among smokers with higher intake ( ? 40 g; OR 1·83; 95 % CI 0·73, 4·62) after adjusting for confounders. The OR for the joint exposure of tobacco smoking and low intake of vegetables and fruits was greater (3·86; 95 % CI 1·74, 8·57; P for trend < 0·001) compared with non-smokers with higher intake after adjusting for confounding variables and human papillomavirus status. Similar results were observed for total fruit, serum total carotene (including ?-, ?- and ?-carotene) and tocopherols. These findings suggest that the effect of nutritional factors on CIN3 is modified by smoking. PMID:21092390

Tomita, Luciana Y; Roteli-Martins, Cecília M; Villa, Luisa L; Franco, Eduardo L; Cardoso, Marly A

2011-03-01

287

PAX1/SOX1 DNA methylation and cervical neoplasia detection: a Taiwanese Gynecologic Oncology Group (TGOG) study.  

PubMed

We aimed to determine whether PAX1/SOX1 methylation could be translated to clinical practice for cervical neoplasia detection when used alone and in combination with current cytology-based Pap screening. We conducted a multicenter case-control study in 11 medical centers in Taiwan from December 2009 to November 2010. Six hundred seventy-six patients were included in the analysis, including 330 in the training set and 346 in the testing set. Multiplex quantitative methylation-specific polymerase chain reaction (PCR) was performed with a TaqMan probe system using a LightCycler 480 Real-Time PCR System (Roche). The level of human papilloma virus (HPV) was analyzed using a Hybrid Capture 2 system (Digene). Receiver operating characteristic curves were generated to obtain the best cutoff values from the training data set. The sensitivities, specificities, and accuracies were validated in the testing set. The sensitivities for methylated ((m)) PAX1(m) and SOX1(m) and HPV testing for detecting CIN3(+) lesions were 0.64, 0.71, and 0.89, and the specificities were 0.91, 0.77, and 0.68, respectively. Combined parallel testing of PAX1(m)/SOX1(m) tests with Pap smearing showed superior specificity (0.84/0.71 vs. 0.66, respectively) and similar sensitivity (0.93/0.96 vs. 0.97) to the combination of Pap smear results and HPV testing. Thus, combined parallel testing using Pap smears and PAX1 or SOX1 methylation tests may provide better performance than a combination of Pap smears with HPV testing in detection for cervical neoplasia. PMID:24799352

Lai, Hung-Cheng; Ou, Yu-Che; Chen, Tze-Chien; Huang, Huei-Jean; Cheng, Ya-Min; Chen, Chi-Hau; Chu, Tang-Yuan; Hsu, Shih-Tien; Liu, Cheng-Bin; Hung, Yao-Ching; Wen, Kuo-Chang; Yu, Mu-Hsien; Wang, Kung-Liahng

2014-08-01

288

Performance characteristics and comparison of two immunochemical and two guaiac fecal occult blood screening tests for colorectal neoplasia.  

PubMed

A new immunochemical test for stool Hb, FlexSure OBT, was compared with the immunochemical HemeSelect and guaiac Hemoccult II and Hemoccult SENSA tests. Blinded development of test cards smeared with stools having added human blood showed better analytical sensitivity of FlexSure OBT (0.2 ml blood/100 g feces), than Hemoccult SENSA (> or =0.5 ml) or Hemoccult II (> or =1.0 ml). All four stool tests were prepared by 403 subjects having endoscopic examinations. The guaiac tests and FlexSure OBT were easy to prepare and develop. The positivity rate of Hemoccult SENSA was 8.7%, Hemoccult II 6%, FlexSure OBT 4.2%, and HemeSelect 3.4%. In this mainly asymptomatic (97%) population, 98% were free of clinically significant neoplasia (five had cancers, three had adenomas > or =1.0 cm). Sensitivity for cancers or adenomas > or =1.0 cm was similar for all tests (62.5-86%, NS) and Hemoccult SENSA had the lowest specificity (92% vs 95-98%, P < 0.05); but both Hemoccult II and Hemoccult SENSA had significantly lower predictive positive values (21% and 14%) than either FlexSure OBT (29%) or HemeSelect (50%) (P < 0.05). If both Hemoccult SENSA and FlexSure OBT were positive in the same subjects (1.7%), sensitivity for cancer or adenomas > or =1.0 cm (50%) was not significantly better than guaiac tests, but specificity (99.2%) and predictive positive (57%) values were improved (P < 0.05). In this population, guaiac tests were as sensitive as immunochemical tests for clinically significant colorectal neoplasia, but with significantly lower predictive positive values. A combination of a sensitive guaiac test (Hemoccult SENSA) and a specific confirmatory test for human Hb (FlexSure OBT) provided high specificity, comparable to HemeSelect. PMID:9365136

Rozen, P; Knaani, J; Samuel, Z

1997-10-01

289

Use of the NucliSENS EasyQ HPV assay in the management of cervical intraepithelial neoplasia.  

PubMed

Persistent infection by high-risk human papillomavirus is a necessary cause for cervical cancer. DNA-based human papillomavirus (HPV) assays show high sensitivity but poor specificity in detecting high-grade cervical lesions. Assays detecting mRNA of the oncoproteins E6 and E7 show higher specificity but lack either detection of all high-risk genotypes or the ability to specify the detected genotypes. The aim of this study was to evaluate the clinical performance of the NucliSENS EasyQ HPV assay in comparison with the Hybrid Capture 2 test (HC2) and the CLART Human Papillomavirus 2 assay (CLART), using a clinical cut-off of cervical intraepithelial neoplasia grade 2 or worse. In the 554 studied women, the lowest HPV positivity rate was detected for NucliSENS EasyQ HPV assay (55.1%), while HC2 and CLART showed similar results (HC2: 77.4%; CLART: 78.0%). In comparison with the other tests, the NucliSENS EasyQ HPV assay showed a lower clinical sensitivity (79.3% vs. 96.4% for HC2 and 95.9% for CLART) but a higher clinical specificity (72.6% vs. 42.8% for HC2 and 42.5% for CLART). Detection of E6/E7 mRNA transcripts may provide a higher specificity for cervical intraepithelial neoplasia grade 2 lesions or worse, since the oncogenic potential of HPV infection depends on the over-expression of these two oncoproteins. PMID:23918542

Oliveira, Ana; Verdasca, Nuno; Pista, Ângela

2013-07-01

290

PAX1/SOX1 DNA methylation and cervical neoplasia detection: a Taiwanese Gynecologic Oncology Group (TGOG) study  

PubMed Central

We aimed to determine whether PAX1/SOX1 methylation could be translated to clinical practice for cervical neoplasia detection when used alone and in combination with current cytology-based Pap screening. We conducted a multicenter case–control study in 11 medical centers in Taiwan from December 2009 to November 2010. Six hundred seventy-six patients were included in the analysis, including 330 in the training set and 346 in the testing set. Multiplex quantitative methylation-specific polymerase chain reaction (PCR) was performed with a TaqMan probe system using a LightCycler 480 Real-Time PCR System (Roche). The level of human papilloma virus (HPV) was analyzed using a Hybrid Capture 2 system (Digene). Receiver operating characteristic curves were generated to obtain the best cutoff values from the training data set. The sensitivities, specificities, and accuracies were validated in the testing set. The sensitivities for methylated (m) PAX1m and SOX1m and HPV testing for detecting CIN3+ lesions were 0.64, 0.71, and 0.89, and the specificities were 0.91, 0.77, and 0.68, respectively. Combined parallel testing of PAX1m/SOX1m tests with Pap smearing showed superior specificity (0.84/0.71 vs. 0.66, respectively) and similar sensitivity (0.93/0.96 vs. 0.97) to the combination of Pap smear results and HPV testing. Thus, combined parallel testing using Pap smears and PAX1 or SOX1 methylation tests may provide better performance than a combination of Pap smears with HPV testing in detection for cervical neoplasia. PMID:24799352

Lai, Hung-Cheng; Ou, Yu-Che; Chen, Tze-Chien; Huang, Huei-Jean; Cheng, Ya-Min; Chen, Chi-Hau; Chu, Tang-Yuan; Hsu, Shih-Tien; Liu, Cheng-Bin; Hung, Yao-Ching; Wen, Kuo-Chang; Yu, Mu-Hsien; Wang, Kung-Liahng

2014-01-01

291

Development of squamous neoplasia in esophageal iodine-unstained lesions and the alcohol and aldehyde dehydrogenase genotypes of Japanese alcoholic men.  

PubMed

We investigated the development of esophageal neoplasia in biopsy specimens of the distinct iodine-unstained lesions (DIULs) ? 5 mm detected in 280 of 2,115 Japanese alcoholic men who underwent screening by esophageal iodine staining. Low-grade intraepithelial neoplasia (LGIN) was diagnosed in 155 of them, high-grade intraepithelial neoplasia (HGIN) in 57, and invasive SCC in 35. The size of the DIULs increased with the degree of neoplasia. Most LGINs were flat and were missed before iodine staining. Some DIULs became a light pink color (PC) about 2 min after staining, and 2.6, 56.1 and 96.0% of the LGIN, HGIN and invasive SCC lesions, respectively, were PC-sign-positive. Multiple DIULs of any size markedly increased the risk of LGIN [adjusted OR (95%CI) = 10.1 (7.12-14.5)], HGIN [27.9 (14.6-53.4)] and invasive SCC [21.6 (10.1-46.4)], and were strongly associated with the presence vs. absence of DIULs ? 5 mm [13.3 (9.21-19.1)], inactive heterozygous aldehyde dehydrogenase-2 (ALDH2*1/*2) vs. ALDH2*1/*1 [2.60 (1.79-3.78)], and less-active alcohol dehydrogenase-1B (ADH1B*1/*1) vs. ADH1B*2 allele [2.61 (1.87-3.64)]. The combination of ALDH2*1/*2 and ADH1B*1/*1 synergistically increased the risk of LGIN [4.53 (2.17-9.47)], HGIN [10.4 (4.34-24.7)] and invasive SCC [21.7 (7.96-59.3)]. Esophageal neoplasia developed at earlier ages in those with ALDH2*1/*2. Biopsy-proven HGIN was diagnosed as invasive SCC in 15 (39.5%) of 38 patients after endoscopic mucosectomy or surgery. In conclusion, large size, non-flat appearance, positive PC sign and multiplicity of DIULs and ALDH2*1/*2 and ADH1B*1/*1 were associated with development of esophageal neoplasia in Japanese alcoholics. Biopsy-proven HGIN should be totally resected for both diagnostic and therapeutic purposes. PMID:21796615

Yokoyama, Akira; Hirota, Teruyuki; Omori, Tai; Yokoyama, Tetsuji; Kawakubo, Hirofumi; Matsui, Toshifumi; Mizukami, Takeshi; Mori, Shuka; Sugiura, Hitoshi; Maruyama, Katsuya

2012-06-15

292

In situ and intraductal epithelial proliferations of prostate: definitions and treatment implications. Part 1: Prostatic intraepithelial neoplasia.  

PubMed

What's known on the subject? and What does the study add? In the era of extended biopsy sampling of the prostate, multifocal high-grade prostatic intraepithelial neoplasia (HGPIN) is associated with a significantly higher rate of cancer diagnosis than unifocal HGPIN or a benign diagnosis. In addition, the cancers that are subsequently diagnosed in men with HGPIN on their initial biopsy tend to be smaller, lower grade and more commonly organ-confined. This has led to a reappraisal of the need and timing of repeat biopsies. The present paper provides a series of recommendations on the optimal timing of repeat biopsies in men with HGPIN on biopsy, based on the current available evidence. This is the first of a two part series reviewing the nature and clinical significance of in situ cellular proliferations in the prostate gland. This first part examines prostatic intraepithelial neoplasia (PIN), while the second part in the next supplement discusses intraductal carcinoma and ductal adenocarcinoma of the prostate. PIN is a precursor lesion in the development of some forms of adenocarcinoma of the prostate. In the 1990 s, high-grade PIN (HGPIN) on biopsy was a significant predictor of carcinoma, but this was due to incomplete sampling with sextant biopsies. With more extensive sampling in the last decade, the likelihood of identifying cancer after a diagnosis of HGPIN is not significantly different from a benign diagnosis. In several recent studies, it is now recognised that multifocal HGPIN is a better predictor of cancer than unifocal HGPIN. Most cases of cancer will be detected in the vicinity of the HGPIN, but up to 40% of cancers will occur in different sextants. In assessing potential markers for carcinoma in men with HGPIN on biopsy, ?-methylacyl coenzyme-A racemase (AMACR) has emerged as a promising diagnostic tool. HGPIN with strong staining for AMACR is associated with a higher rate of cancer detection in subsequent biopsies compared with AMACR-negative HGPIN. Also, AMACR positivity in HGPIN is more commonly seen adjacent to carcinoma, and this may provide guidance as to the site of future biopsies. PMID:22458488

Clouston, David; Bolton, Damien

2012-04-01

293

Phase I dose de-escalation trial of alpha-difluoromethylornithine in patients with grade 3 cervical intraepithelial neoplasia.  

PubMed

alpha-Difluoromethylornithine (DFMO) is a suicide inhibitor of ornithine decarboxylase and potent antiproliferative chemopreventive agent. We conducted a dose de-escalation Phase I trial of DFMO in patients with grade 3 cervical intraepithelial neoplasia to determine an optimal dose of DFMO using ornithine decarboxylase activity and polyamine modulation as surrogate biomarkers and to evaluate its toxicity. Thirty patients with biopsy-confirmed grade 3 cervical intraepithelial neoplasia were assigned sequentially to one of five DFMO doses (1.000, 0.500, 0.250, 0.125, or 0.060 g/m2) given daily for 31 days. One patient was excluded from analysis for protocol violation. Polyamine levels were assessed in cervical tissue, plasma, and RBCs. Tissue and blood samples were obtained before and after treatment with DFMO. All patients underwent loop excision of the cervix at the end of the study for complete histological evaluation and definitive treatment of the premalignant condition. No major clinical toxicity was observed at any DFMO dose. A reduction in tissue spermidine to spermine (SPD:SPM) ratio and an increase in plasma arginine levels were observed among patients receiving 1.000 g/m2/day (P < 0.05). A nonsignificant reduction in SPD:SPM ratio was also observed in the 0.500 g/m2/day dose group, and a nonsignificant increase in plasma arginine level was observed down to the 0.125 g/m2/day dose level. There was no evidence of modulation of other polyamines or precursors. Fifteen patients experienced a complete (5 patients) or partial (10 patients) histological response. In conclusion, DFMO was well tolerated and significantly modulated tissue SPD:SPM ratio and plasma arginine level at the dose of 1.000 g/m2/day. To clarify whether DFMO has activity at lower doses, these results will be tested in a three-armed double-blinded Phase II study using placebo and DFMO doses of 0.500 and 0.125 g/m2/day. PMID:9516915

Mitchell, M F; Tortolero-Luna, G; Lee, J J; Hittelman, W N; Lotan, R; Wharton, J T; Hong, W K; Nishioka, K

1998-02-01

294

Expression of 19 microRNAs in glioblastoma and comparison with other brain neoplasia of grades I-III.  

PubMed

Several biomarkers have been proposed as useful parameters to better specify the prognosis or to delineate new target therapy strategies for glioblastoma patients. MicroRNAs could represent putative target molecules, considering their role in tumorigenesis, cancer progression and their specific tissue expression. Although several studies have tried to identify microRNA signature for glioblastoma, a microRNA profile is still far from being well-defined. In this work the expression of 19 microRNAs (miR-7, miR-9, miR-9?, miR-10a, miR-10b, miR-17, miR-20a, miR-21, miR-26a, miR-27a, miR-31, miR-34a, miR-101, miR-137, miR-182, miR-221, miR-222, miR-330, miR-519d) was evaluated in sixty formalin-fixed and paraffin-embedded glioblastoma samples using a locked nucleic acid real-time PCR. Moreover, a comparison of miRNA expressions was performed between primary brain neoplasias of different grades (grades IV-I). The analysis of 14 validated miRNA expression in the 60 glioblastomas, using three different non-neoplastic references as controls, revealed a putative miRNA signature: mir-10b and miR-21 were up-regulated, while miR-7, miR-31, miR-101, miR-137, miR-222 and miR-330 were down-regulated in glioblastomas. Comparing miRNA expression between glioblastoma group and gliomas of grades I-III, 3 miRNAs (miR-10b, mir-34a and miR-101) showed different regulation statuses between high-grade and low-grade tumors. miR-10b was up-regulated in high grade and significantly down-regulated in low-grade gliomas, suggesting that could be a candidate for a GBM target therapy. This study provides further data for the identification of a miRNA profile for glioblastoma and suggests that different-grade neoplasia could be characterized by different expression of specific miRNAs. PMID:24412053

Visani, Michela; de Biase, Dario; Marucci, Gianluca; Cerasoli, Serenella; Nigrisoli, Evandro; Bacchi Reggiani, Maria Letizia; Albani, Fiorenzo; Baruzzi, Agostino; Pession, Annalisa

2014-03-01

295

The angiotensin-I-converting enzyme inhibitor enalapril and aspirin delay progression of pancreatic intraepithelial neoplasia and cancer formation in a genetically engineered mouse model of pancreatic cancer  

Microsoft Academic Search

Background and aimsThere are no chemopreventive strategies for pancreatic cancer or its precursor lesions, pancreatic intraepithelial neoplasia (PanINs). Recent evidence suggests that aspirin and inhibitors of angiotensin-I converting enzyme (ACE inhibitors) have potential chemopreventive properties. In this study, we used a genetically engineered mouse model of pancreatic cancer to evaluate the chemopreventive potential of these drugs.MethodsDrug treatment was initiated at

Volker Fendrich; Nai-Ming Chen; Meike Neef; Jens Waldmann; Malte Buchholz; Georg Feldmann; Emily P Slater; Anirban Maitra; Detlef K Bartsch

2010-01-01

296

A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma  

Microsoft Academic Search

MULTIPLE endocrine neoplasia type 2 (MEN 2) comprises three clinically distinct, dominantly inherited cancer syndromes. MEN 2A patients develop medullary thyroid carcinoma (MTC) and phaeochromocytoma. MEN 2B patients show in addition ganglioneuromas of the gastrointestinal tract and skeletal abnormalities. In familial MTC, only the thyroid is affected. Germ-line mutations of the RET proto-oncogene have recently been reported in association with

Robert M. W. Hofstra; Rudy M. Landsvater; Isabella Ceccherini; Rein P. Stulp; Tineke Stelwagen; Yin Luo; Barbara Pasini; Jo W. M. Hoppener; Hans Kristian Ploos van Amstel; Giovanni Romeo; Cornells J. M. Lips; Charles H. C. M. Buys

1994-01-01

297

Birt-Hogg-Dubé renal tumors are genetically distinct from other renal neoplasias and are associated with up-regulation of mitochondrial gene expression  

Microsoft Academic Search

BACKGROUND: Germline mutations in the folliculin (FLCN) gene are associated with the development of Birt-Hogg-Dubé syndrome (BHDS), a disease characterized by papular skin lesions, a high occurrence of spontaneous pneumothorax, and the development of renal neoplasias. The majority of renal tumors that arise in BHDS-affected individuals are histologically similar to sporadic chromophobe renal cell carcinoma (RCC) and sporadic renal oncocytoma.

