Sample records for neoplasia polmonare con

  1. Ocular surface squamous neoplasia

    Microsoft Academic Search

    Graham A. Lee; Lawrence W. Hirst

    1995-01-01

    Ocular surface squamous neoplasia presents as a spectrum from simple dysplasia to carcinoma in situ to invasive squamous cell carcinoma involving the conjunctiva as well as the cornea. It is a distinct clinical entity, although it has been known by a variety of different names thorughout the literature. Most commonly it arises in the limbal region, occurring particularly in elderly

  2. [Anal intraepithelial neoplasia].

    PubMed

    de Parades, Vincent; Fathallah, Nadia; Barret, Maximilien; Zeitoun, Jean-David; Lemarchand, Nicolas; Molinié, Vincent; Weiss, Laurence

    2013-01-01

    Anal intraepithelial lesions are caused by chronic infection with oncogenic types of human papillomavirus. Their incidence and prevalence are increasing, especially among patients with HIV infection. Their natural history is not well known, but high-grade intraepithelial lesions seem to have an important risk to progress to squamous cell carcinoma. Their treatment can be achieved by many ways (surgery, coagulation, imiquimod, etc.) but there is a high rate of recurrent lesions. Pretherapeutic evaluation should benefit from high-resolution anoscopy. Periodic physical examination and anal cytology may probably be interesting for screening the disease among patients with risk factors. Vaccine against oncogenic types of papillomavirus may prevent the development of anal intraepithelial neoplasia. PMID:23122632

  3. Multiple endocrine neoplasia (MEN) I

    MedlinePLUS

    ... neoplasia (MEN) type I is a disease passed down through families, in which one or more of the endocrine glands are overactive or form a tumor. Endocrine glands most commonly involved include: Pancreas Parathyroid Pituitary

  4. Inflammatory polyps and aural neoplasia.

    PubMed

    Fan, Timothy M; de Lorimier, Louis-Philippe

    2004-03-01

    Although aural neoplasia is a relatively uncommon entity in companion animals, it remains a group of heterogeneous conditions that can have a significant negative impact on quality and duration of life of dogs and cats. Chronic ear disease that responds poorly or partially to empiric therapy should raise the suspicion that an underlying condition, such as neoplasia, may be the perpetrator of inflammation. Early diagnosis followed by appropriate therapy improves the likelihood of disease control and prolonged survival. PMID:15062621

  5. Surgery for cervical intraepithelial neoplasia

    PubMed Central

    Martin-Hirsch, Pierre PL; Paraskevaidis, Evangelos; Bryant, Andrew; Dickinson, Heather O; Keep, Sarah L

    2014-01-01

    Background Cervical intraepithelial neoplasia (CIN) is the most common pre-malignant lesion. Atypical squamous changes occur in the transformation zone of the cervix with mild, moderate or severe changes described by their depth (CIN 1, 2 or 3). Cervical intraepithelial neoplasia is treated by local ablation or lower morbidity excision techniques. Choice of treatment depends on the grade and extent of the disease. Objectives To assess the effectiveness and safety of alternative surgical treatments for CIN. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE and EMBASE (up to April 2009). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria Randomised controlled trials (RCTs) of alternative surgical treatments in women with cervical intraepithelial neoplasia. Data collection and analysis Two review authors independently abstracted data and assessed risks of bias. Risk ratios that compared residual disease after the follow-up examination and adverse events in women who received one of either laser ablation, laser conisation, large loop excision of the transformation zone (LLETZ), knife conisation or cryotherapy were pooled in random-effects model meta-analyses. Main results Twenty-nine trials were included. Seven surgical techniques were tested in various comparisons. No significant differences in treatment failures were demonstrated in terms of persistent disease after treatment. Large loop excision of the transformation zone appeared to provide the most reliable specimens for histology with the least morbidity. Morbidity was lower than with laser conisation, although the trials did not provide data for every outcome measure. There were not enough data to assess the effect on morbidity when compared with laser ablation. Authors’ conclusions The evidence suggests that there is no obvious superior surgical technique for treating cervical intraepithelial neoplasia in terms of treatment failures or operative morbidity. PMID:20556751

  6. Marine mammal neoplasia: a review.

    PubMed

    Newman, S J; Smith, S A

    2006-11-01

    A review of the published literature indicates that marine mammal neoplasia includes the types and distributions of tumors seen in domestic species. A routine collection of samples from marine mammal species is hampered, and, hence, the literature is principally composed of reports from early whaling expeditions, captive zoo mammals, and epizootics that affect larger numbers of animals from a specific geographic location. The latter instances are most important, because many of these long-lived, free-ranging marine mammals may act as environmental sentinels for the health of the oceans. Examination of large numbers of mortalities reveals incidental proliferative and neoplastic conditions and, less commonly, identifies specific malignant cancers that can alter population dynamics. The best example of these is the presumptive herpesvirus-associated metastatic genital carcinomas found in California sea lions. Studies of tissues from St. Lawrence estuary beluga whales have demonstrated a high incidence of neoplasia and produced evidence that environmental contamination with high levels of polychlorinated biphenols and dichlorophenyl trichloroethane might be the cause. In addition, viruses are suspected to be the cause of gastric papillomas in belugas and cutaneous papillomas in Florida manatees and harbor porpoises. While experimental laboratory procedures can further elucidate mechanisms of neoplasia, continued pathologic examination of marine mammals will also be necessary to follow trends in wild populations. PMID:17099143

  7. 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.

  8. Update on Pancreatic Intraepithelial Neoplasia

    PubMed Central

    Hruban, Ralph H; Maitra, Anirban; Goggins, Michael

    2008-01-01

    Pancreatic intraepithelial neoplasia (PanIN) is a histologically well-defined precursor to invasive ductal adenocarcinoma of the pancreas. PanINs are remarkably common lesions, particularly in the elderly population. Molecular studies have helped establish the progression of PanIN to invasive cancer, and recently genetically engineered mouse models have been generated that recapitulate the entire spectrum of lesions from precursor to invasive pancreatic cancer. Some PanIN lesions produce lobulocentric atrophy of the pancreatic parenchyma, and, when multifocal, this lobulocentric atrophy may be detectable using currently available imaging techniques such as endoscopic ultrasound. The association of acinar-ductal metaplasia with PanIN lesions has led some to hypothesize that PanINs develop from acinar cells that undergo acinar-ductal metaplasia. PMID:18787611

  9. Neoplasias de células plasmáticas (incluso mieloma múltiple)

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento del mieloma múltiple y otras neoplasias de células plasmáticas, así como referencias a estudios clínicos, investigación, estadísticas y otros temas relacionados.

  10. Review article: Marine mammal neoplasia: A review

    Microsoft Academic Search

    Shelley Newman; S A Smith

    2006-01-01

    A review of the published literature indicates that marine mammal neoplasia includes the types and distributions of tumors seen in domestic species. A routine collection of samples from marine mammal species is hampered, and, hence, the literature is principally composed of reports from early whaling expeditions, captive zoo mammals, and epizootics that affect larger numbers of animals from a specific

  11. Renal Neoplasia in Coypus ( Myocastor coypus)

    Microsoft Academic Search

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

    1999-01-01

    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

  12. The foamy variant of pancreatic intraepithelial neoplasia

    Microsoft Academic Search

    Jorge Albores-Saavedra; Mariana Weimersheimer-Sandoval; Fredy Chable-Montero; Daniel Montante-Montes de Oca; Ralph H. Hruban; Donald Earl Henson

    2008-01-01

    Foamy gland adenocarcinoma is a variant of pancreatic ductal carcinoma, whose precursor has not been described. We describe here the morphologic and immunohistochemical features of the pancreatic intraepithelial neoplasia (PanIN) lesions associated with invasive foamy pancreatic adenocarcinoma. The staining properties and morphologic and immunohistochemical features of 3 foamy PanIN lesions were compared with those of 7 pancreatic foamy gland adenocarcinomas.

  13. Suppression of intestinal neoplasia by DNA hypomethylation

    Microsoft Academic Search

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

    1995-01-01

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

  14. Pancreatic Intraepithelial Neoplasia Revisited and Updated

    Microsoft Academic Search

    B. Sipos; S. Frank; T. Gress; S. Hahn; G. Klöppel

    2009-01-01

    Most pancreatic neoplasms are classified as ductal adenocarcinoma because they show a ductal phenotype, making a ductal origin very likely. The duct lesions that may give rise to pancreatic ductal adenocarcinoma have been called pancreatic intraepithelial neoplasia (PanIN). A classification system for these lesions distinguishes between three grades of PanIN. Molecular studies revealed that PanIN-2 and PanIN-3 lesions represent a

  15. Persistent human papillomavirus infection and cervical neoplasia.

    PubMed

    Ferenczy, Alex; Franco, Eduardo

    2002-01-01

    The development of cervical cancer is preceded by precursor lesions (cervical intraepithelial neoplasia). Evidence-based epidemiological and molecular data suggest that persistent infections with human papillomavirus (HPV) types that carry ahigh oncogenic risk are the intermediate endpoints, leading to both intraepithelial and invasive cervical neoplasia. Integration of highly oncogenic HPVs into host-cell chromosomes is followed by binding of HPV E6 and E7 oncoproteins to tumour-suppressor genes p53 and RB, respectively. This process results in impaired tumour-suppressor-gene function, involving DNA repair, decreased apoptosis, and eventual cell immortalisation. Mutations causing chromosomal alterations, loss of heterozygosity, and proto-oncogene and telomerase activation in immunopermissive individuals have important roles in virus-induced cervical carcinogenesis. The so-called non-European variants of HPV 16 and 18 may increase the degradation potential of p53. HPV 16 is polymorphic and, although the evidence is controversial, the Arg/Arg genotype of p53 could have greater susceptibility to HPV-E6 degradation than the other genotypes. The coincident interplay between the non-European genomic variants of HPV 16/18 and p53 Arg/Arg may explain, at least in part, the persistence of HPV infection and tumour progression in women with cervical neoplasia. Further epidemiological and molecular research is needed, to gain insight into HPV-mediated cervical carcinogenesis. The evidence highlights the need to develop appropriate prophylactic HPV vaccines and diagnostic and screening tests. PMID:11905599

  16. Human papillomavirus in vaginal intraepithelial neoplasia.

    PubMed

    Chao, Angel; Chen, Tse-Ching; Hsueh, Chuen; Huang, Chu-Chun; Yang, Jung-Erh; Hsueh, Swei; Huang, Huei-Jean; Lin, Cheng-Tao; Tang, Yun-Hsin; Liou, Jui-Der; Chang, Chee-Jen; Chou, Hung-Hsueh; Lai, Chyong-Huey

    2012-08-01

    There are limited data on the prevalence and distribution of human papillomavirus (HPV) genotypes in vaginal intraepithelial neoplasia (VAIN). We sought to clarify this issue in a series of 450 VAIN cases with a confirmed diagnosis between 1990 and 2006. HPV genotyping was performed using paraffin-embedded specimens and polymerase chain reaction (PCR)-based methods. Multiple HPV types were validated by E6 type-specific PCR and direct sequencing. The HPV genotypes of the vaginal and cervical neoplasms were compared for those with incident VAIN and a history of previous/concomitant cervical neoplasms. Ki-67 was performed for supporting diagnosis of VAIN. Of these 450 VAIN cases (median age, 59 years; range, 19-93), two with missing paraffin blocks and 54 with poor DNA quality were excluded. HPV was detected in 273/394 (69.3%) VAIN, and multiple infections were found in 17.9% of HPV-positive samples. The leading types were HPV16 (35.5%), HPV58 (9.9%), HPV52 (9.9%), HPV39 (8.4%), HPV33 (7.3%) and HPV53 (7.0%). Among the 156 cases with a history of previous cervical neoplasia, 29.0% had concordant HPV genotypes, while synchronous VAIN samples (n = 49) were more likely to harbor concordant genotypes (58.7%) with the concomitant cervical neoplasm (p = 0.0003). Whether those HPV types in the incident VAIN lesions had existed in the vaginal epithelium at the time of the previous cervical neoplasia or a new acquisition needs to be clarified in prospective follow-up studies. PMID:22095387

