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1

Neoplasia: The Second Decade  

PubMed Central

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

Rehemtulla, Alnawaz

2008-01-01

2

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

3

Multiple Endocrine Neoplasia  

Microsoft Academic Search

\\u000a Several genetic syndromes are associated with multiple endocrine tumors. In this chapter, we focus on Multiple Endocrine Neoplasia\\u000a (MEN) types 2 and 1. Von Hippel Lindau and Neurofibromatosis will be discussed in other sections.

Yariv J. Houvras; Gilbert H. Daniels

4

Multiple endocrine neoplasia  

Microsoft Academic Search

Multiple endocrine neoplasia (MEN) is characterized by tumours involving two or more endocrine glands within a single patient. There are two major forms of MEN: type 1 (MEN1, Wermer's syndrome) and type 2 (MEN2, Sipple's syndrome). MEN1 is characterized by the combined occurrence of tumours in the parathyroids, pancreatic islet cells and anterior pituitary; MEN2 is characterized by the association

Rajesh V. Thakker

2009-01-01

5

Multiple endocrine neoplasia  

Microsoft Academic Search

\\u000a The multiple endocrine neoplasia (MEN) syndromes are a family of genetic conditions characterized by a predisposition to the\\u000a development of neoplasms in multiple endocrine glands. The pathologic change in affected glands is characteristically multicentric\\u000a and may be expressed as hyperplasia, adenoma, or carcinoma. The MEN syndromes are inherited in an autosomal dominant manner\\u000a and are classified according to the pattern

Julie A. Miller; Jeffrey A. Norton

6

Multiple Endocrine Neoplasia Syndromes  

PubMed Central

The multiple endocrine neoplasia (MEN) syndromes consist of three distinct disease entities. They have in common adenomatous, carcinomatous or hyperplastic involvement of a variety of endocrine glands, and an autosomal dominant inheritance. MEN I includes hyperparathyroidism, islet cell and pituitary tumors. The components of MEN IIa are hyperparathyroidism, medullary thyroid carcinoma and pheochromocytoma. MEN IIb includes multiple neuromas, medullary thyroid carcinoma and pheochromocytoma. Effective tests are available for the early detection of components of the syndromes in potentially affected patients. Screening can lead to therapeutic intervention before clinical sequelae ensue. PMID:6247851

Pont, Allan

1980-01-01

7

Multiple endocrine neoplasia type 2  

Microsoft Academic Search

Multiple Endocrine Neoplasia Type 2 (MEN2) is a rare hereditary complex disorder characterized by the presence of medullary thyroid carcinoma (MTC), unilateral or bilateral pheochromocytoma (PHEO) and other hyperplasia and\\/or neoplasia of different endocrine tissues within a single patient. MEN2 has been reported in approximately 500 to 1000 families worldwide and the prevalence has been estimated at approximately 1:30,000. Two

Francesca Marini; Alberto Falchetti; Francesca Del Monte; Silvia Carbonell Sala; Isabella Tognarini; Ettore Luzi; Maria Luisa Brandi

2006-01-01

8

Lobular neoplasia: morphology and management.  

PubMed

Context.-Lobular neoplasia encompasses a spectrum of disease, including atypical lobular hyperplasia and lobular carcinoma in situ. Although classic forms of lobular neoplasia are predominantly heralded as a risk marker, the pleomorphic form of lobular carcinoma in situ is generally regarded as a more aggressive subtype and a possible cancer precursor, and thus is treated in a manner more similar to ductal carcinoma in situ than classic forms of lobular neoplasia. Objective.-To focus on the morphologic spectrum of lobular neoplasia as highlighted by 3 cases and current management recommendations. Areas of diagnostic challenge and controversy are addressed. Data Sources.-A review of the pertinent published literature and current national guidelines was conducted. Conclusions.-Correct classification of classic lobular neoplasia and pleomorphic lobular carcinoma in situ is critical because of differences in clinical management, with current treatment strategies focused on risk reduction for patients with classic lobular neoplasia and eradication of the lesion for those with pleomorphic lobular carcinoma in situ. PMID:25268198

Jorns, Julie; Sabel, Michael S; Pang, Judy C

2014-10-01

9

Tissue eosinophilia in head and neck squamous neoplasia: an update.  

PubMed

Eosinophils are multifunctional granulocytes that play an imperative role in health and disease. They have also been found to be a crucial component of peri- and intratumoral inflammatory infiltrate. Tumor-associated tissue eosinophilia (TATE) has been observed and described in many tumors, including head and neck neoplasia. The process of eosinophil recruitment and its function in tumors has not been exactly defined yet. Correlation of tissue eosinophilia with prognosis has shown variable results ranging from favourable to unfavourable prognosis or even having no influence on patients outcome. Eosinophils are hypothesized to have tumor defensive as well as tumor promotive function. This dichotomous role of tissue eosinophilia with regard to prognosis has also been noted in head and neck neoplasia and premalignancies. So, the present review attempts to discuss TATE and its possible pros and cons in head and neck neoplasia. PMID:25265347

Jain, M; Kasetty, S; Khan, S; Jain, N K

2014-09-01

10

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

11

Intrathoracic neoplasia: Epidemiology and etiology  

SciTech Connect

Neoplasms of the thorax encompass those derived from the thoracic wall, trachea, mediastinum, lungs and pleura. They represent a wide variety of lesions including benign and malignant tumors arising from many tissues. The large surface area, 60 to 90 m{sup 2} in man, represented by the respiratory epithelium and associated thoracic structures are ideal targets for carcinogens carried by inspired air. The topic of discussion in this report is the epidemiology, etiology, and mechanisms of spontaneous intrathoracic neoplasia in animals and man. Much of what we know or suspect about thoracic neoplasia in animals has been extrapolated from experimentally-induced neoplasms.

Weller, R.E.

1992-05-01

12

Genetics Home Reference: Multiple endocrine neoplasia  

MedlinePLUS

... is a group of disorders that affect the body's network of hormone-producing glands (the endocrine system). Hormones are chemical messengers that travel through the bloodstream and regulate the ... Multiple endocrine neoplasia typically involves tumors (neoplasia) in ...

13

Angiogenesis in Vulvar Intraepithelial Neoplasia  

Microsoft Academic Search

Vulvar intraepithelial neoplasia (VIN) has been reported to be a precursor of invasive vulvar cancer. Switching to the angiogenic phenotype is considered a key step in tumor growth. Microvessel density (MVD) and vascular endothelial growth factor (VEGF), a highly angiogenic peptide, are important parameters of tumor angiogenesis. Forty-three histologic slides with 38 VIN I–III lesions were immunohistochemically stained for factor

Dagmar Bancher-Todesca; Andreas Obermair; Selcuk Bilgi; Petra Kohlberger; Christian Kainz; Gerhard Breitenecker; Sepp Leodolter; Gerald Gitsch

1997-01-01

14

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

15

Multiple endocrine neoplasia type 1  

Microsoft Academic Search

Combined clinical and laboratory investigations of multiple endocrine neoplasia type 1 (MEN1) have resulted in an increased understanding of this disorder which may be inherited as an autosomal dominant condition. Defining the features of each disease manifestation in MEN1 has improved patient management and treatment, and has also facilitated a screening protocol to be instituted. The application of the techniques

A A J Pannett; R V Thakker

1999-01-01

16

Endoscopic therapies for Barrett's neoplasia  

PubMed Central

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

2014-01-01

17

Combinatorial chemoprevention of intestinal neoplasia  

Microsoft Academic Search

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

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

2000-01-01

18

Multiple endocrine neoplasia type 2  

Microsoft Academic Search

Opinion statement  Multiple endocrine neoplasia type 2 (MEN-2) is a hereditary syndrome that is transmitted in an autosomal dominant pattern.\\u000a MEN-2A, MEN-2B, and familial medullary thyroid cancer (MTC) comprise the MEN-2 syndrome. A germline mutation in the RET proto-oncogene\\u000a is responsible for the MEN-2 syndrome. Recent data indicate that in 99% of MEN-2 cases, a germline RET mutation can be identified

Michael E. Gertner; Electron Kebebew

2004-01-01

19

Multiple Endocrine Neoplasia Type I  

Microsoft Academic Search

Opinion statement  Multiple endocrine neoplasia type I is a rare autosomal dominant disorder with many endocrine and nonendocrine manifestations.\\u000a Hyperparathyroidism, islet cell tumors, and pituitary tumors are diagnosed most commonly in these patients. There is controversy\\u000a regarding treatment of the different manifestations and screening modalities of this disorder because no large series has\\u000a determined the best therapeutic approach. Our institution advocates

Rasa Zarnegar; Laurent Brunaud; Orlo H. Clark

2002-01-01

20

Neoplasias mielodisplásicas o mieloproliferativas: Tratamiento (PDQ®)  

Cancer.gov

Resumen de información revisada por expertos acerca del tratamiento de las neoplasias mielodisplásicas o mieloproliferativas incluso las leucemias mielomonocíticas crónicas o juveniles y la LMC atípica.

21

Neoplasias mielodisplásicas o mieloproliferativas: Tratamiento (PDQ®)  

Cancer.gov

Resumen de información revisada por expertos acerca del tratamiento de las neoplasias mielodisplásicas o mieloproliferativas, incluso las leucemias mielomonocíticas crónicas o juveniles, y la LMC atípica.

22

Non?operative breast pathology: lobular neoplasia  

PubMed Central

Lobular neoplasia is a relatively uncommon lesion, which is frequently diagnosed in biopsy specimens taken for other reasons. Although the histological features of this lesion are well known, its biological significance as a “risk indicator” or “breast cancer precursor” has been a matter of debate. This review provides an update on recent clinicopathological and molecular data on lobular neoplasia and how these have changed the way these lesions are perceived and, most importantly, managed. Furthermore, the current recommendations for the management of lobular neoplasia diagnosed on core needle biopsies proposed in the National Health Service Breast Cancer Screening guidelines are discussed. PMID:17182661

Reis?Filho, Jorge S; Pinder, Sarah E

2007-01-01

23

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

24

[Multiple endocrine neoplasia type 2].  

PubMed

The term multiple endocrine neoplasia (MEN) was introduced by Steiner et al. in 1968 to describe disorders that include a combination of endocrine tumors. The Wermer syndrome was designed as MEN 1 and the Sipple syndrome as MEN 2. Sizemore et al. (1974) completed that the MEN 2 category included 2 subgroups: patients with medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid disease and a normal appearance (MEN 2A) and other without parathyroid disease but with mucosal neuromas and mesodermal abnormalities (MEN 2B). MTC is usually the first tumor diagnosed. The diagnosis of MTC has several implications: disease extent should be evaluated, pheochromocytoma and hyperparathyroidism should be screened and whether the MTC is sporadic or hereditary should be determined by a direct analysis of the RET proto-oncogene. Here, the pathological characteristics, genetic abnormalities, and clinical features of MEN 2 are discussed. The diagnostic and therapeutic approaches used to patients with clinical disease and carriers identified through familiar screening are also described. Progresses related especially to genetic screening and earlier intervention have permitted an improvement in the long-term outcome. However, treatment for disseminated disease is still ineffective. PMID:16444355

Maia, Ana Luiza; Gross, Jorge Luiz; Puñales, Marcia Khaled

2005-10-01

25

Prostatic intraepithelial neoplasia: an overview.  

PubMed

Prostatic intraepithelial neoplasia (PIN) is the most established precursor of prostatic carcinoma. The presence of prominent nucleoli within an existing duct structure is an easy way to identify the disorder. Four main patterns of high-grade PIN (HGPIN) have been described: tufting, micropapillary, cribriform, and flat. In addition to exhibiting similar cytologic features, both HGPIN and prostatic carcinoma are associated with increased incidence and severity with age, and with high rates of occurrence in the peripheral zone of the prostate. HGPIN and prostate cancer share genetic and molecular markers as well, with PIN representing an intermediate stage between benign epithelium and invasive malignant carcinoma. The clinical significance of HGPIN is that it identifies patients at risk for malignancy. With the increased use of extended biopsy protocols, clinicians are more likely to identify HGPIN and less likely to miss concurrent carcinoma. Androgen deprivation therapy decreases the prevalence and extent of PIN, and may play a role in chemoprevention. Preliminary studies suggest that selective estrogen receptor modulators may also prevent the progression of HGPIN to prostate cancer. PMID:16985875

Brawer, Michael K

2005-01-01

26

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

27

Fractal Analysis of Cervical Intraepithelial Neoplasia  

PubMed Central

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

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

2014-01-01

28

High-grade prostatic intraepithelial neoplasia  

Microsoft Academic Search

High-grade prostatic intraepithelial neoplasia (PIN) is now accepted as the most likely preinvasive stage of adenocarcinoma, almost two decades after its first formal description. PIN has a high predictive value as a marker for adenocarcinoma, and its identification warrants repeat biopsy for concurrent or subsequent invasive carcinoma. The only method of detection is biopsy; PIN does not significantly elevate serum

David G Bostwick; Junqi Qian

2004-01-01

29

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

30

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.

31

Vulvar Intraepithelial Neoplasia: New concepts and strategy  

Microsoft Academic Search

Vulvar intraepithelial neoplasia (VIN) is a rare condition which can develop into an invasive\\u000acarcinoma. This skin-disease affects mainly young women, and causes many severe and\\u000along-lasting symptoms such as pruritus, vulvodynia and psychosexual dysfunction. Over\\u000a80% of VIN-affected women present with multifocal vulvar disease, and often neoplastic\\u000achanges can be found in the entire lower genital tract. Clinically, it

Seters van M

2008-01-01

32

REMBRANDT - Repository for Molecular Brain Neoplasia Data  

Cancer.gov

REpository for Molecular BRAin Neoplasia DaTa (REMBRANDT) is a robust bioinformatics knowledgebase framework that leverages data warehousing technology to host and integrate clinical and functional genomics data from clinical trials involving patients suffering from Gliomas. The knowledge framework will provide researchers with the ability to perform ad hoc querying and reporting across multiple data domains, such as Gene Expression, Chromosomal aberrations and Clinical data.

33

The Genetics of Multiple Endocrine Neoplasia (MEN)  

Microsoft Academic Search

Multiple Endocrine Neoplasia (MEN) refers to the family of diseases characterized by hyperplasia and\\/or tumoral proliferation in various organs derived from the neural crest. MEN are transmitted in an autosomal dominant fashion in affected pedigrees with a high degree of penetrance. MEN 1 and MEN 2A\\/B loci have recently been mapped, respectively, to chromosomes 11 and 10 by linkage analysis

A. Calender; I. Schuffenecker; G. M. Lenoir

1992-01-01

34

The Hirschsprung's-multiple endocrine neoplasia connection  

PubMed Central

The risk of patients with Hirschsprung's disease later developing multiple endocrine neoplasia remains a matter of concern. The multiple endocrine neoplasia 2–Hirschsprung's disease association has been shown to cosegregate in Hirschsprung's disease patients with both short- and long-segment aganglionosis, although patients with long-segment aganglionosis a to carry the greatest risk. The Hirschsprung's disease–medullary thyroid carcinoma relationship also appears to be bi-directional, and activation or suppression of the rearranged during transfection gene appeared to vary over succeeding generations within the same family. Rearranged during transfection gene variations are associated with both conditions. The cosegregation of Hirschsprung's disease and multiple endocrine neoplasia 2 is particularly interesting as it involves both “switch off” and “switch on” of the rearranged during transfection proto-oncogene in the same patient. This cosegregation mostly relates to the cysteine-rich area on RET-620 (the “Janus gene”). The mechanism whereby rearranged during transfection influences gene activation in multiple endocrine neoplasia 2 is complex, but genetic variations impair the rearranged during transfection tyrosine kinase response to tyrosine kinase activation, thus appearing to dictate downstream signaling cascade responses. Better understanding of the RET-620 relationship allows for a more cost-effective method of identifying those at risk by focusing rearranged during transfection gene testing to this specific area as a “hot spot”. The clinical awareness of possible medullary thyroid carcinoma has led to timely intervention and early treatment of this chemo- and radioresistant tumor with poor prognosis. Establishment of “risk” by genetic testing has become a classic model of molecular medicine being integrated into patient care and offering rearranged during transfection-directed prophylactic surgical management. In addition, novel approaches to treatment based on this genetic knowledge have already shown early promise in randomized clinical trials. PMID:22584708

Moore, Sam W.; Zaahl, Monique

2012-01-01

35

Sebaceous neoplasia and Torre-Muir syndrome  

PubMed Central

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

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

2007-01-01

36

Lethality of Multiple Endocrine Neoplasia Type I  

Microsoft Academic Search

. The lethality of the endocrine tumors associated with multiple endocrine neoplasia type I (MEN-I), particularly\\u000a the pancreatic islet cell tumors, has been controversial. We evaluated the cause and age of death in MEN-I kindreds. Our database\\u000a contains 34 distinct kindreds with 1838 members. Reliable death data are available for 103 people (excluding accidents and\\u000a age < 18 years). We

Gerard M. Doherty; John A. Olson; Margaret M. Frisella; Terry C. Lairmore; Jeffrey A. Norton

1998-01-01

37

High-Grade Prostatic Intraepithelial Neoplasia  

PubMed Central

High-grade prostatic intraepithelial neoplasia (HGPIN) has been established as a precursor to prostatic adenocarcinoma. HGPIN shares many morphological, genetic, and molecular signatures with prostate cancer. Its predictive value for the development of future adenocarcinoma during the prostate-specific antigen screening era has decreased, mostly owing to the increase in prostate biopsy cores. Nevertheless, a literature review supports that large-volume HGPIN and multiple cores of involvement at the initial biopsy should prompt a repeat biopsy of the prostate within 1 year. No treatment is recommended for HGPIN to slow its progression to cancer. PMID:22670187

Miocinovic, Ranko; Magi Galluzzi, Cristina; Klein, Eric A

2012-01-01

38

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

39

Pancreatic paracoccidioidomycosis simulating malignant neoplasia: Case report  

PubMed Central

Paracoccidioidomycosis is a systemic granulomatous disease caused by fungus, and must be considered in the differential diagnosis of intra-abdominal tumors in endemic areas. We report a rare case of paracoccidioidomycosis in the pancreas. A 45-year-old man was referred to our institution with a 2-mo history of epigastric abdominal pain that was not diet-related, with night sweating, inappetence, weight loss, jaundice, pruritus, choluria, and acholic feces, without signs of sepsis or palpable tumors. Abdominal ultrasonography (US) showed a solid mass of approximately 7 cm × 5.5 cm on the pancreas head. Abdominal computerized tomography showed dilation of the biliary tract, an enlarged pancreas (up to 4.5 in the head region), with dilation of the major pancreatic duct. The patient underwent exploratory laparotomy, and the surgical description consisted of a tumor, measuring 7 to 8 cm with a poorly-defined margin, adhering to posterior planes and mesenteric vessels, showing an enlarged bile duct. External drainage of the biliary tract, Roux-en-Y gastroenteroanastomosis, lymph node excision, and biopsies were performed, but malignant neoplasia was not found. Microscopic analysis showed chronic pancreatitis and a granulomatous chronic inflammatory process in the choledochal lymph node. Acid-alcohol resistant bacillus and fungus screening were negative. Fine-needle aspiration of the pancreas was performed under US guidance. The smear was compatible with infection by Paracoccidioides brasiliensis. We report a rare case of paracoccidioidomycosis simulating a malignant neoplasia in the pancreas head. PMID:24039371

Lima, Talles Bazeia; Domingues, Maria Aparecida Custódio; Caramori, Carlos Antonio; Silva, Giovanni Faria; de Oliveira, Cássio Vieira; Yamashiro, Fábio da Silva; Franzoni, Letícia de Campos; Sassaki, Lígia Yukie; Romeiro, Fernando Gomes

2013-01-01

40

Solid Tumors Associated with Multiple Endocrine Neoplasias  

PubMed Central

We present an update on molecular and clinical genetics of solid tumors associated with the various multiple endocrine neoplasias (MEN) syndromes. MEN type 1 (MEN 1) describes the association of pituitary, parathyroid, pancreatic islet cell tumors with a variety of many other lesions; MEN type 2 (MEN 2) conditions represent at least four different syndromes that associate pheochromocytoma with medullary thyroid carcinoma, hyperparathyroidism, and a number of other manifestations. Other pheochromocytoma-associated syndromes include von Hippel-Lindau disease, neurofibromatosis 1, and the recently defined paraganglioma syndromes type 1, 3 and 4, the Carney-Stratakis syndrome and the Carney triad. Carney-Stratakis syndrome is characterized by the association of paragangliomas and familial gastrointestinal stromal tumors (GIST). In the Carney triad, patients can manifest GIST, lung chondroma, paraganglioma, adrenal adenoma and pheochromocytoma, esophageal leiomyoma and other conditions. Carney complex is yet another form of MEN that is characterized by skin tumors and pigmented lesions, myxomas, schwannomas, and various endocrine neoplasias. PMID:20951316

Almeida, Madson Q.; Stratakis, Constantine A.

2010-01-01

41

Treatment of vulvar intraepithelial neoplasia with topical imiquimod  

Microsoft Academic Search

Background: Alternatives to surgery are needed for the treatment of vulvar intraepithelial neoplasia. We investigated the effectiveness of imiquimod 5% cream, a topical immuneresponse modulator, for the treatment of this condition. Methods: Fifty-two patients with grade 2 or 3 vulvar intraepithelial neoplasia were randomly assigned to receive either imiquimod or placebo, applied twice weekly for 16 weeks. The primary outcome

Manon van Seters; Marc van Beurden; Kate ten F. J. W; Ilse Beckmann; M. J. C. Eijkemans; C. J. M. Meijer; N. K. Aaronson; K. Aaronson; C. Heijmans-Antonissen; Freek J. Zijlstra; T. J. M. Helmerhorst

2008-01-01

42

Vulvar intraepithelial neoplasia and microinvasive carcinoma of the vulva  

Microsoft Academic Search

The pathological, cytological, and clinical features of vulvar intraepithelial neoplasia (VIN) are described. The rate of progression of VIN III to an invasive carcinoma is very low and spontaneous regression can occur. These features prevent the drawing of a direct analogy between vulvar and cervical intraepithelial neoplasia. The concept of microinvasive carcinoma of the vulva is discussed, and it is

C H Buckley; E B Butler; H Fox

1984-01-01

43

Pregnancy complicated by multiple endocrine neoplasia type IIA (Sipple's syndrome)  

Microsoft Academic Search

A patient with preexisting multiple endocrine neoplasia type IIA had normal 24-hour urinary metanephrine and vanillylmandelic acid excretions before and during pregnancy. After a benign prenatal course, the patient had a term spontaneous vaginal delivery. Multiple endocrine neoplasia type IIA antedating pregnancy may be associated with a normal obstetric outcome in the absence of a pheochromocytoma. (Am J Obstet Gynecol

Joseph R. Wax; M EGGLESTONJR; Katherine E. Teague

1997-01-01

44

Genitoanal human papillomavirus infection and associated neoplasias.  

PubMed

Human papillomavirus (HPV) infection is the most common sexually transmitted virus infection; about 40 out of 150 known HPV genotypes have been associated with genitoanal lesions in the female and male. They have been divided into low-risk (LR) and high-risk (HR) HPV types according to the association of each HPV genotype with genitoanal benign warts, genitoanal cancer and precursor lesions. For the most part, genitoanal HPV infection is equally common in men and in women. Genitoanal HPVs are predominantly transmitted by sexual intercourse. In a minor number of individuals where HR HPV infection has persisted, malignant squamous-cell tumors may develop. There are 15 mucosal oncogenic HPV types which are the etiological factor of cervical cancer and other genitoanal cancers. DNAs of HR HPV types are present in 100% of all cervical carcinomas and in 100% of the precursor lesions, the cervical intraepithelial neoplasias 2 and 3. HPV-16 and -18 alone account for 70% of the oncogenic mucosal HPV types identified. HR HPV types, mostly HPV-16 and -18, are the causes of vaginal and vulvar cancers in females, anal cancers in both genders and cancer of the penis in men. While anal cancers are linked to HR HPVs in more than 80% of cases, only 40% of vulvar cancers and 50% of penile cancers are HPV positive. Genitoanal cancers have a similar anatomy, histology and similar risk factors as well as natural histories. About 60% of vulvar and 50% of penile cancers are HPV negative, but associated with chronic inflammatory disorders, mainly lichen sclerosus. Clinical manifestations of LR HPVs in both sexes are genitoanal warts (condylomata acuminata), which are benign highly infectious tumors. The highest rate of warts is observed in females 16-24 years of age. In males the peak is at the age of 20-24 years. Diagnosis of genitoanal warts should exclude other sexually transmitted infections and diseases. A high number of genitoanal dermatoses, benign tumors, malignant squamous-cell neoplasias and cancer precursors may mimic condylomata acuminata. These malignant counterparts have to be ruled out by biopsy and a thorough histological workup. Therapy of manifest genitoanal HPV-associated lesions has profited from the development of local immunotherapy with imiquimod and local therapy with green tea derivatives (sinecatechin) 10% (Europe) and 15% (USA). Disease recurrence is a crucial problem with treatment, one that could potentially be reduced with the use of immunomodulating agents such as immuquimod and sinecatachins. Recently primary prevention of genitoanal clinical manifestations associated with HPV-6, -11, -16 and -18 including cancer precursors (intraepithelial neoplasias) has become true by the release of prophylactic quadrivalent (HPV-6, -11, -16, -18) and bivalent (HPV-16, -18) vaccines. These vaccines consist of HPV L1 virus-like particles which induce high anti-L1 serum-neutralizing antibody concentrations. Dermatologists and venereologists, general practitioners and pediatricians should cooperate with gynecologists to vaccinate young women and men in order to increase vaccination rates. In Australia and Scotland, an immense efficacy has been observed both regarding the prevention of benign genitoanal warts and cancer precursors caused by the vaccine HPV types. An absolute prerequisite of such a successful prevention against HPV-associated neoplasias is the administration of the vaccine before the first sexual contact. PMID:24643181

Gross, Gerd

2014-01-01

45

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

46

Photochemoprevention of cutaneous neoplasia through natural products.  

PubMed

Non-melanoma skin cancers such as squamous cell carcinoma and basal cell carcinoma are the most common types of human tumors, representing 30% of the new cases of malignancies diagnosed each year. Ultraviolet radiation (UV) from the sun is a major cause of non-melanoma skin cancer in humans. The prevention and mainly the photochemoprevention with natural products represent a simple but very effective strategy in the management of cutaneous neoplasia. Here we review the progress in the research of new and existing agents developed to protect the skin exposed to UV. We also discuss the current state of knowledge on their photosuppression mechanism in humans as well as in animal models, and efficiency in cancer prevention. PMID:19300410

Filip, A; Clichici, S; Daicoviciu, D; Adriana, M; Postescu, I D; Perde-Schrepler, M; Olteanu, D

2009-03-01

47

Modeling human endothelial cell transformation in vascular neoplasias  

PubMed Central

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

Wen, Victoria W.; MacKenzie, Karen L.

2013-01-01

48

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

49

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

50

[Multiple endocrine neoplasia type 2A].  

PubMed

Multiple endocrine neoplasia (MEN) type 2A, or Sipple syndrome, is a rare autosomal dominantly inherited syndrome, which is characterized as combination of medullary thyroid carcinoma, pheochromocytoma, primary hyperparathyroidism, sometimes with rarer inherited disorders like Hirschsprung disease and cutaneous lichen amyloidosis. Syndrome is caused by germinative mutations in c-ret protooncogene, which are typical for different MEN 2 syndromes. We report a clinical case of MEN 2A. A 43-year-old female patient was operated on for pheochromocytoma 7 years after diagnosis and treatment of spread medullary thyroid carcinoma. This is the most common combination of MEN 2A tumors. Diagnosis was based upon clinical data, tumors combinations and analysis of inherited endocrine pathology in first-line relatives. This syndrome has already been diagnosed in Lithuania, but in the last decade after determining the genetic basis of MEN 2 and applying modern genetic examinations in clinical praxis, the strategy of diagnostics and prophylaxis of this syndrome has changed and survival prognosis for patients with this syndrome has improved. Conception of pathogenesis and clinical features of MEN 2A syndrome, genetic selection of inheritors of this syndrome is one more step in early cancer diagnosis, which allows to use cancer prevention measures in time, to apply effective treatment and improve patients' prognosis. Reporting this clinical case of MEN 2A we aimed to pay attention of general practitioners to this rare, but in Lithuania diagnosed too, syndrome and its clinic, diagnostic, and treatment features. PMID:16607064

Juodele, Linas; Krasauskas, Virgilijus; Zindzius, Algimantas; Juozaityte, Elona; Pundzius, Juozas

2006-01-01

51

Primary hyperparathyroidism and multiple endocrine neoplasia (MEN).  

PubMed

In about 80% of the cases, primary hyperparathyroidism (pHPT) is caused by a single parathyroid adenoma. However, the disease may be complicated by involvement of more than one parathyroid gland or by the combination with other endocrine tumors (syndrome of multiple endocrine neoplasia = MEN). This presentation deals with our experience in such conditions. During 11 years, 98 cases of pHPT were seen (90 in Ulm from 1968 to 1979, 8 since then in Heidelberg). In 9 patients, 2 to 4 parathyroids were in hyperfunction. A recurrence of pHPT was diagnosed after symptomfree intervals of 2 - 13 years in 5 patients. Data are presented of 4 patients suffering from MEN type I (Wermer syndrome): 3 had Zollinger-Ellison syndrome and pHPT, and the 4th insulinoma and pHPT. Whereas pHPT is the most frequent endocrinopathy in MEN type I, it is rarely seen in MEN type II, the Sipple syndrome (combination of medullary thyroid carcinoma, MTC, and pheochromocytoma). Among 20 own cases with MTC and 10 others with pheochromocytoma, no pHPT was observed. The common basis for the development of MEN syndromes is Pearse's concept of the diffuse neuroendocrine system (DNES). PMID:6122257

Ziegler, R; Minne, H; Raue, F

1982-01-01

52

Gestational trophoblastic neoplasia in the 1990s.  

PubMed Central

Major advances have been achieved during the past 40 years in the epidemiology, etiology, pathology, endocrinology, immunology, diagnosis, and treatment of molar pregnancy (MP) and gestational trophoblastic neoplasia (GTN). MP is now recognized as composing two distinct entities--complete and partial, with distinct histopathology, genetics, and clinical presentations. Proper management is dependent on a thorough understanding of each type. Early diagnosis and effective treatment of patients with GTN has resulted in 100 percent cure rates in non-metastatic disease and in the majority of patients with metastases. In most instances, resistant disease leading to death results from delayed diagnosis and overwhelming tumor burden. Moreover, in most instances successful treatment can be accomplished with preservation of fertility and normal pregnancy outcome anticipated. A rare variant of choriocarcinoma called placental site trophoblastic tumor (PSTT) has been described, which, although curable by surgery when localized, is usually fatal when disseminated. It is anticipated that during the decade of the nineties the scientific work in progress will lead to earlier diagnosis and improved survival in resistant cases. PMID:1667240

Goldstein, D. P.

1991-01-01

53

Pigmented squamous intraepithelial neoplasia of the esophagus  

PubMed Central

Squamous cell carcinoma (SCC) usually lacks melanocytes within the tumor. A few reports have documented invasive SCC or SCC in situ (intraepithelial neoplasia, IEN) with melanocytic hyperplasia within the tumor, referred to as pigmented SCC, in some organs. However, case series of pigmented SCC or IEN of the esophagus have not yet been reported. This is the first study to analyze the incidence and clinicopathological features of pigmented SCC or IEN of the esophagus. We reviewed 18 surgically-resected and 122 endoscopically-resected esophageal specimens, including 79 cases of IEN. Three cases of pigmented IEN were observed in this series, and all of them were located in the middle to lower third of the esophagus. Two of 3 cases had melanocytosis in the non-neoplastic squamous epithelium around the IEN. The incidence of pigmented IEN was 2.5% of all endoscopically resected specimens and 3.8% of IEN cases. No pigmented invasive SCC was detected in both endoscopically-resected and surgically-resected specimens. The mechanism of pigmentation of esophageal IEN is unknown. However, production of melanocyte chemotactic factors by tumor cells has been demonstrated in pigmented SCC of the oral mucosa. Moreover, two of 3 cases of pigmented IEN in the present series had melanocytosis in the non-neoplastic squamous epithelium, and melanocytosis is thought to be associated with chronic esophagitis, therefore, it has been hypothesized that various stimuli can cause pigmentation in squamous epithelium. Additional studies are needed to clarify the mechanism of pigmentation in squamous IEN of the esophagus. PMID:24040452

Ishida, Mitsuaki; Mochizuki, Yosuke; Iwai, Muneo; Yoshida, Keiko; Kagotani, Akiko; Okabe, Hidetoshi

2013-01-01

54

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

55

Prostatic Intraepithelial Neoplasia is Risk Factor for Adenocarcinoma: Predictive Accuracy in Needle Biopsies  

Microsoft Academic Search

PurposeHigh grade prostatic intraepithelial neoplasia is considered the most likely precursor of prostatic adenocarcinoma. However, the natural history and predictive value of prostatic intraepithelial neoplasia for cancer are unknown.

Deborah Davidson; David G. Bostwick; Junqi Qian; Peter C. Wollan; Joseph E. Oesterling; Richard A. Rudders; Mike Siroky; Magda Stilmant

1995-01-01

56

Vulvar Intraepithelial Neoplasia III: A Viral Disease of Undetermined Progressive Potential  

Microsoft Academic Search

Seventy-three patients with vulvar intraepithelial neoplasia (VIN) grade III were followed for a median of 5 years after primary treatment. Thirty women also had a diagnosis of cervical neoplasia. During the follow-up 26 patients (36%) had one or more vulvar recurrences. Recurrences were seen significantly more often in the patients who also had cervical neoplasia, indicating a common etiology. Microinvasive

Ulla Hørding; Jette Junge; Hemming Poulsen; Finn Lundvall

1995-01-01

57

The Incidence of High Grade Prostatic Intraepithelial Neoplasia in Needle Biopsies  

Microsoft Academic Search

PurposeHigh grade prostatic intraepithelial neoplasia is the most likely precursor of invasive prostate cancer. The identification of prostatic intraepithelial neoplasia in needle biopsy specimens warrants repeat biopsy because of its high predictive value for cancer. The incidence of prostatic intraepithelial neoplasia in contemporary needle biopsies is unknown.

David G. Bostwick; Junqi Qian; Kenneth Frankel

1995-01-01

58

Treatment of vulvar intraepithelial neoplasia with the CO 2 laser  

Microsoft Academic Search

From 1982 to 1987, 18 consecutive patients with vulvar intraepithelial neoplasia were treated with CO2 laser vaporization. Prior genital tract malignancy or premalignancy was seen in 72% of the patients. The area around the commisura posterior was involved in 94% of the cases, and the disease showed multifocal localization in 56%.

Nina Palmgren Colov; Ingrid Thranov; Arne Berget

1990-01-01

59

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

60

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...

61

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

62

Trombosis venosa profunda como marcador de recidiva de una neoplasia  

Microsoft Academic Search

Background and objectiveThere is a bidirectional association between neoplasia and venous thromboembolism (VTE). However, whether this association has an impact in tumor recurrence is unknown. The aim of the study is to assess the incidence of cancer recurrence after diagnosis of VTE and determine if VTE could be a marker for cancer recurrence.

Montserrat Blanch Alerany; Mariona Calvo Campos; Antonio Romera Villegas; Antonio Pérez-Piqueras Gómez; Santiago Riera Batalla; Marc Antoni Cairols Castellote

2009-01-01

63

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

64

Adrenal Involvement in Multiple Endocrine Neoplasia Type 1  

Microsoft Academic Search

Adrenal lesions belong to the spectrum of multiple endocrine neoplasia type 1 (MEN-1) syndrome. However, the prevalence of adrenal involvement, the characteristics, and the clinical management of adrenal lesions have not yet been clearly defined. A total of 66 patients with confirmed MEN1 germline mutations and 1 additional patient with typical manifestations in three organ systems were monitored in a

Peter Langer; Kenko Cupisti; Detlef K. Bartsch; Christoph Nies; Peter E. Goretzki; Matthias Rothmund; Hans D. Röher

2002-01-01

65

Endocrine Surgical Aspects of Multiple Endocrine Neoplasia Syndromes in Children  

Microsoft Academic Search

Background: All patients diagnosed with medullary thyroid carcinoma (MTC) should undergo RET mutation analysis to exclude familial disease – multiple endocrine neoplasia (MEN)-2A and -2B and familial medullary thyroid carcinoma (FMTC). In young patients at risk of genetically determined MTC, the key to a good outcome is an appropriate first operation, and this will depend upon the codon mutation, patient

Barney Harrison

2007-01-01

66

Molecular genetics of multiple endocrine neoplasia types 1 and 2  

Microsoft Academic Search

Six multiple endocrine neoplasia (MEN) syndromes have received a level of attention that might seem disproportionate to their low prevalence. The attention has been given because their hormonal excesses cause striking metabolic expressions and because they might clarify pathways disrupted in more common tumours. The recent discovery of the main gene in each MEN syndrome has furthered our understanding of

Stephen J. Marx

2005-01-01

67

Early orchiopexy: prepubertal intratubular germ cell neoplasia and fertility outcome  

Microsoft Academic Search

Objectives. To investigate the prepubertal prevalence of intratubular germ cell neoplasia of the unclassified type (ITGCNU) and its significance as a predictor of testicular cancer and to evaluate the effect of early orchiopexy (at younger than 2 years of age) on subsequent fertility of patients with bilateral cryptorchidism.Methods. Testicular biopsies (n = 660) from 440 prepubertal patients with cryptorchidism who

Daniel S Engeler; Paul O Hösli; Hubert John; Fridolin Bannwart; Tullio Sulser; Mahul B Amin; Philipp U Heitz; Seife Hailemariam

2000-01-01

68

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

PubMed

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

Sykes, John M; Trupkiewicz, John G

2006-03-01

69

Predictive factors of proximal advanced neoplasia in the large bowel  

PubMed Central

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

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

2014-01-01

70

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

PubMed Central

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

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

2013-01-01

71

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

72

Detection and identification of human papiliomavirus in vulvar intraepithelial neoplasia  

Microsoft Academic Search

Objective  To evaluate the rate and types of human papillomavirus infection in vulvar intraepithelial neoplasia.\\u000a \\u000a \\u000a \\u000a Methods  We detected and identified HPV in 40 VIN cases with 67 lesions using PCR based reverse line blot hybridization and DNA sequencing.\\u000a Among the 40 patients, 13 were diagnosed as VIN III, 11 as VIN II, and 16 as VIN I. 31 patients had multifocal disease.