Jeff A Klomp; David Petillo; Natalie M Niemi; Karl J Dykema; Jindong Chen; Ximing J Yang; Annika Sääf; Peter Zickert; Markus Aly; Ulf Bergerheim; Magnus Nordenskjöld; Sophie Gad; Sophie Giraud; Yves Denoux; Laurent Yonneau; Arnaud Méjean; Viorel Vasiliu; Stéphane Richard; Jeffrey P MacKeigan; Bin T Teh; Kyle A Furge

2010-01-01

298

Case-control study of risk factors for cervical neoplasia in Denmark. II. Role of sexual activity, reproductive factors, and venereal infections  

Microsoft Academic Search

Sexual, reproductive and venereal risk factors for cervical neoplasia were investigated in a population-based case-control study of 586 women with histologically verified, cervical squamous-cell carcinoma in situ, and 59 women with invasive squamous-cell cervical cancer, diagnosed from 1985 to 1986 in Copenhagen. Cases were identified from the computerized Danish Cancer Registry. An age-stratified control group (n=614) was drawn at random

Susanne K. Kjaer; Claus Dahl; Gerda Engholm; Johannes E. Bock; Elsebeth Lynge; Ole M. Jensen

1992-01-01

299

A rapid screening method for the detection of mutations in the RET proto-oncogene in multiple endocrine neoplasia type 2A and familial medullary thyroid carcinoma families  

Microsoft Academic Search

Multiple endocrine neoplasia type 2A (MEN2A) and familial medullary thyroid carcinoma (FMTC) are autosomal dominant inherited cancer syndromes with incomplete penetrance. Following the identification of mutations in the RET proto-oncogene that segregate with the disease phenotype in MEN2A, MEN2B, and FMTC, genetic screening of individuals with mutations in RET may be performed. The authors have employed restriction endonuclease digestion of

D. J. Marsh; S. Andrew; A. L. Richardson

1994-01-01

300

The associations between statin use and prostate cancer screening, prostate size, high-grade prostatic intraepithelial neoplasia (PIN), and prostate cancer  

Microsoft Academic Search

Objective  Prior studies report statins may reduce the risk of advanced prostate cancer. This study investigates the association between\\u000a statin use and the likelihood of having a PSA or DRE test, blood PSA levels, prostate volume, and the severity of lower urinary\\u000a tract symptoms. We also describe the association between statin use and prostate cancer and high-grade prostatic intraepithelial\\u000a neoplasia (PIN)

Jay H. Fowke; Saundra S. Motley; Daniel A. Barocas; Michael S. Cookson; Raoul Concepcion; Susan Byerly; Joseph A. Smith

2011-01-01

301

Risk factors for second primary neoplasia of esophagus in newly diagnosed head and neck cancer patients: a case–control study  

PubMed Central

Background The prevalence of esophageal neoplasia in head and neck (H&N) cancer patients is not low; however, routine esophageal surveillance is not included in staging of newly-diagnosed H&N cancers. We aimed to investigate the risk factors for synchronous esophageal neoplasia and the impact of endoscopy on management of H&N cancer patients. Methods A total of 129 newly diagnosed H&N cancer patients who underwent endoscopy with white-light imaging, narrow-band imaging (NBI) with magnifying endoscopy (ME), and chromoendoscopy with 1.5% Lugol’s solution, before definite treatment were enrolled prospectively. Results 60 esophageal lesions were biopsied from 53 (41.1%) patients, including 11 low-grade, 14 high-grade intraepithelial neoplasia and 12 invasive carcinoma in 30 (23.3%) patients. Alcohol consumption [odds ratio (OR) 5.90, 95% confidence interval (CI) 1.23-26.44], advanced stage (stage III and IV) of index H&N cancers (OR 2.98, 95% CI 1.11-7.99), and lower body mass index (BMI) (every 1-kg/m2 increment with OR 0.87, 95% CI 0.76-0.99) were independent risk factors for synchronous esophageal neoplasia. NBI with ME was the ideal screening tool (sensitivity, specificity, and accuracy of 97.3%, 94.1%, and 96.3%, respectively, for detection of dysplastic and cancerous esophageal lesions). The treatment strategy was modified after endoscopy in 20 (15.5%) patients. The number needed to screen was 6.45 (95% CI 4.60-10.90). Conclusions NBI-ME surveillance of esophagus should be done in newly-diagnosed H&N cancer patients, especially those with alcohol drinking, lower BMI, and advanced stage of primary tumor. PMID:24456340

2013-01-01

302

Single Missense Mutation in the Tyrosine Kinase Catalytic Domain of the RET Protooncogene is Associated with Multiple Endocrine Neoplasia Type 2B  

Microsoft Academic Search

Multiple endocrine neoplasia type 2B (MEN 2B) is a human cancer syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytomas, mucosal neuromas, ganglioneuromas of the intestinal tract, and skeletal and ophthalmic abnormalities. It appears both as an inherited disorder and as de novo disease. Sequence analysis of germ-line DNA from MEN 2B patients revealed the existence of the same point mutation

Katrin M. Carlson; Shenshen Dou; David Chi; N. Scavarda; Koi Toshima; C. E. Jackson; Samuel A. Wells; Paul Goodfellow; Helen Donis-Keller

1994-01-01

303

Characterizing T-cell response in low-grade and high-grade vulval intraepithelial neoplasia, study of CD3, CD4 and CD8 expressions  

Microsoft Academic Search

Objective. The objective of our study was to compare immunocyte infiltrates in vulval epithelium from low-grade and high-grade vulval intraepithelial neoplasia (VIN) lesions to determine if difference in T-cell presence reflected the grade of VIN.Material and methods. Thirty-six vulval specimens were obtained from 24 patients who had previously undergone vulval biopsies for VIN, 14 high-grade diseases (VIN 3 with or

Nahid Gul; Raji Ganesan; David M Luesley

2004-01-01

304

Off-pump coronary artery bypass surgery in patients with coronary artery disease and malign neoplasia: results of ten patients and review of the literature  

Microsoft Academic Search

Cardiopulmonary bypass has been reported to have many effects on the immune system. The aim of this study was to investigate\\u000a the efficiency and usefulness of off-pump coronary artery bypass (OPCAB) surgery on patients who had coronary artery disease\\u000a besides malign neoplasia. We applied OPCAB operations to 217 patients between March 2001 and April 2004, ten of whom had malign

?brahim Özsöyler; Levent Yilik; ?ahin Bozok; Bilgin Emrecan; Mert Kestell?; Nagihan Karahan; Ali Gürbüz

2006-01-01

305

Birt-Hogg-Dubé syndrome: mapping of a novel hereditary neoplasia gene to chromosome 17p12-q11.2  

Microsoft Academic Search

Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant neoplasia syndrome characterized mainly by benign skin tumors, and to a lesser extent, renal tumors and spontaneous pneumothorax. To map the BHD locus, we performed a genome-wide linkage analysis using polymorphic microsatellite markers on a large Swedish BHD family. Evidence of linkage was identified on chromosome 17p12-q11.2, with a maximum LOD score of

Sok Kean Khoo; Maria Bradley; Fung Ki Wong; Mari-Anne Hedblad; Magnus Nordenskjöld; Bin Tean Teh

2001-01-01

306

Risk factors of having high-grade cervical intraepithelial neoplasia/invasive carcinoma in women with atypical glandular cells of undetermined significance smears.  

PubMed

The objective of this study was to find the risk factors of having high-grade cervical intraepithelial neoplasia/invasive carcinoma in women with atypical glandular cells of undetermined significance (AGUS) smears. A retrospective study of the women with AGUS smears during the 3-year period was performed to determine the correlation between the suspected variables and the histopathologic diagnoses. Among 44,071 smears performed, 119 (0.27%) smears were reported as AGUS. Colposcopies were performed in 102 (88.7%) cases, and high-grade cervical intraepithelial neoplasia/invasive carcinoma was found in 18 (17.6%) cases. Among the following variables, which included age, menopausal status, hormonal contraception, history of previous Pap smears, medical diseases, clinical symptoms, and subclassification of AGUS, both hormonal contraception and AGUS favor neoplasia were risk factors with an odds ratio of 5.4 and 5.0, respectively. Although clinical symptoms seemed to be a significant variable in univariate analysis, it appeared as a confounding factor in multivariate analysis. PMID:16681727

Chichareon, S B; Tocharoenvanich, S

2006-01-01

307

Lack of association between the rs2294008 polymorphism in the prostate stem cell antigen gene and colorectal neoplasia: a case-control and immunohistochemical study  

PubMed Central

Background Prostate stem cell antigen (PSCA) has been implicated in the pathogenesis of several solid tumours, either due to changes in protein expression, or through association with the rs2294008 polymorphism in the PSCA gene. To our knowledge, the role of PSCA in the development of colorectal neoplasia has not been explored. We performed a genotyping study to assess for associations between the rs2294008 polymorphism and risk of adenomatous polyps and colorectal cancer. DNA samples were available from 388 individuals with colorectal neoplasia and 496 controls, all of whom had undergone screening colonoscopy. In addition, we performed immunohistochemical staining for PSCA in colonic tissue representing all stages of the adenoma-carcinoma sequence. Results No genotypic associations were found between the rs2294008 polymorphism and the risk of colorectal adenomata or cancer. Immunohistochemical staining did not reveal any alteration in PSCA expression accompanying the adenoma-carcinoma sequence. Conclusion From these data it seems unlikely that PSCA has a role in the initiation or progression of colorectal neoplasia. PMID:22824379

2012-01-01

308

Frequency of multiple endocrine neoplasia type 1 in a group of patients with pituitary adenoma: genetic study and familial screening.  

PubMed

The purpose of this study it was to evaluate the frequency of Multiple Endocrine Neoplasia type 1 (MEN1) in patients with pituitary adenoma and to perform genetic analysis and familial screening of those individuals afflicted with MEN1. 144 patients with pituitary adenoma at Botucatu Medical School, UNESP-Univ Estadual Paulista, were assessed retrospectively for MEN1 during the years of 2005-2011. The patients were evaluated for the presence of primary hyperparathyroidism (PHP) and enteropancreatic tumors. Genetic analysis was performed for the individuals with clinically diagnosed MEN1. Thirteen patients met the diagnostic criteria for MEN1, but three individuals belong to the same family and they were considered as a single MEN1 event, revealing 7.7 % frequency of MEN1 in this patient group. Genetic analysis showed MEN1 mutations in four index cases: IVS4+1 G>A, IVS3-6 C>T, c.1547insC and a new D180A mutation. One patient did not agree to participate in the genetic study and another one was referred for follow up in other hospital. Only polymorphisms were found in the other individuals, one of which was novel. We identified a high frequency of MEN1 in pituitary adenoma patients. Since PHP is one of the most common MEN1 tumor and patients are mostly asymptomatic, we suggest that all pituitary adenoma patients have their calcium profile analyzed. PMID:23334809

Nunes, V S; Souza, G L; Perone, D; Conde, S J; Nogueira, C R

2014-02-01

309

Ultra High-Resolution Anterior Segment Optical Coherence Tomography in the Diagnosis and Management of Ocular Surface Squamous Neoplasia  

PubMed Central

The development of optical coherence tomography (OCT) technology has helped to usher in a new era of in vivo diagnostic imaging of the eye. The utilization of OCT for imaging of the anterior segment and ocular surface has evolved from time-domain devices to spectral-domain devices with greater penetrance and resolution, providing novel images of anterior segment pathology to assist in diagnosis and management of disease. Ocular surface squamous neoplasia (OSSN) is one such pathology that has proven demonstrable by certain anterior segment OCT machines, specifically the newer devices capable of performing ultra high-resolution OCT (UHR-OCT). Distinctive features of OSSN on high resolution OCT allow for diagnosis and differentiation from other ocular surface pathologies. Subtle findings on these images help to characterize the OSSN lesions beyond what is apparent with the clinical examination, providing guidance for clinical management. The purpose of this review is to examine the published literature on the utilization of UHR-OCT for the diagnosis and management of OSSN, as well as to report novel uses of this technology and potential directions for its future development. PMID:24439046

Thomas, Benjamin J.; Galor, Anat; Nanji, Afshan A.; Sayyad, Fouad El; Wang, Jianhua; Dubovy, Sander R.; Joag, Madhura G.; Karp, Carol L.

2014-01-01

310

Bitter melon extract impairs prostate cancer cell-cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model.  

PubMed

Prostate cancer remains the second leading cause of cancer deaths among American men. Earlier diagnosis increases survival rate in patients. However, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment and prevention are necessary for inhibiting disease progression to a hormone refractory state. One of the approaches to control prostate cancer is prevention through diet, which inhibits one or more neoplastic events and reduces the cancer risk. For centuries, Ayurveda has recommended the use of bitter melon (Momordica charantia) as a functional food to prevent and treat human health related issues. In this study, we have initially used human prostate cancer cells, PC3 and LNCaP, as an in vitro model to assess the efficacy of bitter melon extract (BME) as an anticancer agent. We observed that prostate cancer cells treated with BME accumulate during the S phase of the cell cycle and modulate cyclin D1, cyclin E, and p21 expression. Treatment of prostate cancer cells with BME enhanced Bax expression and induced PARP cleavage. Oral gavage of BME, as a dietary compound, delayed the progression to high-grade prostatic intraepithelial neoplasia in TRAMP (transgenic adenocarcinoma of mouse prostate) mice (31%). Prostate tissue from BME-fed mice displayed approximately 51% reduction of proliferating cell nuclear antigen expression. Together, our results suggest for the first time that oral administration of BME inhibits prostate cancer progression in TRAMP mice by interfering cell-cycle progression and proliferation. PMID:21911444

Ru, Peng; Steele, Robert; Nerurkar, Pratibha V; Phillips, Nancy; Ray, Ratna B

2011-12-01

311

Bitter melon extract impairs prostate cancer cell cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model  

PubMed Central

Prostate cancer remains the second leading cause of cancer deaths among American men. Earlier diagnosis increases survival rate in patients. However, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment and prevention are necessary for inhibiting disease progression to a hormone refractory state. One of the approaches to control prostate cancer is prevention through diet, which inhibits one or more neoplastic events and reduces the cancer risk. For centuries, Ayurveda has recommended the use of bitter melon (Momordica charantia) as a functional food to prevent and treat human health related issues. In this study, we have initially used human prostate cancer cells, PC3 and LNCaP, as an in vitro model to assess the efficacy of bitter melon extract (BME) as an anti-cancer agent. We observed that prostate cancer cells treated with BME accumulate during the S phase of the cell cycle, and modulate cyclin D1, cyclin E and p21 expression. Treatment of prostate cancer cells with BME enhanced Bax expression, and induced poly(ADP-ribose) polymerase cleavage. Oral gavage of BME, as a dietary compound, delayed the progression to high grade prostatic intraepithelial neoplasia (PIN) in TRAMP (transgenic adenocarcinoma of mouse prostate) mice (31%). Prostate tissue from BME-fed mice displayed ~51% reduction of PCNA expression. Together, our results suggest for the first time that oral administration of BME inhibits prostate cancer progression in TRAMP mice by interfering cell cycle progression and proliferation. PMID:21911444

Ru, Peng; Steele, Robert; Nerurkar, Pratibha V.; Phillips, Nancy; Ray, Ratna

2011-01-01

312

A novel papillomavirus isolated from a nasal neoplasia in an Italian free-ranging chamois (Rupicapra r. rupicapra).  

PubMed

Most amniotes are the hosts of many, distantly related papillomaviruses (PVs). Infection by PVs can be asymptomatic, or lead instead to benign or malignant lesions. However, PVs infecting animals and associated with malignancies are still largely understudied. In the present study, we communicate the complete genome of a novel PV found in a nasal neoplasia of a free-ranging alpine chamois (Rupicapra r. rupicapra) in an Italian national park. Long-PCR and cloning approaches followed for Sanger sequencing were used to identify the first PV found in chamois. The genome of the novel virus - RrupPV1 - of 7256 bp in length, presents the classical PV structure, and lacks the interE2-L2 region that hosts the E5 gene in AlphaPVs and in DeltaPVs. The nucleotide identity percentage of the L1 ORF, places RrupPV1 together with OaPV3 in the same genus. The latter is a PV isolated from a squamous cell carcinoma in sheep in Sardinia. Full-genome phylogenetic reconstructions suggest that these two viruses are sister taxa, and that both of them are very distantly related to any other known PV. Many cetartiodactyl species are infected by non-monophyletic PVs. Our results exemplify further the multiple links between the infection by certain, distantly related PVs and the development of diverse cancers in animals and highlight the need of a systematic search of oncogenic and non-oncogenic animal PVs. PMID:24910075

Mengual-Chuliá, Beatriz; Domenis, Lorenzo; Robetto, Serena; Bravo, Ignacio G

2014-08-01

313

Skin reactions to human papillomavirus (HPV) 16 specific antigens intradermally injected in healthy subjects and patients with cervical neoplasia.  

PubMed

We have tested the safety and feasibility of a synthetic long peptide-based HPV16-specific skin test to detect cellular immune responses to HPV16 E2, E6 and E7 in vivo. Women with cervical neoplasia (n = 11) and healthy individuals (n = 19) were intradermally challenged with 8 different pools of HPV16 E2, E6 and E7 peptides. The skin test was safe as the injections were perceived as mildly painful and no adverse events were observed. The majority of skin reactions appeared significantly earlier in HPV16+ patients (<8 days) than in healthy subjects (8-25 days). The development of late skin reactions in healthy subjects was associated with the appearance of circulating HPV16-specific T cells and the infiltration of both HPV16-specific CD4+ Th1/Th2 and CD8+ T cells into the skin. These data show that the intradermal injection of pools of HPV16 synthetic long peptides is safe and results in the migration of HPV16-specific T cells into the skin as well as in an increase in the number of circulating HPV16-specific T cells. The use of this test to measure HPV16-specific immunity is currently tested in a low resource setting for the measurement of spontaneously induced T-cell responses as well as in our HPV16 vaccination trials for the detection of vaccine-induced immunity. PMID:18404684

van den Hende, Muriel; van Poelgeest, Mariëtte I E; van der Hulst, Jeanette M; de Jong, Joan; Drijfhout, Jan W; Fleuren, Gert Jan; Valentijn, A Rob P M; Wafelman, Amon R; Slappendel, Gijs M; Melief, Cornelis J M; Offringa, Rienk; van der Burg, Sjoerd H; Kenter, Gemma G

2008-07-01

314

Multiple Endocrine Neoplasia Type 1 with Multiple Leiomyomas Linked to a Novel Mutation in the MEN1 Gene  

PubMed Central

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited syndrome. MEN1 is characterized by the presence of functioning and nonfunctioning tumors or hyperplasia of the pituitary gland, parathyroid glands, and pancreatic islet cells. In addition, MEN1 carriers can have adrenal or thyroid tumors and non-endocrine tumors, such as lipomas, angiofibromas, and leiomyomas. Although leiomyoma is not a major component of MEN1, it is thought to occur more frequently than expected. However, there has been no report of a case of MEN1 with leiomyoma in Korea so far. This report describes a patient with multiple leiomyomas in MEN1. A 50-year-old woman was referred for further evaluation of elevated calcium levels and osteoporosis. Biochemical abnormalities included hypercalcemia with elevated parathyroid hormone. There was hyperprolactinemia with pituitary microadenoma in sella MRI. An abdominal MRI demonstrated adrenal nodules and leiomyomas in the bladder and uterus. Endoscopic ultrasonography demonstrated esophageal leiomyoma and pancreatic islet cell tumor. A subtotal parathyroidectomy with thymectomy was performed. Sequencing of the MEN1 gene in this patient revealed a novel missense mutation (D350V, exon 7). This is the first case of MEN1 accompanied with multiple leiomyomas, parathyroid adenoma, pituitary adenoma, pancreatic tumor, and adrenal tumor. PMID:18729310

Choi, Heekyoung; Kim, Sehyun; Moon, Jae-Hoon; Lee, Yoon Hee; Kang, Eun Seok; Ahn, Chul Woo; Cha, Bong Soo; Lee, Eun Jig; Kim, Kyung Rae; Lee, Hyun Chul; Jeong, Seon Yong; Kim, Hyun Ju; Lim, Sung-Kil

2008-01-01

315

Patients with usual vulvar intraepithelial neoplasia-related vulvar cancer have an increased risk of cervical abnormalities  

PubMed Central

Background: Vulvar squamous cell carcinoma (SCC) originates the following two pathways, related to differentiated (d) vulvar intraepithelial neoplasia (VIN) or to human papillomavirus (HPV)-related usual (u) VIN. Multicentric HPV infections (cervix, vagina and vulva) are common. We hypothesise that patients with a uVIN-related vulvar SCC more often have cervical high-grade squamous intraepithelial lesions (HSILs) compared with women with dVIN-related vulvar SCC. Methods: All vulvar SCCs (201) were classified to be dVIN- (n=164) or uVIN related (n=37). Data with regard to the smear history and cervical histology were retrieved from PALGA, the nationwide Netherlands database of histo- and cytopathology. For HSIL cervical smears of which histology was taken, HPV DNA analysis on both the vulvar and cervical specimens was performed. Results: At least one smear was available in 145 (72%) of the 201 patients. Patients with a uVIN-related vulvar SCC more often had an HSIL compared with patients with a dVIN-related SCC (35 vs 2%, P<0.001). A total of 10 of the 13 HSILs were histologically assessed and identical HPV types were found in the vulva and cervix. Conclusion: These data emphasise the necessity to differentiate between dVIN- and uVIN-related vulvar tumours and to examine the entire lower female ano-genital tract once an uVIN-related lesion is found. PMID:19513077

de Bie, R P; van de Nieuwenhof, H P; Bekkers, R L M; Melchers, W J G; Siebers, A G; Bulten, J; Massuger, L F A G; de Hullu, J A

2009-01-01

316

Safety and tolerability of DIM-based therapy designed as personalized approach to reverse prostatic intraepithelial neoplasia (PIN)  

PubMed Central

Background It has been shown previously that novel formulation of 3,3'-diindolylmethane (DIM) substance with high bioavailability (Infemin) inhibits tumor development due to the tumor growth rate reduction in the xenograft model of prostate cancer. Prostatic intraepithelial neoplasia (PIN) is considered to be promising as a personalized and preventive treatment strategy of prostate cancer (PC). We assessed the safety of Infemin in men with PIN and discussed the interim results. Materials and methods A total of 14 patients with PIN were enrolled. They were randomized to 900 mg DIM or placebo daily for 3 months. Safety was evaluated by adverse events (AEs), laboratory tests and physical examinations. Results and conclusion The trial revealed that Infemin treatment is associated with minimal toxicity and no serious adverse events when administered orally for 3 months. We noted three adverse events including nausea and diarrhea in two patients (14%). Combined 95% confidence interval (CI) was 1.8%–42.8%. Therapy was continued in all cases of adverse events. Good tolerability of DIM-based formulation allows us to recommend it for further clinical trials among men diagnosed with PIN for its efficacy and long-term safety parameters. PMID:25309637

2014-01-01

317

Ultra high-resolution anterior segment optical coherence tomography in the diagnosis and management of ocular surface squamous neoplasia.  