  17. Multiple endocrine neoplasia type 2A.

    PubMed

    Huang, Chiung-Tang; Yang, Wen-Chi; Lin, Sheng-Fung

    2012-06-01

    Multiple endocrine neoplasia type 2A (MEN 2A) is an autosomal dominant inherited cancer syndrome that expresses nonendocrine and endocrine tumors. Here, we describe a 42-year-old man with an initial presentation of low back pain and hypertension. Clinical assessments revealed pheochromocytoma, medullary thyroid carcinoma with bone metastasis, and parathyroid hyperplasia. MEN 2A was diagnosed, and a family history of pheochromocytoma was traced. Surgical resection of the pheochromocytoma of the adrenal gland resulted in a cure of the patient's hypertension. He received systemic chemotherapy with the "MAID" regimen (mesna, doxorubicin, ifosfamide, and dacarbazine) over three cycles of 3 weeks each, and showed a partial response. PMID:22632891

  18. Radiation therapy in the treatment of oral neoplasia.

    PubMed

    Burk, R L

    1996-01-01

    Oral neoplasia occasionally may be treated adequately with a single modality. Multimodality therapy, however, more often is indicated. This article reviews the recommendations of treatment of oral neoplasia focusing on the role of radiation therapy both singly and as a part of multimodality therapy. PMID:8825574

  19. Renal neoplasia in coypus (Myocastor coypus).

    PubMed

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

    1999-09-01

    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

  20. Quantitative proteomics investigation of pancreatic intraepithelial neoplasia

    PubMed Central

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

    2009-01-01

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

  1. Photodynamic therapy of cervical intraepithelial neoplasia

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

    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.

  2. Molecular genetics of pancreatic intraepithelial neoplasia

    PubMed Central

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

    2009-01-01

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

  3. Palmar flexion creases in childhood neoplasia.

    PubMed

    Oorthuys, A M; de Vaan, G A; Behrendt, H; Geerts, S J

    1979-02-01

    About 90% of Caucasian individuals in the general population may observe two transverse palmar flexion creases when their fingers are slightly bent. A small minority may find in one hand a single transverse crease or the usual two creases, of which one seems to cut across the palm to the ulnar margin. Those unusual creases are called simian- or Sydney-creases, respectively. Normal healthy people hardly ever observe them in both hands. We observed those unusual creases, however, in more than 50% of children suffering from different type of malignant neoplasia, quite often in both hands. The difference between patients and controls of similar ages is highly significant. Among patient with childhood acute lymphocytic leukemia the variant creases were mostly of the Sydney type. They most frequently occurred in those patients in whom the disease had become manifest at an early age. Since fathers as well as mothers of the patients showed significantly higher frequencies of unusual creases, the phenomenon seems to be a familial one. A most singular effect is the striking incidence of those creases in younger siblings of the patients. With regard to crease variance our data are essentially similar for lymphoproliferative disorders (ALL and NHML) and embryonic malignant tumors. This might be the first indication of a common host factor in patients with ALL or embryonic tumors occurring in early childhood. We have postulated that this factor may be a regulatory one associated with cellular growth and differentiation in early fetal palmar pads as well as with cell-mediated immune response to early pediatric tumors. The observation of palmar flexion creases may prove to be rewarding in future studies of cellular defense mechanisms in young patients with neoplasia. PMID:283882

  4. Modeling human endothelial cell transformation in vascular neoplasias

    PubMed Central

    Wen, Victoria W.; MacKenzie, Karen L.

    2013-01-01

    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

  5. Quantitative architectural analysis of bronchial intraepithelial neoplasia

    NASA Astrophysics Data System (ADS)

    Guillaud, Martial; MacAulay, Calum E.; Le Riche, Jean C.; Dawe, Chris; Korbelik, Jagoda; Lam, Stephen

    2000-04-01

    Considerable variation exists among pathologist in the interpretation of intraepithelial neoplasia making it difficult to determine the natural history of these lesion and to establish management guidelines for chemoprevention. The aim of the study is to evaluate architectural features of pre-neoplastic progression in lung cancer, and to search for a correlation between architectural index and conventional pathology. Quantitative architectural analysis was performed on a series of normal lung biopsies and Carcinoma In Situ (CIS). Centers of gravity of the nuclei within a pre-defined region of interest were used as seeds to generate a Voronoi Diagram. About 30 features derived from the Voronoi diagram, its dual the Delaunay tessellation, and the Minimum Spanning Tree were extracted. A discriminant analysis was performed to separate between the two groups. The architectural Index was calculated for each of the bronchial biopsies that were interpreted as hyperplasia, metaplasia, mild, moderate or severe dysplasia by conventional histopathology criteria. As a group, lesions classified as CIS by conventional histopathology criteria could be distinguished from dysplasia using the architectural Index. Metaplasia was distinct from hyperplasia and hyperplasia from normal. There was overlap between severe and moderate dysplasia but mild dysplasia could be distinguished form moderate dysplasia. Bronchial intraepithelial neoplastic lesions can be degraded objectively by architectural features. Combination of architectural features and nuclear morphometric features may improve the quantitation of the changes occurring during the intra-epithelial neoplastic process.

  6. Optical coherence tomography in vulvar intraepithelial neoplasia

    NASA Astrophysics Data System (ADS)

    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

    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.

  7. Multiple endocrine neoplasia type 2 and RET: from neoplasia to neurogenesis

    PubMed Central

    Hansford, J.; Mulligan, L.

    2000-01-01

    Multiple endocrine neoplasia type 2 (MEN 2) is an inherited cancer syndrome characterised by medullary thyroid carcinoma (MTC), with or without phaeochromocytoma and hyperparathyroidism. MEN 2 is unusual among cancer syndromes as it is caused by activation of a cellular oncogene, RET. Germline mutations in the gene encoding the RET receptor tyrosine kinase are found in the vast majority of MEN 2 patients and somatic RET mutations are found in a subset of sporadic MTC. Further, there are strong associations of RET mutation genotype and disease phenotype in MEN 2 which have led to predictions of tissue specific requirements and sensitivities to RET activity. Our ability to identify genetically, with high accuracy, subjects with MEN 2 has revolutionised our ability to diagnose, predict, and manage this disease. In the past few years, studies of RET and its normal ligand and downstream interactions and the signalling pathways it activates have clarified our understanding of the roles played by RET in normal cell survival, proliferation, and differentiation, as well as in disease. Here, we review the current knowledge of the normal functions of RET and the effects of mutations of this gene in tumorigenesis and in normal development.???Keywords: multiple endocrine neoplasia type 2; RET; receptor tyrosine kinase PMID:11073534

  8. Immunohistochemistry for cell polarity protein lethal giant larvae 2 differentiates pancreatic intraepithelial neoplasia-3 and ductal adenocarcinoma of the pancreas from lower-grade pancreatic intraepithelial neoplasias.

    PubMed

    Lisovsky, Mikhail; Dresser, Karen; Woda, Bruce; Mino-Kenudson, Mari

    2010-06-01

    Pancreatic intraepithelial neoplasia is a precursor to ductal adenocarcinoma of the pancreas that shows gastric differentiation. Pancreatic intraepithelial neoplasia-3 has the highest potential to progress to adenocarcinoma, and its distinction from lower-grade pancreatic intraepithelial neoplasias is important for clinical management. However, morphologic grading of pancreatic intraepithelial neoplasia suffers from significant interobserver variability. A product of cell polarity gene lethal giant larvae 2 is a marker of gastric foveolar epithelium expressed in a basolateral fashion, which is lost or mislocalized in gastric epithelial dysplasia and adenocarcinoma. In this study, we investigated a role of lethal giant larvae 2 expression in differentiating low-grade pancreatic intraepithelial neoplasias, that is, pancreatic intraepithelial neoplasia-1 and pancreatic intraepithelial neoplasia-2, from pancreatic intraepithelial neoplasia-3 and pancreatic ductal adenocarcinoma. The immunohistochemical patterns of lethal giant larvae 2 expression were examined in normal pancreatic ducts, 48 pancreatic intraepithelial neoplasia lesions of all histologic grades, and 91 adenocarcinomas on a tissue microarray or conventional sections. The expression pattern was recorded as basolateral, cytoplasmic, negative, or combinations of any of them. Whereas normal duct epithelia did not exhibit lethal giant larvae immunoreactivity, all but one lesion of low-grade pancreatic intraepithelial neoplasia showed basolateral lethal giant larvae staining. Conversely, all lesions of pancreatic intraepithelial neoplasia-3 and adenocarcinoma showed loss of lethal giant larvae 2 staining and/or its cytoplasmic localization. Interestingly, a basolateral expression was focally seen in 4 adenocarcinomas with a foamy gland pattern and was always admixed with negatively stained areas. In conclusion, our results show that low-grade pancreatic intraepithelial neoplasias express lethal giant larvae 2 in a basolateral fashion recapitulating expression in normal gastric epithelium. Loss or abnormal lethal giant larvae 2 expression is seen in pancreatic intraepithelial neoplasia-3 and adenocarcinoma and might be useful in separating them from lower-grade pancreatic intraepithelial neoplasias. PMID:20233622

  9. HPV infection, anal intra-epithelial neoplasia (AIN) and anal cancer: current issues

    E-print Network

    Stanley, Margaret A; Winder, David M; Sterling, Jane C; Goon, Peter K C

    2012-09-08

    by a spectrum of intra- epithelial changes, anal intra-epithelial neoplasia (AIN), of varying cytological and histological severity AIN 1 - mild, AIN 2 - moderate, AIN 3 - severe, similar to cer- vical intra-epithelial neoplasia (CIN), that correspond...

  10. Pathology of Treated GI Neoplasia Pathology section seminar

    E-print Network

    Magee, Derek

    Pathology of Treated GI Neoplasia Pathology section seminar Liverpool DDF meeting Tuesday 19th June for LGD #12;#12;p53 #12;BSG/DDF 2012 Pathology Slide Seminar Dr Adrian C Bateman Southampton University Hospitals NHS Foundation Trust Southampton Cellular Pathology #12;History · 56 year old man · Refractory

  11. 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...

  12. Colorectal neoplasia in juvenile polyposis or juvenile polyps.

    PubMed Central

    Giardiello, F M; Hamilton, S R; Kern, S E; Offerhaus, G J; Green, P A; Celano, P; Krush, A J; Booker, S V

    1991-01-01

    Juvenile (retention) polyps are usually solitary lesions in the colorectum but may be multiple in juvenile polyposis. The association between juvenile polyps and colorectal neoplasia is controversial. We present three patients with juvenile polyposis who had colorectal adenomas or adenomatous epithelium in juvenile polyps at ages 3, 4, and 7 years. In a retrospective study of 57 additional patients with one or more juvenile polyps, 10 patients (18%) had colorectal neoplasia including three with adenocarcinoma, two with tubular adenoma, and six with adenomatous epithelium in a juvenile polyp (one had both adenomatous epithelium and an adenocarcinoma). Nine of these 10 patients had juvenile polyposis defined by the presence of at least three juvenile polyps; and eight of the nine had a family history of juvenile polyps. Colorectal neoplasia occurred at young age (mean (SEM) 37 (5) years). Our findings suggest that patients with juvenile polyps who have three or more juvenile polyps or a family history of juvenile polyps should undergo surveillance for colorectal neoplasia. Images Figure 1 PMID:1656892

  13. Colonoscopic Screening of Average-Risk Women for Colorectal Neoplasia

    Microsoft Academic Search

    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

    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

  14. Hematopoietic Neoplasias in Horses: Myeloproliferative and Lymphoproliferative Disorders

    PubMed Central

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

    2010-01-01

    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

  15. In vivo and in vitro hyperspectral imaging of cervical neoplasia

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

    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.