Yi Guo; Juan-hua Wu; Wei Li; Qian Wang; Hui Li

2007-01-01

73

Spontaneous regression of vulvar intraepithelial neoplasia 2-3  

Microsoft Academic Search

Objective: To determine the background and clinical features of a group of women who experienced spontaneous regression of vulvar intraepithelial neoplasia (VIN) 2-3 before treatment was undertaken.Methods: A retrospective review was made of the records of 14 women who experienced spontaneous regression of VIN 2-3.Results: The women were 15–27 years of age (median 19.5 years). Ninety-three percent were non-white. All

Ronald W Jones; Darion M Rowan

2000-01-01

74

Tobacco, alcohol, and p53 overexpression in early colorectal neoplasia  

PubMed Central

Background The p53 tumor suppressor gene is commonly mutated in colorectal cancer. While the effect of p53 mutations on colorectal cancer prognosis has been heavily studied, less is known about how epidemiologic risk factors relate to p53 status, particularly in early colorectal neoplasia prior to clinically invasive colorectal cancer (including adenomas, carcinoma in situ (CIS), and intramucosal carcinoma). Methods We examined p53 status, as measured by protein overexpression, in 157 cases with early colorectal neoplasia selected from three New York City colonoscopy clinics. After collecting paraffin-embedded tissue blocks, immunohistochemistry was performed using an anti-p53 monoclonal mouse IgG2a [BP53-12-1] antibody. We analyzed whether p53 status was different for risk factors for colorectal neoplasia relative to a polyp-free control group (n = 508). Results p53 overexpression was found in 10.3%, 21.7%, and 34.9%, of adenomatous polyps, CIS, and intramucosal cases, respectively. Over 90% of the tumors with p53 overexpression were located in the distal colon and rectum. Heavy cigarette smoking (30+ years) was associated with cases not overexpressing p53 (OR = 1.8, 95% CI = 1.1–2.9) but not with those cases overexpressing p53 (OR = 1.0, 95% CI = 0.4–2.6). Heavy beer consumption (8+ bottles per week) was associated with cases overexpressing p53 (OR = 4.0, 95% CI = 1.3–12.0) but not with cases without p53 overexpression (OR = 1.6, 95% CI = 0.7–3.7). Conclusion Our findings that p53 overexpression in early colorectal neoplasia may be positively associated with alcohol intake and inversely associated with cigarette smoking are consistent with those of several studies of p53 expression and invasive cancer, and suggest that there may be relationships of smoking and alcohol with p53 early in the adenoma to carcinoma sequence. PMID:14604438

Terry, Mary Beth; Neugut, Alfred I; Mansukhani, Mahesh; Waye, Jerome; Harpaz, Noam; Hibshoosh, Hanina

2003-01-01

75

Laryngeal neuroma in multiple endocrine neoplasia type 2B.  

PubMed

Multiple endocrine neoplasia (MEN) type 2 syndrome is an autosomal dominant inherited disease caused by mutations of the RET proto-oncogene, and is clinically divided into three phenotypes: MEN2A, MEN2B, and familial medullary thyroid carcinoma. Although multiple mucosal neuromas are commonly observed in patients with MEN2B, there are only a few reports of laryngeal neuroma. We present here a rare case of laryngeal mucosal neuromas with MEN2B. PMID:24389350

Kudo, Naomi; Matsubara, Atsushi; Abe, Takahisa; Inoue, Taku; Takahata, Junko

2014-08-01

76

[Thorium-induced neoplasia of the spleen? (author's transl)].  

PubMed

A patient is presented in whom multiple lienal circular foci are seen 25 years after application of a thorium-containing contrast medium for vascular visualization, over and above the well-known characteristic ThO2 deposits in the liver and spleen. The article discusses the problem whether these circular foci which meet the angiographic criteria of an angioblastic sarcoma, should be considered as a thiorium-induced neoplasia. PMID:567836

Schumacher, K A; Bargon, G

1978-08-01

77

Intraductal papillary neoplasia of the liver associated with hepatolithiasis  

Microsoft Academic Search

Intraductal papillary growth of neoplastic biliary epithelia with a fine fibrovascular stalk (intraductal papillary neoplasia of liver [IPN-L]) resembling intraductal papillary mucinous neoplasm of pancreas is occasionally associated with hepatolithiasis. In this study, 136 cases of hepatolithiasis in Taiwan, between January 1998 and March 2000, and an additional 21 cases of IPN-L before December 1998, were examined histologically. IPN-L was

Tse-Ching Chen; Yasuni Nakanuma; Yoh Zen; Miin-Fu Chen; Yi-Yin Jan; Ta-Sen Yeh; Cheng Tang-Chiu; Tseng-Tong Kuo; Jun-ichi Kamiya; Koji Oda; Michinari Hamaguchi; Yoshiyuki Ohno; Ling-Ling Hsieh; Yuji Nimura

2001-01-01

78

Multiple Endocrine Neoplasia Type 2: Clinical Manifestations and Management  

Microsoft Academic Search

\\u000a In the 1950s and 1960s, an increasing association was reported between medullary thyroid carcinoma (MTC) and pheochromocytoma,\\u000a two relatively rare conditions. Identification of kindreds affected by the constellation of MTC, pheochromocytoma, and hyperparathyroidism\\u000a led to the recognition of multiple endocrine neoplasia type 2 (MEN-2) as a distinct syndrome in the 1960s [1]. Three distinct,\\u000a but related, MEN-2 syndromes are now

Amber L. Traugott; Jeffrey F. Moley

79

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

80

Pheochromocytoma in multiple endocrine neoplasia type 2: a prospective study  

Microsoft Academic Search

Objective: The aim of this prospective study is to update our knowledge of the chronology of pheochromocytoma occurrence in multiple endocrine neoplasia type 2 (MEN 2), and to better manage MEN 2 patients after the genetic diagnosis. Design: Eighty-seven non-index gene carrier MEN 2 patients were included in this prospective study: 84 patients with MEN 2A (from 52 families) and

Loan Nguyen; Patricia Niccoli-Sire; Philippe Caron; Delphine Bastie; Olivier Chabre; Vincent Rohmer; Jean-Francois Henry; Bernard Conte-Devolx

2001-01-01

81

Genetic Testing in Presymptomatic Diagnosis of Multiple Endocrine Neoplasia  

Microsoft Academic Search

Multiple endocrine neoplasias (MEN) are familial diseases characterized by endocrine neoplasms and transmitted in an autosomal dominant manner. In MEN type I, the major lesions affect parathyroid glands, pancreatic islet cells and anterior pituitary. The MEN-1 gene has been mapped to chomosome 11q13 and a set of DNA-polymorphic markers localized close to this region provides a useful tool for presymptomatic

A. Calender; S. Giraud; I. Schuffenecker; G. M. Lenoir; P. Gaudray; A. Courseaux; N. Porchet; J. P. Aubert; C. X. Zhang

1997-01-01

82

A novel type of human papillomavirus associated with genital neoplasias  

Microsoft Academic Search

The role of human papillomaviruses (HPVs) in the development of genital neoplasias has been well documented1-5. The genomes of two HPV types, HPV16 and HPV18, have been found to be associated with about 70% of invasive carcinomas of the uterine cervix2,4,6. As, under non-stringent hybridization conditions, HPV DNA sequences have been detected in about 90% of cervical carcinomas4,6, it seems

Sylvie Beaudenon; Dina Kremsdorf; Odile Croissant; Stefania Jablonska; Simon Wain-Hobson; Gérard Orth

1986-01-01

83

Gestational trophoblastic neoplasia: A 6 year retrospective study  

PubMed Central

Aims and Objectives: To study the clinical presentations of gestational trophoblastic neoplasia and its response to chemotherapy. Materials and Methods: This is a retrospective study of 28 women of gestational trophoblastic neoplasia evaluated over a period of 6 years from January 2004 to December 2009. Patients were evaluated on the basis of their age, number of deliveries, history of abortion or molar pregnancy, and the treatment received. All patients were scored on the basis of WHO scoring system. Patients with low risk (score /=7) received multiple agent chemotherapy with EMACO regimen. After completion of chemotherapy patients were followed for a minimum of 2 years. The response to treatment was evaluated during follow-up by clinical examination, beta hCG levels and imaging as and when required. Results: Out of 28 women only 27 could be evaluated, because 1 patient was lost to follow-up. Out of 27 patients, 18 patients (66.67%) achieved complete remission with the first-line chemotherapy and additional 25.92% (7/27) achieved complete remission with second line chemotherapy resulting in complete remission of 92.5% (25/27). Conclusion: Gestational trophoblastic neoplasia is curable if patient is properly evaluated and scored. It shows good response to chemotherapy. PMID:24665444

Shrivastava, Sushruta; Kataki, Amal Chandra; Barmon, Debabrata; Deka, Pankaj; Bhuyan, Chidananda; Bhargav, Saikia J.

2014-01-01

84

Activation of ras oncogenes preceding the onset of neoplasia.  

PubMed

The identification of ras oncogenes in human and animal cancers including precancerous lesions indicates that these genes participate in the early stages of neoplastic development. Yet, these observations do not define the timing of ras oncogene activation in the multistep process of carcinogenesis. To ascertain the timing of ras oncogene activation, an animal model system was devised that involves the induction of mammary carcinomas in rats exposed at birth to the carcinogen nitrosomethylurea. High-resolution restriction fragment length polymorphism analysis of polymerase chain reaction-amplified ras sequences revealed the presence of both H-ras and K-ras oncogenes in normal mammary glands 2 weeks after carcinogen treatment and at least 2 months before the onset of neoplasia. These ras oncogenes can remain latent within the mammary gland until exposure to estrogens, demonstrating that activation of ras oncogenes can precede the onset of neoplasia and suggesting that normal physiological proliferative processes such as estrogen-induced mammary gland development may lead to neoplasia if the targeted cells harbor latent ras oncogenes. PMID:2188364

Kumar, R; Sukumar, S; Barbacid, M

1990-06-01

85

Vaginal intraepithelial neoplasia III detected after hysterectomy for benign conditions.  

PubMed

Because primary vaginal cancer is rare, many experts discourage routine cytologic sampling of the vaginal vault following hysterectomy for benign circumstances. The following report describes a case of vaginal intraepithelial neoplasia III (VAIN III) detected by a vaginal vault Papanicolaou smear obtained from an asymptomatic 57-year-old woman 23 years after she had a total abdominal hysterectomy for a benign condition. As VAIN III is a true vaginal cancer precursor, the innocent disregard of recommended screening practices averted significant morbidity and possibility mortality for this otherwise healthy woman. PMID:7807042

Ferris, D G; Messing, M J; Crosby, J H

1995-01-01

86

Analysis of digitized cervical images to detect cervical neoplasia  

NASA Astrophysics Data System (ADS)

Cervical cancer is the second most common malignancy in women worldwide. If diagnosed in the premalignant stage, cure is invariably assured. Although the Papanicolaou (Pap) smear has significantly reduced the incidence of cervical cancer where implemented, the test is only moderately sensitive, highly subjective and skilled-labor intensive. Newer optical screening tests (cervicography, direct visual inspection and speculoscopy), including fluorescent and reflective spectroscopy, are fraught with certain weaknesses. Yet, the integration of optical probes for the detection and discrimination of cervical neoplasia with automated image analysis methods may provide an effective screening tool for early detection of cervical cancer, particularly in resource poor nations. Investigative studies are needed to validate the potential for automated classification and recognition algorithms. By applying image analysis techniques for registration, segmentation, pattern recognition, and classification, cervical neoplasia may be reliably discriminated from normal epithelium. The National Cancer Institute (NCI), in cooperation with the National Library of Medicine (NLM), has embarked on a program to begin this and other similar investigative studies.

Ferris, Daron G.

2004-05-01

87

Integration of HPV16 and HPV18 DNA in vulvar intraepithelial neoplasia  

Microsoft Academic Search

Objective.Vulvar intraepithelial neoplasia (VIN) is a premalignant disease of the lower genital tract. The increased occurrence of high-risk human papillomavirus (HPV) infection seems to be associated with the increasing frequency of VIN. Integration of HPV DNA into host chromosome has been hypothesized to be a critical step in the carcinogenesis of cervical neoplasia resulting in altered expression of two viral

Peter Hillemanns; Xiuli Wang

2006-01-01

88

Recessive Transmission of a Multiple Endocrine Neoplasia Syndrome in the Rat1  

Microsoft Academic Search

We describe a novel hereditary cancer syndrome in the rat that is transmitted by a recessive gene mutation. Animals exhibiting the mutant phenotype develop multiple neuroendocrine malignancies within the first year of life. The endocrine neoplasia is characterized by bilateral adrenal pheochromocytoma, multiple extra-adrenal pheochromocytoma, bilateral medullary thyroid cell neoplasia, bilateral parathyroid hyperplasia, and pituitary adenoma. The appearance of neoplastic

Andreas Fritz; Axel Walch; Kamilla Piotrowska; Michael Rosemann; Ekkehard Schaffer; Karin Weber; Andreas Timper; Gerhild Wildner; Jochen Graw; Heinz Hofler; Michael J. Atkinson

89

Mutations in Apc and p53 Synergize to Promote Mammary Neoplasia  

Microsoft Academic Search

Mutations of Apc and p53 have both been implicated in human and murine mammary neoplasia. To investigate potential interactions between Apc and p53, we conditionally inactivated Apc in both the presence and the absence of functional p53. Apc deficiency on its own leads to the development of metaplasia but not neoplasia. We show here that these areas of metaplasia are

Valerie Meniel; Trevor Hay; Owen J. Sansom; Alan R. Clarke

2005-01-01

90

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

Microsoft Academic Search

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

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

2003-01-01

91

Tumorigenesis in the multiple intestinal neoplasia mouse: Redundancy of negative regulators and  

E-print Network

)? Preliminary studies tested whether a lack of p53 activity affected neoplasia in the intestine of Min (multipleTumorigenesis in the multiple intestinal neoplasia mouse: Redundancy of negative regulators normal and neoplastic growth in the mammal. Positive and negative regulators can act either cell

Dove, William

92

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 ...

93

Il Reiki nell'assistenza infermieristica al paziente anziano con neoplasia avanzata  

Microsoft Academic Search

Summary Reiki is an ancient and simple technique born in Tibetan Sutras and administered by touching lightly different body parts. It is currently used as adjuvant to reduce pain, including cancer pain, to support chemio-radiotherapy, to relieve global pain in advanced and terminal patients. End point of our study is the role of Reiki, as adjuvant to pharmacological therapy, in

Maria Teresa Vitale; Maria Elena La Grassa; Franco Lombardi; Dario Cova; Elisabetta Cofrancesco

2005-01-01

94

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

95

Multiple endocrine neoplasia type IIa associated with Cushing's syndrome.  

PubMed

Multiple Endocrine Neoplasia type IIa (MEN IIa) is an autosomal dominant syndrome characterized by pheochromocytoma, medullary thyroid carcinoma and hyperparathyroidism. Pheochromocytoma occurs in approximately 50% of patients with MEN IIa. This tumor has the capacity to produce ACTH ectopically and manifests as the Cushing syndrome, although it is very rare. We report a 26-year-old woman patient with severe muscle weakness, skin lesions in extremities, hypertension, and new onset diabetes whose laboratory findings included hypokalemia, metabolic alkalosis, high serum level of cortisol, metanephrine, normetanephrine, calcitonin and bilateral adrenal mass in computed tomography as the first clinical manifestations of an ACTH-secreting pheochromocytoma. In the patients with hypertension, new onset diabetes and hypokalemia, the Cushing syndrome and pheochromocytoma should always be ruled out. PMID:24916533

Borzouei, Shiva; Mousavi Bahar, Seyed Habib Allah; Fereydouni, Mohammad Amin; Salimbahrami, Seyed Ahmadreza; Taghipour, Mehrdad

2014-06-01

96

Ocular Surface Squamous Neoplasia Masquerading as Superior Limbic Keratoconjunctivitis  

PubMed Central

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

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

2011-01-01

97

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

98

A Metastatic Ovarian Angiosarcoma Mimicking Hematologic Neoplasia at Diagnosis  

PubMed Central

Angiosarcomas are rare aggressive neoplasms of vascular endothelial origin with a high metastatic rate and poor prognosis. Involvement of the bone marrow by the angiosarcoma is exceedingly uncommon, and there have only been a few cases reported in the literature to date. Clinical manifestations and common laboratory findings of bone marrow involvement can mimic other more common bone marrow-replacing neoplasias such as lymphomas and acute leukemia. A definitive diagnosis is difficult to make from cytologic material, probably due to an associated bone marrow fibrosis, and requires bone marrow trephine biopsy with an immunohistochemical profile. Here we had the opportunity to study a case of metastatic angiosarcoma with positive cytologic findings and an unusual presentation that challenged its primary diagnosis. PMID:24847252

Gaiolla, Rafael Dezen; Duarte, Ivison Xavier; Bacchi, Carlos Eduardo; Paiva, Carlos Eduardo

2014-01-01

99

Myeloid Neoplasias: What Molecular Analyses Are Telling Us  

PubMed Central

In the last decades, cytogenetic and molecular characterizations of hematological disorders at diagnosis and followup have been most valuable for guiding therapeutic decisions and prognosis. Genetic and epigenetic alterations detected by different procedures have been associated to different cancer types and are considered important indicators for disease classification, differential diagnosis, prognosis, response, and individualization of therapy. The search for new biomarkers has been revolutionized by high-throughput technologies. At this point, it seems that we have overcome technological barriers, but we are still far from sorting the biological puzzle. Evidence based on translational research is required for validating novel genetic and epigenetic markers for routine clinical practice. We herein discuss the importance of genetic abnormalities and their molecular pathways in acute myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms. We also discuss how novel genomic abnormalities may interact and reassess concepts and classifications of myeloid neoplasias. PMID:23056961

Gutiyama, Luciana M.; Coutinho, Diego F.; Lipkin, Marina V.; Zalcberg, Ilana R.

2012-01-01

100

Conjunctival melanoma and melanocytic intra-epithelial neoplasia  

PubMed Central

The rarity of conjunctival melanoma has impeded progress in the management of patients with this cancer; however, much progress has occurred in recent years. Primary acquired melanosis is now differentiated histologically into hypermelanosis and conjunctival melanocytic intra-epithelial neoplasia, for which an objective reproducible scoring system has been developed. Mapping and clinical staging of conjunctival disease has improved. Adjunctive radiotherapy and topical chemotherapy have made tumour control more successful, with reduced morbidity. Genetic analyses have identified BRAF and other mutations, which may predict responsiveness to new chemotherapeutic agents, for example Vemurafenib, should metastatic disease develop. Multicentre studies are under way to enhance survival prediction by integrating clinical stage of disease with histological grade of malignancy and genetic abnormalities. Such improved prognostication would not only be more relevant to individual patients, but would also provide greater opportunities for basic science research. PMID:23222568

Kenawy, N; Lake, S L; Coupland, S E; Damato, B E

2013-01-01

101

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

102

Gastroenteropancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1.  

PubMed

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

103

Current Chemotherapeutic Management of Patients with Gestational Trophoblastic Neoplasia  

PubMed Central

Gestational trophoblastic neoplasia (GTN) describes a heterogeneous group of interrelated lesions that arise from abnormal proliferation of placental trophoblasts. GTN lesions are histologically distinct, malignant lesions that include invasive hydatidiform mole, choriocarcinoma, placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT). GTN tumors are generally highly responsive to chemotherapy. Early stage GTN disease is often cured with single-agent chemotherapy. In contrast, advanced stage disease requires multiagent combination chemotherapeutic regimens to achieve a cure. Various adjuvant surgical procedures can be helpful to treat women with GTN. Patients require careful followup after completing treatment and recurrent disease should be aggressively managed. Women with a history of GTN are at increased risk of subsequent GTN, hence future pregnancies require careful monitoring to ensure normal gestational development. This article will review the workup, management and followup of women with all stages of GTN as well as with recurrent disease. PMID:22312558

May, Taymaa; Goldstein, Donald P.; Berkowitz, Ross S.

2011-01-01

104

Uterine arteriovenous malformations following gestational trophoblastic neoplasia: a systematic review.  

PubMed

Uterine arteriovenous malformation (AVM) following gestational trophoblastic neoplasia (GTN) is a rare condition. It can be associated with chronic vaginal bleeding or life-threatening heavy bleeding, even after complete resolution of the tumor following chemotherapy. This analysis aimed to perform an extensive systematic review highlighting clinical symptoms, imaging, management and prognosis of this rare complication of GTN. We also describe an additional case of uterine AVM following GTN. We conducted a literature search using Medline, Embase and Cochrane library to analyze the clinical data of 49 published cases of uterine AVM following GTN. Median age of the women diagnosed with AVM was 29 years (range 15-49). Median gravidity was 2 (range 1-8) and 50% of women were nulligravida. Complete molar pregnancy was the most common initial gestational trophoblastic diagnosis (48%). Overall, 44 patients (88%) were symptomatic and presented with chronic or acute abnormal vaginal bleeding. Only 3 patients had an undetectable HCG level at the time of uterine AVM diagnosis. Hypo-echoic space in the myometrium is the most relevant finding on ultrasonography but the gold standard for the definitive diagnosis of AVMs is angiographic examination. Uterine artery embolization was the most common treatment option performed in 82% of the patients and was successful in controlling the bleeding in 85% of cases. We identified 20 pregnancies after successful embolization of uterine AVM following a GTN and 90% of them were successful. Because of the risk of life-threatening heavy bleeding, the diagnosis of uterine AVM should always be considered in patients with a history of recurrent unexplained vaginal bleeding after gestational trophoblastic neoplasia. Angiographic embolization is successful in the majority of cases and does not appear to compromise future pregnancy. PMID:25126982

Touhami, Omar; Gregoire, Jean; Noel, Patricia; Trinh, Xuan Bich; Plante, Marie

2014-10-01

105

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

106

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

107

Limbal stem cell deficiency following topical mitomycin c treatment of Conjunctival-Corneal intraepithelial neoplasia  

Microsoft Academic Search

PurposeTo report a case of conjunctival-corneal intraepithelial neoplasia (CCIN) in an elderly African American patient treated with topical mitomycin C and the subsequent complication of limbal stem cell deficiency.

Blonie W. Dudney; Monika A. Malecha

2004-01-01

108

Vulval and perianal intraepithelial neoplasia: response to chemoradiotherapy in a woman with idiopathic CD4 lymphocytopenia.  

PubMed

Treatment of multicentric or multifocal anogenital intraepithelial neoplasia is challenging, especially if the patient has immunodeficiency. We report the case of a woman with idiopathic CD4 lymphocytopenia and vulval and perianal intraepithelial neoplasia with early invasive disease, who responded well to radiotherapy combined with chemotherapy. Chemoradiotherapy is often used in the primary treatment of anal carcinomas, but has rarely been reported as a treatment for premalignant anogenital conditions. PMID:22439786

Tomson, N; Sterling, J; Miller, R; Wilson, C; Baldwin, P

2012-12-01

109

A score to estimate the likelihood of detecting advanced colorectal neoplasia at colonoscopy  

PubMed Central

Objective This study aimed to develop and validate a model to estimate the likelihood of detecting advanced colorectal neoplasia in Caucasian patients. Design We performed a cross-sectional analysis of database records for 40-year-old to 66-year-old patients who entered a national primary colonoscopy-based screening programme for colorectal cancer in 73 centres in Poland in the year 2007. We used multivariate logistic regression to investigate the associations between clinical variables and the presence of advanced neoplasia in a randomly selected test set, and confirmed the associations in a validation set. We used model coefficients to develop a risk score for detection of advanced colorectal neoplasia. Results Advanced colorectal neoplasia was detected in 2544 of the 35?918 included participants (7.1%). In the test set, a logistic-regression model showed that independent risk factors for advanced colorectal neoplasia were: age, sex, family history of colorectal cancer, cigarette smoking (p<0.001 for these four factors), and Body Mass Index (p=0.033). In the validation set, the model was well calibrated (ratio of expected to observed risk of advanced neoplasia: 1.00 (95% CI 0.95 to 1.06)) and had moderate discriminatory power (c-statistic 0.62). We developed a score that estimated the likelihood of detecting advanced neoplasia in the validation set, from 1.32% for patients scoring 0, to 19.12% for patients scoring 7–8. Conclusions Developed and internally validated score consisting of simple clinical factors successfully estimates the likelihood of detecting advanced colorectal neoplasia in asymptomatic Caucasian patients. Once externally validated, it may be useful for counselling or designing primary prevention studies. PMID:24385598

Kaminski, Michal F; Polkowski, Marcin; Kraszewska, Ewa; Rupinski, Maciej; Butruk, Eugeniusz; Regula, Jaroslaw

2014-01-01

110

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

111

Pathways of vulvar intraepithelial neoplasia and squamous cell carcinoma.  

PubMed

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

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

2013-01-01

112

[Human papillomavirus infection and cervical intraepithelial neoplasia in dialyzed patients].  

PubMed

Human papillomavirus (HPV) infection is a risk factor for the development of cervical intraepithelial neoplasia (CIN). The incidence of certain cancers such as HPV-associated CIN is higher among dialysis patients than in the general population. In the literature there are few studies on the prevalence of HPV infection among dialyzed women and almost all of these studies concerned women with positive Pap smears. We enrolled 73 hemodialyzed women attending our center from January 2009 to December 2010; 29 denied informed consent and 44 underwent Pap tests and cervical curettage for HPV (mean age 62 ± 15 years). We found HPV positivity in 6 women (prevalence 13.6%). The prevalence of CIN in our sample was also 13.6% (6/44), 83.3% of which HPV related. Since cervical curettage for HPV is a cheap and easy to perform test with high specificity and sensitivity, we believe it is worthwhile including it in the pre-transplant workup of such women to lower the incidence of CIN in dialyzed patients and transplant recipients. PMID:22538949

David, Paola; Tarrano, Elisabetta; De Mauri, Andreana; Navino, Carlo; Brustia, Maddalena; Chiarinotti, Doriana; Gherzi, Roberto; De Leo, Martino

2012-01-01

113

A Drosophila model of multiple endocrine neoplasia type 2.  

PubMed

Dominant mutations in the Ret receptor tyrosine kinase lead to the familial cancer syndrome multiple endocrine neoplasia type 2 (MEN2). Mammalian tissue culture studies suggest that RetMEN2 mutations significantly alter Ret-signaling properties, but the precise mechanisms by which RetMEN2 promotes tumorigenesis remain poorly understood. To determine the signal transduction pathways required for RetMEN2 activity, we analyzed analogous mutations in the Drosophila Ret ortholog dRet. Overexpressed dRetMEN2 isoforms targeted to the developing retina led to aberrant cell proliferation, inappropriate cell fate specification, and excessive Ras pathway activation. Genetic analysis indicated that dRetMEN2 acts through the Ras-ERK, Src, and Jun kinase pathways. A genetic screen for mutations that dominantly suppress or enhance dRetMEN2 phenotypes identified new genes that are required for the phenotypic outcomes of dRetMEN2 activity. Finally, we identified human orthologs for many of these genes and examined their status in human tumors. Two of these loci showed loss of heterozygosity (LOH) within both sporadic and MEN2-associated pheochromocytomas, suggesting that they may contribute to Ret-dependent oncogenesis. PMID:15965261

Read, Renee D; Goodfellow, Paul J; Mardis, Elaine R; Novak, Nancy; Armstrong, Jon R; Cagan, Ross L

2005-11-01

114

Familial multiple endocrine neoplasia: the first 100 years.  

PubMed

In 1903, Erdheim described the case of an acromegalic patient with a pituitary adenoma and three enlarged parathyroid glands. Fifty years later, Underdahl et al reported 8 patients with a syndrome of pituitary, parathyroid, and pancreatic islet adenomas. In 1954, Wermer found that the syndrome was transmitted as a dominant trait. In 1959, Hazard et al described medullary (solid) thyroid carcinoma (MTC), a tumor that later was found to be a component of two endocrine syndromes. The first of these described by Sipple in 1961 comprised pheochromocytoma, MTC, and parathyroid adenoma. The second, described by Williams et al in 1966, was the combination of mucosal neuromas, pheochromocytoma, and MTC. In 1968, Steiner et al introduced the term "multiple endocrine neoplasia" (MEN) to describe disorders featuring combinations of endocrine tumors; they designated the Wermer syndrome as MEN 1 and the Sipple syndrome as MEN 2. In 1974, Sizemore et al concluded that the MEN 2 category included two groups of patients with MTC and pheochromocytoma: one with parathyroid disease and a normal appearance (MEN 2A) and the other without parathyroid disease but with mucosal neuromas and mesodermal abnormalities (MEN 2B). Later, additional nonendocrine conditions (von Recklinghausen neurofibromatosis and von Hippel-Lindau disease) were found accompanying other more recently described familial MEN syndromes, indicating that these diseases are very complicated disorders. PMID:15644784

Carney, J Aidan

2005-02-01

115

Gestational trophoblastic neoplasia with retroperitoneal metastases: A fatal complication  

PubMed Central

Background Gestational Trophoblastic Neoplasia (GTN) is a pathologic entity that can affect any pregnancy and develop long after the termination of the pregnancy. Its course can be complicated by metastases to distant sites such as the lung, brain, liver, kidney and vagina. The therapeutic approach of this condition includes both surgical intervention and chemotherapy. The prognosis depends on many prognostic factors that determine the stage of the disease. Case Report We present a woman with GTN and retroperitoneal metastatic disease who came to our department and was diagnosed as having high risk metastatic GTN. Accordingly she received chemotherapy as primary treatment but unfortunately developed massive bleeding after the first course of chemotherapy, was operated in an attempt to control bleeding but finally succumbed. Conclusion This case demonstrates that GTN, while usually curable, can be a deadly disease requiring improved diagnostic, treatment modalities and chemotherapeutic agents. The gynaecologist should be aware of all possible metastatic sites of GTN and the patient immediately referred to a specialist center for further assessment and treatment. PMID:21192785

2010-01-01

116

[Diagnostic criteria and differential diagnosis of prostatic intraepithelial neoplasia].  

PubMed

Prostatic intraepithelial neoplasia (HGPIN) is considered the most likely precursor of clinically significant prostate cancer. Biopsy remains the only definitive method for detecting these premalignant lesions. In this article we review the diagnostic criteria of HGPIN and discuss histological features that allow their distinction from other benign and malignant lesions. PIN is recognised at low power magnification as a thickened, basophilic and hyperchromatic epithelium in pre-existing acinar duct structures. This important histological feature is due to nuclear crowding and stratification. Distinction between HGPIN and low grade PIN (LGPIN), a lesion with little clinical significance, is made mainly on the presence or absence of prominent nucleoli. HGPIN lesions always retain an intact or fragmented basal cell layer. The different growth patterns of HGPIN (tufting, micropapillary, cribriform and flat) have no clinical significance but should be considered in the differential diagnosis together with normal structures, and both benign and malignant lesions. HGPIN has a high predictive value as a marker for prostate cancer but should not influence therapeutic decisions. Its identification in biopsy specimens warrants close surveillance with repeated biopsy. PMID:9541940

Bonkhoff, H; Remberger, K

1998-01-01

117

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

118

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

119

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

120

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

PubMed Central

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

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

2013-01-01

121

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

122

Architectural patterns of high-grade prostatic intraepithelial neoplasia.  

PubMed

High-grade prostatic intraepithelial neoplasia (PIN) is characterized by cellular proliferations within pre-existing ducts and glands with cytologic changes mimicking adenocarcinoma, including prominent nucleoli, but lacking stromal invasion. To determine the architectural spectrum of high-grade PIN, 60 serially sectioned radical prostatectomy specimens with PIN and cancer were reviewed. Four common patterns of high-grade PIN were identified, usually with multiple patterns in each case: tufting (in 87% of cases), micropapillary (in 85% of cases), cribriform (in 32% of cases), and flat (in 28% of cases). Tumor grade was not significantly associated with any pattern of PIN. Luminal cytoplasmic apical blebs were found in all cases regardless of the pattern of PIN. A variety of associated architectural and cytologic features were observed with high-grade PIN: epithelial arches (in 60% of cases), cellular trabecular epithelial bars (in 22% of cases), "Roman" bridges (in 30% of cases), partial gland involvement (in 82% of cases), basal cell layer disruption with glandular budding (in 23% of cases), large cystic gland involvement (in 10% of cases), involvement by nodular hyperplasia (in 5% of cases), microcalcifications (in 8% of cases), proteinaceous luminal secretions (in 62% of cases), corpora amylacea (in 55% of cases), exfoliated cells of PIN (in 42% of cases), luminal crystalloids (in 3% of cases), and mucinous metaplasia (in 2% of cases). High-grade PIN exhibits a variety of architectural patterns while retaining the distinctive cytoplasmic apical blebs and diagnostic nuclear and nucleolar features. Identification of high-grade PIN warrants a further search for invasive carcinoma, but should not influence or dictate decisions regarding definitive therapy. PMID:8454275

Bostwick, D G; Amin, M B; Dundore, P; Marsh, W; Schultz, D S

1993-03-01

123

Ki-67 and ProExC are useful immunohistochemical markers in esophageal squamous intraepithelial neoplasia.  

PubMed

Esophageal squamous intraepithelial neoplasia has been widely recognized as a precursor lesion for esophageal squamous cell carcinoma. Early detection offers the best prognosis for esophageal squamous cell carcinoma. The differentiation of squamous dysplasia from reactive change and the classification of squamous dysplasia into high-grade or low-grade are sometimes subjective and challenging. In this study, we sought to evaluate multiple biomarkers and to develop clinically useful adjunct tools for difficult esophageal squamous intraepithelial neoplasia cases. Immunohistochemical stains using antibodies against Ki-67, ProExC, p16, and p53 were performed on esophageal biopsy or resection specimens from 25 patients including 35 foci of high-grade dysplasia and 25 foci of low-grade dysplasia, and from 10 control cases containing 52 foci of normal/reactive hyperplasia. In situ hybridization tests for human papillomavirus were performed in 11 cases. The immunostains for all 4 markers were scored as negative, intermediate, and strong according to established criteria. Intermediate and strong Ki-67 and ProExC staining showed similar detecting power and exhibited very high sensitivity and specificity for distinguishing normal/reactive hyperplasia from esophageal squamous intraepithelial neoplasia and normal/reactive hyperplasia from low-grade esophageal squamous intraepithelial neoplasia. Strong Ki-67 staining was exclusively seen in high-grade esophageal squamous intraepithelial neoplasia, which provided additional value in distinguishing high-grade from low-grade esophageal squamous intraepithelial neoplasia. Strong ProExC staining was also seen in most high-grade esophageal squamous intraepithelial neoplasia foci (80%). Although the frequencies of intermediate/strong staining patterns of p53 increased with increasing degree of dysplasia, the sensitivity of p53 was much lower than that of Ki-67 and ProExC. p16 did not show consistent immunostain pattern in the normal/reactive hyperplasia and esophageal squamous intraepithelial neoplasia. Two (18%) of 11 tested cases were positive for human papillomavirus infection. This study demonstrates that both Ki-67 and ProExC can be used as an adjunct tool for diagnosing difficult cases of esophageal squamous intraepithelial neoplasia. PMID:21420715

Wang, Wen-Chuang; Wu, Tsung-Teh; Chandan, Vishal S; Lohse, Christine M; Zhang, Lizhi

2011-10-01

124

Medical interventions for high grade vulval intraepithelial neoplasia  

PubMed Central

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

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

2014-01-01

125

Association of HPV infection and Chlamydia trachomatis seropositivity in cases of cervical neoplasia in Midwest Brazil.  

PubMed

High-risk human papillomavirus (HPV) is considered the main etiological agent for cervical neoplasia. However, the presence of a single type HPV infection alone is unlikely to be sufficient to cause cervical cancer. There is epidemiologic evidence suggesting that HPV and Chlamydia trachomatis play a central role in the etiology of cervical intraepithelial neoplasia and subsequent cervical cancer. To evaluate the HPV prevalence and the seropositivity for C. trachomatis in women referred to the colposcopy clinic due to an abnormal cervical smear and to examine the effect of this association on the severity of cervical neoplasia. Following enrollment, 131 patients underwent colposcopy and biopsies when necessary. HPV DNA was detected by the polymerase chain reaction (PCR) and genotyping was performed by reverse line-blot hybridization assay. C. trachomatis seropositivity was tested by ELISA for the detection of IgG antibodies. The prevalence of HPV infection was 86.3%. Seropositivity for C. trachomatis was 26%. Thirty-one women (27.4%) were positive for C. trachomatis antibodies and HPV-DNA. The most prevalent HPV type in C. trachomatis-seropositive women were HPV 16 (51.6%) and this HPV type was present mainly in neoplasia cases. Positivity for HPV, particularly HPV types 16 and 18, and C. trachomatis seropositivity was significantly associated with a diagnosis of high grade neoplasia. Borderline significance was observed after adjustment for HPV. C. trachomatis seropositivity is associated with high grade neoplasia in women infected with HPV, mainly when the types 16 and 18 were involved. PMID:22585734

da Silva Barros, Narriman Kennia; Costa, Maria Cecília; Alves, Rosane Ribeiro Figueiredo; Villa, Luísa Lina; Derchain, Sophie Françoise Mauricette; Zeferino, Luiz Carlos; Dos Santos Carneiro, Megmar Aparecida; Rabelo-Santos, Silvia Helena

2012-07-01

126

A clinical and pathological overview of vulvar condyloma acuminatum, intraepithelial neoplasia, and squamous cell carcinoma.  

PubMed

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

127

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

PubMed Central

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 leads into the importance of the Papanicolaou smear in prevention of potentially devastating sequelae of this virus. The role of the immune system in the progression of the disease and how it relates to vaccines, as well as treatment and prevention of HPV, are reviewed. PMID:11930025

Jastreboff, A; Cymet, T

2002-01-01

128

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

129

Nonseptic diseases associated with the hoof complex: keratoma, white line disease, canker, and neoplasia.  

PubMed

This article addresses nonseptic diseases associated with the hoof complex, namely keratoma, white line disease, canker, and neoplasia. Keratoma is an uncommon cause of lameness, which may be surgically removed. White line disease, a keratolytic process on the solar surface of the hoof, is treated with therapeutic farriery and resection of the hoof wall when appropriate. Equine canker is an infectious process that results in development of a chronic hypertrophy of the horn-producing tissues. Neoplasia involving the equine foot is rare, and melanoma is the most common type of neoplasm reported. PMID:22981198

Redding, W Rich; O'Grady, Stephen E

2012-08-01

130

Fast-growing pancreatic neuroendocrine carcinoma in a patient with multiple endocrine neoplasia type 1: a case report  

Microsoft Academic Search

INTRODUCTION: Predictive genetic screening and regular screening programs in patients with multiple endocrine neoplasia type 1 are intended to detect and treat malignant tumors at the earliest stage possible. Malignant neuroendocrine pancreatic tumors are the most frequent cause of death in these patients. However, the extent and intervals of screening in patients with multiple endocrine neoplasia type 1 are controversial

Jens Waldmann; Nils Habbe; Volker Fendrich; Emily P Slater; Peter H Kann; Matthias Rothmund; Peter Langer

2008-01-01

131

DCIS and LCIS are confusing and outdated terms. They should be abandoned in favor of ductal intraepithelial neoplasia (DIN) and lobular intraepithelial neoplasia (LIN).  

PubMed

The terms ductal and lobular intraepithelial neoplasia (DIN and LIN) were introduced by Tavossoli 15 years ago, who proposed they should replace, respectively, ductal and lobular carcinoma in situ (DCIS and LCIS). This proposal has been slowly gaining ground. We argue that DCIS and LCIS should now be definitively abandoned. Bringing together 'in situ' and other entities into the simpler and more logical DIN/LIN framework--as has been done with intraepithelial neoplasias of cervix, vagina, vulva, prostate, and pancreas--would eliminate the artificial and illogical distinctions between 'not cancers' (e.g. flat epithelial atypia, atypical ductal hyperplasia--now classified as low grade DIN) and 'cancers' (e.g. DCIS--now considered medium-high grade DIN). Elimination of the term 'carcinoma' from entities that cannot metastasize will reduce confusion among health professionals and patients, and contribute to reducing the risk of overtreatment, as well as reducing adverse psychological reactions in patients. PMID:23643807

Galimberti, Viviana; Monti, Simonetta; Mastropasqua, Mauro Giuseppe

2013-08-01

132

Quality of life and female sexual function after skinning vulvectomy with split-thickness skin graft in women with vulvar intraepithelial neoplasia or vulvar Paget disease.  