PubMed

The development of optical coherence tomography (OCT) technology has helped to usher in a new era of in vivo diagnostic imaging of the eye. The utilization of OCT for imaging of the anterior segment and ocular surface has evolved from time-domain devices to spectral-domain devices with greater penetrance and resolution, providing novel images of anterior segment pathology to assist in diagnosis and management of disease. Ocular surface squamous neoplasia (OSSN) is one such pathology that has proven demonstrable by certain anterior segment OCT machines, specifically the newer devices capable of performing ultra high-resolution OCT (UHR-OCT). Distinctive features of OSSN on high resolution OCT allow for diagnosis and differentiation from other ocular surface pathologies. Subtle findings on these images help to characterize the OSSN lesions beyond what is apparent with the clinical examination, providing guidance for clinical management. The purpose of this review is to examine the published literature on the utilization of UHR-OCT for the diagnosis and management of OSSN, as well as to report novel uses of this technology and potential directions for its future development. PMID:24439046

Thomas, Benjamin J; Galor, Anat; Nanji, Afshan A; El Sayyad, Fouad; Wang, Jianhua; Dubovy, Sander R; Joag, Madhura G; Karp, Carol L

2014-01-01

318

Molecular detection of human papillomavirus in Brazilian women with cervical intraepithelial neoplasia in a northeast Brazilian city.  

PubMed

We examined the prevalence of human papillomavirus (HPV) infection in Brazilian women with cervical intraepithelial neoplasia. Our goal was to identify the types of HPV and their association with risk factors. This prospective cross-sectional study included 97 samples collected from women aged 14-79 years at the public health units of gynecological care in São Luís, MA, Brazil. HPV detection was performed by nested polymerase chain reaction and sequence analysis. The study patients completed a structured questionnaire to provide information regarding their socio-demographic, clinical, and behavioral status. HPV prevalence was found to be 80.4%, with 17 virus types detected, including HPV 16, 18, 58, 6, and 11. Significant associations between HPV infection and age and frequency of doctor visits were identified. The study findings indicate the significance of age and low frequency of visits to the gynecologist as risk factors for genital HPV infection, suggesting that HPV infection-derived cervical cancer could be prevented through orientation programs for women, which include sex education and information regarding screening tests. We also found an increased prevalence of high-risk HPV serotypes in cervical lesions, which reveals an association between cervical lesions and high-risk HPV. PMID:25366799

Nunes, J D C; Vidal, F C B; Ferraro, C T L; Chein, M B C; Brito, L M O; Monteiro, S C M

2014-01-01

319

Quick Chili Con Carne Ingredients  

E-print Network

Quick Chili Con Carne Ingredients: 16 ounces kidney beans, canned 1 pound ground turkey 1/2 onion 1 is cooking, cut the ends off of the onion, and peel off the brown layers. Cut onion in half and place flat side down. Slice into thin strips keeping onion together. Turn and slice again to dice. 4. Slice green

Liskiewicz, Maciej

320

[CONs].  

PubMed

In 2012, USA Preventive Services Task Force revised the guidelines for prostate cancer screening and recommended against prostate specific antigen(PSA)-based screening for prostate cancer for all age groups. This revision had a great impact worldwide. Immediately after the announcement, many expert societies expressed disagreement with this revision, but some of these have gradually come to accept it. When multiple organizations develop guidelines for a particular topic, the recommendations may differ. In this regard, the "standards for developing trustworthy clinical practice guidelines" presented in the report by the Institute of Medicine, will be helpful. The number of cases and the incidence rates of prostate cancer have been rapidly increasing in Japan, especially in the elderly population. Accordingly, sufficient information needs to be provided for appropriate decision-making, considering the balance between the risks and benefits, if cancer screening in the elderly population is to be implemented. PMID:24917002

Sobue, Tomotaka

2014-05-01

321

Immunohistochemical expression of SP-NK-1R-EGFR pathway and VDR in colonic inflammation and neoplasia  

PubMed Central

AIM: To determine the expression of neurokinin-1 receptor (NK-1R), phosphorylated epidermal growth factor receptor (pEGFR), cyclooxygenase-2 (Cox-2), and vitamin D receptor (VDR) in normal, inflammatory bowel disease (IBD), and colorectal neoplasia tissues from Puerto Ricans. METHODS: Tissues from patients with IBD, colitis-associated colorectal cancer (CAC), sporadic dysplasia, and sporadic colorectal cancer (CRC), as well as normal controls, were identified at several centers in Puerto Rico. Archival formalin-fixed, paraffin-embedded tissues were de-identified and processed by immunohistochemistry for NK-1R, pEGFR, Cox-2, and VDR. Pictures of representative areas of each tissues diagnosis were taken and scored by three observers using a 4-point scale that assessed intensity of staining. Tissues with CAC were further analyzed by photographing representative areas of IBD and the different grades of dysplasia, in addition to the areas of cancer, within each tissue. Differences in the average age between the five patient groups were assessed with one-way analysis of variance and Tukey-Kramer multiple comparisons test. The mean scores for normal tissues and tissues with IBD, dysplasia, CRC, and CAC were calculated and statistically compared using one-way analysis of variance and Dunnett’s multiple comparisons test. Correlations between protein expression patterns were analyzed with the Pearson’s product-moment correlation coefficient. Data are presented as mean ± SE. RESULTS: On average, patients with IBD were younger (34.60 ± 5.81) than normal (63.20 ± 6.13, P < 0.01), sporadic dysplasia (68.80 ± 4.42, P < 0.01), sporadic cancer (74.80 ± 4.91, P < 0.001), and CAC (57.50 ± 5.11, P < 0.05) patients. NK-1R in cancer tissue (sporadic CRC, 1.73 ± 0.34; CAC, 1.57 ± 0.53) and sporadic dysplasia (2.00 ± 0.45) were higher than in normal tissues (0.73 ± 0.19). pEGFR was significantly increased in sporadic CRC (1.53 ± 0.43) and CAC (2.25 ± 0.47) when compared to normal tissue (0.07 ± 0.25, P < 0.05, P < 0.001, respectively). Cox-2 was significantly increased in sporadic colorectal cancer (2.20 ± 0.23 vs 0.80 ± 0.37 for normal tissues, P < 0.05). In comparison to normal (2.80 ± 0.13) and CAC (2.50 ± 0.33) tissues, VDR was significantly decreased in sporadic dysplasia (0.00 ± 0.00, P < 0.001 vs normal, P < 0.001 vs CAC) and sporadic CRC (0.47 ± 0.23, P < 0.001 vs normal, P < 0.001 vs CAC). VDR levels negatively correlated with NK-1R (r = -0.48) and pEGFR (r = -0.56) in normal, IBD, sporadic dysplasia and sporadic CRC tissue, but not in CAC. CONCLUSION: Immunohistochemical NK-1R and pEGFR positivity with VDR negativity can be used to identify areas of sporadic colorectal neoplasia. VDR immunoreactivity can distinguish CAC from sporadic cancer. PMID:25684939

Isidro, Raymond A; Cruz, Myrella L; Isidro, Angel A; Baez, Axel; Arroyo, Axel; González-Marqués, William A; González-Keelan, Carmen; Torres, Esther A; Appleyard, Caroline B

2015-01-01

322

An inducible knockout mouse to model the cell-autonomous role of PTEN in initiating endometrial, prostate and thyroid neoplasias.  

PubMed

PTEN is one of the most frequently mutated tumor suppressor genes in human cancers. The role of PTEN in carcinogenesis has been validated by knockout mouse models. PTEN heterozygous mice develop neoplasms in multiple organs. Unfortunately, the embryonic lethality of biallelic excision of PTEN has inhibited the study of complete PTEN deletion in the development and progression of cancer. By crossing PTEN conditional knockout mice with transgenic mice expressing a tamoxifen-inducible Cre-ER(T) under the control of a chicken actin promoter, we have generated a tamoxifen-inducible mouse model that allows temporal control of PTEN deletion. Interestingly, administration of a single dose of tamoxifen resulted in PTEN deletion mainly in epithelial cells, but not in stromal, mesenchymal or hematopoietic cells. Using the mT/mG double-fluorescent Cre reporter mice, we demonstrate that epithelial-specific PTEN excision was caused by differential Cre activity among tissues and cells types. Tamoxifen-induced deletion of PTEN resulted in extremely rapid and consistent formation of endometrial in situ adenocarcinoma, prostate intraepithelial neoplasia and thyroid hyperplasia. We also analyzed the role of PTEN ablation in other epithelial cells, such as the tubular cells of the kidney, hepatocytes, colonic epithelial cells or bronchiolar epithelium, but those tissues did not exhibit neoplastic growth. Finally, to validate this model as a tool to assay the efficacy of anti-tumor drugs in PTEN deficiency, we administered the mTOR inhibitor everolimus to mice with induced PTEN deletion. Everolimus dramatically reduced the progression of endometrial proliferations and significantly reduced thyroid hyperplasia. This model could be a valuable tool to study the cell-autonomous mechanisms involved in PTEN-loss-induced carcinogenesis and provides a good platform to study the effect of anti-neoplastic drugs on PTEN-negative tumors. PMID:23471917

Mirantes, Cristina; Eritja, Núria; Dosil, Maria Alba; Santacana, Maria; Pallares, Judit; Gatius, Sónia; Bergadà, Laura; Maiques, Oscar; Matias-Guiu, Xavier; Dolcet, Xavier

2013-05-01

323

A phase I and pharmacodynamic study of the histone deacetylase inhibitor belinostat plus azacitidine in advanced myeloid neoplasia.  

PubMed

Background We hypothesized that targeting two mechanisms of epigenetic silencing would be additive or synergistic with regard to expression of specific target genes. The primary objective of the study was to establish the maximum tolerated dose (MTD) of belinostat in combination with a fixed dose of azacitidine (AZA). Methods In Part A of the study, patients received a fixed dose of AZA, with escalating doses of belinostat given on the same days 1-5, in a 28 day cycle. Part B was designed to evaluate the relative contribution of belinostat to the combination based on analysis of pharmacodynamic markers, and incorporated a design in which patients were randomized during cycle 1 to AZA alone, or the combination, at the maximally tolerated dose of belinostat. Results 56 patients with myeloid neoplasia were enrolled. Dose escalation was feasible in part A, up to 1000 mg/m(2) dose level of belinostat. In Part B, 18 patients were assessable for quantitative analysis of specific target genes. At day 5 of therapy, MDR1 was significantly up-regulated in the belinostat/AZA arm compared with AZA alone arm (p?=?0.0023). There were 18 responses among the 56 patients. Conclusions The combination of belinostat and AZA is feasible and associated with clinical activity. The recommended phase II dose is 1000 mg/m(2) of belinostat plus 75 mg/m(2) of AZA on days 1-5, every 28 days. Upregulation in MDR1 was observed in the combination arm at day 5 compared with the AZA alone arm, suggesting a relative biologic contribution of belinostat to the combination. PMID:25483416

Odenike, Olatoyosi; Halpern, Anna; Godley, Lucy A; Madzo, Jozef; Karrison, Theodore; Green, Margaret; Fulton, Noreen; Mattison, Ryan J; Yee, Karen W L; Bennett, Meghan; Koval, Gregory; Malnassy, Gregory; Larson, Richard A; Ratain, Mark J; Stock, Wendy

2014-12-01

324

Zyflamend in men with high-grade prostatic intraepithelial neoplasia: results of a phase I clinical trial.  

PubMed

Subjects diagnosed with high-grade prostatic intraepithelial neoplasia (HGPIN) at biopsy are at increased risk for developing prostate cancer (CaP). A prospective clinical trial was done to determine the safety and tolerability of a novel herbal amalgam, Zyflamend (New Chapter, Inc., Brattleboro, VT), with various dietary supplements in subjects with HGPIN. Men ages 40 to 75 years with HGPIN were eligible. Subjects were evaluated for 18 months. Every 3 months, standard blood chemistries and prostate-specific antigen (PSA) were monitored. Rebiopsy was done every 6 months. Tissue was evaluated for HGPIN or CaP and stained for cyclooxygenase-2, nuclear factor kappaB (NF-kappaB), interleukin-6, and thromboxane. Twenty-three subjects were evaluable. The median age was 64.1 years (range 46-75 years), and the mean (+/- SD) PSA level was 6.13 +/- 3.56 ng/mL. Side effects, when present, were mild and gastrointestinal in nature. There were no reported serious adverse events or toxicities. No significant changes in blood chemistries, testosterone, or cardiac function were noted. Forty-eight percent of subjects demonstrated a 25 to 50% decrease in PSA after 18 months. Of subjects who had the 18-month biopsy, 60% (9 of 15) had benign tissue, 26.7% (4 of 15) had HGPIN in one core, and 13.3% (2 of 15) had CaP at 18 months. A reduction in serum C-reactive protein was observed (95% confidence interval [CI] 0.7-1.7, p = .045). Immunoreactive staining demonstrated a reduction in NF-kappaB in the 18-month samples (95% CI 0.8-3.0, p = .017). Zyflamend alone and in combination with various dietary supplements is associated with minimal toxicity and no serious adverse events when administered orally for 18 months. Further studies are warranted to evaluate these agents in patients who are at risk for CaP. PMID:19476738

Capodice, Jillian L; Gorroochurn, Prakash; Cammack, A Sam; Eric, Goluboff; McKiernan, James M; Benson, Mitchell C; Stone, Brian A; Katz, Aaron E

2009-01-01

325

Predictive DNA testing and prophylactic thyroidectomy in patients at risk for multiple endocrine neoplasia type 2A.  

PubMed Central

BACKGROUND: Missense germ-line mutations in the RET protooncogene are associated with multiple endocrine neoplasia type 2A (MEN 2A). Detection of these mutant alleles in kindred members predicts disease inheritance and provides the basis for preventative thyroidectomy. METHODS: A polymerase chain reaction (PCR)-based genetic test for the 19 known RET mutations was designed to study 132 members of 7 kindreds with MEN 2A. Haplotypes also were constructed using genetic markers flanking the MEN 2A locus. Plasma calcitonin (CT) concentrations were determined before and after provocative testing. RESULTS: Direct DNA testing and haplotype analysis showed that 21 of 58 kindred members at risk for disease had inherited a mutation in the RET protooncogene associated with MEN 2A. Plasma CT concentrations were elevated in 9 of the 21 family members, but were normal in 12. After genetic counseling, 13 of the 21 kindred members (6 with normal and seven with elevated plasma CT levels), consented to immediate thyroidectomy. In each patient, the resected thyroid gland showed C-cell hyperplasia with or without medullary thyroid carcinoma. There were no metastases to regional lymph nodes, and postoperative stimulated plasma CT levels were normal. CONCLUSION: The PCR-based direct DNA test for RET mutations is accurate, rapid, and reproducible. For all 132 individuals evaluated, the results of direct DNA analysis were consistent with haplotype studies. The direct test for mutations in the RET protooncogene is the preferred method for screening MEN 2A kindreds. In family members who have inherited a RET mutation, total thyroidectomy is indicated, regardless of the plasma CT values. Images Figure 2A. Figure 2B. Figure 3. Figure 4.,Figure 5. PMID:7916559

Wells, S A; Chi, D D; Toshima, K; Dehner, L P; Coffin, C M; Dowton, S B; Ivanovich, J L; DeBenedetti, M K; Dilley, W G; Moley, J F

1994-01-01

326

Chitinase 3-Like-1 Expression in Colonic Epithelial Cells as a Potentially Novel Marker for Colitis-Associated Neoplasia  

PubMed Central

Chitinase 3-like-1 (CHI3L1/YKL-40) is a protein secreted from restricted cell types including colonic epithelial cells (CECs) and macrophages. CHI3L1 is an inflammation-associated molecule, and its expression is enhanced in persons with colitis and colon cancer. The biological function of CHI3L1 on CECs is unclear. In this study, we investigated the role of CHI3L1 on CECs during the development of colitis-associated neoplasia. We analyzed colonic samples obtained from healthy persons and from persons with ulcerative colitis with or without premalignant or malignant changes. DNA microarray and RT-PCR analyses significantly increased CHI3L1 expression in non-dysplastic mucosa from patients with inflammatory bowel disease (IBD) who had dysplasia/adenocarcinoma compared with that in healthy persons and in patients with IBD who did not have dysplasia. As determined by IHC, CHI3L1 was expressed in specific cell types in the crypts of colonic biopsies obtained from patients with ulcerative colitis who have remote dysplasia. Purified CHI3L1 efficiently activated the NF-?B signaling pathway and enhanced the secretion of IL-8 and TNF-? in SW480 human colon cancer cells. In addition, colon cancer cell proliferation and migration were significantly promoted in response to CHI3L1 in these cells. In summary, CHI3L1 may contribute to the proliferation, migration, and neoplastic progression of CECs under inflammatory conditions and could be a useful biomarker for neoplastic changes in patients with IBD. PMID:21763261

Chen, Chun-Chuan; Pekow, Joel; Llado, Victoria; Kanneganti, Manasa; Lau, Cindy W.; Mizoguchi, Atsushi; Mino-Kenudson, Mari; Bissonnette, Marc; Mizoguchi, Emiko

2011-01-01

327

Trisomy of the Dscr1 gene suppresses early progression of pancreatic intraepithelial neoplasia driven by oncogenic Kras  

SciTech Connect

Highlights: •A single extra copy of Dscr1 restrains progression of PanIN-1A to PanIN-1B lesions. •Dscr1 trisomy attenuates calcineurin–NFAT pathway in neoplastic ductal epithelium. •Dscr1 trisomy leads to upregulation of p15{sup INK4b} in neoplastic ductal epithelium. •A single extra copy of Dscr1 reduces epithelial proliferation in early PanIN lesions. •Dscr1 trisomy may protect Down syndrome individuals from pancreatic cancer. -- Abstract: Individuals with Down syndrome exhibit remarkably reduced incidence of most solid tumors including pancreatic cancer. Multiple mechanisms arising from the genetic complexity underlying Down syndrome has been suggested to contribute to such a broad cancer protection. In this study, utilizing a genetically engineered mouse model of pancreatic cancer, we demonstrate that trisomy of the Down syndrome critical region-1 (Dscr1), an endogenous calcineurin inhibitor localized on chromosome 21, suppresses the progression of pancreatic intraepithelial neoplasia-1A (PanIN-1A) to PanIN-1B lesions without affecting the initiation of PanIN lesions mediated by oncogenic Kras{sup G12D}. In addition, we show that Dscr1 trisomy attenuates nuclear localization of nuclear factor of activated T-cells (NFAT) accompanied by upregulation of the p15{sup Ink4b} tumor suppressor and reduction of cell proliferation in early PanIN lesions. Our data suggest that attenuation of calcineurin–NFAT signaling in neoplastic pancreatic ductal epithelium by a single extra copy of Dscr1 is sufficient to inhibit the progression of early PanIN lesions driven by oncogenic Kras, and thus may be a potential mechanism underlying reduced incidence of pancreatic cancer in Down syndrome individuals.