  16. Genital warts and cervical neoplasia: An epidemiological study

    Microsoft Academic Search

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

    1983-01-01

    Cervical carcinoma and cervical intra-epithelial neoplasia (CIN) are likely to be associated with all sexually transmitted diseases (STDs). To help discover which (if any) of the recognised STDs might actually cause these conditions, a key question is whether one particular such association is much stronger than the others. The present study is therefore only of women newly attending an STD

  17. Lkb1 Deficiency Causes Prostate Neoplasia in the Mouse

    Microsoft Academic Search

    Helen B. Pearson; Afshan McCarthy; Christopher M. P. Collins; Alan Ashworth; Alan R. Clarke

    2008-01-01

    Mutation of LKB1 is the key molecular event underlying Peutz-Jeghers syndrome, a dominantly inherited condition characterized by a predisposition to a range of malignancies, including those of the reproductive system. We report here the use of a Cre-LoxP strategy to directly address the role of Lkb1 in prostate neoplasia. Recombination of a LoxP-flanked Lkb1 allele within all four murine prostate

  18. Genetic Testing in Presymptomatic Diagnosis of Multiple Endocrine Neoplasia

    Microsoft Academic Search

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

    1997-01-01

    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

  19. Minimally Invasive Therapy of Cervical Intraepithelial Neoplasia for Fertility Preservation

    Microsoft Academic Search

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

    2009-01-01

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

  20. Placental-type alkaline phosphatase in cervical neoplasia

    Microsoft Academic Search

    PJ McLaughlin; PH Warne; GE Hutchinson; PM Johnson; DF Tucker

    1987-01-01

    Monoclonal antibodies reactive with placental-type alkaline phosphatase have formed the basis of methods for detection of this oncodevelopmental antigen in patients with pre-invasive and invasive cervical neoplasia, with or without evidence of papilloma virus infection. Disease-related elevations of placental-type alkaline phosphatase were not observed in patients' sera. Solubilised cervical smears or biopsy material, and cervical mucus swabs, often contained substantial

  1. Multiple endocrine neoplasia type 2: achievements and current challenges.

    PubMed

    Machens, Andreas; Dralle, Henning

    2012-01-01

    Incremental advances in medical technology, such as the development of sensitive hormonal assays for routine clinical care, are the drivers of medical progress. This principle is exemplified by the creation of the concept of multiple endocrine neoplasia type 2, encompassing medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism, which did not emerge before the early 1960s. This review sets out to highlight key achievements, such as joint biochemical and DNA-based screening of individuals at risk of developing multiple endocrine neoplasia type 2, before casting a spotlight on current challenges which include: (i) ill-defined upper limits of calcitonin assays for infants and young children, rendering it difficult to implement the biochemical part of the integrated DNA-based/biochemical concept; (ii) our increasingly mobile society in which different service providers are caring for one individual at various stages in the disease process. With familial relationships disintegrating as a result of geographic dispersion, information about the history of the origin family may become sketchy or just unavailable. This is when DNA-based gene tests come into play, confirming or excluding an individual's genetic predisposition to multiple endocrine neoplasia type 2 even before there is any biochemical or clinical evidence of the disease. However, the unrivaled molecular genetic progress in multiple endocrine neoplasia type 2 does not come without a price. Screening may uncover unknown gene sequence variants representing either harmless polymorphisms or pathogenic mutations. In this setting, functional characterization of mutant cells in vitro may generate helpful ancillary evidence with regard to the pathogenicity of gene variants in comparison with established mutations. PMID:22584715

  2. Piroxicam decreases postirradiation colonic neoplasia in the rat

    SciTech Connect

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

    1990-12-01

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

  3. Concurrent Angiomyolipoma and Renal Cell Neoplasia: A Study of 36 Cases

    Microsoft Academic Search

    Rafael E Jimenez; John N. Eble; Victor E. Reuter; Jonathan I. Epstein; Andrew L. Folpe; Mariza de Peralta-Venturina; Pheroze Tamboli; I. David Ansell; David J. Grignon; Robert H. Young; Mahul B. Amin

    2001-01-01

    Little is known about the association of angiomyolipoma and adult renal-cell neoplasia. We studied the clinicopathologic features of 36 patients with concurrent angiomyolipoma and renal-cell neoplasia from the consultation and surgical pathology files of nine institutions. HMB-45 immunoreactivity was analyzed in both neoplasms. Twenty-five sporadic cases of patients with angiomyolipoma and renal-cell neoplasia and 11 cases of patients with tuberous

  4. Spectroscopic Microvascular Blood Detection From the Endoscopically Normal Colonic Mucosa: Biomarker for Neoplasia Risk

    E-print Network

    Ottino, Julio M.

    : Biomarker for Neoplasia Risk HEMANT K. ROY,* ANDREW GOMES, VLADIMIR TURZHITSKY, MICHAEL J. GOLDBERG,* JEREMY their use for pop- ulation screening. Therefore, attention has focused on detecting biomarkers

  5. Ras/Erk MAPK signaling in epidermal homeostasis and neoplasia.

    PubMed

    Khavari, Thomas A; Rinn, John

    2007-12-01

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

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

    Microsoft Academic Search

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

    2003-01-01

    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

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

    E-print Network

    Roblyer, Darren

    benign conditions, such as lichen planus, inflammation, and hyperkeratosis, mimic the clinical presenMultispectral optical imaging device for in vivo detection of oral neoplasia Darren Roblyer Rebecca detection of oral neoplasia. The MDM acquires in vivo images of oral tissue in fluorescence, narrow- band NB

  8. Immunocytochemical analysis of the tumour suppressor protein (p53) in feline neoplasia

    Microsoft Academic Search

    Lubna Nasir; Hilary Krasner; David J Argyle; Alun Williams

    2000-01-01

    Detectable p53 immunostaining in neoplasia generally correlates with the presence of a mutation in the coding region of the p53 gene and may provide insights into the pathogenic mechanisms underlying tumourigenesis. p53 immunoreactivity was examined in 77 feline tumours, selected as a representative sample of 486 specimens submitted for diagnosis and analyzed to estimate the relative frequencies of feline neoplasias.

  9. The role of vitamins in the etiology of cervical neoplasia: an epidemiological review

    Microsoft Academic Search

    A. Schneider; K. Shah

    1989-01-01

    Diet may act as a cofactor in the development of cancer of the cervix. A consistent correlation exists between low tissue concentrations, low serum level, and low intake ofvitamin A, beta-carotene, vitamin C, orfolic acid and an increased prevalence of cervical neoplasia. A moderate effect is seen in clinical trials with vitamin treatment of cervical intraepithelial neoplasias. The studies reviewed

  10. Imaging findings in pancreatic neoplasia and nodular hyperplasia in 19 cats

    Microsoft Academic Search

    Silke Hecht; DOMINIQUE G. PENNINCK; J H Keatin

    2007-01-01

    Pancreatic neoplasia in cats is rare and associated with a poor prognosis, but pancreatic nodular hyperplasia is a common incidental finding. The purpose of this study was to describe radiographic and ultrasonographic findings in cats with pancreatic neoplasia or nodular hyperplasia. Fourteen cats (age 3-18 years) were diagnosed with malignant pancreatic tumors: carcinoma\\/adenocarcinoma (n = 11), lymphoma (n = 1),

  11. In situ increased chemokine expression in human cervical intraepithelial neoplasia.

    PubMed

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

    2015-04-01

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

  12. Clonal expansions in ulcerative colitis identify patients with neoplasia

    PubMed Central

    Salk, Jesse J.; Salipante, Stephen J.; Risques, Rosa Ana; Crispin, David A.; Li, Lin; Bronner, Mary P.; Brentnall, Teresa A.; Rabinovitch, Peter S.; Horwitz, Marshall S.; Loeb, Lawrence A.

    2009-01-01

    Chronic inflammation predisposes to a variety of human cancers. Affected tissues slowly accumulate mutations, some of which affect growth regulation and drive successive waves of clonal evolution, whereas a far greater number are functionally neutral and serve only to passively mark expanding clones. Ulcerative colitis (UC) is an inflammatory bowel disease, in which up to 10% of patients eventually develop colon cancer. Here we have mapped mutations in hypermutable intergenic and intronic polyguanine tracts in patients with UC to delineate the extent of clonal expansions associated with carcinogenesis. We genotyped colon biopsies for length altering mutations at 28 different polyguanine markers. In eight patients without neoplasia, we detected only two mutations in a single individual from among 37 total biopsies. In contrast, for 11 UC patients with neoplasia elsewhere in the colon, we identified 63 mutations in 51 nondysplastic biopsies, and every patient possessed at least one mutant clone. A subset of clones were large and extended over many square centimeters of colon. Of these, some occurred as isolated populations in nondysplastic tissue, considerably distant from neoplastic lesions. Other large clones included regions of cancer, suggesting that the tumor arose within a preexisting clonal field. Our results demonstrate that neutral mutations in polyguanine tracts serve as a unique tool for identifying fields of clonal expansions, which may prove clinically useful for distinguishing a subset of UC patients who are at risk for developing cancer. PMID:19926851

  13. Efficacy of cervical intrarepithelial neoplasia (CIN) treatment by cold coagulation.

    PubMed Central

    Zawislak, A.; Price, J. H.; McClelland, H. R.; Storey, R. G. N.; Caughley, L.

    2003-01-01

    Our objective was to evaluate the efficacy of cold coagulation in the treatment of cervical intraepithelial neoplasia. The study design consisted of a retrospective review of case records of all women treated with cold coagulation from the colposcopy clinics inception in 1980 to 1994. A total of 725 women received treatment with cold coagulation. All grades of CIN were treated. 632 (87.1%) had long term negative follow up. 93 (12.6%) of patients had abnormal cytological follow up, but only 45 (6.2%) required re-treatment. Within the first year after treatment 52 (7.1%) patients presented with persistent cytological abnormalities, 32 (4.4%) required repeated treatment for persistent dyskaryosis. 41 (5.6%) of patients had recurrent cytological abnormalities, 13 (1.8%) required repeated treatment. Recurrence developed between two and 12 years from initial treatment. One case of cervical carcinoma following treatment with cold coagulation was recorded. Our data suggest that cold coagulation appears to be safe, efficient treatment for cervical intraepithelial neoplasia. PMID:12868697

  14. Cyclooxygenase-2 Expression in Hamster and Human Pancreatic Neoplasia1

    PubMed Central

    Yip-Schneider, Michele T; Savage, Jesse J; Hertzler, Dean A; Cummings, William O

    2006-01-01

    Abstract Cyclooxygenase-2 (COX-2) has been implicated in the development of gastrointestinal malignancies. The aim of the present study was to determine COX-2 expression/activity throughout stages of experimental and human pancreatic neoplasia. COX-2 immunohistochemistry was performed in pancreata of hamsters subjected to the carcinogen N-nitrosobis-(2-oxopropyl)amine (BOP) and in human pancreatic tumors. COX-2 activity was determined by prostaglandin E2 assay in tumor versus matched normal pancreatic tissues. The activity of the COX inhibitor sulindac was tested in the PC-1 hamster pancreatic cancer model. COX-2 expression was elevated in all pancreatic intraepithelial neoplasias (PanINs) and adenocarcinomas. In BOP-treated hamsters, there were significant progressive elevations in COX-2 expression throughout pancreatic tumorigenesis. In human samples, peak COX-2 expression occurred in PanIN2 lesions and remained moderately elevated in PanIN3 and adenocarcinoma tissues. COX-2 activity was significantly elevated in hamster and human pancreatic cancers compared to pair-matched normal pancreas. Furthermore, hamster pancreatic tumor engraftment/formation in the PC-1 hamster pancreatic cancer model was reduced 4.9-fold by oral administration of sulindac. Increased COX-2 expression is an early event in pancreatic carcinogeneses. The BOP-induced hamster carcinogenesis model is a representative model used to study the role of COX-2 in well-differentiated pancreatic tumorigenesis. COX inhibitors may have a role in preventing tumor engraftment/formation. PMID:16820089

