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1

Lobular neoplasia.  

PubMed

Lobular neoplasia (LN) is characterized by a dysfunctional E-cadherin-catenin axis, and loss of E-cadherin plays a causative role in the typical morphology of LN cells. LN is both a nonobligate precursor and a risk indicator of invasive breast cancer, and in particular, of invasive lobular carcinoma. Despite the evidence supporting the precursor role of LN, its impact on clinical management has been a matter of controversy, and conservative management remains the mainstay of treatment. In this article, an update is provided on the pathology and genetics of LN, and the management of these lesions in surgical practice is discussed. PMID:24882347

King, Tari A; Reis-Filho, Jorge S

2014-07-01

2

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

3

Multiple Endocrine Neoplasia  

Microsoft Academic Search

\\u000a The term “multiple endocrine neoplasia” was first used by Steiner in the late 1960s when he described three distinct endocrine\\u000a disorders. The first disorder, multiple endocrine neoplasia type I (MEN 1) (also known as Wermer syndrome), described patients\\u000a with familial pituitary, parathyroid, and pancreatic islet cell tumors. The second syndrome, multiple endocrine neoplasia\\u000a type II (MEN 2) (also known as

Christine S. Landry; Thereasa Rich; Camilo Jimenez; Elizabeth G. Grubbs; Jeffrey E. Lee; Nancy D. Perrier

4

Immunohistochemistry of Pancreatic Neoplasia  

PubMed Central

Immunohistochemistry (IHC) is a valuable tool to visualize the distribution and localization of specific cellular components within morphologically preserved tissue sections or cell preparations. It combines the histologic morphology of tissues for detecting the actual antigen distribution, specificity of antibody–antigen interaction for optimal detection, and sensitivity of immunochemical methods for assessing the amount of antigen in tissues. It is routinely used clinically to diagnose type (benign or malignant), stage, and grade of cancer using specific tumor markers. The application of IHC ranges from disease diagnosis and prognosis to drug development and analysis of the pathobiological roles of various molecular players during disease development. Due to better availability of highly specific antibodies and optimal methodologies for performing immunohistochemical studies, IHC is being used at an expanding rate to understand pancreatic tumor biology as well as to study the fate of various molecular markers during the initiation, progression, and metastasis of pancreatic neoplasia. Herein, we describe the detailed protocol for IHC analyses of pancreatic intraepithelial neoplasia in tissues and fine needle aspirates from both human and mouse samples. PMID:23359148

Kaur, Sukhwinder; Shimizu, Tomohiro; Baine, Michael J.; Kumar, Sushil; Batra, Surinder K.

2013-01-01

5

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

6

Multiple endocrine neoplasia type 1  

Microsoft Academic Search

Multiple Endocrine Neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary cancer syndrome presented mostly by tumours of the parathyroids, endocrine pancreas and anterior pituitary, and characterised by a very high penetrance and an equal sex distribution. It occurs in approximately one in 30,000 individuals. Two different forms, sporadic and familial, have been described. The sporadic form presents with

Francesca Marini; Alberto Falchetti; Francesca Del Monte; Silvia Carbonell Sala; Alessia Gozzini; Ettore Luzi; Maria Luisa Brandi

2006-01-01

7

Endoscopic therapies for Barrett's neoplasia.  

PubMed

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

Watson, Thomas J

2014-05-01

8

Early Cervical Neoplasia: Treatment Methods  

PubMed Central

Cervical cancer screening programs have been one of the most important developments in women's health care during the past 50 years. Sound knowledge of the principles and techniques for taking Papanicolaou smears, interpreting results, and investigating abnormalities detected are essential skills for individuals providing primary health care to women. The author briefly reviews the current investigatory methods and the common treatments for cervical intraepithelial neoplasia and early invasive cancer of the cervix. PMID:21233966

Benedet, J.L.

1990-01-01

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

The Vienna classification of gastrointestinal epithelial neoplasia  

Microsoft Academic Search

BACKGROUNDUse of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions.AIMTo develop common worldwide terminology for gastrointestinal epithelial neoplasia.METHODSThirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between

R J Schlemper; R H Riddell; Y Kato; F Borchard; H S Cooper; S M Dawsey; M F Dixon; C M Fenoglio-Preiser; J-F Fléjou; K Geboes; T Hattori; T Hirota; M Itabashi; M Iwafuchi; A Iwashita; Y I Kim; T Kirchner; M Klimpfinger; M Koike; G Y Lauwers; K J Lewin; G Oberhuber; F Offner; A B Price; C A Rubio; M Shimizu; T Shimoda; P Sipponen; E Solcia; M Stolte; H Watanabe; H Yamabe

2000-01-01

11

[Multiple endocrine neoplasia type 2].  

PubMed

Multiple endocrine neoplasia type 2 syndrome (MEN-2) is a rare hereditary cancer syndrome with autosomal dominant trait of inheritance. The most characteristic feature of this syndrome is a complete penetrance of medullary thyroid cancer. On the basis of differences in variable expression of pheochromocytomas, hyperparathyroidism, and other clinical features, MEN-2 is divided into three clinical variants, referred to as MEN-2A, MEN-2B and familial medullary thyroid cancer. In the most frequent variant, MEN-2A syndrome, apart from thyroid carcinoma, this syndrome includes also unilateral or bilateral pheochromocytoma and hyperparathyroidism. In less common MEN-2B, medullary thyroid cancer and pheochromocytoma occur together with complex nervous and skeletal abnormalities. Familial medullary thyroid cancer is a variant of MEN-2 in which individuals affected develop only this neoplasm without other manifestations of MEN-2. It is well known that MEN-2 is caused by mutations of different codons of the RET proto-oncogene. The identification of mutations associated with this syndrome has led to genetic testing to identify patients at risk for MEN-2. There is a significant genotype-phenotype correlation, which allows a more individualised approach to the timing of prophylactic thyroidectomy. In this paper, we review the current views on the etiopathogenesis, clinical presentation, diagnosis and treatment of MEN-2. PMID:22708287

Krysiak, Robert; Okopie?, Bogus?aw

2012-04-01

12

Fluorescence detection of esophageal neoplasia  

NASA Astrophysics Data System (ADS)

White-light endoscopy is well-established and wide used modality. However, despite the many technological advances that have been occurred, conventional endoscopy is suboptimal and usually detects advanced stage lesions. The limitations of standard endoscopy initiate development of spectroscopic techniques, additional to standard endoscopic equipment. One of the most sensitive approaches is fluorescence spectroscopy of gastrointestinal mucosa for neoplasia detection. In the recent study delta-aminolevulinic acid/Protoporphyrin IX (5-ALA/PpIX) is used as fluorescent marker for dysplasia and tumor detection in esophagus. The 5-ALA is administered per os six hours before measurements at dose 20 mg/kg weight. Excitation source has max of emission at 405 nm and light is delivered by the standard light guide of the endoscopic equipment. Through endoscopic instrumental channel a fiber is applied to return information about fluorescence to microspectrometer. Spectral features observed during endoscopic investigations could be distinct as the next regions: 450-630 nm region, where tissue autofluorescence is observed; 630-710 nm region, where fluorescence of PpIX is clearly pronounced; 530-580 nm region, where minima in the autofluorescence signal are observed, related to reabsorption of blood. The lack of fluorescence peaks in the red spectral area for normal mucosa is an indication for selective accumulation of 5-ALA/PpIX only in abnormal sites Very good correlation between fluorescence signals and histology examination of the lesions investigated is achieved.

Borisova, E.; Vladimirov, B.; Avramov, L.

2008-06-01

13

Squamous intraepithelial neoplasia in an ovarian cyst, cervical intraepithelial neoplasia, and human papillomavirus  

Microsoft Academic Search

A case of squamous intraepithelial neoplasia in an ovarian cyst in association with cervical intraepithelial neoplasia (CIN) III is described. In view of the association of human papillomavirus (HPV) and CIN, the possibility that HPV infection could be associated with similar changes in the ovary was postulated. The HPV genome was shown in formalin-fixed tissue of the cervical lesion by

M. J Sworn; H Jones; A. T Letchworth; C. S Herrington; J. O'D McGee

1995-01-01

14

Vaginal intraepithelial neoplasia: a therapeutical dilemma.  

PubMed

Vaginal intraepithelial neoplasia (VaIN) represents a rare and asymptomatic pre-neoplastic lesion. Its natural history and potential evolution into invasive cancer are uncertain. VaIN can occur alone or as a synchronous or metachronous lesion with cervical and vulvar HPV-related intra epithelial or invasive neoplasia. Its association with cervical intraepithelial neoplasia is found in 65% of cases, with vulvar intraepithelial neoplasia in 10% of cases, while for others, the association with concomitant cervical or vulvar intraepithelial neoplasias is found in 30-80% of cases. VaIN is often asymptomatic and its diagnosis is suspected in cases of abnormal cytology, followed by colposcopy and colposcopically-guided biopsy of suspicious areas. In the past, high-grade VaIN and multifocal VaIN have been treated by radical surgery, such as total or partial upper vaginectomy associated with hysterectomy and radiotherapy. The need to maintain the integrity of reproductive capacity has determined the transition from radical therapies to conservative ones, according to the different patients' characteristics. PMID:23267125

Frega, Antonio; Sopracordevole, Francesco; Assorgi, Chiara; Lombardi, Danila; DE Sanctis, Vitaliana; Catalano, Angelica; Matteucci, Eleonora; Milazzo, Giusi Natalia; Ricciardi, Enzo; Moscarini, Massimo

2013-01-01

15

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.

16

Risk of neoplasia in renal transplant patients  

Microsoft Academic Search

SummaryRenal allograft recipients are at an increased risk of neoplasia, although the extent of the problem has not been established in a typical European transplant population. To assess this risk we did a comprehensive, retrospective study of 918 patients transplanted at one centre over 24 years. The centre (Leeds) serves Yorkshire and Humberside, a region in northern England with a

N. J London; S. M Farmery; J. P. A Lodge; E. J Will; A. M Davidson

1995-01-01

17

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

18

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

19

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

20

Increased incidence of pancreatic neoplasia in pernicious anemia  

Microsoft Academic Search

In a Swedish population, 361 patients with pernicious anemia were followed closely during a 7-year period with regard to the occurrence of all forms of malignant neoplasia. In addition to an increased incidence of gastric neoplasia (0.6%\\/year), there seemed to be an increased incidence of pancreatic neoplasia (0.3%\\/year) in the series. With reference to age- and sex-specific incidence rates in

Kurt Borch; Eric Kullman; Stefan Hallhagen; Torbjörn Ledin; Ingemar Ihse

1988-01-01

21

Red-flag technologies in gastric neoplasia.  

PubMed

Given its morbidity and mortality, the early detection and diagnosis of gastric cancer is an area of intense research focus. This article reviews the emerging use of enhanced endoscopic imaging technologies in the detection and management of gastric cancer. The combined use of white-light endoscopy with enhanced imaging technologies, such as magnification narrow-band imaging, chromoendoscopy, and autofluorescence endoscopy, demonstrates promise in the improved ability to detect and delineate gastric neoplasia. However, widespread clinical use is still limited, mainly because of the restricted availability of the technologies. PMID:23735104

Gonzalez, Susana

2013-07-01

22

Risk of colorectal neoplasia in patients with primary sclerosing cholangitis  

Microsoft Academic Search

BACKGROUND & AIMS: Studies implicating primary sclerosing cholangitis as a risk factor for colorectal neoplasia in patients with ulcerative colitis have been limited by small sample size and referral bias. The aim of this study was to determine the relative risk and cumulative incidence of colorectal neoplasia in a large sample of patients with sclerosing cholangitis. METHODS: A sample of

EV Loftus Jr; WJ Sandborn; WJ Tremaine; DW Mahoney; AR Zinsmeister; KP Offord; LJ Melton

1996-01-01

23

Cyclin D1 and human neoplasia.  

PubMed Central

Neoplasia is characterised by abnormal regulation of the cell cycle. Cyclin D1 is a protein derived from the PRAD1, CCND1 or bcl-1 gene on chromosome 11q13, which is involved in both normal regulation of the cell cycle and neoplasia. In the G1 (resting) phase of the cell cycle, cyclin D1 together with its cyclin dependent kinase (cdk) partner, is responsible for transition to the S (DNA synthesis) phase by phosphorylating the product of the retinoblastoma gene (pRB), which then releases transcription factors important in the initiation of DNA replication. Amplification of the CCND1 gene or overexpression of the cyclin D1 protein releases a cell from its normal controls and causes transformation to a malignant phenotype. Analysis of these changes provides important diagnostic information in mantle cell (and related) lymphomas, and is of prognostic value in many cancers. Knowledge of cyclin D1's role in malignancy at the various sites, provides a basis on which future treatment directed against this molecule can proceed. PMID:9624412

Donnellan, R; Chetty, R

1998-01-01

24

GLUT-1 Expression in Pancreatic Neoplasia  

PubMed Central

Objectives GLUT-1 has been found to have an important role in the upregulation of various cellular pathways and implicated in neoplastic transformation correlating with biological behavior in malignancies. However, literature regarding the significance of GLUT-1 expression in pancreatic neoplasia has been limited and controversial. Methods Immunohistochemical expression of GLUT-1 was tested in a variety of pancreatic neoplasia including ductal adenocarcinomas (DAs), pancreatic intraepithelial neoplasms (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and serous cystadenomas. Results There was a progressive increase in the expression of GLUT-1 from low- to higher-grade dysplastic lesions: All higher-grade PanINs/IPMNs (the ones with moderate/high-grade dysplasia) revealed noticeable GLUT-1 expression. Among the 94 DAs analyzed, there were minimal/moderate expression in 46 and significant expression in 24 DAs. However, all 4 clear-cell variants of DAs revealed significant GLUT-1 immunolabeling, as did areas of clear-cell change seen in other DAs. Moreover, all 12 serous cystadenomas expressed significant GLUT-1. GLUT-1 expression was also directly correlated with DA histological grade (P = 0.016) and tumor size (P = 0.03). Conclusions GLUT-1 may give rise to the distinctive clear-cell appearance of these tumors by inducing the accumulation of glycogen in the cytoplasm. Additionally, because GLUT-1 expression was related to histological grade and tumor size of DA, further studies are warranted to investigate the association of GLUT-1 with prognosis and tumor progression. PMID:21206329

Basturk, Olca; Singh, Rajendra; Kaygusuz, Ecmel; Balci, Serdar; Dursun, Nevra; Culhaci, Nil; Adsay, N. Volkan

2011-01-01

25

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

26

Anal Warts and Anal Intradermal Neoplasia  

PubMed Central

For the last five millennia we have been dealing with the annoyance of verrucas. Anogenital human papillomavirus (HPV) infection is the most common sexually transmitted disease in the United States and is increasing in incidence. As in other gastrointestinal conditions, HPV infection can lead to a stepwise transition from normal cells to dysplastic cells and then to invasive anal cancer. Knowledge of the natural history of HPV infection, risk factors, diagnostic tools, and therapeutic methods gives us the tools to adequately prevent, evaluate, treat, and counsel our patients. In this review, the authors detail the diagnosis, management, and treatment of anal condyloma and anal intraepithelial neoplasia with a focus on prevention, early detection, and treatment using current data and technology. PMID:22379403

Echenique, Ignacio; Phillips, Benjamin R.

2011-01-01

27

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

28

Cervical Neoplasia and Cigarette Smoking: Are They Linked?  

PubMed

The presence of tobacco-specific carcinogens in the cervical mucus of smokers and their effect on the local immune system strongly suggest that smoking has an etiologic role in the development of cervical neoplasia. However, it remains unclear whether smoking can affect the initiation of high-grade cervical neoplasia independently from human papillomavirus (HPV) infection. Studies that control for HPV infection may not entirely resolve the issue of the role of smoking in cervical neoplasia. Cigarette smoking may be causative through its effect on oncogenic HPV infection or by altering the immune response system. This article reviews the currently available data assessing the relationship between cigarette smoking and cervical neoplasia. PMID:9746684

Runowicz; Lymberis; Tobias

1997-03-01

29

Vaginal intraepithelial neoplasia: clinical-therapeutic analysis of 33 cases  

Microsoft Academic Search

Vaginal intraepithelial neoplasia (VAIN) represents 1% of all intraepithelial neoplasia of the lower genital tract. Our aim\\u000a was to study the clinical-therapeutic characteristics of patients with VAIN. A retrospective study was made of all cases of\\u000a patients, who attended within the outpatient service between 1993 and 2003, with a diagnosis of VAIN. During this period,\\u000a 84,293 Papanicolaou smears (triple collection)

Eddie F. C. Murta; Milton A. Neves Junior; Luciano R. F. Sempionato; Marcos C. Costa; Paulo J. Maluf

2005-01-01

30

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

31

Neoplasia of the male reproductive tract.  

PubMed

Genital neoplasms in the male horse are relatively uncommon. Squamous cell carcinomas and squamous papillomas are the most commonly diagnosed neoplasms of the penis and prepuce. Geldings appear to be overrepresented for these types of neoplasms, and accumulation of smegma may be a contributing factor. Early diagnosis and treatment are essential for salvaging these organs before lesions become excessively large and invasive or are allowed to metastasize. Newer treatment modalities such as 5-fluorouracil appear to be promising alternatives to surgical excision. Although generally considered to be uncommon, testicular tumors may occur more frequently than previously thought and have the potential for devastating effects on stallion fertility. Cryptorchidism appears to play a role in the development of equine testicular tumors, especially teratomas. Seminoma is by far the most common testicular tumor of the mature stallion. Seminomas are rapidly growing tumors with a greater potential to metastasize in the horse than in other domestic species. Leydig cell and Sertoli cell tumors have been reported but are relatively rare in the stallion. Orchiectomy is the standard treatment for most testicular tumors. In certain circumstances, however, such as neoplasia occurring in the only functional testis, local cryotherapy of testicular tumors may prolong the breeding career of an affected stallion. PMID:9891722

Brinsko, S P

1998-12-01

32

Development and progression of colorectal neoplasia  

PubMed Central

A variety of genetic and molecular alterations underlie the development and progression of colorectal neoplasia (CRN). Most of these cancers arise sporadically due to multiple somatic mutations and genetic instability. Genetic instability includes chromosomal instability (CIN) and microsatellite instability (MSI), which is observed in most hereditary non-polyposis colon cancers (HNPCCs) and accounts for a small proportion of sporadic CRN. Although many biomarkers have been used in the diagnosis and prediction of the clinical outcomes of CRNs, no single marker has established value. New markers and genes associated with the development and progression of CRNs are being discovered at an accelerated rate. CRN is a heterogeneous disease, especially with respect to the anatomic location of the tumor, race/ethnicity differences, and genetic and dietary interactions that influence its development and progression and act as confounders. Hence, efforts related to biomarker discovery should focus on identification of individual differences based on tumor stage, tumor anatomic location, and race/ethnicity; on the discovery of molecules (genes, mRNA transcripts, and proteins) relevant to these differences; and on development of therapeutic approaches to target these molecules in developing personalized medicine. Such strategies have the potential of reducing the personal and socio-economic burden of CRNs. Here, we systematically review molecular and other pathologic features as they relate to the development, early detection, diagnosis, prognosis, progression, and prevention of CRNs, especially colorectal cancers (CRCs). PMID:22112479

Manne, Upender; Shanmugam, Chandrakumar; Katkoori, Venkat R.; Bumpers, Harvey L.; Grizzle, William E.

2012-01-01

33

Histologic classification of penile intraepithelial neoplasia.  

PubMed

Penile squamous cell carcinomas (SCCs) and their corresponding precancerous lesions can be classified in 2 major groups: human papillomavirus (HPV) related and HPV unrelated. In the former (warty and basaloid SCC), there is a predominance of undifferentiated basaloid cells. In the latter (eg, usual, papillary, and verrucous SCC), the predominant cell is larger with abundant eosinophilic cytoplasm. Based on these morphologic features, a new term, "penile intraepithelial neoplasia" (PeIN), was proposed. PeIN was further subclassified into differentiated and undifferentiated, with the latter being subdivided into basaloid, warty, and warty-basaloid subtypes. Macroscopically, PeIN subtypes are indistinguishable. Microscopically, differentiated PeIN is characterized by acanthosis, parakeratosis, enlarged keratinocytes with abundant "pink" cytoplasm (abnormal maturation), and hyperchromatic cells in the basal layer. In basaloid PeIN the epithelium is replaced by a monotonous population of uniform, small, round, and basophilic cells. Warty PeIN is characterized by a spiky surface, prominent atypical parakeratosis, and pleomorphic koilocytosis. Warty-basaloid PeIN show features of both warty and basaloid PeIN. There is a significant association of subtypes of PeIN with specific variants of invasive SCCs. This is a simple and reproducible nomenclature for penile precancerous lesions based on cell type and differentiation. It takes into account the similarities between vulvar and penile pathology and the hypothesis of a bimodal pathway of penile cancer progression. PMID:22641959

Velazquez, Elsa F; Chaux, Alcides; Cubilla, Antonio L

2012-05-01

34

Optical coherence tomography in vulvar intraepithelial neoplasia  

NASA Astrophysics Data System (ADS)

Vulvar squamous cell carcinoma (VSCC) is a gynecological cancer with an incidence of two to three per 100,000 women. VSCC arises from vulvar intraepithelial neoplasia (VIN), which is diagnosed through painful punch biopsy. In this study, optical coherence tomography (OCT) is used to differentiate between normal and VIN tissue. We hypothesize that (a) epidermal layer thickness measured in OCT images is different in normal tissue and VIN, and (b) quantitative analysis of the attenuation coefficient (?oct) extracted from OCT data differentiates VIN from normal vulvar tissue. Twenty lesions from 16 patients are imaged with OCT. Directly after data acquisition, a biopsy is performed. Epidermal thickness is measured and values of ?oct are extracted from 200 OCT scans of normal and VIN tissue. For both methods, statistical analysis is performed using Paired Mann-Whitney-test. Correlation between the two methods is tested using a Spearman-correlation test. Both epidermal layer thickness as well as the ?oct are different between normal vulvar tissue and VIN lesions (p<0.0001). Moreover, no correlation is found between the epidermal layer thickness and ?oct. This study demonstrates that both the epidermal thickness and the attenuation coefficient of vulvar epithelial tissue containing VIN are different from that of normal vulvar tissue.

Wessels, Ronni; de Bruin, Daniel M.; Faber, Dirk J.; van Boven, Hester H.; Vincent, Andrew D.; van Leeuwen, Ton G.; van Beurden, Marc; Ruers, Theo J. M.

2012-11-01

35

Histological Characterization of Biliary Intraepithelial Neoplasia with respect to Pancreatic Intraepithelial Neoplasia  

PubMed Central

Biliary intraepithelial neoplasia (BilIN) is a precursor lesion of hilar/perihilar and extrahepatic cholangiocarcinoma. BilIN represents the process of multistep cholangiocarcinogenesis and is the biliary counterpart of pancreatic intraepithelial neoplasia (PanIN). This study was performed to clarify the histological characteristics of BilIN in relation to PanIN. Using paraffin-embedded tissue sections of surgically resected specimens of cholangiocarcinoma associated with BilIN and pancreatic ductal adenocarcinoma associated with PanIN, immunohistochemical staining was performed using primary antibodies against MUC1, MUC2, MUC5AC, cyclin D1, p21, p53, and S100P. For mucin staining, Alcian blue pH 2.5 was used. Most of the molecules examined here showed similar expression patterns in BilIN and PanIN, in which their expression tended to increase along with the increase in atypia of the epithelial lesions. Significant differences were observed in the increase in mucin production and the expression of S100P in PanIN-1 and the expression of p53 in PanIN-3, when compared with those in BilIN of a corresponding grade. These results suggest that cholangiocarcinoma and pancreatic ductal adenocarcinoma share, at least in part, a common carcinogenic process and further confirm that BilIN can be regarded as the biliary counterpart of PanIN. PMID:24860672

Sasaki, Motoko; Nakanuma, Yasuni

2014-01-01

36

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

37

Succinate dehydrogenase (SDH) and mitochondrial driven neoplasia.  

PubMed

The genes for the succinate dehydrogenase (SDH) subunits SDHA, SDHB, SDHC and SDHD are encoded in the autosome. The proteins are assembled in the mitochondria to form the mitochondrial complex 2, a key respiratory enzyme which links the Krebs cycle and the electron transport chain. Thirty percent of phaeochromocytoma and paraganglioma (PHEO/PGL) are hereditary and perhaps as many as half of these familial cases are caused by germline mutations of the SDH subunits. Negative immunohistochemical staining for the SDHB subunit identifies PHEO/PGL associated with germline mutation of any of the mitochondrial complex 2 components and can be used to triage formal genetic testing of all PHEO/PGL for SDH mutations. PHEO/PGL associated with SDHA mutation also show negative staining for SDHA as well as SDHB.A unique subgroup of gastrointestinal stromal tumours (GISTs) are driven by mitochondrial complex 2 dysfunction. These SDH deficient GISTs can also be definitively identified by negative staining for SDHB and show distinct clinical and morphological features including frequent onset in childhood and young adulthood, gastric location, a tendency to multifocality, absence of KIT and PDGFRA mutations, a prognosis not predicted by size and mitotic rate and a tendency to indolent behaviour of metastases. Some of these SDH deficient GISTs are driven by classical SDH mutations, but the precise mechanisms of tumourigenesis in many (including those associated with the Carney triad) remain unknown. Germline SDHB mutation is associated with a newly recognised type of renal carcinoma which commonly but not always demonstrates distinctive morphology and can also be recognised by negative staining for SDHB.Immunohistochemistry for SDHB therefore has emerged as a useful tool to recognise these distinct neoplasias driven by mitochondrial complex 2 dysfunction and to triage formal genetic testing for the associated syndromes. PMID:22544211

Gill, Anthony J

2012-06-01

38

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

39

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

40

Innate immunity gene polymorphisms and the risk of colorectal neoplasia  

PubMed Central

Inherited variation in genes that regulate innate immunity and inflammation may contribute to colorectal neoplasia risk. To evaluate this association, we conducted a nested case–control study of 451 colorectal cancer cases, 694 colorectal advanced adenoma cases and 696 controls of European descent within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. A total of 935 tag single-nucleotide polymorphisms (SNPs) in 98 genes were evaluated. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association with colorectal neoplasia. Sixteen SNPs were associated with colorectal neoplasia risk at P < 0.01, but after adjustment for multiple testing, only rs2838732 (ITGB2) remained suggestively associated with colorectal neoplasia (ORper T allele = 0.68, 95% CI: 0.57–0.83, P = 7.7 × 10–5, adjusted P = 0.07). ITGB2 codes for the CD18 protein in the integrin beta chain family. The ITGB2 association was stronger for colorectal cancer (ORper T allele = 0.41, 95% CI: 0.30–0.55, P = 2.4 × 10? 9) than for adenoma (ORper T allele = 0.84, 95%CI: 0.69–1.03, P = 0.08), but it did not replicate in the validation study. The ITGB2 rs2838732 association was significantly modified by smoking status (P value for interaction = 0.003). Among never and former smokers, it was inversely associated with colorectal neoplasia (ORper T allele = 0.5, 95% CI: 0.37–0.69 and ORper T allele = 0.72, 95% CI: 0.54–0.95, respectively), but no association was seen among current smokers. Other notable findings were observed for SNPs in BPI/LBP and MYD88. Although the results need to be replicated, our findings suggest that genetic variation in inflammation-related genes may be related to the risk of colorectal neoplasia. PMID:23803696

Berndt, Sonja I.

2013-01-01

41

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

42

Ductal neoplasia of the pancreas: nosologic, clinicopathologic, and biologic aspects.  

PubMed

Most pancreatic neoplasia are of ductal lineage, characterized by tubule (gland), cyst, papilla, or mucin formation and expression of mucin-related glycoproteins and oncoproteins (eg, MUC1, CA19-9, CEA, DUPAN), as well as some subsets of cytokeratin (eg, CK19). Mutations of k-ras oncogene and DPC4 are also common in ductal neoplasia and generally not seen in nonductal tumors. A variety of pancreatic neoplasia fall under the heading of ductal neoplasia. Invasive ductal adenocarcinoma (DA) is the most important and constitutes the vast majority (>85%) of pancreatic tumors. DA is characterized by insidious infiltration and rapid dissemination, despite its relatively well-differentiated histologic appearance. In some variants of DA such as undifferentiated or sarcomatoid, evidence of ductal differentiation may be lacking or only focal. The presumed precursors of DA are microscopic intraductal proliferative changes that are now termed pancreatic intraepithelial neoplasia (PanIN). PanINs comprise a neoplastic transformation ranging from early mucinous change (PanIN-1A) to frank CIS (PanIN-3). A similar (in situ) neoplastic spectrum also characterizes intraductal papillary mucinous neoplasms and mucinous cystic neoplasms, which are cystic ductal-mucinous tumors with varying degrees of papilla formation, and may be associated with invasive carcinoma. As such, these can be regarded as mass-forming preinvasive neoplasia. Some intraductal papillary mucinous neoplasms are associated with invasive carcinoma of the colloid type. Colloid carcinoma of the pancreas appears to be a clinicopathologically distinct tumor with indolent behavior. Whereas most ductal pancreatic neoplasia are characterized by some degree of mucin formation, serous tumors, of which serous (microcystic) adenoma is the sole example, lack mucin formation, presumably because they recapitulate centroacinar ducts. They are typically benign tumors. It is recognized now that pancreatic carcinoma, like other malignant processes, is a genetic disease produced by progressive mutations in cancer-related genes. These alterations can be categorized as "early" such as k-ras mutation, HER-2/neu, PSCA, MUC5, and fascin overexpression; "intermediate" such as p16 inactivation, MUC1, and cyclin D1 overexpression; and finally as "late" such as p53 and DPC4 inactivation, BRCA2 mutation, and overexpression of ki-67, 14-3-3sigma, and mesothelin. Ductal neoplasia is the most important category among pancreatic tumors. It is important to appreciate the different types of ductal tumors because they vary greatly in their clinicopathologic characteristics and prognosis. Understanding the molecular mechanisms of ductal carcinogenesis will help develop more efficient prevention and therapy of these tumors. PMID:16183479

Adsay, Nazmi Volkan; Basturk, Olca; Cheng, Jeanette D; Andea, Aleodor A

2005-10-01

43

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...

44

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

45

Hematopoietic Neoplasias in Horses: Myeloproliferative and Lymphoproliferative Disorders  

PubMed Central

Leukemia, i.e., the neoplasia of one or more cell lines of the bone marrow, although less common than in other species, it is also reported in horses. Leukemia can be classified according to the affected cells (myeloproliferative or lymphoproliferative disorders), evolution of clinical signs (acute or chronic) and the presence or lack of abnormal cells in peripheral blood (leukemic, subleukemic and aleukemic leukemia). The main myeloproliferative disorders in horses are malignant histiocytosis and myeloid leukemia, the latter being classified as monocytic and myelomonocytic, granulocytic, primary erythrocytosis or polycythemia vera and megakaryocytic leukemia. The most common lymphoproliferative disorders in horses are lymphoid leukemia, plasma cell or multiple myeloma and lymphoma. Lymphoma is the most common hematopoietic neoplasia in horses and usually involves lymphoid organs, without leukemia, although bone marrow may be affected after metastasis. Lymphoma could be classified according to the organs involved and four main clinical categories have been established: generalized-multicentric, alimentary-gastrointestinal, mediastinal-thymic-thoracic and cutaneous. The clinical signs, hematological and clinical pathological findings, results of bone marrow aspirates, involvement of other organs, prognosis and treatment, if applicable, are presented for each type of neoplasia. This paper aims to provide a guide for equine practitioners when approaching to clinical cases with suspicion of hematopoietic neoplasia. PMID:24833969

MUÑOZ, Ana; RIBER, Cristina; TRIGO, Pablo; CASTEJÓN, Francisco

2010-01-01

46

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

47

Four cases of neoplasia in captive wild birds.  

PubMed

Four cases of malignant neoplasia in captive wild birds are described: an adenocarcinoma of the adrenal gland in a Mountain duck (Tadorna tadornoides), a malignant melanoma in the thoracic cavity of a Combed duck (Sarkidiornis melanotos), a hepatocellular carcinoma with pulmonary metastasis in an Asian Purple Swamphen (Porphyrio porphyrio), and an undifferentiated carcinoma in the abdomen with metastasis to skeletal muscle in a White-Breasted Waterhen (Amaurornis phoenicurus). The tumors were diagnosed during a 1-year period and represented an incidence of neoplasia of 3.1%. These appear to be the first documented cases of a malignant adrenal gland tumor and a non-ocular melanoma in the order Anseriformes. The hepatocellular carcinoma failed to react with an immunoperoxidase stain for alphafetoprotein. PMID:3579789

Dillberger, J E; Citino, S B; Altman, N H

1987-01-01

48

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

49

Evaluating the role of human papillomaviruses in conjunctival neoplasia  

PubMed Central

Mucosal, cutaneous and Epidermodysplasia verruciformis (EV)-related human papillomaviruses (HPVs) were searched by broad-spectrum PCR in 86 conjunctival neoplasia biopsies and 63 conjunctival non-neoplastic control tissue from Ugandan subjects. Seven different EV-related HPV types, including a putative new HPV, and two mucosal HPVs were detected in 25% (14 out of 56) of HIV-positive, in 10% (three out of 30) of HIV-negative conjunctival neoplasia samples, and rarely (0–1.6%) in control subjects. The absence of high-risk HPVs and the low detection frequency of EV-related HPV types in more advanced tumour stages (10%) raise doubts about their role in conjunctival carcinomas. PMID:16404433

Tornesello, M L; Duraturo, M L; Waddell, K M; Biryahwaho, B; Downing, R; Balinandi, S; Lucas, S B; Buonaguro, L; Buonaguro, F M

2006-01-01

50

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

51

LASER EN EL TRATAMIENTO DE LA NEOPLASIA INTRAEPITELIAL DE VAGINA  

Microsoft Academic Search

SUMMARY Objective: To describe our experience in the treatment of vaginal intra-epithelial neoplasia (VAIN) with the use of CO2 laser. Method: Nineteen patients with the diagnosis of VAIN were treated by this technique. We used a spot size of 1.5 to 2 mm and a power density of 400 to 500 W\\/cm2. The entire lesion in addition to at least

2006-01-01

52

Chlamydia trachomatis infection and risk of cervical intraepithelial neoplasia  

Microsoft Academic Search

ObjectivesHigh-risk human papillomavirus (hrHPV) is the primary cause of cervical cancer. As Chlamydia trachomatis is also linked to cervical cancer, its role as a potential co-factor in the development of cervical intraepithelial neoplasia (CIN) grade 2 or higher was examined.MethodsThe placebo arms of two large, multinational, clinical trials of an HPV6\\/11\\/16\\/18 vaccine were combined. A total of 8441 healthy women

Matti Lehtinen; Kevin A Ault; Erika Lyytikainen; Joakim Dillner; Suzanne M Garland; Daron G Ferris; Laura A Koutsky; Heather L Sings; Shuang Lu; Richard M Haupt; Jorma Paavonen

2011-01-01

53

Multiple Endocrine Neoplasia Type 1: Clinical Manifestations and Management  

Microsoft Academic Search

\\u000a Multiple endocrine neoplasia type I (MEN-1) is an autosomal dominant syndrome associated with anterior pituitary, parathyroid,\\u000a and enteropancreatic endocrine tumors as well as other endocrine and nonendocrine tumors [1]. MEN-1 is defined as the presence\\u000a of two of three main MEN-1-related manifestations, or at least one manifestation plus a first degree relative with at least\\u000a one MEN-1-related manifestation [1,2]. The

Anathea C. Powell; Steven K. Libutti

54

Ras/Erk MAPK signaling in epidermal homeostasis and neoplasia.  

PubMed

Epidermis provides the cutaneous barrier to the external environment and undergoes a continual process of proliferative self-renewal, with human epidermis undergoing complete turnover approximately 1,000 times in a lifetime. Recent work suggests that this ongoing proliferative replenishment of epidermal cells depends, in part, on continual signals for cell division and survival transmitted by the Ras/Erk MAPK pathway. Such constant cell proliferation, however, requires tight regulation to avoid the uncontrolled tissue expansion characteristic of epidermal neoplasia. Recent studies provide new insight into Ras/Erk MAPK pathway function in the control of normal skin development and homeostasis as well as how its deregulation promotes epidermal tumorigenesis. PMID:18000402

Khavari, Thomas A; Rinn, John

2007-12-01

55

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

MedlinePLUS

... X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (often shortened to XMEN ) On ... X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (typically known by the acronym ...

56

Role of the human papilloma virus in the development of cervical intraepithelial neoplasia and malignancy  

Microsoft Academic Search

Human papilloma virus (HPV) is a public health problem as a sexually transmitted disease and as a critical factor in the pathogenesis of various cancers. The clinical manifestations, epidemiology, and virology that are critical to understanding the process of cervical dysplasia and neoplasia are reviewed. A discussion of the cervical transformation zone and the classification of cervical dysplasia and neoplasia

A M Jastreboff; T Cymet

2002-01-01

57

Interobserver variability and aberrant E-cadherin immunostaining of lobular neoplasia and infiltrating lobular carcinoma  

Microsoft Academic Search

The distinction between lobular neoplasia and infiltrating lobular carcinoma from ductal neoplasia and infiltrating duct carcinoma with equivocal histologic features may present a challenge as this distinction has important therapeutic implications. Although E-cadherin staining has been of value in helping to make this determination, the variability of the E-cadherin staining pattern and the immunohistochemistry techniques can be problematic in clinical

Young J Choi; Marguerite M Pinto; Liming Hao; Ali K Riba

2008-01-01

58

Limits of Diagnosis and Molecular Markers for Early Detection of Ulcerative Colitis-Associated Colorectal Neoplasia  

Microsoft Academic Search

The incidence of colorectal neoplasia has been increasing among patients with long-standing and extensive ulcerative colitis (UC), and therefore surveillance colonoscopy has been widely recommended. However, because UC-associated neoplasia is often difficult to detect endoscopically and to discriminate from inflammatory regenerative epithelium histologically, the efficacy of current surveillance remains unsatisfactory. In order to overcome these difficulties, adjunctive modalities for diagnosing

Shigehiko Fujii; Daisuke Katsumata; Takahiro Fujimori

2008-01-01

59

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

60

Deregulation of microRNA expression in thyroid neoplasias.  

PubMed

MicroRNAs (miRNAs) have emerged as a class of powerful gene expression regulators. Acting at the post-transcriptional level, miRNAs modulate the expression of at least one-third of the mRNAs that are encoded by the human genome. The expression of a single gene can be regulated by several miRNAs, and every miRNA has more than one target gene. Thus, the miRNA regulatory circuit, which affects essential cellular functions, is of enormous complexity. Moreover, a fundamental role for miRNAs has been determined in the onset and progression of human cancers. Here, we summarize the main alterations in miRNA expression that have been identified in thyroid neoplasias and examine the mechanisms through which miRNA deregulation might promote thyroid cell transformation. We also discuss how the emerging knowledge on miRNA deregulation could be harnessed for the diagnosis and treatment of thyroid neoplasias. PMID:24247220

Pallante, Pierlorenzo; Battista, Sabrina; Pierantoni, Giovanna Maria; Fusco, Alfredo

2014-02-01

61

Genital warts and cervical neoplasia: an epidemiological study.  

PubMed Central

Cervical carcinoma and cervical intra-epithelial neoplasia (CIN) are likely to be associated with all sexually transmitted diseases (STDs). To help discover which (if any) of the recognised STDs might actually cause these conditions, a key question is whether one particular such association is much stronger than the others. The present study is therefore only of women newly attending an STD clinic, and compares the prevalences of cytological abnormalities of the cervix among 415 women attending with genital warts, 135 with genital herpes, and 458 with trichomoniasis or gonorrhoea. Significantly more genital wart patients (8.1%) than trichomoniasis or gonorrhoea patients (1.9%) showed dyskaryotic changes (adjusted relative risk (RR) = 5.8 with 95% limits 2.5-13.5) at, or a few months before, first attendance, while no excess whatever was seen in women with genital herpes. Moreover, half the women had a subsequent smear (at an average of 3-4 years after first attendance) and, although the diagnosis at first attendance was not related to the onset rate of dyskaryotic changes observed in these subsequent smears, it was related to the onset rate of grade III cervical intra-epithelial neoplasia (CIN III), which was found in 7 previous genital wart patients, in 2 previous trichomonas patients, but in 0 previous genital herpes patients. Thus, our findings suggest that herpes is not directly relevant to dyskaryotic change, but that one or more of the human papilloma viruses that cause genital warts may be. PMID:6688952

Franceschi, S.; Doll, R.; Gallwey, J.; La Vecchia, C.; Peto, R.; Spriggs, A. I.

1983-01-01

62

In situ increased chemokine expression in human cervical intraepithelial neoplasia.  

PubMed

Chemokines play a role in tumor-inflammation and angiogenesis that could be involved in tumor progression. Monocyte chemoattractant protein-1 (MCP-1), Interleukin-8 (IL-8) and macrophage inflammatory proteins (MIP) have been identified in tumor tissues of patients with different neoplasms. Therefore, the aim of the current study was to investigate the expressions of MCP-1, IL-8 and MIP-1?, mononuclear leukocyte infiltration and leukocyte/chemokine expressions in cervical tissues from patients with cervical intraepithelial neoplasia (CIN) and controls. MCP-1, IL-8 and MIP-1? expressions and leukocyte infiltration were determined by indirect immunofluorescence in cervix biopsies from CIN patients (n=65) and 7 normal controls. Increased expressions of MCP-1 and IL-8 in CIN were observed. Increment of lymphocyte infiltration and coexpression of CD3/MCP-1 and CD3/IL-8 were found in CIN. CD3/MCP-1 cell percentage was found decreased and CD3/IL-8 percentage increased according to the CIN evolution. MIP-1? remained similar to control values. The increased expression of MCP-1 and IL-8 in cervical neoplasia may lead to tumor progression. PMID:25661067

Carrero, Yenddy; Mosquera, Jesús; Callejas, Diana; Alvarez-Mon, Melchor

2015-04-01

63

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

64

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

65

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

66

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

67

Thyroid neoplasia following radiation therapy for Hodgkin's lymphoma  

SciTech Connect

The question of thyroid neoplasia following high-dose radiation treatment to the neck and mediastinum for malignant neoplasms such as Hodgkin's lymphoma in children and young adults has been raised recently. Five patients, 19 to 39 years old, were operated on for thyroid neoplasms that developed following cervical and mediastinal radiation therapy for Hodgkin's lymphoma. Three patients had papillary carcinomas and two had follicular adenomas. The latency period between radiation exposure and the diagnosis of thyroid neoplasm ranged from eight to 16 years. This limited series provided strong support for the recommendation that children and young adults who are to receive high-dose radiation therapy to the head, neck, and mediastinum should receive suppressive doses of thyroxine prior to radiation therapy in order to suppress thyrotropin (thyroid-stimulating hormone) and then be maintained on a regimen of suppression permanently.

McHenry, C.; Jarosz, H.; Calandra, D.; McCall, A.; Lawrence, A.M.; Paloyan, E.

1987-06-01

68

Rare Circulating MicroRNAs as Biomarkers of Colorectal Neoplasia  

PubMed Central

Background MicroRNAs (miRNAs) are regulatory RNAs, stable in circulation, and implicated in colorectal cancer (CRC) etiology and progression. Therefore they are promising as early detection biomarkers of colorectal neoplasia. However, many circulating miRNAs are highly expressed in blood cells, and therefore may not be specific to colorectal neoplasia. Methods We selected 7 miRNA candidates with previously reported elevated expression in adenoma tissue but low expression in blood cells (“rare” miRNAs), 2 previously proposed as adenoma biomarkers, and 3 implicated in CRC. We conducted a colonoscopy-based case-control study including 48 polyp-free controls, 43 advanced adenomas, 73 non-advanced adenomas, and 8 CRC cases. miRNAs from plasma were quantified by qRT-PCR. Correlations between miRNA expression levels, adjusted for age and sex, were assessed. We used polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals quantifying the association between expression levels of miRNAs and case groups. We also conducted nonparametric receiver operating characteristic (ROC) analyses and estimated area under the curve (AUC). Results miRNAs with high expression levels were statistically significantly correlated with one another. No miRNAs were significantly associated with non-advanced or advanced adenomas. Strong (ORs >5) and significant associations with CRC were observed for 6 miRNA candidates, with corresponding AUCs significantly >0.5. Conclusions These candidate miRNAs, assayed by qRT-PCR, are probably unsuitable as blood-based adenoma biomarkers. Strong associations between miRNAs and CRC were observed, but primarily with miRNAs highly expressed in blood cells. These results suggest that rare miRNAs will require new detection methods to serve as circulating biomarkers of adenomas. PMID:25286412

Adams, Scott V.; Newcomb, Polly A.; Burnett-Hartman, Andrea N.; Wurscher, Michelle A.; Mandelson, Margaret; Upton, Melissa P.; Zhu, Lee-Ching; Potter, John D.; Makar, Karen W.

2014-01-01

69

Intratubular germ cell neoplasia of the testis: a brief review.  