E-print Network

graft in women with vulvar intraepithelial neoplasia or vulvar Paget disease. V. Lavoué1, 2+* , A.1016/j.ejso.2013.09.014 #12;2 Abstract Objective: Vulvar intraepithelial neoplasia (VIN) and vulvar,version1-9Oct2013 #12;3 Keywords: Vulvectomy; Skin graft; Vulvar intraepithelial neoplasia; Vulvar

Paris-Sud XI, Université de

133

Frequencies and role of regulatory T cells in patients with (pre)malignant cervical neoplasia  

PubMed Central

Oncogenic human papillomavirus (HPV)-infection is crucial for developing cervical cancer and its precursor lesions [cervical intraepithelial neoplasia (CIN)]. Regulatory T cells (Tregs) might be involved in the failure of the immune system to control the development of HPV-induced cancer. We investigated frequencies, phenotype and activity of Tregs in patients with cervical neoplasia. CIN and cervical cancer patients showed increased CD4+/CD25high T cell frequencies in peripheral blood and CD4+ T cell fraction. These CD4+/CD25high T cells represent Tregs as demonstrated by their low proliferation rate, low interferon (IFN)-?/interleukin (IL)-10 ratio, high expression of CD45RO, GITR, CTLA-4, forkhead box P3 (FoxP3) and low CD45RA expression. Moreover, in HPV16+ cervical cancer patients, in-vitro depletion of CD25+ T cells resulted in increased IFN-? T cell responses against HPV16 E6- and E7 peptides. Thus, increased frequencies of Tregs in cervical cancer patients may indeed suppress HPV-specific immunity. Longitudinal analysis of CD4+/CD25high T cell frequencies in patients showed a modest decline 1 year after curative surgery or chemoradiation. This study demonstrates increased frequencies and suppressive activity of Tregs in cervical cancer. These results imply that Tregs may suppress the immune control of cervical neoplasia and furthermore that suppression of immunity by Tregs will be another hurdle to overcome in therapeutic immunization strategies against cervical neoplasia. PMID:17937675

Visser, J; Nijman, H W; Hoogenboom, B-N; Jager, P; van Baarle, D; Schuuring, E; Abdulahad, W; Miedema, F; van der Zee, A G; Daemen, T

2007-01-01

134

Cervical and Vulvar Intraepithelial Neoplasia after Treatment with Oral Isotretinoin for Severe Acne Vulgaris  

Microsoft Academic Search

Oral isotretinoin is the drug of choice for severe acne vulgaris, but its use is still controversial in preventing, treating or stopping the progression of the cervical intraepithelial neoplasia (6-8). It induces cell differentiation, inhibits cell proliferation, stimulates host immune reaction, inhibits the oncogene expression, augments cell- mediated cytotoxicity, and induces apoptosis (5). The isotretinoin has many side effects including

M. N. Al Hallak; N. Zouain

135

Use of the Female Sexual Function Index in Women with Vulvar Intraepithelial Neoplasia  

Microsoft Academic Search

The present investigation extends the validation of the Female Sexual Function Index (FSFI; Rosen et al., 2000) to include women with vulvar excisions for vulvar intraepithelial neoplasia (VIN). No instrument previously has been validated in this population. We administered the instrument to 43 women (n = 43) with VIN treated with vulvar excision and age-matched healthy controls (n = 43).

Wendy M. Likes; Cheryl Stegbauer; Donna Hathaway; Candice Brown; Todd Tillmanns

2006-01-01

136

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

Microsoft Academic Search

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

R. W Jones; Judith Baranyai; S Stables

1997-01-01

137

Serum Concentrations of Tissue Polypeptide Antigen in Patients with Vulvar Intraepithelial Neoplasia and Vulvar Cancer  

Microsoft Academic Search

The aim of the present study was to evaluate the clinical usefulness of the cytokeratin tumor marker tissue polypeptide antigen (TPA) in patients with vulvar cancer. This retrospective study comprises 41 patients with vulvar cancer FIGO stages I–III, 17 patients with vulvar intraepithelial neoplasia (VIN) III, and 40 healthy female controls. Serum concentrations of TPA were measured using a microparticle

Lukas Hefler; Clemens Tempfer; Katrin Frischmuth; Georg Maenner; Nicole Concin; Gerhard Sliutz; Alexander Reinthaller; Sepp Leodolter; Christian Kainz

2000-01-01

138

Vulvar intraepithelial neoplasia III: occult cancer and the impact of margin status on recurrence  

Microsoft Academic Search

Objective: To determine the impact of margin status on disease recurrence and the incidence of occult cancer in women diagnosed with vulvar intraepithelial neoplasia (VIN) III and treated with surgical excision.Methods: Between 1989 and 1995, 73 women were diagnosed preoperatively with VIN III by vulvar biopsy and were treated with surgical resection. Patients were examined postoperatively, and recurrence was diagnosed

Susan C Modesitt; Anne B Waters; Leslie Walton; Wesley C Fowler; Linda Van Le

1998-01-01

139

Vulvar Intraepithelial Neoplasia in Women Infected with Human Immunodeficiency Virus1  

Microsoft Academic Search

The purpose of this study was to determine the response of vulvar intraepithelial neoplasia (VIN) lesions to standard treatment methods in women infected with human immunodeficiency virus (HIV). We reviewed all cases of VIN over a 4-year period at an inner-city hospital. We reviewed the clinical records of these women to abstract demographic information as well as information about tobacco

Abner P. Korn; Priscilla D. Abercrombie; Anne Foster

1996-01-01

140

Vulvar intraepithelial neoplasia: Age, morphological phenotype, papillomavirus DNA, and coexisting invasive carcinoma  

Microsoft Academic Search

Recent studies suggest that subsets of vulvar intraepithelial neoplasia (VIN) may be distinguished based on morphological presentation, the presence or absence of human papillomavirus (HPV) nucleic acids, and patient age. We analyzed 65 VIN lesions, including 15 with associated squamous cell carcinoma, to determine the relationship between pathological parameters associated with common types of VIN (multinucleation, koilocytosis, verruco-papillary morphology, diffuse

Hope K Haefner; James E Tate; Catherine M McLachlin; Christopher P Crum

1995-01-01

141

The pathology and molecular biology of anal intraepithelial neoplasia: comparisons with cervical and vulvar intraepithelial carcinoma  

Microsoft Academic Search

Background: Anal intraepithelial neoplasia (AIN) is a well-described pathological precursor of invasive squamous cell carcinoma which has recently been detected with increasing frequency in immunocompromised patients, particularly those with seropositivity for human immunodeficiency virus (HIV). The epidemiology and natural history of this entity is somewhat unclear, since the overall prevalence in the HIV seronegative population is unknown. Discussion: There is

A. P. Zbar; C. Fenger; J. Efron; M. Beer-Gabel; S. D. Wexner

2002-01-01

142

Photodynamic Therapy of Vulvar Intraepithelial Neoplasia III Using Topically Applied 5-Aminolevulinic Acid  

Microsoft Academic Search

Objectives. The aim of this study was twofold: first, to determine the feasibility of photodynamic therapy (PDT) of vulvar intraepithelial neoplasia III (VIN III) using topically applied 5-aminolevulinic acid (ALA) for photosensitization, and second, to compare PDT results with those of laser evaporation and local excision.Methods. Fifteen patients with VIN III had 10 g of 10% ALA gel applied to

Mathias K. Fehr; René Hornung; Viola A. Schwarz; René Simeon; Urs Haller; Pius Wyss

2001-01-01

143

Vulvar intraepithelial neoplasia—The need for auditable measures of management  

Microsoft Academic Search

ObjectivesSurgical excision is currently the standard treatment for vulvar intraepithelial neoplasia (VIN). To date it has proved difficult to evaluate the management of VIN in reported series due to heterogeneity in datasets. The objective of this study was to justify standardised data presentation to permit comparison between series and facilitate determination of an optimal strategy for management of VIN. We

Ram Athavale; R. Naik; K. A. Godfrey; P. Cross; M. H. Hatem; A. de Barros Lopes

2008-01-01

144

The extent and multicentricity of high-grade prostatic intraepithelial neoplasia in clinically localized prostatic adenocarcinoma  

Microsoft Academic Search

High-grade prostatic intraepithelial neoplasia (PIN) is considered the most likely precursor of invasive prostatic adenocarcinoma, and is characterized by cellular proliferations within preexisting ducts and glands with cytological changes mimicking cancer. The extent and multicentricity of this clinically important histopathologic lesion have not been fully defined. We sought to determine whether the extent and zonal distribution of PIN are related

Junqi Qian; Peter Wollan; David G Bostwick

1997-01-01

145

MYELOID NEOPLASIA Perturbed hematopoiesis in the Tc1 mouse model of Down syndrome  

E-print Network

MYELOID NEOPLASIA Perturbed hematopoiesis in the Tc1 mouse model of Down syndrome Kate A. Alford,1 Kingdom Trisomy of human chromosome 21 (Hsa21) results in Down syndrome (DS), a disorder that affects many(14):2928-2937) Introduction Down syndrome (DS) results from trisomy of human chromosome 21 (Hsa21, trisomy 21) and is the most

Li, Zhe

146

Does the modality of surgical treatment of cervical intra-epithelial neoplasia effect outcomes?  

Microsoft Academic Search

This review examines the efficacy and morbidity of surgery by either local ablative and excisional therapies for treating cervical intra-epithelial neoplasia (CIN). The effectiveness and morbidity of the various forms of treatment have been generally evaluated by uncontrolled observational studies. Hence, direct comparison of treatment effects of alternative treatments is unreliable because of variable patient selection, treatment outcomes and follow-up

Pierre. L Martin-Hirsch; George Koliopoulos; Evangelos Paraskevaidis

2002-01-01

147

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

148

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...

149

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

Microsoft Academic Search

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

Kent E. Kruckeberg; Stephen N. Thibodeau

150

Cancer Prevention Research Objective Detection and Delineation of Oral Neoplasia Using  

E-print Network

Cancer Prevention Research Objective Detection and Delineation of Oral Neoplasia Using is easily accessible to inspection, patients with oral cancer most often present at a late stage, leading. Head and neck cancer, including cancers of the oral cavity, currently ranks as the sixth most common

Roblyer, Darren

151

The significance of lobular neoplasia on needle core biopsy of the breast  

PubMed Central

The management of a core biopsy diagnosis of lobular neoplasia is controversial. Detailed radiological–pathological review of 47 patients with cores showing classical lobular neoplasia was performed (patients with pleomorphic lobular carcinoma in situ (LCIS) or associated risk lesions were considered separately). Immediate surgical excision in 25 patients showed invasive carcinoma in 7, ductal carcinoma in situ (DCIS) in 1 and pleomorphic LCIS in 1; radiological–pathological review showed that the core biopsy missed a mass in 5, missed calcification in 2 and that calcification appeared adequately sampled in 2. Nineteen patients had follow-up of at least 2 years. Four patients developed malignancy at the site of the core biopsy (invasive carcinoma in three, DCIS in one); one carcinoma was mammographically occult, one patient had dense original mammograms and two had calcifications apparently adequately sampled by the core. In conclusion, most carcinomas identified at the site of core biopsy showing lobular neoplasia were the result of the core missing the radiological lesion, emphasising the importance of multidisciplinary review and investigation of any discordance. Some carcinomas were found after apparently adequate core biopsy, raising the question of whether excision biopsy should be considered after all core biopsy diagnoses of lobular neoplasia. PMID:18389278

Menon, S.; Porter, G. J. R.; Evans, A. J.; Ellis, I. O.; Elston, C. W.; Hodi, Z.

2008-01-01

152

Spectrum and Risk of Neoplasia in Werner Syndrome: A Systematic Review  

E-print Network

(`premature aging') syndrome which is associated with an elevated risk of cancer. Objectives: Our studySpectrum and Risk of Neoplasia in Werner Syndrome: A Systematic Review Julia M. Lauper1,2 , Alison Abstract Background: Werner syndrome (WS) is an autosomal recessive genetic instability and progeroid

Monnat, Ray

153

The significance of lobular neoplasia on needle core biopsy of the breast.  

PubMed

The management of a core biopsy diagnosis of lobular neoplasia is controversial. Detailed radiological-pathological review of 47 patients with cores showing classical lobular neoplasia was performed (patients with pleomorphic lobular carcinoma in situ (LCIS) or associated risk lesions were considered separately). Immediate surgical excision in 25 patients showed invasive carcinoma in 7, ductal carcinoma in situ (DCIS) in 1 and pleomorphic LCIS in 1; radiological-pathological review showed that the core biopsy missed a mass in 5, missed calcification in 2 and that calcification appeared adequately sampled in 2. Nineteen patients had follow-up of at least 2 years. Four patients developed malignancy at the site of the core biopsy (invasive carcinoma in three, DCIS in one); one carcinoma was mammographically occult, one patient had dense original mammograms and two had calcifications apparently adequately sampled by the core. In conclusion, most carcinomas identified at the site of core biopsy showing lobular neoplasia were the result of the core missing the radiological lesion, emphasising the importance of multidisciplinary review and investigation of any discordance. Some carcinomas were found after apparently adequate core biopsy, raising the question of whether excision biopsy should be considered after all core biopsy diagnoses of lobular neoplasia. PMID:18389278

Menon, S; Porter, G J R; Evans, A J; Ellis, I O; Elston, C W; Hodi, Z; Lee, A H S

2008-05-01

154

Surgical approach in patients with hyperparathyroidism in multiple endocrine neoplasia type 1: total versus partial parathyroidectomy  

PubMed Central

Usually, primary hyperparathyroidism is the first endocrinopathy to be diagnosed in patients with multiple endocrine neoplasia type 1, and is also the most common one. The timing of the surgery and strategy in multiple endocrine neoplasia type 1/hyperparathyroidism are still under debate. The aims of surgery are to: 1) correct hypercalcemia, thus preventing persistent or recurrent hyperparathyroidism; 2) avoid persistent hypoparathyroidism; and 3) facilitate the surgical treatment of possible recurrences. Currently, two types of surgical approach are indicated: 1) subtotal parathyroidectomy with removal of at least 3–3½ glands; and 2) total parathyroidectomy with grafting of autologous parathyroid tissue. Transcervical thymectomy must be performed with both of these procedures. Unsuccessful surgical treatment of hyperparathyroidism is more frequently observed in multiple endocrine neoplasia type 1 than in sporadic hyperparathyroidism. The recurrence rate is strongly influenced by: 1) the lack of a pre-operative multiple endocrine neoplasia type 1 diagnosis; 2) the surgeon's experience; 3) the timing of surgery; 4) the possibility of performing intra-operative confirmation (histologic examination, rapid parathyroid hormone assay) of the curative potential of the surgical procedure; and, 5) the surgical strategy. Persistent hyperparathyroidism seems to be more frequent after subtotal parathyroidectomy than after total parathyroidectomy with autologous graft of parathyroid tissue. Conversely, recurrent hyperparathyroidism has a similar frequency in the two surgical strategies. To plan further operations, it is very helpful to know all the available data about previous surgery and to undertake accurate identification of the site of recurrence. PMID:22584722

Tonelli, Francesco; Giudici, Francesco; Cavalli, Tiziana; Brandi, Maria Luisa

2012-01-01

155

Surgical approach in patients with hyperparathyroidism in multiple endocrine neoplasia type 1: total versus partial parathyroidectomy.  

PubMed

Usually, primary hyperparathyroidism is the first endocrinopathy to be diagnosed in patients with multiple endocrine neoplasia type 1, and is also the most common one. The timing of the surgery and strategy in multiple endocrine neoplasia type 1/hyperparathyroidism are still under debate. The aims of surgery are to: 1) correct hypercalcemia, thus preventing persistent or recurrent hyperparathyroidism; 2) avoid persistent hypoparathyroidism; and 3) facilitate the surgical treatment of possible recurrences. Currently, two types of surgical approach are indicated: 1) subtotal parathyroidectomy with removal of at least 3-3 K glands; and 2) total parathyroidectomy with grafting of autologous parathyroid tissue. Transcervical thymectomy must be performed with both of these procedures. Unsuccessful surgical treatment of hyperparathyroidism is more frequently observed in multiple endocrine neoplasia type 1 than in sporadic hyperparathyroidism. The recurrence rate is strongly influenced by: 1) the lack of a pre-operative multiple endocrine neoplasia type 1 diagnosis; 2) the surgeon's experience; 3) the timing of surgery; 4) the possibility of performing intra-operative confirmation (histologic examination, rapid parathyroid hormone assay) of the curative potential of the surgical procedure; and, 5) the surgical strategy. Persistent hyperparathyroidism seems to be more frequent after subtotal parathyroidectomy than after total parathyroidectomy with autologous graft of parathyroid tissue. Conversely, recurrent hyperparathyroidism has a similar frequency in the two surgical strategies. To plan further operations, it is very helpful to know all the available data about previous surgery and to undertake accurate identification of the site of recurrence. PMID:22584722

Tonelli, Francesco; Giudici, Francesco; Cavalli, Tiziana; Brandi, Maria Luisa

2012-01-01

156

Multiple endocrine neoplasia type 2 (Sipple's syndrome): clinical and cytogenetic analysis of a kindred  

Microsoft Academic Search

This report describes the clinical and cytogenetic analysis of a kindred with multiple endocrine neoplasia type 2 (MEN-2 or Sipple's syndrome) in two generations. Medullary thyroid carcinoma was present in five members either as a large or as an occult tumour. Phaeochromocytoma was demonstrated in one severely hypertensive relative and urine vanillylmandelic acid (VMA) was increased in one normotensive member.

A Zatterale; M Stabile; V Nunziata; G Di Giovanni; R Vecchione; V Ventruto

1984-01-01

157

Intestinal and oncocytic variants of pancreatic intraepithelial neoplasia. A morphological and immunohistochemical study  

Microsoft Academic Search

We report 2 previously undescribed morphological variants of pancreatic intraepithelial neoplasia (PanIN). The first variant with an intestinal phenotype was associated with mucinous carcinomas that occurred in the tail of the pancreas of 2 men (60 and 65 years old). The carcinomas lacked the characteristic ovarian-like stroma of mucinous cystic neoplasms observed in female patients and did not show a

Jorge Albores-Saavedra; Jianhua Wu; Terri Crook; Robin H. Amirkhan; Lamar Jones; Ralph H. Hruban

2005-01-01

158

Characteristics of the Danish families with multiple endocrine neoplasia type 1  

Microsoft Academic Search

Multiple endocrine neoplasia type 1 (MEN1) is caused by autosomal dominantly inherited mutations in the MEN1 gene. Here, we report 25 MEN1 mutations – of which 12 are novel – found in 36 Danish families with MEN1 or variant MEN1 disease. Furthermore, one FIHP family was found to have an earlier reported mutation. The mutations were predominantly found in exons

Anne Charlotte Jäger; Lennart Friis-Hansen; Thomas v. O. Hansen; Peter C. Eskildsen; Karsten Sølling; Ulrich Knigge; Carsten P. Hansen; Per H. Andersen; Kim Brixen; Ulla Feldt-Rasmussen; Jens Peter Kroustrup; Charlotte L. Mollerup; Jens F. Rehfeld; Mogens Blichert-Toft; Finn C. Nielsen

2006-01-01

159

Surgical management of insulinoma associated with multiple endocrine neoplasia type I  

Microsoft Academic Search

Insulinoma in patients with multiple endocrine neoplasia (MEN) is a rare condition that because of its usual multicentricity presents difficulties not encountered in sporadic patients. In contrast to gastrinoma, which is the most common pancreatic neoplasm associated with MEN I, malignancy and duodenal tumors are much less common for patients with insulinomas, and excellent palliative medication is not available. Accordingly,

Diarmuid S. O'Riordain; Timothy O'Brien; Jon A. van Heerden; F. J. Service; Clive S. Grant

1994-01-01

160

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

Microsoft Academic Search

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

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

1987-01-01

161

Baseline Cytology, Human Papillomavirus Testing, and Risk for Cervical Neoplasia: A 10Year Cohort Analysis  

Microsoft Academic Search

Background: Annual Pap smear screening has been favored over less frequent screening in the United States to minimize the risk of cervical cancer. We evaluated whether simulta- neous screening with a Pap test and human papillomavirus (HPV) testing is useful for assessing the risk for cervical intraepithelial neoplasia (CIN) 3 or cervical cancer. Meth- ods: We enrolled 23 702 subjects

Mark E. Sherman; Attila T. Lorincz; David R. Scott; Sholom Wacholder; Philip E. Castle; Andrew G. Glass; Iwona Mielzynska-Lohnas; Brenda B. Rush; Mark Schiffman

2003-01-01

162

Intratubular germ cell neoplasia of the human testis: heterogeneous protein expression and relation to invasive potential.  

PubMed

Testicular germ cell cancer develops from premalignant intratubular germ cell neoplasia, unclassified cells that are believed to arise from failure of normal maturation of fetal germ cells from gonocytes (OCT4(+)/MAGEA4(-)) into pre-spermatogonia (OCT4(-)/MAGEA4(+)). Intratubular germ cell neoplasia cell subpopulations based on stage of germ cell differentiation have been described, however the importance of these subpopulations in terms of invasive potential has not been reported. We hypothesized that cells expressing an immature (OCT4(+)/MAGEA4(-)) germ cell profile would exhibit an increased proliferation rate compared with those with a mature profile (OCT4(+)/MAGEA4(+)). Therefore, we performed triple immunofluorescence and stereology to quantify the different intratubular germ cell neoplasia cell subpopulations, based on expression of germ cell (OCT4, PLAP, AP2?, MAGEA4, VASA) and proliferation (Ki67) markers, in testis sections from patients with preinvasive disease, seminoma, and non-seminoma. We compared these subpopulations with normal human fetal testis and with seminoma cells. Heterogeneity of protein expression was demonstrated in intratubular germ cell neoplasia cells with respect to gonocyte and spermatogonial markers. It included an embryonic/fetal germ cell subpopulation lacking expression of the definitive intratubular germ cell neoplasia marker OCT4, that did not correspond to a physiological (fetal) germ cell subpopulation. OCT4(+)/MAGEA4(-) cells showed a significantly increased rate of proliferation compared with the OCT4(+)/MAGEA4(+) population (12.8 versus 3.4%, P<0.0001) irrespective of histological tumor type, reflected in the predominance of OCT4(+)/MAGEA4(-) cells in the invasive tumor component. Surprisingly, OCT4(+)/MAGEA4(-) cells in patients with preinvasive disease showed significantly higher proliferation compared to those with seminoma or non-seminoma (18.1 versus 10.2 versus 7.2%, P<0.05, respectively). In conclusion, this study has demonstrated that OCT4(+)/MAGEA4(-) cells are the most frequent and most proliferative cell population in tubules containing intratubular germ cell neoplasia, which appears to be an important factor in determining invasive potential of intratubular germ cell neoplasia to seminomas. PMID:24457464

Mitchell, Rod T; E Camacho-Moll, Maria; Macdonald, Joni; Anderson, Richard A; Kelnar, Christopher J H; O'Donnell, Marie; Sharpe, Richard M; Smith, Lee B; Grigor, Ken M; Wallace, W Hamish B; Stoop, Hans; Wolffenbuttel, Katja P; Donat, Roland; Saunders, Philippa Tk; Looijenga, Leendert Hj

2014-09-01

163

Confocal laser endomicroscopy for detection of neoplasia in Barrett's esophagus: a meta-analysis.  

PubMed

Barrett's esophagus (BE) is associated with an increased risk of esophageal adenocarcinoma, and the recommended guideline for detection of neoplasia is surveillance endoscopy with random four-quadrant biopsies. Recently, a novel technique, confocal laser endomicroscopy (CLE), has emerged and enabled the endoscopist to perform a real-time histologic assessment of the gastrointestinal tract. We aimed to assess the accuracy of CLE in diagnosing BE-associated neoplasia by pooling data of existing trials. Databases including PubMed, EMBASE, the Cochrane Library, the Science Citation Index and momentous meeting abstracts were searched and evaluated by two reviewers independently. Meta-analysis was performed. Pooling data were conducted in a fixed effect model or a random effects model. Eight studies involving 709 patients and 4008 specimens were analyzed. In a per-patient analysis, the pooled sensitivity of CLE for detection of neoplasia was 89% (95% confidence interval [CI], 0.80-0.95), and the specificity was 75% (95% CI, 0.69-0.81). The area under the curve under the summary receiver operating characteristic was 0.9472. In a per-location analysis, the pooled sensitivity of CLE for detection of neoplasia was 70% (95% CI, 0.65-0.74), and the specificity was 91% (95% CI, 0.90-0.92). The area under the curve under the summary receiver operating characteristic was 0.9509. CLE is a reasonable, promising modality for management of patients with BE; more prospective trials need doing to determine whether it is superior to traditional method in diagnosing BE-associated neoplasia. PMID:23672425

Wu, J; Pan, Y-M; Wang, T-T; Hu, B

2014-04-01

164

Multiple endocrine neoplasia, type II: a combined surgical and genetic approach to treatment.  

PubMed Central

A family with multiple endocrine neoplasia, type II living in southeastern Ontario is described. Twenty individuals are known to have had medullary carcinoma of the thyroid, pheochromocytoma or both, the diagnosis of multiple endocrine neoplasia. type II is strongly suspected in five other individuals in the earlier generations. In this family the diseases seems to be transmitted by an autosomal dominant gene. A screening program set up for the family in 1977 has in 2 years identified four asymptomatic individuals (three with medullary carcinoma of the thyroid and one with this carcinoma and a pheochromocytoma). The family background, clinical picture, treatment and some of the problems of the screening program are described. PMID:7214269

Partington, M W; Ghent, W R; Sears, E V; Simpson, N E

1981-01-01

165

The role of surgery in the management of gestational trophoblastic neoplasia.  

PubMed

Although sensitive human chorionic gonadotropin assays and advances in chemotherapy have assumed primary importance in the management of gestational trophoblastic neoplasia, surgery remains important in the overall care of these patients. Management of molar pregnancies consists of surgical evacuation and subsequent monitoring. Hysterectomy decreases the risk of post-molar trophoblastic disease in appropriate patients and, when incorporated to primary management of gestational trophoblastic neoplasia, can decrease the chemotherapy requirements of patients with low-risk disease. In patients with high-risk disease, surgical intervention is frequently required to control complications of disease or as therapy to stabilize patients during chemotherapy. Hysterectomy, thoracotomy, or other extirpative procedures may be integrated into the management of patients with chemorefractory disease. Interventional procedures are useful adjuncts to control bleeding from metastases. PMID:23803756

Doll, Kemi M; Soper, John T

2013-07-01

166

Germ line mutation analysis in families with multiple endocrine neoplasia type 2A or familial medullary thyroid carcinoma  

Microsoft Academic Search

The RET proto-oncogene has been identified as the multiple endocrine neoplasia type 2 disease gene. An association between specific RET mutation and disease phenotype has been reported. We present the phenotype-genotype of 12 Greek families with multiple endocrine neoplasia type 2A (MEN 2A) or familial medullary thyroid carcinoma (FMTC). Seventy members were studied and DNA analysis for RET mutations was

Helen J Karga; Maria K Karayianni; Dimitrios A Linos; Sofia C Tseleni; Konstantine D Karaiskos; Peter D Papapetrou

1998-01-01

167

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

168

HPV-related vulvar intraepithelial neoplasia: Outcome of different management modalities  

Microsoft Academic Search

Objective: To evaluate the outcome of various management schemes for HPV-related vulvar intraepithelial neoplasia (VIN, usual type). Methods: Retrospective chart review of patients with histologically diagnosed grade 2\\/3-VIN who had at least one year of follow-up. The variables that were collected included patient characteristics, management modalities, and clinical outcome. Results: Fifty patients with a median age of 45 years old

I. Bruchim; S. Mahmud; E. Tunitsky; K. Grzywacz; A. Ferenczy

2007-01-01

169

Treatment for Vulvar Intraepithelial Neoplasia II\\/III Bowenoid or Basaloid with Imiquimod 5% cream  

Microsoft Academic Search

Objetives : To evaluate efficacy and safety of Imiquimod 5% for the treatment of VIN II\\/III Bowenoid or Basaloid. To evaluate recurrences following treatment. Material and method : Eight patients less than 55 years (32-51), mean (39.7), with VIN II\\/III Bowenoid or Basaloid diagnosed by biopsy were treated with Imiquimod 5%. Patients with other intraepithelial neoplasia (IEN) of the lower

Secco G; Perrotta M; Lugones L; Pesce R; Testa R; Claudia Marchitelli

170

The contribution of MIB 1 in the accurate grading of vulvar intraepithelial neoplasia  

Microsoft Academic Search

AIM: To determine the interobserver variation in scoring presence and grade of vulvar intraepithelial neoplasia (VIN) in haematoxylin\\/eosin (H\\/E) slides, MIB 1 slides, and the combined use of H\\/E and MIB 1 slides. METHODS: 10 slides were stained with H\\/E and MIB 1 with each of the following diagnoses: normal vulvar skin, VIN 1, VIN 2, and VIN 3. Six

M. van Beurden; A. J. de Craen; H. C. de Vet; J. L. G. Blaauwgeers; P. Drillenberg; M. P. W. Gallee; N. W. de Kraker; F. B. Lammes; F. J. ten Kate

1999-01-01

171

Disturbed Patterns of Immunocompetent Cells in Usual-Type Vulvar Intraepithelial Neoplasia  

Microsoft Academic Search

Genital infection with human papillomavirus (HPV) is usually transient, as the immune system is capable of eliminating the virus. When immunity ''fails'' andthe infection persists, vulvar intraepithelial neoplasia (VIN) may develop. In this study, we examinedthe distribution of inflammatory cells in 51 patients with HPV-associatedusual-type VIN andin 19 healthy controls. Frozen vulvar tissue samples were testedfor the presence of HPV-DNA,

Manon van Seters; Ilse Beckmann; Claudia Heijmans-Antonissen; Marc van Beurden; Patricia C. Ewing; Freek J. Zijlstra; Theo J. M. Helmerhorst; Alex KleinJan

172

Evaluation of CO 2 Laser Excision or Vaporization for the Treatment of Vulvar Intraepithelial Neoplasia  

Microsoft Academic Search

Objective. Ourobjective was to evaluate the results of laser surgery in patients with vulvar intraepithelial neoplasia (VIN).Methods. From January 1990 to December 1996, 52 patients with histologically proven VIN were treated with CO2 laser vaporization or laser excision. The analysis included anamnestic characteristics, clinical aspects, types of treatment, correlation of the preoperative biopsy with the excised pathologic specimen, and follow-up

M. Sideri; L. Spinaci; N. Spolti; F. Schettino

1999-01-01

173

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

PubMed

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

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

2008-12-01

174

Undemutrition as a risk factor for cervical intraepithelial neoplasia: A case?control analysis  

Microsoft Academic Search

To evaluate the relationship between cervical intraepithelial neoplasia (CIN) and undemutrition, a pair?matched case?control study was conducted in a low?income urban population. As a broad measure of nutritional status, serum albumin, serum ferritin, hematocrit, percent desirable weight, and percent calories consumed as protein were examined. Cases (n = 102) had biopsy?confirmed CIN I, II, or III, and clinic controls (n

Craig F. Amburgey; Juliet VanEenwyk; Faith G. Davis; Phyllis E. Bowen; Victoria Persky; Jack Goldberg

1993-01-01

175

Computed Tomographic Virtual Colonoscopy to Screen for Colorectal Neoplasia in Asymptomatic Adults  

Microsoft Academic Search

background We evaluated the performance characteristics of computed tomographic (CT) virtual colonoscopy for the detection of colorectal neoplasia in an average-risk screening pop- ulation. methods A total of 1233 asymptomatic adults (mean age, 57.8 years) underwent same-day vir- tual and optical colonoscopy. Radiologists used the three-dimensional endoluminal display for the initial detection of polyps on CT virtual colonoscopy. For the

Perry J. Pickhardt; J. Richard Choi; Inku Hwang; James A. Butler; Michael L. Puckett; Hans A. Hildebrandt; Roy K. Wong; Pamela A. Nugent; Pauline A. Mysliwiec; William R. Schindler

2003-01-01

176

Exclusion of linkage between the loci for multiple endocrine neoplasia type-2 (MEN2) and HLA  

Microsoft Academic Search

Data from five nuclear families within a large kindred with multiple endocrine neoplasia type-2 (MEN-2) or Sipple's syndrome exclude linkage between the disease locus and the loci in the HLA complex. There were seven recombinants and seven non-recombinants in the four families with phase known data and total lod score of-2.659 for a recombination fraction of 0.1.

Nancy E. Simpson; Judy Falk

1982-01-01

177

Intraoperative Parathormone Measurement in Patients with Multiple Endocrine Neoplasia Type I Syndrome and Hyperparathyroidism  

Microsoft Academic Search

.   Total or subtotal parathyroidectomy is considered the treatment of choice for multiple endocrine neoplasia type I (MEN-I)-associated\\u000a primary hyperparathyroidism (HPT). However, persistent or recurrent HPT is frequently observed. The development of a rapid\\u000a two-site immunoradiometric assay (IRMA) method for measuring intact parathormone (PTH) has provided a valuable tool for recognizing\\u000a possible surgical failures. Our experience includes 16 MEN-I patients

Francesco Tonelli; Simona Spini; Mariasilvia Tommasi; Gianfranco Gabbrielli; Andrea Amorosi; Alessandro Brocchi; Maria Luisa Brandi

2000-01-01

178

Genotype\\/Phenotype Correlation of Multiple Endocrine Neoplasia Type 1 Gene Mutations in Sporadic Gastrinomas  

Microsoft Academic Search

Multiple endocrine neoplasia type 1 (MEN1) gene mutations are reported in some gastrinomas occurring in patients without MEN1 as well as in some other pancreatic endocrine tumors (PETs). In some inherited syndromes phenotype-genotype correlations exist for dis- ease severity, location, or other manifestations. The purpose of the present study was to correlate mutations of the MEN1 gene in a large

STEPHAN U. GOEBEL; CHRISTINA HEPPNER; A. LEE BURNS; STEPHEN J. MARX; ALLEN M. SPIEGEL; ZHENGPING ZHUANG; IRINA A. LUBENSKY; FATHIA GIBRIL; ROBERT T. JENSEN

2010-01-01

179

Mechanisms of Disease: multiple endocrine neoplasia type 1—relation to chromatin modifications and transcription regulation  

Microsoft Academic Search

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary tumor syndrome characterized by tumors of the parathyroid glands, the pancreatic islets, the pituitary gland, the adrenal glands, as well as by neuroendocrine carcinoid tumors, often at a young age. Causal to the syndrome are germline mutations of the MEN1 tumor-suppressor gene. Identification of gene-mutation carriers has enabled presymptomatic diagnosis and

Koen MA Dreijerink; Jo WM Höppener; HT Marc Timmers; Cornelis JM Lips

2006-01-01

180

Screening for Multiple Endocrine Neoplasia Type 1 and Hormonal Production in Apparently Sporadic Neuroendocrine Tumors  

Microsoft Academic Search

Screening was performed in 130 consecutive patients with appar- ently sporadic neuroendocrine tumors (NET) to assess the prevalence of multiple endocrine neoplasia type 1 (MEN1) and hormonal pro- duction. Screening for MEN1 included measurement of serum cal- cium and PTH (PTH-(1- 84)), gastrin, PRL, and insulin-like growth factor type I (IGF-I) levels. MEN1 genetic testing was performed in patients with

ERIC BAUDIN; JEAN-MICHEL BIDART; PHILIPPE ROUGIER; VLADIMIR LAZAR; PIERRE RUFFIE; JACQUES ROPERS; MICHEL DUCREUX; FREDERIC TROALEN; JEAN-CHRISTOPHE SABOURIN; ETIENNE COMOY; PHILIPPE LASSER; THIERRY DEBAERE; MARTIN SCHLUMBERGER

2010-01-01

181

Predictive Genetic Screening and Clinical Findings in Multiple Endocrine Neoplasia Type I Families  

Microsoft Academic Search

.   Germline mutations of the MEN1 gene have been identified as the causative genetic defect of multiple endocrine neoplasia type I (MEN-I), an autosomal dominantly\\u000a inherited condition. To establish the basis for predictive family screening we evaluated the spectrum of MEN1 gene mutations in MEN-I patients treated at our institution. Relatives at risk were subjected to predictive genetic screening\\u000a after

Ina Kopp; Detlef Bartsch; Anja Wild; Thomas Schilling; Christoph Nies; Anders Bergenfelz; Harald Rieder; Babette Simon; Matthias Rothmund

2001-01-01

182

Care for patients with multiple endocrine neoplasia type 1: the current evidence base  

Microsoft Academic Search

Multiple endocrine neoplasia type 1 (MEN1) is a rare disease caused by mutations in the MEN1 gene on chromosome 11. It is characterized by the occurrence of primary hyperparathyroidism (pHPT), duodenopancreatic neuroendocrine\\u000a tumours (pNET), pituitary tumours (PIT), adrenal adenomas (ADR) and neuroendocrine tumours (NET) of the stomach, bronchus\\u000a and thymus. MEN1 is a syndrome with high penetrance and high morbidity.

C. R. C. Pieterman; M. R. Vriens; K. M. A. Dreijerink; R. B. van der Luijt; G. D. Valk

2011-01-01

183

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

184

Large and asymptomatic pancreatic islet cell tumor in a patient with multiple endocrine neoplasia type 1  

Microsoft Academic Search

The major phenotypes of multiple endocrine neoplasia type 1 (MEN 1) consist of three lesions characterized by hyperparathyroidism,\\u000a pituitary tumors, and endocrine pancreatic tumors. The endocrine pancreatic tumors are a significant cause of disease-related\\u000a mortality in MEN 1. Although symptomatic pancreatic tumors such as insulinoma and gastrinoma should be resected, the management\\u000a of asymptomatic pancreatic tumors is not established. In

Makoto Sato; Minoru Kihara; Akiko Nishitani; Koji Murao; Shoji Kobayashi; Akira Miyauchi; Jiro Takahara

2000-01-01

185

Presentation and Outcome of Pancreaticoduodenal Endocrine Tumors in Multiple Endocrine Neoplasia Type 1 Syndrome  

Microsoft Academic Search

Aim: To assess presentation and outcome of pancreaticoduodenal endocrine tumors (PDETs) in a single center series of multiple endocrine neoplasia type 1 (MEN1) patients. Methods: Retrospective analysis of prospectively collected data of MEN1 patients observed at the University of Verona. Results: Thirty-one MEN1 patients had PDETs, including 16 nonfunctioning (NF), 6 insulinomas and 9 Zollinger-Ellison syndrome (ZES). In 16 of

Maria Vittoria Davì; Letizia Boninsegna; Luca Dalle Carbonare; Marco Toaiari; Paola Capelli; Aldo Scarpa; Giuseppe Francia; Massimo Falconi

2011-01-01

186

Management of Pancreatic Endocrine Tumors in Multiple Endocrine Neoplasia Type 1  

Microsoft Academic Search

Introduction  Pancreatic endocrine tumors (PETs) occur in at least 50% of patients with multiple endocrine neoplasia type 1 (MEN1) and are\\u000a the leading cause of disease-specific mortality. However, the timing and extent of surgery for MEN1-related PETs is controversial\\u000a owing to the indolent tumor growth seen in most patients and the desire to avoid complications associated with insulin dependence.\\u000a To help

Maria A. Kouvaraki; Suzanne E. Shapiro; Gilbert J. Cote; Jeffrey E. Lee; James C. Yao; Steven G. Waguespack; Robert F. Gagel; Douglas B. Evans; Nancy D. Perrier

2006-01-01

187

Update on Familial Pituitary Tumors: from Multiple Endocrine Neoplasia Type 1 to Familial Isolated Pituitary Adenoma  

Microsoft Academic Search

Background: Pituitary adenomas occur in a familial setting in about 5% of all cases and over half of these are due to multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). Since the late 1990s, we have described non-MEN1\\/CNC familial pituitary tumors that include all tumor phenotypes and have named this condition ‘familial isolated pituitary adenoma’ (FIPA). Clinical features

Adrian F. Daly; Maria A. Tichomirow; Albert Beckers

2009-01-01

188

Protein kinase A and its role in human neoplasia: the Carney complex paradigm  

Microsoft Academic Search

The type 1 alpha regulatory subunit (R1a) of cAMP-dependent protein kinase A (PKA) (PRKAR1A )i s an important regulator of the serine-threonine kinase activity catalyzed by the PKA holoenzyme. Carney complex (CNC) describes the association 'of spotty skin pigmentation, myxomas, and endocrine overactivity'; CNC is in essence the latest form of multiple endocrine neoplasia to be described and affects the

I Bossis; A Voutetakis; F Sandrini; K J Griffin; C A Stratakis

2004-01-01

189

Are Patients with Multiple Endocrine Neoplasia Type I Prone to Premature Death?  