  15. A Multiscale Model Evaluates Screening for Neoplasia in Barrett's Esophagus.

    PubMed

    Curtius, Kit; Hazelton, William D; Jeon, Jihyoun; Luebeck, E Georg

    2015-05-01

    Barrett's esophagus (BE) patients are routinely screened for high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) through endoscopic screening, during which multiple esophageal tissue samples are removed for histological analysis. We propose a computational method called the multistage clonal expansion for EAC (MSCE-EAC) screening model that is used for screening BE patients in silico to evaluate the effects of biopsy sampling, diagnostic sensitivity, and treatment on disease burden. Our framework seamlessly integrates relevant cell-level processes during EAC development with a spatial screening process to provide a clinically relevant model for detecting dysplastic and malignant clones within the crypt-structured BE tissue. With this computational approach, we retain spatio-temporal information about small, unobserved tissue lesions in BE that may remain undetected during biopsy-based screening but could be detected with high-resolution imaging. This allows evaluation of the efficacy and sensitivity of current screening protocols to detect neoplasia (dysplasia and early preclinical EAC) in the esophageal lining. We demonstrate the clinical utility of this model by predicting three important clinical outcomes: (1) the probability that small cancers are missed during biopsy-based screening, (2) the potential gains in neoplasia detection probabilities if screening occurred via high-resolution tomographic imaging, and (3) the efficacy of ablative treatments that result in the curative depletion of metaplastic and neoplastic cell populations in BE in terms of the long-term impact on reducing EAC incidence. PMID:26001209

  16. Analysis of digitized cervical images to detect cervical neoplasia

    NASA Astrophysics Data System (ADS)

    Ferris, Daron G.

    2004-05-01

    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.

  17. Microtopographic Inspection and Fractal Analysis of Skin Neoplasia

    NASA Astrophysics Data System (ADS)

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

    2008-04-01

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

  18. Myeloid Neoplasias: What Molecular Analyses Are Telling Us

    PubMed Central

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

    2012-01-01

    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

  19. Cervical neoplasia originating from the vagus nerve in a dog.

    PubMed

    Ruppert, C; Hartmann, K; Fischer, A; Hirschberger, J; Hafner, A; Schmidt, P

    2000-03-01

    An eight-year-old intact male Bernese mountain dog was referred with a history of chronic vomiting, coughing and signs of respiratory distress. Other historical findings included lethargy, weight loss and choking. On presentation, clinical findings were Horner's syndrome, ipsilateral laryngeal hemiplegia, coughing, gagging, respiratory distress and vomiting. Lateral cervical radiographs showed ill-defined mineralisation in the soft tissue ventral to the third cervical vertebra, while ultrasonography of the neck revealed a well marginated heterogeneous mass with focal hyperechogenic lesions and acoustic shadowing. Results of an ultrasound-guided fine needle aspirate suggested neoplasia. At necropsy, a large tumour was detected in the ventral cervical region, originating from the right vagosympathetic trunk. In view of the infiltrating pattern, the cellular pleomorphism and the numerous mitoses on histopathological examination, the tumour was classified as a malignant peripheral nerve sheath tumour. PMID:10759381

  20. Thyroid neoplasia following radiation therapy for Hodgkin's lymphoma

    SciTech Connect

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

    1987-06-01

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

  1. Wilms' tumour gene 1 (WT1) in human neoplasia.

    PubMed

    Keilholz, U; Menssen, H D; Gaiger, A; Menke, A; Oji, Y; Oka, Y; Scheibenbogen, C; Stauss, H; Thiel, E; Sugiyama, H

    2005-08-01

    The transcription factor Wilms' tumour gene 1 (WT1) is important as a prognostic marker as well as in the detection and monitoring of minimal residual disease in leukaemia and myelodysplastic syndromes. Evidence has accumulated over the past decade to show that WT1 is a key molecule for tumour proliferation in a large number of human neoplasms most prominent in acute leukaemias, making it a suitable target for therapeutic strategies. Based on animal results, showing safety and efficacy of immunization with WT1 peptides and protein, early clinical trials in leukaemia have recently been initiated. The First International Conference on WT1 in Human Neoplasia was held in Berlin, March 11--12, 2004. This report reviews the current knowledge on the role of WT1 in tumour promotion and as a diagnostic and therapeutic target, and summarizes the data presented and discussed in this meeting. PMID:15920488

  2. Objective Detection and Delineation of Oral Neoplasia Using Autofluorescence Imaging

    PubMed Central

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

    2009-01-01

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

  3. Three Nordic Berries Inhibit Intestinal Tumorigenesis in Multiple Intestinal Neoplasia\\/1 Mice by Modulating b-Catenin Signaling in the Tumor and Transcription in the Mucosa1-3

    Microsoft Academic Search

    Marjo Misikangas; Anne-Maria Pajari; Essi Paivarinta; Seija I. Oikarinen; Johanna Rajakangas; Maija Marttinen; Heidi Tanayama; Riitta Torronen; Marja Mutanen

    Berries contain a number of compounds that are proposed to have anticarcinogenic properties. We studied the effects and molecular mechanisms of wild berries with different phenolic profiles on intestinal tumorigenesis in multiple intestinal neoplasia\\/1 mice. The mice were fed a high-fat AIN93-G diet (Con) or AIN93-G diets containing 10% (w:w) freeze-dried bilberry, lingonberry (LB), or cloudberry (CB) for 10 wk.

  4. Neoplasias de células plasmáticas (incluso mieloma múltiple)–para profesionales de salud

    Cancer.gov

    Información del Instituto Nacional del Cáncer para profesionales de salud sobre el tratamiento del mieloma múltiple y otras neoplasias de células plasmáticas, así como referencias a estudios clínicos, investigación, estadísticas y otros temas relacionados.

  5. Psychosocial factors and the grade of cervical intra-epithelial neoplasia: a semi-prospective study

    Microsoft Academic Search

    Ellen Stella M Tiersma; Marije L van der Lee; Alexander A. W Peters; Adriaan P Visser; Gert Jan Fleuren; Bert Garssen; Karin M van Leeuwen; Saskia le Cessie; Karl Goodkin

    2004-01-01

    Objective. To study the influence of psychosocial factors on the grade of cervical intra-epithelial neoplasia.Methods. The influence of psychosocial factors on the grade of cervical intra-epithelial neoplasia (CIN) was studied in a group of 342 patients with an abnormal cervical smear. Participants completed a set of questionnaires after colposcopy directed biopsy before knowing the biopsy result. Negatively rated life events,

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

    Microsoft Academic Search

    Paquette

    1992-01-01

    Studies on the etiology of hematopoietic neoplasia (HN) in soft-shell clams, Mya arenaria, have been inconclusive. Petroleum-derived hydrocarbons, polychlorinated-biphenyls and a virus have all been implicated as causative agents. The isolation of 100 nm virus-like particles from neoplastic clams proved conclusively that the causative agent is a retrovirus. The virus can induce a neoplasia in non-neoplastic clams and similar virus

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

    PubMed Central

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

    2009-01-01

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

  8. Gestational trophoblastic neoplasia with retroperitoneal metastases: A fatal complication

    PubMed Central

    2010-01-01

    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

  9. Oncogenic Ras/Src cooperativity in pancreatic neoplasia

    PubMed Central

    Shields, DJ; Murphy, EA; Desgrosellier, JS; Mielgo, A; Lau, SKM; Barnes, LA; Lesperance, J; Huang, M; Schmedt, C; Tarin, D; Lowy, AM; Cheresh, DA

    2011-01-01

    Pancreas cancer is one of the most lethal malignancies and is characterized by activating mutations of Kras, present in 95% of patients. More than 60% of pancreatic cancers also display increased c-Src activity, which is associated with poor prognosis. Although loss of tumor suppressor function (for example, p16, p53, Smad4) combined with oncogenic Kras signaling has been shown to accelerate pancreatic duct carcinogenesis, it is unclear whether elevated Src activity contributes to Kras-dependent tumorigenesis or is simply a biomarker of disease progression. Here, we demonstrate that in the context of oncogenic Kras, activation of c-Src through deletion of C-terminal Src kinase (CSK) results in the development of invasive pancreatic ductal adenocarcinoma (PDA) by 5–8 weeks. In contrast, deletion of CSK alone fails to induce neoplasia, while oncogenic Kras expression yields PDA at low frequency after a latency of 12 months. Analysis of cell lines derived from Ras/Src-induced PDA’s indicates that oncogenic Ras/Src cooperativity may lead to genomic instability, yet Ras/Src-driven tumor cells remain dependent on Src signaling and as such, Src inhibition suppresses growth of Ras/Src-driven tumors. These findings demonstrate that oncogenic Ras/Src cooperate to accelerate PDA onset and support further studies of Src-directed therapies in pancreatic cancer. PMID:21242978

  10. Oncogenic Ras/Src cooperativity in pancreatic neoplasia.

    PubMed

    Shields, D J; Murphy, E A; Desgrosellier, J S; Mielgo, A; Lau, S K M; Barnes, L A; Lesperance, J; Huang, M; Schmedt, C; Tarin, D; Lowy, A M; Cheresh, D A

    2011-05-01

    Pancreas cancer is one of the most lethal malignancies and is characterized by activating mutations of Kras, present in 95% of patients. More than 60% of pancreatic cancers also display increased c-Src activity, which is associated with poor prognosis. Although loss of tumor suppressor function (for example, p16, p53, Smad4) combined with oncogenic Kras signaling has been shown to accelerate pancreatic duct carcinogenesis, it is unclear whether elevated Src activity contributes to Kras-dependent tumorigenesis or is simply a biomarker of disease progression. Here, we demonstrate that in the context of oncogenic Kras, activation of c-Src through deletion of C-terminal Src kinase (CSK) results in the development of invasive pancreatic ductal adenocarcinoma (PDA) by 5-8 weeks. In contrast, deletion of CSK alone fails to induce neoplasia, while oncogenic Kras expression yields PDA at low frequency after a latency of 12 months. Analysis of cell lines derived from Ras/Src-induced PDA's indicates that oncogenic Ras/Src cooperativity may lead to genomic instability, yet Ras/Src-driven tumor cells remain dependent on Src signaling and as such, Src inhibition suppresses growth of Ras/Src-driven tumors. These findings demonstrate that oncogenic Ras/Src cooperate to accelerate PDA onset and support further studies of Src-directed therapies in pancreatic cancer. PMID:21242978