PubMed

Germ cell tumors of the testis may be divided into 3 broad categories according to age at presentation. The tumors in the pediatric age group include teratoma and yolk sac tumor. These tumors are generally not associated with convincing intratubular neoplasia. The second group consists of tumors presenting in third and fourth decade of life and include seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma as well as mixed germ cell tumors. The precursor cell for these tumors is an abnormal gonocyte that fails to differentiate completely into spermatogonia. These abnormal cells stay dormant in the gonad during intrauterine life as well as infancy and childhood, but undergo proliferation during puberty and can be identified as intratubular germ cell neoplasia unclassified (IGCNU). These tumor cells continue to manifest protein expression pattern that resembles primitive germ cells (PLAP, c-KIT, OCT3/4). After a variable interval following puberty, IGCNU cells may acquire ability to penetrate the seminiferous tubules and present as an overt germ cell tumor. Acquisition of isochrome 12 and other genetic abnormalities are usually associated with this transition. The level of DNA methylation generally determines the phenotype of the germ cell tumor. The third type of germ cell tumors is spermatocytic seminoma, which is a rare tumor encountered later in life usually in fifth and sixth decade. The cell of origin of this tumor is probably postpubertal mature spermatogonia which acquire abnormal proliferative capability probably due to gain of chromosome 9 resulting in activation and amplification of genes such as DMRT1. The tumor cells manifest many of the proteins normally expressed by mature sperms such as VASA, SSX2, and occasionally OCT2. Although spermatocytic seminoma may also have an intratubular growth phase, it completely lacks features of IGCNU. PMID:25844678

Al-Hussain, Turki; Bakshi, Nasir; Akhtar, Mohammed

2015-05-01

70

Objective Detection and Delineation of Oral Neoplasia Using Autofluorescence Imaging  

PubMed Central

Although the oral cavity is easily accessible to inspection, patients with oral cancer most often present at a late stage, leading to high morbidity and mortality. Autofluorescence imaging has emerged as a promising technology to aid clinicians in screening for oral neoplasia and as an aid to resection, but current approaches rely on subjective interpretation. We present a new method to objectively delineate neoplastic oral mucosa using autofluorescence imaging. Autofluorescence images were obtained from 56 patients with oral lesions and 11 normal volunteers. From these images, 276 measurements from 159 unique regions of interest (ROI) sites corresponding to normal and confirmed neoplastic areas were identified. Data from ROIs in the first 46 subjects was used to develop a simple classification algorithm based on the ratio of red-to-green fluorescence; performance of this algorithm was then validated using data from the ROIs in the last 21 subjects. This algorithm was applied to patient images to create visual disease-probability maps across the field of view. Histologic sections of resected tissue were used to validate the disease-probability maps. The best discrimination between neoplastic and non-neoplastic areas was obtained at 405 nm excitation; normal tissue could be discriminated from dysplasia and invasive cancer with a 95.9% sensitivity and 96.2% specificity in the training set and with a 100% sensitivity and 91.4% specificity in the validation set. Disease probability maps qualitatively agreed with both clinical impression and histology. Autofluorescence imaging coupled with objective image analysis provided a sensitive and non-invasive tool for the detection oral neoplasia. PMID:19401530

Roblyer, Darren; Kurachi, Cristina; Stepanek, Vanda; Williams, Michelle D.; El-Naggar, Adel K.; Lee, J. Jack; Gillenwater, Ann M.; Richards-Kortum, Rebecca

2009-01-01

71

Advanced colorectal neoplasia risk stratification by penalized logistic regression  

PubMed Central

Colorectal cancer is the second leading cause of death from cancer in the United States. To facilitate the efficiency of colorectal cancer screening, there is a need to stratify risk for colorectal cancer among the 90% of US residents who are considered “average risk.” In this article, we investigate such risk stratification rules for advanced colorectal neoplasia (colorectal cancer and advanced, precancerous polyps). We use a recently completed large cohort study of subjects who underwent a first screening colonoscopy. Logistic regression models have been used in the literature to estimate the risk of advanced colorectal neoplasia based on quantifiable risk factors. However, logistic regression may be prone to overfitting and instability in variable selection. Since most of the risk factors in our study have several categories, it was tempting to collapse these categories into fewer risk groups. We propose a penalized logistic regression method that automatically and simultaneously selects variables, groups categories, and estimates their coefficients by penalizing the L1-norm of both the coefficients and their differences. Hence, it encourages sparsity in the categories, i.e. grouping of the categories, and sparsity in the variables, i.e. variable selection. We apply the penalized logistic regression method to our data. The important variables are selected, with close categories simultaneously grouped, by penalized regression models with and without the interactions terms. The models are validated with 10-fold cross-validation. The receiver operating characteristic curves of the penalized regression models dominate the receiver operating characteristic curve of naive logistic regressions, indicating a superior discriminative performance. PMID:23907780

Lin, Yunzhi; Yu, Menggang; Wang, Sijian; Chappell, Richard; Imperiale, Thomas F.

2014-01-01

72

Advanced colorectal neoplasia risk stratification by penalized logistic regression.  

PubMed

Colorectal cancer is the second leading cause of death from cancer in the United States. To facilitate the efficiency of colorectal cancer screening, there is a need to stratify risk for colorectal cancer among the 90% of US residents who are considered "average risk." In this article, we investigate such risk stratification rules for advanced colorectal neoplasia (colorectal cancer and advanced, precancerous polyps). We use a recently completed large cohort study of subjects who underwent a first screening colonoscopy. Logistic regression models have been used in the literature to estimate the risk of advanced colorectal neoplasia based on quantifiable risk factors. However, logistic regression may be prone to overfitting and instability in variable selection. Since most of the risk factors in our study have several categories, it was tempting to collapse these categories into fewer risk groups. We propose a penalized logistic regression method that automatically and simultaneously selects variables, groups categories, and estimates their coefficients by penalizing the $$L1$$-norm of both the coefficients and their differences. Hence, it encourages sparsity in the categories, i.e. grouping of the categories, and sparsity in the variables, i.e. variable selection. We apply the penalized logistic regression method to our data. The important variables are selected, with close categories simultaneously grouped, by penalized regression models with and without the interactions terms. The models are validated with 10-fold cross-validation. The receiver operating characteristic curves of the penalized regression models dominate the receiver operating characteristic curve of naive logistic regressions, indicating a superior discriminative performance. PMID:23907780

Lin, Yunzhi; Yu, Menggang; Wang, Sijian; Chappell, Richard; Imperiale, Thomas F

2013-07-30

73

Using Risk for Advanced Proximal Colonic Neoplasia to Tailor Endoscopic Screening for Colorectal Cancer  

Cancer.gov

USING RISK FOR ADVANCED PROXIMAL COLONIC NEOPLASIA TO TAILOR ENDOSCOPIC SCREENING FOR COLORECTAL CANCER Thomas F. Imperiale, MD, Ching Y Lin, BS, Indiana University School of Medicine; David R. Wagner, MS, James D. Rogge, MD, Indianapolis Gastroenterology

74

High-dose-rate Intracavitary Brachytherapy in the Management of Cervical and Vaginal Intraepithelial Neoplasia  

Microsoft Academic Search

Purpose: To assess the effectiveness of high-dose rate intracavitary brachytherapy (HDR-ICR) in patients with grade 3 cervical intraepithelial neoplasia (CIN-3) and grade 3 vaginal intraepithelial neoplasia (VAIN-3).Methods and Materials: This was a retrospective analysis in 20 patients with CIN-3 (n = 14) or VAIN-3 (n = 6), average age 61.9 years, managed with HDR-ICR at Kanagawa Cancer Center. Two patients

Ichiro Ogino; Tatsuo Kitamura; Hiroyuki Okajima; Sho Matsubara

1998-01-01

75

Economic burden of vulvar and vaginal intraepithelial neoplasia: retrospective cost study at a German dysplasia centre  

Microsoft Academic Search

Background  Human papillomavirus is responsible for a variety of diseases including grade 2 and 3 vulvar and vaginal intraepithelial neoplasia.\\u000a The aim of this study was to assess parts of the burden of the last diseases including treatment costs. The direct medical\\u000a resource use and cost of surgery associated with neoplasia and related diagnostic procedures (statutory health insurance perspective)\\u000a were estimated,

Monika Hampl; Eduard Huppertz; Olaf Schulz-Holstege; Patrick Kok; Sarah Schmitter

2011-01-01

76

TAILORING COLORECTAL CANCER SCREENING BY CONSIDERING RISK OF ADVANCED PROXIMAL NEOPLASIA  

PubMed Central

BACKGROUND Quantifying risk of advanced proximal colorectal neoplasia might allow tailoring of colorectal cancer screening, with colonoscopy for those at high risk, and less invasive screening for very low-risk persons. METHODS We analyzed findings from 10,124 consecutive adults age ? 50 years who underwent screening colonoscopy to the cecum between September 1995 and August 2008. We quantified the risk of advanced neoplasia (tubular adenoma ? 1 cm; a polyp with villous histology or high-grade dysplasia; or adenocarcinoma) both proximally (cecum to splenic flexure) and distally (descending colon to anus). Prevalence of advanced proximal neoplasia was quantified by age, gender and distal findings. RESULTS Mean (s.d.) age was 57.5 (6.0) years; 44% were women; 7835 (77%) had no neoplasia, and 1856 (18%) had one or more non-advanced adenomas. Overall, 433 subjects (4.3%) had advanced neoplasia (267 distally; 196 proximally; 30 both), 33 (0.33%) of which were adenocarcinoma (18 distal, 15 proximal). Risk of advanced proximal neoplasia increased with age decade (1.13%, 2.00%, and 5.26%, respectively; P=0.001) and was higher in men (relative risk [RR] =1.91; CI, 1.32–2.77). In women younger than 70 years, risk was 1.1% overall (vs. 2.2% in men; RR=1.98; CI, 1.42–2.76) and was 0.86% in those with no distal neoplasia (vs. 1.54% in men; RR=1.81; CI, 1.20–2.74). CONCLUSION Risk of advanced proximal neoplasia is a function of age and gender. Women younger than age 70 have a very low risk, particularly those with no distal adenoma. Sigmoidoscopy with or without occult blood testing may be sufficient and even preferable for screening these subgroups. PMID:23062404

Imperiale, Thomas F.; Glowinski, Elizabeth A.; Lin-Cooper, Ching; Ransohoff, David F.

2012-01-01

77

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. PMID:25550851

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

2014-01-01

78

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

79

Comparison of computed tomography and magnetic resonance imaging for the evaluation of canine intranasal neoplasia  

PubMed Central

Objectives Canine intranasal neoplasia is commonly evaluated using computed tomography to indicate the diagnosis, to determine disease extent, to guide histological sampling location and to plan treatment. With the expanding use of magnetic resonance imaging in veterinary medicine, this modality has been recently applied for the same purpose. The aim of this study was to compare the features of canine intranasal neoplasia using computed tomography and magnetic resonance imaging. Methods Twenty-one dogs with confirmed intranasal neoplasia underwent both computed tomography and magnetic resonance imaging. The images were reviewed retrospectively for the bony and soft tissue features of intranasal neoplasia. Results Overall computed tomography and magnetic resonance imaging performed very similarly. However, lysis of bones bordering the nasal cavity and mucosal thickening was found on computed tomography images more often than on magnetic resonance images. Small amounts of fluid in the nasal cavity were more often seen on magnetic resonance images. However, fluid in the frontal sinuses was seen equally well with both modalities. Clinical Significance We conclude that computed tomography is satisfactory for evaluation of canine intranasal neoplasia, and no clinically relevant benefit is gained using magnetic resonance imaging for intranasal neoplasia without extent into the cranial cavity. PMID:19508490

Drees, R.; Forrest, L. J.; Chappell, R.

2009-01-01

80

Management of cervical intraepithelial neoplasia by carbon dioxide laser.  

PubMed

Between 1976 and 1981, 412 women with biopsy-proven cervical intraepithelial neoplasia (CIN) were treated by means of the carbon dioxide laser. A previous publication reported the author's initial therapeutic results with laser surgery for CIN, carried out between 1976 and 1978. This report includes data on 297 patients who were followed for 6 months to 5 years after laser vaporization and on 55 women treated by laser excisional cone. Major improvements in the technique of carbon dioxide laser vaporization evolved as experience was gained, and related to elimination of the entire squamocolumnar junction, to destruction of neoplastic tissue to a depth of 5 to 7 mm, and to utilization of power densities greater than 1000 watts/cm2. Cures were achieved in 285 of the 297 patients treated by vaporization, ie, the failure rate was 4% (52 of 55 women treated by excisional cone). Complications during this study were minor and usually correlated with delayed bleeding. One patient developed cervical stenosis following laser excisional cone. No patient was found to have invasive carcinoma after laser surgery to the cervix. Because laser vaporization and laser excisional cone are best adapted for the outpatient setting, financial savings accruing to the patient are considerable. Rapid healing, minimal pain, and a general absence of noxious symptomatology also promote early return to work and daily routines. PMID:6811983

Baggish, M S

1982-09-01

81

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

82

Challenges in automated detection of cervical intraepithelial neoplasia  

NASA Astrophysics Data System (ADS)

Cervical Intraepithelial Neoplasia (CIN) is a precursor to invasive cervical cancer, which annually accounts for about 3700 deaths in the United States and about 274,000 worldwide. Early detection of CIN is important to reduce the fatalities due to cervical cancer. While the Pap smear is the most common screening procedure for CIN, it has been proven to have a low sensitivity, requiring multiple tests to confirm an abnormality and making its implementation impractical in resource-poor regions. Colposcopy and cervicography are two diagnostic procedures available to trained physicians for non-invasive detection of CIN. However, many regions suffer from lack of skilled personnel who can precisely diagnose the bio-markers due to CIN. Automatic detection of CIN deals with the precise, objective and non-invasive identification and isolation of these bio-markers, such as the Acetowhite (AW) region, mosaicism and punctations, due to CIN. In this paper, we study and compare three different approaches, based on Mathematical Morphology (MM), Deterministic Annealing (DA) and Gaussian Mixture Models (GMM), respectively, to segment the AW region of the cervix. The techniques are compared with respect to their complexity and execution times. The paper also presents an adaptive approach to detect and remove Specular Reflections (SR). Finally, algorithms based on MM and matched filtering are presented for the precise segmentation of mosaicism and punctations from AW regions containing the respective abnormalities.

Srinivasan, Yeshwanth; Yang, Shuyu; Nutter, Brian; Mitra, Sunanda; Phillips, Benny; Long, Rodney

2007-03-01

83

RAP1 GTPase Overexpression is Associated with Cervical Intraepithelial Neoplasia  

PubMed Central

RAP1 (RAS proximate 1), a small GTP-binding protein of the RAS superfamily, is a putative oncogene that is highly expressed in several malignant cell lines and types of cancers, including some types of squamous cell carcinoma. However, the participation of RAP1 in cervical carcinogenesis is unknown. We conducted a cross-sectional study of paraffin-embedded cervical biopsies to determine the association of RAP1 with cervical intraepithelial neoplasia (CIN). Standard and quantitative immunohistochemistry assessment of RAP1 expression in fixed tissue was performed on 183 paraffin-embedded cervical biopsies that were classified as normal or non-dysplastic mucosa (NDM) (n = 33); CIN grade 1 (n = 84) and CIN grade 2/3 (n = 66). A gradual increase in RAP1 expression in NDM < CIN 1 < CIN 2/3 (p<0.001) specimens was observed and was in agreement with the histopathologic diagnosis. A progressive increase in the RAP1 expression levels increased the risk of CIN 1 [odds ratio (OR) = 3.50; 95% confidence interval (CI) 1.30-10.64] 3.5 fold and the risk of CIN 2/3 (OR?=?19.86, 95% CI 6.40-70.79) nearly 20 fold when compared to NDM. In addition, stereotype ordinal regression analysis showed that this progressive increase in RAP1 expression more strongly impacted CIN 2/3 than CIN 1. Our findings suggest that RAP1 may be a useful biomarker for the diagnosis of CIN. PMID:25856570

Pascoal-Xavier, Marcelo Antonio; Figueiredo, Anna Carolina Cançado; Gomes, Luciana Inácia; Peruhype-Magalhães, Vanessa; Calzavara-Silva, Carlos Eduardo; Costa, Marcelo Azevedo; Reis, Ilka Afonso; Bonjardim, Claudio Antônio; Kroon, Erna Geessien

2015-01-01

84

Thyroid neoplasia in Marshall Islanders exposed to nuclear fallout  

SciTech Connect

We studied the risk of thyroid neoplasia in Marshall Islanders exposed to radioiodines in nuclear fallout from the 1954 BRAVO thermonuclear test. We screened 7266 Marshall Islanders for thyroid nodules; the islanders were from 14 atolls, including several southern atolls, which were the source of the best available unexposed comparison group. Using a retrospective cohort design, we determined the prevalence of thyroid nodularity in a subgroup of 2273 persons who were alive in 1954 and who therefore were potentially exposed to fallout from the BRAVO test. For those 12 atolls previously thought to be unexposed to fallout, the prevalence of thyroid nodules ranged from 0.9% to 10.6%. Using the distance of each atoll from the test site as a proxy for the radiation dose to the thyroid gland, a weighted linear regression showed an inverse linear relationship between distance and the age-adjusted prevalence of thyroid nodules. Distance was the strongest single predictor in logistic regression analysis. A new absolute risk estimate was calculated to be 1100 excess cases/Gy/y/1 X 10(6) persons (11.0 excess cases/rad/y/1 million persons), 33% higher than previous estimates. We conclude that an excess of thyroid nodules was not limited only to the two northern atolls but extended throughout the northern atolls; this suggests a linear dose-response relationship.

Hamilton, T.E.; van Belle, G.; LoGerfo, J.P.

1987-08-07

85

Vulvoperineal reconstruction after excision of anogenital multifocal intraepithelial neoplasia ("MIN").  

PubMed

Over the past 7 years, 12 women have been treated utilising a radical surgical approach for extensive vulval involvement as a component of multifocal intraepithelial neoplasia (MIN) of the female genital tract. The patients were analysed with respect to the anatomical site of involvement, age, presenting complaints and their duration, colposcopic examination, histopathology and surgical treatment. Gynaecologists, general surgeons and plastic surgeons were involved in the surgical treatment which was an initial colostomy followed by a definitive vulvoperineal resection and simultaneous vulval reconstruction using meshed split skin grafts or a combination of skin grafts and local flaps. 17 vulvoperineal reconstructions were done for 12 patients. Three had an incomplete histopathological clearance at the initial operation. Apart from these three patients, one had recurrence of symptoms alone, without any evidence of MIN, which was possibly due to human papilloma virus infection. One patient developed malignant squamous invasion 4 years later, which was cured with surgical excision and reconstruction. Colostomy closure was done after achieving local control of the disease. This staged approach does achieve the objectives of eliminating disease and alleviating symptoms. It preserves function and attempts to reconstruct normal anatomy without compromising the principles of surgical oncology and results in a high patient satisfaction. PMID:8976746

Thomas, S S; Chenoy, R; Fielding, J W; Rollason, T P; Jordan, J A; Bracka, A

1996-12-01

86

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

87

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

88

High Resolution Microendoscopy for Quantitative Diagnosis of Esophageal Neoplasia  

NASA Astrophysics Data System (ADS)

Esophageal cancer is the eighth most common cancer in the world. Cancers of the esophagus account for 3.8% of all cases of cancers, with approximately 482,300 new cases reported in 2008 worldwide. In the United States alone, it is estimated that approximately 18,000 new cases will be diagnosed in 2013, and 15,210 deaths are expected. Despite advances in surgery and chemoradiation therapy, these advances have not led to a significant increase in survival rates, primarily because diagnosis often at an advanced and incurable stage when treatment is more difficult and less successful. Accurate, objective methods for early detection of esophageal neoplasia are needed. Here, quantitative classification algorithms for high resolution miscroendoscopic images were developed to distinguish between esophageal neoplastic and non-neoplastic tissue. A clinical study in 177 patients with esophageal squamous cell carcinoma (ESCC) was performed to evaluate the diagnostic performance of the classification algorithm in collaboration with the Mount Sinai Medical Center in the United States, the First Hospital of Jilin University in China, and the Cancer Institute and Hospital, the Chinese Academy of Medical Science in China. The study reported a sensitivity and specificity of 93% and 92%, respectively, in the training set, 87% and 97%, respectively, in the test set, and 84% and 95%, respectively, in an independent validation set. Another clinical study in 31 patients with Barrett's esophagus resulted in a sensitivity of 84% and a specificity of 85%. Finally, a compact, portable version of the high resolution microendoscopy (HRME) device using a consumer-grade camera was developed and a series of biomedical experimental studies were carried out to assess the capability of the device.

Shin, Dongsuk

89

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

90

Biliary tree gastrinomas in multiple endocrine neoplasia type 1 syndrome  

PubMed Central

AIM: To describe our patients affected with ectopic biliary tree gastrinoma and review the literature on this topic. METHODS: Between January 1992 and June 2012, 28 patients affected by duodenopancreatic endocrine tumors in multiple endocrine neoplasia type 1 (MEN1) syndrome underwent surgery at our institution. This retrospective review article analyzes our experience regarding seventeen of these patients subjected to duodenopancreatic surgery for Zollinger-Ellison syndrome (ZES). Surgical treatment consisted of duodenopancreatectomy (DP) or total pancreatectomy (TP). Regional lymphadenectomy was always performed. Any hepatic tumoral lesions found were removed during surgery. In MEN1 patients, removal of duodenal lesions can sometimes lead to persistence or recurrence of hypergastrinemia. One possible explanation for this unfavorable outcome could be unrecognized ectopic localization of gastrin-secreting tumors. This study described three cases among the seventeen patients who were found to have an ectopic gastrinoma located in the biliary tree. RESULTS: Seventeen MEN1 patients affected with ZES were analyzed. The mean age was 40 years. Fifteen patients underwent DP and two TP. On histopathological examination, duodeno pancreatic endocrine tumors were found in all 17 patients. Eighty-one gastrinomas were detected in the first three portions of the duodenum. Only one gastrinoma was found in the pancreas. The mean number of gastrinomas per patient was 5 (range 1-16). Malignancy was established in 12 patients (70.5%) after lymph node, liver and omental metastases were found. Three patients exhibited biliary tree gastrinomas as well as duodenal gastrinoma(s). In two cases, the ectopic gastrinoma was removed at the same time as pancreatic surgery, while in the third case, the biliary tree gastrinoma was resected one year after DP because of recurrence of ZES. CONCLUSION: These findings suggest the importance of checking for the presence of ectopic gastrinomas in the biliary tree in MEN1 patients undergoing ZES surgery. PMID:24363522

Tonelli, Francesco; Giudici, Francesco; Nesi, Gabriella; Batignani, Giacomo; Brandi, Maria Luisa

2013-01-01

91

Telomere dysfunction suppresses multiple endocrine neoplasia in mice  

PubMed Central

Multiple endocrine neoplasia (MEN) syndrome is typified by the occurrence of tumors in two or more hormonal tissues. Whereas the genetics of MEN syndrome is relatively well understood, the tumorigenic mechanisms for these cancers remain relatively obscure. The Cdk4R24C mouse model develops highly penetrant pituitary tumors and endocrine pancreas adenomas, and, as such, this model is appropriate to gain insight into mechanisms underlying MEN. Using this model, here we provide evidence supporting an important role for telomerase in the pathogenesis of MEN. We observed increased aneuploidy in Cdk4R/R fibroblasts along with significantly elevated telomerase activity and telomere length in Cdk4R/R islets and embryonic fibroblasts. To better understand the role of telomerase, we generated Cdk4R24C mice with inactivation of the mTERC locus, which codes for the essential RNA component of the enzyme telomerase (mTERC?/? Cdk4R/R mice). Embryonic fibroblasts and islets derived from mTERC?/? Cdk4R/R mice exhibit reduced telomere length and proliferative capacity. Further, mTERC?/? Cdk4R/R fibroblasts display reduced transformation potential. Importantly, mTERC?/? Cdk4R/R mice display significantly reduced spontaneous tumorigenesis. Strikingly, we observed dramatic suppression of pituitary tumors and endocrine pancreas adenomas in mTERC?/? Cdk4R/R mice. Telomere dysfunction suppressed tumor initiation and increased latency of tumor development while not affecting the progression of established tumors. In summary, these results are suggestive of an important role for telomerase in tumor development in the Cdk4R24C mouse model, specifically in the genesis of tumors in the pituitary and the endocrine pancreas. PMID:25352948

Lee, Ji-Hyeon; Anver, Miriam; Kost-Alimova, Maria; Protopopov, Alexei; DePinho, Ronald A.; Rane, Sushil G.

2014-01-01

92

Canine neoplasia--population-based incidence of vascular tumours.  

PubMed

We have identified thirteen breeds that are registered in the Norwegian Canine Cancer Register with more than five cases of newly diagnosed, primary vascular neoplasia in the period from 1990 to 1998. Incidence rates have been estimated for the boxer and the Bernese mountain dog because the population at risk is known as a result of the 1992/93-census of the Bernese mountain dog, boxer and bichon frisé. The boxer had a mean annual incidence rate for all types of vascular tumours, for both sexes, of 4.3 cases per 1000 dogs. The sex ratio was close to one, and the age group of highest risk was 10-12 years. For vascular cancer, the mean annual incidence rate for both sexes was 1.5 cases per 1000 dogs, and the age group of highest risk was 10-12 years. The mean annual incidence rate of vascular tumours for the Bernese mountain dog for both sexes was 2.5 cases per 1000 dogs. The male to female incidence ratio was approximately 1/2. The age group of highest incidence rate was 10-11 years for all types of vascular tumours as for the vascular cancer. The mean annual incidence rate for malignant tumours for both sexes was 1.0 cases per year per 1000 dogs. For all thirteen breeds, the relative risk of all types of vascular tumours has been computed ad modum Arnesen. The highest estimated incidence rate of malignant vascular tumours per 1000 dogs was found in the boxer (1.5). The flat-coated retriever and Bernese mountain dog had 1.0 and 0.9, respectively, and the German shepherd had 0.8. The study shows that the German shepherd is not the breed with the highest frequency of vascular tumour when the population at risk is taken into consideration, although the total number of vascular tumours is highest in this breed. PMID:19385282

Moe, Lars; Gamlem, Hans; Dahl, Kjetil; Glattre, Eystein

2008-01-01

93

Toxoplasmosis: antitoxoplasma IgG antibody levels in patients with lymphoid neoplasia in Ibadan, Nigeria.  

PubMed

The serum samples of 50 patients with lymphoid neoplasia, and of 112 control subjects from the normal population were analysed for the presence of antitoxoplasma IgG antibodies by the enzyme-linked immunosorbent assay technique. There was no significant difference between the prevalence rate of antitoxoplasma IgG antibodies in the control subjects (69%) and the patients with lymphoid neoplasia (66%). The prevalence of antitoxoplasma IgG antibody levels of 75 international units (i.u.) per ml and above was significantly higher in the patients (48%) than in the control subjects (18%). Antitoxoplasma IgG antibody levels of 150 i.u. and above per ml indicating active toxoplasmosis were present in 13 (26%) out of the 50 patients with lymphoid neoplasia. None of the sera from the control subjects had antitoxoplasma IgG antibody level up to 150 i.u. per ml of serum. PMID:7653402

Ekweozor, C C; Okpala, L E; Bamgboye, A E; Jegede, O

1994-12-01

94

Histologic Inflammation Is a Risk Factor for Progression to Colorectal Neoplasia in Ulcerative Colitis  

PubMed Central

Background Although inflammation is presumed to contribute to colonic neoplasia in ulcerative colitis (UC), few studies have directly examined this relationship. Aim To determine whether severity of microscopic inflammation over time is an independent risk factor for neoplastic progression in UC. Methods A cohort of patients with UC undergoing regular endoscopic surveillance for dysplasia was studied. Degree of inflammation at each biopsy site had been graded as part of routine clinical care using a highly reproducible histological activity index. Progression to neoplasia was analyzed in proportional hazards models with inflammation summarized in three different ways, and each included as a time-changing covariate: 1) mean inflammatory score (IS-mean); 2) binary inflammatory score (IS-bin); and 3) maximum inflammatory score (IS-max). Potential confounders were analyzed in univariate testing, and, when significant, in a multivariable model. Results Of 418 patients who met inclusion criteria, 15 progressed to advanced neoplasia (high-grade dysplasia, HGD, or colorectal cancer, CRC) and 65 progressed to any neoplasia (low-grade dysplasia, HGD, or CRC). Univariate analysis demonstrated significant relationships between histological inflammation over time and progression to advanced neoplasia (HR=3.0; 95% CI 1.4-6.3 for IS-mean, HR=3.4; 95% CI 1.1-10.4 for IS-bin; and HR=2.2; 95%CI 1.2-4.2 for IS-max). This association was maintained in multivariable proportional hazards analysis. Conclusion The severity of microscopic inflammation over time is an independent risk factor for developing advanced colorectal neoplasia among patients with longstanding UC. PMID:17919486

Gupta, Roopali Bansal; Harpaz, Noam; Itzkowitz, Steven; Hossain, Sabera; Matula, Sierra; Kornbluth, Asher; Bodian, Carol; Ullman, Thomas

2007-01-01

95

Immunohistochemical localization of human papilloma virus in conjunctival neoplasias: A retrospective study  

PubMed Central

Background: The extent of association of human papilloma virus (HPV) in human conjunctival neoplasias has been debated in studies originating from different parts of the world, but no substantial evidence has been generated on Indian subjects. This prompted us to carry out a retrospective study on conjunctival neoplasias diagnosed over the past 12 years. Materials and Methods: Histopathological and immunohistochemical analysis of 65 specimens of ocular neoplasias and 30 normal controls diagnosed between 1991 and 2002 at a tertiary eye care hospital, was undertaken. Formalin-fixed, paraffin-embedded tissues were reviewed for confirming histopathological diagnosis, presence of koilocytosis and changes related to actinic keratosis. Immunohistochemical analysis was done using HPV-specific monoclonal antibodies. Clinicopathological correlation and the association of HPV antigen with the histopathological features were performed. Results: Out of the 65 cases analyzed, 35 were papillomas and 30 were ocular surface squamous neoplasias (OSSN). The mean age was 48 years with a male preponderance. Histologically, koilocytosis was observed in 17.1% of papillomas and 36.6% of OSSN. Actinic keratosis was present in 33% of OSSN. Immunohistochemically 17.1% conjunctival papillomas stained positive for HPV antigen, all cases of OSSN were negative for HPV. There was no correlation between koilocytosis or actinic keratosis and the detection of HPV antigen. Conclusions: The association between HPV and conjunctival neoplasias is variable in different geographical areas and also depends on the methods of detection used. This study warrants the need for applying more advanced techniques at a molecular level to determine the possible etiology of HPV in conjunctival neoplasias among Asian-Indians. PMID:17699945

Sharma, Anjana; Panda, Anita

2007-01-01

96

Long-term results of less than total parathyroidectomy for hyperparathyroidism in multiple endocrine neoplasia type 1  

Microsoft Academic Search

Background. Our aim was to assess long-term results after less than total parathyroidectomy for hyperparathyroidism in multiple endocrine neoplasia type 1. Methods. Of 1888 patients undergoing operation at our institution for primary hyperparathyroidism between 1972 and 2001, 83 (4.4%) had multiple endocrine neoplasia type 1. Outcome data were available for 79; 66 underwent subtotal parathyroidectomy, 55 (83%) of these with

Laurent C Arnalsteen; Piero F Alesina; Jean Louis Quiereux; Stephen G Farrel; Francois N Patton; Bruno M Carnaille; Catherine M Cardot-Bauters; Jean Louis Wemeau; Charles A. G Proye

2002-01-01

97

Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis: A meta-analysis  

Microsoft Academic Search

Background: Published data on the risk of colorectal neoplasia in patients with ulcerative colitis with and without primary sclerosing cholangitis are conflicting. A meta-analysis was performed to synthesize available publications and to compare the risk of colorectal neoplasia in patients with ulcerative colitis with and without primary sclerosing cholangitis. Methods: By using MEDLINE and manual search methods, studies were identified

Roy M. Soetikno; Otto S. Lin; Paul A. Heidenreich; Harvey S. Young; Michael O. Blackstone

2002-01-01

98

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

99

Human Papilloma Virus Infection and Cervical Intraepithelial Neoplasia in Transplanted Patients  

Microsoft Academic Search

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

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

2008-01-01

100

MYELOID NEOPLASIA The derivation of diagnostic markers of chronic myeloid leukemia progression  

E-print Network

MYELOID NEOPLASIA The derivation of diagnostic markers of chronic myeloid leukemia progression from, limited molecular markers ex- ist that can determine where in the spec- trum of chronic myeloid leukemia-based treat- ment strategy at diagnosis. (Blood. 2009; 114:3292-3298) Introduction Chronic myeloid leukemia

Raftery, Adrian

101

Rare Somatic Inactivation of the Multiple Endocrine Neoplasia Type 1 Gene in Secondary Hyperparathyroidism of Uremia  

Microsoft Academic Search

The molecular pathway of autonomous growth of the parathyroid glands in uremic patients is poorly understood. Loss of heterozygosity at the recently identified multiple endocrine neoplasia type 1 (MEN1) gene locus on chromosome 11q13 has been found in a subset of para- thyroid glands from patients with refractory hyperparathyroidism. To clarify the role of the MEN1 gene in parathyroid tumorigenesis,

HIDEKI TAHARA; YASUO IMANISHI; TOMOMI YAMADA; YOSHIHIRO TSUJIMOTO; TSUTOMU TABATA; TAKASHI INOUE; MASAAKI INABA; HIROTOSHI MORII; YOSHIKI NISHIZAWA

2010-01-01

102

The appearance of the adrenal glands on computed tomography in multiple endocrine neoplasia type 1  

Microsoft Academic Search

Aims: To review the morphology of the adrenal glands in multiple endocrine neoplasia type 1 (MEN1) on computed tomography (CT) to compare the results with established normal values for adrenal size and nodularity and to correlate adrenal size with serum cortisol secretory dynamics. Materials and methods: Two observers independently reviewed the adrenal CT in 28 patients with MEN1, measuring the

S A Whitley; V J Moyes; K M Park; A M Brooke; A B Grossman; S L Chew; A G Rockall; J P Monson; R H Reznek

2008-01-01

103

Disease Persistence in Patients with Cervical Intraepithelial Neoplasia Undergoing Electrosurgical Conization  

Microsoft Academic Search

Objective. Cone margin status has been reported to be the most important predictor of residual disease in patients with cervical intraepithelial neoplasia (CIN) undergoing electrosurgical excisional treatment. The primary aim of this study of patients treated with electrosurgical conization was to evaluate the association of cone margin status and other clinical and pathologic factors with the probability of residual disease.Methods.

Silvano Costa; Maria De Nuzzo; Fanny E. Infante; Benedetta Bonavita; Marica Marinelli; Anna Rubino; Valeria Rambelli; Donatella Santini; Paolo Cristiani; Lauro Bucchi

2002-01-01

104

Surveillance using trimodal imaging endoscopy after endoscopic submucosal dissection for superficial gastric neoplasia  

PubMed Central

AIM: To evaluate the effectiveness of trimodal imaging endoscopy (TME) to detect another lesion after endoscopic submucosal dissection (ESD) for superficial gastric neoplasia (SGN). METHODS: Surveillance esophagogastroduodenoscopy (EGD) using a TME was conducted in 182 patients that had undergone ESD for SGN. Autofluorescence imaging (AFI) was conducted after white-light imaging (WLI). When SGN was suspicious, magnifying endoscopy with narrow-band imaging (ME-NBI) was conducted. Final diagnoses were made by histopathologic findings of biopsy specimens. The detection rates of lesions in WLI, AFI, and NBI, and the characteristics of lesions detected by WLI and ones missed by WLI but detected by AFI were examined. The sensitivity, specificity, and accuracy of endoscopic diagnosis using WLI, AFI and ME-NBI were evaluated. RESULTS: In 242 surveillance EGDs, 27 lesions were determined pathologically to be neoplasias. Sixteen early gastric cancers and 6 gastric adenomas could be detected by WLI. Sixteen lesions were reddish and 6 were whitish. Five gastric neoplasias were missed by WLI but were detected by AFI, and all were whitish and protruded gastric adenomas. There was a significant difference in color and pathology between the two groups (P = 0.006). Sensitivity, specificity and accuracy in ME-NBI were higher than those in both WLI and AFI. Specificity and accuracy in AFI were lower than those in WLI. CONCLUSION: Surveillance using trimodal imaging endoscopy might be useful for detecting another lesion after endoscopic submucosal dissection for superficial gastric neoplasia. PMID:25473189

Imaeda, Hiroyuki; Hosoe, Naoki; Kashiwagi, Kazuhiro; Ida, Yosuke; Nakamura, Rieko; Suzuki, Hidekazu; Saito, Yoshimasa; Yahagi, Naohisa; Iwao, Yasushi; Kitagawa, Yuko; Hibi, Toshifumi; Ogata, Haruhiko; Kanai, Takanori

2014-01-01

105

Not Just Skin Deep: A Case Report of Multiple Endocrine Neoplasia Type 1  

PubMed Central

Multiple endrocrine neoplasia (MEN) type 1 is characterized by mainly a triad of pancreatic, pituitary and parathyroid involvement. This is a case report of a 41-year-old male in whom recognition of collagenoma and gingival papule led to the identification of MEN type 1. Often the recognition of such dermatological manifestations help in the presymptomatic diagnosis of complex syndromes. PMID:22837571

Simi, SM; Narayanan, Beena; Nandakumar, G

2012-01-01

106

THE INDUCTION OF COLON NEOPLASIA IN MALE RATS EXPOSED TO TRIHALOMETHANES (THMS) IN THE DRINKING WATER  

EPA Science Inventory

THE INDUCTION OF COLON NEOPLASIA IN MALE RATS EXPOSED TO TRIHALO METHANES (THMs) IN THE DRINKING WATER Christopher Sistrunk and Tony DeAngelo, North Carolina Central University and US Environmental Protection Agency The THMs are the most widely distributed and the most co...

107

The contribution of growth hormone to mammary neoplasia Perry Jo K 1  

E-print Network

The contribution of growth hormone to mammary neoplasia Perry Jo K 1 , Mohankumar Kumarasamypet M 1 of growth hormone (GH) on longitudinal growth are well established, the observation that GH contributes therapeutic approach for treatment of breast cancer. Author Keywords Growth hormone ; breast cancer ; mammary

Paris-Sud XI, Université de

108

Vaginal intraepithelial neoplasia: treatment by carbon dioxide laser and risk factors for failure  

Microsoft Academic Search

Objective: To evaluate the effectiveness of CO2 laser ablation of vaginal intraepithelial neoplasia (VAIN) and to define prognostic factors. Study Design: Medical records of 24 patients with VAIN II or III, treated by CO2 laser ablation from 1990 to 1998 were reviewed. The grade, location, and focality of the lesions, the age, follow-up period and menopausal status of the patients,

Omer T Yalcin; Thomas J Rutherford; Setsuko K Chambers; Joseph T Chambers; Peter E Schwartz

2003-01-01

109

Treatment of Vaginal Intraepithelial Neoplasia with Laser Ablation and Upper Vaginectomy  

Microsoft Academic Search

To assess the effectiveness of laser ablation and upper vaginectomy in the treatment of vaginal intraepithelial neoplasia (VAIN), we have reviewed the charts of 52 patients managed with laser ablation (28 patients) and upper colpectomy (24 patients). On the basis of our results, patient selection and operator skill have a significant influence on the outcome. In posthysterectomy patients with VAIN3

Emmanuel Diakomanolis; Alexandros Rodolakis; Zanis Boulgaris; Georgios Blachos; Stylianos Michalas

2002-01-01

110

Clinical Features and Risk of Recurrence among Patients with Vaginal Intraepithelial Neoplasia  

Microsoft Academic Search

Objective. The best treatment modality and factors affecting recurrence among women with vaginal intraepithelial neoplasia (VAIN) are yet to be determined. The aims of the current study were to describe the clinical features, results of treatment, and factors affecting recurrence among patients with VAIN.Methods. We conducted a retrospective review of 121 women with VAIN after confirming the histologic diagnosis. Patient

Jeffrey A. Dodge; Gamal H. Eltabbakh; Sharon L. Mount; R. Paige Walker; Ann Morgan

2001-01-01

111

Cavitational Ultrasonic Surgical Aspiration for the Treatment of Vaginal Intraepithelial Neoplasia  

Microsoft Academic Search

Objective. The aim of this study is to determine whether cavitational ultrasonic surgical aspiration (CUSA) is effective and safe for treating vaginal intraepithelial neoplasia (VAIN).Methods. We conducted a retrospective chart review of 46 patients who were treated with CUSA for VAIN in a single gynecologic oncology practice between 1981 and 1999.Results. At initial presentation, 39% of treated patients had grade

Jubilee B. Robinson; Charlotte C. Sun; Diane Bodurka-Bevers; Dwight D. Im; Neil B. Rosenshein

2000-01-01

112

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

113

A long-sought needle in the haystack: the multiple endocrine neoplasia type 1 gene  

Microsoft Academic Search

The recent identification of the gene underlying the pathogenesis of multiple endocrine neoplasia type 1 (MEN1) by Chandrasekharappa et al. is a significant advancement and will help to elucidate mechanisms of tumorigenesis in endocrine glands and provides more accurate tools to identify gene carriers at an early stage (1). MEN1 is an autosomal dominant cancer syndrome predominantly characterized by tumors

Peter Kopp

1997-01-01

114

Human papillomavirus type distribution in vulval intraepithelial neoplasia determined using PapilloCheck DNA Microarray.  

PubMed

Vulval intraepithelial neoplasia is a precursor of vulval carcinoma, and is frequently associated with human papillomavirus (HPV) infection. Estimates of HPV prevalence in vulval intraepithelial neoplasia vary widely in the UK. The objective of this study was to assess HPV infection in a sample of women with vulval intraepithelial neoplasia, confirmed histologically, and determine the proportion of disease associated with HPV types targeted by prophylactic HPV vaccines. HPV infection was assessed in biopsies from 59 patients using the Greiner Bio-One PapilloCheck® DNA chip assay. Valid results were obtained for 54 cases. HPV infection was present in 43 of the 54 cases (79.6%: 95% CI 67.1-88.2%). The most common HPV types were HPV 16 (33/54: 61.1%), HPV 33 (8/54: 14.8%), HPV 6 (5/54: 9.3%), and HPV 42 (3/54: 5.6%). The mean age of HPV positive women was significantly less than the mean age of HPV negative women. This is the largest UK series of vulval intraepithelial neoplasia in which HPV type has been investigated, and 34/54 (63.0%, 95% CI: 49.6-78.6%) cases were associated with HPV 16/18, which are targeted by current prophylactic HPV vaccines. PMID:21618551

Bryant, Dean; Rai, Nirmala; Rowlands, Gareth; Hibbitts, Sam; Jones, Joanne; Tristram, Amanda; Fiander, Alison; Powell, Ned

2011-08-01

115

Distribution of human papillomavirus genotypes among cervical intraepithelial neoplasia and invasive cancers in Macao.  

PubMed

Macao is a densely populated city situated in East Asia where a relatively high prevalence of human papillomavirus (HPV) types 52 and 58 has been reported in women with invasive cervical cancer. To provide data for a population-specific estimation on the impact of HPV vaccines, paraffin-embedded tissues collected from women with invasive cervical cancer or cervical intrapeitheilal neoplasia grade 2 or 3 confirmed histologically were examined for HPV using the INNO-LiPa kit. Of the 35 HPV-positive patients with invasive cancer, one HPV type was detected in 68.6%, and 31.4% were co-infected with more than one HPV type. Overall, HPV 16, HPV 18, HPV 52, and HPV 54 were the most common types found respectively in 57.1%, 17%, 11.4%, and 8.5% of patients with invasive cervical cancer. Among the 59 HPV-positive patients with cervical intraepithelial neoplasia grade 2/3, 55.9% hardbored one HPV type, and 44.1% had co-infections. The common HPV types found included HPV 16 (52.5%), HPV 52 (23.7%), HPV 58 (18.7%), and HPV 33 (17%). Although HPV 11 (a low-risk type) was also found commonly in invasive cervical cancers (14.3%) and cervical intraepithelial neoplasia grade 2/3 (15.3%), the fact that they all existed as co-infections with another high-risk type suggested HPV 11 was not the cause of the lesion. The current vaccines targeting HPV 16/18 are expected to cover 62.9-74.3% of invasive cervical cancers and 32.2-55.9% of cervical intraepithelial neoplasia 2/3 in Macao. Widespread HPV vaccination is expected to reduce substantially the disease burden associated with cervical neoplasia in Macao. PMID:20648616

Hlaing, Thazin; Yip, Yuk-Ching; Ngai, Karry L K; Vong, Heong-Ting; Wong, Sio-In; Ho, Wendy C S; Batalha, Sellma L S C; Chan, Paul K S

2010-09-01

116

Methylation status of normal background mucosa is correlated with occurrence and development of neoplasia in the distal colon.  

PubMed

The aim of this study is to evaluate the methylation status of normal colonic mucosa in relation to the stage of neoplasia arising from the mucosa. The methylation status of 2 age-related loci (ESR1 and MYOD1) and global methylation (the mean of Alu and Sat2) in the normal colonic mucosa of 156 patients with and without colorectal neoplasia were examined. The distal colon and proximal colon were analyzed separately because neoplasia is biologically and clinically different between these sites. The methylation status was determined by MethyLight using percentage of methylated reference (PMR). In the distal colon, methylation of the age-related loci decreased as the stage of neoplasia increased (patients with no neoplasia or with adenoma < or =9 mm versus patients with advanced adenoma or with invasive cancer: ESR1-PMR median, 21.0 versus 15.7; P = .015; MYOD1-PMR median, 5.35 versus 3.80; P = .0037, respectively). Interestingly, global methylation was inversely correlated with the stage of neoplasia (59.7 versus 61.5; P = .054). In contrast, the proximal colon showed no significant correlations. The methylation of MYOD1 in the normal mucosa was significantly correlated with K-ras mutation in neoplastic tissue arising from the mucosa. Specific epigenetic changes in normal colonic mucosa may be correlated with the occurrence and development of neoplasia in the distal colon. PMID:19733896

Hiraoka, Sakiko; Kato, Jun; Horii, Joichiro; Saito, Shunsuke; Harada, Keita; Fujita, Hideyuki; Kuriyama, Motoaki; Takemoto, Koji; Uraoka, Toshio; Yamamoto, Kazuhide

2010-01-01

117

Optimal fluorescence excitation wavelengths for detection of squamous intra-epithelial neoplasia: results from an animal model  

NASA Astrophysics Data System (ADS)

Using the hamster cheek pouch carcinogenesis model, we explore which fluorescence excitation wavelengths are useful for the detection of neoplasia. 42 hamsters were treated with DMBA to induce carcinogenesis, and 20 control animals were treated only with mineral oil. Fluorescence excitation emission matrices were measured from the cheek pouches of the hamsters weekly. Results showed increased fluorescence near 350-370 nm and 410 nm excitation and decreased fluorescence near 450-470 nm excitation with neoplasia. The optimal diagnostic excitation wavelengths identified using this model - 350-370 nm excitation and 400-450 nm excitation - are similar to those identified for detection of human oral cavity neoplasia.