Lee, Jang Choon; Shin, Jimin; Baek, Kwan-Hyuck, E-mail: khbaek@skku.edu

2013-10-11

328

A Transcript Map for the 2.8-Mb Region Containing the Multiple Endocrine Neoplasia Type 1?Locus  

PubMed Central

Multiple endocrine neoplasia type 1 (MEN 1) is an inherited cancer syndrome in which affected individuals develop multiple parathyroid, enteropancreatic, and pituitary tumors. The locus for MEN1 is tightly linked to the marker PYGM on chromosome 11q13, and linkage analysis places the MEN1 gene within a 2-Mb interval flanked by the markers D11S1883 and D11S449. Loss of heterozygosity studies in MEN 1 and sporadic tumors suggest that the MEN1 gene encodes a tumor suppressor and have helped to narrow the location of the gene to a 600-kb interval between PYGM and D11S449. Focusing on this smaller MEN1 interval, we have identified and mapped 12 transcripts to this 600-kb region. A precise ordered map of 33 transcripts, including 12 genes known to map to this region, was generated for the 2.8-Mb D11S480–D11S913 interval. Fifteen candidate genes (of which 10 were examined exhaustively) were evaluated by Southern blot and/or dideoxy fingerprinting analysis to identify the gene harboring disease-causing mutations. [The sequence data described in this paper have been submitted to GenBank under accession nos. EST06996, U93236, AF001540–AF001547, AF001433–AF001436, AF001891–AF001893, N55476, R19205, and W37647 (see Table 1 for listing of transcripts). The BAC clone sequences have been submitted to GenBank under accession nos. AC000134, AC000159, and AC000353.] PMID:9253601

Guru, Siradanahalli C.; Agarwal, Sunita K.; Manickam, Pachiappan; Olufemi, Shodimu-Emmanuel; Crabtree, Judy S.; Weisemann, Jane M.; Kester, Mary Beth; Kim, Young S.; Wang, Yingping; Emmert-Buck, Michael R.; Liotta, Lance A.; Spiegel, Allen M.; Boguski, Mark S.; Roe, Bruce A.; Collins, Francis S.; Marx, Stephen J.; Burns, Lee; Chandrasekharappa, Settara C.

1997-01-01

329

Human papillomavirus, high-grade intraepithelial neoplasia and killer immunoglogulin-like receptors: a Western Australian cohort study  

PubMed Central

Background Human papillomavirus (HPV) is the causative agent in cervical cancer and HPV genotypes 16 and 18 cause the majority of these cancers. Natural killer (NK) cells destroy virally infected and tumour cells via killer immunoglobulin-like receptors (KIR) that recognize decreased MHC class I expression. These NK cells may contribute to clearance of HPV infected and/or dysplastic cells, however since KIR controls NK cell activity, KIR gene variation may determine outcome of infection. Methods KIR gene frequencies were compared between 147 patients with a history of high-grade cervical intraepithelial neoplasia (CIN) and a control population of 187, to determine if any KIR genes are associated with high-grade CIN. In addition a comparison was also made between cases of high grade CIN derived from 30 patients infected with HPV 16/18 and 29 patients infected with non-16/18 HPV to determine if KIR variation contributes to the disproportional carcinogenesis derived from HPV 16/18 infection. Results High-grade CIN was weakly associated with the absence of KIR2DL2 and KIR2DS2 (p?=?0.046 and 0.049 respectively, OR 0.6; 95% CI 0.4 – 0.9) but this association was lost after correction for multi-gene statistical analysis. No difference in KIR gene frequencies was found between high-grade CIN caused by HPV 16/18 and non-16/18. Conclusion No strong association between KIR genes, high-grade CIN and HPV genotype was found in the Western Australian population. PMID:24011088

2013-01-01

330

Research Resource: Estrogen-Driven Prolactin-Mediated Gene-Expression Networks in Hormone-Induced Prostatic Intraepithelial Neoplasia  

PubMed Central

Cotreatment with testosterone (T) and 17?-estradiol (E2) is an established regimen for inducing of prostatic intraepithelial neoplasia (PIN) and prostate cancer in rodent models. We previously used the pure antiestrogen ICI 182,780 (ICI) and bromocriptine, a dopamine receptor agonist, to inhibit PIN induction and systemic hyperprolactinemia in Noble rats and found that the carcinogenic action of T+E2 is mediated directly by the effects of E2 on the prostate and/or indirectly via E2-induced hyperprolactinemia. In this study, we delineate the specific action(s) of E2 and prolactin (PRL) in early prostate carcinogenesis by an integrated approach combining global transcription profiling, gene ontology, and gene-network mapping. We identified 2504 differentially expressed genes in the T+E2-treated lateral prostate. The changes in expression of a subset of 1990 genes (?80%) were blocked upon cotreatment with ICI and bromocriptine, respectively, whereas those of 262 genes (?10%) were blocked only by treatment with ICI, suggesting that E2-induced pituitary PRL is the primary mediator of the prostatic transcriptional response to the altered hormone milieu. Bioinformatics analyses identified hormone-responsive gene networks involved in immune responses, stromal tissue remodeling, and the ERK pathway. In particular, our data suggest that IL-1? may mediate, at least in part, hormone-induced changes in gene expression during PIN formation. Together, these data highlight the importance of pituitary PRL in estrogen-induced prostate tumorigenesis. The identification of both E2- and pituitary PRL-responsive genes provides a comprehensive resource for future investigations of the complex mechanisms by which changes in the endocrine milieu contribute to prostate carcinogenesis in vivo. PMID:20861223

Tam, Neville N.C.; Szeto, Carol Y.Y.; Freudenberg, Johannes M.; Fullenkamp, Amy N.; Medvedovic, Mario; Ho, Shuk-Mei

2010-01-01

331

Altered membrane lipid composition and functional parameters of circulating cells in cockles (Cerastoderma edule) affected by disseminated neoplasia.  

PubMed

Membrane lipid composition and morpho-functional parameters were investigated in circulating cells of the edible cockle (Cerastoderma edule) affected by disseminated neoplasia (neoplastic cells) and compared to those from healthy cockles (hemocytes). Membrane sterol levels, phospholipid (PL) class and subclass proportions and their respective fatty acid (FA) compositions were determined. Morpho-functional parameters were evaluated through total hemocyte count (THC), mortality rate, phagocytosis ability and reactive oxygen species (ROS) production. Both morpho-functional parameters and lipid composition were profoundly affected in neoplastic cells. These dedifferentiated cells displayed higher THC (5×), mortality rate (3×) and ROS production with addition of carbonyl cyanide m-chloro phenylhydrazone (1.7×) but lower phagocytosis ability (½×), than unaffected hemocytes. Total PL amounts were higher in neoplastic cells than in hemocytes (12.3 and 5.1 nmol×10(-6) cells, respectively). However, sterols and a particular subclass of PL (plasmalogens; 1-alkenyl-2-acyl PL) were present in similar amounts in both cell type membranes. This led to a two times lower proportion of these membrane lipid constituents in neoplastic cells when compared to hemocytes (20.5% vs. 42.1% of sterols in total membrane lipids and 21.7% vs. 44.2% of plasmalogens among total PL, respectively). Proportions of non-methylene interrupted FA- and 20:1n-11-plasmalogen molecular species were the most impacted in neoplastic cells when compared to hemocytes (?× and ¼×, respectively). These changes in response to this leukemia-like disease in bivalves highlight the specific imbalance of plasmalogens and sterols in neoplastic cells, in comparison to the greater stability of other membrane lipid components. PMID:23333874

Le Grand, Fabienne; Soudant, Philippe; Marty, Yanic; Le Goïc, Nelly; Kraffe, Edouard

2013-01-01

332

Cytomegalovirus-induced salivary gland pathology: AREG, FGF8, TNF-?, and IL-6 signal dysregulation and neoplasia.  

PubMed

Mucoepidermoid carcinoma (MEC) is the most common malignant tumor originating in major and minor salivary glands (SGs). Although the precise multifactorial etiology of human SG-MEC is largely unknown, we have recently shown that cytomegalovirus (CMV) is an important component of MEC tumorigenesis. Despite the well-documented overexpression of the EGFR ? ERK signaling pathway in SG-MEC, there has been limited to no clinical success with inhibition of this pathway. Using our previously characterized mouse model of CMV-induced SG dysplasia/neoplasia, we report that inhibitors of the EGFR ? ERK pathway do not ameliorate or rescue well-established pathology, either singly or in combination, but they do inhibit the evolution of progressive pathogenesis ("disease tolerance") in the face of mounting CMV burden. Failure to rescue SG pathology, suggested a possible increase in the ligand levels of alternative pathways that share cell proliferation and survival effectors (e.g. ERK and PI3K). Here we present evidence of a highly significant upregulation of ligands for the EGFR, FGFR, IL-6R, and TNFR signaling pathways, all of which converge upon the Raf/MEK/ERK amplifier module. This explains our finding that even in the presence of the highest nontoxic dose of an ERK phosphorylation inhibitor, pERK is undiminished. Given the considerable pathway crosstalk, a deep understanding of subversion and dysregulation of the SG interactome by CMV is a priori quite daunting. Circumventing this dilemma, we present evidence that concurrent inhibition of ERK phosphorylation (U0126) and CMV replication (acyclovir) obviates progressive pathogenesis and results in complete SG rescue (tumor regression). These findings provide a mechanistic foundation for potential clinical trials that utilize similar concurrent treatment with extant FDA-approved drugs. PMID:23399805

Melnick, Michael; Deluca, Krysta A; Sedghizadeh, Parish P; Jaskoll, Tina

2013-04-01

333

Epizootic neoplasia of the lateral line system of lake trout (Salvelinus namaycush) in New York's Finger Lakes.  

PubMed

This article documents an epizootic of inflammation and neoplasia selectively affecting the lateral line system of lake trout (Salvelinus namaycush) in 4 Finger Lakes in New York from 1985 to 1994. We studied more than 100 cases of this disease. Tumors occurred in 8% (5/64) of mature and 21% (3/14) of immature lake trout in the most severely affected lake. Lesions consisted of 1 or more neoplasm(s) in association with lymphocytic inflammation, multifocal erosions, and ulcerations of the epidermis along the lateral line. Lesions progressed from inflammatory to neoplastic, with 2-year-old lake trout showing locally extensive, intense lymphocytic infiltrates; 2- to 3-year-old fish having multiple, variably sized white masses up to 3 mm in diameter; and fish over 5 years old exhibiting 1 or more white, cerebriform masses greater than 1 cm in diameter. Histologic diagnoses of the tumors were predominantly spindle cell sarcomas or benign or malignant peripheral nerve sheath neoplasms, with fewer epitheliomas and carcinomas. Prevalence estimates did not vary significantly between sexes or season. The cause of this epizootic remains unclear. Tumor transmission trials, virus isolation procedures, and ultrastructural study of lesions failed to reveal evidence of a viral etiology. The Finger Lakes in which the disease occurred did not receive substantially more chemical pollution than unaffected lakes in the same chain during the epizootic, making an environmental carcinogen an unlikely primary cause of the epizootic. A hereditary component, however, may have contributed to this syndrome since only fish of the Seneca Lake strain were affected. PMID:23528941

Spitsbergen, J M; Frattini, S A; Bowser, P R; Getchell, R G; Coffee, L L; Wolfe, M J; Fisher, J P; Marinovic, S J; Harr, K E

2013-05-01

334

Risk Factors for the Presence of Anal Intraepithelial Neoplasia in HIV+ Men Who Have Sex with Men  

PubMed Central

Objective Anal Intraepithelial Neoplasia (AIN) is present in the majority of HIV+ men who have sex with men (MSM) and routine AIN-screening is subject of discussion. In this study we analysed a wide range of potential risk factors for AIN in order to target screening programs. Methods We screened 311 HIV+ MSM by high resolution anoscopy, with biopsies of suspect lesions. HIV-parameters, previous sexual transmitted infections (STI’s), anal pathology, sexual practices and substance use were analysed in relation to AIN by uni- and multivariable logistic regression. Results AIN (any grade) was found in 175/311 MSM (56%), high grade (HG)AIN in 30%. In the univariable analysis, years since HIV diagnosis, years of antiretroviral therapy (cART) and anal XTC use decreased AIN risk, while a history of anogenital warts and use of GHB (?-hydroxybutyric acid) increased this risk. In the multivariable analysis three parameters remained significant: years of cART (OR=0.92 per year, p=0.003), anal XTC use (OR=0.10, p=0.002) and GHB use (OR=2.60, p=0.003). No parameters were significantly associated with HGAIN, but there was a trend towards increased risk with anal enema use prior to sex (>50 times ever; p=0.07) and with a history of AIN (p=0.06). CD4 count, STI’s, anal pathology, smoking, number of sex partners and anal fisting were not associated with (HG)AIN. Conclusion GHB use increases the risk for AIN, while duration of cART and anal XTC use are negatively correlated with AIN. Given the high prevalence of AIN in HIV+ MSM, these associations are not helpful to guide a screening program. PMID:24367625

Richel, Olivier; De Vries, Henry J. C.; Dijkgraaf, Marcel G. W.; Van Noesel, Carel J. M.; Prins, Jan M.

2013-01-01

335

Cytokine expression in the cervical stroma of HIV-positive and HIV-negative women with cervical intraepithelial neoplasia.  

PubMed

Cervical intraepithelial neoplasias (CINs) are a major public health issue. The prevalence of CINs is higher in women with the human immunodeficiency virus (HIV). The objective of this study was to determine whether there are differences in the immune responses in the cervical stroma of HIV-infected and -uninfected women with CIN. The responses were assessed according to the immunohistochemical expression of cytokines interleukin (IL)-4, IL-12, interferon gamma (IFN-?), and tumor growth factor beta (TGF-?). In addition, we determined whether there were differences in the local immune responses between patients with CIN1 and CIN 2/3. A cross-sectional study was performed using material collected by cervical conization in HIV-infected and -uninfected women with CIN. The conization was performed using loop electrical excision procedure (LEEP) from January 1999 to May 2004. The evaluation of cytokines in the cervical stroma was based on immunohistochemistry. No differences were found between the two groups of women regarding HIV status. However, the associations between IL-12 expression and CIN 2/3 (p=0.016) in HIV-infected women and between IL-4 expression and CIN 1 (p=0.0456) in HIV-infected women were significant when the interaction between HIV infection and lesion grade was assessed. Additionally, a significant association between TGF-? expression and CIN 2/3 in both groups was observed regardless of HIV infection (p=0.000). An interaction between HIV infection and CIN grade was detected because IL-12 and IL-4 expression increased in the presence of HIV infection. Regarding the CIN grade, there was a high prevalence of TGF-? in CIN 2/3 lesions, which reflected the predominance of an immunoregulatory environment. PMID:25014220

Guimarães, Mirian Viviane Maciel Barros; Michelin, Márcia Antoniazi; Lucena, Adriana Almeida de Souza; Lodi, Claudia Teixeira da Costa; Lima, Maria Inês de Miranda; Murta, Eddie Fernando Cândido; Melo, Victor Hugo

2014-09-01

336

Cooperation between ectopic FGFR1 and depression of FGFR2 in induction of prostatic intraepithelial neoplasia in the mouse prostate.  

PubMed

Disruption of the regulatory communication from the stroma to the epithelium mediated by the FGF7/10-FGFR2 signaling axis in the prostate and expression of ectopic FGFR1 in prostatic epithelial cells often correlate with prostate cancer progression both in human and in experimental animals. Ectopic expression of constitutively active FGFR1 mutant (caFGFR1) at low levels in prostate epithelial cells induces low- to intermediate-grade prostatic intraepithelial neoplasia (PIN) within 6-8 months and high-grade PIN in 20-25 months. Depression of the FGFR2 signaling in the prostate also disturbs homeostasis in the prostate and induces prostate hyperplasia. To study whether PIN lesions induced by the caFGFR1 were expression-level dependent, and whether expression of the caFGFR1 and depression of the FGFR2 signaling in the prostate synergistically disturbed prostate homeostasis, we generated two new strains of ARR2PBi-caFGFR1 transgenic mice, which highly expressed caFGFR1 in prostatic epithelial cells. The mice were crossed with KDNR mice to generate ARR2PBi-caFGFR1/KDNR bigenic mice. The ARR2PBi-caFGFR1 mice developed high-grade PIN within 8 months, which was significantly faster than the mice expressing caFGFR1 at low levels. In addition, depression of the FGFR2 signaling clearly promoted perturbation of cellular homeostasis induced by the caFGFR1. The results demonstrated that the PIN development in caFGFR1 transgenic mice was caFGFR1 dosage-dependent, and indicated that the ectopic FGFR1 and the resident FGFR2 in epithelial cells had opposite impacts on intercompartmental homeostasis in the prostate. The bigenic mice provide a model with cooperative aberrations in the fibroblast growth factor signaling axis for evaluation of tumor-initiating events in prostate tumorigenesis. PMID:14695195

Jin, Chengliu; McKeehan, Kerstin; Guo, Wei; Jauma, Scot; Ittmann, Michael M; Foster, Barbara; Greenberg, Norman M; McKeehan, Wallace L; Wang, Fen

2003-12-15

337

Fibroblast growth factor 8 isoform B overexpression in prostate epithelium: a new mouse model for prostatic intraepithelial neoplasia.  

PubMed

Fibroblast growth factor 8 isoform b (FGF8b), a mitogenic and transforming polypeptide, was demonstrated to be naturally up-regulated in prostatic premalignant and malignant lesions in men. We generated four independent lines of transgenic mice with targeted overexpression of FGF8b in the prostatic epithelium using an improved rat probasin promoter, ARR(2)PB. Transgene expression in the prostate tissue was readily demonstrated by reverse transcription-PCR and localized to the prostatic epithelium by in situ hybridization. The histopathology of the prostate tissues was followed in different age groups of the various lines but most extensively in one line (line 3), starting from 1 month of age up to 24 months. Prostatic hyperplasia appeared in the lateral and ventral prostates in some animals as early as 2-3 months and in other lobes between 6 and 16 months. Beginning at 5-7 months, dysplasia, akin to what may be considered low-grade prostatic intraepithelial neoplasia (LGPIN) in humans, was detected. During the first 14 months, 100% of animals exhibited multifocal epithelial hyperplasia; 35% also had areas of LGPIN. This profile changed in subsequent months (15-24 months) to a higher incidence of LGPIN (66%) along with high-grade PIN (HGPIN) lesions (51%). Similar to HGPIN, stromal proliferation and appearance of papillary hyperplasia with atypia displayed a delayed pattern. The affected stroma consisted primarily of the smooth muscle cell component. The incidence of chronic inflammation, mostly involving T cells, was higher in the prostate of the transgenic mice relative to controls; however, the presence of a direct correlation between inflammation and hyperplasia or preneoplastic lesions was not identified. These transgenic mice represent a "natural" animal model for investigating the mechanism of development and progression of prostatic diseases, such as prostatic hyperplasia and preneoplastic lesions. PMID:12208767

Song, Zhigang; Wu, Xiantuo; Powell, William C; Cardiff, Robert D; Cohen, Michael B; Tin, Robert T; Matusik, Robert J; Miller, Gary J; Roy-Burman, Pradip

2002-09-01

338

Angiogenin-stimulated Ribosomal RNA Transcription Is Essential for Initiation and Survival of AKT-induced Prostate Intraepithelial Neoplasia  

PubMed Central

Angiogenin (ANG), originally identified as an angiogenic ribonuclease, has recently been shown to play a direct role in prostate cancer cell proliferation by mediating ribosomal RNA (rRNA) transcription. ANG is upregulated in human prostate cancer and is the most significantly upregulated gene in AKT-driven prostate intraepithelial neoplasia (PIN) in mice. Enhanced cell proliferation in the PIN lesions requires increased ribosome biogenesis, a multistep process involving an orchestrated production of ribosomal proteins and rRNA. AKT is known to enhance ribosomal protein production through the mammalian target of rapamycin (mTOR) pathway. However, it was unknown how rRNA is proportionally increased. Here, we report that ANG is essential for AKT-driven PIN formation and survival. We showed that upregulation of ANG in the AKT over-expressing mouse prostates is an early and lasting event. It occurs before PIN initiation and lasts beyond PIN is fully developed. Knocking-down ANG expression by intraprostate injection of lentivirus-mediated ANG-specific siRNA prevents AKT-induced PIN formation without affecting AKT expression and its signaling through the mTOR pathway. Neomycin, an aminoglycoside that blocks nuclear translocation of ANG, and N65828, a small-molecule enzymatic inhibitor of the ribonucleolytic activity of ANG, both prevent AKT-induced PIN formation and reverse established PIN. They also decrease nucleolar organizer region (NOR), restore cell size, and normalize luminal architectures of the prostate despite continuous activation of AKT. All three types of the ANG inhibitor suppress rRNA transcription of the prostate luminal epithelial cells and inhibit AKT-induced PIN indicating an essential role of ANG in AKT-mediated cell proliferation and survival. PMID:19258415

Ibaragi, Soichiro; Yoshioka, Norie; Kishikawa, Hiroko; Hu, Jamie K.; Sadow, Peter M.; Li, Ming; Hu, Guo-fu

2009-01-01

339

HPV-negative vulvar intraepithelial neoplasia (VIN) with basaloid histologic pattern: an unrecognized variant of simplex (differentiated) VIN.  