Microsoft Academic Search

.   Multiple endocrine neoplasia type I (MEN-I) is an autosomal dominant disorder characterized by endocrinopathies involving\\u000a the anterior pituitary gland, parathyroid glands, and pancreas. The long-term prognosis for patients affected with this disorder\\u000a is uncertain. To better characterize this prognosis, we performed a retrospective review of all patients with MEN-I treated\\u000a at a single institution during the period 1951–1997. A

Patrick G. Dean; Jon A. van Heerden; David R. Farley; Geoffrey B. Thompson; Clive S. Grant; W. Scott Harmsen; Duane M. Ilstrup

2000-01-01

190

An oncogenic role for the multiple endocrine neoplasia type 1 gene in prostate cancer  

Microsoft Academic Search

Prostate cancer is the second leading cause of cancer related deaths in US men, largely because of metastasis, which is ultimately fatal. A better understanding of metastasis biology will lead to improved prognostication and therapeutics. We previously reported 11q13.1 gain was independently predictive of recurrence after radical prostatectomy. Multiple endocrine neoplasia I (MEN1) maps to this region of copy number

P L Paris; S Sridharan; A B Hittelman; Y Kobayashi; S Perner; G Huang; J Simko; P Carroll; M A Rubin; C Collins

2009-01-01

191

Evaluation of quality of life of patients submitted to pulmonary resection due to neoplasia  

Microsoft Academic Search

Objective: To evaluate the health-related quality of life of patients submitted to resection of the pulmonary parenchyma due to neoplasia. Methods: The Medical Outcomes Study 36-item Short-Form Health Survey was used to evaluate patients in the preoperative period and on postoperative days 30, 90 and 180. We used the GEE statistical model, in which the dependent variable (quality of life)

IVETE ALONSO; BREDDA SAAD; NEURY JOSÉ BOTEGA; IVAN FELIZARDO; CONTRERA TORO

2006-01-01

192

DNA quantification in cervical intraepithelial neoplasia thick tissue sections by confocal laser scanning microscopy.  

PubMed

Image analysis of tissue biopsies for determination of DNA content as an early marker of neoplasia is hampered by the complexity of corrections necessary to dea with nuclear truncation and overlap in thin sections. The use of confocal laser scanning microscopy (CLSM) for measurement of cellular DNA content on whole cells within thick tissue sections offers the advantage of preservation of cellular architecture, capacity for 3-dimensional analysis, and absence of sectioning artifacts. We have applied this technique to pararosaniline-Feulgen stained human cervical tissues graded from normal to cervical intraepithelial neoplasia (CIN) III. For the purpose of comparison, 15 microns sections were stained and mapped so that the same cell population could be analyzed by both integrated optical density and fluorescence intensity. Distribution of DNA content from normal cervical epithelial cells 2-3 layers out from the basal cell layer measured by both methodologies showed a stable G0/G1 population with no observable S-phase or G2 cells. Cells measured from areas of increasing CIN grade showed progressively higher DNA content values that were not observable in normal tissue. Although these data are preliminary they suggest that CLSM can be used to identify aneuploid states within defined structural areas of pre-invasive neoplasia. PMID:9027598

Crist, K A; Kim, K; Goldblatt, P J; Boone, C W; Kelloff, G J; You, M

1996-01-01

193

Effects of combination endocrine treatment on normal prostate, prostatic intraepithelial neoplasia, and prostatic adenocarcinoma.  

PubMed Central

AIMS--To investigate the effect of combination endocrine treatment (CET) or luteinising hormone releasing hormone agonist and flutamide on non-neoplastic prostate, prostatic intraepithelial neoplasia, and prostatic adenocarcinoma. METHODS--The morphology, including the mitotic activity, of 12 radical prostatectomies from patients with prostatic adenocarcinoma pretreated for three months with CET was evaluated in haematoxylin and eosin stained sections and compared with an untreated age and stage matched control group. RESULTS--A differential effect on the non-neoplastic prostate was observed. In fact, the transition zone of the treated prostate showed simplification of the glandular lobules: the ducts and acini were small without undulations of the epithelial border and with a prominent basal cell layer. Within the peripheral zone there was inconspicuous branching of the ducts and acini which looked dilatated and lined by flattened atrophic epithelium. Prostatic intraepithelial neoplasia occurred in scattered ducts and acini in the peripheral zone of 10 of the 12 patients. The epithelial cell lining showed a prominent basal cell layer. A certain degree of secretory cell type stratification was always present. However, crowding was less evident than in the untreated prostate because of cytoplasmic clearing and enlargement as a result of coalescence of vacuoles. The treated adenocarcinomas had neoplastic acini which looked small and shrunken, and areas of individual infiltrating tumour cells separated by abundant interglandular connective tissue. The secretory cells of the nonneoplastic, prostatic intraepithelial neoplasia, and prostatic adenocarcinoma lesions had inconspicuous nucleoli, nuclear shrinkage, chromatin condensation, and cytoplasmic clearing. Apoptotic bodies were easily identifiable in all the cell layers. The lumina were rich in macrophages, sloughed secretory cells with degenerative features, and apoptotic bodies. Mitoses were not observed in any of the treated non-neoplastic prostate, prostatic intraepithelial neoplasia, or prostatic adenocarcinomas, whereas the mitotic frequency increased from non-neoplastic prostate through prostatic intraepithelial neoplasia up to prostatic adenocarcinomas in the untreated specimens. CONCLUSIONS--CET before radical prostatectomy causes regressive epithelial changes together with enhanced apoptosis and blocked mitotic activity. Images PMID:7525657

Montironi, R; Magi-Galluzzi, C; Muzzonigro, G; Prete, E; Polito, M; Fabris, G

1994-01-01

194

Prevenzione della infezione incrociata nella Fibrosi Cistica: come delle iniziative relativamente semplici hanno migliorato la prognosi in soggetti affetti da fibrosi cistica in Danimarca  

Microsoft Academic Search

La maggioranza dei pazienti adulti con fibrosi cistica (FC) contraggono infezione batterica polmonare cronica. I più comuni agenti patogeni nella FC nel mondo sono i seguenti: • Pseudomonas aeruginosa (P. aeruginosa), seguito da • Staffilococco aureo (S. aureus), • Complesso Burkholderia cepacia (B. cepacia), • Achromobacter xylosoxidans (A. xylosoxidans), • Stenotrophomonas maltophilia (S. maltophilia) • Micobatteri non tubercolosi (MNT). La

Claus Moser; Niels Høiby

195

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

196

Prevalence and predictors of recurrent neoplasia after ablation of Barrett's esophagus  

PubMed Central

Background The incidence and risk factors for recurrence of dysplasia after ablation of Barrett's esophagus (BE) have not been well defined. Objective To determine the rate and predictors of dysplasia/neoplasia recurrence after photodynamic therapy (PDT) in BE. Setting Retrospective analysis of a prospective cohort of BE patients seen at a specialized BE unit. Methods Patients underwent a standard protocol assessment with esophagogastroduodenoscopy and 4-quadrant biopsies every centimeter at 3-month intervals after ablation. Recurrence was defined as the appearance of any grade of dysplasia or neoplasia after 2 consecutive endoscopies without dysplasia. Entry histology, demographics, length of BE, presence and length of diaphragmatic hernia, EMR, stricture formation, nonsteroidal anti-inflammatory drug use, smoking, and the presence of nondysplastic BE or squamous epithelium were assessed for univariate associations. Time-to-recurrence analysis was done by using Cox proportional hazards regression. A multivariate model was constructed to establish independent associations with recurrence. Results A total of 363 patients underwent PDT with or without EMR. Of these, 261 patients were included in the final analysis (44 lost to follow-up, 46 had residual dysplasia, and 12 had no dysplasia at baseline). Indication for ablation was low-grade dysplasia (53 patients, 20%), high-grade dysplasia (152 patients, 58%), and intramucosal cancer (56 patients, 21%). Median follow-up was 36 months (interquartile range 18-79 months). Recurrence occurred in 45 patients. Median time to recurrence was 17 months (interquartile range 8-45 months). Significant predictors of recurrence on the multivariate model were older age (hazard ratio [HR] 1.04, P=.029), presence of residual nondysplastic BE (HR 2.88, P=.012), and a history of smoking (HR 2.68, P=.048). Limitations Possibility of missing prevalent dysplasia despite aggressive surveillance. Conclusion Recurrence of dysplasia/neoplasia after PDT ablation is associated with advanced age, smoking, and residual BE. PMID:19959164

Badreddine, Rami J.; Prasad, Ganapathy A.; Wang, Kenneth K.; Wong Kee Song, Louis M.; Buttar, Navtej S.; Dunagan, Kelly T.; Lutzke, Lori S.; Borkenhagen, Lynn S.

2010-01-01

197

Genetic variation in the lipoxygenase pathway and risk of colorectal neoplasia.  

PubMed

Arachidonate lipoxygenase (ALOX) enzymes metabolize arachidonic acid to generate potent inflammatory mediators and play an important role in inflammation-associated diseases. We investigated associations between colorectal cancer risk and polymorphisms in ALOX5, FLAP, ALOX12, and ALOX15, and their interactions with nonsteroidal anti-inflammatory drug (NSAID) use. We genotyped fifty tagSNPs, one candidate SNP, and two functional promoter variable nucleotide tandem repeat (VNTR) polymorphisms in three US population-based case-control studies of colon cancer (1,424 cases/1,780 controls), rectal cancer (583 cases/775 controls), and colorectal adenomas (485 cases/578 controls). Individuals with variant genotypes of the ALOX5 VNTR had a decreased risk of rectal cancer, with the strongest association seen for individuals with one or more alleles of >5 repeats (wild type = 5, OR>5/?5 = 0.42, 95% CI 0.20-0.92; P = 0.01). Four SNPs in FLAP (rs17239025), ALOX12 (rs2073438), and ALOX15 (rs4796535 and rs2619112) were associated with rectal cancer risk at P ? 0.05. One SNP in FLAP (rs12429692) was associated with adenoma risk. A false discovery rate (FDR) was applied to account for false positives due to multiple testing; the ALOX15 associations were noteworthy at 25% FDR. Colorectal neoplasia risk appeared to be modified by NSAID use in individuals with variant alleles in FLAP and ALOX15. One noteworthy interaction (25% FDR) was observed for rectal cancer. Genetic variability in ALOXs may affect risk of colorectal neoplasia, particularly for rectal cancer. Additionally, genetic variability in FLAP and ALOX15 may modify the protective effect of NSAID use against colorectal neoplasia. PMID:23404351

Kleinstein, Sarah E; Heath, Laura; Makar, Karen W; Poole, Elizabeth M; Seufert, Brenna L; Slattery, Martha L; Xiao, Liren; Duggan, David J; Hsu, Li; Curtin, Karen; Koepl, Lisel; Muehling, Jill; Taverna, Darin; Caan, Bette J; Carlson, Christopher S; Potter, John D; Ulrich, Cornelia M

2013-05-01

198

Genetic Variation in the Lipoxygenase Pathway and Risk of Colorectal Neoplasia  

PubMed Central

Arachidonate lipoxygenase (ALOX) enzymes metabolize arachidonic acid to generate potent inflammatory mediators and play an important role in inflammation-associated diseases. We investigated associations between colorectal cancer risk and polymorphisms in ALOX5, FLAP, ALOX12, and ALOX15, and their interactions with non-steroidal anti-inflammatory drug (NSAID) use. We genotyped fifty tagSNPs, one candidate SNP, and two functional promoter variable nucleotide tandem repeat (VNTR) polymorphisms in three US population-based case-control studies of colon cancer (1424 cases/1780 controls), rectal cancer (583 cases/775 controls), and colorectal adenomas (485 cases/578 controls). Individuals with variant genotypes of the ALOX5 VNTR had decreased risk of rectal cancer, with the strongest association seen for individuals with one or more alleles of >5 repeats (wildtype=5, OR>5/?5=0.42, 95% CI 0.20-0.92; p=0.01). Four SNPs in FLAP (rs17239025), ALOX 12 (rs2073438), and ALOX15 (rs4796535 and rs2619112) were associated with rectal cancer risk at p?0.05. One SNP in FLAP (rs12429692) was associated with adenoma risk. A false discovery rate (FDR) was applied to account for false positives due to multiple testing; the ALOX15 associations were noteworthy at 25% FDR. Colorectal neoplasia risk appeared to be modified by NSAID use in individuals with variant alleles in FLAP and ALOX15. One noteworthy interaction (25% FDR) was observed for rectal cancer. Genetic variability in arachidonate lipoxygenases may affect risk of colorectal neoplasia, particularly for rectal cancer. Additionally, genetic variability in FLAP and ALOX15 may modify the protective effect of NSAID use against colorectal neoplasia. PMID:23404351

Kleinstein, Sarah E.; Heath, Laura; Makar, Karen W.; Poole, Elizabeth M.; Seufert, Brenna L.; Slattery, Martha L.; Xiao, Liren; Duggan, David J.; Hsu, Li; Curtin, Karen; Koepl, Lisel; Muehling, Jill; Taverna, Darin; Caan, Bette J.; Carlson, Christopher S.; Potter, John D.; Ulrich, Cornelia M.

2013-01-01

199

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

200

JC Virus Infection in Colorectal Neoplasia That Develops after Liver Transplantation  

PubMed Central

Purpose Liver transplant recepients (LTRs) have an increased risk of colorectal neoplasia. The mechanism responsible for this is unknown. JCV encodes for TAg and has been implicated in colorectal carcinogenesis. We hypothesized that the use of immunosuppression in LTRs facilitates activation of JCV and is responsible for the increased risk of neoplasia. Experimental Design JCV TAg DNA and protein expression were determined in normal colonic epithelium (n = 15) and adenomatous polyps (n = 26) from LTRs and compared with tissue samples from control patients (normal colon, n = 21; adenomas, n = 40). Apoptosis and proliferation were determined by M30 and Ki-67 immunoreactivity, respectively. Results JCV TAg DNA was found in 10 of 15 (67%) of normal colonic mucosa from LTRs compared with 5 of 21 (24%) of control normal mucosa (P = 0.025). JCV TAg DNA was detected in 16 of 26 (62%) of the adenomas from LTRs and in 20 of 40 (50%) of control adenomas. JCV TAg protein was expressed in 13 of 26 (50%) adenomas from LTRs versus 2 of 40 (5%) of adenomas from controls (P < 0.001). In adenomas from LTRs, the mean proliferative activity was higher compared with controls (60.3 ± 3.2% versus 42.7 ± 2.8%, P < 0.001), whereas mean apoptotic indices were lower in LTRs (0.29 ± 0.08% versus 0.39 ± 0.06%, P = 0.05). Conclusions The presence of JCV in the colorectal mucosa and adenomas from LTRs, in concert with the use of immunosuppressive agents, suggests that JCV may undergo reactivation, and the subsequent TAg protein expression might explain the increased risk of colorectal neoplasia in LTRs. PMID:18927316

Selgrad, Michael; Koornstra, Jan Jacob; Fini, Lucia; Blom, Marloes; Huang, Rong; DeVol, Edward B.; Ek, Wytske Boersma-van; Dijkstra, Gerard; Verdonk, Robert C.; deJong, Steven; Goel, Ajay; Williams, Sharenda L.; Meyer, Richard L.; Haagsma, Elizabeth B.; Ricciardiello, Luigi; Boland, C. Richard

2010-01-01

201

A cluster of vulvar cancer and vulvar intraepithelial neoplasia in young Australian Indigenous women  

Microsoft Academic Search

Objective  To describe the epidemiological features of a possible disease cluster of vulvar cancer and pre-cancers in Australian Indigenous\\u000a women living in the Northern Territory (NT) of Australia.\\u000a \\u000a \\u000a \\u000a Methods  We identified NT-resident women with a confirmed histological diagnosis of vulvar cancer or high-grade vulvar intraepithelial\\u000a neoplasia (VIN) between 1 January 1996 and 31 December 2005.\\u000a \\u000a \\u000a \\u000a Results  Seventy-one women were identified; 32 diagnosed with

John R. Condon; Alice R. Rumbold; Jane C. Thorn; Margaret M. O’Brien; Margaret J. Davy; Ibrahim Zardawi

2009-01-01

202

Epigenetic Alterations as Contributors to the Pathogenesis, Detection, Prognosis and Treatment of Human Preinvasive Neoplasia  

Microsoft Academic Search

\\u000a The study of molecular processes driving human neoplasia development is achieving critical gains in terms of better detection\\u000a and treatment. Current medicine already benefits from discovering genetic signatures of distinct cancers, and therapies have\\u000a become more specifically targeted to the molecular aberrations defining parti­cular cancers (e.g.: chronic myelogenous leukemia\\u000a is now diagnosed by detecting the t(9;22)(q34;q11) translocation, and therapy is

Stefan David; Stephen J. Meltzer

203

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

PubMed Central

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

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

2014-01-01

204

The Evolution of Methotrexate as a Treatment for Ectopic Pregnancy and Gestational Trophoblastic Neoplasia: A Review  

PubMed Central

Methotrexate was developed in 1949 as a synthetic folic acid analogue to compete with folic acid and thus interfere with cell replication. While initially developed as a potential treatment for acute lymphoblastic leukaemia, a serendipitous observation led to methotrexate's use to effect the dramatic cure of a case of advanced choriocarcinoma. This prompted the exploration for the potential of methotrexate to treat other conditions involving disordered trophoblastic tissue. Methotrexate has subsequently revolutionized the treatment of two pregnancy-related conditions—gestational trophoblastic neoplasia and ectopic pregnancy. This article reviews the development of modern treatment protocols that use methotrexate to medically treat these two important gynaecological conditions. PMID:22462004

Skubisz, Monika M.; Tong, Stephen

2012-01-01

205

[Diagnosis and treatment of multiple endocrine neoplasia type 2A: a case report and literature review].  

PubMed

We report a case of multiple endocrine neoplasia (MEN) type 2A and summarize the clinical characteristics, diagnosis and treatment of this condition. The diagnosis of MEN type 2A relies on a comprehensive evaluation of the findings of ultrasound, CT and laboratory examinations, and early diagnosis and treatment is critical to improving the prognosis. Genetic testing of RET is the gold standard for diagnosis of MEN type 2A and 2B. Surgical intervention currently remains the primary choice of treatments of this disease. PMID:24968855

Yu, Ruofei; Wu, Ziqing; Li, Aimin; Jin, Guoping; Luo, Rongcheng

2014-06-01

206

Treatment of vulvar intraepithelial neoplasia using topical imiquimod 5% cream in a genitourinary medicine clinic setting.  

PubMed

In the last five years, options for the treatment of vulvar intraepithelial neoplasia (VIN) have come to include the use of the immune response modifier imiquimod, following case reports of its efficacy in the USA and Europe. Despite topical imiquimod 5% cream being frequently prescribed for the treatment of ano-genital warts, there are no reports of it being used for the treatment of VIN in a genitourinary medicine setting. In this case report self-administered topical imiquimod 5% cream proved an effective treatment for undifferentiated VIN2/3 and should be considered as an alternative therapy in a genitourinary medicine setting. PMID:17326867

McQuillan, O; Morgan, E

2007-01-01

207

Adrenal involvement in multiple endocrine neoplasia type 1: results of 7 years prospective screening  

Microsoft Academic Search

Background  Adrenal tumors are a common manifestation of the multiple endocrine neoplasia type 1 (MEN-1) syndrome. Prevalence in recent\\u000a studies varies between 9 and 45%. A genotype–phenotype correlation has been described as well as the development of adrenocortical\\u000a carcinomas. Long-term prospective data are still lacking.\\u000a \\u000a \\u000a \\u000a Materials and methods  Thirty-eight MEN-1 patients with proven germline mutations have been prospectively observed in a regular

J. Waldmann; D. K. Bartsch; P. H. Kann; V. Fendrich; M. Rothmund; P. Langer

2007-01-01

208

Multiple endocrine neoplasia type 2 (Sipple's syndrome): clinical and cytogenetic analysis of a kindred.  

PubMed Central

This report describes the clinical and cytogenetic analysis of a kindred with multiple endocrine neoplasia type 2 (MEN-2 or Sipple's syndrome) in two generations. Medullary thyroid carcinoma was present in five members either as a large or as an occult tumour. Phaeochromocytoma was demonstrated in one severely hypertensive relative and urine vanillylmandelic acid (VMA) was increased in one normotensive member. Serum parathormone (PTH) was normal in all but one normocalcaemic patient of this family who did not have a history of nephrolithiasis. Prometaphase banding failed to detect a 20p12.2 deletion or chromosome instability as observed in some MEN-2 families. Images PMID:6143828

Zatterale, A; Stabile, M; Nunziata, V; Di Giovanni, G; Vecchione, R; Ventruto, V

1984-01-01

209

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

210

Fast-growing pancreatic neuroendocrine carcinoma in a patient with multiple endocrine neoplasia type 1: a case report  

PubMed Central

Introduction Predictive genetic screening and regular screening programs in patients with multiple endocrine neoplasia type 1 are intended to detect and treat malignant tumors at the earliest stage possible. Malignant neuroendocrine pancreatic tumors are the most frequent cause of death in these patients. However, the extent and intervals of screening in patients with multiple endocrine neoplasia type 1 are controversial as neuroendocrine tumors are usually slow growing. Here we report the case of a patient who developed a fast-growing neuroendocrine carcinoma within 15 months of a laparoscopic distal pancreatic resection. Case presentation We followed a group of 45 patients with multiple endocrine neoplasia type 1 by an annual screening program in the Department of Visceral, Thoracic, and Vascular Surgery at the University Hospital Marburg in cooperation with the Department of Radiology and the Division of Endocrinology. A man with multiple endocrine neoplasia type 1 who was diagnosed with a recurrent primary hyperparathyroidism underwent a distal pancreatic resection for a non-functional neuroendocrine tumor. In the context of our regular screening program, a large non-functional neuroendocrine tumor was diagnosed in the pancreatic head 15 months after the first pancreatic surgery. Therefore, we performed an enucleation and regional lymph node resection. At histology, the diagnosis of a neuroendocrine carcinoma with one lymph node metastasis was established. There was no evidence of recurrence 9 months after re-operation. Conclusion Fast-growing neuroendocrine tumors are rare in patients with multiple endocrine neoplasia type 1. The intervals, both postoperative and in newly diagnosed pancreatic lesions, in patients with multiple endocrine neoplasia type 1 should be reduced to 6 months to establish the early diagnosis of rapidly progressive disease in a small subset of patients. PMID:19017391

Waldmann, Jens; Habbe, Nils; Fendrich, Volker; Slater, Emily P; Kann, Peter H; Rothmund, Matthias; Langer, Peter

2008-01-01

211

Overlapping biomarkers, pathways, processes and syndromes in lymphatic development, growth and neoplasia.  

PubMed

Recent discoveries in molecular lymphology, developmental biology, and tumor biology in the context of long-standing concepts and observations on development, growth, and neoplasia implicate overlapping pathways, processes, and clinical manifestations in developmental disorders and cancer metastasis. Highlighted in this review are some of what is known (and speculated) about the genes, proteins, and signaling pathways and processes involved in lymphatic/blood vascular development in comparison to those involved in cancer progression and spread. Clues and conundra from clinical disorders that mix these processes and mute them, including embryonic rests, multicentric nests of displaced cells, uncontrolled/invasive "benign" proliferation and lymphogenous/hematogenous "spread", represent a fine line between normal development and growth, dysplasia, benign and malignant neoplasia, and "metastasis". Improved understanding of these normal and pathologic processes and their underlying pathomechanisms, e.g., stem cell origin and bidirectional epithelial-mesenchymal transition, could lead to more successful approaches in classification, treatment, and even prevention of cancer and a whole host of other diseases. PMID:22798218

Witte, Marlys H; Dellinger, Michael T; Papendieck, Cristobal M; Boccardo, Francesco

2012-10-01

212

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

PubMed

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

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

2008-01-01

213

C-C chemokine receptor 1 expression in human hematolymphoid neoplasia.  

PubMed

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

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

2010-03-01

214

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

215

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

216

Clinical value of tumor doubling estimations in multiple endocrine neoplasia type II.  

PubMed

Experience with children with multiple endocrine neoplasia (MEN) type IIb has emphasized that medullary thyroid cancer (MTC) in MEN IIb is more aggressive than in MEN IIa. Earlier ages of onset and apparently more rapid growth of MTC in MEN IIb suggest that these tumors have earlier ages of conversion to malignant states and/or shorter doubling times. The age at which a hyperplastic C cell becomes a malignant cell and the true doubling time cannot be estimated presently. Maximum volume-doubling times of 35 and 75 days (21 to 26 doublings) were calculated from tumor size and age at operation in five patients with MEN IIb aged 2 to 5 years. Calculations in 20 patients with MEN IIa revealed maximum doubling times of 110 to 440 days, with ages ranging from 7 to 29 years and number of doubling ranging from 18 to 38. Positive provocative calcitonin tests in two adult patients with MEN IIa after 10 to 11 years of repeated negative tests suggest a minimum doubling time of 190 to 210 days. Such experience emphasizes that negative stimulated calcitonin tests less than 11 years after operation do not provide assurance of cures for MTC in MEN IIa although negative tests after more than 5 years for MEN IIb are encouraging. Calculations of volume doublings accounting for various-sized tumors are compatible with Knudson's two-mutational-event theory on the initiation of neoplasia. PMID:6150555

Jackson, C E; Talpos, G B; Block, M A; Norum, R A; Lloyd, R V; Tashjian, A H

1984-12-01

217

Isoprenylcysteine carboxylmethyltransferase deficiency exacerbates KRAS-driven pancreatic neoplasia via Notch suppression  

PubMed Central

RAS is the most frequently mutated oncogene in human cancers. Despite decades of effort, anti-RAS therapies have remained elusive. Isoprenylcysteine carboxylmethyltransferase (ICMT) methylates RAS and other CaaX-containing proteins, but its potential as a target for cancer therapy has not been fully evaluated. We crossed a Pdx1-Cre;LSL-KrasG12D mouse, which is a model of pancreatic ductal adenocarcinoma (PDA), with a mouse harboring a floxed allele of Icmt. Surprisingly, we found that ICMT deficiency dramatically accelerated the development and progression of neoplasia. ICMT-deficient pancreatic ductal epithelial cells had a slight growth advantage and were resistant to premature senescence by a mechanism that involved suppression of cyclin-dependent kinase inhibitor 2A (p16INK4A) expression. ICMT deficiency precisely phenocopied Notch1 deficiency in the Pdx1-Cre;LSL-KrasG12D model by exacerbating pancreatic intraepithelial neoplasias, promoting facial papillomas, and derepressing Wnt signaling. Silencing ICMT in human osteosarcoma cells decreased Notch1 signaling in response to stimulation with cell-surface ligands. Additionally, targeted silencing of Ste14, the Drosophila homolog of Icmt, resulted in defects in wing development, consistent with Notch loss of function. Our data suggest that ICMT behaves like a tumor suppressor in PDA because it is required for Notch1 signaling. PMID:24216479

Court, Helen; Amoyel, Marc; Hackman, Michael; Lee, Kyoung Eun; Xu, Ruliang; Miller, George; Bar-Sagi, Dafna; Bach, Erika A.; Bergo, Martin O.; Philips, Mark R.

2013-01-01

218

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

Microsoft Academic Search

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

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

219

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

220

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

221

Differentiated vulvar intraepithelial neoplasia contains Tp53 mutations and is genetically linked to vulvar squamous cell carcinoma  

Microsoft Academic Search

Differentiated vulvar intraepithelial neoplasia is a unique precursor to vulvar squamous cell carcinoma that is typically HPV-negative and frequently associated with nuclear p53 staining. These features imply a mode of pathogenesis involving somatic mutations. However, the genetic relationship of differentiated vulvar intraepithelial neoplasm and vulvar squamous cell carcinoma and the role of Tp53 mutations in this process have not been

Alvaro P Pinto; Alexander Miron; Yosuf Yassin; Nicolas Monte; Terri Y C Woo; Karishma K Mehra; Fabiola Medeiros; Christopher P Crum

2010-01-01

222

Expression of Ki67 in Vulvar Carcinoma and Vulvar Intraepithelial Neoplasia III: Correlation with Clinical Prognostic Factors  

Microsoft Academic Search

Objectives. In vulvar carcinoma, the expression of Ki-67 has been previously found to correlate with patient outcome. The objective of the study was to determine whether a specific pattern of expression was associated with occult vulvar cancer in patients with vulvar intraepithelial neoplasia (VIN) III and whether patterns of Ki-67 expression correlated with other clinical prognostic factors.Methods. 19 women with

Susan C. Modesitt; Pamela A. Groben; Leslie A. Walton; Wesley C. Fowler; Linda Van Le

2000-01-01

223

The role of angiogenesis in vulvar cancer, vulvar intraepithelial neoplasia, and vulvar lichen sclerosus as determined by microvessel density analysis  

Microsoft Academic Search

ObjectivesWe compared microvessel density (MVD) in normal, benign, preneoplastic, and neoplastic (squamous cell carcinoma (SCC)) vulvar disease to ascertain if this parameter could identify cases with lichen sclerosus (LS) and high-grade vulvar intraepithelial neoplasia (VIN3) at risk of developing malignancy.

Jamna Saravanamuthu; Wendy M. N Reid; David S. t George; Julie C Crow; Kerstin J Rolfe; Allan B MacLean; Christopher W Perrett

2003-01-01

224

Increased Prevalence of Colorectal Neoplasia in Korean Patients with Sporadic Duodenal Adenomas: A Case-Control Study  

PubMed Central

Background/Aims Recent data from Western populations have suggested that patients with sporadic duodenal adenomas are at a higher risk for the development of colorectal neoplasia. In this study, we compared the frequency of colorectal neoplasia in patients with sporadic duodenal adenomas to healthy control subjects. Methods This retrospective case-control study used the databases of 3 teaching hospitals in Gyeonggi-do Province, South Korea. The colonoscopy findings of patients with sporadic duodenal adenomas were compared with those of age- and gender-matched healthy individuals who had undergone gastroduodenoscopies and colonoscopies during general screening examinations. Results Between 2001 and 2008, 45 patients were diagnosed endoscopically with sporadic duodenal adenomas; 26 (58%) of these patients received colonoscopies. Colorectal neoplasia (42% vs 21%; odds ratio [OR], 2.8; 95% confidence interval [CI], 1.1 to 7.4) and advanced colorectal adenoma (19% vs 3%; OR, 9.0; 95% CI, 1.6 to 50.0) were significantly more common in patients with sporadic duodenal adenomas than in healthy control subjects. Conclusions Compared with healthy individuals, patients with sporadic duodenal adenomas were at a significantly higher risk for developing colorectal neoplasia. Such at-risk patients should undergo routine screening colonoscopies. PMID:22195240

Chung, Woo Chul; Lee, Bo-In; Roh, Sang Young; Kwak, Jae Wuk; Hwang, Sun-Mee; Ko, Yoon Ho; Oh, Jung-Hwan; Cho, Hyunjung; Chae, Hiun-Suk

2011-01-01

225

Z .Biochimica et Biophysica Acta 1332 1997 F25F48 Studies of neoplasia in the Min mouse 1  

E-print Network

Z .Biochimica et Biophysica Acta 1332 1997 F25­F48 Studies of neoplasia in the Min mouse 1 Alex R . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . F29 3. Phenotypic comparison of Min and FAP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . F30 3.2. Timing of intestinal tumor formation in Min mice

Dove, William

226

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

227

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

E-print Network

of Medicine, Henry Ford Hospital, Detroit Summary Multiple endocrine neoplasia type 2A (MEN2A) is a rare cancer syndrome that is inherited in an appar- ently autosomal dominant fashion. Previous linkage studies had assigned the MEN2A locus to chromo- some 10 in the pericentromeric region. We recently have

Kidd, Kenneth

228

Natural course of small adrenal lesions in multiple endocrine neoplasia type 1: an endoscopic ultrasound imaging study  

Microsoft Academic Search

Objective: Adrenal lesion is one of the features of multiple endocrine neoplasia type 1 (MEN1). This study aimed to assess prevalence, natural course and clinical relevance of small adrenal lesions without clinical symptoms, endocrine activity, or mechanical problems and thus without clear indication for surgical therapy by endoscopic ultrasound (EUS). Design and methods: Forty-nine patients with familial MEN1 were studied.

S Schaefer; M Shipotko; S Meyer; D Ivan; K J Klose; J Waldmann; P Langer; P H Kann

2008-01-01

229

Discriminate gene lists derived from cDNA microarray profiles of limited samples permit distinguishing mesenchymal neoplasia ex vivo  

Microsoft Academic Search

Background Mesenchymal neoplasia comprises a heterogeneous group of tumors with over 200 benign neoplasms and 100 sarcomas. Currently, tumors are classified using histologic and immunocytologic characteristics, with diagnostic error rates reported as high as 40% of cases. As a feasibility study, our goal was to generate a preliminary discriminatory gene list for selected mesenchymal tumors, including sarcomas. This technique may

David E. Joyner; Mark L. Wade; Aniko Szabo; Jeffrey Bastar; Cheryl M. Coffin; Karen H. Albritton; Philip S. Bernard; R. Lor Randall

2005-01-01

230

Expression Profiles Provide Insights into Early Malignant Potential and Skeletal Abnormalities in Multiple Endocrine Neoplasia Type 2B Syndrome Tumors  

Microsoft Academic Search

Identifying the molecular basis for genotype-phenotype correlations in human diseases has direct implications for understanding the disease process and hence for the identification of potential therapeutic targets. To this end, we performed microarray expression analysis on benign (pheochromocytomas) and malignant (medullary thyroid carcinomas, MTCs) tumors from patients with multiple endocrine neoplasia (MEN) type 2A or 2B, related syndromes that result

Sanjay Jain; Mark A. Watson; Mary K. DeBenedetti; Yuji Hiraki; Jeffrey F. Moley; Jeffrey Milbrandt

2004-01-01

231

Molecular genetic diagnostic program of multiple endocrine neoplasia type 2A and familial medullary thyroid carcinoma syndromes in Hungary  

Microsoft Academic Search

Medullary thyroid carcinoma (MTC) occurs usually in sporadic form, but about a quarter of the cases are hereditary and appear as part of one of the multiple endocrine neoplasia type 2 (MEN2) syndromes. Mutations in the RET protooncogene are known to be the cause of the MEN2A and familial medullary thyroid carcinoma (FMTC) syndromes in the majority of the families.

I Klein; O Ésik; V Homolya; F Szeri; A Váradi

2001-01-01

232

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

233

Magnetic resonance imaging of the natural history of in situ mammary neoplasia in transgenic mice: a pilot study  

Microsoft Academic Search

INTRODUCTION: Because of the small size of in situ mammary cancers in mouse models, high-resolution imaging techniques are required to effectively observe how lesions develop, grow and progress over time. The purpose of this study was to use magnetic resonance (MR) imaging to track in vivo the transition from in situ neoplasia to invasive cancer in a transgenic mouse model

Sanaz A Jansen; Suzanne D Conzen; Xiaobing Fan; Erica J Markiewicz; Gillian M Newstead; Gregory S Karczmar

2009-01-01

234

The Use of in vivo Real-Time Optical Imaging for Esophageal Neoplasia  

PubMed Central

Esophageal adenocarcinoma carries a poor prognosis, as it typically presents at a late stage. Thus, a major research priority is the development of novel diagnostic imaging strategies that can detect neoplastic lesions earlier and more accurately than current techniques. Advances in optical imaging allow clinicians to obtain real-time histopathologic information with instant visualization of cellular architecture and the potential to identify neoplastic tissue. The various endoscopic imaging modalities for esophageal neoplasia can be grouped into two major categories: (a) wide-field imaging, a comparatively lower-resolution view for imaging larger surface areas, and (b) high-resolution imaging, which allows individual cells to be visualized. This review will provide an overview of the various forms of real-time optical imaging in the diagnosis and management of Barrett's esophagus and esophageal adenocarcinoma. PMID:22069213

Vila, Peter M.; Thekkek, Nadhi; Richards-Kortum, Rebecca; Anandasabapathy, Sharmila

2012-01-01

235

Localization of cellular retinoid-binding proteins in human cervical intraepithelial neoplasia and invasive carcinoma.  

PubMed Central

Cellular retinoic acid-binding protein (CRABP) and cellular retinol-binding protein (CRBP) were localized in biopsies of normal squamous epithelium, cervical intraepithelial neoplasia (CIN), and invasive squamous cell cancer of the cervix uteri by immunohistochemistry. In both the normal stratified squamous epithelium of the exocervix and low-grade CIN, CRABP I was present predominantly in the basal layer of the epithelium. The more superficial, differentiated cell layers lacked immunoreactive protein. In high-grade CIN (CIN2-3), the distribution of CRABP I was altered. Immunoreactive CRABP I was detected in all layers of high-grade CIN. In squamous cell carcinoma of the cervix, CRABP I was detected in cells throughout the tumor but was minimal in cells demonstrating squamous differentiation. In contrast to CRABP I, CRBP was diffusely present throughout the cervical epithelium irrespective of the state of differentiation or the presence of disease. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:1329518

Hillemanns, P.; Tannous-Khuri, L.; Koulos, J. P.; Talmage, D.; Wright, T. C.