Coghlan, Lezlee; Utzinger, Urs; Drezek, Rebekah A.; Heintzelmann, Doug; Zuluaga, Andres F.; Brookner, Carrie; Richards-Kortum, Rebecca R.; Gimenez-Conti, Irma; Follen, Michele

2000-12-01

118

Human papilloma virus testing in patient follow-up post cone biopsy due to high-grade cervical intraepithelial neoplasia  

Microsoft Academic Search

ObjectivesWe evaluated the contribution of the human papilloma virus (HPV) load in planning follow-up and management of women post cone biopsy for high-grade cervical intraepithelial neoplasia (CIN2–3).

Benny Almog; Ronni Gamzu; Michael J Kuperminc; Ishai Levin; Ofer Fainaru; Jakov Niv; Amiram Bar-Am

2003-01-01

119

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

PubMed

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. PMID:25678969

Preda, Veronica; Sywak, Mark; Learoyd, Diana

2015-01-01

120

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. PMID:25678969

Preda, Veronica; Sywak, Mark; Learoyd, Diana

2015-01-01

121

Abraham Lincoln's marfanoid mother: the earliest known case of multiple endocrine neoplasia type 2B?  

PubMed

The nature and cause of President Abraham Lincoln's unusual physical features have long been debated, with the greatest attention directed at two monogenic disorders of the transforming growth factor ? system: Marfan syndrome and multiple endocrine neoplasia type 2B. The present report examines newly discovered phenotypic information about Lincoln's biological mother, Nancy Hanks Lincoln, and concludes that (a) Lincoln's mother was skeletally marfanoid, (b) the President and his mother were highly concordant for the presence of numerous facial features found in various transforming growth factor ? disorders, and (c) Lincoln's mother, like her son, had hypotonic skeletal muscles, resulting in myopathic facies and 'pseudodepression'. These conclusions establish that mother and son had the same monogenic autosomal dominant marfanoid disorder. A description of Nancy Hanks Lincoln as coarse-featured, and a little-known statement that a wasting disease contributed to her death at age 34, lends support to the multiple endocrine neoplasia type 2B hypothesis. PMID:22504423

Sotos, John G

2012-07-01

122

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

123

Thymic Neuroendocrine Carcinoma (Carcinoid) in Multiple Endocrine Neoplasia Type 1 Syndrome: The Italian Series  

Microsoft Academic Search

Neuroendocrine tumors may occur in the setting of multiple endocrine neoplasia type 1 (MEN1) syndrome. Among these, a probably underestimated prevalence of well differentiated neuroendocrine thymic carcinoma (carcinoid), a neoplasm characterized by very aggressive behavior, has been de- scribed. We report characterization of the seven Italian cases inwhichthisassociationoccurredamongaseriesof221MEN1 patients (41 sporadic and 180 familial cases; prevalence, 3.1%). All of the

P. Ferolla; A. Falchetti; P. Filosso; P. Tomassetti; G. Tamburrano; N. Avenia; G. Daddi; F. Puma; R. Ribacchi; F. Santeusanio; G. Angeletti; M. L. Brandi

2005-01-01

124

Intraductal papillary mucinous neoplasia- a challenging diagnosis in a patient with paraneoplastic rheumatoid arthritis. Case report.  

PubMed

Intraductal papillary mucinous neoplasias (IPMNs) of the pancreas are potentially malignant tumors, and associated also with extrapancreatic carcinomas. We present the case of a 80 year old man with IPMN and late onset of rheumatoid arthritis. The particularity of this case is the discordance between the clinical picture and the imaging worrisome features, together with the surgery-requiring mixed-type of IPMN, despite the late possible paraneoplastic onset of rheumatoid arthritis. PMID:25745669

Grigorescu, Ioana; Cismaru, Andrei; Chira, Romeo; Catinean, Adrian; Dumitrascu, Dan Lucian

2015-03-01

125

An evaluation of treatment modalities in cervical intra-epithelial neoplasia.  

PubMed

The scheme of management of cervical intra-epithelial neoplasia presently utilized in the colposcopy service at Groote Schuur Hospital, Cape Town, is outlined, and the results of the treatment of 721 patients with the various modalities currently available are analysed. It is concluded that a radical approach (total hysterectomy was performed in 42,4% of the patients) is justified by the results obtained; the place of conservative methods of treatment, including cone biopsy, is discussed. PMID:6836441

Atad, J; Bloch, B

1983-04-01

126

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

127

Multiple endocrine neoplasia syndromes, children, Hirschsprung’s disease and RET  

Microsoft Academic Search

Multiple endocrine neoplasia (MEN) type 2 syndromes are autosomal dominant clinical associations characterized by a common\\u000a clinical feature, medullary thyroid carcinoma (MTC). The ability to accurately predict the risk by genetic RET proto-oncogene\\u000a analysis has resulted in the active follow-up of children at risk for developing early metastatic tumours and which can be\\u000a prevented by prophylactic thyroidectomy. The C634 and

S. W. Moore; M. G. Zaahl

2008-01-01

128

Prognostic factors in patients with Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1  

Microsoft Academic Search

Background & Aims: Risk factors of metachronous liver metastases and death are not well known in patients with the Zollinger–Ellison syndrome and multiple endocrine neoplasia type 1. These factors were retrospectively determined in 77 patients. Methods: Data chart review was performed. Results: Median follow-up was 102 months (range, 12–366). Surgery was performed on 48 patients, including 9 of the 10

Guillaume Cadiot; Albert Vuagnat; Isabelle Doukhan; Arnaud Murat; Guillaume Bonnaud; Brigitte Delemer; Gérard Thiéfin; Albert Beckers; Michel Veyrac; Charles Proye; Philippe Ruszniewski; Michel Mignon

1999-01-01

129

Loss of p53 enhances the induction of colitis-associated neoplasia by dextran sulfate sodium.  

PubMed

Loss of p53 function is an early event in colitis-associated neoplasia in humans. We assessed the role of p53 in a mouse model of colitis-associated neoplasia. Colitis was induced in p53-/-, p53+/- and p53+/+ mice using three or four cycles of dextran sulfate sodium (DSS) followed by 120 days of water. Mice were examined for incidence, multiplicity and types of neoplastic lesions. Lesions were examined for mutations in beta-catenin (exon 3), K-ras (codons 12/13) and p53 (exons 5-8) by sequencing and for cellular localization of beta-catenin by immunohistochemistry. The incidence of neoplastic lesions was 57, 20 and 20% in p53-/-, p53+/- and p53+/+ mice, respectively (P = 0.013). p53-/- mice had a greater number of total lesions (P < 0.0001), cancers (P = 0.001) and dysplasias (P = 0.009) per mouse than either p53+/- or p53+/+ mice. Flat lesions were associated with the p53-/- genotype, whereas polypoid lesions were associated with the p53+/- and p53+/+ genotypes (P < 0.0001). beta-Catenin mutations were present in 75% of lesions of p53+/+ mice and absent in lesions from p53-/- mice (P = 0.055). Nuclear expression of beta-catenin was seen only in polypoid lesions (91%). No K-ras or p53 mutations were detected. These data indicate that loss of p53 enhances the induction of colitis-associated neoplasia, particularly flat lesions, and dysregulation of beta-catenin signaling plays an important role in the formation of polypoid lesions in this mouse model. As observed in humans, p53 plays a protective role in colitis-associated neoplasia in the DSS model. PMID:17557903

Chang, Wen-Chi L; Coudry, Renata A; Clapper, Margie L; Zhang, Xiaoyan; Williams, Kara-Lynn; Spittle, Cynthia S; Li, Tianyu; Cooper, Harry S

2007-11-01

130

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

131

Inflammation and Atrophy Precede Prostatic Neoplasia in a PhIP-Induced Rat Model1  

PubMed Central

Abstract 2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) has been implicated as a major mutagenic heterocyclic amine in the human diet and is carcinogenic in the rat prostate. To validate PhIP-induced rat prostatic neoplasia as a model of human prostate cancer progression, we sought to study the earliest histologic and morphologic changes in the prostate and to follow progressive changes over time. We fed sixty-seven 5-week-old male Fischer F344 rats with PhIP (400 ppm) or control diets for 20 weeks, and then sacrificed animals for histomorphologic examination at the ages of 25, 45, and 65 weeks. Animals treated with PhIP showed significantly more inflammation (P = .002, > .001, and .016 for 25, 45, and 65 weeks, respectively) and atrophy (P = .003, > .001, and .006 for 25, 45, and 65 weeks, respectively) in their prostate glands relative to controls. Prostatic intraepithelial neoplasia (PIN) occurred only in PhIP-treated rats. PIN lesions arose in areas of glandular atrophy, most often in the ventral prostate. Atypical cells in areas of atrophy show loss of glutathione S-transferase ? immunostaining preceding the development of PIN. None of the animals in this study developed invasive carcinomas, differing from those in previous reports. Overall, these findings suggest that the pathogenesis of prostatic neoplasia in the PhIP-treated rat prostate proceeds from inflammation to postinflammatory proliferative atrophy to PIN. PMID:16984728

Borowsky, Alexander D; Dingley, Karen H; Ubick, Esther; Turteltaub, Kenneth W; Cardiff, Robert D; DeVere-White, Ralph

2006-01-01

132

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

133

Human papillomavirus infection of the uterine cervix of women without cytological signs of neoplasia.  

PubMed Central

One hundred and six patients were studied whose cervical smears showed only non-specific inflammatory changes. Screening for genital pathogens yielded only a few positive cases. Histological examination of biopsy specimens taken by colposcopically directed tissue sampling showed cervical intraepithelial neoplasia in 13 of the women (12.3%). Deoxyribonucleic acid (DNA) hybridisation techniques were used to detect human papillomavirus, which was found in 24 patients (22.6%). In a second group of 104 patients with normal cervical cytology tissue biopsy samples were obtained and examined histologically but in no case was cervical intraepithelial neoplasia found. On DNA hybridisation, however, 12 patients (11.5%) were found to be positive for human papillomavirus. In this group finding human papillomavirus DNA was usually associated with a columnar ectopy. An association between human papillomavirus type 16 DNA and both cervical intraepithelial neoplasia and cervical cancer is well established. In this study it was type 16 which occurred most frequently in both groups. Images p1262-a PMID:3022864

Toon, P G; Arrand, J R; Wilson, L P; Sharp, D S

1986-01-01

134

Combination of Paris and Vienna Classifications may Optimize Follow-Up of Gastric Epithelial Neoplasia Patients  

PubMed Central

Background The aim of this study was to evaluate the efficiency of the combination of Paris and Vienna classifications in a follow-up study of gastric epithelial neoplasia (GEN) patients. Material/Methods This study was conducted between January 2003 and September 2010, during which 170 biopsy-proven GEN patients were followed up by gastroenterologists and pathologists according to our follow-up regimen (modified Vienna classification). Results In total, 161 patients with low-grade neoplasia (LGN) and 9 patients with high-grade neoplasia (HGN) were randomly enrolled in our study. Eighteen patients with depressed appearance were observed, of which 9 patients had HGN and 9 patients had low-grade dysplasia (LGD). Three patients with type 0-IIa were observed with low-grade adenoma (LGA), and type 0–I was observed in 2 patients with LGN. Endoscopic or surgical treatments were performed to avoid potential malignancy or bleeding. Two patients with ulcer lesions, 2 patients with non-depressed type 0 appearance, and 3 patients without visible lesions were shown to have higher-grade lesions during follow-up. The misdiagnosis rate of forceps biopsy – 62.07% – was determined by comparing pre- and post-resection diagnoses of 29 patients. Conclusions The combination of the Paris and Vienna classifications for GEN may optimize the follow-up routines for patients with suspicious precancerous lesions and may significantly improve the detection of early gastric cancer (EGC) while helping gastroenterologists select the best therapy option. PMID:25841675

Hu, Wen; Ai, Xin-Bo; Zhu, Yi-Miao; Han, Tie-Mei; Shen, Bo; Pan, Wen-Sheng

2015-01-01

135

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

136

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

137

Combination of Paris and Vienna Classifications may Optimize Follow-Up of Gastric Epithelial Neoplasia Patients.  

PubMed

Background The aim of this study was to evaluate the efficiency of the combination of Paris and Vienna classifications in a follow-up study of gastric epithelial neoplasia (GEN) patients. Material and Methods This study was conducted between January 2003 and September 2010, during which 170 biopsy-proven GEN patients were followed up by gastroenterologists and pathologists according to our follow-up regimen (modified Vienna classification). Results In total, 161 patients with low-grade neoplasia (LGN) and 9 patients with high-grade neoplasia (HGN) were randomly enrolled in our study. Eighteen patients with depressed appearance were observed, of which 9 patients had HGN and 9 patients had low-grade dysplasia (LGD). Three patients with type 0-IIa were observed with low-grade adenoma (LGA), and type 0-I was observed in 2 patients with LGN. Endoscopic or surgical treatments were performed to avoid potential malignancy or bleeding. Two patients with ulcer lesions, 2 patients with non-depressed type 0 appearance, and 3 patients without visible lesions were shown to have higher-grade lesions during follow-up. The misdiagnosis rate of forceps biopsy - 62.07% - was determined by comparing pre- and post-resection diagnoses of 29 patients. Conclusions The combination of the Paris and Vienna classifications for GEN may optimize the follow-up routines for patients with suspicious precancerous lesions and may significantly improve the detection of early gastric cancer (EGC) while helping gastroenterologists select the best therapy option. PMID:25841675

Hu, Wen; Ai, Xin-Bo; Zhu, Yi-Miao; Han, Tie-Mei; Shen, Bo; Pan, Wen-Sheng

2015-01-01

138

Effects of oncological treatments on semen quality in patients with testicular neoplasia or lymphoproliferative disorders  

PubMed Central

Pretherapy sperm cryopreservation in young men is currently included in good clinical practice guidelines for cancer patients. The aim of this paper is to outline the effects of different oncological treatments on semen quality in patients with testicular neoplasia or lymphoproliferative disorders, based on an 8-year experience of the Cryopreservation Centre of a large public hospital. Two hundred and sixty-one patients with testicular neoplasia and 219 patients with lymphoproliferative disorders who underwent chemotherapy and/or radiotherapy and pretherapy semen cryopreservation were evaluated. Sperm and hormonal parameters (follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, inhibin B levels) were assessed prior to and 6, 12, 18, 24 and 36 months after the end of cancer treatment. At the time of sperm collection, baseline FSH level and sperm concentration were impaired to a greater extent in patients with malignant testicular neoplasias than in patients with lymphoproliferative disorders. Toxic effects on spermatogenesis were still evident at 6 and 12 months after the end of cancer therapies, while an improvement of seminal parameters was observed after 18 months. In conclusion, an overall increase in sperm concentration was recorded about 18 months after the end of cancer treatments in the majority of patients, even if it was not possible to predict the evolution of each single case ‘a priori'. For this reason, pretherapy semen cryopreservation should be considered in all young cancer patients. PMID:23542137

Di Bisceglie, Cataldo; Bertagna, Angela; Composto, Emanuela R; Lanfranco, Fabio; Baldi, Matteo; Motta, Giovanna; Barberis, Anna M; Napolitano, Emanuela; Castellano, Elena; Manieri, Chiara

2013-01-01

139

Early identification of cervical neoplasia with Raman spectroscopy and advanced methods for biomedical applications  

NASA Astrophysics Data System (ADS)

Early detection of malignant tumours, or their precursor lesions, can dramatically improve patient outcome. High risk human Papillomavirus (HPV), particularly HPV16, infection can lead to the initiation and development of uterine cervical neoplasia. Bearing this in mind the identification of the effects of HPV infection may have clinical value. In this manuscript we investigate the application of Raman microspectroscopy to detect the presence of HPV in cultured cells when compared with normal cells. We also investigate the effect of sample fixation, which is a common clinical practice, on the ability of Raman spectroscopy to detect the presence of HPV. Raman spectra were acquired from Primary Human Keratinocytes (PHK), PHK expressing the E7 gene of HPV 16 (PHK E7) and CaSki cells, an HPV16 containing cervical carcinoma derived cell line. The average Raman spectra display variations, mostly in peaks relating to DNA and proteins, consistent with HPV gene expression and the onset of neoplasia in both live and fixed samples. Principle component analysis was used to objectively discriminate between the cells types giving sensitivities up to 100% for the comparison between PHK and CaSki. These results show that Raman spectroscopy can discriminate between cell lines representing different stages of cervical neoplasia. Furthermore Raman spectroscopy was able to identify cells expressing the HPV 16 E7 gene suggesting the approach may be of value in clinical practice. Finally this technique was also able to detect the effects of the virus in fixed samples demonstrating the compatibility of this technique with current cervical screening methods. However if Raman spectroscopy is to make a significant impact in clinical practice the long acquisition times must be addressed. In this report we examine the potential for beam shaping and advanced to improve the signal to noise ration hence subsequently facilitating a reduction in acquisition time.

Jess, Phillip R. T.; Smith, Daniel D. W.; Mazilu, Michael; Cormack, Iain; Riches, Andrew C.; Herrington, C. Simon; Dholakia, Kishan

2008-02-01

140

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

141

Biological similarities and differences between pancreatic intraepithelial neoplasias and intraductal papillary mucinous neoplasms  

Microsoft Academic Search

Background: Ever since the classification of pancreatic intraepithelial neoplasia (PanIN) was published, studies on the precursor lesions\\u000a of pancreatic cancer have been advancing along a new directions, using standardized terminology. There are few studies that\\u000a have examined the biological differences between PanIN and intraductal papillary mucinous neoplasm (IPMN) in detail.\\u000a \\u000a \\u000a Aims: PanIN and IPMN, which are similar in morphology, were

Toshiyuki Moriya; Wataru Kimura; Shuho Semba; Fumiaki Sakurai; Ichiro Hirai; Jinfeng Ma; Akira Fuse; Kunihiko Maeda; Mitsunori Yamakawa

2005-01-01

142

Secondary excision for cervical intraepithelial neoplasia: an evaluation of two treatment methods.  

PubMed

A small proportion of women require repeat treatments for cervical intraepithelial neoplasia (CIN). This study aimed to compare the effectiveness of two cervical excisional techniques offered within a London teaching hospital (large loop excision of the transformation zone (LLETZ) and laser cone biopsy) when carried out as secondary procedures. A significantly larger volume of tissue was excised following laser cone biopsy, however the depth of the specimen did not differ significantly. A trend for a larger percentage of secondary specimens, resulting in complete endo-cervical margins and a larger proportion of women achieving cytology negative for CIN post-treatment was shown within the laser cone biopsy group. PMID:20604658

Bowring, J; Tulloch, I; Phadnis, S V; Young, M P A; Evans, H; Walker, P

2010-01-01

143

Dextran sulfate sodium-induced colitis-associated neoplasia: a promising model for the development of chemopreventive interventions.  

PubMed

Individuals diagnosed with ulcerative colitis face a significantly increased risk of developing colorectal dysplasia and cancer during their lifetime. To date, little attention has been given to the development of a chemopreventive intervention for this high-risk population. The mouse model of dextran sulfate sodium (DSS) - induced colitis represents an excellent preclinical system in which to both characterize the molecular events required for tumor formation in the presence of inflammation and assess the ability of select agents to inhibit this process. Cyclic administration of DSS in drinking water results in the establishment of chronic colitis and the development of colorectal dysplasias and cancers with pathological features that resemble those of human colitis-associated neoplasia. The incidence and multiplicity of lesions observed varies depending on the mouse strain used (ie, Swiss Webster, C57BL/6J, CBA, ICR) and the dose (0.7%-5.0%) and schedule (1-15 cycles with or without a subsequent recovery period) of DSS. The incidence of neoplasia can be increased and its progression to invasive cancer accelerated significantly by administering DSS in combination with a known colon carcinogen (azoxymethane (AOM), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-1- methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)) or iron. More recent induction of colitis-associated neoplasia in genetically defined mouse strains has provided new insight into the role of specific genes (ie, adenomatous polyposis coli (Apc), p53, inducible nitric oxide synthase (iNOS), Msh2) in the development of colitis-associated neoplasias. Emerging data from chemopreventive intervention studies document the efficacy of several agents in inhibiting DSS-induced neoplasia and provide great promise that colitis-associated colorectal neoplasia is a preventable disease. PMID:17723178

Clapper, Margie Lee; Cooper, Harry Stanley; Chang, Wen-Chi Lee

2007-09-01

144

Progression of naive intraepithelial neoplasia genome to aggressive squamous cell carcinoma genome of uterine cervix.  

PubMed

Although cervical intraepithelial neoplasia (CIN) is considered a neoplasia, its genomic alterations remain unknown. For this, we performed whole-exome sequencing and copy number profiling of three CINs, a microinvasive carcinoma (MIC) and four cervical squamous cell carcinomas (CSCC). Both total mutation and driver mutation numbers of the CINs were significantly fewer than those of the MIC/CSCCs (P = 0.036 and P = 0.018, respectively). Importantly, PIK3CA was altered in all MIC/CSCCs by either mutation or amplification, but not in CINs. The CINs harbored significantly lower numbers of copy number alterations (CNAs) than the MIC/CSCCs as well (P = 0.036). Pathway analysis predicted that the MIC/CSCCs were enriched with cancer-related signalings such as cell adhesion, mTOR signaling pathway and cell migration that were depleted in the CINs. The mutation-based estimation of evolutionary ages identified that CIN genomes were younger than MIC/CSCC genomes. The data indicate that CIN genomes harbor unfixed mutations in addition to human papilloma virus infection but require additional driver hits such as PIK3CA, TP53, STK11 and MAPK1 mutations for CSCC progression. Taken together, our data may explain the long latency from CIN to CSCC progression and provide useful information for molecular diagnosis of CIN and CSCC. PMID:25738363

Jung, Seung-Hyun; Choi, Youn Jin; Kim, Min Sung; Baek, In-Pyo; Lee, Sung Hak; Lee, Ah Won; Hur, Soo Young; Kim, Tae-Min; Lee, Sug Hyung; Chung, Yeun-Jun

2015-02-28

145

Isolated hemihyperplasia (hemihypertrophy): report of a prospective multicenter study of the incidence of neoplasia and review.  

PubMed

Hemihyperplasia is characterized by asymmetric growth of cranium, face, trunk, limbs, and/or digits, with or without visceral involvement. It may be an isolated finding in an otherwise normal individual, or it may occur in several syndromes. Although isolated hemihyperplasia (IHH) is of unknown cause, it may represent one end of the clinical spectrum of the Wiedemann-Beckwith syndrome (WBS). Uniparental paternal disomy of 11p15.5 or altered expression of insulin-like growth factor 2 (IGF2) from the normally silent maternal allele have been implicated as causes of some cases of WBS. IHH and other mild manifestations of WBS may represent patchy overexpression of the IGF2 gene following defective imprinting in a mosaic fashion. The natural history of IHH varies markedly. An association among many overgrowth syndromes and a predisposition to neoplasia is well recognized. Heretofore the risk for tumor development in children with IHH was unknown. We report on the results of a prospective multicenter clinical study of the incidence and nature of neoplasia in children evaluated because of IHH. One hundred sixty-eight patients were ascertained. A total of 10 tumors developed in nine patients, for an overall incidence of 5.9%. Tumors were of embryonal origin (similar to those noted in other overgrowth disorders), including Wilms tumor, hepatoblastoma, adrenal cell carcinoma, and leiomyosarcoma of the small bowel in one case. These data support a tumor surveillance protocol for children with IHH similar to that performed in other syndromes associated with overgrowth. PMID:9781907

Hoyme, H E; Seaver, L H; Jones, K L; Procopio, F; Crooks, W; Feingold, M

1998-10-01

146

Multiple endocrine neoplasias in a dog: corticotrophic tumour, bilateral adrenocortical tumours, and pheochromocytoma.  

PubMed

In a 10-year-old ovariohysterectomized standard Schnauzer, the finding of dexamethasone-resistant hypersecretion of cortisol, the results of computed tomography, and elevated plasma concentrations of ACTH suggested the presence of both adrenocortical tumour and pituitary-dependent hyperadrenocorticism. The dog made an uneventful recovery after bilateral adrenalectomy and remained in good health for 31/2 years with substitution for the induced hypoadrenocorticism. Then the enlarged pituitary caused neurological signs and eventually euthanasia was performed. The surgically excised right adrenal contained a well-circumscribed tumour of differentiated adrenocortical tissue and in the left adrenal there were two adrenocortical tumours and a pheochromocytoma. The unaffected parts of the adrenal cortices were well developed and without regressive transformation. At necropsy there were no metastatic lesions. The cells of the pituitary tumour were immunopositive for ACTH and had characteristics of malignancy. The present combination of corticotrophic tumour, adrenocortical tumours, and pheochromocytoma may be called 'multiple endocrine neoplasia' (MEN), but does not correspond to the inherited combinations of diseases known in humans as the MEN-1 and the MEN-2 syndromes. It is suggested that the co-existence of hyperadrenocorticism and pheochromocytoma may be related to the vascular supply of the adrenals. Some chromaffin cells of the adrenal medulla are directly exposed to cortical venous blood, and intra-adrenal cortisol is known to stimulate catecholamine synthesis and may promote adrenal medullary hyperplasia or neoplasia. PMID:9563161

Thuróczy, J; van Sluijs, F J; Kooistra, H S; Voorhout, G; Mol, J A; van der Linde-Sipman, J S; Rijnberk, A

1998-04-01

147

Evolving concepts in breast lobular neoplasia and invasive lobular carcinoma, and their impact on imaging methods.  

PubMed

Invasive lobular carcinoma (ILC) and lobular neoplasia (LN) are two distinct conditions that still pose challenges regarding to their classification, diagnosis and management. Although they share similar cellular characteristics, such as discohesive neoplastic cells and absence of e-cadherin staining, they represent completely different conditions. LN encompasses atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS), which are currently considered risk factors and non-obligatory precursors of breast neoplasia. These lesions are diagnosed as incidental findings in percutaneous biopsies or appear as non-specific clusters of punctate calcifications in mammograms. ILC is the second most common breast malignancy and has typical histological features, such as infiltrative growth and low desmoplasia. These histological features are reflected in imaging findings and constitute the reasons for typical subtle mammographic features of ILC, as architectural distortion or focal asymmetries. Ultrasonography (US) may detect almost 75 % of the ILCs missed by mammography and represents the modality of choice for guiding biopsies. Magnetic resonance imaging (MRI) exhibits a high sensitivity for the diagnosis of ILC and for detecting synchronous lesions. Teaching Points • LN includes ALH and LCIS, risk factors and non-obligatory precursors of breast cancer.• Absence of e-cadherin staining is crucial for differentiation among ductal and lobular lesions. • ILC has typical histological features, such as infiltrative growth and low desmoplasia. • Mammographic features of ILC are often subtle and reflect the histological features. • MRI exhibits a high sensitivity for the diagnosis of ILC and for detecting synchronous lesions. PMID:24633840

Oliveira, Tatiane M G; Elias, Jorge; Melo, Andrea F; Teixeira, Sara R; Filho, Salomão C; Gonçalves, Larissa M; Faria, Francesca M; Tiezzi, Daniel G; Andrade, Jurandyr M; Muglia, Valdair

2014-04-01

148

Assessment of a custom-built Raman spectroscopic probe for diagnosis of early oesophageal neoplasia  

NASA Astrophysics Data System (ADS)

We evaluate the potential of a custom-built fiber-optic Raman probe, suitable for in vivo use, to differentiate between benign, metaplastic (Barrett's oesophagus), and neoplastic (dysplastic and malignant) oesophageal tissue ex vivo on short timescales. We measured 337 Raman spectra (?ex=830 nm Pex=60 mW t=1 s) using a confocal probe from fresh (298) and snap-frozen (39) oesophageal tissue collected during surgery or endoscopy from 28 patients. Spectra were correlated with histopathology and used to construct a multivariate classification model which was tested using leave one tissue site out cross-validation in order to evaluate the diagnostic accuracy of the probe system. The Raman probe system was able to differentiate, when tested with leave one site out cross-validation, between normal squamous oesophagus, Barrett's oesophagus and neoplasia with sensitivities of (838% to 6%) and specificities of (89% to 99%). Analysis of a two group model to differentiate Barrett's oesophagus and neoplasia demonstrated a sensitivity of 88% and a specificity of 87% for classification of neoplastic disease. This fiber-optic Raman system can provide rapid, objective, and accurate diagnosis of oesophageal pathology ex vivo. The confocal design of this probe enables superficial mucosal abnormalities (metaplasia and dysplasia) to be classified in clinically applicable timescales paving the way for an in vivo trial.

Almond, L. Max; Hutchings, Jo; Kendall, Catherine; Day, John C. C.; Stevens, Oliver A. C.; Lloyd, Gavin R.; Shepherd, Neil A.; Barr, Hugh; Stone, Nick

2012-08-01

149

Risk for gastric neoplasias in patients with chronic atrophic gastritis: A critical reappraisal  

PubMed Central

Chronic atrophic gastritis (CAG) is an inflammatory condition characterized by the loss of gastric glandular structures which are replaced by connective tissue (non-metaplastic atrophy) or by glandular structures inappropriate for location (metaplastic atrophy). Epidemiological data suggest that CAG is associated with two different types of tumors: Intestinal-type gastric cancer (GC) and type?I?gastric carcinoid (TIGC). The pathophysiological mechanisms which lead to the development of these gastric tumors are different. It is accepted that a multistep process initiating from Helicobacter pylori-related chronic inflammation of the gastric mucosa progresses to CAG, intestinal metaplasia, dysplasia and, finally, leads to the development of GC. The TIGC is a gastrin-dependent tumor and the chronic elevation of gastrin, which is associated with CAG, stimulates the growth of enterochromaffin-like cells with their hyperplasia leading to the development of TIGC. Thus, several events occur in the gastric mucosa before the development of intestinal-type GC and/or TIGC and these take several years. Knowledge of CAG incidence from superficial gastritis, its prevalence in different clinical settings and possible risk factors associated with the progression of this condition to gastric neoplasias are important issues. This editorial intends to provide a brief review of the main studies regarding incidence and prevalence of CAG and risk factors for the development of gastric neoplasias. PMID:22493541

Vannella, Lucy; Lahner, Edith; Annibale, Bruno

2012-01-01

150

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

PubMed

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

Akerström, Göran; Stålberg, Peter; Hellman, Per

2012-01-01

151

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

152

Comparison of six immunohistochemical markers for the histologic diagnosis of neoplasia in Barrett's esophagus.  

PubMed

In esophageal neoplasms, the histopathologic differentiation between Barrett's esophagus with or without intraepithelial neoplasia and adenocarcinoma is often challenging. Immunohistochemistry might help to differentiate between these lesions. The expression of CDX2, LI-cadherin, mucin 2 (MUC2), blood group 8 (BG8, Lewis(y)), claudin-2, and villin was investigated in normal gastroesophageal (n?=?23) and in Barrett's (n?=?17) mucosa, in low-grade (n?=?12) and high-grade (n?=?9) intraepithelial neoplasia (IEN) as well as in esophageal adenocarcinoma (n?=?16), using immunohistochemistry. For CDX2 and LI-cadherin, the immunoreactivity score was highest in IEN while for MUC2, BG8, and villin, it dropped gradually from Barrett's via IEN to adenocarcinoma, and expression of Claudin-2 was only weak and focal in all lesions. The expression of MUC2 and LI-cadherin differed significantly between all examined lesions except between low-grade and high-grade IEN. MUC2 and LI-cadherin are useful immunohistochemical markers for the differentiation between normal glandular mucosa, Barrett's mucosa, IEN, and invasive carcinoma of the esophagus; however, none of the examined markers was helpful for the differentiation between low-grade and high-grade IEN. PMID:20844891

Weimann, Andreas; Rieger, Anja; Zimmermann, Mathias; Gross, Monica; Hoffmann, Peter; Slevogt, Hortense; Morawietz, Lars

2010-11-01

153

Ocular surface squamous neoplasia in patients with HIV infection in sub-Saharan Africa  

PubMed Central

Purpose of review Ocular surface squamous neoplasia (OSSN) in sub-Saharan countries is an aggressive tumor that affects younger patients and appears to be increasing in incidence. There are data to suggest the association of this disease with solar radiation exposure, HIV, and human papilloma virus (HPV). This trend possibly reflects the association of the high incidence of HIV, concomitant high incidence of exposure to HPV, and the solar radiation exposure that people in this region of the world receive. We undertook a PubMed search with the terms ‘ocular surface squamous neoplasia’, ‘conjunctival carcinoma’, ‘HIV’ and ‘HPV’, and ‘sub-Saharan/Africa’ to ascertain the scope of the problem and to review the available data, with an emphasis on publications of 2009 and the first quarter of 2010. Recent findings There is increasing evidence of a significant association between HIV seropositivity and OSSN. The role of HPV as contributing to the cause of OSSN is being investigated. Summary Patients with conjunctival cancer in sub-Saharan Africa are typically younger and more than 50% have underlying HIV infection. Initial presentation can be asymptomatic; however, many of these patients have advanced disease before they seek medical help and OSSN appears to have a more aggressive clinical course in sub-Saharan Africa. Treatment in Africa is primarily surgical. Chemotherapy and antiviral agents have been used. A diagnosis of OSSN in younger patients in sub-Saharan Africa should prompt HIV serotesting. PMID:20639761

Nagaiah, Govardhanan; Stotler, Christy; Orem, Jackson; Mwanda, Walter O.; Remick, Scot C.

2014-01-01

154

Risk factors for conjunctival squamous cell neoplasia: a matched case-control study  

PubMed Central

Aims: To identify roles of human papillomavirus (HPV) infection and solar elastosis as the risk factors for conjunctival squamous cell neoplasia (CSCN). Methods: 30 consecutive pathological specimens, ranging from conjunctival intraepithelial neoplasia, carcinoma in situ, to invasive squamous cell carcinoma were retrieved from tissue archives. 30 controls were disease free conjunctiva from age and sex matched patients undergoing extracapsular cataract extraction. Two masked pathologists studied haematoxylin and eosin stains on paraffin embedded conjunctival tissues. Elastic stain for solar elastosis was blindly interpreted in comparison with negative and positive controls. HPV infection was studied by polymerase chain reaction and dot hybridisation. Results: The mean age of CSCN patients was 54.9 years. The male to female ratio was 1:1. Solar elastosis was seen in 53.3% of CSCN and in 3.3% of controls with an odds ratio of 16.0 (95% CI, 2.49 to 670.96; p value = 0.0003). HPV DNA were not detected in any of the specimens. Conclusion: Solar elastosis is much more frequently found in CSCN cases than in their matched controls and is a risk factor for CSCN. These data are insufficient to conclude that HPV infection is a risk factor for CSCN. PMID:12642297

Tulvatana, W; Bhattarakosol, P; Sansopha, L; Sipiyarak, W; Kowitdamrong, E; Paisuntornsug, T; Karnsawai, S

2003-01-01

155

Genotyping human papillomavirus type 16 isolates from persistently infected promiscuous individuals and cervical neoplasia patients.  

PubMed Central

Nucleotide sequence variation in the noncoding region of the genome of human papillomavirus type 16 (HPV16) was determined by direct sequencing and single-strand conformation polymorphism analysis of DNA fragments amplified by PCR. Individuals of diverse sexual promiscuity and/or cervicopathology were studied. In a group of 14 healthy, monogamous HPV16-positive females, only two HPV16 sequence variants could be documented. Among 17 females and 3 males with multiple sex partners and living in the same geographical region, nine sequence variants were found, whereas among 7 patients with cervical neoplasia from another region, five variants were detected. Although numbers are limited, in the group of individuals at high risk of acquiring a sexually transmitted disease or with cervical neoplasia, a larger number of HPV16 sequence variants was encountered (two types among 14 individuals versus nine types among 20; Fisher's exact test, P = 0.07). Seven of the individuals were sampled repeatedly over time. For these persistently infected women, no differences in HPV16 sequences were detected, irrespective of promiscuity, and persistence of a single viral variant, spread over multiple anatomic sites, for more than 2 years could be demonstrated. This indicates that viral persistence may be a common feature and that successful superinfection with a new variant may be rare, despite a potentially high frequency of viral reinoculation. PMID:8576353

van Belkum, A; Juffermans, L; Schrauwen, L; van Doornum, G; Burger, M; Quint, W

1995-01-01

156

Prevalence and Risk Factors of Sexually Transmitted Infections and Cervical Neoplasia in Women from a Rural Area of Southern Mozambique  

PubMed Central

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

157

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

158

Expression of survivin, bcl-2, P53 and bax in breast carcinoma and ductal intraepithelial neoplasia (DIN 1a).  

PubMed

Survivin is a recently discovered member of the family of proteins that inhibits apoptosis. This anti-apoptotic compound can be detected in most types of cancer and expression is associated with a poor prognosis. We, immunohistochemically, investigated the expression of survivin in breast carcinomas and intraductal epithelial neoplasia of the breast to determine whether expression of this protein is associated with clinicopathological parameters such as grade, stage, mitotic rate. In 34 out of 43 cases (79.1%) of breast carcinoma and 22 out of 62 cases (35.4%) of intraductal epithelial neoplasia with mild, moderate and severe ductal epithelial, cell hyperplasia stained positively for survivin. None of the histological parameters analyzed were significantly correlated with survivin expression in breast carcinomas. In the carcinoma cases, survivin expression was positively correlated with expression of bcl-2, but was not correlated with expression of p53, bax, c-erbB-2 and estrogen, or progesterone. Some of the intraductal epithelial neoplasia cases with moderate or severe ductal epithelial hyperplasia stained positively for both survivin and p53. Breast carcinomas exhibited a significant expression of survivin, p53, and bcl-2 compared to breast with intraductal epithelial neoplasia. Survivin was not correlated with any of the clinicopathological parameters studied, however it could be a useful tool in early carcinomas and florid, severe ductal epithelial hyperplasia. PMID:15149158

Kayaselcuk, F; Nursal, T Z; Polat, A; Noyan, T; Yildirim, S; Tarim, A; Seydioglu, G

2004-03-01

159

Influence of multiple endocrine neoplasia type 1 on gastric endocrine cells in patients with the Zollinger-Ellison syndrome  

Microsoft Academic Search

The influences of multiple endocrine neoplasia type 1 (MEN 1), hypergastrinaemia, age, and sex on gastric endocrine cell densities were studied in 48 patients with the Zollinger-Ellison syndrome of either the sporadic type (n = 31) or associated with MEN 1 (n = 17). The mean fundic argyrophil cell density was higher in women (p < 0.05). It showed no

T Lehy; G Cadiot; M Mignon; P Ruszniewski; S Bonfils

1992-01-01

160

Current surgical management of Zollinger–Ellison syndrome (ZES) in patients without multiple endocrine neoplasia-type 1 (MEN1)  

Microsoft Academic Search

The role of surgery in the management of patients with sporadic (not part of multiple endocrine neoplasia type 1) Zollinger–Ellison syndrome (ZES) is controversial. In this setting, 60–90% of gastrinomas are malignant and medical therapy can control the gastric acid hypersecretion in virtually every patient. Therefore, the progression of tumor is the major determinant of survival. Surgery will cure approximately

Jeffrey A. Norton; Robert T. Jensen

2003-01-01

161

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

162

Pathologic aspects of gastrinomas in patients with Zollinger-Ellison syndrome with and without multiple endocrine neoplasia type I  

Microsoft Academic Search

During the three decades since the recognition of the Zollinger-Ellison syndrome (ZES), major progress has been made in the diagnosis and treatment of this disease. However, the many failed operations in patients with ZES, the existence of primary lymph node gastrinomas, and the surgical approach of patients with ZES and multiple endocrine neoplasia type I (MEN-I) have remained controversial issues.

Miriam Pipeleers-Marichal; Christian Donow; Philipp U. Heitz; Günter Klöppel

1993-01-01

163

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

164

High Incidence of Breast and Endometrial Neoplasia Resembling Human Cowden Syndrome in pten1\\/2 Mice  

Microsoft Academic Search

PTEN is one of the most commonly mutated tumor suppressor genes in human cancer. PTEN mutations have been implicated in the development of a variety of human neoplasia, including high-grade glioblastoma, pros- tate, breast, endometrial, and thyroid carcinoma. Germ-line mutations of PTEN cause Cowden's syndrome (CS), a multiple hamartoma condition resulting in increased susceptibility for the development of cancer. When

Vuk Stambolic; Ming-Sound Tsao; David Macpherson; Akira Suzuki; William B. Chapman; Tak W. Mak

165

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

166

Cervical Neoplasia-Related Factors and Decreased Prevalence of Uterine Fibroids among a Cohort of African-American Women  

PubMed Central

Objective To investigate whether the previously reported inverse association between cervical neoplasia and uterine fibroids is corroborated. Design Cross-sectional analysis of enrollment data from an ongoing prospective study of fibroid development. Setting Detroit, Michigan area. Patients(s) Self-reported data on abnormal Pap smear, colposcopy and cervical treatment were obtained from 1,008 African-American women ages 23-34 with no previous fibroid diagnosis and no reported history of HPV vaccination. Presence of fibroids was assessed at a standardized ultrasound examination. Intervention(s) None. Main Outcome Measure(s) The association between the 3 cervical neoplasia-related variables and presence of fibroids was evaluated with logistic regression to estimate age-adjusted and multivariable-adjusted odds ratios (ORs). Result(s) Of the analysis sample, 46%, 29% and 14% reported a prior abnormal Pap smear, colposcopy and cervical treatment, respectively. Twenty-five percent had fibroids at ultrasound. Those reporting cervical treatment had a 39% [aOR: 0.61, 95%CI (0.38-0.96)] reduction in fibroid risk. Weak non-significant associations were found for abnormal Pap smear and colposcopy. Conclusion(s) Although a protective-type association of cervical neoplasia with uterine fibroids seems counter intuitive, a causal pathway is possible, and the findings are consistent with two prior studies. Further investigation is needed on the relationship between fibroids and cervical neoplasia and HPV-related mechanisms. PMID:24268705

Moore, Kristen R.; Smith, Jennifer S.; Laughlin-Tommaso, Shannon K.; Baird, Donna D.

2013-01-01

167

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

168

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

2015-05-01

169

[Various neuroendocrine tumors in a family with multiple endocrine neoplasia type 1].  

PubMed

When multiple endocrine tumors are detected more tests are required to diagnose endocrine tumor syndromes. The authors report the case history of a patient with clinical manifestation of multiplex endocrine neoplasia type 1 (parathyroid adenoma, pancreatic neuroendocrine tumor, pituitary tumor, adrenal gland tumors and thymic neuroendocrine carcinoma). Genetic screening proved a novel stop codon mutation of the MEN1 gene in the patient and in two other members of the family. The son of the index patient showed clinical symptoms of pancreatic neuroendocrine tumor (insulinoma) and parathyroid adenoma. One of the two daughters was also positive for the same mutation, however, she had no clinical symptoms. The authors review current knowledge on the genetic background of multiple endocrine syndrome type 1, the role of menin and the usefulness of gene mutation screening. PMID:24334135

Sepp, Krisztián; Valkusz, Zsuzsanna

2013-12-22

170

BCR-ABL negative myeloproliferative neoplasia: a review of involved molecular mechanisms.  

PubMed

The clonal bone marrow stem cell disorders essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) belong to the group of Philadelphia chromosome negative myeloproliferative neoplasia (Ph- MPN). In 2005 the JAK2(V617F) mutation was discovered which has generated more insight in the pathogenetic mechanism of the MPNs. More mutations have been detected in MPN patients since. However, the underlying cause of MPN has not been discovered so far. The mechanism of increased angiogenesis in MPNs and the development of fibrosis in the bone marrow in PMF patients and in some ET and PV patients is still not known. This review will focus on the most important molecular pathogenetic mechanisms in MPN patients. PMID:25196073

Koopmans, Suzanne M; Schouten, Harry C; van Marion, Ariënne M W

2015-02-01

171

Protein kinase D1 drives pancreatic acinar cell reprogramming and progression to intraepithelial neoplasia  

NASA Astrophysics Data System (ADS)

The transdifferentiation of pancreatic acinar cells to a ductal phenotype (acinar-to-ductal metaplasia, ADM) occurs after injury or inflammation of the pancreas and is a reversible process. However, in the presence of activating Kras mutations or persistent epidermal growth factor receptor (EGF-R) signalling, cells that underwent ADM can progress to pancreatic intraepithelial neoplasia (PanIN) and eventually pancreatic cancer. In transgenic animal models, ADM and PanINs are initiated by high-affinity ligands for EGF-R or activating Kras mutations, but the underlying signalling mechanisms are not well understood. Here, using a conditional knockout approach, we show that protein kinase D1 (PKD1) is sufficient to drive the reprogramming process to a ductal phenotype and progression to PanINs. Moreover, using 3D explant culture of primary pancreatic acinar cells, we show that PKD1 acts downstream of TGF? and Kras, to mediate formation of ductal structures through activation of the Notch pathway.

Liou, Geou-Yarh; Döppler, Heike; Braun, Ursula B.; Panayiotou, Richard; Scotti Buzhardt, Michele; Radisky, Derek C.; Crawford, Howard C.; Fields, Alan P.; Murray, Nicole R.; Wang, Q. Jane; Leitges, Michael; Storz, Peter

2015-02-01

172

[Primary retroperitoneal carcinoid tumor associated with multiple endcrine neoplasia (men) type 1: a case report].  

PubMed

We report an extremely rare case of a 69-year-old man having a retroperitoneal carcinoid tumor associated with multiple endocrine neoplasia (MEN) type 1. The patient whose son and daughter were previously diagnosed with MEN type 1 was admitted to the Department of Endocrinology at our hospital for evaluation of this disorder. Computed tomography (CT) and ultrasonography revealed a parathyroid and retroperitoneal tumor (43 mm x 34 mm). The patient did not consent to surgical management of the tumor; however three years later, a follow-up CT revealed tumor enlargement (55 mm x 50 mm). We were unable to rule out a malignancy, and subsequently resected the tumor. A pathological diagnosis of retroperitoneal carcinoid was made. No local recurrence or metastasis have been observed for 21 months. PMID:22390089

Chiba, Syuji; Numakura, Kazuyuki; Satoyoshi, Kiyofumi; Saito, Mitsuru; Horikawa, Yohei; Takayama, Koichiro; Nara, Taketoshi; Kanda, Sohei; Miura, Yoshiko; Maita, Shinya; Tsuruta, Hiroshi; Obara, Takashi; Kumazawa, Teruaki; Narita, Shintaro; Tsuchiya, Norihiko; Satoh, Shigeru; Habuchi, Tomonori

2011-11-01

173

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

174

Familial Cushing syndrome due to thymic carcinoids in a multiple endocrine neoplasia type 1 kindred.  