  11. Pharmacological Intervention through Dietary Nutraceuticals in Gastrointestinal Neoplasia.

    PubMed

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

    2014-11-01

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

  12. Microscopic features of colorectal neoplasia in inflammatory bowel diseases.

    PubMed

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

    2014-03-28

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

  13. Minimally invasive therapy of cervical intraepithelial neoplasia for fertility preservation.

    PubMed

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

    2009-09-01

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

  14. The aetiology and associations of conjunctival intraepithelial neoplasia

    PubMed Central

    Kiire, C A; Dhillon, B

    2006-01-01

    Aim To summarise the main causes and associations of conjunctival intraepithelial neoplasia (CIN) found in the literature to date. Method Literature search using Ovid databases on the NHS Scotland E?library, Medline, and the Cochrane Library. The internet search engine Google Scholar was also used to identify relevant articles. Results The main causes and associations of CIN in the literature are sun exposure and distance from the equator; human papillomavirus infection, increased p53 expression, and HIV seropositivity. It has been found that in HIV positive individuals CIN is on the increase with people being affected with more aggressive tumours at younger ages. Conclusion Given that CIN is becoming more common in HIV infected populations and that it has the potential to cause severe disability, it is important to improve our understanding of the condition. Early identification of CIN by an understanding of its aetiology and associations may enable the implementation of preventative measures to reduce its incidence and potentially lead to the diagnosis and further management of conditions such as HIV. Young people presenting with CIN in particular may benefit from HIV testing. PMID:16361679

  15. Stepwise radical endoscopic resection for eradication of Barrett's oesophagus with early neoplasia in a cohort of 169 patients

    Microsoft Academic Search

    Roos E Pouw; Stefan Seewald; Joep J Gondrie; Pierre H Deprez; Hubert Piessevaux; Heiko Pohl; Thomas Rösch; Nib Soehendra; Jacques J Bergman

    2010-01-01

    Background and AimsEndoscopic resection is safe and effective to remove early neoplasia (ie,high-grade intra-epithelial neoplasia\\/early cancer) in Barrett's oesophagus. To prevent metachronous lesions during follow-up, the remaining Barrett's oesophagus can be removed by stepwise radical endoscopic resection (SRER). The aim was to evaluate the combined experience in four tertiary referral centres with SRER to eradicate Barrett's oesophagus with early neoplasia.MethodsDesign:

  16. Tissue prostanoids as biomarkers for chemoprevention of colorectal neoplasia

    PubMed Central

    Yang, Vincent W.; Geiman, Deborah E.; Hubbard, Walter C.; Spannhake, Ernst W.; Hylind, Linda M.; Hamilton, Stanley R.; Giardiello, Francis M.

    2009-01-01

    Recent studies indicate that sulindac, a nonsteroidal anti-inflammatory drug (NSAID), lowers mucosal prostanoid levels and regresses colorectal adenomas in patients with familial adenomatous polyposis (FAP). To determine whether they are biomarkers for sulindac-mediated chemoprevention of colorectal adenomas, levels of 5 prostanoids [prostaglandin (PG) D2, PGE2, PGF2?, thromboxane B2, and 6-keto-PGF1?] in the normal-appearing rectal mucosa from 7 FAP patients with a history of subtotal colectomy and ileorectal anastomosis and 4 FAP patients without surgery, were measured in the absence or presence of exogenously added arachidonic acid before the initiation and at the end of 3 months of sulindac treatment. The addition of arachidonic acid resulted in a uniform increase in the levels of all 5 prostanoids although this increase was selectively attenuated in patients with ileorectal anastomosis who took sulindac. In the latter patients, arachidonic acid also augmented the inhibition of prostanoid synthesis by sulindac. In contrast, sulindac failed to attenuate the increase in prostanoid levels resulting from arachidonic acid in patients without previous surgery. Importantly, when measured in the presence of arachidonic acid, the reduction in the levels of all 5 prostanoids due to sulindac was statistically correlated with a reduction in the size and number of adenomas in the two groups of patients combined. These results suggest that tissue prostanoids measured in the presence of arachidonic acid may serve as sensitive and reliable biomarkers in monitoring the clinical responsiveness of FAP patients undergoing chemoprevention for colorectal neoplasia with NSAIDs. PMID:10680778

  17. Multiple endocrine neoplasias: advances and challenges for the future.

    PubMed

    Alevizaki, M; Stratakis, C A

    2009-07-01

    Several important advances have been made over the last 2 years, since the last international workshop on multiple endocrine neoplasias (MENs) that was held in Marseilles, France (MEN2006). The series of articles that are included in this issue summarize the most important of these advances as they were presented in Delphi, Greece, during the 11th International Workshop on MENs, September 25-27, 2008 (MEN2008). This editorial summarizes some of these advances: the identification of the AIP, and the PDE11A and PDE8B genes by genome-wide association (GWA) studies as predisposing genes for pituitary and adrenal tumours, respectively, the discovery of p27 mutations in a new form of MEN similar to MEN type 1 (MEN 1) that is now known as MEN 4, the molecular investigations of Carney triad (CT), a disorder that associates paragangliomas (PGLs), gastrointestinal stromal tumour (GISTs), and pulmonary chondromas (PCH) with pheochromocytomas and adrenocortical adenomas and other lesions, and the molecular elucidation of the association of GISTs with paragangliomas (Carney-Stratakis syndrome) that is now known to be because of SDHB, SDHC, and SDHD mutations. Molecular investigations in Carney complex (another MEN also described by Dr. Carney, who during the meeting, along with Dr. Charles E. ('Gene') Jackson was honoured for his life-long and many contributions to the field) have also revealed the role of cyclic AMP signalling in tumorigenesis. As our knowledge of the molecular causes of MENs increases, the challenge is to translate these discoveries in better treatments for our patients. Indeed, new advances in the preventive diagnosis and molecular treatment of MEN 1 and MEN 2, respectively, continued unabated, and an update on this front was also presented at MEN2008 and is included in this issue. PMID:19522821

  18. Current treatment options for management of anal intraepithelial neoplasia

    PubMed Central

    Weis, Stephen E

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  20. Molecular heterogeneity and prognostic implications of synchronous advanced colorectal neoplasia

    PubMed Central

    Malesci, A; Basso, G; Bianchi, P; Fini, L; Grizzi, F; Celesti, G; Di Caro, G; Delconte, G; Dattola, F; Repici, A; Roncalli, M; Montorsi, M; Laghi, L

    2014-01-01

    Background: It is uncertain whether synchronous colorectal cancers (S-CRCs) preferentially develop through widespread DNA methylation and whether they have a prognosis worse than solitary CRC. As tumours with microsatellite instability (MSI) may confound the effect of S-CRC methylation on outcome, we addressed this issue in a series of CRC characterised by BRAF and MS status. Methods: Demographics, clinicopathological records and disease-specific survival (DSS) were assessed in 881 consecutively resected CRC undergoing complete colonoscopy. All tumours were typed for BRAFc.1799T>A mutation and MS status, followed by search of germ-line mutation in patients with MSI CRC. Results: Synchronous colorectal cancers (50/881, 5.7%) were associated with stage IV microsatellite-stable (MSS) CRC (19/205, 9.3%, P=0.001) and with HNPCC (9/32, 28%, P<0.001). BRAF mutation (60/881, 6.8%) was associated with sporadic MSI CRC (37/62, 60%, P<0.001) but not with S-CRC (3/50, 6.0%, P=0.96). Synchronous colorectal cancer (HR 1.82; 95% CI 1.15–2.87; P=0.01), synchronous advanced adenoma (HR 1.81; 95% CI 1.27–2.58; P=0.001), and BRAFc.1799T>A mutation (HR 2.16; 95% CI 1.25–3.73; P=0.01) were stage-independent predictors of death from MSS CRC. Disease-specific survival of MSI CRC patients was not affected by S-CRC (HR 0.74; 95% CI 0.09–5.75; P=0.77). Conclusion: Microsatellite-stable CRCs have a worse prognosis if S-CRC or synchronous advanced adenoma are diagnosed. The occurrence and the enhanced aggressiveness of synchronous MSS advanced neoplasia are not associated with BRAF mutation. PMID:24434431

  1. High Resolution Microendoscopy for Quantitative Diagnosis of Esophageal Neoplasia

    NASA Astrophysics Data System (ADS)

    Shin, Dongsuk

    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.

  2. Treatment strategy for gastric non-invasive intraepithelial neoplasia diagnosed by endoscopic biopsy

    PubMed Central

    Nishida, Tsutomu; Tsutsui, Shusaku; Kato, Motohiko; Inoue, Takuya; Yamamoto, Shunsuke; Hayashi, Yoshito; Akasaka, Tomofumi; Yamada, Takuya; Shinzaki, Shinichiro; Iijima, Hideki; Tsujii, Masahiko; Takehara, Tetsuo

    2011-01-01

    Treatment strategies, whether as follow-up or “total incisional biopsy” for gastric noninvasive intraepithelial neoplasia diagnosed by examination of an endoscopic forceps biopsy specimen, are controversial due to problems associated with the diagnostic accuracy of endoscopic forceps biopsy and questions about the safety and efficacy of endoscopic treatment. Based on the histological findings of the biopsy specimen, it is difficult to differentiate between reactive or regenerative changes, inflammation and neoplastic changes, intraepithelial and invasive tumors. Therefore, gastric neoplasia diagnosed as noninvasive intraepithelial often develop into invasive carcinoma during follow-up. Recent advances in endoscopic modalities and treatment devices, such as image-enhanced endoscopy and high-frequency generators, may make endoscopic treatment, such as endoscopic submucosal dissection (ESD), a therapeutic option for gastric intraepithelial neoplasia, including low-grade neoplasms. Future studies are required to evaluate whether ESD is a valid strategy for gastric intraepithelial neoplasm with regard to safety and cost effectiveness. PMID:22180842

  3. RETROSPECTIVE EVALUATION OF CASES OF NEOPLASIA IN A CAPTIVE POPULATION OF EGYPTIAN FRUIT BATS (ROUSETTUS AEGYPTIACUS).

    PubMed

    Olds, June E; Burrough, Eric R; Fales-Williams, Amanda J; Lehmkuhl, Aaron; Madson, Darin; Patterson, Abby J; Yaeger, Michael J

    2015-06-01

    Reports of neoplasia in Chiroptera species are rare. (6 , 10) This retrospective study describes five types of neoplasia identified within a captive population of male Egyptian fruit bats ( Rousettus aegyptiacus ) housed in a zoo from 2004 through November of 2014. Tumor types identified include fibrosarcoma, cutaneous lymphoma, benign focal bronchioloalveolar neoplasm, anaplastic sarcoma, and sebaceous epithelioma. To the author's knowledge, aside from a recent report of focal brochioloalveolar adenoma, (8) these tumor types have not previously been described in the Rousettus species, nor in chiropterans in general. Based upon these findings and other recent publications regarding R. aegyptiacus , neoplasia does appear to be a significant cause of morbidity and mortality in captive members of this megachiropterid species. PMID:26056887

  4. “Intrafollicular neoplasia” of nodular lymphocyte predominant Hodgkin lymphoma. Description of a hypothetic early step of the disease

    Microsoft Academic Search

    Antonino Carbone; Annunziata Gloghini

    The 2008 “WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues” has addressed the problem of intrafollicular neoplasia\\/“in situ” lesion for follicular lymphoma (FL). The concept of “intrafollicular neoplasia” has also been proposed for other lymphomas in which the putative normal counterpart of the tumor cell is located in the germinal center (GC) or the mantle zone or the marginal

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

    SciTech Connect

    Paquette, G.E.