PubMed

Vulvar intraepithelial neoplasia (VIN) is classified into 2 clinicopathologic subtypes, classic, related to human papillomavirus (HPV) infection and affecting relatively young women, and simplex (differentiated), negative for HPV and affecting elderly women. Histologically, classic VIN may be basaloid and characterized by a replacement of the whole epidermis by a homogeneous population of small, "undifferentiated" keratinocytes, which are diffusely positive for p16(INK4a) and negative for p53. Simplex VIN is characterized by atypia of the basal layer with high degree of cellular differentiation and shows negative staining for p16(INK4a) and frequent positivity for p53. Simplex VIN is frequently associated with squamous cell hyperplasia and lichen sclerosus. From a series of 110 invasive squamous cell carcinomas of the vulva negative for HPV by highly sensitive polymerase chain reaction, 51 had VIN lesions located at least 1 cm away from the tumor. In 4 (7.8%) cases, the VIN had basaloid histologic features. All cases showed obvious architectural disorganization with a homogeneous population of basaloid, undifferentiated keratinocytes with scanty cytoplasm replacing the whole epidermis. Immunohistochemically, all cases were negative for p16(INK4a) and strongly positive for p53 with suprabasilar extension of positive cells. All patients were postmenopausal (median age 61.0 y; range, 45-76). Squamous cell hyperplasia was identified in 1 case and lichen sclerosus in 1 case. The invasive squamous cell carcinoma was of keratinizing type in 3 cases and basaloid in 1 case. In conclusion, simplex, HPV-negative VIN may occasionally have basaloid morphology. Immunostaining for p16(INK4a) and p53 protein may be helpful in the identification of these lesions and the differential diagnosis with classic, HPV-positive basaloid VIN. PMID:19730361

Ordi, Jaume; Alejo, Maria; Fusté, Victòria; Lloveras, Belen; Del Pino, Marta; Alonso, Immaculada; Torné, Aureli

2009-11-01

340

RISK FOR CERVICAL INTRAEPITHELIAL NEOPLASIA GRADE 3 OR WORSE IN RELATION TO SMOKING AMONG WOMEN WITH PERSISTENT HUMAN PAPILLOMAVIRUS INFECTION  

PubMed Central

Background Smoking has been associated with cervical cancer. We examined whether smoking increases the risk for high-grade cervical lesions in women with high-risk human papillomavirus (HPV) infection. Methods In a population-based cohort study, 8,656 women underwent a structured interview, and subsequently cervical cells were obtained for HPV DNA testing. Women with high-risk HPV infection and no prevalent cervical disease at baseline (n=1,353) were followed through the Pathology Data Bank for cervical lesions for up to 13 years. Separate analyses of women with persistent high-risk HPV infection were also conducted. Hazard ratios (HRs) for a diagnosis of cervical intraepithelial neoplasia grade 3 or worse/high-grade squamous intraepithelial lesions or worse (CIN3+) and the corresponding 95% confidence intervals (CIs) were calculated in the 2 groups. Results Among high-risk HPV positive women an increased risk for CIN3+ was associated with long-term smoking (?10 years) and heavy smoking (?20 cigarettes/day). In the subgroup of women with persistent HPV infection heavy smoking was also associated with a statistically significantly higher risk for CIN3+ than never smoking (HR, 1.85; 95% CI, 1.05–3.22, adjusted for length of schooling, parity and HPV type at baseline). The average number of cervical cytology screening tests per year during follow-up did not explain the differences in risk in relation to smoking (p=0.4). Conclusions Smoking is associated with an increased risk for subsequent high-grade cervical lesions in women with persistent high-risk HPV infection. Impact Our study adds to the understanding of the role of smoking in the natural history of HPV and cervical carcinogenesis. PMID:23019238

Jensen, Kirsten Egebjerg; Schmiedel, Sven; Frederiksen, Kirsten; Norrild, Bodil; Iftner, Thomas; Kjær, Susanne K.

2014-01-01

341

VEGF elicits epithelial-mesenchymal transition (EMT) in prostate intraepithelial neoplasia (PIN)-like cells via an autocrine loop  

SciTech Connect

Vascular endothelial growth factor (VEGF) is overexpressed during the transition from prostate intraepithelial neoplasia (PIN) to invasive carcinoma. We have mimicked such a process in vitro using the PIN-like C3(1)/Tag-derived Pr-111 cell line, which expresses low levels of VEGF and exhibits very low tumorigenicity in vivo. Elevated expression of VEGF164 in Pr-111 cells led to a significant increase in tumorigenicity, invasiveness, proliferation rates and angiogenesis. Moreover, VEGF164 induced strong changes in cell morphology and cell transcriptome through an autocrine mechanism, with changes in TGF-beta1- and cytoskeleton-related pathways, among others. Further analysis of VEGF-overexpressing Pr-111 cells or following exogenous addition of recombinant VEGF shows acquisition of epithelial-mesenchymal transition (EMT) features, with an increased expression of mesenchymal markers, such as N-cadherin, Snail1, Snail2 (Slug) and vimentin, and a decrease in E-cadherin. Administration of VEGF led to changes in TGF-beta1 signaling, including reduction of Smad7 (TGF-beta inhibitory Smad), increase in TGF-betaR-II, and translocation of phospho-Smad3 to the nucleus. Our results suggest that increased expression of VEGF in malignant cells during the transition from PIN to invasive carcinoma leads to EMT through an autocrine loop, which would promote tumor cell invasion and motility. Therapeutic blockade of VEGF/TGF-beta1 in PIN lesions might impair not only tumor angiogenesis, but also the early dissemination of malignant cells outside the epithelial layer.

Gonzalez-Moreno, Oscar [Laboratory of Novel Therapeutic Targets, Division of Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Avda. Pio XII, 55, 31008 Pamplona (Spain)] [Laboratory of Novel Therapeutic Targets, Division of Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Avda. Pio XII, 55, 31008 Pamplona (Spain); Lecanda, Jon [Digna Biotech, and Department of Biochemistry, University of Navarra, Pamplona (Spain)] [Digna Biotech, and Department of Biochemistry, University of Navarra, Pamplona (Spain); Green, Jeffrey E. [Laboratory of Cancer Biology and Genetics, NCI, NIH, Bethesda , MD (United States)] [Laboratory of Cancer Biology and Genetics, NCI, NIH, Bethesda , MD (United States); Segura, Victor [Unit of Proteomics, Genomics and Bioinformatics, CIMA, University of Navarra, Pamplona (Spain)] [Unit of Proteomics, Genomics and Bioinformatics, CIMA, University of Navarra, Pamplona (Spain); Catena, Raul; Serrano, Diego [Laboratory of Novel Therapeutic Targets, Division of Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Avda. Pio XII, 55, 31008 Pamplona (Spain)] [Laboratory of Novel Therapeutic Targets, Division of Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Avda. Pio XII, 55, 31008 Pamplona (Spain); Calvo, Alfonso, E-mail: acalvo@unav.es [Laboratory of Novel Therapeutic Targets, Division of Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Avda. Pio XII, 55, 31008 Pamplona (Spain)] [Laboratory of Novel Therapeutic Targets, Division of Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Avda. Pio XII, 55, 31008 Pamplona (Spain)

2010-02-15

342

Evaluation of Ki67, p16 and CK17 Markers in Differentiating Cervical Intraepithelial Neoplasia and Benign Lesions  

PubMed Central

Background: Cervical intraepithelial neoplasia (CIN) is a premalignant lesion capable of progressing to cervical cancer. Despite the existing well-defined criteria, the histomorphologic diagnosis is subject to high rates of discordance among pathologists. The aim of this study was to evaluate Ki-67 (MIB-1), CK17 and p16 INK4a (p16) markers by immunohistochemical methods in differentiating CIN from benign cervical lesions. Methods: The present study reviewed and re-classified 77 cervical biopsies, originally diagnosed as 31 non-CIN, and 46 CIN, as 54 non-CIN, and 23 CIN based on at least two similar diagnoses. Immunostaining by Ki67, p16 and CK17 markers was performed on all cases and the results were compared with pervious and consensus diagnosis. Results: The overall agreement between pervious and consensus diagnosis was 67.5% (Kappa=0.39, P<0.001). The sensitivity and specificity of Ki67 immunostaining were 95.6% and 85.1% respectively, while for p16 the corresponding values were 91.3% and 98.1%. The overall agreement, for both p16 and Ki67, with consensus diagnosis were significant (P<0.001). The sensitivity and specificity of CK17 negative staining in CIN detection were 39.1% and 40.7% respectively. Conclusion: Ki67 and p16 markers are recommended as complementary tests for differentiating between dysplastic and non-dysplastic lesions. CK17 does not discriminate between immature metaplasia with and without dysplasia. PMID:23645953

Sari Aslani, Fatemeh; Safaei, Akbar; Pourjabali, Masoumeh; Momtahan, Mozhdeh

2013-01-01

343

Computacion inteligente con organismos vivos  

E-print Network

resoluci´on. 2 / 37 #12;Computaci´on y M´aquinas ... VIVAS e INTELIGENTES 3 / 37 #12;Modelo de computaci tediosas... ... y otras tareas inteligentes. 7 / 37 #12;M´aquinas de prop´osito espec´ifico Desde el ´abacoComputaci´on inteligente con organismos vivos Mario de Jes´us P´erez Jim´enez Grupo de Investigaci

Jiménez, Mario de J. Pérez

344

The Jak2 Inhibitor, G6, Alleviates Jak2-V617F-Mediated Myeloproliferative Neoplasia by Providing Significant Therapeutic Efficacy to the Bone Marrow1  

PubMed Central

We recently developed a Janus kinase 2 (Jak2) small-molecule inhibitor called G6 and found that it inhibits Jak2-V617F-mediated pathologic cell growth in vitro, ex vivo, and in vivo. However, its ability to inhibit Jak2-V617F-mediated myeloproliferative neoplasia, with particular emphasis in the bone marrow, has not previously been examined. Here, we investigated the efficacy of G6 in a transgenic mouse model of Jak2-V617F-mediated myeloproliferative neoplasia. We found that G6 provided therapeutic benefit to the peripheral blood as determined by elimination of leukocytosis, thrombocytosis, and erythrocytosis. G6 normalized the pathologically high plasma concentrations of interleukin 6 (IL-6). In the liver, G6 eliminated Jak2-V617F-driven extramedullary hematopoiesis. With respect to the spleen, G6 significantly reduced both the splenomegaly and megakaryocytic hyperplasia. In the critically important bone marrow, G6 normalized the pathologically high levels of phospho-Jak2 and phospho-signal transducer and activator of transcription 5 (STAT5). It significantly reduced the megakaryocytic hyperplasia in the marrow and completely normalized the M/E ratio. Most importantly, G6 selectively reduced the mutant Jak2 burden by 67%on average, with virtual elimination of mutant Jak2 cells in one third of all treated mice. Lastly, clonogenic assays using marrow stem cells from the myeloproliferative neoplasm mice revealed a time-dependent elimination of the clonogenic growth potential of these cells by G6. Collectively, these data indicate that G6 exhibits exceptional efficacy in the peripheral blood, liver, spleen, and, most importantly, in the bone marrow, thereby raising the possibility that this compound may alter the natural history of Jak2-V617F-mediated myeloproliferative neoplasia. PMID:22131881

Kirabo, Annet; Park, Sung O; Majumder, Anurima; Gali, Meghanath; Reinhard, Mary K; Wamsley, Heather L; Zhao, Zhizhuang Joe; Cogle, Christopher R; Bisht, Kirpal S; Keserü, György M; Sayeski, Peter P

2011-01-01

345

todasuvida: Las personas con diabetes son ms  

E-print Network

diabetes Controlesu todasuvida: Las personas con diabetes son más propensas a padecer de enfermedades del corazón que quienes no tienen diabetes. Boletín 631 D Las personas con diabetes tienen mayor- res relacionados con la diabetes, como derrame cerebral, mala circulación en las piernas y pies e

346

Una tarde con Héctor Mendoza  

E-print Network

hay más. Mira, realmente, les voy a contar. Lo que me sucede ahora es que me he preocupado terriblemente por la teoría de la actuación, y lo que estoy haciendo son textos teóricos sobre la actuación. Ahora lo que hago es una obra mezclada con la... teoría de la actuación. Siento que tomar un texto de los Siglos de Oro, que son textos que ya me son muy familiares, entonces, se me facilita muchísimo más para su manejo; en este sentido, ¿no? Ahora, yo siento que se me facilita también tomar un texto...

Padró n-Leó n, Bá rbara A.; Peale, C. George

1999-10-01

347

Risk of preterm delivery with increasing depth of excision for cervical intraepithelial neoplasia in England: nested case-control study  

PubMed Central

Objective To determine the association between depth of excision of cervical intraepithelial neoplasia and risk of preterm birth. Design Case-control study nested in record linkage cohort study. Setting 12 hospitals in England. Participants From a cohort of 11?471 women with at least one histological sample taken at colposcopy and a live singleton birth (before or after colposcopy), 1313 women with a preterm birth (20-36 weeks) were identified and frequency matched on maternal age at delivery, parity, and study site to 1313 women with term births (38-42 weeks). Main outcome measures Risk of preterm birth and very/extreme preterm birth by depth of excisional treatment of the cervical transformation zone. Results After exclusions, 768 preterm births (cases) and 830 term births after colposcopy remained. The risk of preterm birth was no greater in women with a previous small (<10 mm) excision (absolute risk 7.5%, 95% confidence interval 6.0% to 8.9%) than in women with a diagnostic punch biopsy (7.2%, 5.9% to 8.5%). Women with a medium (10-14 mm) (absolute risk 9.6%; relative risk 1.28, 0.98 to 1.68), large (15-19 mm) (15.3%; 2.04, 1.41 to 2.96), or very large (?20 mm) excision (18.0%; 2.40, 1.53 to 3.75) had a higher risk of preterm delivery than those with small excision. The same pattern was seen in 161 women with very/extremely preterm births (20-31 weeks) and with increasing volume excised. Most births were conceived more than three years after colposcopy, and the risk of preterm delivery did not seem to depend on time from excision to conception. Conclusions The risk of preterm birth is at most minimally affected by a small excision. Larger excisions, particularly over 15 mm or 2.66 cm3, are associated with a doubling of the risk of both preterm and very preterm births. The risk does not decrease with increasing time from excision to conception. Efforts should be made to excise the entire lesion while preserving as much healthy cervical tissue as possible. Close obstetric monitoring is warranted for women who have large excisions of the cervical transformation zone. PMID:25378384

Castanon, Alejandra; Landy, Rebecca; Brocklehurst, Peter; Evans, Heather; Peebles, Donald; Singh, Naveena; Walker, Patrick; Patnick, Julietta

2014-01-01

348

Thoracotomy in refractory gestational trophoblastic neoplasia with lung metastasis after normalization of serum beta human chorionic gonadotropin (?-hCG) with salvage chemotherapy  

PubMed Central

Objective To assess the need for pulmonary surgery in the treatment of refractory gestational trophoblastic neoplasia with lung metastasis after normalization of serum beta human chorionic gonadotropin (?-hCG) level with salvage chemotherapy. Materials and methods A review of medical records of patients with refractory gestational trophoblastic neoplasia who underwent pulmonary surgery and received combined chemotherapy between January 1995 and December 2008 at the Peking Union Medical College Hospital was retrospectively performed. The positive pathologic findings in surgical specimens were defined as trophoblastic cells documented in the specimen. Pathologic findings were reported. Results There were 21 patients with preoperative normal ?-hCG. Of 21 patients, six (28.6%) had positive pathologic findings. The positive pathologic findings remained at 27.3% in 11 patients who had received no less than two cycles of consolidation chemotherapy before pulmonary surgery. Univariate analysis found that no variables in patient characteristics were associated with pathologic findings. At the median follow-up of 78 months (9–186 months), 85.7% (18 of 21) patients were alive, and no statistical difference was observed in the disease-free survival between the patients with positive and negative pathologic findings. The 5-year overall survival was 72.2%. Conclusion Pulmonary surgery is valuable in the treatment of refractory patients with lung metastasis after normalization of serum ?-hCG level following salvage chemotherapy, irrespective of viable trophoblasts in surgical specimens. Further study will be necessary to clarify the importance of this observation. PMID:24511240

Feng, Fengzhi; Hu, Huiying; Wu, Lei; Ren, Tong; Wan, Xirun; Xiang, Yang

2014-01-01

349

Comparison of captive lifespan, age-associated liver neoplasias and age-dependent gene expression between two annual fish species: Nothobranchius furzeri and Nothobranchius korthause.  

PubMed

Nothobranchius is a genus of annual fish broadly distributed in South-Eastern Africa and found into temporary ponds generated during the rain seasons and their lifespan is limited by the duration of their habitats. Here we compared two Nothobranchius species from radically different environments: N. furzeri and N. korthausae. We found a large difference in life expectancy (29- against 71-weeks of median life span, 40- against 80-weeks of maximum lifespan, respectively), which correlates with a diverse timing in the onset of several age dependent processes: our data show that N. korthause longer lifespan is associated to retarded onset of age-dependent liver-neoplasia and slower down-regulation of collagen 1 alpha 2 (COL1A2) expression in the skin. On the other hand, the expression of cyclin B1 (CCNB1) in the brain was strongly age-regulated, but with similar profiles in N. furzeri and N. korthausae. In conclusion, our data suggest that the different ageing rate of two species of the same genus could be used as novel tool to investigate and better understand the genetic bases of some general mechanism leading to the complex ageing process, providing a strategy to unravel some of the genetic mechanisms regulating longevity and age-associate pathologies including neoplasias. PMID:25315356

Baumgart, Mario; Di Cicco, Emiliano; Rossi, Giacomo; Cellerino, Alessandro; Tozzini, Eva Terzibasi

2015-02-01

350

Mucin glycoproteins in neoplasia  

Microsoft Academic Search

Mucins are high molecular weight glycoproteins that are heavily glycosylated with many oligosaccharide side chains linked O-glycosidically to the protein backbone. With the recent application of molecular biological methods, the structures of apomucins and regulation of mucin genes are beginning to be understood. At least nine human mucin genes have been identified to date. Although a complete protein sequence is

Young S. Kim; James Gum; Inka Brockhausen

1996-01-01

351

Regular Article MYELOID NEOPLASIA  

E-print Network

and engraftment of BCR-ABL11 leukemic stem cells in the bone marrow niche Daniela S. Krause,1,2 Katherine-selectin in the recipient bone marrow endothelium significantly reduced engraftment by BCR-ABL1­expressing stem cells in most patients. Allogeneic hematopoietic stem cell (HSC) trans- plantation remains the only proven

von Andrian, Ulrich H.

352

¡Truco Con Agua!  

NSDL National Science Digital Library

En esta actividad los aprendices aprenderán un truco de magia donde la magia es la presión del aire. Los participantes tomarán un vaso de agua medio lleno y lo taparán con un pedazo de plástico o cartón. Sosteniendo la tarjeta contra el vaso, lo voltearán boca abajo y cuando quiten la mano debajo del vaso, ¡abracadabra! no se caerá el agua. En la tira cómica, Mateo explica a los aprendices que la presión que hace el aire en todas las direcciones es la que sostiene la tarjeta.

Science, Lawrence H.