PubMed

The objective of this study is to present a familial Cushing syndrome (CS) caused by multiple endocrine neoplasia type 1 (MEN-1)-associated thymic carcinoid. Immunohistochemistry, gene sequencing, loss of heterozygosity analysis, and Western blot were used to determine the expression of ACTH in MEN-1-related thymic tumors, MEN1 gene mutation, the pattern and extent of allelic deletion, and the expression of Menin in MEN-1-associated tumors, respectively. Tumor cells from thymus ectopic-secreted ACTH. A deletion involving the MEN1 gene locus was confirmed. The expression of Menin in MEN-1-associated tumors declined. To conclude, we presented an unusual kindred of MEN-1, which pointed out the significance of making screening of MEN-1 for both male and female patients with CS and thymic carcinoid. PMID:24452869

Li, Xiaohua; Su, Jing; Zhao, Li; Wu, Jingcheng; Ding, Xiaoying; Fang, Fang; Wu, Yijie; Sun, Haiyan; Peng, Yongde

2014-09-01

175

Natural history of intraductal papillary mucinous neoplasia: How much do we really know?  

PubMed

Information on the natural history of intraductal papillary mucinous neoplasia (IPMN) is currently inadequate due to a lack of carefully orchestrated long-term follow-up on a large cohort of patients with asymptomatic disease. Based on the available data, one can draw the conclusions that main duct IPMN is commonly associated with malignancy and an aggressive operative stance should be taken with resection being offered to most patients who are suitable operative candidates. In contrast, the majority of branch type IPMN with a diameter of less than 3 cm can be safely followed with routine surveillance imaging provided they lack the high-risk covariates of age, symptomatology, nodularity or wall thickness. PMID:21160846

Ball, Chad G; Howard, Thomas J

2010-10-27

176

Two case reports of pilot percutaneous cryosurgery in familial multiple endocrine neoplasia type 1.  

PubMed

We report 2 cases of familial multiple endocrine neoplasia type 1 syndrome (MEN 1) in related Malaysian Chinese individuals: the son had simultaneous primary lesions in the pancreatic tail, parathyroid, adrenal gland, and hypophysis, with metastatic tumors in the left lung, mediastinum and spine; his mother had simultaneous primary lesions in the pancreatic head, parathyroid, and hypophysis, with metastatic tumors in the liver, spine, ilium, chest wall, and rib. Genetic testing of the 2 patients showed the same mutation in exon 9 of MEN1 (c.1288G>T, Glu430, encoding a stop codon). The tumors with the poorest prognosis and clinical sequelae were in the pancreas of both patients, and these were treated by percutaneous cryoablation. The number of hypoglycemic episodes in the son improved for more than 120 days, and the abdominal space occupying lesion resolved in his mother. PMID:23407484

Li, Jialiang; Zhang, Changming; Chen, Jibing; Yao, Fei; Zeng, Jianying; Huang, Liwen; Yang, Xiuli; Liu, Weiqun; Chen, Feng; Xu, Keqiang; Yang, Daming; Niu, Lizhi; Zuo, Jiansheng; Xu, Kecheng; Liu, DePei

2013-03-01

177

Multiple endocrine neoplasia type 1 with upper gastrointestinal hemorrhage and perforation: a case report and review.  

PubMed

Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary syndrome known to predispose subjects to endocrine neoplasms in a variety of tissues such as the parathyroid glands, pituitary gland, pancreas and gastrointestinal tract. We herein report a patient with a past history of pituitary adenoma, presenting with symptoms of chronic diarrhea for nearly one year and a sudden upper gastrointestinal hemorrhage as well as perforation without signs. Nodules in the duodenum and in the uncinate process and tail of pancreas and enlargement of the parathyroid glands were detected on preoperative imaging. Gastroscopy revealed significant ulceration and esophageal reflux diseases. The patient underwent subtotal parathyroidectomy and autotransplantation, pylorus-preserving pancreaticoduodenectomy and pancreatic tail resection and recovered well. The results observed in our patient suggest that perforation and bleeding of intestine might be symptoms of Zollinger-Ellison Syndrome in patients with MEN1. PMID:23482249

Lu, Ying-Ying; Zhu, Feng; Jing, Da-Dao; Wu, Xie-Ning; Lu, Lun-Gen; Zhou, Gen-Quan; Wang, Xing-Peng

2013-02-28

178

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

179

A Special Role of the Group 17,18 Chromosomes in Reticuloendothelial Neoplasia  

PubMed Central

The hypothesis is advanced that abnormalities of the chromosome group 17,18 play a special role in the genesis and/or evolution of some reticuloendothelial neoplasms. Aberrations of the group 17,18 chromosomes in tumour cells exceed in variety the reported anomaliesof any other chromosome. Both the frequency of these aberrations and their nature make them most unlikely to be due to chance. They appear to be non-random, often occurring in every cell of a tumour, and like the Ph1 anomaly in chronic granulocytic leukaemia, mightpossess aetiological significance. The Ep- and Eqchromosomal anomalies resemble the Ph1 in being fine structural modifications, which occur as acquired lesions only in neoplasms, often in tumour cells with otherwise normal karyotypes. Aberration of the group 17,18 chromosomes may sometimes be secondary to neoplasia but nevertheless of evolutionary significance for the tumour cells. Changes leading to relative or absolute excess of long-arm material of chromosome 18 may confer survival advantage upon cells, particularly if a normal complement of short-arm material is simultaneously retained. However, specific deletion of the distal part of the long arms of No. 18 may also favour cell survival. The short arms of chromosome 18 may carry genes limiting cell reproduction, while the long arms carry material promoting proliferation. More distally on the long arms, there may be genes which also limit reproduction. Disturbances affecting the balance between these components of the genome may be important in inception of neoplasia or subsequent evolution of tumour cell lines. PMID:4913770

Spiers, A. S. D.; Baikie, A. G.

1970-01-01

180

Cervical intraepithelial neoplasia in Jordan: A ten year retrospective cytoepidemiologic study.  

PubMed

Occurrence of cervical intraepithelial neoplasia (CIN) was studied in 10,659 females attending obstetric and gynecology clinics in Jordan. The frequency rate of intraepithelial neoplasia was 1.1% in 7743 Jordanian females and 2916 non-Jordanian residents of younger age during the period from 1982 to 1991 inclusive. The incidence rate in 2649 Jordanian females, selected because they attended only for routine checkup, was 49 per 100,000. There were 121 CIN cases which were graded into Grade I (21%), II (48%) and III (31%) respectively. Histological grading correlated with cytology in 70% of the cases while in the remaining 30%, cytologic underrating by one grade was noted; evidence against any overdiagnosis of CIN in our series. Study of the human papillomavirus (HPV) was outside the scope of this effort. However, circumcision in male partners and marital status were associated with a lower frequency of CIN. Age at marriage and average duration, parity, breast feeding, the contraceptive pill, socioeconomic status and menstrual disorders showed no relationship to the frequency of CIN in our patients. Any differences in the latter between Jordanian and non-Jordanian females are believed due to cultural factors. Conization in 27 cases proved effective at 30 months' follow-up. Occurrence of CIN in Jordanian females appears substantial although much lower than that seen in high incidence zones, while its incidence in the general female population remains to be determined. This study shows for the first time the value of Papanicolaou (Pap) smears in Jordanian females over 20 years of age with special emphasis on those over 35 years of age attending obstetric and gynecology clinics. PMID:17590606

Dajani, Y F; Maayta, U M; Abu-Ghosh, Y R

1995-07-01

181

Unique variants of human papillomavirus genotypes 52 and 58 and risk of cervical neoplasia.  

PubMed

Human papillomavirus (HPV) 52 and 58 are oncogenic HPV types prevalent in Asia. Our study aims to explore intratypic variants of HPV 52 and 58 in Taiwan. A total of 11,923 women were enrolled from seven townships in 1991-1992. HPV DNA in their cervical cells was detected and typed by EasyChip® HPV blot. Among 424 participants infected with HPV 52 and/or 58, nucleotide variations were determined in cervical cell samples of 406 participants by the polymerase chain reaction sequencing of the long control region, E6 and E7 genes. Nonprototype-like variants including lineages B and C were detected in 278 (99.3%) of 280 HPV 52 samples. The prototype and prototype-like group (lineage A) of HPV58 was found in 132 (98.5%) of 134 HPV 58 samples, with sublineage A1, A2 and A3 variant in 14.2, 27.6 and 56.7%, respectively. Among women infected with single HPV 52 type, the C variant (vs. B variant) was associated with an increased prevalence of cytologically diagnosed high-grade squamous intraepithelial lesion or worse lesions showing an age-adjusted odds ratio (95% confidence interval, CI) of 5.2 (1.0-27.6) and an increased prevalence of histologically confirmed high-grade cervical intraepithelial neoplasia or more severe lesions with an age-adjusted odds ratio (95% CI) of 7.6 (1.3-43.8). It was concluded that frequency distributions of HPV 52 and 58 variants in Taiwan were different from those in European and American populations. The association between C variant of HPV 52 and prevalence of cervical neoplasia needs further validation. PMID:20949622

Chang, Ya-Ju; Chen, Hui-Chi; Lee, Bor-Heng; You, San-Lin; Lin, Ching-Yu; Pan, Mei-Hung; Chou, Yi-Chun; Hsieh, Chang-Yao; Chen, Yi-Ming A; Cheng, Yu-Juen; Chen, Chien-Jen

2011-08-15

182

Methylation of HPV18, HPV31, and HPV45 Genomes and Cervical Intraepithelial Neoplasia Grade 3  

PubMed Central

Background Persistent infections with carcinogenic human papillomavirus (HPV) types are the necessary cause of cervical cancer. We recently demonstrated that the HPV16 genome is strongly methylated in cervical precancer compared with transient infections. However, the extent of methylation in other HPV types and its role in progression to cancer is poorly understood. Methods We analyzed whole-genome methylation patterns of the three next most carcinogenic HPV genotypes: HPV31 (closely related to HPV16), and two other closely related types, HPV18 and HPV45. DNA was extracted from cervical cytology specimens from 92 women with precancer and 96 women infected with HPV31, HPV18, or HPV45, but who had no cytological or histological abnormalities. After bisulfite modification, genome-wide pyrosequencing was performed covering 80–106 sites. We calculated differences in median methylation, odds ratios, areas under the curve, and Spearman rank correlation coefficients for methylation levels between different sites. All statistical tests were two-sided. Results For all three HPV types, we observed strongly elevated methylation levels at multiple CpG sites in the E2, L2, and L1 regions among women with cervical intraepithelial neoplasia grade 3 compared with women with transient infections. We observed high correlation of methylation patterns between phylogenetically related types. The highest areas under the curve were 0.81 for HPV31, 0.85 for HPV18, and 0.98 for HPV45. Differential methylation patterns in cervical intraepithelial neoplasia grade 3 patients with multiple infections suggest that methylation can clarify which of the infections is causal. Conclusions Carcinogenic HPV DNA methylation indicates transforming HPV infections. Our findings show that methylation of carcinogenic HPV types is a general phenomenon that warrants development of diagnostic assays. PMID:23093560

Wentzensen, Nicolas; Sun, Chang

2012-01-01

183

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

184

Association of human papilloma virus with pterygia and ocular-surface squamous neoplasia  

PubMed Central

There are more microorganisms that colonize the human body than resident cells; some are commensal whereas others are pathogenic. Pathogenic microorganisms are sensed by the innate or adaptive immune system, an immune response is initiated, and the infection is often cleared. Some microorganisms have developed strategies to evade immune defenses, ensuring their long-term survival with potentially devastating consequences for the host. Approximately 18% of all cancers can be attributed to infective agents; the most common being Helicobacter pylori, Human papilloma virus (HPV) and Hepatitis B and C virus in causing stomach, cervical and liver carcinoma, respectively. This review focuses on whether HPV infection is necessary for initiating pterygia, a common benign condition and ocular-surface squamous neoplasia (OSSN), a rare disease with metastatic potential. The search engine PubMed was used to identify articles from the literature related to HPV and pterygium or conjunctival neoplasia. From 34 investigations that studied HPV in pterygia and OSSN, a prevalence rate of 18.6% (136/731) and 33.8% (144/426), respectively, was recorded. The variation in HPV prevalence (0–100%) for both disease groups may have arisen from study-design faults and the techniques used to identify the virus. Overall, the data suggest that HPV is not necessary for initiating either condition but may be a co-factor in susceptible hosts. Currently, over 60 million people worldwide have been immunized with HPV vaccines, but any effect on pterygium and OSSN development may not be known for some time as these lesions can evolve over decades or occur in older individuals. PMID:22134594

Di Girolamo, N

2012-01-01

185

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

186

The clinical value of in vivo confocal microscopy for diagnosis of ocular surface squamous neoplasia  

PubMed Central

Purpose To determine the reliability and efficiency of in vivo confocal microscopy for the diagnosis of ocular surface squamous neoplasia (OSSN). Methods A case series with five consecutive cases of OSSN were investigated retrospectively, of which the characteristics and subspecial types had been estimated by in vivo confocal microscopy before surgery. The structure and cellular features of OSSN were analyzed with other examinations, such as anterior-segment optical coherence tomography (AS-OCT), and confirmed by histopathological biopsy. Results The tumors revealed red gelatinous surfaces with vascular dilatation on the ocular surface of the conjunctival and corneal epithelium in anterior segment photography. Involvement of only corneal epithelium was observed by AS-OCT in three cases, whereas the Bowman's layer and anterior stroma were also invaded in the other two cases. In vivo confocal microscopy showed cellular anisocytosis and enlarged nuclei with high nuclear to cytoplasmic ratio in three cases diagnosed as conjunctival intraepithelial neoplasia; moreover, nests were partially formed by isolated keratinized, binucleated, and actively mitotic dysmorphic epithelial cells in the other two cases diagnosed as carcinoma in situ and ocular surface squamous carcinoma (OSSC). The characteristics assessed from histopathological biopsy were similar to that revealed by in vivo confocal microscopy in all five cases. Conclusion In vivo confocal microscopy analysis of cytological characteristics of OSSN is a safe, relatively noninvasive, and effective diagnostic tool in detecting characteristics of OSSN before surgical resection. Although in vivo confocal microscopy cannot replace excisional biopsy for definitive diagnosis, it can be valuable for initial diagnosis and management of patients with OSSN. PMID:22402703

Xu, Y; Zhou, Z; Xu, Y; Wang, M; Liu, F; Qu, H; Hong, J

2012-01-01

187

The epidemiology of ocular surface squamous neoplasia in a Veterans Affairs population  

PubMed Central

Purpose To evaluate the epidemiology of ocular surface squamous neoplasia (OSSN) and its associated risk factors in a South Florida Veterans Affairs Hospital population. Design Retrospective case-control study. Methods Participants 28 confirmed cases of OSSN from 24,179 veterans who received care at the Miami Veterans Affairs Healthcare System (VA) and affiliated satellite eye clinics between March 1, 2007, and March 1, 2012. Methods Data extracted from the veterans administration database comprised of demographic information and medical diagnosis information (based on International Classification of Disease (ICD-9) codes). Main Outcome Measures The period prevalence of OSSN and identification of factors associated with the presence of disease. Results The period prevalence of OSSN in our population was 0.1%. Studied risk factors included ultra-violet (UV)-related dermatologic diseases (melanoma, squamous and basal cell cancer, and actinic keratosis), UV-related ocular conditions (pterygium). human immunodeficiency virus (HIV) seropositivity, human papilloma virus (HPV)-related diseases, and tobacco use. The presence of a skin malignancy (squamous cell carcinoma (SCC) and/or basal cell carcinoma (BCC)) and pterygium were found to be significantly associated with the presence of OSSN (odds ratio (OR) 4.40, 95% confidence interval (CI) 2.03–9.55, p <0.0005 and OR 16.2 95% CI 7.11–36.9, p <0.0005, respectively). Conclusions The presence of neoplasias and ocular conditions related to sun exposure were the most important risk factors for the presence of OSSN in a South Florida VA population consistent with previous epidemiological reports worldwide. PMID:23974890

McClellan, Andrew J.; McClellan, Allison L.; Pezon, Candido F.; Karp, Carol L.; Feuer, William; Galor, Anat

2013-01-01

188

Association of human papilloma virus with pterygia and ocular-surface squamous neoplasia.  

PubMed

There are more microorganisms that colonize the human body than resident cells; some are commensal whereas others are pathogenic. Pathogenic microorganisms are sensed by the innate or adaptive immune system, an immune response is initiated, and the infection is often cleared. Some microorganisms have developed strategies to evade immune defenses, ensuring their long-term survival with potentially devastating consequences for the host. Approximately 18% of all cancers can be attributed to infective agents; the most common being Helicobacter pylori, Human papilloma virus (HPV) and Hepatitis B and C virus in causing stomach, cervical and liver carcinoma, respectively. This review focuses on whether HPV infection is necessary for initiating pterygia, a common benign condition and ocular-surface squamous neoplasia (OSSN), a rare disease with metastatic potential. The search engine PubMed was used to identify articles from the literature related to HPV and pterygium or conjunctival neoplasia. From 34 investigations that studied HPV in pterygia and OSSN, a prevalence rate of 18.6% (136/731) and 33.8% (144/426), respectively, was recorded. The variation in HPV prevalence (0-100%) for both disease groups may have arisen from study-design faults and the techniques used to identify the virus. Overall, the data suggest that HPV is not necessary for initiating either condition but may be a co-factor in susceptible hosts. Currently, over 60 million people worldwide have been immunized with HPV vaccines, but any effect on pterygium and OSSN development may not be known for some time as these lesions can evolve over decades or occur in older individuals. PMID:22134594

Di Girolamo, N

2012-02-01

189

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

190

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

the substratum; WAP, whey acidic protein; 2D, two-dimensional; 3D, three-dimensional; d, cell deformation; FJournal of Mammary Gland Biology and Neoplasia, Vol. 9, No. 4, October 2004 ( C 2004) DOI: 10

Nelson, Celeste M.

191

Germline RET 634 Mutation Positive MEN 2A-related C-Cell Hyperplasias Have Genetic Features Consistent with Intraepithelial Neoplasia  

Microsoft Academic Search

C-cell hyperplasias are normally multifocal in multiple endo- crine neoplasia type 2A. We compared clonality, microsatel- lite pattern of tumor suppressor genes, and cellular kinetics of C-cell hyperplasia foci in each thyroid lobe. We selected 11 females from multiple endocrine neoplasia type 2A kindred treated with thyroidectomy due to hypercal- citoninemia. C-cell hyperplasia foci were microdissected for DNA extraction to

SALVADOR J. DIAZ-CANO; MANUEL DE MIGUEL; ALFREDO BLANES; ROBERT TASHJIAN; HUBERT J. WOLFE

2010-01-01

192

In vivo diagnosis of murine pancreatic intraepithelial neoplasia and early-stage pancreatic cancer by molecular imaging  

PubMed Central

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with poor patient outcome often resulting from late diagnosis in advanced stages. To date methods to diagnose early-stage PDAC are limited and in vivo detection of pancreatic intraepithelial neoplasia (PanIN), a preinvasive precursor of PDAC, is impossible. Using a cathepsin-activatable near-infrared probe in combination with flexible confocal fluorescence lasermicroscopy (CFL) in a genetically defined mouse model of PDAC we were able to detect and grade murine PanIN lesions in real time in vivo. Our diagnostic approach is highly sensitive and specific and proved superior to clinically established fluorescein-enhanced imaging. Translation of this endoscopic technique into the clinic should tremendously improve detection of pancreatic neoplasia, thus reforming management of patients at risk for PDAC. PMID:21628592

Eser, Stefan; Messer, Marlena; Eser, Philipp; von Werder, Alexander; Seidler, Barbara; Bajbouj, Monther; Vogelmann, Roger; Meining, Alexander; von Burstin, Johannes; Algül, Hana; Pagel, Philipp; Schnieke, Angelika E.; Esposito, Irene; Schmid, Roland M.; Schneider, Günter; Saur, Dieter

2011-01-01

193

Transgenic mouse models that explore the multistep hypothesis of intestinal neoplasia  

PubMed Central

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

1993-01-01

194

Increasing expression of gastrointestinal phenotypes and p53 along with histologic progression of intraductal papillary neoplasia of the liver  

Microsoft Academic Search

Intraductal papillary neoplasia of the liver (IPN-L) was recently proposed as the name for intraductal papillary proliferation of neoplastic biliary epithelium with a fine fibrovascular stalk resembling intraductal papillary mucinous neoplasm of the pancreas. We histochemically and immunohistochemically examined IPN-L alone or associated with hepatolithiasis, with an emphasis on the gastrointestinal metaplasia, nuclear p53 expression, and histologic progression. A total

Tomonori Shimonishi; Yoh Zen; Tse-Ching Chen; Miin-Fu Chen; Yi-Yin Jan; Ta-Sen Yeh; Yuji Nimura; Yasuni Nakanuma

2002-01-01

195

HPV 16 and cigarette smoking as risk factors for high-grade cervical intra-epithelial neoplasia  

Microsoft Academic Search

Although genital human papillomavirus (HPV) infection is well established as the etiologic agent for cervical intra- epithelial neoplasia (CIN), little is known about the cofactors involved in the development of high-grade lesions or the progression of low-grade to high-grade lesions. In our study of HPV-infected women with CIN (163 CIN I, 51 CIN II and 44 CIN III), women with

Gloria Y. F. Ho; Anna S. Kadish; Robert D. Burk; Jayasri Basu; Prabhudas R. Palan; Magdy Mikhail; Seymour L. Romney

1998-01-01

196

Trend of human papillomavirus genotypes in cervical neoplasia observed in a newly developing township in yangon, myanmar.  

PubMed

Persistent infection with oncogenic types of human papillomavirus (HPV) is the most important risk factor associated with cervical cancer. This study detected the oncogenic HPV genotypes in cervical neoplasia in relation to clinicopathological findings using a cross-sectional descriptive method in 2011 and 2012. Cervical swabs and colposcopy-directed cervical biopsy tissues were collected from 108 women (median age 45 years;range 20-78) showing cervical cytological changes at Sanpya General Hospital, Yangon, Myanmar. HPV DNA testing and genotyping were performed by polymerase chain reaction and restriction fragment length polymorphism. HPV was identified in women with cervical intraepithelial neoplasia (CIN) 1 (44.4%), CIN2 (63.2%), CIN3 (70.6%), and squamous cell carcinoma (SCC) (74.1%). The association between cervical neoplasia and HPV positivity was highly significant (p?0.008). Most patients infected with HPV were between 40-49 years of age, and the youngest were in the 20- to 29-year-old age group. The most common genotype was HPV 16 (65.6%) with the following distribution:70% in CIN1, 41.7% in CIN2, 91.7% in CIN3, and 60% in SCC. HPV-31 was the second-most frequent (21.9%):30% in CIN1, 33.3% in CIN2, 8.3% in CIN3, and 15% in SCC. The third-most frequent-genotype was HPV-18 (7.8%):8.3% in CIN1, and 20% in SCC. Another genotype was HPV-58 (4.7%):16.7% in CIN1 and 5% in SCC. The majority of CIN/SCC cases were associated with HPV genotypes 16, 31, 18, and 58. If oncogenic HPV genotypes are positive, the possibility of cervical neoplasia can be predicted. Knowledge of the HPV genotypes distribution can predict the effectiveness of the currently used HPV vaccine. PMID:25703171

Mu Mu Shwe; Kyi Kyi Nyunt; Okada, Shigeru; Harano, Teruo; Hlaing Myat Thu; Hla Myat Mo Mo; Mo Mo Win; Khin Khin Oo; Khin Thet Wai; Khin Saw Aye; Myo Khin

2015-02-01

197

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

198

High-Dose-Rate Brachytherapy in the Management of High-Grade Intraepithelial Neoplasia of the Vagina  

Microsoft Academic Search

The majority of women with high-grade intraepithelial neoplasia (VAIN 3) are over 60 years of age and have a history of premalignant or malignant disease of the cervix. Although the natural history of VAIN is not well defined, high-grade lesions are premalignant. Ablative treatment with laser or 5-fluorouracil cream is commonly unsatisfactory. Several series have reported a low rate of

Craig MacLeod; Alan Fowler; Chris Dalrymple; Ken Atkinson; Peter Elliott; Jonathan Carter

1997-01-01

199

Prediction of persistent vaginal intraepithelial neoplasia in previously hysterectomized women by high-risk HPV DNA detection  

Microsoft Academic Search

Aim: To estimate the incidence and latency of Vaginal Intraepithelial Neoplasia (VAIN) in women previously hysterectomized for benign\\/malign pathology and to evaluate the role of high risk HPVs in the prediction of persistent or recurrent disease.Subjects and methods: 830 women with prior hysterectomy for benign\\/malign pathologies followed by cytological scraping and vaginal colposcopy. Forty-four patients presented VAIN lesions confirmed by

A. Frega; J. Piazze; A. Cerekja; G. Vetrano; M. Moscarini

2007-01-01

200

Gene Expression Profiles in Pancreatic Intraepithelial Neoplasia Reflect the Effects of Hedgehog Signaling on Pancreatic Ductal Epithelial Cells  

Microsoft Academic Search

Invasive pancreatic cancer is thought to develop through a series of noninvasive duct lesions known as pancreatic intraepithelial neoplasia (PanIN). We used cDNA microarrays interrogating 15,000 transcripts to identify 49 genes that were differentially expressed in microdissected early PanIN lesions (PanIN-1B\\/2) compared with microdissected normal duct epithelium. In this analysis, a cluster of extrapancreatic foregut markers, including pepsinogen C, MUC6,

Nijaguna B. Prasad; Andrew V. Biankin; Noriyoshi Fukushima; Anirban Maitra; Surajit Dhara; Abdel G. Elkahloun; Ralph H. Hruban; Michael Goggins; Steven D. Leach

201

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

202

Third-generation autofluorescence endoscopy for the detection of early neoplasia in Barrett's esophagus: a pilot study.  

PubMed

In Barrett's esophagus (BE), second-generation autofluorescence imaging (AFI-II) improves targeted detection of high-grade intra-epithelial neoplasia (HGIN) and early cancer (EC), yet suffers from high false-positive (FP) rates. The newest generation AFI (AFI-III) specifically targets fluorescence in malignant cells and may therefore improve detection of early neoplasia and reduce FP rate. The aim was to compare AFI-III with AFI-II for endoscopic detection of early neoplasia in BE. BE patients with endoscopically inconspicuous neoplasia underwent two diagnostic endoscopies (AFI-II/AFI-III) in a single session. End-points: number of patients and lesions with HGIN/EC detected with AFI-II and AFI-III after white-light endoscopy (WLE) and the value of reinspection of AFI-positive areas with WLE and narrow-band imaging. Forty-five patients were included (38 males, age 65 years). Nineteen patients showed HGIN/EC. AFI-II inspection after WLE increased detection of HGIN/EC from 9 to 15 patients (47 to 79%); AFI-III increased detection from 9 to 17 patients (47 to 89%). WLE plus random biopsies diagnosed 13/19 (68%) HGIN/EC patients. One hundred and four abnormal AFI areas were inspected; 23 (22%) showed HGIN/EC. AFI-II increased detection of HGIN/EC from 10 to 18 lesions (43 to 78%). AFI-III increased detection from 10 to 20 lesions (43-87%). FP rate was 86% for AFI-II and AFI-III. Reinspection with WLE or narrow-band imaging reduced FP rate to 21% and 22%, respectively, but misclassified HGIN/EC lesions as unsuspicious in 54% and 31%, respectively. This first feasibility study on third-generation AFI again showed improved targeted detection of HGIN/EC in BE. However, the results do not suggest AFI-III performs significantly better than conventional AFI-II. PMID:23795645

Boerwinkel, D F; Holz, J A; Aalders, M C G; Visser, M; Meijer, S L; Van Berge Henegouwen, M I; Weusten, B L A M; Bergman, J J G H M

2014-04-01

203

Distribution of Human Papillomavirus 52 and 58 Genotypes, and Their Expression of p16 and p53 in Cervical Neoplasia  

PubMed Central

Background This study investigates the prevalence of human papillomavirus (HPV) 52 and 58 genotypes among women residing in Busan, and the expression of p16 and p53 proteins in cervical neoplasia with HPV 52 and 58 infections. Methods A total of three hundred fifteen cases were analyzed using the HPV DNA chip test for HPV genotypes, and of these, we retrospectively examined p16 and p53 expression in 62 cases of cervical tissues infected with HPV 52 and 58 using immunohistochemistry. Results HPV 52 and 58 genotypes were identified in 62 (54.9%) out of 113 high-risk, HPV-infected cases. Of the cases examined, there were 19 single HPV 52 infections (16.8%), 23 single HPV 58 infections (20.4%), 4 multiple HPV 52 infections (3.5%), and 16 multiple HPV-58 infections (14.2%). Immunoreactivity of p16 and p53 was observed in 41 (66.1%) and 23 (37.1%) of the 62 cases of cervical neoplasia infected with HPV 52 and 58 genotypes, respectively. Conclusions This study demonstrates a high prevalence of HPV 52 and 58 genotypes, in addition to HPV 16, among high-risk strains of cervical neoplasia in Korea. These findings suggest that development of more vaccines would be beneficial for the prevention of the various HPV genotypes. PMID:24627691

Kim, Tae Eun; Kim, Hwal Woong

2014-01-01

204

Two cases of neoplasia of basal cell origin affecting the axillary region in anseriform species.  

PubMed

Neoplasms of the skin are occasionally seen in domestic birds but are uncommon in nondomestic birds. An 8-year-old male hooded merganser (Lophodytes cucullatus) was presented with bilateral axillary ulcerative lesions that improved but did not resolve with empiric antibiotic and antifungal therapy. Skin biopsies were taken, and bilateral feather folliculomas were diagnosed on histopathologic examination. The duck was euthanatized because of the poor prognosis. A 9-year-old Indian runner duck (Anas platyrhynchos) was presented with an ulcerative lesion, with pseudomembrane and serocellular crust affecting the axillary region. This mass was diagnosed as a basosquamous carcinoma. The mass was surgically excised, and no recurrence was observed. Feather folliculomas are usually considered benign neoplasms in domestic birds and may be primarily ulcerative, exudative, bilateral, and symmetric in location. Basosquamous carcinoma may have a similar gross appearance. It is unknown if the axillary region may be an area with increased incidence of neoplasia in birds. This appears to be the first report of feather folliculoma and basosquamous carcinoma in Anseriforme species. Feather folliculomas and other neoplasms, such as basosquamous carcinoma, should be considered as a differential diagnosis in ulcerative or proliferative skin lesions in birds. PMID:19999766

Bradford, Carol; Wack, Allison; Trembley, Sarah; Southard, Teresa; Bronson, Ellen

2009-09-01

205

In vivo Diagnosis of Cervical Intraepithelial Neoplasia Using 337-nm- Excited Laser-Induced Fluorescence  

NASA Astrophysics Data System (ADS)

Laser-induced fluorescence at 337-nm excitation was used in vivo to differentiate neoplastic [cervical intraepithelial neoplasia (CIN)], nonneoplastic abnormal (inflammation and human papilloma viral infection), and normal cervical tissues. A colposcope (low-magnification microscope used to view the cervix with reflected light) was used to identify 66 normal and 49 abnormal (5 inflammation, 21 human papilloma virus infection, and 23 CIN) sites on the cervix in 28 patients. These sites were then interrogated spectroscopically. A two-stage algorithm was developed to diagnose CIN. The first stage differentiated histologically abnormal tissues from colposcopically normal tissues with a sensitivity, specificity, and positive predictive value of 92%, 90%, and 88%, respectively. The second stage differentiated preneoplastic and neoplastic tissues from nonneoplastic abnormal tissues with a sensitivity, specificity, and positive predictive value of 87%, 73%, and 74%, respectively. Spectroscopic differences were consistent with a decrease in the absolute contribution of collagen fluorescence, an increase in the absolute contribution of oxyhemoglobin attenuation, and an increase in the relative contribution of reduced nicotinamide dinucleotide phosphate [NAD(P)H] fluorescence as tissue progresses from normal to abnormal in the same patient. These results suggest that in vivo fluorescence spectroscopy of the cervix can be used to diagnose CIN at colposcopy.

Ramanujam, N.; Mitchell, M. F.; Mahadevan, A.; Warren, S.; Thomsen, S.; Silva, E.; Richards-Kortum, R.

1994-10-01

206

Anti-cytokine autoantibodies are associated with opportunistic infection in patients with thymic neoplasia.  

PubMed

Patients with thymic malignancy have high rates of autoimmunity leading to a variety of autoimmune diseases, most commonly myasthenia gravis caused by anti-acetylcholine receptor autoantibodies. High rates of autoantibodies to cytokines have also been described, although prevalence, spectrum, and functionality of these anti-cytokine autoantibodies are poorly defined. To better understand the presence and function of anti-cytokine autoantibodies, we created a luciferase immunoprecipitation system panel to search for autoantibodies against 39 different cytokines and examined plasma from controls (n = 30) and patients with thymic neoplasia (n = 17). In this screen, our patients showed statistically elevated, but highly heterogeneous immunoreactivity against 16 of the 39 cytokines. Some patients showed autoantibodies to multiple cytokines. Functional testing proved that autoantibodies directed against interferon-?, interferon-?, interleukin-1? (IL-1?), IL-12p35, IL-12p40, and IL-17A had biologic blocking activity in vitro. All patients with opportunistic infection showed multiple anti-cytokine autoantibodies (range 3-11), suggesting that anti-cytokine autoantibodies may be important in the pathogenesis of opportunistic infections in patients with thymic malignancy. This study was registered at http://clinicaltrials.gov as NCT00001355. PMID:20716769

Burbelo, Peter D; Browne, Sarah K; Sampaio, Elizabeth P; Giaccone, Giuseppe; Zaman, Rifat; Kristosturyan, Ervand; Rajan, Arun; Ding, Li; Ching, Kathryn H; Berman, Arlene; Oliveira, Joao B; Hsu, Amy P; Klimavicz, Caitlin M; Iadarola, Michael J; Holland, Steven M

2010-12-01

207

Anti-cytokine autoantibodies are associated with opportunistic infection in patients with thymic neoplasia  

PubMed Central

Patients with thymic malignancy have high rates of autoimmunity leading to a variety of autoimmune diseases, most commonly myasthenia gravis caused by anti-acetylcholine receptor autoantibodies. High rates of autoantibodies to cytokines have also been described, although prevalence, spectrum, and functionality of these anti-cytokine autoantibodies are poorly defined. To better understand the presence and function of anti-cytokine autoantibodies, we created a luciferase immunoprecipitation system panel to search for autoantibodies against 39 different cytokines and examined plasma from controls (n = 30) and patients with thymic neoplasia (n = 17). In this screen, our patients showed statistically elevated, but highly heterogeneous immunoreactivity against 16 of the 39 cytokines. Some patients showed autoantibodies to multiple cytokines. Functional testing proved that autoantibodies directed against interferon-?, interferon-?, interleukin-1? (IL-1?), IL-12p35, IL-12p40, and IL-17A had biologic blocking activity in vitro. All patients with opportunistic infection showed multiple anti-cytokine autoantibodies (range 3-11), suggesting that anti-cytokine autoantibodies may be important in the pathogenesis of opportunistic infections in patients with thymic malignancy. This study was registered at http://clinicaltrials.gov as NCT00001355. PMID:20716769

Burbelo, Peter D.; Sampaio, Elizabeth P.; Giaccone, Giuseppe; Zaman, Rifat; Kristosturyan, Ervand; Rajan, Arun; Ding, Li; Ching, Kathryn H.; Berman, Arlene; Oliveira, Joao B.; Hsu, Amy P.; Klimavicz, Caitlin M.; Iadarola, Michael J.; Holland, Steven M.

2010-01-01

208

Optical coherence tomography and its role for delineating the thickness of keratinocyte dysplasia and neoplasia.  

PubMed

Optical coherence tomography (OCT) can produce cross-sectional and en face, non-invasive, real-time images of skin. OCT produces high-resolution images at a micrometre resolution and has a maximum 2-mm penetration depth, which places OCT in the imaging gap between ultrasound and confocal microscopy. Much OCT research has been performed on keratinocyte dysplasia and neoplasia, primarily including basal cell carcinoma (BCC) and actinic keratosis. In regards to BCC and actinic keratosis, architectural disarray of the epidermis is an overall characteristic finding in OCT images. OCT can reliably differentiate between normal and lesional skin, which is of great importance when identifying tumour borders. Therefore, it has been suggested that OCT may aid in the evaluation of sub-surface tumour margins prior to surgical and non-invasive treatments of keratinocyte neoplastic lesions. Studies on in vivo presurgical margin assessments found that OCT correctly identified the laterally defined tumour margin in 84% of cases and that the borders determined by the surgeon never came below the OCT margin, indicating the utility of OCT. These reports imply a scope for reducing the final size of an excision defect using OCT. The main limitation to assessing tumour thickness using OCT is its maximum scan depth of 2 mm, indicating that the primary potential of OCT may lie in the evaluation of superficial tumours. PMID:25561212

Themstrup, Lotte; Jemec, Gregor B E

2015-01-01

209

Gene expression changes in progression of cervical neoplasia revealed by microarray analysis of cervical neoplastic keratinocytes.  

PubMed

To evaluate the gene expression changes involved in neoplastic progression of cervical intraepithelial neoplasia. Using microarray analysis, large-scale gene expression profile was carried out on HPV16-CIN2, HPV16-CIN3, and normal cervical keratinocytes derived from two HPV16-CIN2, two HPV-CIN3 lesions, and two corresponding normal cervical tissues, respectively. Differentially expressed genes were analyzed in normal cervical keratinocytes compared with HPV16-CIN2 keratinocytes and in HPV16-CIN2 keratinocytes compared with HPV16-CIN3 keratinocytes; 37 candidate genes with continuously increasing or decreasing expression during CIN progression were identified. One of these genes, phosphoglycerate dehydrogenase, was chosen for further characterization. Quantitative reverse transcription-polymerase chain reaction and immunohistochemical analysis confirmed that expression of phosphoglycerate dehydrogenase consistently increases during progression of CIN toward cancer. Gene expression changes occurring during CIN progression were investigated using microarray analysis, for the first time, in CIN2 and CIN3 keratinocytes naturally infected with HPV16. Phosphoglycerate dehydrogenase is likely to be associated with tumorigenesis and may be a potential prognostic marker for CIN progression. PMID:25205602

Rotondo, John Charles; Bosi, Silvia; Bassi, Cristian; Ferracin, Manuela; Lanza, Giovanni; Gafà, Roberta; Magri, Eros; Selvatici, Rita; Torresani, Stefania; Marci, Roberto; Garutti, Paola; Negrini, Massimo; Tognon, Mauro; Martini, Fernanda

2015-04-01

210

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

211

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

212

Amyloid associated with neoplasia in two captive tricolour sharkminnows Balantiocheilus melanopterus Bleeker.  

PubMed

Amyloid associated with pancreatic adenocarcinoma was discovered in two captive adult tricolour sharkminnows Balantiocheilus melanopterus Bleeker found dead in a freshwater display. Enlarged abdomens expanded by bloody ascitic fluid and grossly visible masses of abnormal tissue were present surrounding sections of the stomach and intestine. Histologically, the masses were composed of areas of well-organized exocrine pancreatic acini interspersed with cords of poorly differentiated, spindle-shaped cells that compressed and effaced normal parenchyma. These cells possessed small numbers of cytoplasmic zymogen granules; the exocrine nature of these cells was confirmed using transmission electron microscopy (TEM). Fibrovascular connective tissue of the hepatopancreas and mesenteries was expanded by lightly eosinophilic, hyaline, homogeneous acellular material. Similar material greatly expanded the tunica media of large blood vessels in the hepatopancreas. After staining with Congo red or thioflavin T, this material exhibited red-green dichroism under polarized light or bright green fluorescence under ultraviolet light (255 nm), respectively. The non-branching fibrils, of indeterminate length, had an approximate diameter of 10-20 nm using TEM. Although exocrine pancreatic neoplasia is relatively common in fish, the presence of amyloid is not. To our current knowledge, the latter has not yet been described in association with a neoplastic lesion in fish. PMID:25117633

Russell, S; Tubbs, L; McLelland, D J; LePage, V; Young, K M; Huber, P; Lumsden, J S

2015-06-01

213

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

214

Genetic analysis of 24 French families with multiple endocrine neoplasia type 2A  

SciTech Connect

The gene for multiple endocrine neoplasia type 2A (MEN2A) has been mapped to the pericentromeric region of chromosome 10 by linkage analysis. Thirty-four families with multiple cases of medullary carcinoma of the thyroid (MTC), including 24 families with origins in France, have been typed with nine polymorphic markers spanning the centromere of chromosome 10. No recombination was observed between the MEN2A locus and either of the four loci D10Z1 (lod score 12.79), D10S102 (lod score 6.38), D10S94 (lod score 7.76), and D10S34 (lod score 5.94). There was no evidence for genetic linkage heterogeneity in the panel of 34 families. Haplotypes were constructed for a total of 11 polymorphisms in the MEN2A region, for mutation bearing chromosomes in 24 French families and for 100 spouse controls. One haplotype was present in four MEN2A families but was not observed in any control (P<0.1). Two additional families share a core segment of this haplotype near the MEN2A gene. It is likely that these six families have a common affected ancestor. Because the incidence of pheochromocytoma among carriers varies from 0% to 74% within these six families, it is probable that additional factors modify the expression of the MEN2A gene. 39 refs., 5 figs., 4 tabs.

Narod, S.A.; Morgan, K. (McGill Univ., Montreal (Canada)); Lavoue, M.F.; Lenoir, G.M.; Sobol, H. (Centre Leon Berard, Lyon (France)); Calmettes, C. (Centrale Hospitalier Unite Sainte Antoine, Paris (France)); Goodfellow, P.J. (Univ. of British Columbia, Vancouver (Canada))

1992-09-01

215

Effects of dietary high fat on prostate intraepithelial neoplasia in TRAMP mice  

PubMed Central

Increased fat intake is known to be a major cause of prostate cancer. In this study, we investigated the effect of dietary high fat on prostate intraepithelial neoplasia using transgenic adenocarcinoma mouse prostate (TRAMP) mice. Six-week-old male TRAMP mice were fed AIN93G (control group, 4.0 kcal/kg, n=6) and AIN93G-HFD (experimental group, 4.8 kcal/kg, n=7) for 10 weeks. Prostate histopathology, urogenital tract (UGT) weight, epididymal white adipose tissue weight, argyrophilic nucleolar organizer regions (AgNORs) counts, and serum leptin levels were examined. AIN93G-HFD fed group showed progressed neoplastic lesions in the prostate (P<0.05) compared to AIN93G fed group. AIN93G-HFD intake resulted in a increase in the weight of UGT (P<0.05) and epididymal white adipose tissue. The number of Ag-NOR positive dots significantly increased in each prostate lobe and final serum leptin levels in AIN93G-HFD fed group were about twice those of AIN93G fed group (P<0.05). Dietary high fat was related to the prostate cancer progression in the early stage of TRAMP mice and increased serum leptin levels, suggesting that the regulation of dietary components could delay the progression of prostate cancer. PMID:23573107

Park, Sung-Hoon; Chang, Seo-Na; Baek, Min-Won; Kim, Dong-Jae; Na, Yi-Rang; Seok, Seung-Hyeok; Lee, Byoung-Hee; Kim, Kyung-Sul

2013-01-01

216

Lesions indefinite for intraepithelial neoplasia and OLGA staging for gastric atrophy.  

PubMed

Gastric intraepithelial neoplasia (IEN; formerly dysplasia) is an advanced precancerous lesion. Lesions indefinite for IEN mimic the IEN phenotype but lack some morphologic attributes of IEN. Indefinite for IEN lesions may arise in native foveolae (atypical foveolar hyperproliferation [aFH]) or intestinalized glands (hyperproliferative intestinal metaplasia [HIM]). The clinicopathologic outcome of such lesions is debated. We retrospectively studied the clinicopathologic behavior of 129 consecutive indefinite for IEN lesions (HIM, 98; aFH, 31; median follow-up, 31 months) and correlated outcome with the extent and topography of mucosal atrophy (assessed by OLGA staging) at the initial endoscopy/biopsy. At enrollment, aFH never coexisted with severe/extensive atrophy (all cases were in low-risk OLGA stages [0-II]), whereas HIM was associated with low- and high-risk OLGA stages (0-II, 73; III-IV, 25). At follow-up, IEN was never documented among cases enrolled as aFH, while follow-up endoscopy/biopsy documented 6 neoplastic intraepithelial lesions among 98 cases of HIM (6%, all had high-risk OLGA stages at initial biopsy). OLGA staging can stratify indefinite for IEN lesions into different risk classes, potentially contributing to decisions for a patient-specific follow-up strategy. PMID:22523210

Fassan, Matteo; Pizzi, Marco; Farinati, Fabio; Nitti, Donato; Zagonel, Vittorina; Genta, Robert M; Rugge, Massimo

2012-05-01

217

CAHM, a long non-coding RNA gene hypermethylated in colorectal neoplasia.  

PubMed

The CAHM gene (Colorectal Adenocarcinoma HyperMethylated), previously LOC100526820, is located on chromosome 6, hg19 chr6:163?834?097-163?834?982. It lacks introns, encodes a long non-coding RNA (lncRNA) and is located adjacent to the gene QKI, which encodes an RNA binding protein. Deep bisulphite sequencing of ten colorectal cancer (CRC) and matched normal tissues demonstrated frequent hypermethylation within the CAHM gene in cancer. A quantitative methylation-specific PCR (qMSP) was used to characterize additional tissue samples. With a threshold of 5% methylation, the CAHM assay was positive in 2/26 normal colorectal tissues (8%), 17/21 adenomas (81%), and 56/79 CRC samples (71%). A reverse transcriptase-qPCR assay showed that CAHM RNA levels correlated negatively with CAHM % methylation, and therefore CAHM gene expression is typically decreased in CRC. The CAHM qMSP assay was applied to DNA isolated from plasma specimens from 220 colonoscopy-examined patients. Using a threshold of 3 pg methylated genomic DNA per mL plasma, methylated CAHM sequences were detected in the plasma DNA of 40/73 (55%) of CRC patients compared with 3/73 (4%) from subjects with adenomas and 5/74 (7%) from subjects without neoplasia. Both the frequency of detection and the amount of methylated CAHM DNA released into plasma increased with increasing cancer stage. Methylated CAHM DNA shows promise as a plasma biomarker for use in screening for CRC. PMID:24799664

Pedersen, Susanne K; Mitchell, Susan M; Graham, Lloyd D; McEvoy, Aidan; Thomas, Melissa L; Baker, Rohan T; Ross, Jason P; Xu, Zheng-Zhou; Ho, Thu; LaPointe, Lawrence C; Young, Graeme P; Molloy, Peter L

2014-08-01

218

Natural history of high-grade cervical intraepithelial neoplasia: a review of prognostic biomarkers.  