1992-01-01

236

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

PubMed

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

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

2005-03-01

237

Diagnosis and surgical treatment of multiple endocrine neoplasia type 2A  

PubMed Central

Background This study aims to introduce the diagnosis and surgical treatment of the rare disease multiple endocrine neoplasia type 2A (MEN 2A). Methods Thirteen cases of MEN 2A were diagnosed as medullary thyroid carcinoma (MTC) and pheochromocytoma by biochemical tests and imaging examination. They were treated by bilateral adrenal tumor excision or laparoscopic surgery. Results Nine patients were treated by bilateral adrenal tumor excision and the remaining four were treated by laparoscopic surgery for pheochromocytoma. Ten patients were treated by total thyroidectomy and bilateral lymph nodes dissection and the remaining three were treated by unilateral thyroidectomy for MTC. Up to now, three patients have died of MTC distant metastasis. Conclusions We confirmed that MEN 2A can be diagnosed by biochemical tests and imaging examination when genetic testing is not available. Surgical excision is the predominant way to treat MEN 2A; pheochromocytoma should be excised at first when pheochromocytoma and MTC occur simultaneously. PMID:24400812

2014-01-01

238

Liver X Receptors Protect from Development of Prostatic Intra-Epithelial Neoplasia in Mice  

PubMed Central

LXR (Liver X Receptors) act as “sensor” proteins that regulate cholesterol uptake, storage, and efflux. LXR signaling is known to influence proliferation of different cell types including human prostatic carcinoma (PCa) cell lines. This study shows that deletion of LXR in mouse fed a high-cholesterol diet recapitulates initial steps of PCa development. Elevation of circulating cholesterol in Lxr??-/- double knockout mice results in aberrant cholesterol ester accumulation and prostatic intra-epithelial neoplasia. This phenotype is linked to increased expression of the histone methyl transferase EZH2 (Enhancer of Zeste Homolog 2), which results in the down-regulation of the tumor suppressors Msmb and Nkx3.1 through increased methylation of lysine 27 of histone H3 (H3K27) on their promoter regions. Altogether, our data provide a novel link between LXR, cholesterol homeostasis, and epigenetic control of tumor suppressor gene expression. PMID:23675307

Pommier, Aurelien J. C.; Dufour, Julie; Alves, Georges; Viennois, Emilie; De Boussac, Hugues; Trousson, Amalia; Volle, David H.; Caira, Francoise; Val, Pierre; Arnaud, Philippe; Lobaccaro, Jean-Marc A.; Baron, Silvere

2013-01-01

239

Classic lobular neoplasia on core biopsy: a clinical and radio-pathologic correlation study with follow-up excision biopsy.  

PubMed

There are no consensus guidelines for the management of lobular neoplasia diagnosed on core biopsy as the highest risk factor for cancer. This study aimed to assess the risk of upgrade (invasive carcinoma or ductal carcinoma in situ) at the site of the lobular neoplasia and any clinical, radiological or pathologic factors associated with the upgrade. We reviewed all cases with a diagnosis of lobular neoplasia on core biopsy from June 2006 to June 2011. Any cases with radio-pathologic discordance, coexistent lesion that required excision (atypical ductal hyperplasia, flat epithelial atypia, duct papilloma or radial scar) or non-classic variant of lobular carcinoma in situ (pleomorphic, mixed ductal and lobular, lobular carcinoma in situ with necrosis) were excluded from the study. Core biopsy indications included calcification in 35 (40%), non-mass like enhancement in 19 (22%), mass lesion in 31 (36%) and mass as well as calcification in two cases (2%). Follow-up excisions were studied for the presence of upgrade. The study cohort included 87 cases and showed an upgrade of 3.4% (95% confidence interval: 1-10%). Three cases showed an upgrade (one ductal carcinoma in situ and two invasive cancers). All upgraded cases were breast imaging-reporting and data system score ?4 and associated with atypical duct hyperplasia or in situ or invasive cancer in prior or concurrent biopsies in either breast. The number of cores and lobules involved, pagetoid duct involvement, presence of microcalcification in lobular neoplasia, needle gauge and number of cores obtained showed no correlation with the upgrade. Our results suggest that with radio-pathologic concordance and no prior biopsy proven risk for breast cancer, core biopsy finding of lobular neoplasia as the highest risk lesion can be appropriately and safely managed with clinical and radiologic follow-up as an alternative to surgical excision. PMID:23307062

Chaudhary, Shweta; Lawrence, Loretta; McGinty, Geraldine; Kostroff, Karen; Bhuiya, Tawfiqul

2013-06-01

240

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

PubMed

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

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

2011-09-01

241

HPV-related squamous neoplasia of the lower anogenital tract: an update and review of recent guidelines.  

PubMed

Squamous cell carcinomas of the lower anogenital tract that are related to human papillomavirus (HPV) infection represent a significant disease burden worldwide. The diagnosis and management of their noninvasive precursors has been the subject of extensive study and debate over several decades, accompanied by an evolving understanding of HPV biology. Recent new consensus recommendations for the pathologic diagnosis of these precursor lesions were published in 2012, the result of the Lower Anogenital Squamous Terminology project cosponsored by the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Most salient among the new guidelines are the recommendation to switch to a 2-tiered nomenclature (high-grade squamous intraepithelial lesion and low-grade squamous intraepithelial lesion) rather than the traditional 3-tiered "intraepithelial neoplasia" terminology, and the recommendation to expand use of the immunohistochemical marker p16 to distinguish between low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion/intraepithelial neoplasia 2. The goals of the project were to align diagnostic terminology with our knowledge of HPV biology, increase reproducibility, consolidate diverse systems of nomenclature, and ultimately better determine a patient's true cancer risk. The clinical guidelines for screening and management of cervical intraepithelial neoplasia have also been recently updated, most notably with a lengthening of screening intervals. In this review, we focus on the new guidelines put forth for pathologic diagnosis of HPV-related anogenital neoplasia, with discussion of the evidence behind them and their potential implications. We also provide an update on relevant biomarkers, clinical recommendations, and the newest developments relating to cervical neoplasia. PMID:25105936

Maniar, Kruti P; Nayar, Ritu

2014-09-01

242

5-Aminosalicylates Reduce the Risk of Colorectal Neoplasia in Patients with Ulcerative Colitis: An Updated Meta-Analysis  

PubMed Central

Background Although the chemopreventive effect of 5-aminosalicylates on patients with ulcerative colitis has been extensively studied, the results remain controversial. This updated review included more recent studies and evaluated the effectiveness of 5-aminosalicylates use on colorectal neoplasia prevention in patients with ulcerative colitis. Methods Up to July 2013, we searched Medline, Embase, Web of Science, Cochrane CENTRAL, and SinoMed of China for all relevant observational studies (case-control and cohort) about the effect of 5-aminosalicylates on the risk of colorectal neoplasia among patients with ulcerative colitis. The Newcastle-Ottawa Scale was used to assess the quality of studies. Adjusted odds ratios (ORs) were extracted from each study. A random-effects model was used to generate pooled ORs and 95% confidence intervals (95%CI). Publication bias and heterogeneity were assessed. Results Seventeen studies containing 1,508 cases of colorectal neoplasia and a total of 20,193 subjects published from 1994 to 2012 were analyzed. 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis (OR 0.63; 95%CI 0.48–0.84). Pooled OR of a higher average daily dose of 5-aminosalicylates (sulfasalazine ? 2.0 g/d, mesalamine ? 1.2 g/d) was 0.51 [0.35–0.75]. Pooled OR of 5-aminosalicylates use in patients with extensive ulcerative colitis was 1.00 [0.53–1.89]. Conclusion Our pooled results indicated that 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis, especially in the cases with a higher average daily dose of 5-aminosalicylates use. However, the chemopreventive benefit of 5-aminosalicylates use in patients with extensive ulcerative colitis was limited. PMID:24710620

Zhao, Li-Na; Li, Jie-Yao; Yu, Tao; Chen, Guang-Cheng; Yuan, Yu-Hong; Chen, Qi-Kui

2014-01-01

243

Multiple endocrine neoplasia induced by the promiscuous expression of a viral oncogene.  

PubMed Central

There is increasing evidence for the importance of events that govern and influence the interaction between the transformed cell and its host being ultimately responsible for the establishment of the cancer phenotype. To derive an animal model that will allow us to define some of these phenomena at the molecular level, we have chosen to induce the expression of a viral oncogene in all tissue types, with the hope of identifying sites that are more susceptible to malignant transformation. When the gene for simian virus 40 large tumor antigen (T antigen) was placed under the control of a major histocompatibility complex class I gene enhancer, the resulting transgenic mice not only developed choroid plexus papillomas, as seen with wild-type simian virus 40, but also lymphoid hyperplasia and multiple endocrine neoplasias. The development of lymphoid hyperplasia was preceded by an elevated level of expression of T antigen in these tissues at an early age. Surprisingly, the striking thymic hyperplasia has not been observed to progress toward malignancy. The multiple endocrine neoplasias developed later in life and involved the pancreas, pituitary, thyroid, adrenals, and testes. While not preceded by an elevated level of expression of T antigen, once endocrine tumors appeared they quickly progressed toward malignant growth. Although other tissues also exhibited a basal level of expression of the viral oncogene similar to that detected in endocrine tissues, they rarely developed tumors. This transgenic mouse model seems particularly suitable for a molecular understanding of events responsible for certain tissue types being so much more susceptible to neoplastic conversion, with others being so refractory. Images PMID:2452444

Reynolds, R K; Hoekzema, G S; Vogel, J; Hinrichs, S H; Jay, G

1988-01-01

244

Total Laparoscopic Hysterectomy Versus Total Abdominal Hysterectomy: Cohort Review of Patients With Uterine Neoplasia  

PubMed Central

Objective: Retrospective analysis of surgico-pathologic data comparing total laparoscopic hysterectomy (TLH) with total abdominal hysterectomy (TAH) patients with uterine neoplasia Methods: We conducted a chart abstraction of all patients undergoing hysterectomy for uterine neoplasia from September 1996 to November 2004. Patients were assigned to undergo the abdominal or laparoscopic approach based on established clinical safety criteria. Results: The study included 105 patients, 29 with TAH and 76 with TLH. TAH patients were older (68 vs. 61, P=0.021); however, both groups had similar body mass indexes (31) and parities (1.6). Controlling for age, surgical duration was similar (152 minutes). Average blood loss was higher for TAH, (504 vs.138 mL, P<0.001). Hospital stays were significantly longer for patients with TAH than for those with TLH (5.4 vs. 1.8 days, P<0.0001). Uterine weight was greater (197 vs. 135 g, P=0.008) and myometrial invasion deeper in the TAH group (48% outer half vs. 17%, P=0.001). More patients had Stage II or higher disease in the TAH group (35% vs. 17%, P=0.038). More TAH patients needed node dissection (79% vs. 28%, P<.001). Node yields from dissections of 23 TAH cases and 21 laparoscopic cases were similar (17 nodes). Total and reoperative complications from TAH versus TLH were not statistically different in our small sample (14.3 vs. 5.2% total, NS; 10.3 vs. 2.6% reoperative). One conversion was necessary from laparoscopy to laparotomy for unsuspected bulky metastatic disease. Conclusion: Based on clinical selection criteria, TLH performed for endometrial pathology has few complications and is well tolerated by select patients. The advantages are less blood loss and a shorter length of hospital stay for qualified patients. PMID:16121872

Huang, Gloria Shining; Garnier, Anne-Caroline; Dibble, Suzanne L.; Reuland, Mirjam L.; Lopez, Lisbeth; Pinto, Rebecca L.

2005-01-01

245

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

PubMed

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

Brustmann, Hermann; Brunner, Andreas

2013-05-01

246

Surgical approach to medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2  

PubMed Central

We briefly review the surgical approaches to medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2 (medullary thyroid carcinoma/multiple endocrine neoplasia type 2). The recommended surgical approaches are usually based on the age of the affected carrier/patient, tumor staging and the specific rearranged during transfection codon mutation. We have focused mainly on young children with no apparent disease who are carrying a germline rearranged during transfection mutation. Successful management of medullary thyroid carcinoma in these cases depends on early diagnosis and treatment. Total thyroidectomy should be performed before 6 months of age in infants carrying the rearranged during transfection 918 codon mutation, by the age of 3 years in rearranged during transfection 634 mutation carriers, at 5 years of age in carriers with level 3 risk rearranged during transfection mutations, and by the age of 10 years in level 4 risk rearranged during transfection mutations. Patients with thyroid tumor >5 mm detected by ultrasound, and basal calcitonin levels >40 pg/ml, frequently have cervical and upper mediastinal lymph node metastasis. In the latter patients, total thyroidectomy should be complemented by extensive lymph node dissection. Also, we briefly review our data from a large familial medullary thyroid carcinoma genealogy harboring a germline rearranged during transfection Cys620Arg mutation. All 14 screened carriers of the rearranged during transfection Cys620Arg mutation who underwent total thyroidectomy before the age of 12 years presented persistently undetectable serum levels of calcitonin (<2 pg/ml) during the follow-up period of 2–6 years. Although it is recommended that preventive total thyroidectomy in rearranged during transfection codon 620 mutation carriers is performed before the age of 5 years, in this particular family the surgical intervention performed before the age of 12 years led to an apparent biochemical cure. PMID:22584721

Tavares, Marcos R.; Toledo, Sérgio P. A.; Montenegro, Fábio L. M.; Moyses, Raquel A.; Toledo, Rodrigo A.; Sekyia, Tomoko; Cernea, Claudio R.; Brandão, Lenine G.

2012-01-01

247

Transgenic Expression of VEGF in Intestinal Epithelium Drives Mesenchymal Cell Interactions and Epithelial Neoplasia  

PubMed Central

Background & Aims Vascular endothelial growth factor (VEGF) is expressed robustly in human colon neoplasia and is a major new ‘rational’ target of therapy for cancers of the colon and other organs. Nonetheless, the mechanism(s) of action of VEGF-targeted therapies and the biological roles of VEGF in tumorigenesis have not been well defined. We used a transgenic approach to directly test the hypothesis that augmented VEGF expression can drive progression of intestinal neoplasia. Methods Transgenic mouse lines were generated with moderate (vilVEGF1) and high (vilVEGF2) VEGF expression from the intestinal epithelium. vilVEGF1 mice were bred to Min mice (Adenomatous polyposis coli (APC) +/-). Colon epithelial cells from an APC patient were co-cultured with endothelial cells and fibroblasts. Results vilVEGF mice were generally healthy but displayed red small intestines. Vessels were larger and more numerous in the submucosa but not the mucosa. The mucosa showed striking stromal and epithelial hypercellularity, with increased epithelial proliferation. Many crypts formed cysts composed of relatively undifferentiated epithelial cells surrounded by cells with endothelial and myofibroblast markers. Compared to Min controls, vilVEGF1-Min mice developed 6-fold more intestinal adenomas of all sizes, with more advanced histological features. Polycystic masses were also observed. Co-culture of human colonocytes with endothelial cells and fibroblasts directly stimulated colonocyte proliferation. Conclusions Augmented VEGF expression from intestinal epithelium potently stimulated crosstalk with mesenchymal cells and proliferation of normal and neoplastic epithelium. These effects of VEGF, largely occurring prior to the canonical angiogenic switch in tumors, may be in part independent of angiogenesis. PMID:19056388

Boquoi, Amelie; Jover, Rodrigo; Chen, Tina; Pennings, Marieke; Enders, Greg

2010-01-01

248

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, Agnes; Johannes, Frank; Grimm, Christina; Eijsink, Jasper J.H.; Wardenaar, Rene; 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

249

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

250

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

PubMed Central

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

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

2014-01-01

251

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

252

Endoscopic submucosal dissection with a combination of small-caliber-tip transparent hood and flex knife for superficial esophageal neoplasia. Is it safe for elderly patients?  

Microsoft Academic Search

Background  Safety and efficacy of endoscopic submucosal dissection (ESD) for esophageal neoplasias have not been adequately investigated\\u000a in elderly patients. This study was designed to evaluate the safety and efficacy of ESD for esophageal neoplasias in elderly\\u000a patients.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Fifty-three superficial esophageal neoplasias treated with ESD using a combination of small-caliber-tip transparent hood and\\u000a flex knife from May 2006 to June 2009

Naoki IshiiShino; Shino Uchida; Toshiyuki Itoh; Noriyuki Horiki; Michitaka Matsuda; Takeshi Setoyama; Shoko Suzuki; Masayo Uemura; Yusuke Iizuka; Katsuyuki Fukuda; Koyu Suzuki; Yoshiyuki Fujita

2010-01-01

253

I valori di riferimento CECA '71 per la funzionalità polmonare sono ancora validi.  

PubMed

Benché la scelta dei valori teorici per la funzionalità polmonaresia altrettanto importante quanto l'accuratezza e laprecisione della misura originale, l'attenzione ai valori di riferimentoè spesso minima o addirittura assente e moltimedici utilizzano acriticamente il valore teorico proposto didefault dallo strumento... PMID:25078998

Innocenti, A; Quercia, A; Roscelli, F

2014-01-01

254

Prospective follow-up suggests similar risk of subsequent cervical intraepithelial neoplasia grade 2 or 3 among women with cervical intraepithelial neoplasia grade 1 or negative colposcopy and directed biopsy  

Microsoft Academic Search

Objective: The purpose of this study was to determine the risk of cumulative cervical intraepithelial neoplasia (CIN) grade 2 or 3 according to initial colposcopy and directed biopsy results among women with low-grade squamous intraepithelial lesions (LSIL) or human papillomavirus (HPV) DNA positive atypical squamous cells of undetermined significance (ASCUS). Study Design: A 2-year follow-up of 897 cases of LSIL

J. Thomas Cox; Mark Schiffman; Diane Solomon

2003-01-01

255

Development of a Reactive Stroma Associated with Prostatic Intraepithelial Neoplasia in EAF2 Deficient Mice  

PubMed Central

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

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

2013-01-01

256

Detection of Human Papillomavirus in Chronic Cervicitis, Cervical Adenocarcinoma, Intraepithelial Neoplasia and Squamus Cell Carcinoma  

PubMed Central

Background: Cervical cancer is the second most common cancer in women worldwide. Recent studies show that human papillomavirus (HPV) DNA is present in all cervical carcinomas and in some cervicitis cases, with some geographical variation in viral subtypes. Therefore determination of the presence of HPV in the general population of each region can help reveal the role of these viruses in tumors. Objectives: This study aimed to estimate the frequency of infection with HPV in cervicitis, cervical adenocarcinoma, intraepithelial neoplasia and squamus cell carcinoma samples from the Isfahan Province, Iran. Patients and Methods: One hundred and twenty two formalin fixed paraffin embedded tissue samples of crevicitis cases and different cervix tumors including cervical intraepithelial neoplasia (CIN) (I, II, III), squamus cell carcinoma (SCC) and adenocarcinoma were collected from histopathological files of Al-Zahra Hospital in Isfahan. Data about histopathological changes were collected by reexamination of the hematoxylin and eosin stained sections. DNA was extracted and subjected to Nested PCR using consensus primers, MY09/MY11 and GP5+/GP6+, designed for amplification of a conserved region of the genome coding for L1 protein. Results: In total 74.5% of the tested samples were positive for HPV. Amongst the tested tumors 8 out of 20 (40%) of CIN (I, II, III), 5 out of 21 (23.8%) of adenocarcinoma cases and 78 out of 79 chronic cervicitis cases were positive for HPV. Conclusions: The rate of different carcinomas and also the rate of HPV infection in each case were lower than other reports from different countries. This could be correlated with the social behavior of women in the area, where they mostly have only one partner throughout their life, and also the rate of smoking behavior of women in the studied population. On the other hand the rate of HPV infection in chronic cervicitis cases was much higher than cases reported by previous studies. This necessitates more attention to the role of human papillomaviruses in the their induction in the studied area. PMID:25147721

Mirzaie-Kashani, Elahe; Bouzari, Majid; Talebi, Ardeshir; Arbabzadeh-Zavareh, Farahnaz

2014-01-01

257

High-grade prostatic intraepithelial neoplasia with adjacent small atypical glands on prostate biopsy.  

PubMed

With high-grade prostatic intraepithelial neoplasia with adjacent small atypical glands (PINATYP), the issue is whether the small glands represent budding or tangentially sectioned glands off of adjacent high-grade prostatic intraepithelial neoplasia (PIN) or invasive cancer next to high-grade PIN. The histology and significance of PINATYP on biopsy have not been described. Among 574 cases of high-grade PIN lesions on needle biopsy, we identified 71 cases of PINATYP. Most cases were consultations, and 51 cases were available for histologic review. At least 1 follow-up prostate biopsy was performed in each of 55 cases. Immunohistochemistry for high-molecular-weight cytokeratin (HMWCK) was performed on cases in which material was available. The average patient age at diagnosis was 65.5 years (range, 48 to 103 years). The initial digital rectal examination, transrectal ultrasound, serum prostate-specific antigen (PSA) level, PSA velocity, and family history of prostate cancer did not predict cancer on repeat biopsy. In 39% of cases, high-grade PIN had a predominantly flat pattern, and remaining cases showed a predominance of other patterns (tufting, micropapillary, cribriform). The average number of high-grade PIN glands and adjacent small atypical glands were 11.5 (1 to 60) and 5.3 (1 to 21), respectively. The farthest adjacent small atypical gland averaged 0.12 mm from the high-grade PIN (0.01 mm to 0.4 mm), as measured with an ocular micrometer. The following histologic features did not predict cancer on repeat biopsy: more than 1 core involved by the high-grade PIN; number of high-grade PIN glands; number of small atypical glands; distance of small atypical glands from the high-grade PIN; size and percentage of nucleoli; marked nuclear pleomorphism; and mitoses. Overall, the risk of cancer on repeat biopsy was 46%. Two findings predicted a lower risk of cancer on repeat biopsy: younger age (62.2 years benign v 68.3 years cancer; P =.004) and predominantly flat high-grade PIN (P =.007). In our material, PINATYP appears to be a greater risk factor than high-grade PIN alone in predicting cancer on rebiopsy. Although age and predominant pattern of associated high-grade PIN may be helpful in predicting which men with this lesion will have cancer on rebiopsy, they cannot be used reliably; therefore, all men with PINATYP should undergo repeat biopsy. HUM PATHOL 32:389-395. PMID:11331955

Kronz, J D; Shaikh, A A; Epstein, J I

2001-04-01

258

Lymphoproliferative Responses to Human Papillomavirus (HPV) Type 16 Proteins E6 and E7: Outcome of HPV Infection and Associated Neoplasia  

Microsoft Academic Search

Background: Infection with human papillomavirus (HPV) type 16 (HPV16) is a major cause of high-grade cervical intraepithelial neoplasia (CIN). Experiments were planned to evaluate the role of cell-mediated immunity (e.g., lympho- cyte proliferation) against HPV in the natural history of HPV-associated neoplasia and to identify antigenic se- quences of the HPV16 proteins E6 and E7 against which an immune response

Anna S. Kadish; Gloria Y. F. Ho; Robert D. Burk; Yuexian Wang; Seymour L. Romney; Richard Ledwidge; Ruth H. Angeletti

1997-01-01

259

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

Microsoft Academic Search

Background:Vulvar squamous cell carcinoma (SCC) originates the following two pathways, related to differentiated (d) vulvar intraepithelial neoplasia (VIN) or to human papillomavirus (HPV)-related usual (u) VIN. Multicentric HPV infections (cervix, vagina and vulva) are common. We hypothesise that patients with a uVIN-related vulvar SCC more often have cervical high-grade squamous intraepithelial lesions (HSILs) compared with women with dVIN-related vulvar SCC.Methods:All

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

2009-01-01

260

A case of usual (basaloid)-type vulvar intraepithelial neoplasia that failed to respond to imiquimod cream: clinical implications  

Microsoft Academic Search

The authors report a case of usual-type (basaloid-type) vulvar intraepithelial neoplasia (VIN) 3 that failed to respond to\\u000a imiquimod cream. A 51-year-old Japanese woman visited her local gynecologist complaining of vulvar itching. Atypical cells\\u000a were noted in cytology smears, but nine vulvar biopsy specimens showed benign proliferation of epithelial tissue. The patient\\u000a was placed under careful observation for 8 months, when

Takaya Shiozaki; Tsutomu Tabata; Kuniaki Toriyabe; Takashi Motohashi; Eiji Kondo; Kouji Tanida; Toshiharu Okugawa; Norimasa Sagawa

261

Immunohistochemical expression of p16 and p53 in vulvar intraepithelial neoplasia and squamous cell carcinoma of the vulva  

Microsoft Academic Search

This study was undertaken to examine the expression of p16 and p53 in vulvar intraepithelial neoplasia (VIN) and squamous\\u000a cell carcinoma (SCC) of the vulva. We also analyzed the relationship between p16 and p53 immunoexpression in women younger\\u000a vs. older than 55 years of age. Seventyseven histologic samples of vulvar tissue, treated surgically between June 2000 and\\u000a November 2004 at

Mauricio Cordoni Nogueira; Ernesto de Paula Guedes Neto; Marcos Wengrover Rosa; Eduardo Zettler; Cláudio Galleano Zettler

2006-01-01

262

Treatment of vulvar intraepithelial neoplasia with topical imiquimod: Seven years median follow-up of a randomized clinical trial  

Microsoft Academic Search

ObjectiveRecently we reported on the efficacy of imiquimod for treating vulvar intraepithelial neoplasia (VIN) in a placebo-controlled, double-blinded randomized clinical trial (RCT). Four weeks after treatment, a complete response was observed in 35% of patients and a partial response in 46%. All complete responders remained disease-free at 12months follow-up. In the current investigations, we assessed long-term follow-up at least 5years

Annelinde Terlou; Manon van Seters; Patricia C. Ewing; Neil K. Aaronson; Chad M. Gundy; Claudia Heijmans-Antonissen; Wim G. V. Quint; Leen J. Blok; Marc van Beurden; Theo J. M. Helmerhorst

2011-01-01

263

Association of mitochondrial DNA transversion mutations with familial medullary thyroid carcinoma\\/multiple endocrine neoplasia type 2 syndrome  

Microsoft Academic Search

Medullary thyroid carcinoma (MTC) is a malignant tumour of the calcitonin-secreting parafollicular C cells of the thyroid, and occurs sporadically or as a component of the multiple endocrine neoplasia (MEN) type 2\\/familial medullary thyroid carcinoma (FMTC) syndromes. In the present study, we investigated the frequency of mtDNA mutations in 26 MTC tumour specimens (13 sporadic and 13 familial MTC) and

K K Abu-Amero; A S Alzahrani; M Zou; Y Shi

2006-01-01

264

Mitomycin C therapy for corneal intraepithelial neoplasia masquerading as limbal stem cell deficiency with recurrent epithelial defect  

Microsoft Academic Search

Diagnosis of corneal intraepithelial neoplasia was missed in a patient who presented with recurrent large epithelial defects\\u000a with pannus. The patient was eventually diagnosed and successfully treated with topical mitomycin C. Mitomycin C may be preferable\\u000a to surgery in lesions with extensive corneal involvement. Impression cytology should be used for early diagnosis in suspicious\\u000a lesions.

Nikhil S. Gokhale

2011-01-01

265

Mortality, neoplasia, and Creutzfeldt-Jakob disease in patients treated with human pituitary growth hormone in the United Kingdom.  

PubMed Central

OBJECTIVE--To determine the cause of death and incidence of neoplasia in patients treated with human pituitary growth hormone. DESIGN--A long term cohort study established to receive details of death certification and tumour registrations through the Office of Population Censuses and Surveys and NHS central register. PATIENTS--All patients (1246 male, 662 female) treated for short stature with pituitary growth hormone under the Medical Research Council working party and health services human growth hormone committee. MAIN OUTCOME MEASURES--Death or development of neoplasia. RESULTS--110 patients died (68 male, 42 female; aged 0.9-57 years) from 1972 to 1990. Fifty three death were from neoplasia responsible for growth hormone deficiency (27 craniopharyngioma, 24 other intracranial tumour, two leukaemia); two from histiocytosis X; and 13 from pituitary insufficiency. Six patients died of Creutzfeldt-Jakob disease, six of other neurological disorders, and eight of acute infection. Other deaths were apparently unrelated to growth hormone deficiency or its treatment. Seventeen tumours (in 16 patients) were identified during or after growth hormone treatment. Four were in patients with previous intracranial neoplasia and two were after cranial irradiation. Thirteen were intracranial, the others being Hodgkin's lymphoma, osteosarcoma, carcinoma of colon, and basal cell carcinoma. CONCLUSIONS--Recurrence or progression of intracranial tumours and potentially avoidable metabolic consequences of hypopituitarism were the main causes of death. Growth hormone treatment probably did not contribute to new tumour development. Creutzfeldt-Jakob disease after pituitary growth hormone treatment continues to occur in the United Kingdom. This cohort must remain under long term review. PMID:2025705

Buchanan, C R; Preece, M A; Milner, R D

1991-01-01

266

The Pre and Postoperative Value of Endocervical Curettage in the Detection of Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer  

Microsoft Academic Search

Objective.The study was conducted to evaluate the pre- and postoperative value of endocervical curettage (ECC) in the detection of cervical intraepithelial neoplasia and invasive cervical cancer.Methods.Patients undergoing cervical conization were studied retrospectively to evaluate the correlation of grade of preoperative endocervical curettage and the grade of dysplasia in the conization specimen. The role of routine preoperative ECC in satisfactory and

Bruce A. Fine; Glen I. Feinstein; Vincenzo Sabella

1998-01-01

267

Cervical metastases of glucagonoma in a patient with multiple endocrine neoplasia type 1: Report of a case  

Microsoft Academic Search

Multiple endocrine neoplasia type 1 (MEN 1) is a syndrome characterized by tumors of the parathyroid glands, pancreatic islet\\u000a cells, duodenum, and pituitary gland. We report a case of cervical metastases of glucagonoma with MEN 1. The patient was a\\u000a 34-year-old woman admitted to our hospital with epigastric pain. Her medical history included two resections of prolactinoma\\u000a and two upper

Jean M. Butte; Pablo H. Montero; Antonieta Solar; Javiera Torres; Pablo R. Olmos; Ignacio Goñi; Juan C. Quintana; Jorge Martínez; Osvaldo Llanos

2008-01-01

268

Muscarinic receptor subtype-3 gene ablation and scopolamine butylbromide treatment attenuate small intestinal neoplasia in Apcmin/+ mice  

PubMed Central

M3 subtype muscarinic receptors (CHRM3) are over-expressed in colon cancer. In this study, we used Apcmin/+ mice to identify the role of Chrm3 expression in a genetic model of intestinal neoplasia, explored the role of Chrm3 in intestinal mucosal development and determined the translational potential of inhibiting muscarinic receptor activation. We generated Chrm3-deficient Apcmin/+ mice and compared intestinal morphology and tumor number in 12-week-old Apcmin/+Chrm3?/? and Apcmin/+Chrm3+/+ control mice. Compared with Apcmin/+Chrm3+/+ mice, Apcmin/+Chrm3?/? mice showed a 70 and 81% reduction in tumor number and volume, respectively (P < 0.01). In adenomas, ?-catenin nuclear staining was reduced in Apcmin/+Chrm3?/? compared with Apcmin/+Chrm3+/+ mice (P < 0.02). Whereas Apc gene mutation increased the number of crypt and Paneth cells and decreased villus goblet cells, these changes were absent in Apcmin/+Chrm3?/? mice. To determine whether pharmacological inhibition of muscarinic receptor activation attenuates intestinal neoplasia, we treated 6-week-old Apcmin/+ mice with scopolamine butylbromide, a non-subtype-selective muscarinic receptor antagonist. After 8 weeks of continuous treatment, scopolamine butylbromide-treated mice showed a 22% reduction in tumor number (P = 0.027) and a 36% reduction in tumor volume (P = 0.004) as compared with control mice. Compared with Chrm3 gene ablation, the muscarinic antagonist was less efficacious, most probably due to shorter duration of treatment and incomplete blockade of muscarinic receptors. Overall, these findings indicate that interplay of Chrm3 and ?-catenin signaling is important for intestinal mucosal differentiation and neoplasia and provide a proof-of-concept that pharmacological inhibition of muscarinic receptor activation can attenuate intestinal neoplasia in vivo. PMID:21705482

Raufman, Jean-Pierre; Shant, Jasleen; Xie, Guofeng; Cheng, Kunrong; Gao, Xue-Min; Shiu, Brian; Shah, Nirish; Drachenberg, Cinthia B.; Heath, Jonathon; Wess, Jurgen; Khurana, Sandeep

2011-01-01

269

Muscarinic receptor subtype-3 gene ablation and scopolamine butylbromide treatment attenuate small intestinal neoplasia in Apcmin/+ mice.  

PubMed

M3 subtype muscarinic receptors (CHRM3) are over-expressed in colon cancer. In this study, we used Apc(min/+) mice to identify the role of Chrm3 expression in a genetic model of intestinal neoplasia, explored the role of Chrm3 in intestinal mucosal development and determined the translational potential of inhibiting muscarinic receptor activation. We generated Chrm3-deficient Apc(min/+) mice and compared intestinal morphology and tumor number in 12-week-old Apc(min/+)Chrm3(-/-) and Apc(min/+)Chrm3(+/+) control mice. Compared with Apc(min/+)Chrm3(+/+) mice, Apc(min/+)Chrm3(-/-) mice showed a 70 and 81% reduction in tumor number and volume, respectively (P < 0.01). In adenomas, ?-catenin nuclear staining was reduced in Apc(min/+)Chrm3(-/-) compared with Apc(min/+)Chrm3(+/+) mice (P < 0.02). Whereas Apc gene mutation increased the number of crypt and Paneth cells and decreased villus goblet cells, these changes were absent in Apc(min/+)Chrm3(-/-) mice. To determine whether pharmacological inhibition of muscarinic receptor activation attenuates intestinal neoplasia, we treated 6-week-old Apc(min/+) mice with scopolamine butylbromide, a non-subtype-selective muscarinic receptor antagonist. After 8 weeks of continuous treatment, scopolamine butylbromide-treated mice showed a 22% reduction in tumor number (P = 0.027) and a 36% reduction in tumor volume (P = 0.004) as compared with control mice. Compared with Chrm3 gene ablation, the muscarinic antagonist was less efficacious, most probably due to shorter duration of treatment and incomplete blockade of muscarinic receptors. Overall, these findings indicate that interplay of Chrm3 and ?-catenin signaling is important for intestinal mucosal differentiation and neoplasia and provide a proof-of-concept that pharmacological inhibition of muscarinic receptor activation can attenuate intestinal neoplasia in vivo. PMID:21705482

Raufman, Jean-Pierre; Shant, Jasleen; Xie, Guofeng; Cheng, Kunrong; Gao, Xue-Min; Shiu, Brian; Shah, Nirish; Drachenberg, Cinthia B; Heath, Jonathon; Wess, Jürgen; Khurana, Sandeep

2011-09-01

270

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

271

Plasma chromogranin A in patients with sporadic gastro-entero-pancreatic neuroendocrine tumors or multiple endocrine neoplasia type 1  

Microsoft Academic Search

Objective: As circulating chromogranin A (CgA) has been claimed to be the best general neuroendocrine marker so far available, we evaluated the usefulness of CgA determination in the clinical assessment of patients with sporadic gastro-entero-pancreatic neuroendocrine tumors (GEP NETs) or multiple endocrine neoplasia type 1 (MEN 1). Design and methods: Plasma CgA levels were measured using a commercial enzyme-linked immunosorbent

M Peracchi; D Conte; C Gebbia; C Penati; S Pizzinelli; M Arosio; S Corbetta; A Spada

2003-01-01

272

Menin Missense Mutants Associated with Multiple Endocrine Neoplasia Type 1 Are Rapidly Degraded via the Ubiquitin-Proteasome Pathway  

Microsoft Academic Search

MEN1 is a tumor suppressor gene that is responsible for multiple endocrine neoplasia type 1 (MEN1) and that encodes a 610-amino-acid protein, called menin. While the majority of germ line mutations identified in MEN1 patients are frameshift and nonsense mutations resulting in truncation of the menin protein, various missense mutations have been identified whose effects on menin activity are unclear.

Hiroko Yaguchi; Naganari Ohkura; Maho Takahashi; Yuko Nagamura; Issay Kitabayashi; Toshihiko Tsukada

2004-01-01

273

Current approach to the management of gastrinoma and insulinoma in adults with multiple endocrine neoplasia type I  

Microsoft Academic Search

The difficult and controversial diagnostic and therapeutic management of patients having gastrinoma or insulinoma with multiple endocrine neoplasia type I (MEN-I) has been discussed by reference to the literature and a personal series of 45 gastrinoma\\/MEN-I patients followed consecutively at Bichat Hospital. In both gastrinoma\\/ and insulinoma\\/MEN-I patients, anatomic distribution and morphology of tumoral process(es) are usually multiple, diffuse, of

Michel Mignon; Philippe Ruszniewski; Philippe Podevin; Luis Sabbagh; Guillaume Cadiot; Daniel Rigaud; Serge Bonfils

1993-01-01

274

Limited Tumor Involvement Found at Multiple Endocrine Neoplasia Type I Pancreatic Exploration: Can It Be Predicted by Preoperative Tumor Localization?  

Microsoft Academic Search

. Radiologically demonstrable pancreatic endocrine tumors are a frequent requirement for exploration in patients with\\u000a multiple endocrine neoplasia type I (MEN-I). Such delayed intervention is accompanied by a 30% to 50% incidence of pancreatic\\u000a endocrine metastases. This study explores biochemical tumor markers and operative findings in relation to preoperative pancreatic\\u000a radiology in 25 MEN-I patients. They underwent pancreatic surgery with

Britt Skogseid; Kjell Öberg; Göran ?kerström; Barbro Eriksson; Jan-Erik Westlin; Eva Tiensuu Janson; Hampus Eklöf; Claes Juhlin; Jonas Rastad

1998-01-01

275

Causes and Treatment of Recurrent Hyperparathyroidism After Subtotal Parathyroidectomy in the Presence of Multiple Endocrine Neoplasia 1  

Microsoft Academic Search

Background  Subtotal parathyroidectomy (SPTX) is the treatment of choice for hyperparathyroidism in a patient with multiple endocrine\\u000a neoplasia type 1 (HPT-MEN-1). There are scarce data on the causes, timing, and appropriate surgical treatment of patients\\u000a with recurrent HPT-MEN-1. The aim of this study was to investigate the timing, causes, site of recurrence, and surgical treatment\\u000a of recurrent HPT-MEN-1 in patients who

Maria D. Balsalobre Salmeron; Jose Manuel Rodriguez Gonzalez; Joan Sancho Fornos; Albert Goday; Nuria Maria Torregrosa Perez; Antonio Rios Zambudio; Pascual Parrilla Paricio; Antonio Sitges Serra

2010-01-01

276

Phospholipase A2G1B polymorphisms and risk of colorectal neoplasia  

PubMed Central

Pancreatic phospholipase A2, product of PLA2G1B, catalyzes the release of fatty acids from dietary phospholipids.Diet is the ultimate source of arachidonic acid in cellular phospholipids, precursor of eicosanoid signaling molecules, linked to inflammation, cell proliferation and colorectal carcinogenesis. We evaluated the association of PLA2G1B tagging single-nucleotide polymorphisms with colorectal neoplasia risk. A linkage-disequilibrium-based tagSNP algorithm (r2=0.90, MAF?4%) identified three tagSNPs. The SNPs were genotyped on the Illumina platform in three population-based, case-control studies: colon cancer (1424 cases/1780 controls); rectal cancer (583/775); colorectal adenomas (485/578). Evaluating gene-wide associations, principal-component and haplotype analysis were conducted, individual SNPs were evaluated by logistic regression. Two PLA2G1B variants were statistically significantly associated with reduced risk of rectal cancer (rs5637, 3702 G>A Ser98Ser, p-trend=0.03; rs9657930, 1593 C>T, p-trend=0.01); principal component analysis showed that genetic variation in the gene overall was statistically significantly associated with rectal cancer (p=0.02). NSAID users with the rs2070873 variant had a reduced rectal cancer risk (P-inter=0.02). Specific associations were observed with tumor subtypes (TP53/KRAS). The results suggest that genetic polymorphisms in PLA2G1B affect susceptibility to rectal cancer. PMID:24046806

Abbenhardt, Clare; Poole, Elizabeth M; Kulmacz, Richard J; Xiao, Liren; Curtin, Karen; Galbraith, Rachel L; Duggan, David; Hsu, Li; Makar, Karen W; Caan, Bette J; Koepl, Lisel; Owen, Robert W; Scherer, Dominique; Carlson, Christopher S; Potter, John D; Slattery, Martha L; Ulrich, Cornelia M

2013-01-01

277

Interobserver variability in the diagnosis of high-grade prostatic intraepithelial neoplasia and adenocarcinoma.  