2009-01-01

353

Prevalence of high-risk human papillomavirus types in Mexican women with cervical intraepithelial neoplasia and invasive carcinoma  

PubMed Central

Background Prevalence of high risk (HR) human papillomavirus (HPV) types in the states of San Luis Potosí (SLP) and Guanajuato (Gto), Mexico, was determined by restriction fragment length-polymorphism (RFLP) analysis on the E6 ~250 bp (E6-250) HR-HPV products amplified from cervical scrapings of 442 women with cervical intraepithelial neoplasia and invasive carcinoma (280 from SLP and 192 from Gto). Fresh cervical scrapings for HPV detection and typing were obtained from all of them and cytological and/or histological diagnoses were performed on 383. Results Low grade intraepithelial squamous lesions (LSIL) were diagnosed in 280 cases (73.1%), high grade intraepithelial squamous lesions (HSIL) in 64 cases (16.7%) and invasive carcinoma in 39 cases (10.2%). In the 437 cervical scrapings containing amplifiable DNA, only four (0.9%) were not infected by HPV, whereas 402 (92.0%) were infected HR-HPV and 31 (7.1%) by low-risk HPV. RFLP analysis of the amplifiable samples identified infections by one HR-HPV type in 71.4%, by two types in 25.9% and by three types in 2.7%. The overall prevalence of HR-HPV types was, in descending order: 16 (53.4%) > 31 (15.6%) > 18 (8.9%) > 35 (5.6) > 52 (5.4%) > 33 (1.2%) > 58 (0.7%) = unidentified types (0.7%); in double infections (type 58 absent in Gto) it was 16 (88.5%) > 31 (57.7%) > 35 (19.2%) > 18 (16.3%) = 52 (16.3%) > 33 (2.8%) = 58 (2.8%) > unidentified types (1.0%); in triple infections (types 33 and 58 absent in both states) it was 16 (100.0%) > 35 (54.5%) > 31 (45.5%) = 52 (45.5%) > 18 (27.3%). Overall frequency of cervical lesions was LSIL (73.1%) > HSIL (16.7%) > invasive cancer (10.2%). The ratio of single to multiple infections was inversely proportional to the severity of the lesions: 2.46 for LSIL, 2.37 for HSIL and 2.15 for invasive cancer. The frequency of HR-HPV types in HSIL and invasive cancer lesions was 16 (55.0%) > 31 (18.6%) > 35 (7.9%) > 52 (7.1%) > 18 (4.3%) > unidentified types (3.6%) > 33 (2.9%) > 58 (0.7%). Conclusion Ninety percent of the women included in this study were infected by HR-HPV, with a prevalence 1.14 higher in Gto. All seven HR-HPV types identifiable with the PCR-RFLP method used circulate in SLP and Gto, and were diagnosed in 99.3% of the cases. Seventy-one percent of HR-HPV infections were due to a single type, 25.9% were double and 2.7% were triple. Overall frequency of lesions was LSIL (73.1%) > HSIL (16.7%) > invasive cancer (10.2%), and the ratio of single to multiple infections was inversely proportional to severity of the lesions: 2.46 for LSIL, 2.37 for HSIL and 2.15 for invasive cancer. The frequency of HR-HPV types found in HSIL and invasive cancer was 16 (55.0%) > 31 (18.6%) > 35 (7.9%) > 52 (7.1%) > 18 (4.3%) > unidentified types (3.6%) > 33 (2.9%) > 58 (0.7%). Since the three predominant types (16, 31 and 18) cause 77.9% of the HR-HPV infections and immunization against type 16 prevents type 31 infections, in this region the efficacy of the prophylactic vaccine against types 16 and 18 would be close to 80%. PMID:18307798

López-Revilla, Rubén; Martínez-Contreras, Luz A; Sánchez-Garza, Mireya

2008-01-01

354

Multiple therapeutic and preventive effects of 3,3?-diindolylmethane on cancers including prostate cancer and high grade prostatic intraepithelial neoplasia  

PubMed Central

Abstract Cruciferous vegetables belong to the plant family that has flowers with four equal-sized petals in the pattern of a crucifer cross. These vegetables are an abundant source of dietary phytochemicals, including glucosinolates and their hydrolysis products such as indole-3-carbinol (I3C) and 3,3?-diindolylmethane (DIM). By 2013, the total number of natural glucosinolates that have been documented is estimated to be 132. Recently, cruciferous vegetable intake has garnered great interest for its multiple health benefits such as anticancer, antiviral infections, human sex hormone regulation, and its therapeutic and preventive effects on prostate cancer and high grade prostatic intraepithelial neoplasia (HGPIN). DIM is a hydrolysis product of glucosinolates and has been used in various trials. This review is to provide an insight into the latest developments of DIM in treating or preventing both prostate cancer and HGPIN. PMID:25332705

Zhang, William Weiben; Feng, Zhenqing; Narod, Steven A.

2014-01-01

355

Endoscopic Mucosal Resection Results in Change of Histologic Diagnosis in Barrett’s Esophagus Patients with Visible and Flat Neoplasia: A Multicenter Cohort Study  

PubMed Central

Background There are limited data on the effect of endoscopic mucosal resection (EMR) on changes of histopathologic diagnosis for Barrett’s esophagus (BE) patients undergoing endoscopic eradication therapy (EET); especially those without visible lesions. Aim To compare the frequency of changes of diagnosis by EMR compared with pre-EMR biopsy diagnosis for patients with and without visible lesions. Methods In this multicenter outcomes project, patients with Barrett’s-related neoplasia undergoing EET at three tertiary-care centers were included. Patients undergoing biopsies followed by EMR within six months were included. The main outcome measures were frequency of overall change of histopathologic diagnosis, change based on pre-EMR biopsy diagnosis, and change based on the presence of visible lesions. Results One-hundred and thirty-eight BE patients (low-grade dysplasia (LGD) 15 (10.9 %), high-grade dysplasia (HGD) 87 (63 %), esophageal adenocarcinoma (EAC) 36 (26.1 %)) were included; 114 (82.6 %) patients had visible lesions. EMR resulted in a change of diagnosis for 43 (31.1 %) patients (upgrade 14 (10.1 %); downgrade 29 (21 %)). For HGD patients, EMR downstaged dysplasia grade for 17 (19.5 %) cases and upstaged it to EAC for nine (10.3 %) cases. There was a change of diagnosis for 26 (29.9 %) HGD patients, irrespective of the presence or absence of visible lesions (p = 0.76). For EAC patients, EMR downstaged dysplasia grade in 10 (27.8 %) cases. There was a change of diagnosis for 10 (27.8 %) EAC patients, irrespective of the presence or absence of endoscopically visible lesions (p = 0.48). Conclusions EMR results in a change of diagnosis for approximately 30 % of BE patients with early neoplasia (with and without visible lesions) referred for EET. PMID:23633158

Wani, Sachin; Abrams, Julian; Edmundowicz, Steven A.; Gaddam, Srinivas; Hovis, Christine E.; Green, Daniel; Gupta, Neil; Higbee, April; Bansal, Ajay; Rastogi, Amit; Early, Dayna; Lightdale, Charles J.

2015-01-01

356

Genetic Polymorphisms of Alcohol Dehydrogense-1B and Aldehyde Dehydrogenase-2, Alcohol Flushing, Mean Corpuscular Volume, and Aerodigestive Tract Neoplasia in Japanese Drinkers.  

PubMed

Genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) modulate exposure levels to ethanol/acetaldehyde. Endoscopic screening of 6,014 Japanese alcoholics yielded high detection rates of esophageal squamous cell carcinoma (SCC; 4.1 %) and head and neck SCC (1.0 %). The risks of upper aerodigestive tract SCC/dysplasia, especially of multiple SCC/dysplasia, were increased in a multiplicative fashion by the presence of a combination of slow-metabolizing ADH1B*1/*1 and inactive heterozygous ALDH2*1/*2 because of prolonged exposure to higher concentrations of ethanol/acetaldehyde. A questionnaire asking about current and past facial flushing after drinking a glass (??180 mL) of beer is a reliable tool for detecting the presence of inactive ALDH2. We invented a health-risk appraisal (HRA) model including the flushing questionnaire and drinking, smoking, and dietary habits. Esophageal SCC was detected at a high rate by endoscopic mass-screening in high HRA score persons. A total of 5.0 % of 4,879 alcoholics had a history of (4.0 %) or newly diagnosed (1.0 %) gastric cancer. Their high frequency of a history of gastric cancer is partly explained by gastrectomy being a risk factor for alcoholism because of altered ethanol metabolism, e.g., by blood ethanol level overshooting. The combination of H. pylori-associated atrophic gastritis and ALDH2*1/*2 showed the greatest risk of gastric cancer in alcoholics. High detection rates of advanced colorectal adenoma/carcinoma were found in alcoholics, 15.7 % of 744 immunochemical fecal occult blood test (IFOBT)-negative alcoholics and 31.5 % of the 393 IFOBT-positive alcoholics. Macrocytosis with an MCV???106 fl increased the risk of neoplasia in the entire aerodigestive tract of alcoholics, suggesting that poor nutrition as well as ethanol/acetaldehyde exposure plays an important role in neoplasia. PMID:25427912

Yokoyama, Akira; Mizukami, Takeshi; Yokoyama, Tetsuji

2015-01-01

357

Intraepithelial macrophage infiltration is related to a high number of regulatory T cells and promotes a progressive course of HPV-induced vulvar neoplasia.  

PubMed

Human papilloma virus (HPV)-induced usual-type vulvar intraepithelial neoplasia (uVIN) is infiltrated by myeloid cells but the type and role of these cells is unclear. We used triple immunofluorescent confocal microscopy to locate, identify and quantify myeloid cells based on their staining pattern for CD14, CD33 and CD163 in a cohort of 43 primary and 20 recurrent uVIN lesions, 21 carcinomas and 26 normal vulvar tissues. The progressive course of uVIN is characterized by an increase in both intraepithelial and stromal mature M1 and M2 macrophages. While the M2 macrophages outnumber M1 macrophages in healthy controls and uVIN, they are matched in number by M1 macrophages in cancer. Importantly, uVIN patients with a dense intraepithelial infiltration with mature CD14+ macrophages (irrespective of M1 or M2 type) displayed approximately a six times higher risk to develop a recurrence and a high number of these cells constituted an independent prognostic factor for recurrence. In addition, a dense intraepithelial CD14+ cell infiltration was associated with high numbers of intraepithelial CD4+ Tregs and low numbers of stromal CD8+TIM3+ T cells. Patients with low numbers of intraepithelial CD14+ cells and high numbers of stromal CD8+TIM3+ cells showed the best recurrence-free survival. These data clearly show the importance of the local immune response in HPV-induced vulvar neoplasia and may be of help in predicting the prognosis of patients or their response to immunotherapy. PMID:25220265

van Esch, Edith M G; van Poelgeest, Mariette I E; Trimbos, J Baptist M Z; Fleuren, Gert Jan; Jordanova, Ekaterina S; van der Burg, Sjoerd H

2015-02-15

358

One year of sitagliptin treatment protects against islet amyloid-associated ?-cell loss and does not induce pancreatitis or pancreatic neoplasia in mice  

PubMed Central

The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin is an attractive therapy for diabetes, as it increases insulin release and may preserve ?-cell mass. However, sitagliptin also increases ?-cell release of human islet amyloid polypeptide (hIAPP), the peptide component of islet amyloid, which is cosecreted with insulin. Thus, sitagliptin treatment may promote islet amyloid formation and its associated ?-cell toxicity. Conversely, metformin treatment decreases islet amyloid formation by decreasing ?-cell secretory demand and could therefore offset sitagliptin's potential proamyloidogenic effects. Sitagliptin treatment has also been reported to be detrimental to the exocrine pancreas. We investigated whether long-term sitagliptin treatment, alone or with metformin, increased islet amyloid deposition and ?-cell toxicity and induced pancreatic ductal proliferation, pancreatitis, and/or pancreatic metaplasia/neoplasia. hIAPP transgenic and nontransgenic littermates were followed for 1 yr on no treatment, sitagliptin, metformin, or the combination. Islet amyloid deposition, ?-cell mass, insulin release, and measures of exocrine pancreas pathology were determined. Relative to untreated mice, sitagliptin treatment did not increase amyloid deposition, despite increasing hIAPP release, and prevented amyloid-induced ?-cell loss. Metformin treatment alone or with sitagliptin decreased islet amyloid deposition to a similar extent vs untreated mice. Ductal proliferation was not altered among treatment groups, and no evidence of pancreatitis, ductal metaplasia, or neoplasia were observed. Therefore, long-term sitagliptin treatment stimulates ?-cell secretion without increasing amyloid formation and protects against amyloid-induced ?-cell loss. This suggests a novel effect of sitagliptin to protect the ?-cell in type 2 diabetes that appears to occur without adverse effects on the exocrine pancreas. PMID:23736544

Aston-Mourney, Kathryn; Subramanian, Shoba L.; Zraika, Sakeneh; Samarasekera, Thanya; Meier, Daniel T.; Goldstein, Lynn C.

2013-01-01

359

Comparison of the efficacy of methotrexate and actinomycin D in the treatment of patients with stage I low risk gestational trophoblastic neoplasia (GTN)  

PubMed Central

Background: Gestational trophoblastic neoplasia (GTN) refers to malignant lesions that arise from abnormal proliferation of placental trophoblast. Even in its metastatic forms GTN is curable with a cure rate of 90-100 %. Currently, methotrexate with or without folic acid, andactinomycin D is recommended for low risk GTN. The aim of this study is to compare the efficacy of methotrexate and actinomycin D as the first-line single chemotherapeutic agents for women with low-risk gestational trophoblastic neoplasia (LR-GTN). Methods: A total of 30 women with LR-GTN were randomized to receive a weekly pulsed dose of 40 mg/m (2) of methotrexate intramuscularly (n=15) or a pulsed intravenous bolus of 1.25 mg/m (2) of actinomycin D every 2 weeks (n=15). An additional cycle was administered as consolidation treatment following normalization of the serum level of beta-human chorionic gonadotropin (?10 IU/L). Results: Complete remission was achieved in 53.3% of patients in the methotrexate group and 86.7% in the actinomycin D group (p?0.04). The mean number of treatment cycles needed to achieve response was lower in the actinomycin D group (4.3 vs. 6.5). The mean duration from beginning of treatment till achieving complete remission was 9.6 weeks for the Act group and 13 weeks for the MTX group. Conclusion: Actinomycin D may be a better option than methotrexate as a first-line chemotherapy agent for patients with LR-GTN but larger multicenter randomized controlled trials should be conducted to establish the most appropriate regimen for these patients. PMID:25405143

Shahbazian, Nahid; Razi, Taghi; Razi, Shima; Yazdanpanah, Leila

2014-01-01

360

Immunohistochemical assessment of a unique basal pattern of p53 expression in ulcerative-colitis-associated neoplasia using computer-assisted cytometry  

PubMed Central

Background The basal pattern of p53 expression, defined as its immunoreactivity confined to the basal half of the glands, is associated with early neoplastic lesions in ulcerative colitis (UC). However, their clinical utility of this finding is limited by the use of “visual estimation” (approximate immunoreactivity on the basis of scanning the stained slide, without formal counting). This study was designed to analyze the basal pattern of p53 using computer-assisted cytometry and to identify the optimal cutoff value for discriminating between UC-associated early-stage neoplasia and regenerative atypia. Methods The specimens were obtained from eight UC patients undergoing colectomy and were classified according to the criteria by the Research Committee of Inflammatory Bowel Disease of the Ministry of Health and Welfare in Japan. Patients with classes UC-IIa (indefinite for dysplasia, probably regenerative), UC-IIb (indefinite for dysplasia, probably dysplastic), and UC-III (definitive dysplasia) were enrolled in the study. Based on the percentage of immunoreactive cells in the basal half of the crypt with visual estimation, basal positivity of p53 was classified into three categories: grade 1 (1 - 9%), grade 2 (10 - 19%), and grade 3 (?20%). Next, crypts classified as grade 3 by visual estimation were analyzed by computer-assisted image analysis. Results Using visual estimation, grade-3 p53 basal positivity was observed in 46.0% of UC-IIa crypts (128 of 278), 61.9% of UC-IIb crypts (39 of 63), and 94.2% of UC-III crypts (81 of 86). Using image analysis, the median p53 basal positivities were 30.3% in UC-IIa, 52.3% in UC-IIb, and 65.4% in UC-III (P ?0.002). A receiver operating characteristics curve was generated to determine the method’s diagnostic utility in differentiating UC-IIa from UC-III. In this cohort, the sensitivity was 0.78; the specificity was 0.98; the negative predictive value was 87.4%; the positive predictive value was 95.5%, and the accuracy was 90.2% with a cutoff value for p53 basal positivity of 46.1%. Conclusions Our findings indicate that assessing p53 basal positivity by image analysis with an optimal threshold represents an alternative to visual estimation for the accurate diagnosis of UC-associated early-stage neoplasia. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3588120501252608 PMID:24886509

2014-01-01

361

In-Vivo Nonlinear Optical Microscopy (NLOM) of Epithelial-Connective Tissue Interface (ECTI) Reveals Quantitative Measures of Neoplasia in Hamster Oral Mucosa  

PubMed Central

The epithelial-connective tissue interface (ECTI) plays an integral role in epithelial neoplasia, including oral squamous cell carcinoma (OSCC). This interface undergoes significant alterations due to hyperproliferating epithelium that supports the transformation of normal epithelium to precancers and cancer. We present a method based on nonlinear optical microscopy to directly assess the ECTI and quantify dysplastic alterations using a hamster model for oral carcinogenesis. Neoplastic and non-neoplastic normal mucosa were imaged in-vivo by both multiphoton autofluorescence microscopy (MPAM) and second harmonic generation microscopy (SHGM) to obtain cross-sectional reconstructions of the oral epithelium and lamina propria. Imaged sites were biopsied and processed for histopathological grading and measurement of ECTI parameters. An ECTI shape parameter was calculated based on deviation from the linear geometry (?Linearity) seen in normal mucosa was measured using MPAM-SHGM and histology. The ECTI was readily visible in MPAM-SHGM and quantitative shape analysis showed ECTI deformation in dysplasia but not in normal mucosa. ?Linearity was significantly (p < 0.01) higher in dysplasia (0.41±0.24) than normal (0.11±0.04) as measured in MPAM-SHGM and results were confirmed in histology which showed similar trends in ?Linearity. Increase in ?Linearity was also statistically significant for different grades of dysplasia. In-vivo ?Linearity measurement alone from microscopy discriminated dysplasia from normal tissue with 87.9% sensitivity and 97.6% specificity, while calculations from histology provided 96.4% sensitivity and 85.7% specificity. Among other quantifiable architectural changes, a progressive statistically significant increase in epithelial thickness was seen with increasing grade of dysplasia. MPAM-SHGM provides new noninvasive ways for direct characterization of ECTI which may be used in preclinical studies to investigate the role of this interface in early transformation. Further development of the method may also lead to new diagnostic approaches to differentiate non-neoplastic tissue from precancers and neoplasia, possibly with other cellular and layer based indicators of abnormality. PMID:25633927

Pal, Rahul; Yang, Jinping; Ortiz, Daniel; Qiu, Suimin; Resto, Vicente; McCammon, Susan; Vargas, Gracie

2015-01-01

362

ERBB2 in Cat Mammary Neoplasias Disclosed a Positive Correlation between RNA and Protein Low Expression Levels: A Model for erbB-2 Negative Human Breast Cancer  

PubMed Central

Human ERBB2 is a proto-oncogene that codes for the erbB-2 epithelial growth factor receptor. In human breast cancer (HBC), erbB-2 protein overexpression has been repeatedly correlated with poor prognosis. In more recent works, underexpression of this gene has been described in HBC. Moreover, it is also recognised that oncogenes that are commonly amplified or deleted encompass point mutations, and some of these are associated with HBC. In cat mammary lesions (CMLs), the overexpression of ERBB2 (27%–59.6%) has also been described, mostly at the protein level and although cat mammary neoplasias are considered to be a natural model of HBC, molecular information is still scarce. In the present work, a cat ERBB2 fragment, comprising exons 10 to 15 (ERBB2_10–15) was achieved for the first time. Allelic variants and genomic haplotype analyses were also performed, and differences between normal and CML populations were observed. Three amino acid changes, corresponding to 3 non-synonymous genomic sequence variants that were only detected in CMLs, were proposed to damage the 3D structure of the protein. We analysed the cat ERBB2 gene at the DNA (copy number determination), mRNA (expression levels assessment) and protein levels (in extra- and intra protein domains) in CML samples and correlated the last two evaluations with clinicopathological features. We found a positive correlation between the expression levels of the ERBB2 RNA and erbB-2 protein, corresponding to the intracellular region. Additionally, we detected a positive correlation between higher mRNA expression and better clinical outcome. Our results suggest that the ERBB2 gene is post-transcriptionally regulated and that proteins with truncations and single point mutations are present in cat mammary neoplastic lesions. We would like to emphasise that the recurrent occurrence of low erbB-2 expression levels in cat mammary tumours, suggests the cat mammary neoplasias as a valuable model for erbB-2 negative HBC. PMID:24386251

Abreu, Rui M. V.; Bastos, Estela; Amorim, Irina; Gut, Ivo G.; Gärtner, Fátima; Chaves, Raquel

2013-01-01

363

Design and methods of a population-based natural history study of cervical neoplasia in a rural province of Costa Rica: the Guanacaste Project.  