PubMed

The natural history of high-grade cervical intraepithelial neoplasia (CIN) is largely unpredictable and current histopathological examination is unable to differentiate between lesions that will regress and those that will not. Therefore, most high-grade lesions are currently treated by surgical excision, leading to overtreatment and unnecessary complications. Prognostic biomarkers may differentiate between lesions that will regress and those that will not, making individualized treatment of high-grade CIN possible. This review identifies several promising prognostic biomarkers. These biomarkers include viral genotype and viral DNA methylation (viral factors), human leukocyte antigen-subtypes, markers of lymphoproliferative response, telomerase amplification and human papillomavirus-induced epigenetic effects (host factors) and Ki-67, p53 and pRb (cellular factors). All identified biomarkers were evaluated according to their role in the natural history of high-grade CIN and according to established criteria for evaluation of biomarkers (prospective-specimen-collection, retrospective-blinded-evaluation [PROBE] criteria). None of the biomarkers meets the PROBE criteria for clinical applicability and more research on prognostic biomarkers in high-grade CIN is necessary. PMID:25703310

Koeneman, Margot M; Kruitwagen, Roy Fpm; Nijman, Hans W; Slangen, Brigitte Fm; Van Gorp, Toon; Kruse, Arnold-Jan

2015-04-01

219

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

220

Noninvasive imaging of oral neoplasia with a high-resolution fiber-optic microendoscope  

PubMed Central

Background The purpose of this study was to evaluate the ability of high-resolution microendoscopy to image and quantify changes in cellular and architectural features seen in early oral neoplasia in vivo. Methods A high-resolution microendoscope (HRME) was used to image intact, resected oral squamous carcinoma specimens. HRME images were reviewed and classified as non-neoplastic or neoplastic by expert clinicians. An algorithm based on quantitative morphologic features was also used to classify each image. Results were compared to the histopathologic diagnosis. Results HRME images were obtained from 141 sites in resected specimens from 13 patients. Subjective image interpretation yielded sensitivity and specificity of 85% to 90% and 80% to 85%, respectively, whereas the objective classification algorithm achieved sensitivity and specificity of 81% and 77%, respectively. Conclusion High-resolution microendoscopy of intact oral mucosa can provide images with sufficient detail to classify oral lesions by both subjective image interpretation and objective image analysis. © 2011 Wiley Periodicals, Inc. Head Neck, 2011 PMID:21413101

Muldoon, Timothy J; Roblyer, Darren; Williams, Michelle D; Stepanek, Vanda MT; Richards–Kortum, Rebecca; Gillenwater, Ann M

2011-01-01

221

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

222

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

223

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

224

A matched observational study of canine survival with primary intraocular melanocytic neoplasia.  

PubMed

A retrospective histopathologic study was performed to evaluate the effect of primary intraocular melanocytic neoplasia on canine survival. Tumor size, location within the globe, extent of infiltration, and mitotic index were analyzed for their potential to predict survival. A total of 244 cases of dogs with melanocytic tumors submitted to the Comparative Ocular Pathology Laboratory of Wisconsin from 1988 to 1998 were evaluated. Histopathologic criteria (mitotic index, cytologic features of anaplasia) were used to differentiate 188 benign melanocytomas from 56 malignant melanomas. Signalment evaluation of age, sex, and breed revealed similarities in both tumor populations, with the majority of tumors discovered in 9-year-old, female/spayed, mixed-breed dogs. A greater percentage of left eyes (66%) vs. right eyes (47%) was found in the melanoma population, but an equal distribution was found in the melanocytoma population (48% and 52%, respectively). The majority of tumors arose from the anterior uveal tract (79% in the melanocytoma and 95% in the malignant melanoma populations). The German Shepherd breed was predisposed in the limbal distribution. At the time of enucleation, most tumors had invaded the sclera, but did not show extrascleral extension (51% in the melanocytoma and 61% in the malignant melanoma populations). Survival analysis showed a significant difference in survival between control and malignant melanoma populations (P = 0.0081) and was suggestive of a difference between the melanocytoma and melanoma populations (P = 0.031). Tumor extension, tumor size, and mitotic index were not found to be reliable predictors of survival. PMID:11397263

Giuliano, E.A.; Chappell, R.; Fischer, B.; Dubielzig, R.R.

1999-01-01

225

Multiple endocrine neoplasia type 1- presenting multiple lipomas and hypoglycemia onset  

PubMed Central

Summary Background: Multiple endocrine neoplasia type 1 (MEN1), also called Wermer syndrome, is an autosomal dominant disorder characterized by tumors of the parathyroid glands, the anterior pituitary, and the endocrine pancreas. Case Report: Here, we report a case of MEN1. Our patient was a 44-year-old woman who manifested typical features of MEN1, including insulinoma, pituitary tumors, and parathyroidoma, and exhibited multiple lipomas and a gastrinoma with duodenal ulcers. She was admitted to our hospital because of recurrent massive bleeding of the upper gastrointestinal tract and hypoglycemia. The first operation for pituitary tumors was performed when she was 40 years old. According to these examinations and her clinical course, the patient was diagnosed with insulinoma and gastrinoma. She subsequently underwent surgery for the pancreatic tumors. The majority of these tumor cells were immunohistochemically positive for insulin and negative for glucagon. Conclusions: This case suggests that multiple lipomas, insulinoma and gastrinoma may provide clues for a diagnosis of MEN1. PMID:23569534

Li, Jianzhong; Zeng, Lixian; Yang, Yidong; Zhan, Yashi; Tao, Jin; Wu, Bin

2012-01-01

226

Expression of p16 in conjunctival intraepithelial neoplasia does not correlate with HPV-infection.  

PubMed

The aim of our study was to identify the frequency of expression of p16(INK4a) (CDKN2A) and HPV (human papilloma virus) in different grades of conjunctival intraepithelial neoplasia (CIN).Twelve specimens including CIN I (2), II (3), III (5), and CIN with beginning invasion (2), as well as 15 control specimens, were stained with antibodies against p16(INK4a) and MIB1. The presence of HPV was examined by PCR.p16 as well as MIB1 were significantly elevated in CIN compared to control specimens (p<0.01) without correlation with the differentiation grade. Only two cases with CIN grade 3 contained HPV 16.As few control specimens also showed increased p16(INK4a) expression, p16(INK4a) seems not to be a very reliable marker for the exact determination of CIN. It could serve as an additional diagnostic tool besides the morphological characterization. Our study suggested that p16(INK4a) elevation is not associated with HPV infection. PMID:19516893

Auw-Haedrich, Claudia; Martin, Gottfried; Spelsberg, Helga; Sundmacher, Rainer; Freudenberg, Nikolaus; Maier, Philip; Reinhard, Thomas

2008-01-01

227

Classifying extrahepatic bile duct metachronous carcinoma by de novo neoplasia site.  

PubMed

Extrahepatic bile duct (EHBD) cancer may occur metachronously, and these cancers are resectable with a favorable prognosis. We aimed to identify the pattern of metachronous EHBD cancer. We classified the cases of metachronous EHBD cancer reported in the literature thus far and investigated two new cases of metachronous EHBD cancer. A 70-year-old female underwent R0 bile duct resection for a type 1 Klatskin tumor (pT1N0M0). A 70-year-old male patient underwent R0 bile duct resection for a middle bile duct cancer (pT2N1M0). Imaging studies of both patients taken at 14 and 24 mo after first surgery respectively revealed a metachronous cholangiocarcinoma that required pancreaticoduodenectomy (PD). Histopathology of the both tumors after PD revealed cholangiocarcinoma invading the pancreas (pT3N0M0). Both patients have been free from recurrence for 6 years and 16 mo respectively after the second surgery. Through a review of the literature on these cases, we classified the pattern of metachronous EHBD cancer according to the site of de novo neoplasia. The proximal remnant bile duct was most commonly involved. Metachronous EHBD cancer should be distinguished from an unresectable recurrent tumor. Classifying metachronous EHBD cancer may be helpful in identifying rare metachronous tumors. PMID:24659897

Kwon, Hyung Jun; Kim, Sang Geol; Chun, Jae Min; Hwang, Yoon Jin

2014-03-21

228

Consistent Condom Use Increases the Regression Rate of Cervical Intraepithelial Neoplasia 2–3  

PubMed Central

Objective Cervical intraepithelial neoplasia grades 2-3 (CIN2-3) are usually treated by cone excision, although only 30% progress to cancer and 6–50% regress spontaneously. The aim of this study was to examine the influence of clinical factors like smoking habits, number of lifetime sexual partners, age at first sexual intercourse, sexual activity span and hormonal versus non-hormonal contraception type on the regression rate of CIN2-3. Methods In this prospective population-based cohort study 170 women aged 25–40 with abnormal cytology and colposcopy-directed biopsies showing first time onset CIN2-3 were consecutively included. The interval between biopsy and cone excision was standardized to minimum 12 weeks. Regression was defined as ?CIN1 in the cone biopsy. Results The regression rate was 22%. Consistent condom use, defined as those women whose partners used condoms for all instances of sexual intercourse, was infrequent (n?=?20, 12%). In univariate analysis consistent condom use, hormonal contraception and age at first sexual intercourse significantly predicted regression. In a multivariate analysis only consistent condom use remained as an independent predictor of regression (regression rate 55%, p?=?0.001, hazard ratio?=?4.4). Conclusion Consistent condom use between punch biopsy and cone excision in first-time onset CIN2-3 patients significantly increases the regression rate. PMID:23028792

Munk, Ane Cecilie; Gudlaugsson, Einar; Malpica, Anais; Fiane, Bent; Løvslett, Kjell I.; Kruse, Arnold-Jan; Øvestad, Irene Tveiterås; Voorhorst, Feja; Janssen, Emiel A. M.; Baak, Jan P. A.

2012-01-01

229

Optical quantitative pathology of cervical intraepithelial neoplasia in human tissues using spatial frequency analysis.  

PubMed

An optical quantitative histological method in human tissues using spatial frequencies is demonstrated. Optical spatial frequency spectra from different stages of human Cervical Intraepithelial Neoplasia (CIN) tissue are evaluated as a potential quantitative pathological tool. The degree of randomness of tissue structures from normal to different stages of CIN tissue can be recognized by spatial frequency analysis. The standard deviation, ? of human normal and CIN tissue, is obtained by assuming the spatial frequency spectra as a Gaussian distribution. A support vector machine classifier (SVM) is trained in the subspace of ?. Twenty-eight normal and CIN samples of varying grades are examined and compared with current diagnostic outcomes. Our results suggest that an excellent accuracy for diagnostic purposes can be achieved. This approach offers a simple, efficient and objective way to supplement histopathology in recognizing alterations from normal to different stages of cervical pre-cancer, which are reflected by spatial information contained within the aperiodic and random structures of the different types of tissue. (© 2015 WILEY-VCH Verlag GmbH &Co. KGaA, Weinheim). PMID:24458694

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

2015-03-01

230

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

231

Scintigraphic portrayal of the syndrome of multiple endocrine neoplasia type-2B  

SciTech Connect

The scintigraphic appearance of the neoplasms in multiple endocrine neoplasia type 2B (MEN-2B) and the interpretations of the image patterns are described. An 18-year-old male patient with the MEN-2B syndrome underwent TI-201 imaging that showed concentrations of TI-201 in the primary medullary thyroid carcinoma (MTC) tumor and in cervical lymph node metastases. After total thyroidectomy and lymph node dissection, the TI-201 image was normal. Catecholamine levels in the blood and urine were only borderline elevated. Yet, greater than normal concentrations of I-131 metaiodobenzylguanidine (I-131 MIBG) were present in both adrenal glands. Computed tomography of the abdomen showed normal adrenal glands. These results were consistent with the diagnosis of adrenal medullary hyperplasia, a precursor of pheochromocytoma. No operation was indicated to remove the adrenal glands. Imaging with TI-201 appears to be useful in identifying sites of MTC in patients with the MEN-2B syndrome. I-131 MIBG imaging, in conjunction with computed tomography of the adrenal glands and appropriate catecholamine measurements, should be performed in patients with the MEN-2B syndrome to determine the status of the adrenal medullae, which then may be classified as normal, hyperplastic, or tumorous with pheochromocytoma.

Yobbagy, J.J.; Levatter, R.; Sisson, J.C.; Shulkin, B.L.; Polley, T.

1988-06-01

232

Multiple oncogenic viruses identified in Ocular surface squamous neoplasia in HIV-1 patients  

PubMed Central

Background Ocular surface squamous neoplasia (OSSN) is a rare cancer that has increased in incidence with the HIV pandemic in Africa. The underlying cause of this cancer in HIV-infected patients from Botswana is not well defined. Results Tissues were obtained from 28 OSSN and 8 pterygia patients. The tissues analyzed from OSSN patients were 83% positive for EBV, 75% were HPV positive, 70% were KSHV positive, 75% were HSV-1/2 positive, and 61% were CMV positive by PCR. Tissues from pterygium patients were 88% positive for EBV, 75% were HPV positive, 50% were KSHV positive, and 60% were CMV positive. None of the patients were JC or BK positive. In situ hybridization and immunohistochemistry analyses further identified HPV, EBV, and KSHV in a subset of the tissue samples. Conclusion We identified the known oncogenic viruses HPV, KSHV, and EBV in OSSN and pterygia tissues. The presence of these tumor viruses in OSSN suggests that they may contribute to the development of this malignancy in the HIV population. Further studies are necessary to characterize the molecular mechanisms associated with viral antigens and their potential role in the development of OSSN. PMID:20346104

2010-01-01

233

Expression of p16 in Conjunctival Intraepithelial Neoplasia Does Not Correlate with HPV-Infection  

PubMed Central

The aim of our study was to identify the frequency of expression of p16INK4a (CDKN2A) and HPV (human papilloma virus) in different grades of conjunctival intraepithelial neoplasia (CIN). Twelve specimens including CIN I (2), II (3), III (5), and CIN with beginning invasion (2), as well as 15 control specimens, were stained with antibodies against p16INK4a and MIB1. The presence of HPV was examined by PCR. p16 as well as MIB1 were significantly elevated in CIN compared to control specimens (p<0.01) without correlation with the differentiation grade. Only two cases with CIN grade 3 contained HPV 16. As few control specimens also showed increased p16INK4a expression, p16INK4a seems not to be a very reliable marker for the exact determination of CIN. It could serve as an additional diagnostic tool besides the morphological characterization. Our study suggested that p16INK4a elevation is not associated with HPV infection. PMID:19516893

Auw-Haedrich, Claudia; Martin, Gottfried; Spelsberg, Helga; Sundmacher, Rainer; Freudenberg, Nikolaus; Maier, Philip; Reinhard, Thomas

2008-01-01

234

Entrevista con Ricardo Halac  

E-print Network

capitalismo, que cada vez es más abstracto, financiero, ingobernable. Pero el racionalismo subsiste en su vieja forma en el pensamiento de izquierda: en la Unión Soviética, en China, en las democracias populares, se está "construyendo11 el hombre nuevo. En... 1968, con la muerte del "Che" Guevara en Bolivia, luego de una campaña "racionalmente" perfecta, los bolivianos se tenían que insubordinar y seguirlo. Entra en crisis entonces el pensamiento racional en el mundo entero. Hasta las grandes religiones...

Glickman, Nora

1990-04-01

235

¡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.

Lawrence Hall of Science

2009-01-01

236

Entrevista con Enrique Buenaventura  

E-print Network

dramaturgia práctica grupai y su extensa labor docente, han ido resultando en un considerable y ponderado corpus teórico sobre la íntima relación del discurso teatral y la historia, especialmente esa historia truncada, manipu lada y camuflada por poderosos... mucho más. Esta manera suya de actuar hizo que todo el mundo se metiera en la guerra y de una manera muy decidida. Entonces se empezó a producir la desmoralización de la Guardia. Como si hubieran ido demasiado lejos con la represión y la matanza. Sí...

Dí ez, Luys A.

1981-04-01

237

A Case of Pancreatic Intraepithelial Neoplasia That Was Difficult to Diagnose Preoperatively  

PubMed Central

A 63-year-old female patient presented to a local physician with pain in her back and epigastric region. An abdominal computed tomography (CT) scan revealed a pancreatic tumor, and the patient was referred to our hospital. Multiple imaging studies that included ultrasonography (US), CT, MRI, and endoscopic US revealed a cystic lesion 3–4 cm in size with node-like projections in the body of the pancreas. The distal main pancreatic duct was also found to be dilated. Endoscopic retrograde pancreatography revealed an irregular stenosis of the main pancreatic duct proximal to the cystic lesion, and malignancy was suspected. The patient was preoperatively diagnosed with pancreatic ductal carcinoma concomitant with intraductal papillary mucinous carcinoma, and a distal pancreatectomy was performed. Rapid pathological diagnosis during surgery revealed positive surgical margins for pancreatic intraepithelial neoplasia (PanIN). Further resection was performed twice, her surgical margin was positive and total pancreatectomy was ultimately conducted. Histopathological findings revealed diffuse microinvasive cancerous lesions corresponding to PanIN-2 (moderate dysplasia) to PanIN-3 (carcinoma in situ) throughout the pancreas. PanIN involves microlesions of the ductal epithelium that may precede pancreatic cancer. Ascertaining changes in PanIN using images provided by diagnostic modalities such as CT and US is challenging. Ductal stenosis and distal cystic lesions resulting from atrophy and fibrosis of pancreatic tissue were noted around PanIN. Considering the possibility of PanIN, a precancerous lesion during differential diagnosis will help to improve early detection and prognosis for patients with pancreatic cancer.

Ito, Hiroyuki; Kawaguchi, Yoshiaki; Kawashima, Yohei; Maruno, Atsuko; Ogawa, Masami; Hirabayashi, Kenichi; Mine, Tetsuya

2015-01-01

238

Address of early stage primary colonic neoplasia by N.O.T.E.S.  

PubMed

Natural Orifice Translumenal Endoscopic Surgery (N.O.T.E.S.) has the capacity to impact greatly on the practice of colorectal surgery. As much as potentially providing an alternative means of operative approach, its consideration and evolution is already also providing a wealth of instrument innovation that seems likely to greatly enhance the endoscopists' armamentarium for advanced endoluminal intervention. Furthermore, its aspirational concept is greatly advancing the progress of single site incision laparoscopic approaches and is speeding appreciation of translumenal assistance and operation. However, if N.O.T.E.S. is to occupy a distinct role in the surgical management of colorectal disease, it needs a niche indication of its own that constitutes a therapeutic advance with considerable clinical benefit for suitable patients. Conversely, sound development of a specific stream-lined operative strategy for N.O.T.E.S-type operations may exert a reciprocal swash upon conventional specialist practice. Thus spurred by N.O.T.E.S, localized resection may become standard therapy for early stage colonic neoplasia regardless of operative access although considerable clinical study is as yet required. Therefore, as much as ensuring feasibility and accuracy in the replication of conventional surgical maneuvers, the dawn of N.O.T.E.S. should be recognized as an opportunity for the inquisition of prevailing surgical principles and prejudices in order that colorectal operations are further honed towards perfection (above all it should be realized that avoidance of abdominal scarring is not the last barrier before surgical nirvana). This may represent the main legacy of transluminal investigation whether or not pure N.O.T.E.S. operating ever becomes a clinical reality in its own right. PMID:19179068

Cahill, R A; Lindsey, I; Cunningham, C

2009-06-01

239

Radiofrequency ablation for early oesophageal squamous neoplasia: Outcomes form United Kingdom registry  

PubMed Central

AIM: To report outcomes on patients undergoing radiofrequency ablation (RFA) for early oesophageal squamous neoplasia from a National Registry. METHODS: A Prospective cohort study from 8 tertiary referral centres in the United Kingdom. Patients with squamous high grade dysplasia (HGD) and early squamous cell carcinoma (ESCC) confined to the mucosa were treated. Visible lesions were removed by endoscopic mucosal resection (EMR) before RFA. Following initial RFA treatment, patients were followed up 3 monthly. Residual flat dysplasia was treated with RFA until complete reversal dysplasia (CR-D) was achieved or progression to invasive Squamous cell cancer defined as infiltration into the submucosa layer or beyond. The main outcome measures were CR-D at 12 mo from start of treatment, long term durability, progression to cancer and adverse events. RESULTS: Twenty patients with squamous HGD/ESCC completed treatment protocol. Five patients (25%) had EMR before starting RFA treatment. CR-D was 50% at 12 mo with a median of 1 RFA treatment, mean 1.5 (range 1-3). Two further patients achieved CR-D with repeat RFA after this time. Eighty per cent with CR-D remain dysplasia free at latest biopsy, with median follow up 24 mo (IQR 17-54). Six of 20 patients (30%) progressed to invasive cancer at 1 year. Four patients (20%) required endoscopic dilatations for symptomatic structuring after treatment. Two of these patients have required serial dilatations thereafter for symptomatic dysphagia with a median of 4 dilatations per patient. The other 2 patients required only a single dilatation to achieve an adequate symptomatic response. One patient developed cancer during follow up after end of treatment protocol. CONCLUSION: The role of RFA in these patients remains unclear. In our series 50% patients responded at 12 mo. These figures are lower than limited published data. PMID:24106401

Haidry, Rehan J; Butt, Mohammed A; Dunn, Jason; Banks, Matthew; Gupta, Abhinav; Smart, Howard; Bhandari, Pradeep; Smith, Lesley Ann; Willert, Robert; Fullarton, Grant; John, Morris; Di Pietro, Massimo; Penman, Ian; Novelli, Marco; Lovat, Laurence B

2013-01-01

240

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

241

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

242

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

PubMed Central

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 on all patients. Women attending the colposcopy clinic had confirmation of abnormal cervical cytology by colposcopic directed biopsy. RESULTS--The mean age of women with CIN (33 years) was significantly greater than that of the women without CIN (28 years) and that of the family planning group (26 years). There was a high prevalence of sexually transmitted pathogens in all women. A significantly higher prevalence of bacterial vaginosis was found in women with CIN compared to those without (50% vs 20%; p = 0.034). The human papilloma virus (HPV) was detected in 46% of women with CIN and 65% of those without CIN. Chlamydia trachomatis (21%) and Trichomonas vaginalis (39%) were detected frequently in women with CIN. C. trachomatis (14%-21%) was detected more frequently than Neisseria gonorrhoeae (3-5%) in all asymptomatic women studied. CONCLUSION--This study demonstrates a high prevalence of sexually transmitted pathogens in women with and without CIN as well as family planning clinic attenders. Bacterial vaginosis was a significant finding in women with CIN. C. trachomatis was detected in a high proportion of all women studied and found more commonly than N. gonorrhoeae. We therefore recommend that all women attending gynaecological services in a developing community be investigated and treated for sexually transmitted diseases. PMID:8244352

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

1993-01-01

243

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

244

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. PMID:25673934

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

2015-01-01

245

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

246

Attributing Oncogenic Human Papillomavirus Genotypes to High-grade Cervical Neoplasia: Which Type Causes the Lesion?  

PubMed

Human papillomavirus (HPV) is found in most women with high-grade cervical intraepithelial neoplasia (CIN) 2/3 in cervical cytology and biopsies. Multiple high-risk HPV (hrHPV) genotypes are present in 15% to 50% of cytology samples. We have shown by laser-capture microscopy (LCM)-polymerase chain reaction (PCR) that each lesion is associated with a single hrHPV type. Attribution of hrHPV types to CIN2/3 is important to understand the oncogenic role of different types and the limitations of cytologic typing. We studied hrHPV genotypes in 257 women with histologic CIN2/3 referred on the basis of abnormal cytology. HPV typing was done on cytology and CIN2/3 biopsies. If the whole-tissue section of the biopsy was positive for multiple hrHPV types, LCM-PCR was performed. We found 181 (70%) single and 71 (28%) multiple hrHPV infections in cytology, with 5 (2%) cases HPV-positive only on whole-tissue section PCR. Of cases with multiple cytologic hrHPV infections, 47/71 (66%) showed a single type in CIN2/3 lesions. In total, in 232 of 257 (90%) women with CIN2/3, a single hrHPV type caused CIN2/3. One was nonattributable on the LCM level. The remaining 24 women had 2 or more contiguous or separated lesions, each associated with a single hrHPV infection. The probability of HPV16 being present in CIN2/3, if detected in cytology, was 0.96 (95% confidence interval=0.90-0.98). LCM-PCR confirms that only 9% of histologic CIN2/3 is associated with multiple hrHPV types, much less than cytology would indicate, and each lesion was associated with a single hrHPV infection. PMID:25353286

van der Marel, Jacolien; Berkhof, Johannes; Ordi, Jaume; Torné, Aureli; Del Pino, Marta; van Baars, Romy; Schiffman, Mark; Wentzensen, Nicolas; Jenkins, David; Quint, Wim G V

2015-04-01

247

Reproducibility of endometrial intraepithelial neoplasia diagnosis is good, but influenced by the diagnostic style of pathologists.  

PubMed

Endometrial intraepithelial neoplasia (EIN) applies specific diagnostic criteria to designate a monoclonal endometrial preinvasive glandular proliferation known from previous studies to confer a 45-fold increased risk for endometrial cancer. In this international study we estimate accuracy and precision of EIN diagnosis among 20 reviewing pathologists in different practice environments, and with differing levels of experience and training. Sixty-two endometrial biopsies diagnosed as benign, EIN, or adenocarcinoma by consensus of two expert subspecialty pathologists were used as a reference comparison to assess diagnostic accuracy of 20 reviewing pathologists. Interobserver reproducibility among the 20 reviewers provided a measure of diagnostic precision. Before evaluating cases, observers were self-trained by reviewing published textbook and/or online EIN diagnostic guidelines. Demographics of the reviewing pathologists, and their impressions regarding implementation of EIN terminology were recorded. Seventy-nine percent of the 20 reviewing pathologists' diagnoses were exactly concordant with the expert consensus (accuracy). The interobserver weighted ? values of 3-class EIN scheme (benign, EIN, carcinoma) diagnoses between expert consensus and each of reviewing pathologists averaged 0.72 (reproducibility, or precision). Reviewing pathologists demonstrated one of three diagnostic styles, which varied in the repertoire of diagnoses commonly used, and their nonrandom response to potentially confounding diagnostic features such as endometrial polyp, altered differentiation, background hormonal effects, and technically poor preparations. EIN diagnostic strategies can be learned and implemented from standard teaching materials with a high degree of reproducibility, but is impacted by the personal diagnostic style of each pathologist in responding to potential diagnostic confounders. PMID:22301705

Usubutun, Alp; Mutter, George L; Saglam, Arzu; Dolgun, Anil; Ozkan, Eylem Akar; Ince, Tan; Akyol, Aytekin; Bulbul, H Dilek; Calay, Zerrin; Eren, Funda; Gumurdulu, Derya; Haberal, A Nihan; Ilvan, Sennur; Karaveli, Seyda; Koyuncuoglu, Meral; Muezzinoglu, Bahar; Muftuoglu, Kamil H; Ozdemir, Necmettin; Ozen, Ozlem; Baykara, Sema; Pestereli, Elif; Ulukus, Emine Cagnur; Zekioglu, Osman

2012-06-01

248

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

249

Analysis of a new histological and molecular-based classification of canine mammary neoplasia.  

PubMed

Canine mammary tumors (CMTs) are morphologically and biologically heterogeneous, prompting several attempts to classify such tumors on the basis of their histopathological characteristics. Recently, molecular-based analysis methods borrowed from human breast cancer research have also been applied to the classification of CMTs. In this study, canine mammary neoplasms (n = 648) occurring in Korea from 2008 to 2011 were analyzed according to the histological classification and grading system proposed by Goldschmidt et al. Furthermore, randomly selected mammary carcinomas (n = 159) were classified according to the molecular subtype using immunohistochemical characteristics. Canine mammary neoplasia accounted for 52.6% (648/1250) of the tumors in female dogs, and 51.7% (340/648) of these were malignant. All of the carcinoma-anaplastic subtypes were grade III tumors (5/5, 100%), while most of the carcinoma-tubular subtypes (15/18, 83.3%) and carcinoma arising in a complex adenoma/mixed-tumor subtype (115/135, 85.2%) were grade I tumors. Tumor cell invasion into lymphatic vessels was most common in the comedocarcinoma, carcinoma-anaplastic, and inflammatory carcinoma subtypes. The most frequently occurring molecular subtype (70/159, 44%) was luminal A. However, the basal-like subtype was the most malignant and was frequently associated with grade III tumors and lymphatic invasion. The carcinoma-solid subtypes were also often of the basal-like subtype. Reclassification of CMTs using the newly proposed histopathological classification system and molecular subtyping could aid in determining the prognosis and the most suitable anticancer treatment for each case. PMID:24003019

Im, K S; Kim, N H; Lim, H Y; Kim, H W; Shin, J I; Sur, J H

2014-05-01

250

Effect of human papillomavirus genotype on severity and prognosis of cervical intraepithelial neoplasia  

PubMed Central

Objective This study evaluated the effect of the specific human papillomavirus (HPV) genotypes on severity and prognosis in cervical intraepithelial neoplasia (CIN) patients. Methods The medical records of 446 patients treated with loop electrosurgical excision procedure (LEEP) were reviewed. The severity of CIN was categorized as CIN1/CIN2 versus CIN3+ including CIN3 and carcinoma in situ (CIS). HPV genotypes were categorized as 1) low risk, 2) intermediate risk, 3) high risk/HPV 16, 4) high risk/HPV 18, and 5) unclassified. Progression was defined as abnormal cytology, including atypical squamous cells, low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion. The margin status and progression free survival (PFS) by HPV genotypes were analyzed in 355 women with three months or more of post-treatment records. Results CIN3+ was the most common CIN type (67.7%), and high risk/HPV 16 (26.9%) was the most common genotype. Intermediate risk (P < 0.01), high risk/HPV 16 (P < 0.01) and high risk/HPV 18 (P < 0.01) were significantly more common in women with CIN3+ than CIN1/CIN2. Patients with high risk/HPV 18 showed the highest rate of positive margins (P < 0.01). The margin status proved to be the only statistically significant factor affecting PFS. Conclusion The proportion of positive margins was significantly different by HPV genotypes and highest in high risk/HPV 18 group. CIN patients with high risk/HPV 18 need to be more carefully tracked than patients with the other HPV genotypes. PMID:24596816

Ku, Chun-Hoe; Lee, Soon-Pyo

2014-01-01

251

Human papillomavirus (HPV) infections and their associations with squamous cell neoplasia.  

PubMed

Current data implicating an etiological role of Human papillomavirus (HPV) infections in precancer lesions (intraepithelial neoplasia) and squamous cell carcinoma of both the genital tract and other sites (oral cavity, larynx, skin, esophagus, nasal cavity, bronchus) can be summarized as follows: a) HPV involvement in benign, precancer, and malignant genital squamous cell lesions has been demonstrated by morphological, immunohistochemical and DNA hybridization techniques; b) HPV infections in the genital tract are sexually transmitted (STD) and associated with the same risk factors as development of cervical carcinoma; c) natural history of cervical HPV lesions is equivalent to that of CIN, i.e. they are potentially progressive to carcinoma in situ; d) latent HPV infections exist in the genital tract of both sexes; e) animal models exist, where papillomaviruses induce malignant transformation; f) HPV 11 induces transformation of human squamous epithelium in vivo (nude mouse renal subcapsule assay); g) malignant transformation of HPV lesions seems to depend on virus type and the physical state of its DNA, i.e. whether or not integrated in the host cell DNA; h) malignant transformation most probably requires synergistic actions between HPV and chemical or physical carcinogens or other infectious agents; i) genetic disposition (at least in animals) significantly contributes to malignant transformation; j) immunological defence mechanisms of the host probably are capable of modifying the course of HPV infection (efficacy in man remains to be elucidated). Many details of the molecular mechanisms still remain to be clarified, however. No applicable model systems exist to elucidate these issues, or the mechanisms leading to the progression to invasive cancer. Improved tissue culture systems for in vitro differentiation of keratinocytes should help in elucidating the biology of papillomaviruses and their interaction with cell division and differentiation. PMID:2829787

Syrjänen, K J

1987-01-01

252

Quality of life in the actinic neoplasia syndrome: The VA Topical Tretinoin Chemoprevention (VATTC) Trial  

PubMed Central

Background Keratinocyte carcinomas (KCs) are the most common malignancies of the skin. As lesions have a low mortality rate, understanding quality-of-life (QoL) factors is necessary in their management. Objective To assess QoL and associated patient characteristics in those with a history of keratinocyte carcinomas. Methods We conducted a cross-sectional study of veterans with a history of KCs enrolled in a randomized controlled trial for chemoprevention of keratinocyte carcinomas. Study dermatologists counted actinic keratoses (AKs) and assessed for skin photodamage. QoL was assessed using Skindex-29 and KC-specific questions. Demographics were self-reported. Results Participants (n = 931) enrolled at 5 clinical sites had worse QoL on all subscales (emotions, functioning, and symptoms) compared to a reference group of patients without skin disease. Univariate analysis demonstrated worse QoL associated with higher AK count, past 5-fluorouracil (5-FU) use, and greater sun sensitivity. Multivariate analysis demonstrated that higher AK count and past 5-FU use were independently related to diminished QoL. Higher comorbidities showed modest associations on the symptoms and functioning subscales. Number of previous KCs was not independently associated with any QoL differences. Limitations Study population may not be generalizable to the general population. Counting of AKs is of limited reliability. Previous 5-FU use is self reported. Conclusions A history of ever use of 5-FU and present AKs was strongly associated with worse QoL. We find it more useful to consider these patients as having the chronic condition “actinic neoplasia syndrome,” whose burden may be best measured by factors other than their history of KCs. PMID:19398145

Weinstock, Martin A.; Lee, Kachiu C.; Chren, Mary-Margaret; Marcolivio, Kimberly

2013-01-01

253

Cytology and Human Papillomavirus Co-Test Results Preceding Incident High-Grade Cervical Intraepithelial Neoplasia  

PubMed Central

Objective High-risk HPV (hrHPV) and cytology co-testing is utilized for primary cervical cancer screening and for enhanced follow-up of women who are hrHPV-positive, cytology negative. However, data are lacking on the utility of this method to detect pre-cancer or cancer in community-based clinical practice. This study describes cytology and hrHPV results preceding high-grade cervical intraepithelial neoplasia, adenocarcinoma in situ, or cervical cancer (i.e., CIN2+) in an integrated health system employing routine co-testing among women aged 30 years and older. Methods We conducted a cross-sectional analysis of adult female members of Kaiser Permanente Northern California (KPNC) with incident CIN2+ between July 2008 and June 2009. The primary outcome was the proportions of cytologic diagnoses and hrHPV co-test results preceding a diagnosis of CIN2+. Cervical cytology and hrHPV testing results were abstracted from electronic medical records. Results Of 1283 CIN2+ cases among adult women, 880 (68.5%) were among women aged 30 years and older and 145/880 (16.5%, 95% CI 14.1–19.1) had only normal cytology during the 12 months prior to diagnosis. Furthermore, 133/880 (15.1%, 95% 12.9–17.7) were preceded by only normal cytology and persistent hrHPV infection (at least 2 positive hrHPV tests) during the 6–36 months preceding CIN2+ diagnosis. Conclusions Incident CIN2+ is frequently preceded by normal cytology and persistent hrHPV infection among women aged 30 years and older; screening strategies that employ HPV testing and cytology may improve the detection of CIN2+ compared with cytology alone. PMID:25793987

Park, Ina U.; Wojtal, Nicole; Silverberg, Michael J.; Bauer, Heidi M.; Hurley, Leo B.; Manos, M. Michele

2015-01-01

254

scribble mutants promote aPKC and JNK-dependent epithelial neoplasia independently of Crumbs  

PubMed Central

Background Metastatic neoplasias are characterized by excessive cell proliferation and disruptions to apico-basal cell polarity and tissue architecture. Understanding how alterations in cell polarity can impact upon tumour development is, therefore, a central issue in cancer biology. The Drosophila gene scribble (scrib) encodes a PDZ-domain scaffolding protein that regulates cell polarity and acts as a tumour suppressor in flies. Increasing evidence also implicates the loss of human Scrib in cancer. In this report, we investigate how loss of Scrib promotes epithelial tumourigenesis in Drosophila, both alone and in cooperation with oncogenic mutations. Results We find that genetically distinct atypical protein kinase C (aPKC)-dependent and Jun N-terminal kinase (JNK)-dependent alterations in scrib mutants drive epithelial tumourigenesis. First, we show that over-expression of the apical cell polarity determinants Crumbs (Crb) or aPKC induces similar cell morphology defects and over-proliferation phenotypes as scrib loss-of-function. However, the morphological and proliferative defects in scrib mutants are independent of Crb function, and instead can be rescued by a dominant negative (kinase dead) aPKC transgene. Secondly, we demonstrate that loss of Scrib promotes oncogene-mediated transformation through both aPKC and JNK-dependent pathways. JNK normally promotes apoptosis of scrib mutant cells. However, in cooperation with oncogenic activated Ras or Notch signalling, JNK becomes an essential driver of tumour overgrowth and invasion. aPKC-dependent signalling in scrib mutants cooperates with JNK to significantly enhance oncogene-mediated tumour overgrowth. Conclusion These results demonstrate distinct aPKC and JNK-dependent pathways through which loss of Scrib promotes tumourigenesis in Drosophila. This is likely to have a direct relevance to the way in which human Scrib can similarly restrain an oncogene-mediated transformation and, more generally, on how the outcome of oncogenic signalling can be profoundly perturbed by defects in apico-basal epithelial cell polarity. PMID:19778415

Leong, Gregory R; Goulding, Karen R; Amin, Nancy; Richardson, Helena E; Brumby, Anthony M

2009-01-01

255

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

256

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

257

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

258

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

259

Progression of epididymal maldevelopment into hamartoma-like neoplasia in VHL disease.  

PubMed

Inactivation of the von Hippel-Lindau (VHL) gene and activation of the hypoxia-inducible factor (HIF) in susceptible cells precedes formation of tumorlets and frank tumor in the epididymis of male VHL patients. We performed detailed histologic and molecular pathologic analysis of tumor-free epididymal tissues from VHL patients to obtain further insight into early epididymal tumorigenesis. Four epididymides from two VHL patients were serially sectioned to allow for three-dimensional visualization of morphologic changes. Areas of interest were genetically analyzed by tissue microdissection, immunohistochemistry for HIF and markers for mesonephric differentiation, and in situ hybridization for HIF downstream target vascular endothelial growth factor. Structural analysis of the epididymides revealed marked deviations from the regular anatomic structure resulting from impaired organogenesis. Selected efferent ductules were represented by disorganized mesonephric cells, and the maldeveloped mesonephric material was VHL-deficient by allelic deletion analysis. Furthermore, we observed maldeveloped mesonephric material near cystic structures, which were also VHL-deficient and were apparent derivatives of maldeveloped material. Finally, a subset of VHL-deficient cells was structurally integrated in regular efferent ductules; proliferation of intraductular VHL-deficient cells manifests itself as papillary growth into the ductular lumen. Furthermore, we clarify that that there is a pathogenetic continuum between microscopic tumorlets and formation of tumor. In multiple locations, three-dimensional reconstruction revealed papillary growth to extend deeply into ductular lumina, indicative of progression into early hamartoma-like neoplasia. We conclude epididymal tumorigenesis in VHL disease to occur in two distinct sequential steps: maldevelopment of VHL-deficient mesonephric cells, followed by neoplastic papillary proliferation. PMID:18813354

Mehta, Gautam U; Shively, Sharon B; Duong, Heng; Tran, Maxine G B; Moncrief, Travis J; Smith, Jonathan H; Li, Jie; Edwards, Nancy A; Lonser, Russell R; Zhuang, Zhengping; Merrill, Marsha J; Raffeld, Mark; Maxwell, Patrick H; Oldfield, Edward H; Vortmeyer, Alexander O

2008-10-01

260

Genetic and Epigenetic Analysis in Korean Patients with Multiple Endocrine Neoplasia Type 1  

PubMed Central

Background Multiple endocrine neoplasia type 1 (MEN1) is a familial syndrome characterized by the parathyroid, pancreas and pituitary tumors. Parathyroid tumors are the most common clinical manifestations, occurring in more than 90% of MEN1 patients. Heterozygous germline mutations of the MENIN gene underlie the tumorigenesis in MEN1 and epigenetic alterations along with germline mutations may contribute to tumorigenesis. Here, we investigated the associations between genotype and phenotype in Korean MEN1 patients. Methods We analyzed medical records from 14 unrelated MEN1 patients who had newly confirmed MENIN germline mutations, together with 14 previous reports in Korea. Aberrant DNA methylations were also examined in MEN1-related parathyroid tumors using the Infinium HumanMethylation 450 BeadChip. Results Total 28 germline mutations of MENIN were relatively highly concentrated in exons 7 and 8 compared to previous reports from Western countries. Six mutations (c.111dupT/p.S38Ffs*79, c.225_226insT/p.T76Yfs*41, c.383_398del16/p.S128Tfs*52, c.746dupT/p.H250Afs*20, c.1150G>T/p.E384*, and c.1508G>A/p.G503N) were newly found in the present study. Of interest, four patients (15%) showed unusual initial presentations and three patients were diagnosed incidentally at the general medical checkup. We also found three distinct sites in exon 2 of MENIN were significantly hypomethylated in the MEN1 parathyroid tumors, comparing correspondent blood samples. Conclusion We also have found a lack of genotype/phenotype correlation in Korean MEN1 patients. There were not a few unusual initial manifestations in MEN1 patients, thus, genetic testing for the MENIN germline mutations can provide important information for the better prognosis. Further studies are warranted to investigate altered DNA methylations in the MENIN gene involved in tumorigenesis. PMID:25309785

Chung, Yoon Jung; Hwang, Sena; Jeong, Jong Ju; Song, Sun Yong; Kim, Se Hoon

2014-01-01

261

GNA15 expression in small intestinal neuroendocrine neoplasia: Functional and signalling pathway analyses.  

PubMed

Gastroenteropancreatic neuroendocrine neoplasia (GEP-NEN) comprises a heterogeneous group of tumours that exhibit widely divergent biological behaviour. The identification of new targetable GPCR-pathways involved in regulating cell function could help to identify new therapeutic strategies. We assessed the function of a haematopoietic stem cell heterotrimeric G-protein, G?15, in gut neuroendocrine cell models and examined the clinical implications of its over expression. Functional assays were undertaken to define the role of GNA15 in the small intestinal NEN cell line KRJ-I and in clinical samples from small intestinal NENs using quantitative polymerase chain reaction, western blot, proliferation and apoptosis assays, immunoprecipitation, immunohistochemistry (IHC) and automated quantitative analysis (AQUA). GNA15 was not expressed in normal neuroendocrine cells but was overexpressed in GEP-NEN cell lines. In KRJ-I cells, decreased expression of GNA15 was associated with inhibition of proliferation, activation of apoptosis and differential effects on pro-proliferative ERK, NF?B and Akt pathway signalling. Moreover, G?15 was demonstrated to couple to the ß1 adrenergic receptor and modulated proliferative signals through this GPCR. Transcript and protein levels of GNA15 were significantly elevated in primary and metastatic tumours compared to normal mucosa and were particularly increased in low Ki-67 expressing tumours. IHC and AQUA revealed that a higher G?15 expression was associated with a poorer survival. GNA15 may have a pathobiological role in SI-NENs. Targeting this signalling mediator could provide an opportunity for the development of new therapeutic strategies for this tumour type. PMID:25701539

Zanini, Sara; Giovinazzo, Francesco; Alaimo, Daniele; Lawrence, Ben; Pfragner, Roswitha; Bassi, Claudio; Modlin, Irvin; Kidd, Mark

2015-05-01

262

High-calorie diet exacerbates prostate neoplasia in mice with haploinsufficiency of Pten tumor suppressor gene  

PubMed Central

Objective Association between prostate cancer and obesity remains controversial. Allelic deletions of PTEN, a tumor suppressor gene, are common in prostate cancer in men. Monoallelic Pten deletion in mice causes low prostatic intraepithelial neoplasia (mPIN). This study tested the effect of a hypercaloric diet on prostate cancer in Pten+/? mice. Methods 1-month old mice were fed a high-calorie diet deriving 45% calories from fat for 3 and 6 months before prostate was analyzed histologically and biochemically for mPIN progression. Because Pten+/? mice are protected against diet-induced insulin resistance, we tested the role of insulin on cell growth in RWPE-1 normal human prostatic epithelial cells with siRNA knockdown of PTEN. Results In addition to activating PI3 kinase/Akt and Ras/MAPkinase pathways, high-calorie diet causes neoplastic progression, angiogenesis, inflammation and epithelial–mesenchymal transition. It also elevates the expression of fatty acid synthase (FAS), a lipogenic gene commonly elevated in progressive cancer. SiRNA-mediated downregulation of PTEN demonstrates increased cell growth and motility, and soft agar clonicity in addition to elevation in FAS in response to insulin in RWPE-1 normal human prostatic cells. Downregulating FAS in addition to PTEN, blunted the proliferative effect of insulin (and IL-6) in RWPE-1 cells. Conclusion High-calorie diet promotes prostate cancer progression in the genetically susceptible Pten haploinsufficient mouse while preserving insulin sensitivity. This appears to be partly due to increased inflammatory response to high-caloric intake in addition to increased ability of insulin to promote lipogenesis. PMID:25737954

Liu, Jehnan; Ramakrishnan, Sadeesh K.; Khuder, Saja S.; Kaw, Meenakshi K.; Muturi, Harrison T.; Lester, Sumona Ghosh; Lee, Sang Jun; Fedorova, Larisa V.; Kim, Andrea J.; Mohamed, Iman E.; Gatto-Weis, Cara; Eisenmann, Kathryn M.; Conran, Philip B.; Najjar, Sonia M.