    1992-01-01

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

  6. Pulmonary lymphangioleiomyoma in a patient with multiple endocrine neoplasia type I.

    PubMed

    Carnevale, V; Romagnoli, E; Remotti, D; D'Erasmo, E; Spagna, G; Pisani, D; Rosso, R; Minisola, S; Mazzuoli, G F

    1997-05-01

    The multiple endocrine neoplasia (M.E.N.) syndromes consist of a group of proliferative disorders that selectively target specific sets of endocrine and soft tissue cells. Here we report a case of lymphangioleiomyoma of the lung in a patient with multiple endocrine neoplasia Type I (M.E.N. I). This is the first time such an association has been reported. In our opinion it could possibly be ascribed to the genetic predisposition to proliferative disorders of patients with M.E.N. syndromes. PMID:9258808

  7. Thymic carcinoids in multiple endocrine neoplasia type 1.

    PubMed Central

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

    1998-01-01

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

  8. Faecal calprotectin levels in a high risk population for colorectal neoplasia

    Microsoft Academic Search

    O Kronborg; M Ugstad; P Fuglerud; B Johne; J Hardcastle; J H Scholefield; K Vellacott; V Moshakis; J R Reynolds

    2000-01-01

    BACKGROUNDFaecal concentrations of the protein calprotectin have been found to be elevated in patients with colorectal neoplasia, suggesting that it might be used as a screening tool for colorectal cancer as well as adenomas.AIMSTo measure the sensitivity and specificity of faecal calprotectin for the detection of adenomas in high risk individuals undergoing colonoscopy. Also, to investigate between and within stool

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

    E-print Network

    Raftery, Adrian

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

  10. A hypothesis to relate salivary tumors with mammary and prostate neoplasias

    Microsoft Academic Search

    Adriana B. Actis

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

  11. World J Urol . Author manuscript High-grade prostatic intraepithelial neoplasia and atypical small acinar

    E-print Network

    Boyer, Edmond

    proliferation (ASAP) in initial 21-core extended biopsy scheme and to determine the prostate cancer detection of prostate cancer. MESH Keywords Aged ; Biopsy ; Humans ; Incidence ; Male ; Middle Aged ; Population neoplasia ; prostate cancer ; saturation biopsy INTRODUCTION In most of the cases, results of prostate

  12. Genetic and clinical analysis in 10 Spanish patients with multiple endocrine neoplasia type 1

    Microsoft Academic Search

    Aránzazu Cebrián; Jose Luis Herrera-Pombo; Juan José Díez; Olga Sánchez-Vilar; Jose Ignacio Lara; Clotilde Vázquez; Antonio Picó; Ana Osorio; Beatriz Martínez-Delgado; Javier Benítez; Mercedes Robledo

    1999-01-01

    Multiple endocrine neoplasia type 1 (MEN 1) is characterised by the combination of tumours of the parathyroid, endocrine pancreas and anterior pituitary glands. In 1988 the MEN 1 gene was mapped to chromosome 11q13 and it was cloned in 1997. This gene contains 10 exons and extends across 9 Kb of genomic DNA; it encodes for a product of 610

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

    Microsoft Academic Search

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

    2004-01-01

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

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

    Microsoft Academic Search

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

    2002-01-01

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

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

    PubMed Central

    Faro, Edited by Sebastian

    2006-01-01

    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.

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

    Microsoft Academic Search

    R. W Jones; Judith Baranyai; S Stables

    1997-01-01

    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.

  17. Parent-of-origin effects in multiple endocrine neoplasia Type 2B

    Microsoft Academic Search

    K. M. Carlson; J. Bracamontes; S. A. Jr. Wells; P. J. Goodfellow; C. E. Jackson; R. Clark; A. Lacroix

    1994-01-01

    Multiple endocrine neoplasia type 2B (MEN 2B) is characterized by medullary thyroid carcinoma, pheochromocytomas, mucosal neuromas, ganglioneuromas, and skeletal and ophthalmic abnormalities. It is observed as both inherited and sporadic disease, with an estimated 50% of cases arising de novo. A single point mutation in the catalytic core region of the receptor tyrosine kinase, RET, has been observed in germ-line

  18. Genetics of Endocrine and Neuroendocrine Neoplasias–for health professionals (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.

  19. Management and evolution of cervical intraepithelial neoplasia during pregnancy and postpartum

    Microsoft Academic Search

    Evangelos Paraskevaidis; George Koliopoulos; Sophia Kalantaridou; Lambrini Pappa; Iordanis Navrozoglou; Kostas Zikopoulos; Dimitrios E Lolis

    2002-01-01

    Objective: To investigate the evolution of cervical intraepithelial neoplasia (CIN), and to evaluate the safety of cytological and colposcopical surveillance of women with CIN during pregnancy. Study design: Ninety-eight women with antenatal cytological and\\/or colposcopical impression of CIN were followed up during pregnancy with cytology and colposcopy every 2 months. A cytological and colposcopical reevaluation 2 months postpartum was done,

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

    Microsoft Academic Search

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

    1995-01-01

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

  1. Selenium-Enriched Broccoli Decreases Intestinal Tumorigenesis in Multiple Intestinal Neoplasia Mice

    Microsoft Academic Search

    Cindy D. Davis; Huawei Zeng; John W. Finley

    Multiple intestinal neoplasia (Min) mice are a good model for the investigation of the effects of dietary alterations in a genetic model for intestinal cancer. Previ- ous studies have shown that selenium-enriched broccoli is protective against chemically induced colon cancer sus- ceptibility. This study investigated whether selenium-en- riched broccoli would be protective against intestinal can- cer susceptibility in Min mice.

  2. Presumed corneal intraepithelial neoplasia associated with contact lens wear and intense ultraviolet light exposure.

    PubMed Central

    Guex-Crosier, Y; Herbort, C P

    1993-01-01

    Corneal intraepithelial neoplasia (CIN) is a rare dysplastic process affecting mostly elderly fair-skinned people. A variant of the disease associated with contact lens wear was recently described. The three cases reported here had a history of contact lens wear together with strong ultraviolet light exposure. These two conditions may represent a serious risk factor for the development of CIN. Images PMID:8457517

  3. High-grade prostatic intraepithelial neoplasia and prostate cancer risk reduction

    Microsoft Academic Search

    Mitchell S. Steiner

    2003-01-01

    High-grade prostatic intraepithelial neoplasia (PIN) is the earliest accepted stage in carcinogenesis, possessing most of the phenotypic and biochemical changes in cancer without invasion of the basal membrane of the acini. The support for high-grade PIN as the main premalignant lesion of prostate cancer is based on several lines of evidence derived from prostate cancer animal models, epidemiological, morphological, genetic,

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

    Microsoft Academic Search

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

    1998-01-01

    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

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

    Microsoft Academic Search

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

    1992-01-01

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

  6. Lymphocytic alveolitis and pleural calcifications in nonoccupational asbestos exposure. Protection against neoplasia?

    PubMed

    Constantopoulos, S H; Dalavanga, Y A; Sakellariou, K; Goudevenos, J; Kotoulas, O B

    1992-12-01

    Inhabitants of the Metsovo area in Northwest Greece (population, 4,000) have been exposed to asbestos through the use of whitewash containing tremolite. This has resulted in endemic pleural calcifications (PCs) and increased incidence of malignant pleural mesothelioma (MPM). In order to evaluate the lung response to the fiber, bronchoalveolar lavage (BAL) was performed in 25 Metsovites; 14 with PCs, three with PCs and neoplasia, five without PCs, and three without PCs but with established neoplasia. There were no differences between the four groups with regard to age or exposure. Twelve Metsovites had lymphocytic alveolitis (BAL lymphocytes > 15%). Eleven belonged to the group with PCs and one belonged to the group without PCs. None of those with neoplasia had alveolitis. The lymphocytes were mainly helper T-cells, and activation markers were more frequent among those with PCs. We have previously reported on the relative absence of PCs in Metsovites with malignant pleural mesothelioma. This observation and the results of the present study suggest that lymphocytic alveolitis correlates with pleural calcifications, whereas both are rarely present in patients with neoplasia. PMID:1456576

  7. Prevalence of neoplasia in 10 New England populations of the soft-shell clam (Mya arenaria)

    Microsoft Academic Search

    Robert S. Brown; Richard E. Wolke; Saul B. Saila; Chris W. Brown

    1977-01-01

    Neoplasia was a prevalent disease of the soft-shell clam and was found in widely geographically distinct sites in New England. Two types of neoplasms were recognized. Most were of hematopoietic origin, except in clams from Maine, which also had gonadal neoplasms. Both types were apparently malignant neoplasms, based on their characteristic anaplastic appearance, invasiveness, metastasis, mitotic activity, associated tissue necrosis,

  8. Reverse transcriptase activity in tissues of the soft shell clam Mya arenaria affected with haemic neoplasia

    Microsoft Academic Search

    M. AboElkhair; S. Synard; A. Siah; J. Pariseau; J. Davidson; G. Johnson; S. J. Greenwood; J. W. Casey; F. C. J. Berthe; A. Cepica

    2009-01-01

    Since all retroviruses possess reverse transcriptase (RT) enzyme, reverse transcriptase activity has been the main supportive evidence of retroviral etiology of haemic neoplasia (HN) in soft shell clams, Mya arenaria. The objective of the present study was to search for a putative retrovirus in various tissues of diseased clams following quantification of RT activity (biochemical indicator of retroviral infection). The

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

    NASA Astrophysics Data System (ADS)

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

    2000-12-01

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

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

    PubMed Central

    Preda, Veronica; Sywak, Mark; Learoyd, Diana

    2015-01-01

    Key Clinical Message We report a patient with multiple endocrine neoplasia type 1 (MEN-1) and an aggressive malignant peripheral nerve sheath tumor (MPNST) arising from a ganglioneuroma of the adrenal gland. Patients with MEN-1 require careful consideration of other tumor associations, including MPNST, as it can portend a poor prognosis. MEN-1 and MPNST have not been reported. We report a patient with multiple endocrine neoplasia type 1 (MEN-1) and an aggressive malignant peripheral nerve sheath tumor (MPNST) arising from a ganglioneuroma of the adrenal gland. Patients with MEN-1 require careful consideration of other tumor associations, including MPNST, as it can portend a poor prognosis. MEN-1 and MPNST have not been reported. PMID:25678969

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

    PubMed

    Sotos, John G

    2012-07-01

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

  12. Condylomata of the uterine cervix and koilocytosis of cervical intraepithelial neoplasia.

    PubMed Central

    Pilotti, S; Rilke, F; De Palo, G; Della Torre, G; Alasio, L

    1981-01-01

    In 202 women with koilocytotic atypia in cervical smears, 136 had predominantly small condylomata of the uterine cervix, and 66 had cervical intraepithelial neoplasia (CIN) of varying degree either with koilocytosis of the neoplasia or associated with condylomata. Koilocytosis correlated well with the histological diagnosis of condylomata, but occasionally it obscured the cytological evidence of CIN. Human papilloma virus particles were found in the cells of condylomata in 10 cases and in those of CIN II with koilocytosis in two cases of 21 examined ultrastructurally. There was evidence that the condyloma of the uterine cervix is a well-defined morphological entity and also that cytopathie changes similar to those seen in condylomata are present in some cases of CIN. Images PMID:6265503

  13. Prevalence of neoplasia in 10 New England populations of the soft-shell clam (Mya arenaria).

    PubMed

    Brown, R S; Wolke, R E; Saila, S B; Brown, C W

    1978-09-29

    Neoplasia was a prevalent disease of the soft-shell clam and was found in widely geographically distinct sites in New England. Two types of neoplasms were recognized. Most were of hematopoietic origin, except in clams from Maine, which also had gonadal neoplasms. Both types were apparently malignant neoplasms, based on their characteristic anaplastic appearance, invasiveness, metastasis, mitotic activity, associated tissue necrosis, and mortality. Diagnosis of neoplasia in the living mollusk was achieved rapidly and accurately by cytologic examination of circulating blood. The etiology of the neoplasms was not identified. In general, nonneoplastic lesions, such as epithelial hyperplasia and accumulations of a orange-brown bodies, were more common in clams from polluted areas. PMID:280191

  14. 2006 Bethesda International Consensus recommendations on the immunophenotypic analysis of hematolymphoid neoplasia by flow cytometry: optimal reagents and reporting for the flow cytometric diagnosis of hematopoietic neoplasia.