PubMed

This paper reports on the enrollment phase of a population-based natural history study of cervical neoplasia in Guanacaste, a rural province of Costa Rica with consistently high rates of invasive cervical cancer. The main goals of the study are to investigate the role of human papillomavirus (HPV) infection and its co-factors in the etiology of high-grade cervical neoplasia, and to evaluate new cervical cancer screening technologies. To begin, a random sample of censal segments was selected and enumeration of all resident women 18 years of age and over was conducted with the aid of outreach workers of the Costa Rican Ministry of Health. Of the 10738 women who were eligible to participate, 10049 (93.6%) were interviewed after giving written informed consent. After the interview on cervical cancer risk factors was administered, a pelvic examination was performed on those women who reported previous sexual activity. The pelvic examination included a vaginal pH determination and collection of cervical cells for cytologic diagnosis using three different techniques. Additional cervical cells were collected for determination of the presence and amount of DNA from 16 different types of HPV, and two photographic images of the cervix were taken and interpreted offsite by an expert colposcopist. Finally, blood samples were collected for immunologic and micronutrient assays. Women with any abnormal cytologic diagnosis or a positive Cervigram, as well as a sample of the whole group, were referred for colposcopy, and biopsies were taken when lesions were observed. The enrollment screening will serve as the basis for a prevalent case-control study, and the members of the cohort free from serious disease will be followed actively, at intervals of no more than a year, to study the natural history of HPV infection and the origins of high-grade squamous intraepithelial lesions (HSIL). Details of the field operation are outlined, with particular reference to the realization of this kind of study in developing countries. Descriptive data on the prevalence of disease and exposure to various risk factors are also presented. PMID:9180057

Herrero, R; Schiffman, M H; Bratti, C; Hildesheim, A; Balmaceda, I; Sherman, M E; Greenberg, M; Cárdenas, F; Gómez, V; Helgesen, K; Morales, J; Hutchinson, M; Mango, L; Alfaro, M; Potischman, N W; Wacholder, S; Swanson, C; Brinton, L A

1997-05-01

364

Opciones de cirugía para mujeres con CDIS o con cáncer de seno  

Cancer.gov

Contiene información sobre los tipos de cirugía de seno, como la operación para conservar el seno y la mastectomía, y ayuda a las mujeres diagnosticadas con CDIS o con cáncer de seno a decidir cuál cirugía es la más conveniente para ellas.

365

Laser capture microdissection–reduced representation bisulfite sequencing (LCM-RRBS) maps changes in DNA methylation associated with gonadectomy-induced adrenocortical neoplasia in the mouse  

PubMed Central

DNA methylation is a mechanism for long-term transcriptional regulation and is required for normal cellular differentiation. Failure to properly establish or maintain DNA methylation patterns leads to cell dysfunction and diseases such as cancer. Identifying DNA methylation signatures in complex tissues can be challenging owing to inaccurate cell enrichment methods and low DNA yields. We have developed a technique called laser capture microdissection-reduced representation bisulfite sequencing (LCM-RRBS) for the multiplexed interrogation of the DNA methylation status of cytosine–guanine dinucleotide islands and promoters. LCM-RRBS accurately and reproducibly profiles genome-wide methylation of DNA extracted from microdissected fresh frozen or formalin-fixed paraffin-embedded tissue samples. To demonstrate the utility of LCM-RRBS, we characterized changes in DNA methylation associated with gonadectomy-induced adrenocortical neoplasia in the mouse. Compared with adjacent normal tissue, the adrenocortical tumors showed reproducible gains and losses of DNA methylation at genes involved in cell differentiation and organ development. LCM-RRBS is a rapid, cost-effective, and sensitive technique for analyzing DNA methylation in heterogeneous tissues and will facilitate the investigation of DNA methylation in cancer and organ development. PMID:23589626

Schillebeeckx, Maximiliaan; Schrade, Anja; Löbs, Ann-Kathrin; Pihlajoki, Marjut; Wilson, David B.; Mitra, Robi D.

2013-01-01

366

A rapid screening method for the detection of mutations in the RET proto-oncogene in multiple endocrine neoplasia type 2A and familial medullary thyroid carcinoma families  

SciTech Connect

Multiple endocrine neoplasia type 2A (MEN2A) and familial medullary thyroid carcinoma (FMTC) are autosomal dominant inherited cancer syndromes with incomplete penetrance. Following the identification of mutations in the RET proto-oncogene that segregate with the disease phenotype in MEN2A, MEN2B, and FMTC, genetic screening of individuals with mutations in RET may be performed. The authors have employed restriction endonuclease digestion of polymerase chain reaction products as an alternative to sequence analysis for rapid identification of mutant gene carriers in families in which MEN2A and RMTC are segregating. Twenty-one Australasian MEN2A and FMTC families have been screened for mutations in a cysteine-rich region of the RET proto-oncogene. Seven independent mutations were identified in key individuals in 16 of these families. The authors have identified a mutation in codon 620, 2053 T {r_arrow}C (Cys620Arg), and two mutations in codon 634 of exon 11 of RET, 2095 T {r_arrow} C (Cys634Arg) and 2096 G {r_arrow} A (Cys634Tyr), all three of which were present in both MEN2A and FMTC families. 7 refs., 1 fig., 1 tab.

Marsh, D.J.; Andrew, S.; Richardson, A.L. [Royal North Shore Hospital, St. Leonards (Australia)] [Royal North Shore Hospital, St. Leonards (Australia); [Univ. of Sydney, New South Wales (Australia)] [and others

1994-09-15

367

Human papillomavirus infection in women who develop high-grade cervical intraepithelial neoplasia or cervical cancer: a case–control study in the UK  

PubMed Central

Human papillomavirus (HPV) testing might identify older women who could be withdrawn from the cervical screening programme, or require less frequent screening. A case–control study using the United Kingdom cervical screening population was set up to help address this issue. Cases comprised 575 women who developed cervical intraepithelial neoplasia (CIN) grade 2 or worse over a 13-year period following a cytologically normal baseline smear, and were stratified by age group (‘under 20', ‘20–39' and 40 years or over). Controls (n=601) were women who remained disease free over this interval and were the same age on average as cases. DNA was extracted from the baseline smears and tested for HPV by PCR using GP5+/6+ consensus primers. HPV+ samples were tested for HPV types 16 and 18 using specific PCR primers. In all, 27.0% of cases tested positive for HPV at baseline, compared with 15.4% of controls (odds ratio (OR)=2.00; 95% confidence interval (CI), 1.50–2.68). Among women aged 40 years or over, the OR for HPV 16 was 8.95 (95% CI, 2.63–30.4). These results support the need for further cervical screening of HPV? older women, as many of the cases were HPV? at baseline. PMID:15827556

Grainge, M J; Seth, R; Coupland, C; Guo, L; Rittman, T; Vryenhoef, P; Johnson, J; Jenkins, D; Neal, K R

2005-01-01

368

Human Papillomavirus Genotyping and E6/E7 mRNA Expression in Greek Women with Intraepithelial Neoplasia and Squamous Cell Carcinoma of the Vagina and Vulva  

PubMed Central

A large proportion of vaginal and vulvar squamous cell carcinomas (SCCs) and intraepithelial neoplasias (VAIN and VIN) are associated with HPV infection, mainly type 16. The purpose of this study was to identify HPV genotypes, as well as E6/E7 mRNA expression of high-risk HPVs (16, 18, 31, 33, and 45) in 56 histology samples of VAIN, VIN, vaginal, and vulvar SCCs. HPV was identified in 56% of VAIN and 50% of vaginal SCCs, 71.4% of VIN and 50% of vulvar SCCs. E6/E7 mRNA expression was found in one-third of VAIN and in all vaginal SCCs, 42.9% of VIN and 83.3% of vulvar SCCs. Our data indicated that HPV 16 was the commonest genotype identified in VAIN and VIN and the only genotype found in SCCs of the vagina and vulva. These findings may suggest, in accordance with other studies, that mRNA assay might be useful in triaging lesions with increased risk of progression to cancer. PMID:22187556

Tsimplaki, Elpida; Argyri, Elena; Michala, Lina; Kouvousi, Maria; Apostolaki, Aikaterini; Magiakos, George; Papassideri, Issidora; Panotopoulou, Efstathia

2012-01-01

369

Spectral classifier design with ensemble classifiers and misclassification-rejection: application to elastic-scattering spectroscopy for detection of colonic neoplasia  

NASA Astrophysics Data System (ADS)

Optical spectroscopy has shown potential as a real-time, in vivo, diagnostic tool for identifying neoplasia during endoscopy. We present the development of a diagnostic algorithm to classify elastic-scattering spectroscopy (ESS) spectra as either neoplastic or non-neoplastic. The algorithm is based on pattern recognition methods, including ensemble classifiers, in which members of the ensemble are trained on different regions of the ESS spectrum, and misclassification-rejection, where the algorithm identifies and refrains from classifying samples that are at higher risk of being misclassified. These ``rejected'' samples can be reexamined by simply repositioning the probe to obtain additional optical readings or ultimately by sending the polyp for histopathological assessment, as per standard practice. Prospective validation using separate training and testing sets result in a baseline performance of sensitivity = .83, specificity = .79, using the standard framework of feature extraction (principal component analysis) followed by classification (with linear support vector machines). With the developed algorithm, performance improves to Se ~ 0.90, Sp ~ 0.90, at a cost of rejecting 20-33% of the samples. These results are on par with a panel of expert pathologists. For colonoscopic prevention of colorectal cancer, our system could reduce biopsy risk and cost, obviate retrieval of non-neoplastic polyps, decrease procedure time, and improve assessment of cancer risk.

Rodriguez-Diaz, Eladio; Castanon, David A.; Singh, Satish K.; Bigio, Irving J.

2011-06-01

370

INFECCION POR CITOMEGALOVIRUS CON COMPROMISO HEPATICO EN ADULTOS INMUNOCOMPETENTES  

Microsoft Academic Search

Resumen Evaluamos retrospectivamente a 73 adultos inmunocompetentes que consultaron entre marzo de 1999 y marzo de 2004 a un centro infectológico ambulatorio por fiebre y astenia, con elevación discreta de las transaminasas y serología compatible con infección reciente por citomegalovirus (CMV). Excluimos a pacientes con antecedentes de transfusiones, adicciones e inmunodeficiencias, así como aquellos con altera- ciones hepáticas preexistentes o

CLAUDIA VUJACICH; GABRIELA VIDIELLA; LAURA BARCELONA; EDGARDO STURBA; DANIEL STAMBOULIAN

371

iCons, 2011 Cholera in Haiti  

E-print Network

© iCons, 2011 Cholera in Haiti Handouts: 1. 1-page explainer of cholera outbreak in Haiti Assignments Part 1: Developing an Explainer 1. In-class written assignment of societal challenge with cholera in Haiti 2. In-class written assignment of scientific investigation relating to cholera 3. Take

Auerbach, Scott M.

372

InterCon Travel Health: Case B  

ERIC Educational Resources Information Center

InterCon provides services to health insurers of foreign tourists who travel to the United States and Canada. Management wants to implement a new information system that will deal with several operational problems, but it is having difficulty securing the capital resources to fund the system's development. After an initial failure, the chief…

Truman, Gregory E.; Pachamanova, Dessislava A.; Goldstein, Michael A.

2010-01-01

373

CON Advising Academic Year 2013-2014  

E-print Network

' personal, academic, and career goals. This advisor/student partnership requires participationCON Advising Academic Year 2013-2014 Advisors: Rita Tower Kelly Fanning Office: Garrand 403 Garrand students to make decisions about their academic, personal and professional pathways, and to encourage

Carter, John

374

Soluble interleukin 2 receptor levels and cervical neoplasia: results from a population-based case-control study in Costa Rica.  

PubMed

Progression from infection with human papillomavirus (HPV) to cervical cancer in some women is thought to involve a permissive host environment, one in which immune response is mobilized in an inappropriate manner. In a previous study (A. Hildesheim et al., Cancer Epidemiol. Biomark. Prev., 6: 807-813, 1997), increasing levels of soluble interleukin 2 receptor (sIL-2R), a known proxy for general immune activation, was found to be positively associated with increasing levels of cervical neoplasia. We attempted to confirm this finding by conducting a nested case-control study of 478 women within a 10,000-woman population-based cohort in Costa Rica. We selected for the study all of the women diagnosed (at enrollment into the cohort) with: (a) low-grade squamous intraepithelial lesions (LSIL, n = 191); (b) high-grade squamous intraepithelial lesions (HSIL, n = 130); or (c) cancer (n = 37). Controls were 120 cytologically normal, HPV-negative women selected from a random sample of the entire cohort. A questionnaire was administered to participants to elicit information on cervical cancer risk factors. All of the women received a pelvic examination during which cervical cells were collected and used for HPV DNA testing by PCR. Blood samples were also collected. Plasma obtained from the blood samples was tested for sIL-2R levels by ELISA. Results indicated that sIL-2R levels increased with age. Among controls, we observed that 44.3% of women over the age of 50 had high levels of sIL-2R (defined as >735 units/ml) compared with 15.8% of women <30 years of age (P = 0.008). When women with cervical disease (LSIL+) were compared with controls, women in the upper quartile of the sIL-2R distribution had an age-adjusted odds ratio (OR) of 2.1 [95% confidence interval (CI), 1.1-4.1]. Comparing each advancing state of neoplasia with its precursor, we found that women with LSIL had higher sIL-2R levels than controls (OR for upper quartile of sIL-2R, 2.3; 95% CI, 1.1-5.2; comparing LSIL cases with controls); women diagnosed with HSIL were similar to the LSIL group (OR for upper quartile of sIL-2R, 1.1; 95% CI, 0.5-2.4; comparing HSIL cases with LSIL cases); and those with cancer had higher sIL-2R levels than subjects with an HSIL diagnosis (OR for upper quartile of sIL-2R = 1.8; 95% CI, 0.5-7.1; comparing cancer cases with HSIL cases). These data suggest that among our study subjects, sIL-2R levels most likely rise as a response to the events of infection and cancerous invasion, but that sIL-2R levels are unlikely to be predictive of disease progression among women with LSIL. PMID:10090303

Ung, A; Kramer, T R; Schiffman, M; Herrero, R; Bratti, M C; Burk, R D; Swanson, C A; Sherman, M E; Hutchinson, M L; Alfaro, M; Morales, J; Balmaceda, I; Hildesheim, A

1999-03-01

375

Hazard evaluation of chemicals that cause accumulation of alpha 2u-globulin, hyaline droplet nephropathy, and tubule neoplasia in the kidneys of male rats.  

PubMed Central

This review paper examines the relationship between chemicals inducing excessive accumulation of alpha 2u-globulin (alpha 2u-g) (CIGA) in hyaline droplets in male rat kidneys and the subsequent development of nephrotoxicity and renal tubule neoplasia in the male rat. This dose-responsive hyaline droplet accumulation distinguishes CIGA carcinogens from classical renal carcinogens. CIGA carcinogens also do not appear to react with DNA and are generally negative in short-term tests for genotoxicity, CIGA or their metabolites bind specifically, but reversibly, to male rat alpha 2u-g. The resulting complex appears to be more resistant to hydrolytic degradation in the proximal tubule than native, unbound alpha 2u-g. Single cell necrosis of the tubule epithelium, with associated granular cast formation and papillary mineralization, is followed by sustained regenerative tubule cell proliferation, foci of tubule hyperplasia in the convoluted proximal tubules, and renal tubule tumors. Although structurally similar proteins have been detected in other species, including humans, renal lesions characteristic of alpha 2u-g nephropathy have not been observed. Epidemiologic investigation has not specifically examined the CIGA hypothesis for humans. Based on cancer bioassays, hormone manipulation studies, investigations in an alpha 2u-g-deficient strain of rat, and other laboratory data, an increased proliferative response caused by chemically induced cytotoxicity appears to play a role in the development of renal tubule tumors in male rats. Thus, it is reasonable to suggest that the renal effects induced in male rats by chemicals causing alpha 2u-g accumulation are unlikely to occur in humans. Images FIGURE 1. FIGURE 2. FIGURE 3. FIGURE 4. FIGURE 5. FIGURE 6. FIGURE 7. FIGURE 8. FIGURE 9. FIGURE 10. FIGURE 11. FIGURE 12. FIGURE 13. PMID:7686485

Hard, G C; Rodgers, I S; Baetcke, K P; Richards, W L; McGaughy, R E; Valcovic, L R

1993-01-01

376

Biliary intraepithelial neoplasia (BilIN) is frequently found in surgical margins of biliary tract cancer resection specimens but has no clinical implications.  

PubMed

Biliary tract cancers are aggressive tumors of which the incidence seems to increase. Resection with cancer-free margins is crucial for curative therapy. However, how often biliary intraepithelial neoplasia (BilIN) occurs in resection margins and what its clinical and therapeutic implications might be is largely unknown. We reexamined margins of resection specimens of adenocarcinoma of the biliary tree including the gallbladder for the presence of BilIN. When present, it was graded. The findings were correlated with clinicopathological parameters and overall survival. Complete examination of the resection margin could be performed on 55 of 78 specimens (71 %). BilIN was detected in the margin in 29 specimens (53 %) and was mainly low-grade (BilIN-1; N?=?14 of 29; 48 %). In resection specimens of extrahepatic cholangiocarcinoma, BilIN was most frequent (N?=?6 of 8; 75 %). BilIN was found in the resection margin more frequently in extrahepatic cholangiocarcinomas (P?=?0.007) and in large primary tumors (P?=?0.001) with lymphovascular (P?=?0.006) and perineural invasion (P?=?0.049). Patients with cancer in the resection margin (R1) had a significantly shorter overall survival than those with resection margins free of tumor (R0) irrespective of the presence of BilIN (R0 vs R1; P?

Matthaei, Hanno; Lingohr, Philipp; Strässer, Anke; Dietrich, Dimo; Rostamzadeh, Babak; Glees, Simone; Roering, Martin; Möhring, Pauline; Scheerbaum, Martin; Stoffels, Burkhard; Kalff, Jörg C; Schäfer, Nico; Kristiansen, Glen

2014-11-26

377

Should Prior FIT Results Be Incorporated as an Additional Variable to Estimate Risk of Colorectal Neoplasia? A Prospective Study of 5,813 Screening Colonoscopies  

PubMed Central

Background Recent studies showed that previous negative results from faecal immunochemical tests (FITs) for colorectal cancer (CRC) screening was associated with lower risk of advanced neoplasia (AN). We evaluated whether prior FIT results should be included to estimate the risk of AN in 2008–2012. Methods A community-based screening practice recruited 5,813 asymptomatic residents aged 50 to 70 years in Hong Kong for CRC screening. We included study participants who had (1). positive FIT with subsequent colonoscopy workup (FIT+ group; n?=?356); (2). negative FIT in three consecutive years and received a colonoscopy (FIT- group; n?=?857); (3). received colonoscopy without FIT (colonoscopy group; n?=?473); and (4). received both colonoscopy and FIT at the same time (combined group; n?=?4,127). One binary logistic regression model evaluated whether prior FIT results were associated with colonoscopy findings of AN. Results The proportion of participants having AN/CRC was 18.0% (FIT+), 5.5% (FIT-), 8.0% (colonoscopy group), and 4.3% (combined group), respectively. When compared with the colonoscopy group, those in the FIT- group were not significantly more or less likely to have AN/CRC (AOR ?=?0.77, 95% C.I.?=?0.51 to 1.18, p ?=?0.230). Having one (AOR?=?0.73, 95% C.I. 0.48–1.12, p?=?0.151) or three consecutive negative FIT result (AOR?=?0.98, 95% C.I. 0.60–1.62, p?=?0.944) were not associated with lower risks of AN/CRC. Subjects in the FIT+ group was 3.32-fold (95% C.I. 2.07 to 5.32, p<0.001) more likely to have AN/CRC. Conclusions These findings indicated that subjects with negative FIT findings could be risk stratified similarly as those who had not previously received FIT. PMID:25479102

Wong, Martin C. S.; Ching, Jessica Y. L.; Chan, Victor C. W.; Shum, Jeffrey P.; Lam, Thomas Y. T.; Luk, Arthur K. C.; Sung, Joseph J. Y.