2015-01-01

263

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

264

HIV and HPV infections and ocular surface squamous neoplasia: systematic review and meta-analysis  

PubMed Central

Background: The frequency of ocular surface squamous neoplasias (OSSNs) has been increasing in populations with a high prevalence of infection with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and infection with human papillomavirus (HPV). We aimed to quantify the association between HIV/AIDS and HPV infection and OSSN, through systematic review and meta-analysis. Methods: The articles providing data on the association between HIV/AIDS and/or HPV infection and OSSN were identified in MEDLINE, SCOPUS and EMBASE searched up to May 2013, and through backward citation tracking. The DerSimonian and Laird method was used to compute summary relative risk (RR) estimates and 95% confidence intervals (95% CI). Heterogeneity was quantified with the I2 statistic. Results: HIV/AIDS was strongly associated with an increased risk of OSSN (summary RR=8.06, 95% CI: 5.29–12.30, I2=56.0%, 12 studies). The summary RR estimate for the infection with mucosal HPV subtypes was 3.13 (95% CI: 1.72–5.71, I2=45.6%, 16 studies). Four studies addressed the association between both cutaneous and mucosal HPV subtypes and OSSN; the summary RR estimates were 3.52 (95% CI: 1.23–10.08, I2=21.8%) and 1.08 (95% CI: 0.57–2.05, I2=0.0%), respectively. Conclusion: Human immunodeficiency virus infection increases the risk of OSSN by nearly eight-fold. Regarding HPV infection, only the cutaneous subtypes seem to be a risk factor. PMID:24030075

Carreira, H; Coutinho, F; Carrilho, C; Lunet, N

2013-01-01

265

Prevalence, treatment and outcomes of coexistent ocular surface squamous neoplasia and pterygium  

PubMed Central

Purpose The purpose of this study was to determine the prevalence of ocular surface neoplasia (OSSN) coexistent with pterygia in South Florida and to study the treatment and related outcomes. Design Non-interventional retrospective study. Participants Two thousand and five patients with surgically excised pterygia at the Bascom Palmer Eye Institute from 2000 – 2010. Methods Pathology reports of patients with pterygia were reviewed for evidence of OSSN. Patients were divided into the following groups: pterygium and no OSSN (group1), clinically suspected OSSN with pterygium (group 2) and unexpected OSSN with pterygium found on histopathology (group 3). Clinical charts of patients in group 2 and 3 were reviewed. Main outcome measures Period prevalence, treatment and outcome. Results In surgically excised pterygia, we found the prevalence of coexistent OSSN to be 1.7% (n=34), of which 41% (n=14) were clinically suspected preoperatively (group 2) and 59% (n=20) were unexpectedly found on histopathology (group 3). Clinically suspected OSSN with pterygia was generally treated with wide surgical margins and cryotherapy, whereas unexpected OSSN with pterygia was treated with simple excision, followed by adjuvant interferon treatment in 30% (n=6). After a mean follow up of 2 years, there were no recurrences in the suspected OSSN group and 2 recurrences in the unexpected OSSN group. The recurrence rate in the latter group was 11% at 1 year and 24% at 2 years. Conclusion OSSN is uncommonly found to coexist with pterygium. The prognosis in suspected OSSN cases is excellent with no recurrences noted despite positive margins in 50% of cases. The recurrence rates of unexpected OSSN mirrors that of OSSN not associated with pterygium, and thus vigilance for recurrence is important. PMID:23107578

Oellers, Patrick; Karp, Carol L.; Sheth, Anoop; Kao, Andrew A.; Abdelaziz, Amany; Matthews, Jared L.; Dubovy, Sander R.; Galor, Anat

2012-01-01

266

LRIG1 as a Potential Novel Marker for Neoplastic Transformation in Ocular Surface Squamous Neoplasia  

PubMed Central

The leucine rich repeats and immunoglobulin-like protein 1 (LRIG1) is a newly discovered negative regulator of epidermal growth factor receptor (EGFR) and a proposed tumor suppressor. It is not universally downregulated in human cancers, and its role in neoplastic transformation and tumorigenesis is not well-documented. In this study, we show the expression of LRIG1 as a novel potential marker for neoplastic transformation in ocular-surface squamous neoplasia (OSSN). The following two groups were included in this study: 1) benign group (3 cases; 1 with papilloma and 2 with dysplasia) and 2) malignant group (3 cases with squamous cell carcinoma (SCC)). In both groups, immunofluorescence analysis was firstly performed for keratins 4, 12, 13, and 15 to characterize the state of differentiation, and for Ki67 to evaluate the proliferation activity. Subsequently, LRIG1 and EGFR expression was analyzed. Either keratin 4 and/or 13, both non-keratinized epithelial cell markers, were generally expressed in both groups, except for 1 severe SCC case. Keratin 15, an undifferentiated basal cell marker, was more strongly expressed in the malignant cases than in the benign cases. The Ki67 index was significantly higher (P<0.002) in the malignant group (33.2%) than in the benign group (10.9%). LRIG1 expression was limited to basal epithelial cells in normal corneal epithelial tissue. Interestingly, LRIG1 was expressed throughout the epithelium in all the benign cases. In contrast, its expression was limited or totally disappeared in the malignant cases. Inversely, EGFR staining was faintly expressed in the benign cases, yet strongly expressed in the malignant cases. Malignant tissue with proliferative potential presented EGFR overexpression and inverse downregulation of LRIG1, consistent with LRIG1 being a suppressor of neoplastic transformation by counteracting the tumor growth property of EGFR. Our findings indicate that downregulation of LRIG1 is possibly a novel potential marker of transformation and tumorigenesis in OSSN cases. PMID:24709893

Nagata, Maho; Nakamura, Takahiro; Sotozono, Chie; Inatomi, Tsutomu; Yokoi, Norihiko; Kinoshita, Shigeru

2014-01-01

267

Ethnic and Gender Disparities in Colorectal Neoplasia Among Hispanic Patients Undergoing Screening Colonoscopy  

PubMed Central

Background & Aims Colorectal cancer (CRC) is a highly prevalent cancer among US Hispanics. In Puerto Rico (PR), CRC is the third cause of cancer death in men and the second cause of cancer death in women. There is limited published data on the prevalence of colorectal neoplasia (CRN) among US Hispanics. We determined the prevalence of CRN (colorectal adenomas and cancer) among asymptomatic screening PR Hispanic subjects and evaluated associated risk factors with CRN. Methods A retrospective review of the medical, endoscopic and pathology records of individuals who underwent first-time screening colonoscopy at an ambulatory gastroenterology practice from January 1, 2008 to December 1, 2009. Prevalence of CRN (overall and advanced) documented by colonoscopy and pathology report was calculated for the complete cohort and by gender. Results Out of the 745 Hispanic individuals who underwent screening colonoscopy during the study period, the prevalence for overall CRN was 25.1% and for advanced CRN ( 1 cm and/or advanced histology) was 4.0%. Prevalence of CRN was higher for men compared to women (32.0% vs. 20.6%, p =0.001; OR=1.92, 95% CI 1.4–2.6). CRN was more frequently located in the proximal colon (67.7% proximal vs. 32.3% distal). Family history of CRC was associated with advanced CRN (OR = 2.73, 95% CI 1.10 – 6.79). Conclusions CRN was more common among Hispanic men compared to women and increased with age. CRN among Hispanics was predominantly located in the proximal colon. Our findings suggest ethnic and gender disparities in CRN patterns, which may be related to genomic admixture and have important implications in screening algorithms for Hispanics. PMID:22542749

Lathroum, Liselle; Ramos-Mercado, Fernando; Hernandez-Marrero, Jessica; Villafaña, Myriam; Cruz-Correa, Marcia

2012-01-01

268

Linkage to chromosome 2q32.2-q33.3 in familial serrated neoplasia (Jass syndrome).  

PubMed

Causative genetic variants have to date been identified for only a small proportion of familial colorectal cancer (CRC). While conditions such as Familial Adenomatous Polyposis and Lynch syndrome have well defined genetic causes, the search for variants underlying the remainder of familial CRC is plagued by genetic heterogeneity. The recent identification of families with a heritable predisposition to malignancies arising through the serrated pathway (familial serrated neoplasia or Jass syndrome) provides an opportunity to study a subset of familial CRC in which heterogeneity may be greatly reduced. A genome-wide linkage screen was performed on a large family displaying a dominantly-inherited predisposition to serrated neoplasia genotyped using the Affymetrix GeneChip Human Mapping 10 K SNP Array. Parametric and nonparametric analyses were performed and resulting regions of interest, as well as previously reported CRC susceptibility loci at 3q22, 7q31 and 9q22, were followed up by finemapping in 10 serrated neoplasia families. Genome-wide linkage analysis revealed regions of interest at 2p25.2-p25.1, 2q24.3-q37.1 and 8p21.2-q12.1. Finemapping linkage and haplotype analyses identified 2q32.2-q33.3 as the region most likely to harbour linkage, with heterogeneity logarithm of the odds (HLOD) 2.09 and nonparametric linkage (NPL) score 2.36 (P = 0.004). Five primary candidate genes (CFLAR, CASP10, CASP8, FZD7 and BMPR2) were sequenced and no segregating variants identified. There was no evidence of linkage to previously reported loci on chromosomes 3, 7 and 9. PMID:21165777

Roberts, Aedan; Nancarrow, Derek; Clendenning, Mark; Buchanan, Daniel D; Jenkins, Mark A; Duggan, David; Taverna, Darin; McKeone, Diane; Walters, Rhiannon; Walsh, Michael D; Young, Bruce W; Jass, Jeremy R; Rosty, Christophe; Gattas, Michael; Pelzer, Elise; Hopper, John L; Goldblatt, Jack; George, Jill; Suthers, Graeme K; Phillips, Kerry; Parry, Susan; Woodall, Sonja; Arnold, Julie; Tucker, Kathy; Muir, Amanda; Drini, Musa; Macrae, Finlay; Newcomb, Polly; Potter, John D; Pavluk, Erika; Lindblom, Annika; Young, Joanne P

2011-06-01

269

Assessment of the "fish tumors or other deformities" beneficial use impairment in brown bullhead (Ameiurus nebulosus): II. Liver neoplasia  

USGS Publications Warehouse

Liver pathology of fishes, including neoplastic and preneoplastic lesions, is widely used as an indicator of exposure to anthropogenic contaminants. By definition, the "fish tumor or other deformities" beneficial use impairment (BUI) at Great Lakes Areas of Concern (AOC) includes neoplastic and preneoplastic liver lesions in brown bullhead (Ameiurus nebulosus) or suckers. Unfortunately, adequate guidelines for defining neoplastic and preneoplastic liver lesions or determining rates at unimpacted control sites were not provided and different criteria have been used. In some cases, only neoplastic changes were used to calculate tumor prevalence, in some both neoplastic and preneoplastic changes and in some it is difficult to determine which changes were included. Using standardized criteria, the prevalence of liver neoplasia was compared at eight AOC during 1998-2000. The Cuyahoga River had the highest prevalence (25.0%), while the Maumee River had the lowest (3.9%). The Buffalo (4.8%), Detroit (5.9%), Ashtabula (6.8%), Niagara (7.5%) and Black (8.9%) rivers were intermediate, as was Presque Isle Bay (7.1%). From 2002 to 2007 the prevalence of liver neoplasia at Presque Isle Bay ranged from a low of 2.1% (2002) to a high of 12.0% (2007). Non-AOC sites, as potential reference sites, also were monitored during this time. By combining years and sites, the prevalence of liver neoplasia in bullhead (aged 2 to 12 years) at inland lakes was 0.7%, at bays/harbors was 1.6% and at tributary sites was 4.1%. This is the same trend (inland lakes < bays/harbors < tributaries < Presque Isle Bay) noted for orocutaneous neoplasms.

Blazer, V.S.; Rafferty, S.D.; Baumman, P.C.; Smith, S.B.; Obert, E.C.

2009-01-01

270

Combined use of vitamin d3 and metformin exhibits synergistic chemopreventive effects on colorectal neoplasia in rats and mice.  

PubMed

Vitamin D3 and metformin are widely used in humans for regulating mineral metabolism and as an antidiabetic drug, respectively; and both of them have been shown to have chemopreventive effects against various tumors. This study was designed to investigate the potential synergistic chemopreventive effects of vitamin D3 and metformin against the development of early colon neoplasia in two models. The first model was a 1,2-dimethylhydrazine dihydrochloride (DMH)-induced colon cancer rat model and the second, a DMH-dextran sodium sulfate (DSS)-induced colitis-associated colon neoplasia mouse model. Compared with either vitamin D3 or metformin alone, combined use of vitamin D3 and metformin showed more pronounced effect in reducing the numbers of aberrant crypt foci (ACF) and tumor in the colon. The most prominent inhibitory effects were observed in the vitamin D3 medium dose (100 IU/kg/d) and metformin medium dose (120 mg/kg/d) combination group. Furthermore, our results showed that enhancement of metformin's chemopreventive effects by vitamin D3 was associated with downregulation of S6P expression, via the AMPK (IGFI)/mTOR pathway. In addition, enhancement of vitamin D3's chemopreventive effects by metformin was associated with inhibition of the protein expressions of c-Myc and Cyclin D1, via the vitamin D receptor/?-catenin pathway. These findings show that the combined use of vitamin D3 and metformin exhibits synergistic effects against the development of early colon neoplasia. They suggest that the combined use of vitamin D3 and metformin may represent a novel strategy for chemoprevention of colorectal cancer. Cancer Prev Res; 8(2); 139-48. ©2014 AACR. PMID:25416412

Li, Wan; Wang, Qi-Long; Liu, Xia; Dong, Shu-Hong; Li, Hong-Xia; Li, Chun-Yang; Guo, Li-Shu; Gao, Jing-Miao; Berger, Nathan A; Li, Li; Ma, Lan; Wu, Yong-Jie

2015-02-01

271

Identification of octadeca-9,11-dienoic acid and its significance in the diagnosis of cervical intraepithelial neoplasia.  

PubMed

In 1987 it was claimed using high performance liquid chromatography (HPLC) that the molar ratio of octadeca-9,11-dienoic acid to its parent linoleic acid (18:2 (9,12)) was raised in malignant and premalignant conditions of the cervix. In this study based on a gas chromatographic procedure which prevents autoxidation and avoids the detection limitations of HPLC, we have shown that assay of these fatty acids has no role to play in the assessment of cervical neoplasia. PMID:2766553

Parham, D M; Ross, P E; Gunstone, F D; Robertson, A J; Duncan, I D

1989-07-14

272

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

273

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

274

Mild Obesity, Physical Activity, Calorie Intake, and the Risks of Cervical Intraepithelial Neoplasia and Cervical Cancer  

PubMed Central

Objective We investigated whether obesity, physical activity, and calorie intake are associated with the risks of cervical intraepithelial neoplasia (CIN) and cervical cancer. Methods We enrolled 1125 women (age, 18–65 years) into a human papillomavirus cohort study established from 2006 to 2012. Multinomial logistic regression models were used to estimate crude and multivariate odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs), and to assess whether body mass index (BMI), height, weight, total calorie intake, and physical activity were associated with the risks of CIN and cervical cancer. Results Cervical cancer risk was positively associated with BMI and inversely associated with physical activity. When compared with women with a normal BMI (18.5–23 kg/m2), the multivariate ORs (95% CIs) for those overweight (23–25 kg/m2) and mild obesity (?25 kg/m2) were 1.25 (0.79–2.00) and 1.70 (1.10–2.63), respectively. When compared with women with the lowest tertile of physical activity (<38.5 MET-hours/week), the ORs (95% CIs) for cervical cancer were 0.95 (0.61–1.48) and 0.61 (0.38–0.98) for women with medium physical activity (38.5–71.9 MET-hours/week) and those with high physical activity (72 MET-hours/week), respectively (p for linear trend ?=?0.03). The CIN2/3 risk was inversely associated with physical activity after adjustment for confounders. Compared with women with low physical activity (< 38.5 MET-hours/week), the ORs (95% CIs) for CIN2/3 were 0.64 (0.40–1.01) and 0.58 (0.36–0.93) for the medium and high physical activity groups, respectively (p for linear trend ?=?0.02). Total calorie intake was not statistically associated with the risks of CIN and cervical cancer after adjustment for confounders. Conclusion Our results indicate that in addition to screening for and treatment of CIN, recommendations on the maintenance of an appropriate BMI with an emphasis on physical activity could be an important preventive strategy against the development of cervical cancer. PMID:23776686

Lee, Jae Kwan; So, Kyeong A.; Piyathilake, Chandrika J.; Kim, Mi Kyung

2013-01-01

275

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

276

Transcontinental communication and quantitative digital histopathology via the Internet; with special reference to prostate neoplasia  

PubMed Central

Objective: To describe practical experiences in the sharing of very large digital data bases of histopathological imagery via the Internet, by investigators working in Europe, North America, and South America. Materials: Experiences derived from medium power (sampling density 2.4 pixels/?m) and high power (6 pixels/?m) imagery of prostatic tissues, skin shave biopsies, breast lesions, endometrial sections, and colonic lesions. Most of the data included in this paper were from prostate. In particular, 1168 histological images of normal prostate, high grade prostatic intraepithelial neoplasia (PIN), and prostate cancer (PCa) were recorded, archived in an image format developed at the Optical Sciences Center (OSC), University of Arizona, and transmitted to Ancona, Italy, as JPEG (joint photographic experts group) files. Images were downloaded for review using the Internet application FTP (file transfer protocol). The images were then sent from Ancona to other laboratories for additional histopathological review and quantitative analyses. They were viewed using Adobe Photoshop, Paint Shop Pro, and Imaging for Windows. For karyometric analysis full resolution imagery was used, whereas histometric analyses were carried out on JPEG imagery also. Results: The three applications of the telecommunication system were remote histopathological assessment, remote data acquisition, and selection of material. Typical data volumes for each project ranged from 120 megabytes to one gigabyte, and transmission times were usually less than one hour. There were only negligible transmission errors, and no problem in efficient communication, although real time communication was an exception, because of the time zone differences. As far as the remote histopathological assessment of the prostate was concerned, agreement between the pathologist's electronic diagnosis and the diagnostic label applied to the images by the recording scientist was present in 96.6% of instances. When these images were forwarded to two pathologists, the level of concordance with the reviewing pathologist who originally downloaded the files from Tucson was as high as 97.2% and 98.0%. Initial results of studies made by researchers belonging to our group but located in others laboratories showed the feasibility of making quantitative analysis on the same images. Conclusions: These experiences show that diagnostic teleconsultation and quantitative image analyses via the Internet are not only feasible, but practical, and allow a close collaboration between researchers widely separated by geographical distance and analytical resources. PMID:12037030

Montironi, R; Thompson, D; Scarpelli, M; Bartels, H G; Hamilton, P W; Da Silva, V D; Sakr, W A; Weyn, B; Van Daele, A; Bartels, P H

2002-01-01

277

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

278

Multiple endocrine neoplasia type 1 and 2: from morphology to molecular pathology 1997.  

PubMed

Multiple Endocrine Neoplasia (MEN) is an inherited syndrome which appears in two major forms referred to as type 1 (MEN-1) and type 2 (MEN-2). MEN-1 is characterized by the occurrence of neuroendocrine parathyroid, pancreas, duodenum and pituitary lesions. In addition to these tumors adrenocortical, lipomatous and neuroendocrine tumors in other locations may develop. The genetic defect of MEN-1 has recently been identified and involves a new form of tumor suppressor gene called mu on chromosome 11q13. It codes for a protein called menin which is expressed in a variety of human tissues and organs. In MEN-1 gene carriers inactivating germline frameshift, nonsense, missense and in-frame deletion mutations scattered throughout the 10 coding exons have been identified. The MEN-2 syndrome is divided into three clinical variants referred to as MEN-2A, MEN-2B and familial medullary thyroid carcinoma (FMTC) which share medullary thyroid carcinomas as part of the disease phenotype. In MEN-2A pheochromocytomas and parathyroid hyperplasia and in MEN-2B additional skeletal abnormalities and ganglioneuromatosis may also be encountered. All three MEN-phenotypes are associated with oncogenic point mutations of the RET protooncogene on chromosome 10q11.2 which encodes a receptor-type tyrosine kinase. Its ligand--the glial cell line derived neurotropic factor (GDNF)--forms a signaling complex with the alpha type of the GDNF receptor. All neuroendocrine tumors of the different MEN-phenotypes may also occur sporadically and there are only few clinical and pathomorphological features which are helpful to discriminate sporadic from MEN-associated neuroendocrine neoplasms. The recent achievements of molecular pathology now allow for the unambiguous identification of MEN gene carriers among patients with neuroendocrine neoplasms by DNA testing for mutations in the mu and RET gene. In this overview, distinct macroscopic and histopathological features of the two MEN phenotypes will be summarized and most recent findings on the molecular pathology of these syndromes will be outlined, together with molecular methods to identify disease-gene carriers. PMID:9474863

Komminoth, P

1997-01-01

279

Arsenic Enhancement of Skin Neoplasia by Chronic Stimulation of Growth Factors  

PubMed Central

Although numerous epidemiological studies have shown that inorganic arsenicals cause skin cancers and hyperkeratoses in humans, there are currently no established mechanisms for their action or animal models. Previous studies in our laboratory using primary human keratinocyte cultures demonstrated that micromolar concentrations of inorganic arsenite increased cell proliferation via the production of keratinocyte-derived growth factors. As recent reports demonstrate that overexpression of keratinocyte-derived growth factors, such as transforming growth factor (TGF)-?, promote the formation of skin tumors, we hypothesized that similar events may be responsible for those associated with arsenic skin diseases. Thus, the influence of arsenic in humans with arsenic skin disease and on mouse skin tumor development in transgenic mice was studied. After low-dose application of tetradecanoyl phorbol acetate (TPA), a marked increase in the number of skin papillomas occurred in Tg.AC mice, which carry the v-Ha-ras oncogene, that received arsenic in the drinking water as compared with control drinking water, whereas no papillomas developed in arsenic-treated transgenic mice that did not receive TPA or arsenic/TPA-treated wild-type FVB/N mice. Consistent with earlier in vitro findings, increases in granulocyte/macrophage colony-stimulating factor (GM-CSF) and TGF-? mRNA transcripts were found in the epidermis at clinically normal sites within 10 weeks after arsenic treatment. Immunohistochemical staining localized TGF-? overexpression to the hair follicles. Injection of neutralizing antibodies to GM-CSF after TPA application reduced the number of papillomas in Tg.AC mice. Analysis of gene expression in samples of skin lesions obtained from humans chronically exposed to arsenic via their drinking water also showed similar alterations in growth factor expression. Although confirmation will be required in nontransgenic mice, these results suggest that arsenic enhances development of skin neoplasias via the chronic stimulation of keratinocyte-derived growth factors and may be a rare example of a chemical carcinogen that acts as a co-promoter. PMID:9846968

Germolec, Dori R.; Spalding, Judson; Yu, Hsin-Su; Chen, G. S.; Simeonova, Petia P.; Humble, Michael C.; Bruccoleri, Alessandra; Boorman, Gary A.; Foley, Julie F.; Yoshida, Takahiko; Luster, Michael I.

1998-01-01

280

Anchoring Hepatic Gene Expression with Development of Fibrosis and Neoplasia in a Toxicant-Induced Fish Model of Liver Injury  

PubMed Central

Fish have been used as laboratory models to study hepatic development and carcinogenesis but not for pathogenesis of hepatic fibrosis. In this study, a dimethylnitrosamine-induced fish model of hepatic injury was developed in Japanese medaka (Oryzias latipes) and gene expression was anchored with the development of hepatic fibrosis and neoplasia. Exposed livers exhibited mild hepatocellular degenerative changes 2 weeks post-exposure. Within six weeks hepatic fibrosis/cirrhosis was evident with development of neoplasia by 10 weeks. Stellate cell activation and development of fibrosis was associated with upregulation of tgfb1,tgfb receptor 2, smad3a, smad3b, ctnnb1, myc, mmp2, mmp14a, mmp14b, timp2a, timp2b, timp3, col1a1a, and col1a1b, and a less pronounced increase in mmp13 and col4a1expression. Tgfb receptor I expression was unchanged. Immunohistochemistry suggested that biliary epithelial cells and stellate cells were the main producers of TGF-?1. This study identified a group of candidate genes likely to be involved in the development of hepatic fibrosis, and demonstrated that the TGF-? pathway likely plays a major role in the pathogenesis. These results support the medaka as a viable fish model of hepatic fibrosis. PMID:23197195

Van Wettere, Arnaud J.; Law, J. Mac; Hinton, David E.; Kullman, Seth W.

2014-01-01

281

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

282

Early onset of neoplasia in the prostate and skin of mice with tissue-specific deletion of Pten  

PubMed Central

PTEN is a tumor suppressor gene mutated in various advanced human neoplasias, including glioblastomas and prostate, breast, endometrial, and kidney cancers. This tumor suppressor is a lipid phosphatase that negatively regulates cell survival and proliferation mediated by phosphatidylinositol 3-kinase/protein kinase B signaling. Using the Cre–loxP system, we selectively inactivated Pten in murine tissues in which the MMTV-LTR promoter is active, resulting in hyperproliferation and neoplastic changes in Pten-null skin and prostate. These phenotypes had early onset and were completely penetrant. Abnormalities in Pten mutant skin consisted of mild epidermal hyperplasia, whereas prostates from these mice exhibited high-grade prostatic intraepithelial neoplasia (HGPIN) that frequently progressed to focally invasive cancer. These data demonstrate that Pten is an important physiological regulator of growth in the skin and prostate. Further, the early onset of HGPIN in Pten mutant males is unique to this animal model and implicates PTEN mutations in the initiation of prostate cancer. Consistent with high PTEN mutation rates in human prostate tumors, these data indicate that PTEN is a critical tumor suppressor in this organ. PMID:14747659

Backman, Stéphanie A.; Ghazarian, Danny; So, Kelvin; Sanchez, Otto; Wagner, Kay-Uwe; Hennighausen, Lothar; Suzuki, Akira; Tsao, Ming-Sound; Chapman, William B.; Stambolic, Vuk; Mak, Tak W.

2004-01-01

283

Neoplasia and Neoplasm Associated Lesions in Laboratory Colonies of Zebrafish Emphasizing Key Influences of Diet and Aquaculture System Design  

PubMed Central

During the past decade the zebrafish has emerged as a leading model for mechanistic cancer research due to its sophisticated genetic and genomic resources, its tractability for tissue targeting of transgene expression, its efficiency for forward genetic approaches to cancer model development, and its cost-effectiveness for enhancer and suppressor screens once a cancer model is established. However, in contrast to other laboratory animal species widely used as cancer models, much basic cancer biology information is lacking in zebrafish. As yet data are not published regarding dietary influences on neoplasm incidences in zebrafish. Little information is available regarding spontaneous tumor incidences or histologic types in wild-type (wt) lines of zebrafish. So far a comprehensive database documenting the full spectrum of neoplasia in various organ systems and tissues in not available for zebrafish as it is for other intensely studied laboratory animal species. This manuscript confirms that as in other species diet and husbandry can profoundly influence tumor incidences and histologic spectra in zebrafish. We show that in many laboratory colonies wt lines of zebrafish exhibit elevated neoplasm incidences and neoplasm associated lesions such as heptocyte megalocytosis. We present experimental evidence showing that certain diet and water management regimens can result in high incidences of neoplasia and neoplasm associated lesions. We document the wide array of benign and malignant neoplasms affecting nearly every organ, tissue and cell type in zebrafish, in some cases as a spontaneous aging change, and in other cases due to carcinogen treatment or genetic manipulation. PMID:23382343

Spitsbergen, Jan M.; Buhler, Donald R.; Peterson, Tracy S.

2014-01-01

284

Disruption of a Sirt1 Dependent Autophagy Checkpoint in the Prostate Results in Prostatic Intraepithelial Neoplasia Lesion Formation  

PubMed Central

The Sirtuin family of proteins (SIRTs) encode a group of evolutionarily conserved, NAD-dependent histone deacetylases, involved in many biological pathways. SIRT1, the human homolog of the yeast Silent Information Regulator 2 (Sir2) gene, deacetylates histones, p300, p53, and the androgen receptor. Autophagy is required for the degradation of damaged organelles and long-lived proteins, as well as for the development of glands such as the breast and prostate. Herein, homozygous deletion of the Sirt1 gene in mice resulted in prostatic intraepithelial neoplasia (PIN) associated with reduced autophagy. Genome-wide gene expression analysis of Sirt1-/- prostates demonstrated that endogenous Sirt1 repressed androgen responsive gene expression and induced autophagy in the prostate. Sirt1 induction of autophagy occurred at the level of autophagosome maturation and completion in cultured prostate cancer cells. These studies provide novel evidence for a checkpoint function of Sirt1 in the development of prostatic intraepithelial neoplasia and further highlight a role for SIRT1 as a tumor suppressor in the prostate. PMID:21189328

Powell, Michael J.; Casimiro, Mathew C.; Cordon-Cardo, Carlos; He, Xiaohong; Yeow, Wen-Shuz; Wang, Chenguang; McCue, Peter A.; McBurney, Michael W.; Pestell, Richard G.

2011-01-01

285

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

286

Array Comparative Genomic Hybridization in Ulcerative Colitis Neoplasia: Single Non-Dysplastic Biopsies Distinguish Progressors from Non-Progressors  

PubMed Central

Approximately 10% of ulcerative colitis patients develop colorectal neoplasia. At present, identification of this subset is markedly limited and necessitates lifelong colonoscopic surveillance for the entire ulcerative colitis population. Better risk markers are needed to focus surveillance onto the patients most likely to benefit. Using array-based comparative genomic hybridization, we analyzed single, non-dysplastic biopsies from three patient groups: ulcerative colitis progressors (n=9) with cancer or high-grade dysplasia at a mean distance of 18 cm from the analyzed site; ulcerative colitis nonprogressors (n=8) without dysplasia during long-term surveillance; and non-ulcerative colitis normal controls (n=2). Genomic DNA from fresh colonic epithelium purified from stroma was hybridized to 287 (low-density) and 4,342 (higher-density) feature bacterial artificial chromosome arrays. Sample-to-reference fluorescence ratios were calculated for individual chromosomal targets and globally across the genome. The low-density arrays yielded pronounced genomic gains and losses in 3 of 9 (33%) ulcerative colitis progressors but in none of the 10 control patients. Identical DNA samples analyzed on the higher density arrays, using a combination of global and individual high variance assessments, distinguished all 9 progressors from all 10 controls. These data confirm that genomic alterations in ulcerative colitis progressors are widespread, even involving single non-dysplastic biopsies far distant from neoplasia. They therefore show promise toward eliminating full colonoscopic surveillance with extensive biopsy sampling in the majority of ulcerative colitis patients. PMID:20802465

Bronner, Mary P.; Skacel, Marek; Crispin, David A.; Hoff, Peter D.; Emond, Mary J.; Lai, Lisa A.; Tubbs, Raymond R.; Rabinovitch, Peter S.; Brentnall, Teresa A.

2010-01-01

287

Autofluorescence imaging and narrow-band imaging for the detection of early neoplasia in patients with Barrett's esophagus.  

PubMed

High-resolution endoscopy (HRE), magnifying endoscopy, auto-fluorescence endoscopy, and narrow-band imaging (NBI) are promising techniques that could improve the detection of early neoplasia and the efficacy of endoscopic surveillance in patients with Barrett's esophagus. HRE improves the detection of lesions by white light, and video autofluorescence imaging (AFI) may have additional value in terms of sensitivity. The strengths ofAFI are its high sensitivity and a high negative predictive value,while potential limitations are its moderate specificity and positive predictive value. NBI enhances the mucosal and vascular patterns (i. e. the mucosal morphology) without the need for chromoendoscopy. The mucosal morphology features may be used to distinguish early neoplasia from nondysplastic Barrett's esophagus. Magnification is required for optimal use of NBI,which is a limitation of this technique. NBI with magnifying endoscopy could, however, be used for targeted inspection of lesions detected first by HRE or AFI. This approach has been shown to reduce the false-positive rate associated with AFI while maintaining its high sensitivity. To date, AFI and NBI have been used separately in two different prototypes, but a prototype endoscope that incorporates all of these techniques has recently become available. It is expected that future refinement of the autofluorescence and narrow-band modules may further increase their diagnostic value and ultimately improve the effectiveness of surveillance of Barrett's esophagus. PMID:16802271

Kara, M A; Bergman, J J

2006-06-01

288

Distribution and pattern of BCL6 mutations throughout the spectrum of B-cell neoplasia  

Microsoft Academic Search

(P F.05), whereas they occur frequently in GC or post-GC neoplasms, including lym- phoplasmacytoid lymphoma, follicular lym- phoma, MALT lymphomas, B-DLCL and Burkitt lymphoma. Among B-DLCL, muta- tions occur frequently in systemic nodal B-DLCL, primary extranodal B-DLCL, CD51 B-DLCL, CD301 B-DLCL, and primary splenic B-DLCL, suggesting a similar histo- genesis of these B-DLCL subsets. Con- versely, mutations are rare in

Daniela Capello; Umberto Vitolo; Laura Pasqualucci; Silvia Quattrone; Giuseppe Migliaretti; Lucia Fassone; Cristiano Ariatti; Daniela Vivenza; Annunziata Gloghini; Cristina Pastore; Carlo Lanza; Josep Nomdedeu; Barbara Botto; Roberto Freilone; Daniela Buonaiuto; Vittorina Zagonel; Eugenio Gallo; Giorgio Palestro; Giuseppe Saglio; Riccardo Dalla-Favera; Antonino Carbone; Gianluca Gaidano

289

Galaxias australes con núcleo doble  

NASA Astrophysics Data System (ADS)

Se estudia una muestra de galaxias australes con núcleo doble a partir de una búsqueda extensiva en la literatura. Se analizan las características morfológicas, fotométricas y espectroscópicas de la muestra. Para algunas galaxias se han realizado observaciones con el espectrógrafo multifunción (EMF) de la Estación Astrofísica de Bosque Alegre a partir de las cuales se determinaron parámetros cinemáticos.

Gimeno, G.; Díaz, R.; Carranza, G.

290

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

291

Pink-color sign in esophageal squamous neoplasia, and speculation regarding the underlying mechanism  

PubMed Central

AIM: To investigate the reasons for the occurrence of the pink-color sign of iodine-unstained lesions. METHODS: In chromoendoscopy, the pink-color sign of iodine-unstained lesions is recognized as useful for the diagnosis of esophageal squamous cell carcinoma. Patients with superficial esophageal neoplasms treated by endoscopic resection were included in the study. Areas of mucosa with and without the pink-color sign were evaluated histologically. The following histologic features that were possibly associated with the pink-color sign were evaluated. The keratinous layer and basal cell layer were classified as present or absent. Cellular atypia was classified as high grade, moderate grade or low grade, based on nuclear irregularity, mitotic figures, loss of polarity, chromatin pattern and nuclear/cytoplasmic ratio. Vascular change was assessed based on dilatation, tortuosity, caliber change and variability in shape. Vessels with these four findings were classified as positive for vascular change. Endoscopic images of the lesions were captured immediately after iodine staining, 2-3 min after iodine staining and after complete fading of iodine staining. Quantitative analysis of color changes after iodine staining was also performed. RESULTS: A total of 61 superficial esophageal neoplasms in 54 patients were included in the study. The lesions were located in the cervical esophagus in one case, the upper thoracic esophagus in 10 cases, the mid-thoracic esophagus in 33 cases, and the lower thoracic esophagus in 17 cases. The median diameter of the lesions was 20 mm (range: 2-74 mm). Of the 61 lesions, 28 were classified as pink-color sign positive and 33 as pink-color sign negative. The histologic diagnosis was high-grade intraepithelial neoplasia (HGIN) or cancer invading into the lamina propria in 26 of the 28 pink-color sign positive lesions. There was a significant association between pink-color sign positive epithelium and HGIN or invasive cancer (P = 0.0001). Univariate analyses found that absence of the keratinous layer and cellular atypia were significantly associated with the pink-color sign. After Bonferroni correction, there were no significant associations between the pink-color sign and presence of the basal membrane or vascular change. Multivariate analyses found that only absence of the keratinous layer was independently associated with the pink-color sign (OR = 58.8, 95%CI: 5.5-632). Quantitative analysis was performed on 10 superficial esophageal neoplasms with both pink-color sign positive and negative areas in 10 patients. Pink-color sign positive mucosa had a lower mean color value in the late phase (pinkish color) than in the early phase (yellowish color), and had similar mean color values in the late and final phases. These findings suggest that pink-color positive mucosa underwent color fading from the color of the iodine (yellow) to the color of the mucosa (pink) within 2-3 min after iodine staining. Pink-color sign negative mucosa had similar mean color values in the late and early phases (yellowish color), and had a lower mean color value in the final phase (pinkish color) than in the late phase. These findings suggest that pink-color sign negative mucosa did not undergo color fading during the 2-3 min after iodine staining, and underwent color fading only after spraying of sodium thiosulfate. CONCLUSION: The pink-color sign was associated with absence of the keratinous layer. This sign may be caused by early fading of iodine staining. PMID:23885140

Ishihara, Ryu; Kanzaki, Hiromitsu; Iishi, Hiroyasu; Nagai, Kengo; Matsui, Fumi; Yamashina, Takeshi; Matsuura, Noriko; Ito, Takashi; Fujii, Mototsugu; Yamamoto, Sachiko; Hanaoka, Noboru; Takeuchi, Yoji; Higashino, Koji; Uedo, Noriya; Tatsuta, Masaharu; Tomita, Yasuhiko; Ishiguro, Shingo

2013-01-01

292

Addition of high-risk HPV testing improves the current guidelines on follow-up after treatment for cervical intraepithelial neoplasia  

Microsoft Academic Search

We assessed a possible role for high-risk human papillomavirus (HPV) testing in the policy after treatment for cervical intraepithelial neoplasia (CIN) 2 or 3 (moderate to severe dysplasia). According to the Dutch guidelines follow-up after treatment consists of cervical cytology at 6, 12 and 24 months. Colposcopy is only performed in case of abnormal cervical cytology. In this observational study

M A E Nobbenhuis; C J L M Meijer; A J C van den Brule; L Rozendaal; F J Voorhorst; E K J Risse; R H M Verheijen; T J M Helmerhorst

2001-01-01

293

Post-transplant malignant neoplasia associated with cyclosporine-based immunotherapy: prevalence, risk factors and survival in feline renal transplant recipients.  

PubMed

The study objective was to compare the prevalence of malignant neoplasia in feline renal transplant recipients (n?=?111) with a control population of cats that did not receive transplantation (n?=?142); and to determine whether the development of post-transplant malignant neoplasia (PTMN) affects long-term survival. Twenty-five (22.5%) renal transplant recipients were diagnosed with PTMN, and of those 14 (56%) were diagnosed with lymphoma. The overall survival time in cats that developed PTMN following renal transplantation (median 646 days, IQR 433-1620 days) was not significantly different from the survival time in cats that did not develop PTMN (median 728 days, IQR 201-1942 days), although median survival after diagnosis of PTMN was only 13 days. Six control cats (4.2%) were diagnosed with malignant neoplasia. Compared to the control population, transplant cats had a 6.6 times higher odds of developing malignant neoplasia and a 6.7 times higher odds of developing lymphoma. PMID:25303015

Wormser, C; Mariano, A; Holmes, E S; Aronson, L R; Volk, S W

2014-10-10

294

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

of the NFI transcription factors in the expression of mammary-gland specific proteins, including whey acidic, whey acidic protein; BLG, -lactoglobulin; STAT, signal transducer and activator of transcription; GRJournal of Mammary Gland Biology and Neoplasia, Vol. 8, No. 2, April 2003 ( C 2003) The Nuclear

Gronostajski, Richard M.

295

THE INDUCTION OF COLORECTAL NEOPLASIA BY A MIXTURE HIGH IN BROMINATED TRIHALOMETHANES (THMS) ADMINISTERED IN THE DRINKING WATER TO MALE F344/N RATS  

EPA Science Inventory

THE INDUCTION OF COLORECTAL NEOPLASIA BY A MIXTURE HIGH IN BROMINA TED TRIHALOMETHANES (THMS) ADMINISTERED IN THE DRINKING W A TER TO MALE F344/N RA TS. Abstract: The THMs are the most widely distributed and concentrated of the chlorine disinfection by-products (D...

296

Ectopic Cushing syndrome secondary to metastatic medullary thyroid cancer in a child with multiple endocrine neoplasia syndrome type 2B: clues to early diagnosis of the paraneoplastic syndromes.  

PubMed

We describe a 13-year-old male with multiple endocrine neoplasia syndrome type 2B with medullary thyroid carcinoma who was diagnosed with ectopic adrenocorticotropin-dependent Cushing syndrome. This report highlights the importance of monitoring for paraneoplastic syndrome in MEN and clues to the diagnosis of this complication provided by growth patterns. PMID:24859505

Singer, Kanakadurga; Heiniger, Nicholas; Thomas, Inas; Worden, Francis P; Menon, Ram K; Chen, Ming

2014-09-01

297

Pigmented squamous intraepithelial neoplasia of the anogenital area: a histopathological and immunohistochemical study of 64 specimens from 45 patients exploring the mechanisms of pigmentation.  

PubMed

Pigmented lesions in the anogenital area encompass a wide variety of disorders including squamous intraepithelial neoplasia. The authors sought to explore the mechanism(s) underlying clinically pigmented squamous intraepithelial neoplasia in the anogenital area. A light-microscopic and immunohistochemical study of 64 lesional specimens from 45 patients (32 women, 13 men; age range, 23-73 years) with pigmented lesions in the anogenital area was performed. Histopathologically, 63 (98%) specimens showed melanin incontinence into the superficial dermis beneath the dysplastic epithelium. A focal or total loss of basilar hyperpigmentation was detected in 30 (48%) and 13 (20%) of lesions, respectively. In 17 (27%) cases, absence of basal layer hyperpigmentation was accompanied by a subepithelial lichenoid infiltrate. Melanin within the upper part of dysplastic areas were seen in 63 cases (98%), whereas dendritic melanocytes colonization, mild in all but 1 specimen case, was observed in 53 (83%) cases. All cases proved to be the usual type of squamous intraepithelial neoplasia; no single case of the simplex (differentiated) variant was present. The main mechanisms of pigmented squamous intraepithelial neoplasia of the anogenital area include melanin incontinence and occurrence of melanin in dysplastic keratinocytes. Colonization of the dysplastic epithelium by dendritic melanocytes seems to contribute, but it is rarely a prominent feature. PMID:24698935

Kacerovska, Denisa; Requena, Luis; Carlson, J Andrew; Santonja, Carlos; Michal, Michal; Bouda, Jiri; Konstantinova, Anastasia M; Kaspirkova, Jana; Fikrle, Tomas; Rotter, Leopold; Kazakov, Dmitry V

2014-06-01

298

mRNA sequencing of novel cell lines from human papillomavirus type-16 related vulval intraepithelial neoplasia: consequences of expression of HPV16 E4 and E5.  

PubMed

Vulval intraepithelial neoplasia is a precursor of vulval cancer and is commonly caused by infection with Human Papillomavirus (HPV). Development of topical treatments for vulval intraepithelial neoplasia requires appropriate in vitro models. This study evaluated the feasibility of primary culture of vulval intraepithelial neoplasia biopsy tissue to produce cell lines for use as in vitro models. A potentially immortal cell line was produced which gave rise to three monoclonal lines. These lines were characterized for HPV genomic integration and for viral gene expression using ligation-mediated PCR and quantitative PCR. Distinct patterns of viral integration and gene expression were observed among the three lines. Integration and expression data were validated using deep sequencing of mRNA. Gene ontology analyses of these data also demonstrated that expression of the HPV16 E4 and E5 proteins resulted in substantial changes in the composition of the cell membrane and extracellular space, associated with alterations in cell adhesion and differentiation. These data illustrate the diverse patterns of HPV gene expression potentially present within a single lesion. The derived cell lines provide useful models to investigate the biology of vulval intraepithelial neoplasia and the interactions between different HPV gene products and potential therapeutic agents. PMID:24898764

Bryant, Dean; Onions, Tiffany; Raybould, Rachel; Flynn, Áine; Tristram, Amanda; Meyrick, Sian; Giles, Peter; Ashelford, Kevin; Hibbitts, Samantha; Fiander, Alison; Powell, Ned

2014-09-01

299

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...

300

Jugando con geometría: Crear secuencias con formas y palabras  

NSDL National Science Digital Library

En esta actividad, los chicos crean secuencias con palabras y formas. Los chicos usan colecciones de triángulos, cuadrados, y rectángulos con palabras adentro. Los chicos organizan las forman en secuencias geométricas que se repiten o que cambian de manera sistemática en cada línea. Los chicos más jóvenes pueden crear secuencias simples; los mayores pueden explorar secuencias que crecen de diferentes maneras. Esta actividad tiene colecciones de palabras en tres niveles de dificultad diferente. Disponible en formato Web y PDF. También disponible en Inglés.