PubMed

High-grade prostatic intraepithelial neoplasia (PIN) is a strong predictor of carcinoma when identified in small-needle biopsy specimens. However, the diagnostic variability of PIN is unknown. Eight pathologists reviewed 321 prostatic biopsy specimens to assess the variability of the diagnosis of high-grade PIN and carcinoma. All of the specimens were classified as negative, high-grade PIN, suspicious for high-grade PIN, carcinoma, or suspicious for carcinoma, more than one diagnosis was permitted, except for negative. We compared diagnoses made by two observers by pairing them for negative versus high-grade PIN, negative versus carcinoma, high-grade PIN versus carcinoma, and all diagnostic categories together. Mean kappa coefficient values for 28 interobserver combinations were 0.451, 0.845, 0.669, and 0.482, respectively, for each of the four comparison combinations considered. Our results indicate a high level of agreement, "almost perfect" (kappa = 0.81-1.0) for carcinoma, "moderate" (kappa = 0.41-0.60) for high-grade PIN, and "substantial" (kappa = 0.61-0.81) for high-grade PIN versus carcinoma. We found that variability was related to the level of interest in prostatic pathology, the conditions of the study, the subjective application of diagnostic criteria, and the influence of peers and clinical colleagues. PMID:8832557

Allam, C K; Bostwick, D G; Hayes, J A; Upton, M P; Wade, G G; Domanowski, G F; Klein, M A; Boling, E A; Stilmant, M M

1996-07-01

278

Putting the brakes on mammary tumorigenesis: Loss of STAT1 predisposes to intraepithelial neoplasias  

PubMed Central

Multiparous Stat1?/? mice spontaneously develop mammary tumors with increased incidence: at an average age of 12 months, 55% of the animals suffer from mammary cancer, although the histopathology is heterogeneous. We consistently observed mosaic expression or down-regulation of STAT1 protein in wild-type mammary cancer evolving in the control group. Transplantation experiments show that tumorigenesis in Stat1?/? mice is partially influenced by impaired CTL mediated tumor surveillance. Additionally, STAT1 exerts an intrinsic tumor suppressing role by controlling and blocking proliferation of the mammary epithelium. Loss of STAT1 in epithelial cells enhances cell growth in both transformed and primary cells. The increased proliferative capacity leads to the loss of structured acini formation in 3D-cultures. Analogous effects were observed when Irf1?/? epithelial cells were used. Accordingly, the rate of mammary intraepithelial neoplasias (MINs) is increased in Stat1?/? animals: MINs represent the first step towards mammary tumors. The experiments characterize STAT1/IRF1 as a key growth inhibitory and tumor suppressive signaling pathway that prevents mammary cancer formation by maintaining growth control. Furthermore, they define the loss of STAT1 as a predisposing event via enhanced MIN formation. PMID:22185785

Schneckenleithner, Christine; Bago-Horvath, Zsuzsanna; Dolznig, Helmut; Neugebauer, Nina; Kollmann, Karoline; Kolbe, Thomas; Decker, Thomas; Kerjaschki, Dontscho; Wagner, Kay-Uwe; Muller, Mathias; Stoiber, Dagmar; Sexl, Veronika

2011-01-01

279

Endoscopic diagnosis of early Barrett's neoplasia: perspectives for advanced endoscopic technology.  

PubMed

Barrett's esophagus (BE) is a metaplastic condition that occurs secondary to gastroesophageal reflux disease. BE is also a precursor to esophageal adenocarcinoma, which, although still rare in Japan, is one of the most rapidly increasing cancers in Western countries. However, the prevalence of gastroesophageal reflux disease has increased significantly over the past few decades in Japan, possibly leading to an incremental rise in BE and the associated inherent risk of adenocarcinoma. Given the poor prognosis of advanced-stage Barrett's adenocarcinoma, endoscopic surveillance is recommended for subjects with BE to detect early neoplasias including dysplasia. However, endoscopic identification of dysplastic lesions is still not sufficiently reliable or subjective, making targeted therapy extremely difficult. Over the past few years, improvements in image resolution, image processing software, and optical filter technology have enabled identification of dysplasia and early cancer in BE patients. We retrieved as many studies on advanced endoscopic technologies in BE as possible from MEDLINE and PubMed. The present review focuses on the emergent clinically available technologies to provide an overview of the technologies, their practical applicability, current status, and future challenges. PMID:24754238

Goda, Kenichi; Kato, Tomohiro; Tajiri, Hisao

2014-05-01

280

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

PubMed

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

Reyes, M Carolina; Cooper, Kumarasen

2014-04-01

281

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

282

PSGR promotes prostatic intraepithelial neoplasia and prostate cancer xenograft growth through NF-?B.  

PubMed

Prostate-specific G-protein-coupled receptor (PSGR), a member of the olfactory subfamily of G-protein-coupled receptors, is specifically expressed in human prostate tissue and overexpressed in prostate cancer (PCa). This expression pattern suggests a possible role in PCa initiation and progression. We developed a PSGR transgenic mouse model driven by a probasin promoter and investigated the role of PSGR in prostate malignancy. Overexpression of PSGR induced a chronic inflammatory response that ultimately gave rise to premalignant mouse prostate intraepithelial neoplasia lesions in later stages of life. PSGR-overexpressing LnCaP cells in prostate xenografts formed larger tumors compared with normal LnCaP cancer cells, suggesting a role of PSGR in the promotion of tumor development. Furthermore, we identified nuclear factor-?B (NF-?B) or RELA as a key downstream target activated by PSGR signaling. We also show that this regulation was mediated in part by the phosphatidylinositol-3-kinase/Akt (PI3K/AKT) pathway, highlighting a collaborative role between PI3K/AKT and NF-?B during tumor inflammation downstream of PSGR in the initial phases of prostate disease.Oncogenesis (2014) 3, e114; doi:10.1038/oncsis.2014.29; published online 11 August 2014. PMID:25111863

Rodriguez, M; Luo, W; Weng, J; Zeng, L; Yi, Z; Siwko, S; Liu, M

2014-01-01

283

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

PubMed

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

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

2012-03-01

284

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

285

Lobular neoplasia of the breast revisited with emphasis on the role of E-cadherin immunohistochemistry.  

PubMed

Lobular neoplasia (LN) is a term that encompasses both lobular carcinoma in situ and atypical lobular hyperplasia. These lesions have been shown to constitute both risk indicators and nonobligate precursors of invasive breast cancer, they are relatively uncommon, and are most often identified in specimens taken for other reasons. Their incidence has increased in the last 2 decades, and novel variants, including a pleomorphic type, have been described. Loss of E-cadherin expression is recognized as a hallmark diagnostic feature of LN and invasive lobular carcinomas, and immunohistochemical (IHC) analysis using anti-E-cadherin antibodies has been proven to be a useful method to differentiate between lobular and ductal lesions. The frequent use of E-cadherin IHC analysis in routine diagnostic histopathology, however, has resulted in confusion with regard to the actual value of IHC with antibodies against E-cadherin and other proteins of the cadherin-catenin complex. This review provides an update on recent clinicopathologic and molecular data on LN and invasive lobular carcinoma and a discussion about the use and limitations of IHC with E-cadherin in diagnostic breast pathology. PMID:23759937

Dabbs, David J; Schnitt, Stuart J; Geyer, Felipe C; Weigelt, Britta; Baehner, Frederick L; Decker, Thomas; Eusebi, Vincenzo; Fox, Stephen B; Ichihara, Shu; Lakhani, Sunil R; Palacios, Jose; Rakha, Emad; Richardson, Andrea L; Schmitt, Fernando C; Tan, Puay-Hoon; Tse, Gary M; Vincent-Salomon, Anne; Ellis, Ian O; Badve, Sunil; Reis-Filho, Jorge S

2013-07-01

286

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

287

Condom and oral contraceptive use and risk of cervical intraepithelial neoplasia in Australian women  

PubMed Central

Objective To assess the association between condom use and oral contraceptive consumption and the risk of cervical intraepithelial neoplasia (CIN). Methods A cross-sectional study was conducted in Perth clinics. A total of 348 women responded to the structured questionnaire. Information sought included demographic and lifestyle characteristics such as the use of condom for contraception, consumption of oral contraceptive, and duration of oral contraceptive usage. Crude and adjusted odds ratio (OR) and associated 95% confidence interval (CI) were calculated using unconditional logistic regression models and reported as estimates of the relative risk. Results The prevalence of CIN was found to be 15.8%. The duration of oral contraceptive consumption among women with abnormal Papanicolaou (Pap) smear result indicating CIN was significantly shorter than those without abnormal Pap smear result (mean±SD, 5.6±5.2 years vs. 8.2±7.6 years; p=0.002). Comparing to ?3 years usage, prolonged consumption of oral contraceptive for ?10 years reduced the risk of CIN (p=0.012). However, use of condom for contraception might not be associated with a reduced risk of CIN after accounting for the effects of confounding factors (adjusted OR, 0.52; 95% CI, 0.05 to 5.11; p=0.577). Conclusion Use of oral contraceptives, but not condoms, for contraception appeared to be inversely associated with CIN. Prolonged use of oral contraceptive demonstrated its benefits of reducing the risk of CIN. PMID:25045430

Lee, Andy H.; Colville, Linda; Xu, Daniel; Binns, Colin W.

2014-01-01

288

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

289

Fiber optic FTIR instrument for in vivo detection of colonic neoplasia  

NASA Astrophysics Data System (ADS)

We demonstrate the proof of concept for use of a fiber optic FTIR instrument to perform in vivo detection of colonic neoplasia as an adjunct to medical endoscopy. FTIR is sensitive to the molecular composition of tissue, and can be used as a guide for biopsy by identifying pre-malignant tissue (dysplasia). First, we demonstrate the use of a silver halide optical fiber to collect mid-infrared absorption spectra in the 950 to 1800 cm-1 regime with high signal-to-noise from biopsy specimens of colonic mucosa tissue ex vivo. We observed subtle differences in wavenumber and magnitude of the absorbance peaks over this regime. We then show that optimal sub-ranges can be defined within this spectral regime and that spectral pre-processing can be performed to classify the tissue as normal, hyperplasia, or dysplasia with high levels of performance. We used a partial least squares discriminant analysis and a leave-one-subject-out crossvalidation strategy to classify the spectra. The results were compared with histology, and the optimal thresholds resulted in an overall sensitivity, specificity, accuracy, and positive predictive value of 96%, 92%, 93%, and 82%, respectively for this technique. We demonstrate that mid-infrared absorption spectra can be collected remotely with an optical fiber and used to identify colonic dysplasia with high accuracy. We are now developing an endoscope compatible optical fiber to use this technique clinically for the early detection of cancer.

Van Nortwick, Matthew; Hargrove, John; Wolters, Rolf; Crawford, James M.; Arroyo, May; Mackanos, Mark; Contag, Christopher H.; Wang, Thomas D.

2009-02-01

290

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

PubMed

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

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

2014-05-01

291

Uptake, yield of neoplasia, and adverse effects of flexible sigmoidoscopy screening  

PubMed Central

Background—A multicentre randomised controlled trial to evaluate screening by "once only" flexible sigmoidoscopy (FS) for prevention of bowel cancer is in progress. ?Aims—To pilot the trial protocol examining rates of attendance, yield of neoplasia, and adverse effects. ?Subjects—A total of 3540 subjects aged 55-64 years in Welwyn Garden City (WGC) and 19 706 in Leicester (LE). ?Methods—Subjects responding positively to an "interest in screening" questionnaire were randomised to invitation for screening or control arms. Small polyps were removed during screening. Colonoscopy was undertaken for high risk polyps (more than two adenomas, size at least 1 cm, villous histology, severe dysplasia, or malignancy). The remainder were discharged. ?Results—In WGC and LE respectively, 59% and 61% indicated an interest in screening, of which 74% and 75% attended. Adenomas were detected in 10% and 9%, respectively, and cancers in 7 per 1000 (in both centres), 55% at Dukes's stage A. The colonoscopy referral rate was 6% in both centres. Mild, short lived bleeding occurred in 3%. One person died following surgery. ?Conclusions—Compliance rates, yield of adenomas, and referral rate for colonoscopy were as expected, but cancer detection rates were higher. Adverse effects following sigmoidoscopy or colonoscopy were mild and transient, but there was one postoperative death. A randomised trial is necessary to evaluate fully the risks and benefits of this intervention. ?? Keywords: screening; colorectal cancer; adenomas; sigmoidoscopy; endoscopy; randomised trial PMID:9616321

Atkin, W; Hart, A; Edwards, R; McIntyre, P; Aubrey, R; Wardle, J; Sutton, S; Cuzick, J; Northover, J

1998-01-01

292

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

PubMed

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

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

2011-10-01

293

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

NASA Astrophysics Data System (ADS)

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

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

1989-06-01

294

Multiple Endocrine Neoplasia Type 1 Deletion in Pancreatic ?-Cells Leads to Development of Insulinomas in Mice  

PubMed Central

The pancreatic ?- and ?-cells are critical components in regulating blood glucose homeostasis via secretion of glucagon and insulin, respectively. Both cell types are typically localized in the islets of Langerhans. However, little is known about the roles of paracrine interactions that contribute to their physiological functions. The lack of suitable cell lines to study ?- and ?-cells interactions have led us to develop an ?-cell-specific Cre-expressing transgenic line utilizing a glucagon promoter sequence, the Glu-Cre transgenic mouse. Here, we demonstrate that the Glu-Cre could specifically and efficiently excise floxed target genes in adult islet ?-cells. We further showed that deletion of the tumor suppressor gene, multiple endocrine neoplasia type 1 (Men1), in ?-cells led to tumorigenesis. However, to our surprise, the lack of Men1 in ?-cells did not result in glucagonomas but rather ?-cell insulinomas. Because deletion of the Men1 alleles was only present in ?-cells, our data suggested that cross communication between ?- and ?-cells contributes to tumorigenesis in the absence of Men1. Together, we believed that the new model systems described here will allow future studies to decipher cellular interactions between islet ?- and ?-cells in a physiological context. PMID:20555035

Shen, H.-C. Jennifer; Ylaya, Kris; Pechhold, Klaus; Wilson, Arianne; Adem, Asha; Hewitt, Stephen M.; Libutti, Steven K.

2010-01-01

295

The use of electrical impedance spectroscopy in the detection of cervical intraepithelial neoplasia.  

PubMed

The objective of this study was to assess the performance of cervical impedance spectroscopy in the detection of cervical intraepithelial neoplasia (CIN) using the new MKIII impedance probe. A prospective observational study recruited women referred to colposcopy with an abnormal Papanicolaou smear. A pencil probe incorporating four gold electrodes was used to measure electrical impedance spectra from cervical epithelium. Colposcopy examinations, including probe positioning, were video recorded to allow for correlation between results obtained from colposcopic impression, histopathologic examination of colposcopic punch biopsies, and impedance measurements. Cervical impedance-derived parameters R, S, R/S, C, and Fc were assessed to see if significant difference in values obtained in CIN and normal epithelium existed. The performance of the probe in identifying women with CIN was also assessed. One hundred seventy-six women were recruited and 1168 points analyzed. Parameters R, S, and Fc showed significant separation of CIN or squamous intraepithelial lesion (SIL) from squamous, mature metaplastic, and columnar epithelium. Sensitivities of 74% and specificity of 53% can be achieved in identifying CIN 2/3 (High-grade SIL) in screened women. We conclude that cervical impedance spectrometry provides a potentially promising real-time screening tool for CIN with similar sensitivity and specificity to currently used screening tests. Further research is ongoing to develop the probe for potential clinical use. PMID:17009978

Abdul, S; Brown, B H; Milnes, P; Tidy, J A

2006-01-01

296

Clinical and biological characteristics of cervical neoplasias with FGFR3 mutation  

PubMed Central

Background We have previously reported activating mutations of the gene coding for the fibroblast growth factor receptor 3 (FGFR3) in invasive cervical carcinoma. To further analyze the role of FGFR3 in cervical tumor progression, we extended our study to screen a total of 75 invasive tumors and 80 cervical intraepithelial neoplasias (40 low-grade and 40 high-grade lesions). Results Using single strand conformation polymorphism (SSCP) followed by DNA sequencing, we found FGFR3 mutation (S249C in all cases) in 5% of invasive cervical carcinomas and no mutation in intraepithelial lesions. These results suggest that, unlike in bladder carcinoma, FGFR3 mutation does not or rarely occur in non invasive lesions. Compared to patients with wildtype FGFR3 tumor, patients with S249C FGFR3 mutated tumors were older (mean age 64 vs. 49.4 years, P = 0.02), and were more likely to be associated with a non-16/18 HPV type in their tumor. Gene expression analysis demonstrated that FGFR3 mutated tumors were associated with higher FGFR3b mRNA expression levels compared to wildtype FGFR3 tumors. Supervised analysis of Affymetrix expression data identified a significant number of genes specifically differentially expressed in tumors with respect to FGFR3 mutation status. Conclusion This study suggest that tumors with FGFR3 mutation appear to have distinctive clinical and biological characteristics that may help in defining a population of patients for FGFR3 mutation screening. PMID:15869706

Rosty, Christophe; Aubriot, Marie-Hélène; Cappellen, David; Bourdin, Jérôme; Cartier, Isabelle; Thiery, Jean Paul; Sastre-Garau, Xavier; Radvanyi, François

2005-01-01

297

Genotyping of human papillomavirus in cervical intraepithelial neoplasia in a high-risk population.  

PubMed

Infection with the human papillomavirus (HPV) is responsible for 99.7% of cervical cancers, the second most prevalent neoplasia in women worldwide and the fifth leading cause of death by cancer in this population. In Chile, the incidence rate is 14.4 cases per 100,000 women per year and it is considered a significant public health problem. The natural history of cervical cancer begins gradually from low-grade and high-grade squamous intraepithelial lesions to an invasive disease. In this study the frequency of HPV types was determined by HPV genotyping with reverse line blot hybridization in 200 cytobrushes of women with preneoplastic lesions in a high-risk population. HPV DNA was found in 89% of the lesions (83.3% of low-grade squamous intraepithelial lesions and 93.6% of high-grade squamous intraepithelial lesions). Multiple HPV infections were found in 14.4% and 15.5% of low- and high-grade lesions, respectively. HPV 16 was the most frequent genotype in single infections, followed by HPV 18. These results show that most of the preneoplastic lesions of the cervix (60%) were associated with HPV 16 and/or HPV 18, supporting the implementation of an HPV vaccination program in this high-risk population. PMID:21360550

Ili, Carmen G; Brebi, Priscilla; López, Jaime; García, Patricia; Leal, Pamela; Suarez, Eugenio; Roa, Juan C

2011-05-01

298

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

299

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

300

The Current Strategy for Managing Pancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1  

PubMed Central

Multiple endocrine neoplasia type 1 (MEN1) is an inherited autosomal dominant disease presenting with pancreatic neuroendocrine tumors (pNETs), parathyroid tumors, or pituitary tumors. Using the PubMed database, we reviewed the literature on information regarding the proper diagnosis and treatment of MEN1-associated pNET. Many cases of MEN1-associated pNET are functioning pNETs. Gastrinomas and insulinomas tend to occur frequently in the duodenum and pancreas, respectively. In addition to diagnostic imaging, the selective arterial secretagogue injection test (SASI test) is useful for localizing functioning pNET. The standard treatment is surgical resection. However, in the case of a functioning pNET, the tumor should first be accurately located using the SASI test before an appropriate surgical method is selected. In cases of a MEN1-associated non-functioning pNET that exceeds 2 cm in diameter, the incidence of distant metastasis is significantly increased, and surgery is recommended. In cases of unresectable pNET, a somatostatin analog has been shown to demonstrate antitumor effects and is considered to be a promising treatment. In addition, molecular-targeted drugs have recently been found to be effective in phase III clinical trials. PMID:22844555

Niina, Yusuke; Fujimori, Nao; Nakamura, Taichi; Igarashi, Hisato; Oono, Takamasa; Nakamura, Kazuhiko; Kato, Masaki; Jensen, Robert T.; Takayanagi, Ryoichi

2012-01-01

301

First Description of Parathyroid Disease in Multiple Endocrine Neoplasia 2A Syndrome  

PubMed Central

Context Hyperparathyroidism and/or parathyroid hyperplasia, medullary thyroid carcinoma (MTC) and pheochromocytomas compose the hallmarks of the multiple endocrine neoplasia type 2A (MEN 2A) syndrome. Revisiting a report in 1939 of a patient with hyperparathyroidism and parathyroid hyperplasia led to a search for evidence of MEN 2A. Evidence Acquisition From medical records and discussion with family members, longitudinal follow-up of the patient and her descendants was obtained. Molecular diagnostics were integrated in the care of subsequent generations. The literature on hyperparathyroidism and MEN 2A was reviewed. Results Children of the proband exhibited all components of MEN 2A and the RET mutation of 634 TGC>zCGC. The pedigree was typical for this mutation. Papers on anthropologic studies demonstrate skeletal evidence of hyperparathyroidism in humans centuries ago. Conclusions The initial report of the proband preceded the publications defining both MTC and MEN 2A. The values of in-depth family histories and genetic analyses are exemplified. PMID:19034701

Sisson, James C.; Giordano, Thomas J.; Raymond, Victoria M.; Doherty, Gerard M.; Gruber, Stephen B.

2009-01-01

302

Multiple endocrine neoplasia 2B presenting with pseudo-Hirschsprung's disease.  

PubMed Central

Multiple endocrine neoplasia type 2B (MEN 2B) is a rare syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and typical phenotypic features, such as marfanoid habitus, multiple mucosal ganglioneuromas and thickened corneal nerves. Individuals with MEN 2B may develop megacolon and pseudo-obstruction due to intestinal ganglioneuromatosis simulating Hirschsprung's (HSCR) disease. We hereby describe the clinical and genetic features of a 21-year-old male patient with MEN 2B associated with pseudo-HSCR disease. The patient had MTC, pheochromocytoma, marfanoid habitus, multiple mucosal ganglioneuromas, thickened corneal nerves and severe gastrointestinal involvement. Emergent laparotomy was performed when he was presented with acute bowel obstruction. The myenteric and submucosal nerve plexuses in the small and large intestines were composed of diffusely hyperplasic, disorganized, mature ganglion cells. Genetic testing revealed a de novo ret proto-oncogene germline mutation in codon 918 in exon 16. Megacolon and pseudo-obstruction similar to the HSCR disease may develop in patients with MEN 2B. However, the observed dysmotility is the result of an abnormal proliferation of intramural ganglion cells in contrast to the absence of enteric ganglia which were present in the HSCR disease. Attentiveness about the phenotypic characteristics and unusual findings might lead to early and correct diagnosis of the MEN 2B syndrome. This approach improves the survival rate and quality of life considerably. Images Figure 1 PMID:16749656

Erdogan, Murat Faik; Gulec, Bulent; Gursoy, Alptekin; Pekcan, Mesut; Azal, Omer; Gunhan, Omer; Bayer, Atilla

2006-01-01

303

Uterine artery pulsatility index: a predictor of methotrexate resistance in gestational trophoblastic neoplasia  

PubMed Central

Background: Neo-angiogenesis is a hallmark of cancer. The aim of this study was to test the hypothesis, in a prospective patient cohort, that in low-risk gestational trophoblastic neoplasia (LR-GTN) the uterine artery pulsatility index (UAPI), a measure of tumour vascularity, can predict resistance to methotrexate chemotherapy (MTX-R). Methods: 286 LR-GTN patients (Charing Cross Hospital (CXH) score 0–8, or FIGO score 0–6) were treated with methotrexate between January 2008 and June 2011 at CXH. During staging investigations, patients underwent a Doppler ultrasound to assess the UAPI. Results: 239 patients were assessable for both UAPI and MTX-R. The median UAPI was lower (higher vascularity) in MTX-R compared with MTX-sensitive patients (0.8 vs 1.4, P<0.0001). In multivariate logistic regression, UAPI?1 predicted MTX-R, independent of both CXH and FIGO scores. The risk of MTX-R in patients with a FIGO score of 6 and UAPI?1 was 100% vs 20% in patients with UAPI>1 (?2 P<0.0001). Conclusion: UAPI represents an independently validated clinically useful predictor of MTX-R in LR-GTN. Further, consideration of whether to incorporate UAPI into the FIGO scoring system is now warranted so that patients with a score of 6 and a UAPI ?1 might be upstaged and offered combination chemotherapy rather than MTX. PMID:22374461

Agarwal, R; Harding, V; Short, D; Fisher, R A; Sebire, N J; Harvey, R; Patel, D; Savage, P M; Lim, A K P; Seckl, M J

2012-01-01

304

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

305

Prevalence and distribution of prostatic intraepithelial neoplasia in salvage radical prostatectomy specimens after radiation therapy.  

PubMed

High-grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of prostate cancer. The effect of radiation therapy (RT) on the prevalence of PIN is uncertain. We studied 86 patients who underwent salvage radical prostatectomy after irradiation failure at the Mayo Clinic. The prevalence, volume, multicentricity, spatial proximity to cancer, and architectural patterns of PIN were evaluated. High-grade PIN was identified in 53 (62%) of 86 prostatectomy specimens. Multiple architectural patterns were usually observed, including tufting in 87%, micropapillary in 66%, cribriform in 38%, and flat in 17%. The mean volume of PIN was 0.12 cm3 (range, 0.05-1.20 cm3). PIN was usually multicentric (70%), with a mean number of PIN foci of 2.5 (range, 1-10). Ninety-four percent of PIN foci were located within 2 mm of invasive cancer. There was no correlation between PIN and pathologic stage, surgical margin, tumor size, DNA ploidy, post-RT Gleason score, time interval from RT to biopsy-proven recurrence, postoperative prostate-specific antigen level, distant metastasis-free survival, or cancer-specific survival. Our examination of salvage radical prostatectomy specimens indicated that the prevalence and extent of PIN appeared to be reduced after RT compared to published studies of prostatectomies without prior RT. PMID:10403303

Cheng, L; Cheville, J C; Pisansky, T M; Sebo, T J; Slezak, J; Bergstralh, E J; Neumann, R M; Singh, R; Pacelli, A; Zincke, H; Bostwick, D G

1999-07-01

306

Prevalence of intratubular germ cell neoplasia in cryptorchid testes of infertile men  

PubMed Central

Background: Cryptorchidism is a common malformation in neonates; surgery or medical treatments are applied during childhood. Untreated cryptorchid testes are in the risk of intratubular germ cell neoplasia (IGCN) and consequently invasive testicular tumors which could be shown by immunohistochemistry staining for placental like acid phosphatase (PLAP) marker. Objective: We designed this study to know the prevalence of IGCN in untreated cryptorchid testes of infertile men, in our infertility center as a refferal center. Materials and Methods: In this cross-sectional study we assessed H&E slides of testicular samples of 13 adult infertile patients with impalpable intra-abdominal testes seeking infertility treatment; then we stained them by PLAP marker. Results: Three (23.08%) samples were positive for PLAP marker means presence of IGCN in testis. One of them showed seminoma besides IGCN. Conclusion: According to the results of this study and the fact that there are adult untreated cryptorchid patients in our country yet, it is suggested to pay more attention in clinical examination, assessment and follow up of such patients for malignancy screening. PMID:24639765

Pourkeramati, Fatemeh; Soltanghoraee, Haleh; Amirjannati, Naser; Akhondi, Mohammad Mehdi; Reza Khorram Khorshid, Hamid Reza

2013-01-01

307

Multiple endocrine neoplasias type 2B and RET proto-oncogene  

PubMed Central

Multiple Endocrine Neoplasia type 2B (MEN 2B) is an autosomal dominant complex oncologic neurocristopathy including medullary thyroid carcinoma, pheochromocytoma, gastrointestinal disorders, marphanoid face, and mucosal multiple ganglioneuromas. Medullary thyroid carcinoma is the major cause of mortality in MEN 2B syndrome, and it often appears during the first years of life. RET proto-oncogene germline activating mutations are causative for MEN 2B. The 95% of MEN 2B patients are associated with a point mutation in exon 16 (M918/T). A second point mutation at codon 883 has been found in 2%-3% of MEN 2B cases. RET proto-oncogene is also involved in different neoplastic and not neoplastic neurocristopathies. Other RET mutations cause MEN 2A syndrome, familial medullary thyroid carcinoma, or Hirschsprung's disease. RET gene expression is also involved in Neuroblastoma. The main diagnosis standards are the acetylcholinesterase study of rectal mucosa and the molecular analysis of RET. In our protocol the rectal biopsy is, therefore, the first approach. RET mutation detection offers the possibility to diagnose MEN 2B predisposition at a pre-clinical stage in familial cases, and to perform an early total prophylactic thyroidectomy. The surgical treatment of MEN 2B is total thyroidectomy with cervical limphadenectomy of the central compartment of the neck. When possible, this intervention should be performed with prophylactic aim before 1 year of age in patients with molecular genetic diagnosis. Recent advances into the mechanisms of RET proto-oncogene signaling and pathways of RET signal transduction in the development of MEN 2 and MTC will allow new treatment possibilities. PMID:22429913

2012-01-01

308

Progression of Epididymal Maldevelopment Into Hamartoma-like Neoplasia in VHL Disease1  

PubMed Central

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 GB; 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

2008-01-01

309

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

310

Interobserver variability and the effect of education in the histopathological diagnosis of differentiated vulvar intraepithelial neoplasia.  

PubMed

No published data concerning intraobserver and interobserver variability in the histopathological diagnosis of differentiated vulvar intraepithelial neoplasia (DVIN) are available, although it is widely accepted to be a subtle and difficult histopathological diagnosis. In this study, the reproducibility of the histopathological diagnosis of DVIN is evaluated. Furthermore, we investigated the possible improvement of the reproducibility after providing guidelines with histological characteristics and tried to identify histological characteristics that are most important in the recognition of DVIN. A total number of 34 hematoxylin and eosin-stained slides were included in this study and were analyzed by six pathologists each with a different level of education. Slides were reviewed before and after studying a guideline with histological characteristics of DVIN. Kappa statistics were used to compare the interobserver variability. Pathologists with a substantial agreement were asked to rank items by usefulness in the recognition of DVIN. The interobserver agreement during the first session varied between 0.08 and 0.54, which slightly increased during the second session toward an agreement between -0.01 and 0.75. Pathologists specialized in gynecopathology reached a substantial agreement (kappa 0.75). The top five of criteria indicated to be the most useful in the diagnosis of DVIN included: atypical mitosis in the basal layer, basal cellular atypia, dyskeratosis, prominent nucleoli and elongation and anastomosis of rete ridges. In conclusion, the histopathological diagnosis of DVIN is difficult, which is expressed by low interobserver agreement. Only in experienced pathologists with training in gynecopathology, kappa values reached a substantial agreement after providing strict guidelines. Therefore, it should be considered that specimens with an unclear diagnosis and/or clinical suspicion for DVIN should be revised by a pathologist specialized in gynecopathology. When adhering to suggested criteria the diagnosis of DVIN can be made easier. PMID:23370772

van den Einden, Loes C G; de Hullu, Joanne A; Massuger, Leon F A G; Grefte, Johanna M M; Bult, Peter; Wiersma, Anne; van Engen-van Grunsven, Adriana C H; Sturm, Bart; Bosch, Steven L; Hollema, Harry; Bulten, Johan

2013-06-01

311

Phosphorylated S6 as an immunohistochemical biomarker of vulvar intraepithelial neoplasia.  

PubMed

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

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

2013-11-01

312

Prostatic atrophy: its spatial proximity to carcinoma and intraepithelial neoplasia based on annotation of digital slides.  

PubMed

Whether atrophy is a precursor to high-grade prostatic intraepithelial neoplasia (HGPIN) and cancer is controversial. A virtual slide set comprising 48 prostatectomy cases was used to investigate associations among the amounts and spacing of these entities. Foci of atrophy without inflammation (A), atrophy with inflammation (AI), cancer (by patterns), and HGPIN were digitally annotated. Atrophy's proximity to cancer and HGPIN was assessed with two measurements: abutment (touching) or nearness (?2 ?m without touching). Area sums per specimen were computed for A, AI, cancer, and HGPIN. Abutment rates of AI and A foci to cancer were 23% versus 21% (p = NS); for nearness, 29% of AI foci were near to cancer versus 12% of A (P = .0001). Abutment or nearness of A and AI to HGPIN were in the 1.4% to 2.4% range. When A, AI, or HGPIN abutted cancer, it was disproportionately to Gleason grade 3 cancer foci even after adjusting for the lesser frequency of higher-grade cancer foci. Area sums of A, AI, or (A + AI) per specimen showed no correlations with those of HGPIN, and mostly negative ones with area sum and with tumor volume of cancer. In conclusion, atrophy with inflammation showed some preferential spatial association to cancer, although area sums of atrophy with or without inflammation correlated negatively with those of cancer. These divergent spatial associations suggest that atrophy and inflammation in biopsy specimens may have clinical relevance. The frequency of inflammatory atrophy (AI) merging with HGPIN was far less than reported previously, weakening the theory that AI gives rise to HGPIN. PMID:24157066

Iczkowski, Kenneth A; Torkko, Kathleen C; Wilson, R Storey; Lucia, M Scott; Bostwick, David G

2014-01-01

313

Care for patients with multiple endocrine neoplasia type 1: the current evidence base.  

PubMed

Multiple endocrine neoplasia type 1 (MEN1) is a rare disease caused by mutations in the MEN1 gene on chromosome 11. It is characterized by the occurrence of primary hyperparathyroidism (pHPT), duodenopancreatic neuroendocrine tumours (pNET), pituitary tumours (PIT), adrenal adenomas (ADR) and neuroendocrine tumours (NET) of the stomach, bronchus and thymus. MEN1 is a syndrome with high penetrance and high morbidity. Malignant NETs are the most important cause of MEN1-related death. Since 1997 the diagnosis can be made by genetic screening. MEN1 is a complex syndrome and the endocrine manifestations cannot be viewed upon as coinciding sporadic tumours. Differences in epidemiology and pathology between MEN1-related tumours and their sporadic counterparts show that a unique approach is needed. Therefore the care for MEN1 patients should be provided by a centre of expertise. Early genetic diagnosis and periodic screening are important pillars of care. For primary hyperparathyroidism surgery is the most important treatment modality, with a subtotal parathyroid gland resection as the procedure of choice. In neuroendocrine tumours surgery also is the most important treatment modality. Selective tumour enucleation has no place in the surgical treatment of MEN1-related pNETs; the exact procedure depends on the functionality of the tumour. In MEN1-associated pituitary and adrenal adenomas, watchful waiting and medical therapy play more important roles. In the twenty-first century new developments will impact the care for MEN1 patients. These developments should be critically evaluated in clinical research with the ultimate goal of optimizing the care for MEN1 patients on an evidence base. PMID:21061174

Pieterman, C R C; Vriens, M R; Dreijerink, K M A; van der Luijt, R B; Valk, G D

2011-03-01

314

Risk Factors for Persistent Cervical Intraepithelial Neoplasia Grades 1 and 2 Managed by Watchful Waiting  

PubMed Central

Objective This study examines risk factors for persistent cervical intraepithelial neoplasia (CIN) and whether human papillomavirus (HPV) testing predicts persistent lesions. Materials and Methods Women with histologically diagnosed CIN 1 or CIN 2 (n = 206) were followed every 3 months without treatment. HPV genotyping, plasma levels of ascorbic acid, and red blood cell folate were obtained. Cervical biopsy at 12 months determined the presence of CIN. Relative risk (RR) was estimated by log-linked binomial regression models. Results At 12 months, 70% of CIN 1 versus 54% of CIN 2 lesions spontaneously regressed (p< 0.001). Levels of folate or ascorbic acid were not associated with persistent CIN at 12 months. Compared to HPV negative women, those with multiple HPV types (RRs ranged from 1.68 to 2.17 at each follow-up visit) or high-risk types (RRs range = 1.74 to 2.09) were at increased risk for persistent CIN; women with HPV 16/18 had the highest risk (RRs range = 1.91 to 2.21). Persistent infection with a high-risk type was also associated with persistent CIN (RRs range = 1.50 – 2.35). Typing for high-risk HPVs at 6 months only had a sensitivity of 46% in predicting persistence of any lesions at 12 months. Conclusion Spontaneous regression of CIN 1 and CIN 2 occurs frequently within 12 months. HPV infection is the major risk factor for persistent CIN. However, HPV testing cannot reliably predict persistence of any lesion. PMID:21811178

Ho, Gloria Y.F.; Einstein, Mark H.; Romney, Seymour L.; Kadish, Anna S.; Abadi, Maria; Mikhail, Magdy; Basu, Jayasri; Thysen, Benjamin; Reimers, Laura; Palan, Prabhudas R.; Trim, Shelly; Soroudi, Nafisseh; Burk, Robert D.

2013-01-01

315

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

PubMed Central

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

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

2013-01-01

316

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

317

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

318

Increased expression of fibroblast growth factor 6 in human prostatic intraepithelial neoplasia and prostate cancer.  

PubMed

Fibroblast growth factors (FGFs) are known to play an important role in the growth of normal prostatic epithelial cells. In addition to their effects on proliferation, FGFs can promote cell motility, increase tumor angiogenesis, and inhibit apoptosis, all of which play an important role in tumor progression. To determine whether FGFs are overexpressed in human prostate cancers, we analyzed 26 prostate cancer RNAs by reverse transcription-PCR for expression of FGF3, FGF4, and FGF6, which cannot be detected in normal prostate tissue by this technique. Fourteen of 26 prostate cancers expressed FGF6 mRNA. No expression of FGF3 or FGF4 was detected. An ELISA of tissue extracts of normal prostate, high-grade prostatic intraepithelial neoplasia (PIN), and prostate cancer for FGF6 showed that this growth factor was undetectable in normal prostate but was present at elevated levels in 4 of 9 PIN lesions and in 15 of 24 prostate cancers. Immunohistochemical analysis with anti-FGF6 antibody revealed weak staining of prostatic basal cells in normal prostate that was markedly elevated in PIN. In the prostate cancers, the majority of cases revealed expression of FGF6 by the prostate cancer cells themselves. In two cases, expression was present in prostatic stromal cells. Exogenous FGF6 was able to stimulate proliferation of primary prostatic epithelial and stromal cells, immortalized prostatic epithelial cells, and prostate cancer cell lines in tissue culture. FGF receptor 4, which is the most potent FGF receptor for FGF6, is expressed in the human prostate in vivo and in all of the cultured cell lines. Thus, FGF6 is increased in PIN and prostate cancer and can promote the proliferation of the transformed prostatic epithelial cells via paracrine and autocrine mechanisms. PMID:10945637

Ropiquet, F; Giri, D; Kwabi-Addo, B; Mansukhani, A; Ittmann, M

2000-08-01

319

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

PubMed Central

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

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

2014-01-01

320

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.