    PubMed

    Wood, Brent L; Arroz, Maria; Barnett, David; DiGiuseppe, Joseph; Greig, Bruce; Kussick, Steven J; Oldaker, Teri; Shenkin, Mark; Stone, Elizabeth; Wallace, Paul

    2007-01-01

    Immunophenotyping by flow cytometry has become standard practice in the evaluation and monitoring of patients with hematopoietic neoplasia. However, despite its widespread use, considerable variability continues to exist in the reagents used for evaluation and the format in which results are reported. As part of the 2006 Bethesda Consensus conference, a committee was formed to attempt to define a consensus set of reagents suitable for general use in the diagnosis and monitoring of hematopoietic neoplasms. The committee included laboratory professionals from private, public, and university hospitals as well as large reference laboratories that routinely operate clinical flow cytometry laboratories with an emphasis on lymphoma and leukemia immunophenotyping. A survey of participants successfully identified the cell lineage(s) to be evaluated for each of a variety of specific medical indications and defined a set of consensus reagents suitable for the initial evaluation of each cell lineage. Elements to be included in the reporting of clinical flow cytometric results for leukemia and lymphoma evaluation were also refined and are comprehensively listed. The 2006 Bethesda Consensus conference represents the first successful attempt to define a set of consensus reagents suitable for the initial evaluation of hematopoietic neoplasia. PMID:17803189

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

    Microsoft Academic Search

    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

    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

  16. Incidence of squamous neoplasia of the cervix and vagina in des-exposed daughters.

    PubMed

    Hatch; Herbst; Hoover; Noller; Adam; Kaufman; Palmer; Titus-Ernstoff; Hyer; Robboy

    2000-10-01

    PURPOSE: Women exposed to diethylstibestrol (DES) in utero are known to have an excess risk of clear cell adenocarcinoma of the vagina and cervix, in addition to vaginal epithelial changes, but the effect on the incidence of squamous neoplasia is uncertain. This study evaluated the long-term risk of developing high-grade squamous neoplasia of the genital tract among women exposed prenatally to diethylstilbestrol.METHODS: A cohort comprising 3899 DES-exposed and 1374 unexposed daughters was followed for thirteen years (1982-1995) for pathology-confirmed diagnoses of high-grade squamous neoplasia. A pathologist blinded to exposure status reviewed seventy-seven percent of cases. Poisson regression analysis was used to compute relative risks (RR) and 95% confidence intervals (CI) controlling for age, calendar year, screening history and other covariates.RESULTS: The RR (95% CI) among DES-exposed versus unexposed, based on 111 cases of high-grade disease, was 2.12 (1.19-3.77). Adjustment for screening history had little effect, but when the analysis was restricted to a group highly screened before 1982, the risk was reduced. Risk estimates were higher among women exposed earlier in gestation; the RR (95% CI) for exposure within 7 weeks of the last menstrual period was 2.82 (1.43-5.53).CONCLUSIONS: The findings support an association between in utero DES exposure and high-grade squamous neoplasia, although a role for more intensive screening among DES-exposed women in the production of this excess could not be completely ruled out. PMID:11018391

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

    Microsoft Academic Search

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

    2006-01-01

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

  18. Cervical intraepithelial neoplasia outcomes after large loop excision with clear margins

    Microsoft Academic Search

    Evangelos Paraskevaidis; Evangelos D Lolis; George Koliopoulos; Yiannis Alamanos; Stylianos Fotiou; Henry C Kitchener

    2000-01-01

    Objective: To identify risk factors for residual or recurrent cervical intraepithelial neoplasia (CIN) after large loop excision of the transformation zone with clear margins.Methods: We did a case-control study of women treated with loop excision for CIN who had adequate follow-up and in whom margins were believed to be clear. Women with clear margins in whom no subsequent lesions were

  19. Multicomponent Analysis of the Pancreatic Adenocarcinoma Progression Model Using a Pancreatic Intraepithelial Neoplasia Tissue Microarray

    Microsoft Academic Search

    Anirban Maitra; N Volkan Adsay; Pedram Argani; Christine Iacobuzio-Donahue; Angelo De Marzo; John L Cameron; Charles J Yeo; Ralph H Hruban

    2003-01-01

    A multistep model for pancreatic adenocarcinoma has been proposed recently. In this model, well-defined, noninvasive ductal lesions are recognized as precursors of invasive cancer and have been classified under the nomenclature of pancreatic intraepithelial neoplasia, or PanIN. Increasing evidence suggests that PanINs represent true neoplasms of the pancreatic ductal epithelium, accumulating histologic and genetic abnormalities in their progression toward invasive

  20. Pancreatic intraepithelial neoplasia and infiltrating adenocarcinoma: Analysis of progression and recurrence by DPC4 immunohistochemical labeling

    Microsoft Academic Search

    Denis M McCarthy; Daniel J Brat; Robb E Wilentz; Charles J Yeo; John L Cameron; Scott E Kern; Ralph H Hruban

    2001-01-01

    Pancreatic intraepithelial neoplasia (PanIN) is thought to be a precursor lesion of infiltrating pancreatic ductal adenocarcinoma (IPA). DPC4 is a tumor-suppressor gene on chromosome 18q21.1 and is inactivated in approximately 55% of IPAs. Recently, immunohistochemical labeling using a monoclonal antibody to the Dpc4 protein has been shown to mirror DPC4 genetic status in invasive adenocarcinomas of the pancreas. In the

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

    PubMed Central

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

    2013-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Baker, Kevin C.; Bambot, Shabbir

    2011-02-01

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

  3. Human papillomavirus-associated balanoposthitis--a marker for penile intraepithelial neoplasia?

    PubMed

    Wikström, Arne; Hedblad, Mari-Anne; Syrjänen, Stina

    2013-12-01

    The purpose of this study was to analyse, among men treated with diathermy, whether there was a difference in balanoposthitis between men with histopathologically benign human papillomavirus-associated lesions and those with penile intraepithelial neoplasia. Data were derived from patient material from a previously published study. Two clinically identical lesions from the same genital site were collected for analysis with routine histopathology and with nested PCR. In total, 292 men were included, of which 47 (16%) had penile intraepithelial neoplasia. Of those with penile intraepithelial neoplasia, 19/47 (40%) reported problems consistent with balanoposthitis, compared with only 15/245 (6%) patients with benign lesions (p < 0.0001). A statistical difference in percentage distribution was also seen regarding morphology (p = 0.001) and location (p = 0.0003) of the lesions among the men having benign lesions with and without balanoposthitis. It is not possible to take biopsies from patients with genital warts, but this study suggests that one probably should be more observant for genital dysplasia among those men with warts with a history of balanoposthitis than those with no such history. PMID:23970611

  4. The American College of Obstetricians and Gynecologists Committee Opinion no. 631. Endometrial intraepithelial neoplasia.

    PubMed

    2015-05-01

    Endometrial hyperplasia is of clinical significance because it is often a precursor lesion to adenocarcinoma of the endometrium. Making the distinction between hyperplasia and true precancerous lesions or true neoplasia has significant clinical effect because their differing cancer risks must be matched with an appropriate intervention to avoid undertreatment or overtreatment. Pathologic diagnosis of premalignant lesions should use criteria and terminology that clearly distinguish between clinicopathologic entities that are managed differently. At present, the endometrial intraepithelial neoplasia schema is tailored most closely to this objective, incorporating modified pathologic criteria based upon evidence that has become available since the creation of the more widely used 1994 four-class World Health Organization schema (in which atypical hyperplasia is equated with precancerous behavior). The accuracy of dilation and curettage compared with endometrial suction curette in diagnosing precancer and excluding concurrent carcinoma is unclear. Hysteroscopy with directed biopsy is more sensitive than dilation and curettage in the diagnosis of uterine lesions. When clinically appropriate, total hysterectomy for endometrial intraepithelial neoplasia provides definitive assessment of a possible concurrent carcinoma and effectively treats premalignant lesions. Systemic or local progestin therapy is an unproven but commonly used alternative to hysterectomy that may be appropriate for women who are poor surgical candidates or who desire to retain fertility. PMID:25932867

  5. Modeling Inducible Human Tissue Neoplasia Identifies an Extracellular Matrix Interaction Network Involved in Cancer Progression

    PubMed Central

    Reuter, Jason A.; Ortiz-Urda, Susana; Kretz, Markus; Garcia, John; Scholl, Florence A.; Pasmooij, Anna M.G.; Cassarino, David; Chang, Howard Y.; Khavari, Paul A.

    2009-01-01

    To elucidate mechanisms of cancer progression, we generated inducible human neoplasia in 3-dimensionally intact epithelial tissue. Gene expression profiling of both epithelia and stroma at specific time points during tumor progression revealed sequential enrichment of genes mediating discrete biologic functions in each tissue compartment. A core cancer progression signature was distilled using the increased signaling specificity of downstream oncogene effectors and subjected to network modeling. Network topology predicted that tumor development depends upon specific ECM-interacting network hubs. Blockade of one such hub, the ?1 integrin subunit, disrupted network gene expression and attenuated tumorigenesis in vivo. Thus, integrating network modeling and temporal gene expression analysis of inducible human neoplasia provides an approach to prioritize and characterize genes functioning in cancer progression. Significance Investigating tumor progression in patient samples is complicated by etiologic heterogeneity, genetic instability, and an overabundance of precursor lesions that fail to progress. These complexities obscure construction of a dynamic picture of progression from normal tissue to invasive cancer. Here, we generate inducible human neoplasia driven by conditionally active Ras and characterize the sequence of gene expression programs engaged in epithelial tumor tissue and adjacent stroma during carcinogenesis. We show that tumor-intrinsic gene expression can be refined by sufficient downstream oncogene effectors and apply a generalizable network modeling strategy to prioritize targets based upon local interconnectivity. This analysis highlights the importance of tumor-stroma interaction during tumorigenesis and identifies ? integrin as a potential oncotherapeutic that distinguishes normal and neoplastic tissue. PMID:19477427

  6. Immunophenotypic and antigen receptor gene rearrangement analysis in T cell neoplasia.

    PubMed Central

    Knowles, D. M.

    1989-01-01

    The author reviews the immunophenotypic profiles displayed by the major clinicopathologic categories of T cell neoplasia, the immunophenotypic criteria useful in the immunodiagnosis of T cell neoplasia, and the contributions made by antigen receptor gene rearrangement analysis to the understanding of T cell neoplasia. Neoplasms belonging to distinct clinicopathologic categories of T cell neoplasia often exhibit characteristic immunophenotypic profiles. Approximately 80% of lymphoblastic lymphomas and 20% of acute lymphoblastic leukemias express phenotypes consistent with prethymic and intrathymic stages of T cell differentiation, including intranuclear terminal deoxynucleotidyl transferase. Cutaneous T cell lymphomas of mycosis fungoides type usually express pan-T cell antigens CD2, CD5, and CD3, often lack the pan-T cell antigen CD7, and usually express the mature, peripheral helper subset phenotype, CD4+ CD8-. Cutaneous T cell lymphomas of nonmycosis fungoides type and peripheral T cell lymphomas often lack one or more pan-T cell antigens and, in addition, occasionally express the anomalous CD4+ CD8+ or CD4- CD8- phenotypes. T gamma-lymphoproliferative disease is divisable into two broad categories: those cases that are CD3 antigen positive and exhibit clonal T cell receptor beta chain (TCR-beta) gene rearrangements and those cases that are CD3 antigen negative and exhibit the TCR-beta gene germline configuration. Human T cell lymphotropic virus-I (HTLV-I) associated Japanese, Carribean, and sporadic adult T cell leukemia/lymphomas usually express pan-T cell antigens, the CD4+ CD8- phenotype, and various T cell-associated activation antigens, including the interleukin-2 receptor (CD25). Immunophenotypic criteria useful in the immunodiagnosis of T cell neoplasia include, in increasing order of utility, T cell predominance, T cell subset antigen restriction, anomalous T cell subset antigen expression, and deletion of one or more pan-T cell antigens. Only in exceptional circumstances do normal, non-neoplastic T cell populations express the CD4- CD8- or the CD4+ CD8+ phenotype and/or lack one or more pan-T cell antigens. T cell receptor beta chain gene rearrangement analysis represents an accurate, objective, and sensitive molecular genetic marker of T cell lineage and clonality that allows discrimination among non-T cell, polyclonal T cell and monoclonal T cell populations. Non-T cells exhibit the TCR-beta gene germline configuration.(ABSTRACT TRUNCATED AT 400 WORDS) Images Figure 3 Figure 6 Figure 7 PMID:2495724

  7. Quantitative evaluation of in vivo vital-dye fluorescence endoscopic imaging for the detection of Barrett's-associated neoplasia.