TERC

2012-06-26

301

Preliminary accuracy and interobserver agreement for the detection of intraepithelial neoplasia in Barrett’s esophagus with probe-based confocal laser endomicroscopy  

PubMed Central

Background Confocal laser endomicroscopy (CLE) is a rapidly emerging method for in vivo imaging of the GI tract. Objective To determine the preliminary evaluation accuracy and interobserver agreement of probe-based CLE (pCLE) in Barrett’s esophagus (BE). Design Prospective, double-blind review of pCLE images of 40 sites of BE tissue by using matching biopsies as the reference standard. A training set of 20 images with known histology was first reviewed to standardize image interpretation, followed by blinded review of 20 unknown images. Setting Eleven experts in BE imaging from 4 different endoscopy centers from the United States and Europe evaluated the images. Patients This study involved nonconsecutive patients undergoing BE surveillance or evaluation of high-grade intraepithelial neoplasia or early adenocarcinoma. Intervention Intravenous fluorescein pCLE imaging of each site within the BE segment, followed by matching biopsy. Main Outcome Measurements Sensitivity, specificity, and agreement for the pCLE diagnosis of high-grade intraepithelial neoplasia or carcinoma. Results In the validation set (n = 20), 11 cases had high-grade intraepithelial neoplasia or invasive carcinoma. The sensitivity for the diagnosis of neoplasia for the 11 endoscopists was 88% (range 6 of 11 to 11 of 11), and the specificity was 96% (range 7 of 9 to 9 of 9). There was substantial agreement on the pCLE diagnosis (86%, kappa 0.72; 95% confidence interval, 0.58–0.86). Endomicroscopists with prior pCLE experience had an overall sensitivity of 91% (all 10 of 11), specificity of 100% (all 9 of 9), and almost perfect agreement (92%, kappa 0.83; 95% confidence interval, 0.64–1.0). Limitations Small sample size and use of offline video sequences. Conclusion Results suggest that pCLE for the diagnosis of neoplasia in BE has very high accuracy and reliability. PMID:20381042

Wallace, Michael B.; Sharma, Prateek; Lightdale, Charles; Wolfsen, Herbert; Coron, Emmanuel; Buchner, Anna; Bajbouj, Monther; Bansal, Ajay; Rastogi, Amit; Abrams, Julian; Crook, Julia E.; Meining, Alexander

2011-01-01

302

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

303

Simultaneous bilateral laparoscopic adrenalectomy for pheochromocytoma in multiple endocrine neoplasia (MEN) syndrome: Case report with review literature  

PubMed Central

INTRODUCTION Laparoscopic adrenalectomy has gained favour as a preferred surgical approach in the multiple endocrine neoplasia (MEN) type 2 patients. Currently, there is limited literature on bilateral simultaneous laparoscopic adrenalectomy in MEN 2 syndrome. We reported two cases of bilateral pheochromocytoma associated with MEN 2 syndrome cured by simultaneous bilateral laparoscopic adrenalectomy. PRESENTATION OF CASE First patient presented with big lips since childhood and episodic abdominal pain. On investigations, he was diagnosed with features of MEN 2B syndrome. Second patient was hypertensive and presented with abdominal pain. On evaluation she had features of MEN 2A syndrome. DISCUSSION Minimally invasive approach was preferred in both cases. Bilateral simultaneous adrenalectomies were uneventfully done with acceptable operative time and blood loss with rapid perioperative recovery. These cases highlighted the feasibility of laparoscopic simultaneous bilateral adrenalectomy for pheochromocytomas in MEN 2 syndrome. CONCLUSION Laparoscopic simultaneous bilateral adrenalectomy is a safe feasible and preferable technique for pheochromocytomas associated with MEN 2 syndrome. PMID:24981168

Yadav, Kaushal; Bakshi, Ganesh; Prakash, Gagan; Tamhankar, Anup; Verma, Kamlesh

2014-01-01

304

Exploring the tumors of multiple endocrine neoplasia type 1 in mouse models for basic and preclinical studies  

PubMed Central

Most patients (70–90%) with the multiple endocrine neoplasia type 1 (MEN1) syndrome possess germline heterozygous mutations in MEN1 that predisposes to tumors of multiple endocrine and nonendocrine tissues. Some endocrine tumors of the kinds seen in MEN1 that occur sporadically in the general population also possess somatic mutations in MEN1. Interestingly, the endocrine tumors of MEN1 are recapitulated in mouse models of Men1 loss that serve as a valuable resource to understand the pathophysiology and molecular basis of tumorigenesis. Exploring these endocrine tumors in mouse models using in vivo, ex vivo and in vitro methods can help to follow the process of tumorigenesis, and can be useful for preclinical testing of therapeutics and understanding their mechanisms of action. PMID:25685317

Agarwal, Sunita K

2015-01-01

305

Pheochromocytoma in an 8-year-old patient with Multiple Endocrine Neoplasia Type 2A: Implications for Screening  

PubMed Central

Background Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant hereditary cancer syndrome caused by mutations in the RET proto-oncogene. In patients with MEN 2A and 2B the penetrance of pheochromocytoma is variable and childhood pheochromocytoma in the setting of MEN 2 remains rare. Patient and Intervention We present the case of an 8-year-old female with known MEN 2A, C634Y RET mutation, found to have markedly elevated plasma normetanephrines and total metanephrines, and diagnosed with a 6 cm pheochromocytoma requiring laparoscopic unilateral adrenalectomy. Conclusions Given this patient’s age at diagnosis, current screening guidelines should recommend annual screening beginning at age 8 for patients with MEN 2B or for patients with MEN 2A with codons 630 or 634 RET mutations. PMID:23868299

Rowland, Kathryn J; Chernock, Rebecca D; Moley, Jeffrey F

2014-01-01

306

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

307

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

308

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

309

Cervical Intraepithelial Neoplasia in the "Dr. Salvator Vuia" Clinical Obstetrics and Gynecology Hospital - Arad During the 2000-2009 Period  

PubMed Central

ABSTRACT Objectives: This study intends to analyze some statistical data concerning Cervical Intraepithelial Neoplasia diagnosed in our hospital. Material and Methods: Our study concerning the incidence of Cervical Intraepithelial Neoplasia (CIN) covers the 2000-2009 time-span, the data being collected from the Histopathology Exams (HPE) registers. Results: During this period, CIN lesions were discovered in 1256 cases and Cervical Intraglandular Dysplasia (CIGD) in 53 cases. CIN I, CIN II and CIN III lesions represented 65.92%(828 cases), 19.67% (247 cases), and 14.41% (181 cases) of the total CIN cases, respectively. There were 26 cases combined with cervical carcinoma (2.07% of all CIN cases, 3.56% of the 731 cervical cancer cases). The mean patients' age was 44.65± 9.83 years for all cervical dysplasia cases, 44.58± 9.75 years for all CIN cases, 43.81±9.22, 46.50±10.17, and 45.46±11.05 years for CIN I, CIN II, and CIN III, respectively, and 46.45 ± 11.63 years for CIGD. The t-test revealed the following significant differences: all cases versus CIN I (p<0.05) and CIN II (p<0.01), CIGD versus CIN I (p<0.05), all cases versus CIN II (p<0.01), CIN I versus CIN II (p<0.0001) and versus CIN III (p<0.05). The mean age of the 731 cervical cancer cases diagnosed in our hospital during that same period was 52.94±12.96 years,and it was statistically significantly different from the mean ages of patients with CIN I, II and III (p <0.00000001) and with CIGD (p<0.0005). Conclusions: Early detection of CIN is of utmost importance for preventing cervical cancer, a serious and frequent health problem in Romania. PMID:23399814

DASCAU, Voicu; FURAU, Gheorghe; FURAU, Cristian; PAIUSAN, Lucian; RADU, Adriana; STANESCU, Casiana

2012-01-01

310

Identification of Susceptibility Genes for Cancer in a Genome-wide Scan: Results from the Colon Neoplasia Sibling Study  

PubMed Central

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in Americans and is the second leading cause of cancer mortality. Only a minority (?5%) of familial CRC can be explained by known genetic variants. To identify susceptibility genes for familial colorectal neoplasia, the colon neoplasia sibling study conducted a comprehensive, genome-wide linkage scan of 194 kindreds. Clinical information (histopathology, size and number of polyps, and other primary cancers) was used in conjunction with age at onset and family history for classification of the families into five phenotypic subgroups (severe histopathology, oligopolyposis, young, colon/breast, and multiple cancer) prior to analysis. By expanding the traditional affected-sib-pair design to include unaffected and discordant sib pairs, analytical power and robustness to type I error were increased. Sib-pair linkage statistics and Haseman-Elston regression identified 19 linkage peaks, with interesting results for chromosomes 1p31.1, 15q14-q22, 17p13.3, and 21. At marker D1S1665 (1p31.1), there was strong evidence for linkage in the multiple-cancer subgroup (p = 0.00007). For chromosome 15q14-q22, a linkage peak was identified in the full-sample (p = 0.018), oligopolyposis (p = 0.003), and young (p = 0.0009) phenotypes. This region includes the HMPS/CRAC1 locus associated with hereditary mixed polyposis syndrome (HMPS) in families of Ashkenazi descent. We provide compelling evidence linking this region in families of European descent with oligopolyposis and/or young age at onset (?51) phenotypes. We found linkage to BRCA2 in the colon/breast phenotypic subgroup and identified a second locus in the region of D21S1437 segregating with, but distinct from, BRCA2. Linkage to 17p13.3 at marker D17S1308 in the breast/colon subgroup identified HIC1 as a candidate gene. We demonstrated that using clinical information, unaffected siblings, and family history can increase the analytical power of a linkage study. PMID:18313025

Daley, Denise; Lewis, Susan; Platzer, Petra; MacMillen, Melissa; Willis, Joseph; Elston, Robert C.; Markowitz, Sanford D.; Wiesner, Georgia L.

2008-01-01

311

Anal intraepithelial neoplasia in a multisite study of HIV-infected and high-risk HIV-uninfected women  

PubMed Central

Objectives To study anal intraepithelial neoplasia (AIN) and its associations with anal and cervical human papillomavirus (HPV), cervical neoplasia, host immune status, and demographic and behavioral risk factors in women with and at risk for HIV infection. Design Point-prevalence analysis nested within a prospective study of women seen at three clinical centers of the Women’s Interagency HIV Study. Methods In 2001-2003 participants were interviewed, received a gynecological examination, anal and cervical cytology testing and, if abnormal, colposcopy or anoscopy-guided biopsy of visible lesions. Exfoliated cervical and anal specimens were assessed for HPV using PCR and type-specific HPV probing. Logistic regression analyses were performed and odds ratios (OR) estimated risks for AIN. Results 470 HIV-infected and 185 HIV-uninfected women were enrolled. Low-grade AIN (LGAIN) was present in 12% of HIV-infected and 5% of HIV-uninfected women. High-grade AIN (HGAIN) was present in 9% of HIV-infected and 1% of HIV-uninfected women. In adjusted analyses among HIV-infected women, the risk factors for LGAIN were younger age (OR=0.59, 95%CI=0.36-0.97), history of receptive anal intercourse (OR=3.2, 95%CI=1.5-6.8), anal HPV (oncogenic types only OR=11, 95%CI=1.2-103; oncogenic and non-oncogenic types OR=11, 95%CI=1.3-96), and cervical HPV (oncogenic and non-oncogenic types OR=3.5, 95%CI=1.1-11). In multivariable analyses among HIV-infected women, the only significant risk factor for HGAIN was anal HPV infection (oncogenic and non-oncogenic types OR=7.6, 95%CI=1.5-38). Conclusions Even in the era of highly active antiviral therapy, the prevalence of AIN was 16% in HIV-infected women. After controlling for potential confounders, several risk factors for LGAIN differed from risk factors for HGAIN. PMID:19050387

Hessol, Nancy A.; Holly, Elizabeth A.; Efird, Jimmy T.; Minkoff, Howard; Schowalter, Karlene; Darragh, Teresa M.; Burk, Robert D.; Strickler, Howard D.; Greenblatt, Ruth M.; Palefsky, Joel M.

2008-01-01

312

The value of anal cytology and human papillomavirus typing in the detection of anal intraepithelial neoplasia: a review of cases from an anoscopy clinic  

Microsoft Academic Search

Background: Previous studies have reached differing conclusions about the utility of anal cytology as a screening tool for anal intraepithelial neoplasia (AIN). There is a need also to establish whether HPV typing offers a useful adjunct to screening.Methods: We analysed data from 99 consecutive homosexual\\/bisexual male patients (89 HIV-1 positive) who underwent high resolution anoscopy. Follow up visits for these

P A Fox; J E Seet; J Stebbing; N Francis; S E Barton; S Strauss; T G Allen-Mersh; B G Gazzard; M Bower

2005-01-01

313

Loss of Heterozygosity on Chromosome 11q13 in Two Families with Acromegaly\\/Gigantism Is Independent of Mutations of the Multiple Endocrine Neoplasia Type I Gene  

Microsoft Academic Search

Familial acromegaly\\/gigantism occurring in the absence of multi- ple endocrine neoplasia type I (MEN-1) or the Carney complex has been reported in 18 families since the biochemical diagnosis of GH excess became available, and the genetic defect is unknown. In the present study we examined 2 unrelated families with isolated acro- megaly\\/gigantism. In family A, 3 of 4 siblings were

MONICA R. GADELHA; TONI R. PREZANT; KARINA N. UNE; ROBERTA P. GLICK; STANLEY F. MOSKAL; MARIO VAISMAN; SHLOMO MELMED; RHONDA D. KINEMAN; LAWRENCE A. FROHMAN

314

The association between fruit and vegetable consumption and HPV viral load in high-risk HPV-positive women with cervical intraepithelial neoplasia  

Microsoft Academic Search

We evaluated the relationship between the dietary intake of vegetables and fruits, and the risk of cervical intraepithelial\\u000a neoplasia (CIN) and determined whether these associations were modified by human papillomavirus (HPV) viral load. We enrolled\\u000a 1,096 women aged 18–65 to participate in a HPV cohort study from March 2006 up to present. For this analysis, we included\\u000a 328 HPV-positive women

Jong Ha Hwang; Jae Kwan Lee; Tae Jin Kim; Mi Kyung Kim

2010-01-01

315

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

316

Multiple endocrine neoplasia type 2 with malignant pheochromocytoma — Long term follow-up of a case by 131 I-meta-iodobenzylguanidine scintigraphy—  

Microsoft Academic Search

The case of a 33-year-old Japanese man, who has Multiple Endocrine Neoplasia Type 2 (MEN IIa) (Sipple’s syndrome) with malignant\\u000a pheochromocytoma, is reported. He had survived for twelve years since the initial diagnosis of malignant pheochromocytoma.\\u000a Within this period, he had undergone131I-meta-iodobenzylguanidine scintigraphy twice, in 1983 and 1990. This is the first case in Japan of a longterm surviving patient

Hiroyuki Namba; Hideaki Kondo; Shunichi Yamashita; Hironori Kimura; Naokata Yokoyama; Masako Tsuruta; Akira Sato; Motomori Izumi; Hirofumi Kinoshita; Satomi Hakariya; Kuniaki Hayashi; Shigenobu Nagataki

1992-01-01

317

Effect of lansoprazole versus roxatidine on prevention of bleeding and promotion of ulcer healing after endoscopic submucosal dissection for superficial gastric neoplasia  

Microsoft Academic Search

Background  Proton pump inhibitors have been reported to be more useful than histamine-2 receptor antagonists for the prevention of bleeding\\u000a after endoscopic submucosal dissection (ESD) for superficial gastric neoplasia. The aim of this study was to assess the effects\\u000a of the proton pump inhibitor lansoprazole and the histamine-2 receptor antagonist roxatidine for the prevention of bleeding\\u000a and the promotion of ulcer

Hiroyuki Imaeda; Naoki Hosoe; Hidekazu Suzuki; Yoshimasa Saito; Yosuke Ida; Rieko Nakamura; Yasushi Iwao; Haruhiko Ogata; Toshifumi Hibi

318

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

319

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

320

Compatibilidad con audfonos para sordos  

E-print Network

Compatibilidad con audífonos para sordos Hearing Aid Compatibility Q&A Q. What does hearing aid the different features of the phone thoroughly and in different locations, using your hearing aid or cochlear implant, to determine if you hear any interfering noise. Consult a sales representative about phone return

Greenberg, Albert

321

Evaluation of DNA Single and Double Strand Breaks in Women with Cervical Neoplasia Based on Alkaline and Neutral Comet Assay Techniques  

PubMed Central

A hospital-based unmatched case-control study was performed in order to determine the relation of DNA single (ssb) and double (dsb) strand breaks in women with and without cervical neoplasia. Cervical epithelial cells of 30 women: 10 with low grade squamous intraepithelial lesions (LG-SIL), 10 with high-grade SIL (HG-SIL), and 10 without cervical lesions were evaluated using alkaline and neutral comet assays. A significant increase in global DNA damage (ssb + dsb) and dsb was observed in patients with HG-SIL (48.90 ± 12.87 and 23.50 ± 13.91), patients with LG-SIL (33.60 ± 14.96 and 11.20 ± 5.71), and controls (21.70 ± 11.87 and 5.30 ± 5.38; resp.). Pearson correlation coefficient reveled a strong relation between the levels ssb and dsb (r2 = 0.99, P = 0.03, and r2 = 0.94, P = 0.16, resp.) and progression of neoplasia. The increase of dsb damage in patients with HG-SIL was confirmed by DNA breakage detection-FISH (DBD-FISH) on neutral comets. Our results argue in favor of a real genomic instability in women with cervical neoplasia, which was strengthened by our finding of a higher proportion of DNA dsb. PMID:23093842

Cortés-Gutiérrez, Elva I.; Hernández-Garza, Fernando; García-Pérez, Jorge O.; Dávila-Rodríguez, Martha I.; Aguado-Barrera, Miguel E.; Cerda-Flores, Ricardo M.

2012-01-01

322

Genital and cutaneous human papillomavirus (HPV) types in relation to conjunctival squamous cell neoplasia: A case-control study in Uganda  

PubMed Central

Background We investigated the role of infection with genital and cutaneous human papillomavirus types (HPV) in the aetiology of ocular surface squamous neoplasia (which includes both conjunctival intraepithelial neoplasia (CIN) and carcinoma) using data and biological material collected as part of a case-control study in Uganda. Results Among 81 cases, the prevalence of genital and cutaneous HPV types in tumour tissue did not differ significantly by histological grade of the lesion. The prevalence of genital HPV types did not differ significantly between cases and controls (both 38%; Odds ratio [OR] 1.0, 95% confidence interval [CI] 0.4–2.7, p = 1.0). The prevalence of cutaneous HPV types was 22% (18/81) among cases and 3% (1/29) among controls (OR 8.0, 95% CI 1.0–169, p = 0.04). Conclusion We find no evidence of an association between genital HPV types and ocular surface squamous neoplasia. The prevalence of cutaneous HPV was significantly higher among cases as compared to controls. Although consistent with results from two other case-control studies, the relatively low prevalence of cutaneous HPV types among cases (which does not differ by histological grade of tumour) indicates that there remains considerable uncertainty about a role for cutaneous HPV in the aetiology of this tumour. PMID:18783604

de Koning, Maurits NC; Waddell, Keith; Magyezi, Joseph; Purdie, Karin; Proby, Charlotte; Harwood, Catherine; Lucas, Sebastian; Downing, Robert; Quint, Wim GV; Newton, Robert

2008-01-01

323

Dvl2 promotes intestinal length and neoplasia in the ApcMin mouse model for colorectal cancer  

PubMed Central

APC mutations cause activation of Wnt/?-catenin signalling, which invariably leads to colorectal cancer. Similarly, overexpressed Dvl proteins are potent activators of ?-catenin signalling. Screening a large tissue microarray of different staged colorectal tumours by immunohistochemistry, we found that Dvl2 has a strong tendency to be overexpressed in colorectal adenomas and carcinomas, in parallel to nuclear ?-catenin and Axin2 (a universal transcriptional target of Wnt/?-catenin signalling). Furthermore, deletion of Dvl2 reduced the intestinal tumor numbers in a dose-dependent way in the ApcMin model for colorectal cancer. Interestingly, the small intestines of Dvl2 mutants are shortened, reflecting in part a reduction of their crypt diameter and cell size. Consistent with this, mTOR signalling is highly active in normal intestinal crypts where Wnt/?-catenin signalling is active, and activated mTOR signalling (as revealed by staining for phosphorylated 4E-BP1) serves as a diagnostic marker of ApcMin mutant adenomas. Inhibition of mTOR signalling in ApcMin mutant mice by RAD001 (everolimus) reduces their intestinal tumour load, similarly to Dvl2 deletion. mTOR signalling is also consistently active in human hyperplastic polyps, and has a significant tendency for being active in adenomas and carcinomas. Our results implicate Dvl2 and mTOR in the progression of colorectal neoplasia and highlight their potential as therapeutic targets in colorectal cancer. PMID:20663899

Metcalfe, Ciara; Ibrahim, Ashraf E. K.; Graeb, Michael; de la Roche, Marc; Schwarz-Romond, Thomas; Fiedler, Marc; Winton, Douglas J.; Corfield, Anthony; Bienz, Mariann

2010-01-01

324

Prevalence and risk factors of sexually transmitted infections and cervical neoplasia in women's health clinics in Nicaragua  

PubMed Central

Methods: Consecutive women attending women's health clinics in different regions were interviewed and examined for STI, HIV, and cervical neoplasia. Results: Whereas only 30.4% of the 1185 participating women attended the clinics because of STI related complaints, 77.0% reported symptoms after probing. Clinical cervicitis was diagnosed in 32.8%, Chlamydia trachomatis in 4.1%, gonorrhoea in 0.4%, trichomoniasis in 10.2%. Antibodies for syphilis were found in 0.7%, for hepatitis B in 3.7%, and none were HIV seropositive. The STI prevalence was 21.8% in women attending with complaints, 17.3% in symptomatic women after probing, and 14.8% in asymptomatic women. Abnormal Papanicolaou (Pap) smears were found in 7.7%, with high risk human papilloma virus (HPV) types in almost 60%. Male promiscuity was associated with high grade squamous intraepithelial lesions (HSIL) and reported former screening was not shown to be protective. Young age and being employed were risk factors for C trachomatis. Conclusion: Nearly one out of five women attending women's health clinics in Nicaragua had an STI, and one out of 13 a precancerous lesion of the cervix. These clinics provide an opportunity to improve the reproductive health of women by probing for STI symptoms, especially in young women, and by offering cervical screening to casual attendees. Of concern is the high rate of cervical lesions in women with a screening history, underlining the need for proper quality control. PMID:12238655

Claeys, P; Gonzalez, C; Gonzalez, M; Van Renterghem, L; Temmerman, M

2002-01-01

325

[Between anxiety and hope: the experiences of women with vulval intraepithelial neoplasia during their illness trajectory - a qualitative approach].  

PubMed

The vulvar intraepithelial neoplasia (VIN) is a rare chronic skin condition that may progress to an invasive carcinoma of the vulva. Major issues affecting women's health were occurring symptoms, negative influences on sexuality, uncertainty concerning the illness progression and changes in the body image. Despite this, there is little known about the lived experiences of the illness trajectory. Therefore, the aim of this study was to describe the experiences of women with VIN during the illness trajectory. In a secondary data analysis of the foregoing qualitative study we analysed eight narrative interviews with women with VIN by using thematic analysis in combination with critical hermeneutics. Central for these women during their course of illness was a sense of "Hope and Fear". This constitutive pattern reflects the fear of recurrence but also the trust in healing. The eight narratives showed women's experiences during their course of illness occurred in five phases: "there is something unknown"; "one knows, what IT is"; "IT is treated and should heal"; "IT has effects on daily life"; "meanwhile it works". Women's experiences were particularly influenced by the feeling of "embarrassment" and by "dealing with professionals". Current care seems to lack adequate support for women with VIN to manage these phases. We suggest, based on our study and the international literature, that new models of counselling and providing information need to be developed and evaluated. PMID:23535473

Gafner, Dinah; Eicher, Manuela; Spirig, Rebecca; Senn, Beate

2013-04-01

326

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

327

Dissecting Molecular Events in Thyroid Neoplasia Provides Evidence for Distinct Evolution of Follicular Thyroid Adenoma and Carcinoma  

PubMed Central

Benign hypofunctional cold thyroid nodules (CTNs) are a frequent scintiscan finding and need to be distinguished from thyroid carcinomas. The origin of CTNs with follicular morphologic features is unresolved. The DNA damage response might act as a physiologic barrier, inhibiting the progression of preneoplastic lesions to neoplasia. We investigated the following in hypofunctional follicular adenoma (FA) and follicular thyroid cancer (FTC): i) the mutation rate of frequently activated oncogenes, ii) the activation of DNA damage response checkpoints, and iii) the differential proteomic pattern between FA and FTC. Both FTC and FA, which did not harbor RAS, phosphoinositide-3-kinase, or PAX/peroxisome proliferator activated receptor-? mutations, express various proteins in common and others that are more distinctly expressed in FTC rather than in FA or normal thyroid tissue. This finding is in line with the finding of constitutive DNA damage checkpoint activation (p-Chk2, ?-H2AX) and evidence for replicative stress causing genomic instability (increased cyclin E, retinoblastoma, or E2F1 mRNA expression) in FTC but not FA. We discuss the findings of the increased expression of translationally controlled tumor protein, phosphatase 2A inhibitor, and DJ-1 in FTC compared with FA identified by proteomics and their potential implication in follicular thyroid carcinogenesis. Our present findings argue for the definition of FA as a truly benign entity and against progressive development of FA to FTC. PMID:21983636

Krause, Kerstin; Prawitt, Susanne; Eszlinger, Markus; Ihling, Christian; Sinz, Andrea; Schierle, Katrin; Gimm, Oliver; Dralle, Henning; Steinert, Frank; Sheu, Sien-Yi; Schmid, Kurt W.; Fuhrer, Dagmar

2011-01-01

328

A subset of familial colorectal neoplasia kindreds linked to chromosome 9q22.2-31.2  

PubMed Central

Colorectal cancer is the second most leading cause of cancer death among adult Americans. Two autosomal dominant hereditary forms of the disease, familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, together account for perhaps 5% of all cases. However, in ?20% of additional colon cancer cases, the affected individuals report a family history of colon cancer in a first-degree relative. Similar familial clusters of colon cancer and early-onset colon adenomas have also been reported. To determine whether such familial aggregations arise by chance or reflect a hereditary colon cancer susceptibility, we conducted a whole genome scan to test for genetic linkage in 53 kindreds in which two or more siblings were affected by age 65 or younger with colon cancer or with advanced colon adenomas that were >1 cm in size or that showed high-grade dysplasia. In this cohort we found genetic linkage of disease (P = 0.00045) to chromosomal region 9q22.2-31.2 in a pattern consistent with autosomal dominant disease alleles. These data suggest that a single locus can contribute to disease susceptibility in a subset of patients with nonsyndromic forms of familial colorectal neoplasia. PMID:14566058

Wiesner, Georgia L.; Daley, Denise; Lewis, Susan; Ticknor, Christine; Platzer, Petra; Lutterbaugh, James; MacMillen, Melissa; Baliner, Boris; Willis, Joseph; Elston, Robert C.; Markowitz, Sanford D.

2003-01-01

329

Differential expression of keratins 10, 17, and 19 in normal cervical epithelium, cervical intraepithelial neoplasia, and cervical carcinoma.  

PubMed Central

AIM: To examine the value of immunohistochemistry in defining a keratin profile to aid cervical histopathological diagnosis. METHODS: Immunohistochemical localisation of keratins 17, 10, and 19 was studied in 268 cervical biopsies from 216 women including normal epithelia (with and without human papilloma virus), low and high grade cervical intraepithelial neoplasia, and invasive carcinoma. The percentage of positive immunostaining was scored using a Kontron MOP videoplan image analyser. RESULTS: All major categories of cervical epithelia expressed these keratins to varying degrees. The median percentage of immunostaining for keratin 10 was 40% in normal tissue compared with just 1% in invasive carcinoma (p < 0.0001). The medians for keratin 17 were 0% in the normal group and 80% in carcinomas (p < 0.0001). By contrast, there was no significant difference in staining for keratin 19. Using a combination of the keratin 10 and 17 percentages, it was possible to separate the carcinomas from the benign conditions with a sensitivity of 100% and a specificity of 93%. Further analyses within the groups revealed more extensive staining for keratins 10 and 19 in reserve cell hyperplasia, immature squamous metaplasia, and congenital transformation zone. CONCLUSIONS: The morphological variety within the cervix is reflected, in part, by distinct keratin patterns. There are striking differences in the patterns of keratins 10 and 17 between infiltrating squamous carcinoma and normal cervical epithelia. PMID:10343611

Maddox, P; Sasieni, P; Szarewski, A; Anderson, M; Hanby, A

1999-01-01

330

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

331

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

332

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

333

An Intelligent Clinical Decision Support System for Patient-Specific Predictions to Improve Cervical Intraepithelial Neoplasia Detection  

PubMed Central

Nowadays, there are molecular biology techniques providing information related to cervical cancer and its cause: the human Papillomavirus (HPV), including DNA microarrays identifying HPV subtypes, mRNA techniques such as nucleic acid based amplification or flow cytometry identifying E6/E7 oncogenes, and immunocytochemistry techniques such as overexpression of p16. Each one of these techniques has its own performance, limitations and advantages, thus a combinatorial approach via computational intelligence methods could exploit the benefits of each method and produce more accurate results. In this article we propose a clinical decision support system (CDSS), composed by artificial neural networks, intelligently combining the results of classic and ancillary techniques for diagnostic accuracy improvement. We evaluated this method on 740 cases with complete series of cytological assessment, molecular tests, and colposcopy examination. The CDSS demonstrated high sensitivity (89.4%), high specificity (97.1%), high positive predictive value (89.4%), and high negative predictive value (97.1%), for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In comparison to the tests involved in this study and their combinations, the CDSS produced the most balanced results in terms of sensitivity, specificity, PPV, and NPV. The proposed system may reduce the referral rate for colposcopy and guide personalised management and therapeutic interventions. PMID:24812614

Bountris, Panagiotis; Haritou, Maria; Pouliakis, Abraham; Margari, Niki; Kyrgiou, Maria; Spathis, Aris; Pappas, Asimakis; Panayiotides, Ioannis; Paraskevaidis, Evangelos A.; Karakitsos, Petros; Koutsouris, Dimitrios-Dionyssios

2014-01-01

334

A case of Zollinger-Ellison syndrome in multiple endocrine neoplasia type 1 with urolithiasis as the initial presentation.  

PubMed

Zollinger-Ellison syndrome (ZES) is characterized by gastrinoma and resultant hypergastrinemia, which leads to recurrent peptic ulcers. Because gastrinoma is the most common pancreatic endocrine tumor seen in multiple endocrine neoplasia type I (MEN 1), the possibility of gastrinoma should be investigated carefully when patients exhibit symptoms associated with hormonal changes. Ureteral stones associated with hyperparathyroidism in the early course of MEN 1 are known to be its most common clinical manifestation; appropriate evaluation and close follow-up of patients with hypercalcemic urolithiasis can lead to an early diagnosis of gastrinoma. We report a patient with ZES associated with MEN 1, and urolithiasis as the presenting entity. A 51-year-old man visited the emergency department with recurrent epigastric pain. He had a history of calcium urinary stone 3 years ago, and 2 years later he had 2 operations for multiple jejunal ulcer perforations; these surgeries were 9 months apart. He was taking intermittent courses of antiulcer medication. Multiple peripancreatic nodular masses, a hepatic metastasis, parathyroid hyperplasia, and a pituitary microadenoma were confirmed by multimodal imaging studies. We diagnosed ZES with MEN 1 and performed sequential surgical excision of the gastrinomas and the parathyroid adenoma. The patient received octreotide injection therapy and close follow-up. PMID:23877214

Lee, Na Eun; Lee, Young Jae; Yun, So Hee; Lee, Jae Un; Park, Moon Sik; Kim, Joong Keun; Kim, Ji Woong; Cho, Jin Woong

2013-06-01

335

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

336

Ependymoma and Carcinoid Tumor Associated with Ovarian Mature Cystic Teratoma in a Patient with Multiple Endocrine Neoplasia I  

PubMed Central

Ovarian teratomas rarely undergo new neoplastic transformation and account for a small percentage of malignant ovarian germ cell neoplasms. Here we report a case of a 51-year-old woman with multiple endocrine neoplasia type I (MEN I) who was found to have an ependymoma and neuroendocrine tumor (trabecular carcinoid) associated with mature cystic teratoma of her left ovary. The ependymoma component displayed cells with round nuclei and occasional small nucleoli which were focally arranged in perivascular pseudorosettes and true rosettes. Rare mitoses were identified. No necrosis was present. Immunohistochemical staining was positive for S-100 and GFAP. The Ki67 proliferation index was very low (2-3%). In contrast, the endocrine tumor component was composed of small uniform cells with eosinophilic cytoplasm, round nuclei, and speckled chromatin. Immunohistochemical staining was positive for synaptophysin and focally positive for chromogranin. This rare case illustrates that MEN I may have an influence on the pathogenesis of ovarian teratomas as they undergo malignant transformation. PMID:24818031

Spaulding, Reed; Alatassi, Houda; Stewart Metzinger, Daniel; Moghadamfalahi, Mana

2014-01-01

337

The Multiple Endocrine Neoplasia Type 1 (MEN1) Tumor Suppressor Regulates Peroxisome Proliferator-Activated Receptor ?-Dependent Adipocyte Differentiation?  

PubMed Central

Menin, the product of the MEN1 (multiple endocrine neoplasia type 1) tumor suppressor gene, is involved in activation of gene transcription as part of an MLL1 (mixed-lineage leukemia 1)/MLL2 (KMT2A/B)-containing protein complex which harbors methyltransferase activity for lysine 4 of histone H3 (H3K4). As MEN1 patients frequently develop lipomas and peroxisome proliferator-activated receptor ? (PPAR?) is expressed in several MEN1-related tumor types, we investigated regulation of PPAR? activity by menin. We found that menin is required for adipocyte differentiation of murine 3T3-L1 cells and PPAR?-expressing mouse embryonic fibroblasts. Menin augments PPAR? target gene expression through recruitment of H3K4 methyltransferase activity. Menin interacts directly with the activation function 2 transcription activation domain of PPAR? in a ligand-independent fashion. Ligand-dependent coactivation, however, is dependent on the LXXLL motif of menin and the intact helix 12 of PPAR?. We propose that menin is an important factor in PPAR?-mediated adipogenesis and that loss of PPAR? function may contribute to lipoma development in MEN1 patients. PMID:19596783

Dreijerink, Koen M. A.; Varier, Radhika A.; van Beekum, Olivier; Jeninga, Ellen H.; Höppener, Jo W. M.; Lips, Cornelis J. M.; Kummer, J. Alain; Kalkhoven, Eric; Timmers, H. T. Marc

2009-01-01

338

Intra-ampullary Papillary-Tubular Neoplasm (IAPN): Characterization of Tumoral Intraepithelial Neoplasia Occurring Within the Ampulla  

PubMed Central

Background There has been no uniform terminology for systematic analysis of mass-forming preinvasive neoplasms (which we term tumoral intraepithelial neoplasia) that occur specifically within the ampulla. Here, we provide a detailed analysis of these neoplasms, which we propose to refer to as intra-ampullary papillary-tubular neoplasm (IAPN). Materials and Methods Three hundred and seventeen glandular neoplasms involving the ampulla were identified through a review of 1469 pancreatoduodenectomies and 11 ampullectomies. Eighty-two neoplasms characterized by substantial preinvasive exophytic component that grew almost exclusively (>75%) within the ampulla (in the ampullary channel or intraampullary portions of the very distal segments of the common bile duct or pancreatic duct) were analyzed. Results (1) Clinical: The mean age was 64 years, male/female ratio was 2.4, and mean tumor size was 2.7 cm. (2) Pathology: The tumors had a mixture of both papillary and tubular growth (each constituting at least 25% of the lesion) in 57%; predominantly (>75%) papillary in 23%, and predominantly (>75%) tubular in 20%. High-grade dysplasia was present in 94% of cases, of which 39% showed focal (<25% of the lesion), 28% showed substantial (25% to 75%), and 27% showed extensive (>75%) high-grade dysplasia. In terms of cell-lineage morphology, 45% had a mixture of patterns. However, when evaluated with a forced-binary approach as intestinal (INT) versus gastric/pancreatobiliary (GPB) based on the predominant pattern, 74% were classified as INT and 26% as GPB. (3) Immunohistochemistry: Percent sensitivity/specificity of cell-lineage markers were, for INT phenotype: MUC2 85/78 and CDX2 94/61; and for GBP: MUC1 89/79, MUC5AC 95/69, and MUC6 83/76, respectively. Cytokeratin 7 and 20 were coexpressed in more than half. (4) Invasive carcinoma: In 64 cases (78%), there was an associated invasive carcinoma. Size of the tumor and amount of dysplasia correlated with the incidence of invasion. Invasive carcinoma was of INT-type in 58% and of pancreatobiliary-type in 42%. Cell lineage in the invasive component was the same as that of the preinvasive component in 84%. All discrepant cases were pancreatobiliary-type invasions, which occurred in INT-type preinvasive lesions. (5) Outcome: The overall survival of invasive cases were significantly worse than that of noninvasive ones (57% vs. 93%; P = 0.01); and 3 years, 69% versus 100% (P = 0.08); and 5 years, 45% versus 100% (P = 0.07), respectively. When compared with 166 conventional invasive carcinomas of the ampullary region, invasive IAPNs had significantly better prognosis with a mean survival of 51 versus 31 months (P<0.001) and the 3-year survival of 69% versus 44% (P<0.01). Conclusions Tumoral intraepithelial neoplasia occurring within the ampulla are highly analogous to pancreatic or biliary intraductal papillary and tubular neoplasms as evidenced by their papillary and/or tubular growth, variable cell lineage, and spectrum of dysplastic change (adenoma-carcinoma sequence), and thus we propose to refer to these as IAPN. IAPNs are biologically indolent; noninvasive examples show an excellent prognosis, whereas those with invasion exhibit a malignant but nevertheless significantly better prognosis than typical invasive ampullary carcinomas unaccompanied by IAPNs. Twenty eight percent (64 of 230) of invasive carcinomas within the ampulla arise in association with IAPNs. PMID:21084962

Ohike, Nobuyuki; Kim, Grace E.; Tajiri, Takuma; Krasinskas, Alyssa; Basturk, Olca; Coban, Ipek; Bandyopadhyay, Sudeshna; Morohoshi, Toshio; Goodman, Michael; Kooby, David A.; Sarmiento, Juan M.; Adsay, N. Volkan

2011-01-01

339

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

340

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

341

TMPRSS2:ERG Gene Fusion Predicts Subsequent Detection of Prostate Cancer in Patients With High-Grade Prostatic Intraepithelial Neoplasia  

PubMed Central

Purpose High-grade prostatic intraepithelial neoplasia (HGPIN) is considered a precursor lesion of prostate cancer (PCa). The predictive value of ERG gene fusion in HGPIN for PCa was interrogated as a post hoc analysis in the context of a randomized clinical trial. Patients and Methods The GTx Protocol G300104 randomly assigned 1,590 men with biopsy-diagnosed HGPIN to receive toremifene or placebo for 3 years or until a diagnosis of PCa was made on prostate biopsy. As part of this phase III clinical trial, a central pathologist evaluated biopsies of patients with isolated HGPIN at baseline and 12, 24, and 36 months of follow-up. ERG immunohistochemistry was performed on biopsies from 461 patients and evaluated for protein overexpression. Results ERG expression was detected in 11.1% of patients (51 of 461 patients) with isolated HGPIN. In the first year and during the 3-year clinical trial, 14.7% and 36.9% of 461 patients were diagnosed with PCa, respectively. Patients with ERG expression were more likely to develop PCa, with 27 (53%) of 51 ERG-positive and 143 (35%) of 410 ERG-negative patients experiencing progression to PCa (P = .014, Fisher's exact test). ERG expression was not associated with age, baseline PSA, Gleason score, or tumor volume. Conclusion This study underscores the necessity of more stringent follow-up for men with HGPIN that is also positive for ERG overexpression. Clinicians should consider molecular characterization of HGPIN as a means to improve risk stratification. PMID:24297949

Park, Kyung; Dalton, James T.; Narayanan, Ramesh; Barbieri, Christopher E.; Hancock, Michael L.; Bostwick, David G.; Steiner, Mitchell S.; Rubin, Mark A.

2014-01-01

342

Multiple endocrine neoplasia type 1 associated with breast cancer: A case report and review of the literature  

PubMed Central

Multiple endocrine neoplasia type 1 (MEN1) is a cancer predisposition syndrome that includes a combination of endocrine and non-endocrine tumors. The present study reports a rare case of MEN1 associated with breast cancer with the MEN1 gene mutation. A 45-year-old female was diagnosed with breast cancer subsequent to presenting with a right breast mass. Pre-operative radiological studies indicated right breast cancer with a suspicious metastatic nodule of the lung. Further studies demonstrated bilateral thyroid nodules, a neuroendocrine tumor of the pancreas, paraganglioma, a left adrenal adenoma, gallstones, uterine subserosal myoma and pituitary macroadenoma. Laboratory examinations revealed hypercalcemia, hypophosphatemia and an increased intact parathyroid hormone level. The workup for the suspected MEN syndrome revealed an increased basal plasma level of insulin-like growth factor-1, prolactin and calcitonin, and an increased 24-h urinary free cortisol level. The patient underwent surgical removal of the breast cancer and the tumors of the pancreas, adrenal gland, thyroid and parathyroid glands, uterus, anterior mediastinum and lung. The pathological diagnosis of the resected breast was of invasive ductal carcinoma. Otherwise the pathological diagnosis was of calcitonin-producing pancreatic endocrine carcinoma, adrenal cortical adenoma, bilateral papillary thyroid carcinomas, parathyroid adenomas, uterine leiomyoma with adenomyosis, a thymic carcinoid tumor and lung hamatoma. Gene analysis was performed to determine the association between gene mutations and the development of tumors in this patient, and a germ-line MEN1 gene mutation was consequently detected. It could be assumed that MEN1 syndrome may have possibly predisposed the present patient to breast cancer. However, additional observations and further studies are required to demonstrate this association. PMID:24959251

JEONG, YOUNG JU; OH, HOON KYU; BONG, JIN GU

2014-01-01

343

Ocular surface squamous neoplasia in HIV-positive and HIV-negative patients and response to 5-fluorouracil in Angola  

PubMed Central

Background Ocular surface squamous neoplasia (OSSN) is becoming increasingly prevalent and aggressive in Sub-Saharan Africa. It is a phenomenon linked with human immunodeficiency virus (HIV) infection, although association rates in Angola are currently unknown. A topical treatment that is effective in HIV-positive and HIV-negative individuals may be preferable to surgery in some contexts. We aimed to estimate the proportion of OSSN associated with HIV in Angola and to report on the success of topical 5-fluorouracil as a primary treatment in HIV-positive and HIV-negative patients. Methods Photographs of OSSNs taken at presentation and following treatment with 5-fluorouracil in patients presenting to Boa Vista Eye Clinic, Angola, between October 2011 and July 2013 were grouped into HIV-positive and HIV-negative groups and analyzed to compare presenting features and treatment response. Eighty-one OSSNs were analyzed for clinical features and 24 met the inclusion criteria for analysis of treatment response. Results Eighty-two patients presented with OSSN between October 2011 and July 2013. Twenty-one (26%) were HIV-positive and typically had OSSNs that exhibited more pathological features than those in HIV-negative patients. Twenty-four (29%) patients met the inclusion criteria for analysis of treatment response; of these, 26 (91%) OSSNs in both groups displayed at least partial resolution after one treatment course. In the HIV-positive group, five of eight patients displayed complete resolution, two showed partial resolution, and one failed. In the HIV-negative group, five of 16 showed complete resolution, ten of 16 had partial resolution, and one failed. Conclusion Individuals presenting with OSSN in Angola are more likely to have HIV infection compared with the general population. Regardless of HIV status, 5-fluorouracil drops can be an effective strategy for management of OSSN without incurring the costs and risks of surgery in the developing world setting. PMID:25506205

Nutt, Robert J; Clements, John L; Dean, William H

2014-01-01

344

Normalized autofluorescence imaging diagnostics in upper GI tract: a new method to improve specificity in neoplasia detection  

PubMed Central

Background & Aims: This study was performed to improve the autofluorescence imaging (AFI) in the upper GI tract by applying a new method of normalized autofluorescence (NAFI) obtained via tri-modal imaging. Objective: NAFI may provide lower false positive rate to achieve ultimately better specificity at acceptable sensitivity. Patients and methods: This is a prospective, controlled single-centre study. 18 patients with suspected esophagus or stomach cancer undergoing esophagogastroduodenoscopy (EGD) were enrolled between February and May 2010. After endoscopy each patient was assigned into one of two groups: (1) non- cancer, including inflammation; (2) cancer group. EGDs were performed using video white light endoscopy, followed by AFI/NAFI. The targeted biopsy samples were taken from the abnormal areas as well as from adjacent mucosa. NAFI was compared versus AFI for cancer diagnostics in terms of specificity and sensitivity. Results: NAFI detected all neoplastic lesions. WLE or NBI detected no additional neoplasia. The AFI displayed mucosal inflammation and carcinomas of esophagus and stomach as dark red color, the normal mucosa background was displayed as light green. The NAFI didn’t differentiate inflamed tissue from normal in majority of cases, but in tumorous mucosa, the cancer areas were detected precisely. AFI shows 100% sensitivity but 50% specificity which correlates with previous literature data. On the other hand, NAFI demonstrated lower sensitivity (88%) but higher specificity compared to AFI (69%). Conclusions: Measuring the NAFI instead of the AFI was found improving the specificity of cancer diagnosis. Use of fiber-optic endoscopes to analyze AFI and possible endoscopic and histological sampling error are the main potential limitations of this method. PMID:23119113

Krauss, Ekaterina; Agaimy, Abbas; Douplik, Alexandre; Albrecht, Heinz; Neumann, Helmut; Hartmann, Arndt; Hohenstein, Ralf; Raithel, Martin; Hahn, Eckhart G; Neurath, Markus F; Mudter, Jonas

2012-01-01

345

The RET protooncogene in sporadic pheochromocytomas: Frequent multiple endocrine neoplasias type 2 - like mutations and new molecular defects  

SciTech Connect

To assess the pathophysiological role of the RET protooncogene in sporadic pheochromocytomas, we examined the two regions of the gene in which molecular defects are specifically associated with the Multiple Endocrine Neoplasias (MEN) type 2A (exons 8-11) and type 2B (exon 16). The sequences of both regions were amplified by RT-PCR or PCR from tumor RNA and/or constitutive DNA. The amplified products were analyzed by denaturing gradient gel electrophoresis using chemical clamps. In 28 patients with unilateral sporadic tumors six RET mutations were found: three in the MEN2A region, and three in the MEN2B region. Five patients had missense mutations: two in the MEN2A region (C634W and D631Y), and three in the MEN2B region (M918T). Analysis of leukocyte DNA in three of these patients confirmed that RET mutations were only present in tumor DNA. The sixth patient had lost exon 10 in the tumor cDNA due to the deletion of the dinucleotide AG at the 3{prime} splice acceptor site of intron 9; this molecular defect was only found in the tumor DNA. Thus RET mutations of the MEN 2A and MEN 2B regions are also found in ca. 20% of sporadic pheochromocytomas. We describe new types of molecular defects of the RET protooncogene in the MEN2A region which involve non-cysteine residues and the loss of exon 10. Further studies should be extended to analyze the entire RET gene. These findings have a profound clinical impact for the management of patients with supposedly sporadic pheochromocytomas.