2014-01-01

378

Predictors of persistent cytologic abnormalities after treatment of cervical intraepithelial neoplasia in Soweto, South Africa: a cohort study in a HIV high prevalence population  

PubMed Central

Background In the presence of both HIV infection and cervical intraepithelial neoplasia (CIN), the risk of cancer development despite treatment may be greater. We investigated clinical predictors of persistent cytological abnormalities in women who had had a large loop excision of the transformation zone (LLETZ). Methods Women with high grade squamous intraepithelial lesions or worse (HSIL), less severe abnormalities which persisted and any abnormality in women who are HIV-infected, were referred to the colposcopy clinic. HIV infection was ascertained by self-report. A LLETZ was performed on all patients with HSIL or higher on Papanicolaou (Pap) smear or colposcopy, LSIL or higher in patients who are HIV-infected, where the colposcopy is inadequate, and when there was a discrepancy between colposcopy and cytology by one or more grades. Women with abnormal follow-up smears were compared to those with normal smears. We examined the association between abnormal follow-up smears and demographic and clinical predictors using logistic regression Results The median time between LLETZ and first follow-up Pap smear was rather short at 122 days. Persistent cytological abnormalities occurred in 49% of our patients after LLETZ. Predictors of persistence included the presence of disease at both margins and HIV infection. Among the latter, disease at the excision margins and CD4+ cell count were important predictors. In these women, disease at the endocervical margin, both margins, and disease only at the ectocervical margin were associated with increased odds of persistent abnormalities on follow-up cervical smear. Conclusion We showed extremely high risk of cytological abnormality at follow-up after treatment more so in patients with incomplete excision and in the presence of immunocompromise. It remains uncertain whether recurrent CIN is a surrogate marker for invasive cervical cancer. PMID:18657270

Adam, Yasmin; van Gelderen, Cyril J; de Bruyn, Guy; McIntyre, James A; Turton, Diane A; Martinson, Neil A

2008-01-01

379

Alterations in classical and nonclassical HLA expression in recurrent and progressive HPV-induced usual vulvar intraepithelial neoplasia and implications for immunotherapy.  

PubMed

Immunotherapy of usual vulvar intraepithelial neoplasia (uVIN) is promising; however, many patients still fail to show clinical responses, which could be explained by an immune escape through alterations in human leukocyte antigen (HLA) expression. Therefore, we analyzed a cohort of patients with a primary (n = 43) and subsequent recurrent uVIN lesion (n = 20), vaccine-treated uVIN patients (n = 12), patients with human papillomavirus (HPV)-induced vulvar carcinoma (n = 21) and healthy controls (n = 26) for the expression of classical HLA-class I/II and nonclassical HLA-E/-G and MHC class I chain-related molecule A (MICA). HLA-class I was downregulated in 70% of uVIN patients, including patients with a clinical response to immunotherapy. Downregulation of HLA-class I is probably reversible, as only 15% of the uVIN cases displayed loss of heterozygosity (LOH) and HLA-class I could be upregulated in uVIN keratinocyte cultures by interferon ?. HLA-class I downregulation is more frequently associated with LOH in vulvar carcinomas (25-55.5%). HLA-class II was found to be focally expressed in 65% of uVIN patients. Of the nonclassical molecules, MICA was downregulated in 80% of uVIN whereas HLA-E and -G were expressed in a minority of cases. Their expression was more prominent in vulvar carcinoma. No differences were found between the alterations observed in paired primary and recurrent uVIN. Importantly, downregulation of HLA-B/C in primary uVIN lesions was associated with the development of recurrences and progression to cancer. We conclude that downregulation of HLA is frequently observed in premalignant HPV-induced lesions, including clinical responders to immunotherapy, and is associated with worse clinical outcome. However, in the majority of cases downregulation may still be reversible. PMID:24415578

van Esch, E M G; Tummers, B; Baartmans, V; Osse, E M; Ter Haar, N; Trietsch, M D; Hellebrekers, B W J; Holleboom, C A G; Nagel, H T C; Tan, L T; Fleuren, G J; van Poelgeest, M I E; van der Burg, S H; Jordanova, E S

2014-08-15

380

Diagnostic implications of L1, p16, and Ki-67 proteins and HPV DNA in low-grade cervical intraepithelial neoplasia.  

PubMed

The expressions of p16, Ki-67, and L1 proteins and human papillomavirus DNA were investigated using polymerase chain reaction (HPV/PCR) and catalyzed signal-amplified colorimetric DNA in situ hybridization (CSAC/ISH) as potential molecular markers for the diagnosis and transforming potential of low cervical intraepithelial neoplasia (CIN1). Ki-67 and p16 protein expression increased linearly from control cases to more dysplastic cases (CIN1, CIN2, and CIN3), peaking in squamous cell carcinoma cases (P<0.05). In contrast, L1 expression was inversely correlated with malignant transformation. Patients with CIN1 were divided into 4 groups: L1p16, L1p16, L1p16, and L1p16, and the immunohistochemical results were combined with HPV/PCR, L1/PCR, and high-risk E6/E7 genome and CSAC/ISH data. Malignant transformation correlated with L1p16 patients (100% of CIN2, CIN3, and squamous cell carcinoma cases) and was evident in approximately 23% of CIN1 cases. In addition, the presence of HPV/DNA was evident in 52% of CIN1 cases, and within the L1p16 group. In 4 of 7 cases, the high-risk E6/E7 HPV genome was present and in 1 case it was integrated into the host DNA, as confirmed using CSAC/ISH. In patients with CIN1, investigating the presence of HPV/DNA using PCR and the presence of the high-risk E6/E7 genome is necessary to distinguish high-risk oncogenic patient groups from low-risk groups. This study highlights the importance of combining immunohistochemical analysis with HPV/PCR and CSAC/ISH to identify patients with CIN1 with a risk of neoplastic progression. PMID:21979598

Gatta, Luisa Benerini; Berenzi, Angiola; Balzarini, Piera; Dessy, Enrico; Angiero, Francesca; Alessandri, Giulio; Gambino, Angela; Grigolato, Piergiovanni; Benetti, Anna

2011-11-01

381

Adjunctive HPV in-situ hybridization (ISH) assay as an aid in the diagnosis of cervical intraepithelial neoplasia in cervical tissue specimens: an analytical and functional characterization.  

PubMed

The purpose of this study was to develop and analytically and functionally validate a new human papillomavirus (HPV) in-situ hybridization (ISH) assay and to determine whether the use of this assay combined with hemotoxylin and eosin (H&E) staining could potentially improve the diagnostic accuracy of interpreting cervical intraepithelial neoplasia (CIN) in human cervical tissue specimens. An automated HPV ISH assay was developed using probes that targeted the broad spectrum of HPV genotypes most commonly associated with CIN. In an exploratory study, tissue sections (n=118) were stained with H&E alone and H&E with HPV ISH and evaluated by 6 general surgical pathologists. Results were compared with diagnoses established by expert pathologists on H&E alone. The change in specificity (diagnosis of no-CIN) and sensitivity (diagnosis of CIN) using H&E plus HPV versus H&E alone was determined. The HPV ISH assay detected 21 HPV genotypes and demonstrated no cross-reactivity to Epstein-Barr virus, cytomegalovirus, herpes simplex virus (HSV)-1, HSV-2, or human placental DNA. The assay detected HPV in a range of 1 to 600 copies on CaSki, HeLa, and SiHa xenografts. Use of this assay with H&E staining improved the average diagnostic specificity of the surgical pathologists from 68.5% to 89.9% (P<0.001), with fewer false-positive CIN 1 results (122 vs. 39). The diagnostic sensitivity was similar for assessments made with H&E alone and those made with HPV plus H&E (93.1% vs. 93.6%). In conclusion, a new automated broad-spectrum HPV ISH assay combined with H&E-stained slides contributed to better ascertainment of CIN than H&E staining alone. PMID:23018222

Zhang, Wenjun; Kapadia, Monesh; Sugarman, Michael; Free, Heather; Upchurch, Catherine; Gniewek, Richard; White, Katie; Miller, Melanie; Vladich, Frank; Ferenczy, Alex; Wright, Thomas C; Stoler, Mark H; Pestic-Dragovich, Lidija

2012-11-01

382

Interphase FISH analysis of PTEN in histologic sections shows genomic deletions in 68% of primary prostate cancer and 23% of high-grade prostatic intra-epithelial neoplasias.  

PubMed

Prostate cancer (CaP) is characterized by the accumulation of both genetic and epigenetic alterations that transform premalignant lesions to invasive carcinoma. However, the molecular events underlying this critical transition are poorly understood. One of the important genes that might play a role in CaP development is the PTEN gene. At the present time, there has been no systematic analysis of the incidence of genomic PTEN deletion by fluorescence in situ hybridization (FISH) in CaP and associated preneoplastic histologic lesions. This study assesses the frequency of PTEN deletion by interphase FISH analysis in CaP and prostatic intra-epithelial neoplasia (PIN). Dual-color FISH was performed using DNA probes for bands 10q23.3 (PTEN locus) and chromosome 10 centromere using 35 radical prostatectomy specimens. PTEN deletions were not found in 3/3 of stroma, 6/6 samples of benign glandular epithelium, and 12/12 samples of low-grade PIN. However, PTEN deletions were found in 3/13 (23%) of high-grade PIN and 24/35 (68%) of CaP. Concordance was observed between PTEN deletion status and the overall cellular PTEN protein expression levels, as assessed by immunohistochemistry. The high frequency of PTEN deletion observed in CaP versus precursor lesions implicates a pivotal role for PTEN haploinsufficiency in the transition from preneoplastic PIN to CaP. Moreover, this observation is an important consideration for novel therapeutic trials in CaP in which biologic efficacy is influenced by the activity level of PTEN. These findings draw attention to the usefulness of this relatively simple FISH assay for future applications in clinical laboratories. PMID:16938570

Yoshimoto, Maisa; Cutz, Jean-Claude; Nuin, Paulo A S; Joshua, Anthony M; Bayani, Jane; Evans, Andrew J; Zielenska, Maria; Squire, Jeremy A

2006-09-01

383

Clinicopathological analysis of intraductal proliferative lesions of prostate: intraductal carcinoma of prostate, high-grade prostatic intraepithelial neoplasia, and atypical cribriform lesion.  

PubMed

Intraductal carcinoma of the prostate (IDC-P) and high-grade prostatic intraepithelial neoplasia (HGPIN) are two distinct intraductal lesions; the former is usually associated with invasive carcinoma and has an aggressive course while the latter is considered a precancerous lesion. In addition, there are morphologically lesions not well characterized that fall between IDC-P and HGPIN, consequently termed "atypical cribriform lesions (ACLs)." Using whole mount radical prostatectomy specimens, we evaluated the relationship between these intraductal proliferative lesions and clinicopathological parameters. In this study, ACLs were characterized as a loose cribriform intraductal proliferation with greater architectural complexity when compared to HGPIN, but lacking significant nuclear pleomorphism and/or comedonecrosis. Of 901 radical prostatectomies (2006-2012), IDC-P, ACL, and HGPIN were recorded in 155, 22, 436 cases, respectively. Patients with IDC-P showed more aggressive pathologic features when compared to HGPIN. Invasive cancers in patients with ACL had higher Gleason score (P=.00016), larger tumor volume (P=.025), and more advanced pT stage (P=.023) than those with HGPIN. Cases with ACL showed a higher risk of biochemical recurrence than those with HGPIN and a lower risk than those with IDC-P based on log-rank tests (P=.0045 and P=.0069, respectively). In multivariate analysis, the presence of HGPIN was identified as an independent predictor for infrequent biochemical recurrence (P=.0058). We confirmed IDC-P as a marker of adverse pathologic features and clinical aggressiveness. Our results suggest that ACL should be distinguished from HGPIN and these lesions mandate active clinical surveillance. PMID:24842280

Miyai, Kosuke; Divatia, Mukul K; Shen, Steven S; Miles, Brian J; Ayala, Alberto G; Ro, Jae Y

2014-08-01

384

Effects of a flaxseed mixture and plant oils rich in alpha-linolenic acid on the adenoma formation in multiple intestinal neoplasia (Min) mice.  

PubMed

Flaxseed is a dietary source of possible chemopreventive compounds such as lignans and alpha-linolenic acid (ALA). To study the effects of a flaxseed mixture on adenoma formation in multiple intestinal neoplasia mice, the mice were fed a diet containing 2.7 % flaxseed, 4.5 % fibre and 3.7 % ALA. To elucidate the effect of oils of the mixture we also composed a diet without flaxseed but with the same oil composition. The median number of adenomas in the small intestine was fifty-four for the control group, and thirty-seven (P=0.023) and forty-two (P=0.095) for flaxseed and oil groups, respectively. Compared with controls (1.2 mm), the adenoma size was smaller in the flaxseed (0.9 mm; P=0.002) and oil (1.0 mm; P=0.012) groups. Both diets changed the proportions of n-3 and n-6 fatty acids in the colonic mucosa. Membrane beta-catenin and protein kinase C (PKC)-zeta levels were reduced in the adenoma v. mucosa (P<0.05), and an inverse association was found between the membrane PKC-zeta in the mucosa and the adenoma number (r -0.460, P=0.008, n 32). Only the flaxseed diet increased lignan levels in the caecum (P=0.002) and in plasma (P=0.002) but they were not associated with tumour formation. The results suggest that the preventive effect of flaxseed on colon carcinogenesis may be due to the oil part of flaxseed, and the loss of beta-catenin and PKC-zeta from the membranes of the mucosal tissue may play a permissive role in intestinal tumour development. PMID:16197574

Oikarinen, Seija I; Pajari, Anne-Maria; Salminen, Irma; Heinonen, Satu-Maarit; Adlercreutz, Herman; Mutanen, Marja

2005-10-01

385

Differentiated vulvar intraepithelial neoplasia is often found in lesions, previously diagnosed as lichen sclerosus, which have progressed to vulvar squamous cell carcinoma.  

PubMed

Lichen sclerosus is considered to be the precursor lesion of vulvar squamous cell carcinoma, of which only 2-5% progress to squamous cell carcinoma. Differentiated vulvar intraepithelial neoplasia (VIN) has been proposed to be the direct precursor lesion, but this is a recently recognized, and a difficult to diagnose, entity, which may easily be mistaken for a benign dermatosis. The aim of this study was to test the hypothesis that of all lesions that have been diagnosed as lichen sclerosus in the past, a part might currently be diagnosed as differentiated VIN, and to identify histopathological differences between lichen sclerosus lesions with and without progression to vulvar squamous cell carcinoma. All lichen sclerosus slides were revised by two expert gynecopathologists and histopathological characteristics were documented. After revision of lichen sclerosus biopsies without progression (n = 61), 58 were reclassified as lichen sclerosus. Revision of lichen sclerosus biopsies with progression yielded concordant diagnoses in 18 of 60 cases (30%). Of 60 lesions, 25 (42%) were reclassified as differentiated VIN. The median time from differentiated VIN to vulvar squamous cell carcinoma was shorter (28 months) than that from lichen sclerosus to vulvar squamous cell carcinoma (84 months) (P < 0.001). Lichen sclerosus that progressed to squamous cell carcinoma, but did not meet the criteria for differentiated VIN, more often showed parakeratosis (P = 0.004), dyskeratosis (P < 0.001), hyperplasia (P = 0.048) and basal cellular atypia (P = 0.009) compared with lichen sclerosus without progression. In conclusion, differentiated VIN diagnosis has been frequently missed and is associated with rapid progression to squamous cell carcinoma. Patients with lichen sclerosus with dyskeratosis and parakeratosis, hyperplasia and/or basal cellular atypia should be kept under close surveillance as these lesions also tend to progress to squamous cell carcinoma. PMID:21057461

van de Nieuwenhof, Hedwig P; Bulten, Johan; Hollema, Harrie; Dommerholt, Rianne G; Massuger, Leon F A G; van der Zee, Ate G J; de Hullu, Joanne A; van Kempen, Leon C L T

2011-02-01

386

Type-specific persistence or regression of human papillomavirus genotypes in women with cervical intraepithelial neoplasia 1: A prospective cohort study  

PubMed Central

Objective To evaluate the type-specific human papillomavirus (HPV) persistence or regression in women with or less than low-grade cervical intraepithelial neoplasia (CIN). Methods This prospective cohort study included patients with or less than cytological low-grade squamous intraepithelial lesion (or histologically CIN 1 when biopsy was performed) combined with HPV infection. The cohort was collected from July 2006 to November 2011 at Korea University Guro Hospital. Follow-up was performed with liquid-based Papanicolaou test, hybrid capture 2 test, AnyplexTM II HPV 28 Detection, colposcopic biopsy if necessary every 4 months. All patients were prospectively observed without treatment. Results One hundred and thirty-seven patients were enrolled. Of these, 21 patients whose minimum follow-up periods were less than 8 months were excluded. Finally, one hundred sixteen patients were included and followed-up. Median follow-up period was 16 months. In case of high-risk HPVs, HPV 53 was the most prevalent type, followed by HPV 52, 68, 66, and 16. HPV 16 took 10.6 months to regress spontaneously, which was the longest period among the 10 most prevalent high-risk HPV genotypes. In case of spontaneous regression, HPV clearance was always accompanied by lesion clearance. A total of 13 patients showed disease progression either cytologically or histologically. Two cases of CIN 3 were confirmed by colposcopy-directed biopsy during follow-up, which were subsequently managed by conization. Conclusion HPV 16 is the most persistent HPV genotypes. Studies with longer term follow-up and larger sample size are needed to demonstrate whether persistence of HPV 16 is directly correlated with progression of low-grade lesions.

Cho, Hyun Woong; So, Kyeong A; Lee, Jae Kwan

2015-01-01

387

Risk Factors for Cervical Intraepithelial Neoplasia in HIV-Infected Women on Antiretroviral Treatment in Côte d'Ivoire, West Africa  

PubMed Central

Background Facing the dual burden of invasive cervical cancer and HIV in sub-Saharan Africa, the identification of preventable determinants of Cervical Intraepithelial Neoplasia (CIN) in HIV-infected women is of paramount importance. Methods A cervical cancer screening based on visual inspection methods was proposed to HIV-infected women in care in Abidjan, Côte d'Ivoire. Positively screened women were referred for a colposcopy to a gynaecologist who performed directed biopsies. Results Of the 2,998 HIV-infected women enrolled, 132 (4.4%) CIN of any grade (CIN+) were identified. Women had been followed-up for a median duration of three years [IQR: 1–5] and 76% were on antiretroviral treatment (ART). Their median most recent CD4 count was 452 [IQR: 301–621] cells/mm3. In multivariate analysis, CIN+ was associated with a most recent CD4 count >350 cells/mm3 (OR: 0.3; 95% CI: 0.2–0.6) or ?200–350 cells/mm3 (OR 0.6; 95% CI 0.4–1.0) (Ref: <200 cells/mm3 CD4) (p<10?4). Conclusions The presence of CIN+ is less common among HIV-infected women with limited or no immune deficiency. Despite the potential impact of immunological recovery on the reduction of premalignant cervical lesions through the use of ART, cervical cancer prevention, including screening and vaccination remains a priority in West Africa while ART is rolled-out. PMID:24595037

Jaquet, Antoine; Horo, Apollinaire; Ekouevi, Didier K.; Toure, Badian; Coffie, Patrick A.; Effi, Benjamin; Lenaud, Severin; Messou, Eugene; Minga, Albert; Sasco, Annie J.; Dabis, François

2014-01-01

388

MTHFR/p53 polymorphisms as genetic factors for cervical intraepithelial neoplasia and cervical cancer in HPV-infected Mexican women.  

PubMed

We performed a case-control association study to evaluate the association between common polymorphisms in MTHFR (C677T and A1298C) and the Arg72Pro polymorphism in the p53 gene and the risk for cervical intraepithelial neoplasia (CIN) or invasive cervical cancer (ICC) in Mexican HPV-infected women. We included 131 women with diagnosis of CIN grade I-II and 78 with CIN III or ICC; as controls we also included 274 women with normal Pap smear and negative HPV test. Genotyping for MTHFR and p53 polymorphisms was performed by PCR-RFPLs. HPV was tested by Hybrid Capture II. Odds ratios and 95% confidence intervals were estimated. Genotype frequencies for the 3 studied polymorphisms were distributed according to the Hardy-Weinberg equilibrium. The A