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

2014-01-01

321

Partial orchiectomy and testis intratubular germ cell neoplasia: World literature review  

PubMed Central

Approximately 5% of all patients diagnosed with testicular cancer may have contralateral intratubular germ cell neoplasia (ITGCN) and may develop contralateral germ cell tumor. Here, we present a historical review and current literature regarding ITGCN and partial orchiectomy. The PubMed world literature search was performed for articles written in the English language. Search terms used were: Partial orchiectomy and ITGCN, with a return of 322 articles. Articles obtained were from the United States, Germany, Denmark and the Netherlands as well as a few case reports from Australia, France, Turkey and Spain. A critical review of the literature was performed. Partial orchiectomy is an option for the management of testicular malignancy in a select group of patients in whom radical orchiectomy is not desirable, including those with a solitary testicle, bilateral concurrent malignancies and a desire for paternity or being independent from androgen supplementation. Reports have demonstrated the feasibility of partial orchiectomy, but there are strict surgical criteria; tumor less than 2 cm in size, maintenance of cold ischemia, meticulous dissection to maintain testicular blood supply and biopsying of adjacent testicular parenchyma to ensure negative margins and absence of concurrent ITGCN. Partial orchiectomy is followed by testicular irradiation of 18-20 Gy; this radiation dose reduces fertility but maintains leydig cell function with androgen independence. Patients with a history of testicular carcinoma have a 5% chance of developing a metachronous contralateral tumor. Partial orchiectomy is a technically challenging procedure that requires close follow-up, but may represent a reasonable management option in selected patients. PMID:21976922

Bazzi, Wassim M.; Raheem, Omer A.; Stroup, Sean P.; Kane, Christopher J.; Derweesh, Ithaar H.; Downs, Tracy M.

2011-01-01

322

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

323

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

PubMed Central

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.

2013-01-01

324

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

325

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 ANGELICA GALICIA; MARINA, VICENTE MADRID; CASTRO, JORGE SALMERON; JIMENEZ, ALFREDO ANTUNEZ; MENDOZA-HERNANDEZ, GUILLERMO; McCARRON, ELIZABETH LANGLEY; ROMAN, MARGARITA BAHENA; CASTRO-ROMERO, JULIETA IVONE

2014-01-01

326

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

327

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

328

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

329

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

PubMed Central

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

Cal?skan, Selahattin; Ozturk, Metin Ishak; Gunes, Mustafa; Karaman, M. Ihsan

2011-01-01

330

MANTENIMIENTO CON PILATES FUNDAMENTACIN  

E-print Network

MANTENIMIENTO CON PILATES FUNDAMENTACI�N Esta disciplina pretende fusionar la gimnasia de mantenimiento con los beneficios que conlleva el método Pilates. Para ello vamos a definir el método Pilates como un sistema de entrenamiento físico y mental creado a principios del siglo XX por Joseph Pilates

Escolano, Francisco

331

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

332

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

333

Screening of Patients with Multiple Endocrine Neoplasia Type 1 (MEN1): A Critical Analysis of Its Value  

Microsoft Academic Search

Background  Screening of multiple endocrine neoplasia type 1 (MEN-1) patients is widely recommended because one-fifth succumb to malignant\\u000a neoplasms. However, recommendations for screening modalities and intervals are based mostly on nonprospective data.\\u000a \\u000a \\u000a \\u000a Methods  Thirty-five of 48 MEN-1 patients were evaluated at least twice by an annual screening program in a single-center, prospective,\\u000a nonrandomized study between 1997 and 2006. The screening program comprised

Jens Waldmann; Volker Fendrich; Nils Habbe; Detlef K. Bartsch; Emily P. Slater; Peter H. Kann; Matthias Rothmund; Peter Langer

2009-01-01

334

Sonographic Findings of Medullary Thyroid Carcinoma Leading to Diagnosis of Multiple Endocrine Neoplasia Type 2a during Pregnancy  

PubMed Central

Multiple endocrine neoplasia (MEN) type 2a (Sipple's syndrome) is characterized by medullary thyroid carcinoma and pheochromocytoma, and in a smaller percentage of cases, multiglandular parathyroid hyperplasia. This autosomal-dominant syndrome is due to a mutation in the rearranged during transfection (RET) proto-oncogene located on chromosome 10cen–10q11.2 and rarely complicates pregnancy. We present an unusual case in a patient with an enlarged thyroid with sonographic findings characteristic of thyroid cancer, which led to diagnosis and subsequent management of RET proto-oncogene-positive MEN type 2a complicating pregnancy. PMID:23705087

Sherer, David M.; Dalloul, Mudar; Salame, Ghadir; Shah, Tana; Serur, Eli; Zinn, Harry L.; Abulafia, Ovadia

2011-01-01

335

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

336

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

337

HPV Genotype Distribution in Cervical Intraepithelial Neoplasia among HIV-Infected Women in Pune, India  

PubMed Central

Background The distribution of HPV genotypes, their association with rigorously confirmed cervical precancer endpoints, and factors associated with HPV infection have not been previously documented among HIV-infected women in India. We conducted an observational study to expand this evidence base in this population at high risk of cervical cancer. Methods HIV-infected women (N?=?278) in Pune, India underwent HPV genotyping by Linear Array assay. Cervical intraepithelial neoplasia (CIN) disease ascertainment was maximized by detailed assessment using cytology, colposcopy, and histopathology and a composite endpoint. Results CIN2+ was detected in 11.2% while CIN3 was present in 4.7% participants. HPV genotypes were present in 52.5% (146/278) and ‘carcinogenic’ HPV genotypes were present in 35.3% (98/278) HIV-infected women. ‘Possibly carcinogenic’ and ‘non/unknown carcinogenic’ HPV genotypes were present in 14.7% and 29.5% participants respectively. Multiple (?2) HPV genotypes were present in half (50.7%) of women with HPV, while multiple ‘carcinogenic’ HPV genotypes were present in just over a quarter (27.8%) of women with ‘carcinogenic’ HPV. HPV16 was the commonest genotype, present in 12% overall, as well as in 47% and 50% in CIN2+ and CIN3 lesions with a single carcinogenic HPV infection, respectively. The carcinogenic HPV genotypes in declining order of prevalence overall included HPV 16, 56, 18, 39, 35, 51, 31, 59, 33, 58, 68, 45 and 52. Factors independently associated with ‘carcinogenic’ HPV type detection were reporting ?2 lifetime sexual partners and having lower CD4+ count. HPV16 detection was associated with lower CD4+ cell counts and currently receiving combination antiretroviral therapy. Conclusion HPV16 was the most common HPV genotype, although a wide diversity and high multiplicity of HPV genotypes was observed. Type-specific attribution of carcinogenic HPV genotypes in CIN3 lesions in HIV-infected women, and etiologic significance of concurrently present non/unknown carcinogenic HPV genotypes await larger studies. PMID:22723879

Mane, Arati; Nirmalkar, Amit; Risbud, Arun R.; Vermund, Sten H.; Mehendale, Sanjay M.; Sahasrabuddhe, Vikrant V.

2012-01-01

338

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

PubMed

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

2014-04-01

339

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

340

The extent and multicentricity of high-grade prostatic intraepithelial neoplasia in clinically localized prostatic adenocarcinoma.  

PubMed

High-grade prostatic intraepithelial neoplasia (PIN) is considered the most likely precursor of invasive prostatic adenocarcinoma, and is characterized by cellular proliferations within preexisting ducts and glands with cytological changes mimicking cancer. The extent and multicentricity of this clinically important histopathologic lesion have not been fully defined. We sought to determine whether the extent and zonal distribution of PIN are related to prostate cancer. A total of 195 whole-mounted radical prostatectomy specimens were evaluated. All patients had clinically localized cancer, and none had received preoperative therapy. The zonal location and multicentricity of PIN were recorded, and the volume of PIN was measured using a grid-counting method according to pattern (tufting, micropapillary, cribriform, and flat) and spatial proximity to cancer (less than or equal to 2 mm from cancer, and greater than 2 mm from cancer). The results were correlated with patient age, prostate volume, cancer volume, pathological stage, and Gleason grade. High-grade PIN was identified in 86% of cases, usually with multiple architectural patterns of PIN in each positive case: tufting (97% of cases), micropapillary (66% of cases), cribriform (19% of cases), and flat (21% of cases). The mean volume of PIN was 1.32 cm3 (standard error [SE], 0.10; range, 0 to 8.12 cm3), and was greater for PIN within 2 mm of cancer (mean, 1.0 cm3) than for PIN more than 2 mm from cancer (mean, 0.3 cm3). PIN was usually multicentric (64.5% of cases) and located in the nontransition zone (63%) or all zones (36%) of the prostate. There was a positive correlation of total volume of PIN and volume of cancer, but this correlation was significant only for PIN within 2 mm of cancer. The volume of PIN was positively correlated with age, pathological stage, and Gleason score; most of these positive correlations were caused by PIN within 2 mm of cancer rather than that greater than 2 mm from cancer. Our results indicate that the extent and zonal distribution of high-grade PIN and carcinoma are strongly associated, and that PIN is frequently multicentric. This supports the hypothesis that PIN is a premalignant lesion. PMID:9023393

Qian, J; Wollan, P; Bostwick, D G

1997-02-01

341

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

NASA Astrophysics Data System (ADS)

Early detection of neoplasia in patients with Barrett's esophagus is essential to improve outcomes. The aim of this ex vivo study was to evaluate the ability of high-resolution microendoscopic imaging and quantitative image analysis to identify neoplastic lesions in patients with Barrett's esophagus. Nine patients with pathologically confirmed Barrett's esophagus underwent endoscopic examination with biopsies or endoscopic mucosal resection. Resected fresh tissue was imaged with fiber bundle microendoscopy; images were analyzed by visual interpretation or by quantitative image analysis to predict whether the imaged sites were non-neoplastic or neoplastic. The best performing pair of quantitative features were chosen based on their ability to correctly classify the data into the two groups. Predictions were compared to the gold standard of histopathology. Subjective analysis of the images by expert clinicians achieved average sensitivity and specificity of 87% and 61%, respectively. The best performing quantitative classification algorithm relied on two image textural features and achieved a sensitivity and specificity of 87% and 85%, respectively. This ex vivo pilot trial demonstrates that quantitative analysis of images obtained with a simple microendoscope system can distinguish neoplasia in Barrett's esophagus with good sensitivity and specificity when compared to histopathology and to subjective image interpretation.

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

2010-03-01

342

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

343

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

344

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

PubMed Central

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

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

2011-01-01

345

Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans  

PubMed Central

MENX is a recessive multiple endocrine neoplasia-like syndrome in the rat. The tumor spectrum in MENX overlaps those of human multiple endocrine neoplasia (MEN) types 1 and 2. We mapped the MenX locus to the distal part of rat chromosome 4, excluding the homologs of the genes responsible for the MEN syndromes (RET and MEN1) and syndromes with an endocrine tumor component (VHL and NF1). We report the fine mapping of the disease locus and the identification of a homozygous frameshift mutation in Cdkn1b, encoding the cyclin-dependent kinase inhibitor p27Kip1. As a consequence of the mutation, MENX-affected rats show dramatic reduction in p27Kip1 protein. We have identified a germ-line nonsense mutation in the human CDKN1B gene in a MEN1 mutation-negative patient presenting with pituitary and parathyroid tumors. Expanded pedigree analysis shows that the mutation is associated with the development of an MEN1-like phenotype in multiple generations. Our findings demonstrate that germ-line mutations in p27Kip1 can predispose to the development of multiple endocrine tumors in both rats and humans. PMID:17030811

Pellegata, Natalia S.; Quintanilla-Martinez, Leticia; Siggelkow, Heide; Samson, Elenore; Bink, Karin; Hofler, Heinz; Fend, Falko; Graw, Jochen; Atkinson, Michael J.

2006-01-01

346

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

347

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

348

Screening for colorectal cancer and advanced colorectal neoplasia in kidney transplant recipients: cross sectional prevalence and diagnostic accuracy study of faecal immunochemical testing for haemoglobin and colonoscopy  

PubMed Central

Objective To investigate whether screening kidney transplant recipients aged over 50 years for colorectal cancer with a faecal immunochemical test for haemoglobin might be justified, by determining the prevalence of advanced colorectal neoplasia and evaluating the diagnostic accuracy of faecal haemoglobin testing compared with colonoscopy in a population of kidney transplant recipients at otherwise average risk. Design Cross sectional prevalence and diagnostic accuracy study with index test of faecal haemoglobin and reference standard of colonoscopy. Setting Outpatient clinics in metropolitan and regional hospitals in South Australia. Participants 229 kidney transplant recipients aged 50 years and over, who were at least 6 months (mean 9.0 (SD 8.4) years) post-transplant and otherwise at average risk of colorectal cancer, completed the study between June 2008 and October 2011. Interventions Faecal immunochemical testing (Enterix Insure) for human haemoglobin, followed by colonoscopy with histological evaluation of retrieved samples. Main outcome measures Prevalence of advanced colorectal neoplasia, defined as an adenoma at least 10 mm in diameter, villous features, high grade dysplasia, or colorectal cancer; sensitivity, specificity, and predictive values of faecal haemoglobin testing for advanced neoplasia compared with colonoscopy. Results Advanced colorectal neoplasia was found in 29 (13%, 95% confidence interval 9% to 18%) participants, including 2% (n=4) with high grade dysplasia and 2% (n=5) with colorectal cancer. Faecal testing for haemoglobin was positive in 12% (n=28); sensitivity, specificity, and positive and negative predictive values for advanced neoplasia were 31.0% (15.3% to 50.8%), 90.5% (85.6% to 94.2%), 32.1% (15.9% to 52.4%), and 90.1% (85.1% to 93.8%). Colonoscopy was well tolerated, with no significant adverse outcomes. To identify one case of advanced neoplasia, 8 (6 to 12) colonoscopies were needed. Conclusions Kidney transplant recipients aged over 50 years have a high prevalence of advanced colorectal neoplasia. Faecal haemoglobin screening for colorectal neoplasia has similar performance characteristics in transplant recipients to those reported in general population studies, with poor sensitivity but reasonable specificity. Surveillance colonoscopy might be a more appropriate approach in this population. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12608000154303. PMID:22833618

2012-01-01

349

Magnified and enhanced computed virtual chromoendoscopy in gastric neoplasia: A feasibility study  

PubMed Central

AIM: To evaluate the feasibility of a new computed virtual chromoendoscopy (CVC) device (M i-scan) in the diagnosis of gastric neoplasia. METHODS: Patients with superficial lesions no larger than 1.0 cm found during high definition endoscopy were included. Those with advanced or obviously protruded or depressed lesions, lesions larger than 1.0 cm and/or lesions which were not amenable to observation by zoom function were excluded. The endoscopist was required to give the real-time descriptions of surface pit patterns of the lesions, based on surface pattern classification of enhanced magnification endoscopy. According to previous reports, types?I-III represent non-neoplastic lesions, and types IV-V represent neoplastic lesions. Diagnosis with M i-scan and biopsy was performed before histopathological diagnosis. Magnified images of gastric lesions with and without enhancement were collected for further analysis. The diagnostic yield of real-time M i-scan and effects on magnification image quality by tone enhancement (TE), surface enhancement (SE) and color enhancement (CE) were calculated. The selected images were sent to another endoscopist. The endoscopist rated the image quality of each lesion at 3 levels. Ratings of image quality were based on visualization of pit pattern, vessel and demarcation line. RESULTS: One hundred and eighty-three patients were recruited. Five patients were excluded for advanced gastric lesions, 1 patient was excluded for poor preparation and 2 patients were excluded for superficial lesions larger than 1.0 cm; 132 patients were excluded for no lesions found by high definition endoscopy. In the end, 43 patients with 43 lesions were included. Histopathology revealed 10 inflammation, 14 atrophy, 10 metaplasia, 1 low grade dysplasia (LGD), 5 high grade dysplasia (HGD) and 3 cancers. For 7 lesions classified into type?I, histopathology revealed 6 atrophy and 1 metaplasia; for 10 lesions classified into type II, histopathology revealed 2 inflammation, 7 atrophy and 1 metaplasia; for 10 lesions classified into type III, histopathology revealed 1 inflammation, 8 metaplasia and 1 LGD; for 9 lesions classified into type IV, histopathology revealed 4 inflammation, 1 atrophy and 4 HGD; for 7 lesions classified into type V, histopathology revealed 3 inflammation, 1 HGD and 3 cancers. A total of 172 still images, including 43 images by white light (MWL) and 129 images by M i-scan (43 with TE, 43 with SE and 43 with CE), were selected and sent to the endoscopist who did the analysis. General image quality of M i-scan with TE and SE was significantly better than that of MWL (TE, 4.55 ± 1.07; SE, 4.30 ± 1.02; MWL, 3.25 ± 0.99; P < 0.001). Visualization of pit pattern was significantly improved by M i-scan with SE (1.93 ± 0.25 vs 1.50 ± 0.50, P < 0.001). Microvessel visualization was significantly improved by M i-scan with TE (1.23 ± 0.78 vs 0.76 ± 0.73, P < 0.001). Demarcation line visualization was improved by M i-scan with both TE and SE (TE, 1.75 ± 0.52; SE, 1.56 ± 0.59; MWL, 0.98 ± 0.44; P < 0.001). M i-scan with CE did not show any significant improvements of image quality in general or in the 3 key parameters. Although M i-scan with TE and SE slightly increased the diagnostic yield of MWL, there was no significant difference (P > 0.1). CONCLUSION: Although digital enhancement improves the image quality of magnification endoscopy, its value in improving the diagnostic yield seems to be limited. PMID:23864787

Li, Chang-Qing; Li, Ya; Zuo, Xiu-Li; Ji, Rui; Li, Zhen; Gu, Xiao-Meng; Yu, Tao; Qi, Qing-Qing; Zhou, Cheng-Jun; Li, Yan-Qing

2013-01-01

350

Prevalence and predictors of Cervical Intraepithelial Neoplasia among HIV infected women at Bugando Medical Centre, Mwanza-Tanzania  

PubMed Central

Introduction Cancer of the cervix rank the second most common cause of cancer related deaths among women in Sub-Saharan Africa. It is estimated that 529, 409 new cases are diagnosed annually with a mortality rate approaching 274,883 per year. Cervical Intraepithelial Neoplasia (CIN) precedes almost all cervical cancers. The incidence rate of CIN among HIV infected women is five times higher as compared to the rate in HIV negative women. The screening for cervical dysplasia and an appropriate management in women with CIN are effective methods for preventing cervical cancer. This study was done to determine the prevalence and predictors of CIN among a HIV infected women attending Care and Treatment centre (CTC) at Bugando Medical Centre (BMC). Methods A cross sectional survey was undertaken among HIV infected women aged 18 years and above attending at BMC CTC clinic between February and March 2013. Visual Inspection with Acetic acid (VIA) was used as the screening method for detection of CIN. Socio-demographic, reproductive and clinical information was obtained from participants and the blood was collected for CD4 lymphocyte count. Cervical punch biopsy for histological examination was performed for those who had VIA positive test. Data were entered and analyzed using STATA Version 12.0 soft ware. Results A total number of 95 (26.8%) participants had positive VIA test among three hundred and fifty-five (355) HIV infected women. Histology results showed; 4(4.2%) were normal, 26 (27.4%) had an inflammatory lesion, 58(61.1%) had CIN and 7(7.3%) had invasive cervical cancer. CIN was found to be associated with a history of multiple sexual partners (P<0.001), a history of genital warts (P<0.001), and a history of STI (P = 0.010). Conclusion The Cervical Intraepithelial Neoplasia is a problem among HIV infected women. A history of multiple sexual partners, a history of genital warts, a history STI and a low baseline CD4 T lymphocyte were significant predictors for CIN. Screening for Cervical Intraepithelial Neoplasia is recommended for all women with HIV. PMID:24228805

2013-01-01

351

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

352

Differentiated vulvar intraepithelial neoplasia is often found in lesions, previously diagnosed as lichen sclerosus, which have progressed to vulvar squamous cell carcinoma  

Microsoft Academic Search

Lichen sclerosus is considered to be the precursor lesion of vulvar squamous cell carcinoma, of which only 2–5% progress to squamous cell carcinoma. Differentiated vulvar intraepithelial neoplasia (VIN) has been proposed to be the direct precursor lesion, but this is a recently recognized, and a difficult to diagnose, entity, which may easily be mistaken for a benign dermatosis. The aim

Hedwig P van de Nieuwenhof; Johan Bulten; Harrie Hollema; Rianne G Dommerholt; Leon F A G Massuger; Ate G J van der Zee; Joanne A de Hullu; Leon C L T van Kempen

2011-01-01

353

High level of SOX9 in the prostate contributes to increased proliferation and can cooperate with PTEN loss to accelerate neoplasia formation  

PubMed Central

Developmental pathways have been shown to be important in the initiation and progression of cancer in various tissues. We showed that the transcription factor SOX9 is expressed in the epithelia of the mouse embryonic prostate and is required for proper prostate development. We have performed an in vivo investigation into the role of SOX9 in prostate cancer in mouse and human. Studies on Pten and Nkx3.1 mutant mice show that cells with an increased level of SOX9 appear within the epithelia at the early stages of prostate neoplasia and this high expression correlates with all stages of neoplastic progression. Using genetically modified mice we show that overexpression of SOX9 in prostate epithelia leads to an increase in cell proliferation without inducing hyperplasia. In mice that were heterozygous for the conditional mutant allele of Pten, overexpression of SOX9 gave rise to an earlier induction of high-grade prostate intraepithelial neoplasia. Consistent with this role, loss of Sox9 in prostate epithelia led to a decrease in proliferating cells in normal and in homozygous Pten mutant mice with prostate neoplasia. Analysis of a cohort of 880 human prostate cancer samples showed that SOX9 expression is associated with increasing Gleason grades and higher Ki67 staining. These studies identify SOX9 as part of a developmental pathway that is reactivated in prostate neoplasia where it is involved in regulating proliferation and suggests it can contribute to carcinogenesis in specific genetic contexts. PMID:20103652

Thomsen, Martin K.; Ambroisine, Laurence; Wynn, Sarah; Cheah, Kathryn S. E.; Foster, Christopher S.; Fisher, Gabrielle; Berney, Daniel M.; M?ller, Henrik; Reuter, Victor E.; Scardino, Peter; Cuzick, Jack; Ragavan, Narasimhan; Singh, Paras B.; Martin, Francis L.; Butler, Christopher M.; Cooper, Colin S.; Swain, Amanda

2010-01-01

354

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...

355

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

Abstract 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

2014-09-20

356

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...

357

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

358

Mutation Analysis of Glial Cell Line-Derived Neurotrophic Factor, a Ligand for an RET\\/Coreceptor Complex, in Multiple Endocrine Neoplasia Type 2 and Sporadic Neuroendocrine Tumors  

Microsoft Academic Search

Causative germline missense mutations in the RET proto-onco- gene have been associated with over 92% of families with the inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN 2). MEN 2A is characterized primarily by medullary thyroid carcinoma (MTC) and pheochromocytoma, both tumors of neural crest origin. Parathy- roid hyperplasia or adenoma is also seen in MEN 2A, but rarely

DEBBIE J. MARSH; ZIMU ZHENG; ANDREW ARNOLD; SCOTT D. ANDREW; DIANA LEAROYD; ANDREA FRILLING; PAUL KOMMINOTH; HARTMUT P. H. NEUMANN; BRUCE A. J. PONDER; BARRETT J. ROLLINS; GEOFFREY I. SHAPIRO; BRUCE G. ROBINSON; LOIS M. MULLIGAN; CHARIS ENG

359

Entrevistas con Eduardo Pavlovsky  

E-print Network

ahora se estudia con microcirugía es que cada golpe produce una microhemorragia; es decir, que no se ven a la visión normal pero cuando haces una autopsia, te das cuenta que el cerebro del boxeador tiene microhemorragias. De alguna manera los...

Giella, Miguel Á ngel

1985-10-01

360

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

PubMed Central

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

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

2013-01-01

361

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

PubMed Central

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

Bang, Ji Young

2014-01-01

362

Villoglandular papillary adenocarcinoma of cervix associated with cervical intraepithelial neoplasia: a case report and review of literature.  

PubMed

Well differentiated villoglandular adenocarcinoma of uterine cervix is a rare tumour which usually occurs in young women. It is considered to be an indolent tumour with favorable prognosis and most of them were treated by conservative procedures. We report a 35 year old lady who came with complaints of 3 months amenorrhoea and an episode of spontaneous bleeding. Urine pregnancy test was negative. Physical examination revealed a cervical polyp. Histopathological findings were consistent with villoglandular papillary adenocarcinoma associated with high grade cervical intraepithelial neoplasia (CIN-3). Left parametrial and left ureteral involvement, proved by biopsy, causing left hydroureteronephrosis was detected. The patient was thus found to be in an advanced stage, stage- III b (FIGO). The patient is currently undergoing radiotherapy. A review of literature showed that only occasional cases showing disease spread have been reported, suggesting caution in the management and regular follow up of the patient. PMID:18306568

Srilatha, P S; Roy, Alfred

2007-10-01

363

Effects of MDM2 promoter polymorphisms on the development of cervical neoplasia in a Southeastern Brazilian population.  

PubMed

Abstract We investigated the importance of two adjacent functional polymorphisms in the Murine Double Minute 2 (MDM2) gene, SNP285 G?>?C and SNP309 T?>?G, for the development of cervical lesions in a Southeastern Brazilian population (293 cases and 184 controls). MDM2 genotyping was performed by PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) and/or DNA sequencing. MDM2 SNP309 has potential as a biomarker of cervical neoplasia in non-smokers, patients with family history of cancer, or those who had late sexual debut (>16 years). Besides, this polymorphism may help identify women at risk of developing severe cervical lesion at a young age (<30 years). PMID:25271042

Vargas-Torres, Sandra Liliana; Portari, Elyzabeth Avvad; Klumb, Evandro Mendes; Guillobel, Heloisa Carneiro da Rocha; Camargo, Maria José de; Russomano, Fábio Bastos; Macedo, Jacyara Maria Brito

2014-12-01

364

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

365

Cognitive behavioural therapy for depression in multiple endocrine neoplasia type IIB: a 1-year follow-up.  

PubMed

This case report describes a 24-year-old man diagnosed with multiple endocrine neoplasia type IIB and major depression. Because cognitive behavioural therapy (CBT) has proven effective in the treatment of major depression in the general population and patients with cancer, we decided to adapt and use this therapy and evaluate its impact on major depression and the patient's quality of life. The therapy was conducted individually in 15 sessions that were given over a span of 25?weeks. The data show that therapy was a useful treatment that reduced depression according to the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria and self-report instruments. CBT also helped improve the patient's quality of life, and it was considered to be an acceptable intervention for the patient, with ongoing positive results 1?year after the last psychotherapy session. CBT is a potential option for treating depression in this population but further research is needed. PMID:24898996

Mejía-Castrejón, Jessica; Landa-Ramírez, Edgar

2014-01-01

366

The Expanding Family of SMARCB1(INI1)-deficient Neoplasia: Implications of Phenotypic, Biological, and Molecular Heterogeneity.  

PubMed

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

Agaimy, Abbas

2014-11-01

367

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

PubMed Central

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

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

2014-01-01

368

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

369

The Con Test  

ERIC Educational Resources Information Center

In this article, the author describes the format of the Con Test, an Australian television game show which followed the same general rules and game play as the UK show PokerFace. At the end of each round a contestant needs to decide whether or not he or she should fold. A contestant needs to know how likely it is that he or she is in last place.…

Fletcher, Michael

2009-01-01

370

Burning wood in the kitchen increases the risk of cervical neoplasia in HPV-infected women in Honduras.  

PubMed

There is suggestive evidence that the use of wood for cooking increases the risk of invasive cervical cancer. We investigated this association in women with cervical neoplasia in Honduras. Women aged 20-64 years with cervical intraepithelial neoplasia (CIN) grade I (n = 44), CIN II (n = 36) or CIN III (n = 45) were recruited from screening programs in Tegucigalpa City and each was matched by age and clinic to 2 controls (241 total) without cervical abnormalities. The clinics selected women of low socioeconomic status. Cervical scrapes were tested for the presence of human papillomavirus (HPV) DNA using a general primer set directed against the L1 open reading frame, and HPV genotyping was performed. Odds ratios (ORs) were computed through conditional logistic regression; p-values were from tests for linear trend of risk with increasing exposure. HPV DNA was detected in 48% of women with CIN I, 67% with CIN II and 89% with CIN III. The ORs were 1.5, 2.5 and 38.3 respectively. At univariate analysis, age at first intercourse was consistently lower among cases than controls. Risk was reduced by 50% or more in all 3 CIN classes when initiation of sexual activity at age 20 years or older was compared with initiation before age 16 years (p = 0.013 for CIN I). No effect was observed for smoking, oral contraceptives or previous cytologic screening. Effects for number of sexual partners, parity, age at first pregnancy and education were in the expected directions but never persisted after adjustment for HPV. Chronic exposure to wood smoke significantly increased the risk of CIN III (p = 0.022). However, women who said "No" when asked if they ever used wood in the kitchen had a higher risk than those with low or intermediate exposure. This was taken as evidence that the initial screening question had either been misunderstood or that answers were biased. Restricting the analysis to women who reported exposure yielded positive associations in all CIN classes with for CIN III ORs of 2.3 for 25-34 and 9.5 for 35+ years compared with women who had 1-14 years of exposure (p = 0.017). A multivariate analysis of the complete dataset (n = 366) allowed for separate ORs for HPV in each CIN class. Inclusion of age at first intercourse significantly improved this model (p = 0.021). Adding exposure to wood smoke further improved the model only if an interaction between woodsmoke and HPV was allowed for. If, as the data suggest, it was assumed that wood smoke had its effect among HPV-positives only, there was a significant linear dose-response relationship between exposure to woodsmoke and risk of CIN (p = 0.026). This association was independent of other risk factors including education, parity and number of sexual partners. ORs in the final model were 0.37 for age at first intercourse 20 years or higher and 5.69 for more than 35 years of exposure to wood burning in the kitchen. The present study suggests that the use of wood for cooking is a risk factor for cervical neoplasia that deserves further study, given its high prevalence in developing countries. PMID:11802219

Velema, Johan P; Ferrera, Annabelle; Figueroa, Manuel; Bulnes, Ricardo; Toro, Luis A; de Barahona, Odessa; Claros, Jose M; Melchers, Willem J G

2002-02-01

371

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

372

Dicer Is Required for Maintenance of Adult Pancreatic Acinar Cell Identity and Plays a Role in Kras-Driven Pancreatic Neoplasia  

PubMed Central

The role of miRNA processing in the maintenance of adult pancreatic acinar cell identity and during the initiation and progression of pancreatic neoplasia has not been studied in detail. In this work, we deleted Dicer specifically in adult pancreatic acinar cells, with or without simultaneous activation of oncogenic Kras. We found that Dicer is essential for the maintenance of acinar cell identity. Acinar cells lacking Dicer showed increased plasticity, as evidenced by loss of polarity, initiation of epithelial-to-mesenchymal transition (EMT) and acinar-to-ductal metaplasia (ADM). In the context of oncogenic Kras activation, the initiation of ADM and pancreatic intraepithelial neoplasia (PanIN) were both highly sensitive to Dicer gene dosage. Homozygous Dicer deletion accelerated the formation of ADM but not PanIN. In contrast, heterozygous Dicer deletion accelerated PanIN initiation, revealing complex roles for Dicer in the regulation of both normal and neoplastic pancreatic epithelial identity. PMID:25405615

Wang, Yue J.; McAllister, Florencia; Bailey, Jennifer M.; Scott, Sherri-Gae; Hendley, Audrey M.; Leach, Steven D.; Ghosh, Bidyut

2014-01-01

373

Nam Con Son Basin  

SciTech Connect

The Nam Con Son basin is the largest oil and gas bearing basin in Vietnam, and has a number of producing fields. The history of studies in the basin can be divided into four periods: Pre-1975, 1976-1980, 1981-1989, and 1990-present. A number of oil companies have carried out geological and geophysical studies and conducted drilling activities in the basin. These include ONGC, Enterprise Oil, BP, Shell, Petro-Canada, IPL, Lasmo, etc. Pre-Tertiary formations comprise quartz diorites, granodiorites, and metamorphic rocks of Mesozoic age. Cenozoic rocks include those of the Cau Formation (Oligocene and older), Dua Formation (lower Miocene), Thong-Mang Cau Formation (middle Miocene), Nam Con Son Formation (upper Miocene) and Bien Dong Formation (Pliocene-Quaternary). The basement is composed of pre-Cenozoic formations. Three fault systems are evident in the basin: north-south fault system, northeast-southwest fault system, and east-west fault system. Four tectonic zones can also be distinguished: western differentiated zone, northern differentiated zone, Dua-Natuna high zone, and eastern trough zone.

Tin, N.T.; Ty, N.D.; Hung, L.T.

1994-07-01

374

The most common chromosome aberration detected by high-resolution comparative genomic hybridization in vulvar intraepithelial neoplasia is not seen in vulvar squamous cell carcinoma  

Microsoft Academic Search

We analyzed genetic changes in condylomas (four cases), vulvar intraepithelial neoplasia I–III (VIN I–III, eleven cases), and primary vulvar squamous cell carcinomas (VSCC, ten cases) by high-resolution comparative genomic hybridization (HR-CGH) and flowcytometry. All samples were also human papilloma virus (HPV)-genotyped. Gain of chromosome 1, the aberration most often seen in VIN III (67%), was not seen in HPV-positive or

T. Bryndorf; M. Kirchhoff; J. Larsen; B. Andreasson; B. Bjerregaard; H. Westh; H. Rose; C. Lundsteen

2004-01-01

375

Specific intraepithelial localization of mast cells in differentiated vulvar intraepithelial neoplasia and its possible contribution to vulvar squamous cell carcinoma development  

Microsoft Academic Search

AIMS: The aetiology of vulvar squamous cell carcinomas (SCC) that are not causally associated with high-risk human papillomavirus remains largely elusive. The aim of this study was to analyse the inflammatory response in its presumed precursor lesions, lichen sclerosus (LS) and differentiated vulvar intraepithelial neoplasia (dVIN), and provide evidence that dVIN is a likely precursor of vulvar SCC. METHODS AND

H. P. van de Nieuwenhof; K. M. Hebeda; J. Bulten; I. Otte-Holler; L. F. A. G. Massuger; J. A. de Hullu; L. C. L. T. van Kempen

2010-01-01

376

Anti-HPV16 E2 protein T-cell responses and viral control in women with usual vulvar intraepithelial neoplasia and their healthy partners  

Microsoft Academic Search

T-cell responses (proliferation, intracellular cytokine synthesis and IFN? ELISPOT) against human papillomavirus 16 (HPV16) E2 peptides were tested during 18 months in a longitudinal study in eight women presenting with HPV16-related usual vulvar intraepithelial neoplasia (VIN) and their healthy male partners. In six women, anti-E2 proliferative responses and cytokine production (single IFN? and\\/or dual IFN?\\/IL2 and\\/or single IL2) by CD4+

Remi Cheynier

2012-01-01

377

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

378

COMMENTS Molecular Analysis of the ret and GDNF Genes in a Family with Multiple Endocrine Neoplasia Type 2A and Hirschsprung Disease  

Microsoft Academic Search

The clinical association between multiple endocrine neoplasia type 2 (MEN2) and Hirschsprung disease (HSCR) is infrequent. Germline mutations of the ret protooncogene are the underlying cause of the MEN2 syndromes and a proportion of cases of HSCR. In this report, we describe a new kindred in which the MEN2 and HSCR phenotypes are associated with a single C620S point mutation

SALUD BORREGO; CHARIS ENG; BEATRIZ SANCHEZ; MARIA-EUGENIA SAEZ; ELENA NAVARRO; GUILLERMO ANTINOLO

2010-01-01

379

Single oligoarray-based detection of specific M918T mutation in RET oncogene in multiple endocrine neoplasia type 2B  

Microsoft Academic Search

The most important mutation associated with Multiple Endocrine Neoplasia type 2B (MEN 2B) is the change of thymine to cytosine\\u000a in codon 918 of exon 16 in the RET oncogene (ATG ? ACG). The aim of this work was to develop a single oligoarray by using tandem hybridization to detect the\\u000a T918C\\/RET mutation for MEN 2B patients. Two genetically non-related families were

R. A. Pacheco-Rivera; E. Hernández-Zamora; B. González-Yebra; K. Beattie; R. Maldonado-Rodríguez; J. C. Santiago-Hernández; M. E. Medrano-Ortiz de Zárate; M. Salcedo

380

Pancreatic -Cell-specific Ablation of the Multiple Endocrine Neoplasia Type 1 (MEN1) Gene Causes Full Penetrance of Insulinoma Development in Mice1  

Microsoft Academic Search

The function of the predisposition gene to multiple endocrine neoplasia type 1 (MEN1) syndrome remains largely unknown. Previous studies demonstrated that null mutation of the Men1 gene caused mid-gestation lethality in mice, whereas heterozygous Men1 knockout mice developed multiple endocrine tumors late in life. To seek direct evidence on the causal role of menin in suppressing tumor development, we generated

Philippe Bertolino; Wei-Min Tong; Pedro Luis Herrera; Huguette Casse; Chang Xian Zhang; Zhao-Qi Wang

2003-01-01

381

Differential Expression of Erythropoietin and Its Receptor in von Hippel-LindauAssociated and Multiple Endocrine Neoplasia Type 2Associated Pheochromocytomas  

Microsoft Academic Search

Pheochromocytoma is a neuroendocrine tumor associated with a va- riety of genetic disorders, which include von Hippel-Lindau disease (VHL), multiple endocrine neoplasia type 2 (MEN 2), neurofibroma- tosis type 1, hereditary paraganglioma, and succinate dehydrogenase gene-related tumors. Previous studies of VHL-associated and MEN 2-associated pheochromocytomas suggest morphological, biochemi- cal, and clinical differences exist among the tumors, but the process by

Timothy W. A. Vogel; Frederieke M. Brouwers; Irina A. Lubensky; Alexander O. Vortmeyer; Robert J. Weil; McClellan M. Walther; Edward H. Oldfield; W. Marston Linehan; Karel Pacak; Zhengping Zhuang

2010-01-01

382

RET Germline Mutations Identified by Exome Sequencing in a Chinese Multiple Endocrine Neoplasia Type 2A\\/Familial Medullary Thyroid Carcinoma Family  

Microsoft Academic Search

BackgroundWhole exome sequencing provides a labor-saving and direct means of genetic diagnosis of hereditary disorders in which the pathogenic gene harbors a large cohort of exons. We set out to demonstrate a suitable example of genetic diagnosis of MEN 2A\\/FMTC (multiple endocrine neoplasia type 2\\/familial medullary thyroid carcinoma) using this approach.Methodology\\/Principal FindingsWe sequenced the whole exome of six individuals from

Xiao-Ping Qi; Ju-Ming Ma; Zhen-Fang Du; Rong-Biao Ying; Jun Fei; Hang-Yang Jin; Jian-Shan Han; Jin-Quan Wang; Xiao-Ling Chen; Chun-Yue Chen; Wen-Ting Liu; Jia-Jun Lu; Jian-Guo Zhang; Xian-Ning Zhang; Amanda Ewart Toland

2011-01-01

383

Living with Multiple Endocrine Neoplasia Type 1: Decent Care-Insufficient Medical and Genetic Information A Qualitative Study of MEN 1 Patients in a Swedish Hospital  

Microsoft Academic Search

This qualitative study explores how 29 Swedish patients with Multiple Endocrine Neoplasia type 1 (MEN1) experience living\\u000a with the condition, appraisal of the clinical follow-up program, and surveys their future expectations. The aim of this study\\u000a is to build knowledge about this patient group in order to provide optimal care. The participants describe physical, psychological,\\u000a and social limitations in their

Nina Strømsvik; Karin Nordin; Gunilla Berglund; Lars F. Engebretsen; Mats G. Hansson; Eva Gjengedal

2007-01-01

384

Comparison of thoracic radiographs and single breath-hold helical CT for detection of pulmonary nodules in dogs with metastatic neoplasia.  