Beldjord, C.; Desclaux-Arramond, F.; Raffin-Sanson, M. [Universitat Rene Descartes, Paris (France)] [and others

1994-09-01

346

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

2015-04-01

347

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

348

Unique Gene Expression Profile Associated with an Early-Onset Multiple Endocrine Neoplasia (MEN1)-Associated Pituitary Adenoma  

PubMed Central

Context: Multiple endocrine neoplasia type 1 (MEN1) is caused by mutations in the menin (MEN1) gene. The mechanism(s) by which MEN1 mutations lead to pituitary tumor formation remain(s) unknown. Objective: The aim of the study was to identify the pediatric MEN1-associated pituitary tumor transcriptome. Patients and Methods: A patient harboring a MEN1 mutation (c.525C>G; p.H139D) who presented with an early-onset mammosomatotroph pituitary adenoma was studied. Microarray analysis was performed in the tumor sample and compared with the profile observed in normal pituitaries and in a sporadic mammosomatotropinoma. Validation of the microarray results was performed using quantitative real-time PCR and immunohistochemical analysis for selected genes. Results: In the MEN1-associated pituitary adenoma, 59 and 24 genes were found to be significantly up- and down-regulated, respectively. The up-regulated genes included those involved in cell growth and maintenance, apoptosis, growth arrest, and tumorigenesis. Moreover, we observed decreased expression in genes neuroendocrine in nature and related to growth or apoptosis. Only 21 of the 59 genes differentially expressed in the MEN1-associated adenoma showed a similar expression profile to that seen in the sporadic mammosomatotropinoma; for some genes an opposite expression profile was observed. Conclusions: We identified changes in the transcriptome that occur in pituitary GH- and PRL-producing cells after the loss of menin expression; some of the gene changes are necessary for tumor evolution, and others may be tertiary. Nevertheless, the rare overlap between the expression profiles of the MEN1 tumor vs. that of its sporadic counterpart suggests that these tumors evolve along different molecular pathways. PMID:21917868

Farrell, William E.; Azevedo, Monalisa F.; Batista, Dalia L.; Smith, Alastair; Bourdeau, Isabelle; Horvath, Anelia; Boguszewski, Margaret; Quezado, Martha

2011-01-01

349

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

350

Chronic kidney disease, severe arterial and arteriolar sclerosis and kidney neoplasia: on the spectrum of kidney involvement in MELAS syndrome  

PubMed Central

Background MELAS syndrome (MIM ID#540000), an acronym for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes, is a genetically heterogeneous mitochondrial disorder with protean manifestations and occasional kidney involvement. Interest in the latter is rising due to the identification of cases with predominant kidney involvement and to the hypothesis of a link between mitochondrial DNA and kidney neoplasia. Case presentation We report the case of a 41-year-old male with full blown MELAS syndrome, with lactic acidosis and neurological impairment, affected by the "classic" 3243A > G mutation of mitochondrial DNA, with kidney cancer. After unilateral nephrectomy, he rapidly developed severe kidney functional impairment, with nephrotic proteinuria. Analysis of the kidney tissue at a distance from the two tumor lesions, sampled at the time of nephrectomy was performed in the context of normal blood pressure, recent onset of diabetes and before the appearance of proteinuria. The morphological examination revealed a widespread interstitial fibrosis with dense inflammatory infiltrate and tubular atrophy, mostly with thyroidization pattern. Vascular lesions were prominent: large vessels displayed marked intimal fibrosis and arterioles had hyaline deposits typical of hyaline arteriolosclerosis. These severe vascular lesions explained the different glomerular alterations including ischemic and obsolescent glomeruli, as is commonly observed in the so-called "benign" arteriolonephrosclerosis. Some rare glomeruli showed focal segmental glomerulosclerosis; as the patient subsequently developed nephrotic syndrome, these lesions suggest that silent ischemic changes may result in the development of focal segmental glomerulosclerosis secondary to nephron loss. Conclusions Nephron loss may trigger glomerular sclerosis, at least in some cases of MELAS-related nephropathy. Thus the incidence of kidney disease in the "survivors" of MELAS syndrome may increase as the support therapy of these patients improves. PMID:22353239

2012-01-01

351

Multiple endocrine neoplasia type 1 associated with breast cancer: A case report and review of the literature.  

PubMed

Multiple endocrine neoplasia type 1 (MEN1) is a cancer predisposition syndrome that includes a combination of endocrine and non-endocrine tumors. The present study reports a rare case of MEN1 associated with breast cancer with the MEN1 gene mutation. A 45-year-old female was diagnosed with breast cancer subsequent to presenting with a right breast mass. Pre-operative radiological studies indicated right breast cancer with a suspicious metastatic nodule of the lung. Further studies demonstrated bilateral thyroid nodules, a neuroendocrine tumor of the pancreas, paraganglioma, a left adrenal adenoma, gallstones, uterine subserosal myoma and pituitary macroadenoma. Laboratory examinations revealed hypercalcemia, hypophosphatemia and an increased intact parathyroid hormone level. The workup for the suspected MEN syndrome revealed an increased basal plasma level of insulin-like growth factor-1, prolactin and calcitonin, and an increased 24-h urinary free cortisol level. The patient underwent surgical removal of the breast cancer and the tumors of the pancreas, adrenal gland, thyroid and parathyroid glands, uterus, anterior mediastinum and lung. The pathological diagnosis of the resected breast was of invasive ductal carcinoma. Otherwise the pathological diagnosis was of calcitonin-producing pancreatic endocrine carcinoma, adrenal cortical adenoma, bilateral papillary thyroid carcinomas, parathyroid adenomas, uterine leiomyoma with adenomyosis, a thymic carcinoid tumor and lung hamatoma. Gene analysis was performed to determine the association between gene mutations and the development of tumors in this patient, and a germ-line MEN1 gene mutation was consequently detected. It could be assumed that MEN1 syndrome may have possibly predisposed the present patient to breast cancer. However, additional observations and further studies are required to demonstrate this association. PMID:24959251

Jeong, Young Ju; Oh, Hoon Kyu; Bong, Jin Gu

2014-07-01

352

Cervical Surgery for Cervical Intraepithelial Neoplasia and Prolonged Time to Conception of a Live Birth: A Case-Control Study  

PubMed Central

Objective To determine whether women with a history of surgery for cervical intraepithelial neoplasia (CIN) are at increased risk of sub-fertility, measured as time to pregnancy of more than 12 months. Design Case-control study Setting Iowa Health in Pregnancy Study (IHIPS), a population-based case-control study of preterm and small-for-gestational-age (SGA) live birth outcomes (5/2002-5/2005), United States. Sample Women with an intended pregnancy and a history of either one prior cervical surgery (n=152), colposcopy-only (n=151), or no prior cervical surgery or colposcopy (n=1021). Methods Cervical treatment history, pregnancy intention, time to pregnancy, and other variables were self-reported by computer-assisted telephone interviews. Odds ratios were calculated using logistic regression to estimate the risk of prolonged time to pregnancy among women with a history of cervical surgery or colposcopy alone compared to untreated women (referent group). Main Outcome Measure Prolonged time to pregnancy (ie, >1 year) Results Prolonged time to pregnancy was most prevalent among treated women (16.4%) compared to untreated women (8.4%) and women with colposcopy only (8.6%) (p=0.039). After adjusting for covariates, women with prior cervical surgery had more than a two-fold higher risk of prolonged time to pregnancy compared to untreated women (aOR=2.09, 95% CI 1.26-3.46). In contrast, women with a history of colposcopy-only had a risk equivalent to that among untreated women (aOR=1.02, 95% CI 0.56-1.89). Conclusions Women with a history of cervical treatment for CIN are at increased risk of sub-fertility, measured as time to pregnancy of more than 12 months. PMID:23489374

Spracklen, Cassandra N.; Harland, Karisa K.; Stegmann, Barbara J.; Saftlas, Audrey F.

2013-01-01

353

Lack of commensal flora in H. pylori-infected INS-GAS mice reduces gastritis and delays intraepithelial neoplasia  

PubMed Central

Background & Aims Transgenic, insulin–gastrin (INS–GAS) mice have high circulating levels of gastrin. On a FVB/N background, these mice develop spontaneous atrophic gastritis and gastrointestinal intraepithelial neoplasia (GIN) with 80% prevalence 6 months after Helicobacter pylori infection. GIN is associated with gastric atrophy and achlorhydria, predisposing mice to non-helicobacter microbiota overgrowth. We determined if germ-free INS–GAS mice spontaneously develop GIN and if H. pylori accelerates GIN in gnotobiotic INS–GAS mice. Methods We compared gastric lesions and levels of mRNA, serum inflammatory mediators, antibodies, and gastrin among germ-free and H. pylori-monoinfected INS-GAS mice. Microbiota composition of specific pathogen-free (SPF) INS-GAS mice was quantified by pyro-sequencing. Results Germ-free INS-GAS mice had mild hypergastrinemia but did not develop significant gastric lesions until they were 9 months old; they did not develop GIN through 13 months. H. pylori monoassociation caused progressive gastritis, epithelial defects, oxyntic gland atrophy, marked foveolar hyperplasia and dysplasia, and strong serum and tissue proinflammatory immune responses (particularly in male mice) between 5 and 11 months post infection (P<0.05, compared with germ-free controls). Only 2 of 26 female, whereas 8 of 18 male, H. pylori-infected INS-GAS mice developed low- to high-grade GIN by 11 months post infection. Stomachs of H. pylori-infected SPF male mice had significant reductions in Bacteroidetes and significant increases in Firmicutes. Conclusions Gastric lesions take 13 months longer to develop in germ-free INS–GAS mice than male SPF INS-GAS mice. H. pylori-monoassociation accelerated gastritis and GIN but caused less-severe gastric lesions and delayed onset of GIN compared to H. pylori-infected INS-GAS mice with complex gastric microbiota. Changes of gastric microbiota composition might promote GIN in the achlorhydric stomachs of SPF mice. PMID:20950613

Lofgren, Jennifer L.; Whary, Mark T.; Ge, Zhongming; Muthupalani, Sureshkumar; Taylor, Nancy S.; Mobley, Melissa; Potter, Amanda; Varro, Andrea; Eibach, Daniel; Suerbaum, Sebastian; Wang, Timothy C.; Fox, James G.

2010-01-01

354

[Management of testicular intraepithelial neoplasia (TIN)--a review based on the principles of evidence-based medicine].  

PubMed

Testicular intraepithelial neoplasia (TIN; also called carcinoma in situ of the testis) is the uniform precursor of testicular germ cell tumors. There is general agreement on the biological significance of TIN, however, the treatment is still a matter of dispute. The present review summarizes the treatment options currently available. In general, the management of TIN has to be adapted to the particular clinical situation of the patient. Eradication of TIN usually implies the loss of fertility. Therefore, fertility aspects should be considered before any kind of treatment is employed. Usually, patients with TIN have only small residual potential of fertility. Nonetheless, individual patients may qualify for sperm banking or cryopreservation of testicular tissue for future sperm extraction (TESE) and assisted fertilization. The most common clinical situation is the case of contralateral TIN in the presence of unilateral testicular cancer. Low dose radiotherapy to the testis with 18 Gy is the standard management option in these patients. The same procedure may be applied to solitary testicles after partial orchiectomy for germ cell tumors. During follow-up, testosterone levels should be evaluated every six months. If chemotherapy is required due to metastatic disease of the primary tumor management of TIN should be deferred. After chemotherapy 30% of TIN cases will persist and approximately 42% will recur in the later course. Repeat biopsy should be done six months after completion of chemotherapy or later. Only in cases with persistent TIN additional radiotherapy should be administered. If one testicle is afflicted with TIN while the other testis is in healthy condition (conceivable in infertility cases or patients with primary extragonadal germ cell tumors), then the TIN-bearing testis should be excised. Radiotherapy is not feasible in these cases because of shielding problems with the healthy testis. PMID:11233474

Dieckmann, K P; Classen, J; Souchon, R; Loy, V

2001-01-15

355

Sarcoidlike reaction of neoplasia causing hypermetabolic thoracic adenopathy in setting of extrathoracic malignancy: report of two cases and a review of the differential diagnostic considerations.  

PubMed

The development of noncaseating granulomas in a patient with underlying malignancy and no symptoms or signs suggestive of systemic sarcoid is often referred to as a sarcoidlike reaction and is estimated to occur in a small but significant portion of cancer patients. The pathogenesis is poorly understood, but the entity is hypothesized to be an immune phenomenon representing a host defense mechanism against the spread of tumor cells. Sarcoidlike reactions can occur at any time from the time of diagnosis to several years afterward and may occur in lymph nodes draining a malignant tumor, in the tumor itself, and even in nonregional tissues. Like sarcoid, sarcoidlike reactions of neoplasia can demonstrate hypermetabolic lymph nodes on (18)F-FDG PET imaging and thus be readily confused with metastatic disease. We describe 2 cases of a sarcoidlike reaction of neoplasia presenting as hypermetabolic thoracic lymph nodes on (18)F-FDG PET/CT obtained for follow-up of extrathoracic malignancies: one a 73-y-old woman with a history of stage III head and neck squamous cell carcinoma and the other a 34-y-old woman with recurrent giant cell tumor of the sacrum. In both instances, the differential diagnosis for the finding of hypermetabolic thoracic lymph nodes included the possibility of a sarcoidlike reaction, though tissue sampling was pursued to exclude the more worrisome presence of metastatic disease or, less likely, a new primary malignancy. We review the topic of sarcoidlike reactions of neoplasia as well as the analytic approach to hypermetabolic mediastinal and hilar lymph nodes encountered on (18)F-FDG PET/CT. PMID:23015478

Craun, Jonathan B; Banks, Kevin P; Clemenshaw, Michael N; Moren, Ronald W

2012-12-01

356

Vaginal delivery in a patient with pheochromocytoma, medullary thyroid cancer, and primary hyperparathyroidism (multiple endocrine neoplasia type 2A, Sipple's syndrome)  

PubMed Central

Multiple endocrine neoplasia 2A (MEN 2A), or Sipple's syndrome is a rare inherited dominant syndrome, characterised by medullary thyroid carcinoma, adrenal pheochromocytoma and hyperparathyroidism, due to specific RET proto-oncogene mutations. The women with MEN 2A syndrome are at risk of complicated pregnancy because of unrecognised pheochromocytoma and transmission of RET mutation to the progeny. We report a case of a woman with MEN 2A diagnosed in early pregnancy. Alpha-blockade medical therapy was used effectively and time was given for fetal maturation. Uncomplicated vaginal delivery performed under epidural analgesia. Six weeks postpartum adrenalectomy, thyroidectomy and parathyroidectomy were performed uneventfully. PMID:25191209

Muzannara, Muhammad Anas; Tawfeeq, Nasser; Nasir, Mahmood; Al Harbi, Mohammed Khulaif; Geldhof, Georges; Dimitriou, Vassilios

2014-01-01

357

MYC Overexpression Induces Prostatic Intraepithelial Neoplasia and Loss of Nkx3.1 in Mouse Luminal Epithelial Cells  

PubMed Central

Lo-MYC and Hi-MYC mice develop prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinoma as a result of MYC overexpression in the mouse prostate[1]. However, prior studies have not determined precisely when, and in which cell types, MYC is induced. Using immunohistochemistry (IHC) to localize MYC expression in Lo-MYC transgenic mice, we show that morphological and molecular alterations characteristic of high grade PIN arise in luminal epithelial cells as soon as MYC overexpression is detected. These changes include increased nuclear and nucleolar size and large scale chromatin remodeling. Mouse PIN cells retained a columnar architecture and abundant cytoplasm and appeared as either a single layer of neoplastic cells or as pseudo-stratified/multilayered structures with open glandular lumina—features highly analogous to human high grade PIN. Also using IHC, we show that the onset of MYC overexpression and PIN development coincided precisely with decreased expression of the homeodomain transcription factor and tumor suppressor, Nkx3.1. Virtually all normal appearing prostate luminal cells expressed high levels of Nkx3.1, but all cells expressing MYC in PIN lesions showed marked reductions in Nkx3.1, implicating MYC as a key factor that represses Nkx3.1 in PIN lesions. To determine the effects of less pronounced overexpression of MYC we generated a new line of mice expressing MYC in the prostate under the transcriptional control of the mouse Nkx3.1 control region. These “Super-Lo-MYC” mice also developed PIN, albeit a less aggressive form. We also identified a histologically defined intermediate step in the progression of mouse PIN into invasive adenocarcinoma. These lesions are characterized by a loss of cell polarity, multi-layering, and cribriform formation, and by a “paradoxical” increase in Nkx3.1 protein. Similar histopathological changes occurred in Hi-MYC mice, albeit with accelerated kinetics. Our results using IHC provide novel insights that support the contention that MYC overexpression is sufficient to transform prostate luminal epithelial cells into PIN cells in vivo. We also identified a novel histopathologically identifiable intermediate step prior to invasion that should facilitate studies of molecular pathway alterations occurring during early progression of prostatic adenocarcinomas. PMID:20195545

Iwata, Tsuyoshi; Schultz, Denise; Hicks, Jessica; Hubbard, Gretchen K.; Mutton, Laura N.; Lotan, Tamara L.; Bethel, Carlise; Lotz, Matthew T.; Yegnasubramanian, Srinivasan; Nelson, William G.; Dang, Chi V.; Xu, MengMeng; Anele, Uzoma; Koh, Cheryl M.; Bieberich, Charles J.; De Marzo, Angelo M.

2010-01-01

358

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

359

The relationship between HIV infection and cervical intraepithelial neoplasia among women attending two family planning clinics in Nairobi, Kenya.  

PubMed

Women attending 2 family planning clinics in Nairobi, Kenya, were enrolled in a study of risk factors for HIV infection between October 1989 and May 1991. Data were obtained using a structured questionnaire on social, demographic, medical, and sexual behavior. During pelvic examination, were obtained specimens, for a Papanicolaou (PAP) smear and for sexually transmitted disease (STDs). 4058 women had an interpretable smear (with both squamous and endocervical cells present). 82 of the 4058 (women 2.0% had cytological evidence of cervical intraepithelial neoplasia (CIN): 58 had CIN-I, 23 had CIN 11, and 1 had CIN III. Single women were at a reduced ask for CIN (multivariate odds ratio = OR, 0.25; 95% confidence interval = CI, 0.07-0.86). There was no consistent association between number of pregnancies and CIN, although there was some evidence of a protective effect of later age at first pregnancy (P for linear trend = 0.07 and 0.35 in the crude and multivariate analyses, respectively). Age at first intercourse of at least 19 years compared with an age of 16 years of under was protective against CIN (OR, 0.45; 95% CI, 0.20-0.97). Having more than one lifetime sex partner increased the risk of CIN (OR, 1.60; 95% CI, 0.86-2.99). Positive syphilis serology was associated with a doubling of risk (OR, 2.28; 95% CI, 0.6%-7.63). Oral, intrauterine, or injectable contraception was not significantly associated with CIN. Ten (4.9%) of the 205 HIV-seropositive women had CIN, compared with 72 (1.9%) of the 3853 HIV-seronegative women (OR, 2.69; 95% CI, 1.29-5.49). This positive association remained after controlling for sexual behavior and other risk factors. On clinical examination, enlarged cervical, axillary, or inguinal lymph nodes were detected in 5.1% of the HIV-seropositive women compared with 1.7% of the HIV-seronegative women. CIN was more common among 204 HIV-seropositive women with symptoms or signs consistent with immunodeficiency (weight loss, fever, diarrhea); however, none of these associations reached statistical significance. PMID:8318180

Maggwa, B N; Hunter, D J; Mbugua, S; Tukei, P; Mati, J K

1993-05-01

360

Differences in human papillomavirus type distribution in high-grade cervical intraepithelial neoplasia and invasive cervical cancer in Europe.  

PubMed

Knowledge of differences in human papillomavirus (HPV)-type prevalence between high-grade cervical intraepithelial neoplasia (HG-CIN) and invasive cervical cancer (ICC) is crucial for understanding the natural history of HPV-infected cervical lesions and the potential impact of HPV vaccination on cervical cancer prevention. More than 6,000 women diagnosed with HG-CIN or ICC from 17 European countries were enrolled in two parallel cross-sectional studies (108288/108290). Centralised histopathology review and standardised HPV-DNA typing were applied to formalin-fixed paraffin-embedded cervical specimens dated 2001-2008. The pooled prevalence of individual HPV types was estimated using meta-analytic methods. A total of 3,103 women were diagnosed with HG-CIN and a total of 3,162 with ICC (median ages: 34 and 49 years, respectively), of which 98.5 and 91.8% were HPV-positive, respectively. The most common HPV types in women with HG-CIN were HPV16/33/31 (59.9/10.5/9.0%) and in ICC were HPV16/18/45 (63.3/15.2/5.3%). In squamous cell carcinomas, HPV16/18/33 were most frequent (66.2/10.8/5.3%), and in adenocarcinomas, HPV16/18/45 (54.2/40.4/8.3%). The prevalence of HPV16/18/45 was 1.1/3.5/2.5 times higher in ICC than in HG-CIN. The difference in age at diagnosis between CIN3 and squamous cervical cancer for HPV18 (9 years) was significantly less compared to HPV31/33/'other' (23/20/17 years), and for HPV45 (1 year) than HPV16/31/33/'other' (15/23/20/17 years). In Europe, HPV16 predominates in both HG-CIN and ICC, whereas HPV18/45 are associated with a low median age of ICC. HPV18/45 are more frequent in ICC than HG-CIN and associated with a high median age of HG-CIN, with a narrow age interval between HG-CIN and ICC detection. These findings support the need for primary prevention of HPV16/18/45-related cervical lesions. PMID:22752992

Tjalma, Wiebren A; Fiander, Alison; Reich, Olaf; Powell, Ned; Nowakowski, Andrzej M; Kirschner, Benny; Koiss, Robert; O'Leary, John; Joura, Elmar A; Rosenlund, Mats; Colau, Brigitte; Schledermann, Doris; Kukk, Kersti; Damaskou, Vasileia; Repanti, Maria; Vladareanu, Radu; Kolomiets, Larisa; Savicheva, Alevtina; Shipitsyna, Elena; Ordi, Jaume; Molijn, Anco; Quint, Wim; Raillard, Alice; Rosillon, Dominique; De Souza, Sabrina Collas; Jenkins, David; Holl, Katsiaryna

2013-02-15

361

Fascin expression in cervical normal squamous epithelium, cervical intraepithelial neoplasia, and superficially invasive (stage IA1) squamous carcinoma of the cervix.  

PubMed

The aims of this study were to: investigate fascin expression in normal cervix, cervical intraepithelial neoplasia (CIN), and stage IA1 squamous cell carcinoma (SCC).Fascin immunostaining was performed in cervical biopsies showing normal squamous epithelium (n=10), CIN 1 (n=10), CIN 2-3 without invasion (n=11), and CIN 2-3 adjacent to SCC (n=40); SCC was also present in 27 of the latter cases.Fascin expression in normal squamous epithelium was restricted to basal and parabasal cells, whereas there was increased staining in immature squamous metaplasia and in most CIN lesions. Full thickness staining was more frequent in high grade CIN adjacent to invasion than in CIN 2-3 alone. Eighteen SCCs (67%) were fascin positive and seven cases showed accentuated staining at the tumour-stromal interface (invasive front). There was no consistent relationship between fascin expression in CIN lesions and in corresponding carcinomas. Fascin staining in reactive stromal cells sometimes made identification of the invasive neoplastic cells difficult.Fascin is overexpressed in most CIN lesions and this may be a marker of increased invasive potential in high grade CIN. However, fascin staining does not distinguish low and high grade CIN or in situ and invasive squamous neoplasia. Therefore fascin has limited diagnostic utility in demonstrating superficial stromal invasion. PMID:24977742

Koay, M H E; Crook, M; Stewart, C J R

2014-08-01

362

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

363

Regular Article MYELOID NEOPLASIA  

E-print Network

-MNs).3 7/del(7q) is also found in myelodysplastic syndromes, AMLs arising from myeloproliferative disorders, and the long-term outcome for patients is typically poor. The median overall survival disorders characterized by chromosome 7 abnormalities, the CDS was mapped to a 2.52-Mb region of 7q22

Grossman, Robert

364

Chemoprevention of gastrointestinal neoplasia.  

PubMed

Cancer chemoprevention is defined as the pharmacologic intervention, by drugs or nutrient-components, with the process of carcinogenesis, in order to prevent the development of invasive malignant neoplasms. This preventive attempt is particularly challenging in cancer types, which have a long subclinical developmental phase, because of their low cellular proliferation rate and their slow pre-clinical evolution, until they become clinically detectable and therapeutically as well as prognostically relevant. Therefore, only certain specific cancer types are presently in the focus of clinical chemoprevention. Among the GI tract cancer, colorectal (CRC) as well as esophageal cancer have raised the most attention over the past decades, as they both share a long precancerous stage (the adenoma in CRC and Barrett's esophagus in the case of esophageal adenocarcinoma) which provides a window of opportunity to intervene and prevent development of cancer.In this review, we will focus on both CRC as well as esophageal adenocarcinoma (EAC). PMID:23605648

Half, Elizabeth; Arber, Nadir

2013-05-01

365

Neoplasia of aortic intima  

PubMed Central

Two cases of arterial obstruction, in the region of the aortic bifurcation, are described. In both cases, cellular proliferation of neoplastic type was found to be causing the obstruction, and in one case small embolic metastases were found in the lower limbs and lungs. No primary tumour was found in any site other than the aortic intima itself. Two apparently similar cases have been reported in recent years. It is suggested that this condition, although probably very rare, may be overlooked for several reasons unless obstructive aortic lesions are examined histologically as a routine. Images PMID:14227427

Sladden, R. A.

1964-01-01

366

Multiple Endocrine Neoplasia Syndromes  

MedlinePLUS

... tend to grow more slowly than cancerous islet cell tumors that develop in people who do not have type 1 disease. Some people with type 1 disease develop pituitary gland tumors. Some of these tumors produce the ...

367

Generación de Electricidad con Energías Renovables (ER)  

Microsoft Academic Search

Los funcionarios argumentaron, entre otros, sobre la sostenibilidad energética a largo plazo, la producción de electricidad con Energías Renovables-ER (biomasa, eólico, solar, geotérmico, mareomotriz, e hidráulica con capacidad menor de 20 MW), la contaminación ambiental y las externalidades que produce, y las iniciativas sobre el uso de ER que han adoptado países mas adelantados como Alemania y España. El Vice-Ministro

Jaime E. Luyo

2008-01-01

368

ORNL/CON-462 Methodology for  

E-print Network

ORNL/CON-462 Methodology for the Evaluation of a 4000-Home Geothermal Heat Pump Retrofit at Fort agency thereof. #12;ORNL/CON-462 Methodology for the Evaluation of a 4000-Home Geothermal Heat Pump of the Fort Polk bid documents and the resultant performance contract between the Army and Co-Energy Group

Oak Ridge National Laboratory

369

AwareCon: Situation Aware Context Communication  

Microsoft Academic Search

Ubicomp environments impose tough constraints on networks, including immediate communication, low energy consumption, minimal maintenance and ad- ministration. With the AwareCon network, we address these challenges by prescribing an integrated architecture that differs from classical networking by featuring an aware- ness of the surrounding situation and context. In various settings, where AwareCon was implemented on tiny battery driven devices, we

Michael Beigl; Albert Krohn; Tobias Zimmer; Christian Decker; Philip Robinson

2003-01-01

370

CLINICS 2012;67(S1):173-178 DOI:10.6061/clinics/2012(Sup01)29 REVIEW Surgical management of pancreatico-duodenal tumors in multiple endocrine neoplasia syndrome type 1  

E-print Network

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

Göran A Kerström; Peter Sta Lberg; Per Hellman

371

Circulating Soluble Neuropilin-1 in Patients with Early Cervical Cancer and Cervical Intraepithelial Neoplasia Can Be Used as a Valuable Diagnostic Biomarker  

PubMed Central

Objective. To investigate soluble neuropilin-1 (sNRP-1) in circulating and NRP-1 protein in cervical tissues from patients with cervical cancer or cervical intraepithelial neoplasia (CIN). Methods. sNRP-1 was measured in 64 preoperative patients and 20 controls. NRP-1 protein in cervical tissue was detected in 56 patients and 20 controls. Results. Both sNRP-1 and NRP-1 proteins were correlated with stage. sNRP-1 presented a high diagnostic ability of cervical cancer and CIN, with a sensitivity of 70.97% and a specificity of 73.68%. Conclusions. sNRP-1 in circulating can serve as a possible valuable diagnostic biomarker for cervical cancer and CIN.

Yang, Shouhua; Cheng, Henghui; Huang, Zaiju; Wang, Xiaoling; Wan, Yinglu; Cai, Jing; Wang, Zehua

2015-01-01

372

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

373

Multiple therapeutic and preventive effects of 3,3'-diindolylmethane on cancers including prostate cancer and high grade prostatic intraepithelial neoplasia.  

PubMed

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

2014-09-01

374

[The consequences of subcutaneous India ink injection to produce factitial disease. Bilateral mastectomy, lymph node dissection, irradiation, and continued suspicion of neoplasia].  

PubMed

A 68-year-old woman with insulin-dependent diabetes mellitus presented with blue nodules on the ventral aspect of the thorax. According to the past history, these lesions had developed repeatedly. She had already had bilateral mastectomies and lymph node dissection. The histologic diagnosis was always mastitis with plasma cells and no neoplasia. Yet another biopsy was taken; the subcutis was stained blue-black. Histology revealed exogenous black pigment and mastitis. With Raman spectroscopy the pigment was identified as carbon black, which is a component of India ink. These findings together with the unusual course of the disease suggested the diagnosis of an artificial disorder. The likely conclusion is that our patient, over years, used her own (insulin) syringe to inject India ink into her skin and subcutaneous tissue; the damaging effect and tissue reaction was probably caused by preservatives such as phenol. PMID:17924082

Schlegel, C; Teufel, M; Häfner, H-M; Schaller, M; Metzler, G; Biedermann, T

2008-07-01

375

A critical evaluation of the use of the Schiller test in selecting blocks from the uterine cervix in suspected intraepithelial neoplasia.  

PubMed Central

The value of dipping cervical cone biopsy specimens in iodine (the Schiller test) as a method of deciding which areas should be selected for histological examination was assessed. Schiller positive and negative areas were recorded in macroscopic specimen images from fifty specimens of cervix. The results were compared with the histological presence or absence of cervical intraepithelial neoplasia (CIN) or invasive malignancy. In 84% of cases the test was a reliable means of predicting the presence or absence of squamous CIN; in two cases it was positive in association with endocervical adenocarcinoma in situ. A false positive and false negative Schiller's test was present in three cases (6%) each. Had this method been adopted as the sole means of selecting blocks for histological examination the areas of CIN would have been missed in 6% of cases. Therefore it is not a sound alternative to the submission of all tissue for histological examination. PMID:8533180

Heatley, M. K.

1995-01-01

376

The Breakpoint Region of the Most Common Isochromosome, i(17q), in Human Neoplasia Is Characterized by a Complex Genomic Architecture with Large, Palindromic, Low-Copy Repeats  

PubMed Central

Although a great deal of information has accumulated regarding the mechanisms underlying constitutional DNA rearrangements associated with inherited disorders, virtually nothing is known about the molecular processes involved in acquired neoplasia-associated chromosomal rearrangements. Isochromosome 17q, or “i(17q),” is one of the most common structural abnormalities observed in human neoplasms. We previously identified a breakpoint cluster region for i(17q) formation in 17p11.2 and hypothesized that genome architectural features could be responsible for this clustering. To address this hypothesis, we precisely mapped the i(17q) breakpoints in 11 patients with different hematologic malignancies and determined the genomic structure of the involved region. Our results reveal a complex genomic architecture in the i(17q) breakpoint cluster region, characterized by large (?38–49-kb), palindromic, low-copy repeats, strongly suggesting that somatic rearrangements are not random events but rather reflect susceptibilities due to the genomic structure. PMID:14666446

Barbouti, Aikaterini; Stankiewicz, Pawel; Nusbaum, Chad; Cuomo, Christina; Cook, April; Höglund, Mattias; Johansson, Bertil; Hagemeijer, Anne; Park, Sung-Sup; Mitelman, Felix; Lupski, James R.; Fioretos, Thoas

2004-01-01

377

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

378

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

379

Bilateral granulosa cell tumors: a novel malignant manifestation of multiple endocrine neoplasia 1 syndrome found in a patient with a rare menin in-frame deletion  

PubMed Central

Introduction Multiple endocrine neoplasia 1 (MEN1) is a cancer syndrome resulting from mutations of the MEN1 gene. The syndrome is characterized by neoplasia of the parathyroid and pituitary glands, and malignant tumors of the endocrine pancreas. Other manifestations include benign lipomas, angiofibromas, and carcinoid tumors commonly originating in the colon, thymus, and lung. This is the first report of MEN1 syndrome manifesting as bilateral granulosa cell ovarian tumors, and which is associated with a rare intronic mutation of the MEN1 gene. Case report A 41-year-old woman presented with abdominal pain, increasing abdominal girth, and dysmenorrhea. Ultrasound demonstrated enlarged ovaries and uterine fibroids. After an exploratory laparotomy, she subsequently underwent bilateral salpingo–oophorectomy with hysterectomy where the pathology revealed bilateral cystic granulosa cell tumors of the ovaries. Additional workup including computed tomography imaging discovered a thymic mass, which the pathology showed was malignant, along with a pancreatic mass suspicious for a neuroendocrine tumor. Hyperparathyroidism was also discovered and was found to be secondary to a parathyroid adenoma. Genetic testing revealed an exceedingly rare mutation in the MEN1 gene (c.654 + 1 G>A). Discussion Mutations of the menin gene leading to MEN1 syndrome are classically nonsense or missense mutations producing a dysfunctional protein product. Recently, researchers described a novel mutation of MEN1 (c.654 + 1 G>A) in a male proband meeting the criteria for clinical MEN1 syndrome. Functional analysis performed on the stable mutant protein showed selective disruption of the transforming growth factor beta signaling pathway, yet it maintained its wild-type ability to inhibit nuclear factor kappa B and to suppress JunD transcriptional activity. Conclusion To our knowledge, this is the first report of MEN1 syndrome associated with bilateral granulosa cell malignancy. We postulate that this presentation may be due to the novel menin gene mutation recently described. PMID:25733923

Hall, Michael J; Innocent, Julie; Rybak, Christina; Veloski, Colleen; Scott, Walter J; Wu, Hong; Ridge, John A; Hoffman, John P; Borghaei, Hossein; Turaka, Aruna; Daly, Mary B

2015-01-01

380

Genistein, a soya isoflavone, prevents azoxymethane-induced up-regulation of WNT/?-catenin signalling and reduces colon pre-neoplasia in rats.  

PubMed

The present study aimed to explore the role(s) of the soya isoflavone genistein (GEN) in preventing the development of colon pre-neoplasia, using Wingless/int (WNT)/?-catenin as a molecular marker of colon abnormality. Specifically, the effects on the WNT/?-catenin signalling pathway from GEN were examined by using an azoxymethane (AOM)-induced rat colon cancer model. Male Sprague-Dawley rats were fed a control (CTL), a soya protein isolate (SPI) or a GEN diet from gestation to 13 weeks of age. The first sampling was conducted at 7 weeks of age for pre-AOM analysis. The remaining rats were injected with AOM at 7 weeks of age. The descending colon was collected 6 weeks later for the evaluation of aberrant crypt foci (ACF), gene expression and nuclear protein accumulation. AOM injection induced aberrant nuclear accumulation of ?-catenin in the CTL group but not in the SPI or GEN group. Moreover, the WNT target genes Cyclin D1 and c-Myc were repressed by SPI and GEN. Meanwhile, SPI and GEN suppressed the expression of WNT signalling genes including Wnt5a, Sfrp1, Sfrp2 and Sfrp5 to the similar level to that of the pre-AOM period. Rats fed SPI and GEN had a decreased number of total aberrant crypts. GEN feeding also resulted in a reduced number of ACF with N = 3 per foci. The reduction of WNT/?-catenin signalling was correlated with the decrease in total aberrant crypts. By testing WNT/?-catenin signalling as a biomarker of colon carcinogenic potential, we showed the novel role of GEN as a suppressor of carcinogen-induced WNT/?-catenin signalling in preventing the development of early colon neoplasia. PMID:22716201

Zhang, Yukun; Li, Qian; Zhou, Dan; Chen, Hong

2013-01-14

381

DIVERSAS MANERAS DE GENERAR ENERGIA CON  

E-print Network

DE OLAS #12;PAISES CON MAYOR CAPACIDAD HIDROELECTRICA Country Annual Hydroelectric Energy Production hydroelectric generating system. Three Gorges Dam Gezhouba Dam #12;COSTO PROMEDIO DE PRODUCCION (KWH) #12;U

Gilbes, Fernando

382

Trastorno por déficit de atención con hiperactividad: comorbilidad con trastornos depresivos y de ansiedad  

Microsoft Academic Search

El estudio analiza el perfil comórbido del Trastorno por Déficit de Atención con Hiperactividad (TDAH) y trastornos depresivos y\\/o de ansiedad (TI), explorando el modelo que predice esta asocia- ción psicopatológica. Se analiza una muestra de 90 casos con TDAH (6-16 años) y mediante investi- gación diferencial se compara la agrupación TDAH+TI con la ausencia de esta comorbilidad. El caso

José Antonio López-Villalobos; Isabel Serrano Pintado; Juan Delgado Sánchez-Mateos

2004-01-01

383

Ependimoma myxopapilar sacro gigante con osteolisis  

PubMed Central

Objetivo: la presentación de un caso de una paciente con un ependimoma sacro con extensa infiltración y destrucción ósea local. Descripción del caso: una mujer de 53 años acudió a la consulta por dolor lumbosacro y alteraciones sensitivas perineales y esfinterianas. La imágenes por Resonancia Magnética (IRM) y la Tomografía Axial Computada (TAC) mostraron una lesión expansiva gigante a nivel S2-S4 con extensa osteólisis e invasión de tejidos adyacentes. Se realizó una exéresis tumoral completa con mejoría del estatus funcional. La anatomía patológica informó ependimoma mixopapilar. Discusión: la extensión de la resección quirúrgica es el mejor predictor de buen pronóstico. El tratamiento radiante se reserva como opción adyuvante para las resecciones incompletas y recidiva tumoral. La quimioterapia sólo debería utilizarse en casos en que la cirugía y la radioterapia estén contraindicadas. Conclusión: Los ependimomas mixopapilares sacros con destrucción ósea y presentación intra y extradural son muy infrecuentes y deben ser tenidos en cuenta entre los diagnósticos diferenciales preoperatorios. Su resección total, siempre que sea posible, es la mejor alternativa terapéutica. PMID:25165615

Ajler, Pablo; Landriel, Federico; Goldschmidt, Ezequiel; Campero, Álvaro; Yampolsky, Claudio

2014-01-01

384

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.

385

Aleaciones con memoria de forma, una filosofía diferente en la ingeniería y el diseño con materias  

Microsoft Academic Search

Los materiales con memoria de forma también llamados materiales inteligentes poseen propiedades que los diferencian del resto de materiales. Estas propiedades no son propiedades mejoradas respecto a los materiales convencionales, sino que son nuevas propiedades que hacen que el proceso de diseño con materiales haya de ser modificado. La comprensión de estas nuevas propiedades y la estandarización de todos los

Fco. Javier Peña Andrés

2002-01-01

386

The iCons Four Year Curriculum Plan Contact: iCons@cns.umass.edu  

E-print Network

program offered by the College of Natural Sciences at the University their evolution in the iCons Program. Students' reflections in their portfolios) YEAR 1 (Spring 2013) iCons-1 (4 CR) 1 section: Tues/Thurs "Global Challenges

Auerbach, Scott M.

387

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

PubMed Central

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. However, most sporadic tumors lack FLCN mutations and the extent to which the BHDS-derived renal tumors share genetic defects associated with the sporadic tumors has not been well studied. Methods BHDS individuals were identified symptomatically and FLCN mutations were confirmed by DNA sequencing. Comparative gene expression profiling analyses were carried out on renal tumors isolated from individuals afflicted with BHDS and a panel of sporadic renal tumors of different subtypes using discriminate and clustering approaches. qRT-PCR was used to confirm selected results of the gene expression analyses. We further analyzed differentially expressed genes using gene set enrichment analysis and pathway analysis approaches. Pathway analysis results were confirmed by generation of independent pathway signatures and application to additional datasets. Results Renal tumors isolated from individuals with BHDS showed distinct gene expression and cytogenetic characteristics from sporadic renal oncocytoma and chromophobe RCC. The most prominent molecular feature of BHDS-derived kidney tumors was high expression of mitochondria-and oxidative phosphorylation (OXPHOS)-associated genes. This mitochondria expression phenotype was associated with deregulation of the PGC-1?-TFAM signaling axis. Loss of FLCN expression across various tumor types is also associated with increased nuclear mitochondrial gene expression. Conclusions Our results support a genetic distinction between BHDS-associated tumors and other renal neoplasias. In addition, deregulation of the PGC-1?-TFAM signaling axis is most pronounced in renal tumors that harbor FLCN mutations and in tumors from other organs that have relatively low expression of FLCN. These results are consistent with the recently discovered interaction between FLCN and AMPK and support a model in which FLCN is a regulator of mitochondrial function. PMID:21162720

2010-01-01

388

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

389

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

390

DIVERSAS MANERAS DE GENERAR ENERGIA CON  

E-print Network

;PAISES CON MAYOR CAPACIDAD HIDROELECTRICA Country Annual Hydroelectric Energy Production (TW-Rivera #12;The Three Gorges Dam project in Hubei, China, is the world's largest hydroelectric generating convirtio en la fuente principal de energia en Puerto Rico #12;23/feb/2008 Wave Power Energía de las Olas

Gilbes, Fernando

391

Equivariant con guration spaces Colin Rourke  

E-print Network

by thinking of the con guration as a set of charged particles and using the electric eld they generate (see 8(X) is a nite disjoint collection of little discs in M which is closed under the action of G and such that each

Rourke, Colin

392

Google Scholar: the pros and the cons  

Microsoft Academic Search

Purpose – To identify the pros and the cons of Google Scholar. Design\\/methodology\\/approach – Chronicles the recent history of the Google Scholar search engine from its inception in November 2004 and critiques it with regard to its merits and demerits. Findings – Feels that there are massive content omissions presently but that, with future changes in its structure, Google Scholar

Péter Jacsó

2005-01-01

393

Interacción, Motivación y Emociones con Videojuegos  

Microsoft Academic Search

El principal objetivo de este trabajo es comprender como se construye el conocimiento y se adquieren competencias en una comunidad virtual de aprendizaje soportada en una plataforma telemática integrada con un juego 3D de rol masivo. Para ello, hemos diseñado actividades formativas colaborativas que nos permitirán modelar las interacciones de una comunidad de aprendizaje virtual producidas en juegos de rol

Carina S. González; Francisco Blanco

394

The Pros and Cons of Artificial Reefs  

NSDL National Science Digital Library

This lesson plan asks students to consider whether artificial reefs (human-made objects in the ocean or sea) are good for marine ecosystems. Students will look at pictures of artificial reefs and read articles describing the pros and cons of these structures. They will conclude by writing paragraphs explaining whether they think a new artificial reef should be created in Florida waters.

395

Interacción con Entornos Virtuales en teléfonos móviles  

Microsoft Academic Search

En este trabajo presentamos un sistema para la navegación en entornos virtuales 3D sobre teléfonos móviles. Tradicionalmente la interacción con el teléfono móvil se ha realizado utilizando el teclado como dispositivo de interacción. Sin embargo, gracias a las capacidades de los nuevos terminales es posible aprovechar dispositivos como la cámara incorporada o los acelerómetros para implementar interacciones basadas en movimientos

Jesús Gimeno; Marcos Fernández; Pedro Morillo; Lucía Vera

396

The pros and cons of hospital employment.  

PubMed

The pros and cons of hospital employment vary significantly in today's economic environment. This chapter summarizes the advantages and disadvantages of hospital employment with an emphasis on the critical aspect of formalizing an agreement with the hospital employer to prevent future salary reductions and/or termination. PMID:23924751

Bert, Jack M

2013-09-01

397

Descubre la biblioteca con Gua rpida  

E-print Network

provenientes de los recursos electrónicos y del repositorio institucional #12;Acceso desde la página web de la, revistas, audiovisuales, mapas, ... Repositorio UAM: tesis doctorales, proyectos de investigación, revistas Repositorio · Algunas suscripciones a recursos electrónicos #12;Enlace con el documento Acceso mediante el

Autonoma de Madrid, Universidad

398

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

399

5-bp Classical Satellite DNA Loci from Chromosome-1 Instability in Cervical Neoplasia Detected by DNA Breakage Detection/Fluorescence in Situ Hybridization (DBD-FISH).  

PubMed

We aimed to evaluate the association between the progressive stages of cervical neoplasia and DNA damage in 5-bp classical satellite DNA sequences from chromosome-1 in cervical epithelium and in peripheral blood lymphocytes using DNA breakage detection/fluorescence in situ hybridization (DBD-FISH). A hospital-based unmatched case-control study was conducted in 2011 with a sample of 30 women grouped according to disease stage and selected according to histological diagnosis; 10 with low-grade squamous intraepithelial lesions (LG-SIL), 10 with high-grade SIL (HG-SIL), and 10 with no cervical lesions, from the Unidad Medica de Alta Especialidad of The Mexican Social Security Institute, IMSS, Mexico. Specific chromosome damage levels in 5-bp classical satellite DNA sequences from chromosome-1 were evaluated in cervical epithelium and peripheral blood lymphocytes using the DBD-FISH technique. Whole-genome DNA hybridization was used as a reference for the level of damage. Results of Kruskal-Wallis test showed a significant increase according to neoplastic development in both tissues. The instability of 5-bp classical satellite DNA sequences from chromosome-1 was evidenced using chromosome-orientation FISH. In conclusion, we suggest that the progression to malignant transformation involves an increase in the instability of 5-bp classical satellite DNA sequences from chromosome-1. PMID:23429197

Cortés-Gutiérrez, Elva I; Ortíz-Hernández, Brenda L; Dávila-Rodríguez, Martha I; Cerda-Flores, Ricardo M; Fernández, José Luis; López-Fernández, Carmen; Gosálvez, Jaime

2013-01-01

400

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

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