PubMed

Imaging studies in people indicate that x-ray computed tomography (CT) is a more sensitive technique than thoracic radiography for the detection of pulmonary metastasic neoplasia. Systematic studies comparing CT and thoracic radiographic techniques in veterinary patients have not been performed. The present retrospective study was designed to directly compare the efficacy of these 2 techniques in detecting pulmonary nodules in dogs. Eighteen dogs with histologically confirmed pulmonary metastatic neoplasia had contemporaneous thoracic radiographs and pulmonary CT scans compared. Quantitative analyses included estimation of pulmonary nodule size, number, and lobar distribution on thoracic radiographs and CT images. Only 9% of CT-detected pulmonary nodules were identified on thoracic radiographs (P < .003). The lower size threshold was approximately 1 mm to detect pulmonary nodules on CT images and 7-9 mm to reliably detect nodules on radiographs (P < .0001). Additionally, pulmonary nodules were detected in a significantly greater number of lung lobes using CT as compared with thoracic radiographs (P < .0001). These data indicate that CT is significantly more sensitive than thoracic radiography for detecting soft-tissue nodules in dogs. As such, thoracic CT should be considered in any patient with neoplasia that has potential for pulmonary metastasis to more reliably stage the disease, particularly when accurate characterization of the extent and distribution of pulmonary metastatic disease affects therapeutic planning. PMID:16734082

Nemanic, Sarah; London, Cheryl A; Wisner, Erik R

2006-01-01

385

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

386

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

387

[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

388

Elevated level of anterior gradient-2 in pancreatic juice from patients with pre-malignant pancreatic neoplasia  

PubMed Central

Background Pancreatic intraepithelial neoplasias (PanINs) are precursors of malignant pancreatic cancer, an ideal stage for early cancer detection. We applied quantitative proteomics to identify aberrantly elevated proteins in pancreatic juice samples derived from patients with PanIN3. Results Twenty proteins were found elevated in all three PanIN juices by at least two-fold. Among these proteins, anterior gradient-2 (AGR2) was found to be 2-10 fold elevated in PanIN3 juice samples analyzed by quantitative proteomics. An ELISA assay was developed to evaluate AGR2 levels in 51 pancreatic juice samples and 23 serum samples from patients with pancreatic cancer, pre-malignant lesions (including PanIN3, PanIN2, Intraductal Papillary Mucinous Neoplasms (IPMNs)) and benign disease controls (including chronic pancreatitis). AGR2 levels in the pancreatic juice samples were found significantly elevated in patients with pre-malignant conditions (PanINs and IPMNs) as well as pancreatic cancer compared to control samples (p ? 0.03). By ROC analysis, the AGR2 ELISA achieved 67% sensitivity at 90% specificity in predicting PanIN3 juice samples from the benign disease controls. Conclusions These results suggest that elevation of AGR2 levels in pancreatic juice occurs in early pancreatic cancer progression and could be further investigated as a potential candidate juice biomarker for early detection of pancreatic cancer. PMID:20550709

2010-01-01

389

RET gene mutations (genotype and phenotype) of multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma.  

PubMed

The rapid technical advances in molecular biology and accelerating improvements in genomic and proteomic diagnostics have led to increasingly personalized strategies for cancer therapy. Such an approach integrates the genomic, proteomic, and molecular information unique to the individual to provide an accurate genetic diagnosis, molecular risk assessment, informed family counseling, therapeutic profiling, and early preventative management that best fits the particular needs of each patient. The discovery of mutations in the RET proto-oncogene resulting in variable onset and severity of multiple endocrine neoplasia type 2 (MEN2) was the first step in developing direct genetic testing for at-risk individuals. Patients with germline RET mutations may undergo risk assessment and appropriate intervention based on specific mutations. Moreover, family members of affected individuals receive counseling based on understanding of the genetic transmission of the disease. Increasingly, clinicians are able to make therapeutic choices guided by an informative biomarker code. Improvements in detection and management of patients with MEN2 resulting from understanding of the RET proto-oncogene are evidence of the benefits of personalized cancer medicine. This review describes the discovery of the RET proto-oncogene, the association between genotype and phenotype, and the role of mutation analysis on diagnosis and treatment of MEN2. PMID:24699901

Krampitz, Geoffrey W; Norton, Jeffrey A

2014-07-01

390

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

PubMed

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

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

2014-08-01

391

Periampullary localized pancreatic intraepithelial neoplasia-3 (PanIN-3): evaluation with contrast-enhanced MR cholangiography (MRCP)  

PubMed Central

Background The early determination of premalignant lesions of pancreas can prevent unnecessary excessive surgical procedures and can reduce morbidity and mortality. Pancreatic intraepithelial neoplasia-3 (PanIN-3) is a preinvasive form of adenocarcinoma (carcinoma in situ). PanINs have not taken place in the literature of radiology yet, it should be considered in differential diagnosis of pancreatic cystic lesions. Case report A patient with preliminary diagnosis of chronic cholecystitis who had choledocolithiasis and periampullary pancreatic cyst detected by noncontrast-enhanced (NCE) and contrast-enhanced (CE) magnetic resonance cholangiography (MRCP) is presented. Pathological examination results of gallbladder and pancreatic cyst were reported as gallbladder adenocarcinoma and PanIN-3, respectively. Conclusions Pancreatic cystic lesions with thin septa which enhances slightly with the administration of contrast material may represent PanIN-3. In patients with cystic pancreatic lesion localized at periampullary region, using CE-MRCP together with NCE-MRCP could be useful in the evaluation of pancreatic cystic masses as well as other abdominal pathologies. PMID:22933970

Algin, Oktay; Ozmen, Evrim; Ersoy, Pamir Eren; Karaoglanoglu, Mustafa

2011-01-01

392

No evidence for post-transcriptional control of albumin and alpha-fetoprotein gene expression in developing rat liver neoplasia.  

PubMed Central

Rot analysis of hybridization data using highly labeled alpha-fetoprotein (AFP) and albumin (32P)cDNA probes has been used to quantitate AFP and albumin mRNA sequences in RNA preparations from different subcellular fractions of developing rat liver and Morris hepatoma 7777. In addition, size analysis of these mRNA sequences has been carried out by electrophoretic fractionation on agarose gels containing methylmercury hydroxyde and hybridization to radioactive cloned albumin and AFP cDNA probes. In all the tissues examined (fetal, newborn and adult rat liver, and hepatoma 7777) most of the albumin and AFP mRNA sequences were found associated with the polysomes as mature mRNA molecules; less than 2% of these sequences were present in the nuclear or the non polysomal cytoplasmic compartments. The number of AFP mRNA molecules was found to decrease in parallel in all the cellular compartments during rat liver development. In Morris hepatoma 7777 the content of albumin mRNA was considerably decreased in all the cellular fractions as compared to normal liver. These results demonstrate that post-transcriptional control mechanisms leading to an accumulation of non-functional mRNA molecules are not implicated in the changes of expression of albumin and AFP genes during rat liver development and neoplasia. Images PMID:6176942

Nahon, J L; Gal, A; Frain, M; Sell, S; Sala-Trepat, J M

1982-01-01

393

[Multiple endocrine neoplasia type I or Werner syndrome. What is important to know about surgery of a rate disease].  

PubMed

Multiple endocrine neoplasia type 1 (MEN1) is a rare but misleading disease. The diagnosis is evocated when two main lesions are present (parathyroid, endocrine pancreas, pituary gland) but also when a family tree shows recurrent lesions. Other lesions must be taken into account (adrenal glands, neuroendocrine thymic or bronchic lesions, cutaneous lesions, lipomas, nervous central system tumors). Any surgical cure without knowing the MEN1 background leads to failure. Specific treatment of each lesion is reviewed. Genetic diagnosis is possible but the mutation is not found in all cases. Nevertheless, when the mutation is known in a family, a negative genetic test allows to exclude the disease. Prognosis is related to hepatic metastases and to thymic neuroendocrine tumors which are rare (2.1%) but aggressive. As a general rule, any apparently isolated endocrine lesion such hyperparathyroidism must prompt the surgeon to look for another endocrine lesion and to look for an abnormal family tree with recurent monoglandular or pluriglandular lesions. PMID:12491633

Goudet, P; Calender, A; Cougard, P; Murat, A; Henry, J F; Kraimps, J L; Cadiot, G; Peix, J L; Sarfati, E; Mignon, M; Proye, C

2002-10-01

394

Epigenetic inactivation of the candidate tumor suppressor USP44 is a frequent and early event in colorectal neoplasia.  

PubMed

In mouse models, loss of the candidate tumor suppressor gene Ubiquitin Specific Protease 44 (USP44) is associated with aneuploidy and cancer. USP44 is also transcriptionally silenced in human cancers. Here we investigated the molecular mechanism of USP44 silencing and whether this correlated with aneuploidy in colorectal adenomas. DNA methylation at the USP44 CpG island (CGI) promoter was measured using combined bisulfite restriction analysis (COBRA) in colorectal cancer (CRC) cell lines (n = 18), and with COBRA and bisulfite sequencing in colorectal adenomas (n = 89) and matched normal colonic mucosa (n = 51). The USP44 CGI was hypermethylated in all CRC cell lines, in most colorectal adenomas (79 of 89, 89%) but rarely in normal mucosa samples (3 of 51, 6%). USP44 expression was also compared between normal mucosa and paired hypermethylated adenomas in six patients using qRT-PCR. Hypermethylation of the USP44 CGI in adenomas was associated with a 1.8 to 5.5-fold reduction in expression compared with paired normal mucosa. Treatment of CRC cell lines with the DNA hypomethylating agent decitabine resulted in a 14 to 270-fold increase in USP44 expression. Whole genome SNP array data showed that gain or loss of individual chromosomes occurred in adenomas, but hypermethylation did not correlate with more aneuploidy. In summary, our data shows that USP44 is epigenetically inactivated in colorectal adenomas, but this alone is not sufficient to cause aneuploidy in colorectal neoplasia. PMID:24837038

Sloane, Mathew A; Wong, Jason Wh; Perera, Dilmi; Nunez, Andrea C; Pimanda, John E; Hawkins, Nicholas J; Sieber, Oliver M; Bourke, Michael J; Hesson, Luke B; Ward, Robyn L

2014-08-01

395

Methylenetetrahydrofolate Reductase C677T Polymorphism and Susceptibility to Cervical Cancer and Cervical Intraepithelial Neoplasia: A Meta-Analysis  

PubMed Central

Background A number of studies have explored the association between methyl enetetrahydrofolate reductase (MTHFR) C677T polymorphism and susceptibility to cervical cancer and cervical intraepithelial neoplasia (CIN). However, results remained controversial. To address this gap, we decided to conduct a meta-analysis of all available published studies. Methods Electronic literature searches of the PubMed, EmBase and Medline databases were performed up to April 30, 2012. Fixed-effects or random-effects model was used to calculate the pooled ORs for different genetic models. Results A total of 12 case-control studies were ultimately identified. No statistical correlation was found between C677T variants and cervical cancer for the overall population. However, subgroup analyses on the White women pointed to a significant protective effect for individuals heterozygous or homozygous for the T-allele (for CT vs. CC: OR?=?0.72, 95% CI 0.59–0.88; for TT vs. CC: OR?=?0.69, 95% CI?=?0.49–0.97; for CT+TT vs. CC: OR?=?0.71, 95% CI 0.59–0.86). C677T variants were associated with neither combined nor stratified CIN among the overall population. Conclusions This meta-analysis suggests that White women with mutant C677T genotypes might have a lower risk of cervical cancer, yet lacking enough statistical robustness. Further investigations are needed to get more insight into the role of this polymorphism in cervical carcinogenesis. PMID:23029458

Zhang, Qiong Hua; Hu, Ting Ting; Luo, Min Hong; Li, Mei Qing; Chen, Qing

2012-01-01

396

Decreased expression of retinoic acid receptors, transforming growth factor beta, involucrin, and cornifin in cervical intraepithelial neoplasia.  

PubMed

Cervical intraepithelial neoplasia (CIN) I, II, and III represent a spectrum of premalignant epithelial changes and are ideal targets for application of chemoprevention strategies. Intermediate end point biomarkers are increasingly being used as surrogate end points to monitor clinical chemoprevention trials. To identify potential biomarkers in cervical epithelium, we analyzed the expression of nuclear retinoic acid receptor (RAR) mRNA by in situ hybridization, involucrin, cornifin, and transforming growth factors (TGFs) beta1 and beta2 by immunohistochemistry in cervical specimens, which contained adjacent normal epithelium and CIN lesions from 52 patients. These biomarkers were expressed in all adjacent normal cervical epithelia, whereas all CIN lesions including CIN I, CIN II, and CIN III exhibited decreased expression of RAR-alpha by 55.8%, RAR-beta by 64.7%, RAR-gamma by 54.9%, involucrin by 80.8%, cornifin by 88.5%, TGF-beta1 by 89.7%, and TGF-beta2 by 85.7%. Viewed as a whole, these biomarkers were down-regulated in 100% of the CIN lesions. Because all of these biomarkers can be modulated in vitro by retinoids, they may serve as intermediate biomarkers for retinoid chemoprevention trials in the patients with CIN lesions. PMID:10389939

Xu, X C; Mitchell, M F; Silva, E; Jetten, A; Lotan, R

1999-06-01

397

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

398

Evaluation of HPV infection and smoking status impacts on cell proliferation in epithelial layers of cervical neoplasia.  

PubMed

Accurate cervical intra-epithelial neoplasia (CIN) lesion grading is needed for effective patient management. We applied computer-assisted scanning and analytic approaches to immuno-stained CIN lesion sections to more accurately delineate disease states and decipher cell proliferation impacts from HPV and smoking within individual epithelial layers. A patient cohort undergoing cervical screening was identified (n?=?196) and biopsies of varying disease grades and with intact basement membranes and epithelial layers were obtained (n?=?261). Specimens were sectioned, stained (Mib1), and scanned using a high-resolution imaging system. We achieved semi-automated delineation of proliferation status and epithelial cell layers using Otsu segmentation, manual image review, Voronoi tessellation, and immuno-staining. Data were interrogated against known status for HPV infection, smoking, and disease grade. We observed increased cell proliferation and decreased epithelial thickness with increased disease grade (when analyzing the epithelium at full thickness). Analysis within individual cell layers showed a ?50% increase in cell proliferation for CIN2 vs. CIN1 lesions in higher epithelial layers (with minimal differences seen in basal/parabasal layers). Higher rates of proliferation for HPV-positive vs. -negative cases were seen in epithelial layers beyond the basal/parabasal layers in normal and CIN1 tissues. Comparing smokers vs. non-smokers, we observed increased cell proliferation in parabasal (low and high grade lesions) and basal layers (high grade only). In sum, we report CIN grade-specific differences in cell proliferation within individual epithelial layers. We also show HPV and smoking impacts on cell layer-specific proliferation. Our findings yield insight into CIN progression biology and demonstrate that rigorous, semi-automated imaging of histopathological specimens may be applied to improve disease grading accuracy. PMID:25210770

Guillaud, Martial; Buys, Timon P H; Carraro, Anita; Korbelik, Jagoda; Follen, Michele; Scheurer, Michael; Storthz, Karen Adler; van Niekerk, Dirk; MacAulay, Calum E

2014-01-01

399

Risk Factors for the Presence of Anal Intraepithelial Neoplasia in HIV+ Men Who Have Sex with Men  

PubMed Central

Objective Anal Intraepithelial Neoplasia (AIN) is present in the majority of HIV+ men who have sex with men (MSM) and routine AIN-screening is subject of discussion. In this study we analysed a wide range of potential risk factors for AIN in order to target screening programs. Methods We screened 311 HIV+ MSM by high resolution anoscopy, with biopsies of suspect lesions. HIV-parameters, previous sexual transmitted infections (STI’s), anal pathology, sexual practices and substance use were analysed in relation to AIN by uni- and multivariable logistic regression. Results AIN (any grade) was found in 175/311 MSM (56%), high grade (HG)AIN in 30%. In the univariable analysis, years since HIV diagnosis, years of antiretroviral therapy (cART) and anal XTC use decreased AIN risk, while a history of anogenital warts and use of GHB (?-hydroxybutyric acid) increased this risk. In the multivariable analysis three parameters remained significant: years of cART (OR=0.92 per year, p=0.003), anal XTC use (OR=0.10, p=0.002) and GHB use (OR=2.60, p=0.003). No parameters were significantly associated with HGAIN, but there was a trend towards increased risk with anal enema use prior to sex (>50 times ever; p=0.07) and with a history of AIN (p=0.06). CD4 count, STI’s, anal pathology, smoking, number of sex partners and anal fisting were not associated with (HG)AIN. Conclusion GHB use increases the risk for AIN, while duration of cART and anal XTC use are negatively correlated with AIN. Given the high prevalence of AIN in HIV+ MSM, these associations are not helpful to guide a screening program. PMID:24367625

Richel, Olivier; De Vries, Henry J. C.; Dijkgraaf, Marcel G. W.; Van Noesel, Carel J. M.; Prins, Jan M.

2013-01-01

400

Risk evaluation for the development of cervical intraepithelial neoplasia: Development and validation of risk-scoring schemes.  

PubMed

Cervical cancer screening guidelines do not comprehensively define what constitutes high risk. This study developed and validated simple risk-scoring schemes to improve Papanicolaou smear screening for women at high risk. Four cumulative risk score (CRS) schemes were derived respectively for the development of cervical intraepithelial neoplasia grade 1 (CIN1) and grade 2 or worse (CIN2+) using community-based case-control data (n?=?1523). By calculating the area under the receiver operating characteristic (AU-ROC) curve, these schemes were validated in a Papanicolaou smear follow-up cohort (n?=?967) and a hospital-based cytology screening population (n?=?217). A high DNA load of high-risk human papillomavirus (HR-HPV) was the main predictor for CIN1 and CIN2+, although age, married status combined with the number of sexual partners, active and passive smoking and age at sexual debut also affected associated lesions. In the training set, only the HPV-testing-contained CIN2+ CRS scheme presented an excellent discrimination for identifying CIN2+ (AU-ROC?=?0.866). Using a CRS cutoff value of 4 to identify CIN2+, the sensitivity and specificity of predicting CIN2+ for the 3- and 5-year follow-ups were 100% and 90.8%, and 83.3% and 90.4%, respectively, in the validation cohort. In the hospital-based validation population, the CRS scheme showed comparable discrimination for CIN2+ detection (sensitivity 88.2% and specificity 84.6%). Women with CRS ?4 had a 5.4% and 9.1% of 3- and 5-year cumulative incidence, respectively, and a 40.5-fold hazard ratio of developing CIN2+. In conclusion, combined with HR-HPV testing and verified risk factors, a simple CRS scheme could effectively improve the implementation of CIN2+ screening. PMID:24841989

Lee, Chien-Hung; Peng, Chiung-Yu; Li, Ruei-Nian; Chen, Yu-Chieh; Tsai, Hsiu-Ting; Hung, Yu-Hsiu; Chan, Te-Fu; Huang, Hsiao-Ling; Lai, Tai-Cheng; Wu, Ming-Tsang

2015-01-15

401

Effects of BRCA1 transgene expression on murine mammary gland development and mutagen-induced mammary neoplasia.  

PubMed

To characterize the role of BRCA1 in mammary gland development and tumor suppression, a transgenic mouse model of BRCA1 overexpression was developed. Using the mouse mammary tumor virus (MMTV) promoter/enhancer, transgenic mice expressing human BRCA1 or select mutant controls were generated. Transgenic animals examined during adolescence were shown to express the human transgene in their mammary glands. The mammary glands of 13-week-old virgin homozygous MMTV-BRCA1 mice presented the morphology of moderately increased lobulo-alveolar development. The mammary ductal trees of both hemizygous and homozygous MMTV-BRCA1t340 were similar to those of control non-transgenic littermates. Interestingly, both hemi- and homozygous mice expressing a splice variant of BRCA1 lacking the N-terminal RING finger domain (MMTV-BRCA1sv) exhibited marked mammary lobulo-alveolar development, particularly terminal end bud proliferation. Morphometric analyses of mammary gland whole mount preparations were used to measure epithelial staining indices of ~35% for homozygous MMTV-BRCA1 mice and ~60% for both hemizygous and homozygous MMTV-BRCA1sv mice versus ~25% for non-transgenic mice. Homozygous MMTV-BRCA1 mice showed delayed development of tumors when challenged with 7,12 dimethylbenzanthracene (DMBA), relative to non-transgenic and homozygous BRCA1t340 expressing mice. In contrast, homozygous MMTV-BRCA1sv transgenic animals were sensitized to DMBA treatment and exhibited a very rapid onset of mammary tumor development and accelerated mortality. MMTV-BRCA1 effects on mortality were restricted to DMBA-induced tumors of the mammary gland. These results demonstrate in vivo roles for BRCA1 in both mammary gland development and in tumor suppression against mutagen-induced mammary gland neoplasia. PMID:17505536

Hoshino, Arichika; Yee, Cindy J; Campbell, Mel; Woltjer, Randall L; Townsend, Rebecca L; van der Meer, Riet; Shyr, Yu; Holt, Jeffrey T; Moses, Harold L; Jensen, Roy A

2007-01-01

402

Thoracic and duodenopancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1: natural history and function of menin in tumorigenesis.  

PubMed

Mutations of the multiple endocrine neoplasia type 1 (MEN1) gene lead to loss of function of its protein product menin. In keeping with its tumor suppressor function in endocrine tissues, the majority of the MEN1-related neuroendocrine tumors (NETs) show loss of heterozygosity (LOH) on chromosome 11q13. In sporadic NETs, MEN1 mutations and LOH are also reported, indicating common pathways in tumor development. Prevalence of thymic NETs (thNETs) and pulmonary carcinoids in MEN1 patients is 2-8%. Pulmonary carcinoids may be underreported and research on natural history is limited, but disease-related mortality is low. thNETs have a high mortality rate. Duodenopancreatic NETs (dpNETs) are multiple, almost universally found at pathology, and associated with precursor lesions. Gastrinomas are usually located in the duodenal submucosa while other dpNETs are predominantly pancreatic. dpNETs are an important determinant of MEN1-related survival, with an estimated 10-year survival of 75%. Survival differs between subtypes and apart from tumor size there are no known prognostic factors. Natural history of nonfunctioning pancreatic NETs needs to be redefined because of increased detection of small tumors. MEN1-related gastrinomas seem to behave similar to their sporadic counterparts, while insulinomas seem to be more aggressive. Investigations into the molecular functions of menin have led to new insights into MEN1-related tumorigenesis. Menin is involved in gene transcription, both as an activator and repressor. It is part of chromatin-modifying protein complexes, indicating involvement of epigenetic pathways in MEN1-related NET development. Future basic and translational research aimed at NETs in large unbiased cohorts will clarify the role of menin in NET tumorigenesis and might lead to new therapeutic options. PMID:24389729

Pieterman, C R C; Conemans, E B; Dreijerink, K M A; de Laat, J M; Timmers, H Th M; Vriens, M R; Valk, G D

2014-06-01

403

Epizootic neoplasia of the lateral line system of lake trout (Salvelinus namaycush) in New York's Finger Lakes.  

PubMed

This article documents an epizootic of inflammation and neoplasia selectively affecting the lateral line system of lake trout (Salvelinus namaycush) in 4 Finger Lakes in New York from 1985 to 1994. We studied more than 100 cases of this disease. Tumors occurred in 8% (5/64) of mature and 21% (3/14) of immature lake trout in the most severely affected lake. Lesions consisted of 1 or more neoplasm(s) in association with lymphocytic inflammation, multifocal erosions, and ulcerations of the epidermis along the lateral line. Lesions progressed from inflammatory to neoplastic, with 2-year-old lake trout showing locally extensive, intense lymphocytic infiltrates; 2- to 3-year-old fish having multiple, variably sized white masses up to 3 mm in diameter; and fish over 5 years old exhibiting 1 or more white, cerebriform masses greater than 1 cm in diameter. Histologic diagnoses of the tumors were predominantly spindle cell sarcomas or benign or malignant peripheral nerve sheath neoplasms, with fewer epitheliomas and carcinomas. Prevalence estimates did not vary significantly between sexes or season. The cause of this epizootic remains unclear. Tumor transmission trials, virus isolation procedures, and ultrastructural study of lesions failed to reveal evidence of a viral etiology. The Finger Lakes in which the disease occurred did not receive substantially more chemical pollution than unaffected lakes in the same chain during the epizootic, making an environmental carcinogen an unlikely primary cause of the epizootic. A hereditary component, however, may have contributed to this syndrome since only fish of the Seneca Lake strain were affected. PMID:23528941

Spitsbergen, J M; Frattini, S A; Bowser, P R; Getchell, R G; Coffee, L L; Wolfe, M J; Fisher, J P; Marinovic, S J; Harr, K E

2013-05-01

404

TERT Promoter Mutations Occur Early in Urothelial Neoplasia and are Biomarkers of Early Disease and Disease Recurrence in Urine  

PubMed Central

Activating mutations occur in the promoter of the telomerase reverse transcriptase (TERT) gene in 66% of muscle-invasive urothelial carcinomas. To explore their role in bladder cancer development, and to assess their utility as urine markers for early detection, we sequenced the TERT promoter in 76 well-characterized papillary and flat noninvasive urothelial carcinomas, including 28 pTa low-grade (pTa LG) transitional cell carcinomas (TCC), 31 pTa high-grade (pTa HG) TCCs, and 17 pTis carcinoma in situ (CIS) lesions. We also evaluated the sequence of the TERT promoter in a separate series of 14 early bladder neoplasms and matched follow-up urine samples to determine if urine TERT status was an indicator of disease recurrence. A high rate of TERT promoter mutation was observed in both papillary and flat lesions, as well as in low- and high-grade noninvasive urothelial neoplasms (mean: 74%). Additionally, among patients whose tumors harbored TERT promoter mutations, the same mutations were present in follow-up urines in seven of eight patients that recurred but in none of 6 patients that did not recur (P <0.001). TERT promoter mutations occur in both papillary and flat lesions, are the most frequent genetic alterations identified to date in noninvasive precursor lesions of the bladder, are detectable in urine, and appear to be strongly associated with bladder cancer recurrence. These provocative results suggest that TERT promoter mutations may offer a useful urinary biomarker, for both early detection and monitoring of bladder neoplasia. PMID:24121487

Kinde, Isaac; Munari, Enrico; Faraj, Sheila F.; Hruban, Ralph H.; Schoenberg, Mark; Bivalacqua, Trinity; Allaf, Mohamad; Springer, Simeon; Wang, Yuxuan; Diaz, Luis A.; Kinzler, Kenneth W.; Vogelstein, Bert; Papadopoulos, Nickolas; Netto, George J.

2014-01-01

405

TERT promoter mutations occur early in urothelial neoplasia and are biomarkers of early disease and disease recurrence in urine.  

PubMed

Activating mutations occur in the promoter of the telomerase reverse transcriptase (TERT) gene in 66% of muscle-invasive urothelial carcinomas. To explore their role in bladder cancer development and to assess their utility as urine markers for early detection, we sequenced the TERT promoter in 76 well-characterized papillary and flat noninvasive urothelial carcinomas, including 28 pTa low-grade transitional cell carcinomas (TCC), 31 pTa high-grade TCCs, and 17 pTis carcinoma in situ lesions. We also evaluated the sequence of the TERT promoter in a separate series of 14 early bladder neoplasms and matched follow-up urine samples to determine whether urine TERT status was an indicator of disease recurrence. A high rate of TERT promoter mutation was observed in both papillary and flat lesions, as well as in low- and high-grade noninvasive urothelial neoplasms (mean: 74%). In addition, among patients whose tumors harbored TERT promoter mutations, the same mutations were present in follow-up urines in seven of eight patients that recurred but in none of the six patients that did not recur (P < 0.001). TERT promoter mutations occur in both papillary and flat lesions, are the most frequent genetic alterations identified to date in noninvasive precursor lesions of the bladder, are detectable in urine, and seem to be strongly associated with bladder cancer recurrence. These provocative results suggest that TERT promoter mutations may offer a useful urinary biomarker for both early detection and monitoring of bladder neoplasia. PMID:24121487

Kinde, Isaac; Munari, Enrico; Faraj, Sheila F; Hruban, Ralph H; Schoenberg, Mark; Bivalacqua, Trinity; Allaf, Mohamad; Springer, Simeon; Wang, Yuxuan; Diaz, Luis A; Kinzler, Kenneth W; Vogelstein, Bert; Papadopoulos, Nickolas; Netto, George J

2013-12-15

406

Identification of the modifier of Min 2 (Mom2) locus, a new mutation that influences Apc-induced intestinal neoplasia.  

PubMed

Min (Multiple intestinal neoplasia) mice carry a dominant mutation in the adenomatous polyposis coli (Apc) gene and develop multiple adenomas throughout their intestinal tract (Moser et al. 1990; Su et al 1992). Polyp multiplicity in Min mice is greatly influenced by genetic background. A modifier locus, Mom1 (Modifier of Min 1), was identified and localized to distal mouse chromosome 4 (Moser et al. 1992; Dietrich et al. 1993), and accounts for some of the genetic variance in polyp multiplicity. Mom1 is a semidominant modifier of polyp size and multiplicity in Min mice (Gould and Dove 1997), and encodes the secretory type II nonpancreatic phospholipase A2 (Pla2g2a) gene (MacPhee et al. 1995; Cornier et al. 1997, 2000). We now report the identification of a second Modifier of Min 2 (Mom2) locus that is the result of a spontaneous mutation. One resistant Mom2 allele can suppress 88%-95% of polyps detected in Apc(Min)/+ mice, indicating that Mom2 acts in a dominant fashion. Linkage analysis has localized Mom2 to distal mouse chromosome 18. The effects of the Mom2 locus on reducing polyp multiplicity are stronger than the effects of the Mom1 locus, in both the small and large intestines. Some Apc(Min)/+ mice that carried one resistant Mom2 allele were tumor-free at 21 weeks of age, even in the absence of a resistant Mom1 allele. Thus, the resistant Mom2 allele can, in some cases, completely suppress the penetrance of the Apc(Min) mutation. PMID:11779834

Silverman, Karen A; Koratkar, Revati; Siracusa, Linda D; Buchberg, Arthur M

2002-01-01

407

Cytomegalovirus-induced salivary gland pathology: AREG, FGF8, TNF-?, and IL-6 signal dysregulation and neoplasia.  

PubMed

Mucoepidermoid carcinoma (MEC) is the most common malignant tumor originating in major and minor salivary glands (SGs). Although the precise multifactorial etiology of human SG-MEC is largely unknown, we have recently shown that cytomegalovirus (CMV) is an important component of MEC tumorigenesis. Despite the well-documented overexpression of the EGFR ? ERK signaling pathway in SG-MEC, there has been limited to no clinical success with inhibition of this pathway. Using our previously characterized mouse model of CMV-induced SG dysplasia/neoplasia, we report that inhibitors of the EGFR ? ERK pathway do not ameliorate or rescue well-established pathology, either singly or in combination, but they do inhibit the evolution of progressive pathogenesis ("disease tolerance") in the face of mounting CMV burden. Failure to rescue SG pathology, suggested a possible increase in the ligand levels of alternative pathways that share cell proliferation and survival effectors (e.g. ERK and PI3K). Here we present evidence of a highly significant upregulation of ligands for the EGFR, FGFR, IL-6R, and TNFR signaling pathways, all of which converge upon the Raf/MEK/ERK amplifier module. This explains our finding that even in the presence of the highest nontoxic dose of an ERK phosphorylation inhibitor, pERK is undiminished. Given the considerable pathway crosstalk, a deep understanding of subversion and dysregulation of the SG interactome by CMV is a priori quite daunting. Circumventing this dilemma, we present evidence that concurrent inhibition of ERK phosphorylation (U0126) and CMV replication (acyclovir) obviates progressive pathogenesis and results in complete SG rescue (tumor regression). These findings provide a mechanistic foundation for potential clinical trials that utilize similar concurrent treatment with extant FDA-approved drugs. PMID:23399805

Melnick, Michael; Deluca, Krysta A; Sedghizadeh, Parish P; Jaskoll, Tina

2013-04-01

408

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

409

Caveolin-1 Upregulation Contributes to c-Myc-Induced High-Grade Prostatic Intraepithelial Neoplasia and Prostate Cancer  

PubMed Central

Previously we reported caveolin-1 (Cav-1) overexpression in prostate cancer (PCa) cells and demonstrated that it promotes PCa progression. Here, we report that Cav-1 was overexpressed in 41.7% (15 of 36) of high-grade prostatic intraepithelial neoplasia (HGPIN) specimens obtained during radical prostatectomies. Positive correlations exist between Cav-1–positive (Cav-1+) HGPIN and Cav-1+ primary PCa (rho = 0.655, P< 0.0001) and between Cav-1 and c-Myc expression in HGPIN (rho = 0.41, P = 0.032). To determine whether Cav-1 cooperates with c-Myc in development of premalignant lesions and PCa in vivo, we generated transgenic mice with c-Myc overexpression driven by the ARR2PB promoter. In this ARR2PB–c-myc model, Cav-1 overexpression was found in mouse PIN (mPIN) lesions and PCa cells and was associated with a significantly higher ratio of proliferative to apoptotic labeling in mPIN lesions than in the Cav-1–negative epithelia adjacent to those lesions (10.02 vs 4.34; P = 0.007). Cav-1 overexpression was also associated with increased levels of P-Akt and VEGF-A, which were previously associated with Cav-1–induced PCa cell survival and positive-feedback regulation of cellular Cav-1 levels, respectively. In multiple PCa cell lines, Cav-1 protein (but not mRNA) was induced by c-Myc transfection, whereas VEGF siRNA transfection abrogated c-Myc–induced Cav-1 overexpression, suggesting a c-Myc–VEGF–Cav-1 signaling axis. Overall, our results suggest that Cav-1 is associated with c-Myc in the development of HGPIN and PCa. Further, Cav-1 overexpression in HGPIN is potentially a biomarker for early identification of patients who tend to develop Cav-1+ primary PCa. PMID:22144662

Yang, Guang; Goltsov, Alexei A.; Ren, Chengzhen; Kurosaka, Shinji; Edamura, Kohei; Logothetis, Richard; DeMayo, Francesco J.; Troncoso, Patricia; Blando, Jorge; DiGiovanni, John; Thompson, Timothy C.

2013-01-01

410

American joint committee on cancer staging and clinicopathological high-risk predictors of ocular surface squamous neoplasia: a study from a tertiary eye center in India.  

PubMed

Context .- Ocular surface squamous neoplasia (OSSN) is the most common tumor of conjunctival epithelium associated with risk of permanent visual impairment. It includes conjunctival intraepithelial neoplasia and squamous cell carcinoma. Although American Joint Committee on Cancer-TNM (AJCC-TNM) staging is commonly used in various tumors, it has only recently been described for OSSN. Objectives .- To evaluate the prognostic relevance of AJCC-TNM staging and the clinicopathological features in OSSN. Design .- Sixty-four histopathologically proven cases of OSSN (20 conjunctival intraepithelial neoplasia and 44 squamous cell carcinoma) were included in the study. The AJCC-TNM staging and clinicopathological features of OSSN cases were recorded. Patients were followed up for 17 to 40 months (median, 32 months). Univariate and multivariate analyses were performed to determine the prognostic value of various clinicopathological features. Results .- Longer sunlight exposure (P = .01), diffuse growth pattern (P = .02), larger tumor size (?2 cm) (P = .03), histopathological diagnosis of squamous cell carcinoma (P = .02), and orbital invasion or invasion of adjacent structures (T3 or T4) (P < .001) emerged as significant predictors of reduced recurrence-free survival. Using multivariate analysis, a higher T category (T3 or T4) was the most important prognostic indicator of a poor outcome. Conclusions .- A higher T category (T3 or T4) is an important predictor of clinical outcome, and the use of the AJCC-TNM staging system is recommended in the management of all patients with OSSN. Longer sunlight exposure, larger tumor size (?2 cm), orbital invasion or invasion of adjacent structures (T3 or T4), and a histopathological diagnosis of squamous cell carcinoma are other clinicopathological features of prognostic relevance in patients with OSSN. PMID:25357110

Chauhan, Sheetal; Sen, Seema; Sharma, Anjana; Tandon, Radhika; Kashyap, Seema; Pushker, Neelam; Vanathi, Murugesan; Sharma, Namrata

2014-11-01

411

The Jak2 Inhibitor, G6, Alleviates Jak2-V617F-Mediated Myeloproliferative Neoplasia by Providing Significant Therapeutic Efficacy to the Bone Marrow1  

PubMed Central

We recently developed a Janus kinase 2 (Jak2) small-molecule inhibitor called G6 and found that it inhibits Jak2-V617F-mediated pathologic cell growth in vitro, ex vivo, and in vivo. However, its ability to inhibit Jak2-V617F-mediated myeloproliferative neoplasia, with particular emphasis in the bone marrow, has not previously been examined. Here, we investigated the efficacy of G6 in a transgenic mouse model of Jak2-V617F-mediated myeloproliferative neoplasia. We found that G6 provided therapeutic benefit to the peripheral blood as determined by elimination of leukocytosis, thrombocytosis, and erythrocytosis. G6 normalized the pathologically high plasma concentrations of interleukin 6 (IL-6). In the liver, G6 eliminated Jak2-V617F-driven extramedullary hematopoiesis. With respect to the spleen, G6 significantly reduced both the splenomegaly and megakaryocytic hyperplasia. In the critically important bone marrow, G6 normalized the pathologically high levels of phospho-Jak2 and phospho-signal transducer and activator of transcription 5 (STAT5). It significantly reduced the megakaryocytic hyperplasia in the marrow and completely normalized the M/E ratio. Most importantly, G6 selectively reduced the mutant Jak2 burden by 67%on average, with virtual elimination of mutant Jak2 cells in one third of all treated mice. Lastly, clonogenic assays using marrow stem cells from the myeloproliferative neoplasm mice revealed a time-dependent elimination of the clonogenic growth potential of these cells by G6. Collectively, these data indicate that G6 exhibits exceptional efficacy in the peripheral blood, liver, spleen, and, most importantly, in the bone marrow, thereby raising the possibility that this compound may alter the natural history of Jak2-V617F-mediated myeloproliferative neoplasia. PMID:22131881

Kirabo, Annet; Park, Sung O; Majumder, Anurima; Gali, Meghanath; Reinhard, Mary K; Wamsley, Heather L; Zhao, Zhizhuang Joe; Cogle, Christopher R; Bisht, Kirpal S; Keseru, Gyorgy M; Sayeski, Peter P

2011-01-01

412

Alterations of the p16 INK4a\\/Rb\\/cyclin-D1 pathway in vulvar carcinoma, vulvar intraepithelial neoplasia, and lichen sclerosus  

Microsoft Academic Search

Three different alterations in the p16\\/pRb\\/cyclin-D1 pathway (p16INK4a-promoter hypermethylation and expression of pRb and cyclin-D1) were investigated in a series of 38 cases of vulvar carcinoma (VC), 13 cases of vulvar intraepithelial neoplasia (VIN), and 21 cases of lichen sclerosus (LS). Paraffin blocks from 72 patients were selected for investigation of DNA methylation patterns in the CpG island of p16INK4a

Enrique Lerma; Manel Esteller; James G. Herman; Jaime Prat