    PubMed

    Thekkek, Nadhi; Lee, Michelle H; Polydorides, Alexandros D; Rosen, Daniel G; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca

    2015-05-01

    Current imaging tools are associated with inconsistent sensitivity and specificity for detection of Barrett's-associated neoplasia. Optical imaging has shown promise in improving the classification of neoplasia in vivo. The goal of this pilot study was to evaluate whether in vivo vital dye fluorescence imaging (VFI) has the potential to improve the accuracy of early-detection of Barrett's-associated neoplasia. In vivo endoscopic VFI images were collected from 65 sites in 14 patients with confirmed Barrett's esophagus (BE), dysplasia, oresophageal adenocarcinoma using a modular video endoscope and a high-resolution microendoscope(HRME). Qualitative image features were compared to histology; VFI and HRME images show changes in glandular structure associated with neoplastic progression. Quantitative image features in VFI images were identified for objective image classification of metaplasia and neoplasia, and a diagnostic algorithm was developed using leave-one-out cross validation. Three image features extracted from VFI images were used to classify tissue as neoplastic or not with a sensitivity of 87.8% and a specificity of 77.6% (AUC = 0.878). A multimodal approach incorporating VFI and HRME imaging can delineate epithelial changes present in Barrett's-associated neoplasia. Quantitative analysis of VFI images may provide a means for objective interpretation of BE during surveillance. PMID:25950645

  8. Applications and advancements in the use of high-resolution microendoscopy for detection of gastrointestinal neoplasia.

    PubMed

    Louie, Justin S; Richards-Kortum, Rebecca; Anandasabapathy, Sharmila

    2014-11-01

    The high-resolution microendoscope (HRME) is a novel imaging modality that allows real-time epithelial imaging at subcellular resolution. Used in concert with any standard endoscope, this portable, low cost, "optical biopsy" technology has the ability to provide images of cellular morphology during a procedure. This technology has been the subject of a number of studies investigating its use in screening and surveillance of a range of gastrointestinal neoplasias, including esophageal adenocarcinoma, esophageal squamous cell cancer, colorectal neoplasia, and anal neoplasia. These studies have shown that HRME is a modality that consistently provides high specificity, negative predictive value, and accuracy across different diseases. In addition, they have illustrated that HRME users can be relatively easily trained in a short period of time, and that users have demonstrated solid inter-rater reliability. These features make HRME a potential complement to high-definition white-light imaging, narrow-band imaging, and other red flag technologies in facilitating real-time clinical diagnosis, endoscopic therapy, and margin determination. Further clinical validation is needed to determine whether this translates to reduced procedure times, pathology costs, and follow-up procedures. Finally, the HRME has a relatively simple design compared with other similar technologies, making it portable, simple to maintain, and low cost. This may allow the HRME device to function in both advanced care settings as well as in places with less resources and specialized support systems. As a whole, the HRME device has shown good performance along with low cost and portable construction, and its application in different conditions and settings has been promising. PMID:25108219

  9. HPV-Type Distribution and Reproducibility of Histological Diagnosis in Cervical Neoplasia in Poland.

    PubMed

    Nowakowski, Andrzej; de Souza, Sabrina Collas; Jach, Robert; Rosillon, Dominique; Ksi??ek, Alicja; Holl, Katsiaryna

    2015-07-01

    This study was performed to assess attribution of high grade cervical intraepithelial neoplasia (HG-CIN) and invasive cervical cancer (ICC) to human papillomavirus (HPV) genotypes and secondarily to assess reproducibility of HG-CIN/ICC diagnosis obtained in Poland. Formaldehyde fixed, paraffin embedded blocks of HG-CIN/ICC from two distant institutions were sent to a central laboratory together with original histological diagnoses. Central/expert review of histopathological specimens was performed and agreement between local and central/expert diagnoses was calculated. HPV detection and genotyping in the samples was carried out with the use of SPF10-LiPA25 technology. Results were analyzed for 205 HG-CIN and 193 ICC cases with centrally confirmed diagnoses. Kappa coefficients and 95 % confidence intervals for HG-CIN and ICC diagnoses were: 0.13 (0.09;0.17) and 0.19 (0.11;0.26) respectively. Cohen's kappa coefficients for lesions with representative number of samples ranged from 0.01 for cervical intraepithelial neoplasia grade 2 to 0.75 for adenocarcinoma. HPV DNA was detected in 96.1 and 91.2 % of the confirmed HG-CIN and ICC specimens respectively. HPV positive HG-CIN was most commonly attributed to HPV types: 16 (62.8), 33 (7.8), 31 (6.6), 52 (3.7), 45 (2.6) and 58 (2.6 %). HPV positive ICC was most commonly attributed to HPV types: 16 (72.1), 18 (10.8), 33 (5.7), 45 (3.4) and 31 (1.7 %). Reproducibility of histological diagnosis of HG-CIN/ICC obtained in Poland generally increases with the severity of lesion and is lowest for cervical intraepithelial neoplasia grade 2 and highest for adenocarcinoma. Over 80 % of ICC cases are vaccine-preventable in Poland. PMID:25547828

  10. Human herpesvirus 8-encoded proteins with potential roles in virus-associated neoplasia.

    PubMed

    Nicholas, John

    2007-01-01

    Human herpesvirus 8 (HHV-8) is a gamma-2 herpesvirus, related genetically to simian herpesvirus saimiri (HVS), the prototype virus of this subgroup of the gammaherpesvirus subfamily. HHV-8 DNA is present in all forms of Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL), and in most forms of multicentric Castleman's disease (MCD), especially in HIV infected individuals. Of relevance to attempts to explain the molecular basis of HHV-8 associated neoplasia, are the unique genes specified by this virus, in particular angiogenic cytokines viral interleukin-6 (vIL-6) and viral CC-class chemokines (vCCL-1, vCCL-2, vCCL-3), mitogenic signaling membrane proteins variable ITAM-containing protein (VIP) and latency associated membrane protein (LAMP), pro-survival latently-expressed viral interferon regulatory factor (vIRF3), and the kaposin family of proteins that promote cell growth and cytokine production. Also of relevance are the angiogenic and cytokine-inducing viral G protein-coupled receptor (vGPCR), pro-proliferative and pro-survival latency proteins viral FLICE inhibitory protein (vFLIP) and latency-associated nuclear antigen (LANA), and G1-S phase cell-cycle promoter viral cyclin (v-cyclin), proteins specified also by other gamma-2 herpesviruses. The enormous progress on the characterization of the properties and biological activities of these proteins over the last ten years has provided insight into the potential mechanisms of HHV-8-induced neoplasia. Present data suggest that there operates a combination of cell transformation mediated by latently expressed proteins that promote cell proliferation and survival coupled with paracrine signaling functions mediated by either the viral cytokines or viral receptor-induced secreted cellular proteins. This review discusses the properties of the viral proteins believed to contribute to viral neoplasia via these mechanisms. PMID:17127298

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

    NASA Astrophysics Data System (ADS)

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

    2008-02-01

    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.

  12. Chlamydia trachomatis and cervical intraepithelial neoplasia in married women in a Middle Eastern community.

    PubMed

    Valadan, M; Yarandi, F; Eftekhar, Z; Danvish, S; Fathollahi, M S; Mirsalehian, A

    2010-03-01

    The objective of this study was to determine the association between vaginal Chlamydia infection and cervical intraepithelial neoplasia (CIN). Data were collected in a case-control study for 60 patients with CIN in biopsy and 85 control subjects with normal colposcopy and biopsy. Serum antibodies to C trachomatis were associated with an increased risk for CIN [odds ratio (OR) = 7.3; 95% confidence interval (CI) 1.5-35.2)]. There was also a significant association between presence of inclusion bodies for C. trachomatis and CIN (OR = 5.5; 95% CI 2.4-12.4). These results indicate a strong association between CIN and chlamydial cervicitis. PMID:20795445

  13. Sebaceous neoplasia and the Muir–Torre syndrome: important connections with clinical implications

    PubMed Central

    Shalin, Sara C; Lyle, Stephen; Calonje, Eduardo; Lazar, Alexander J F

    2009-01-01

    Sebaceous neoplasia comprises a spectrum ranging from benign to malignant. Proper histological identification is important for treatment, prognosis and potential association with the Muir–Torre syndrome (MTS). Our increased understanding of the significance and pathogenesis of these tumours has led to improved risk stratification, screening recommendations, and treatment of patients with an initial presentation of a sebaceous tumour. This review focuses on the diagnostic and histological features of sebaceous lesions, the MTS, and recent insights into the molecular pathogenesis of sebaceous tumorigenesis. PMID:20055911

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

    Microsoft Academic Search

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

    2008-01-01

    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

  15. Neoplasia intraepitelial anal: resultados de la aplicación de un protocolo diagnóstico en pacientes de riesgo mediante el uso de citología anal

    Microsoft Academic Search

    Estela Membrilla-Fernández; David Parés; Francisco Alameda; Marta Pascual; Ricard Courtier; María José Gil; Gabriel Vallecillo; Pere Fusté; Miguel Pera; Luis Grande

    2009-01-01

    IntroductionAnal intraepithelial neoplasia is a precursor condition of squamous anal carcinoma. The groups at risk of this lesion are patients with anogenital condylomata, cervical dysplasia, human immunodeficiency virus infection and, in general, patients with HPV infection. The aim of this study was to analyse the results of a diagnostics protocol of Anal Intraepithelial Neoplasia in high risk population using anal

  16. Diagnosis of Retrobulbar Round Cell Neoplasia in a Macaroni Penguin ( Eudyptes chrysolophus ) Through Use of Computed Tomography.

    PubMed

    Woodhouse, Sarah J; Rose, Michelle; Desjardins, Danielle R; Acvp, Dipl; Agnew, Dalen W

    2015-03-01

    A 25-year-old female macaroni penguin ( Eudyptes chrysolophus ) was diagnosed with exophthalmos secondary to retrobulbar neoplasia through use of computed tomography (CT). Histopathologic examination of the mass supported a diagnosis of malignant round cell neoplasia. Immunohistochemical (IHC) labeling was applied to determine cell origin; the neoplastic cells did not label with T-cell marker CD3 or B-cell marker BLA.36 and could not be further characterized. The scleral ossicles precluded evaluation of the retrobulbar space by ultrasonography; therefore, CT scanning is recommended for examination of intraorbital structures in penguin and other avian species. PMID:25867665

  17. Colorectal Neoplasia Differentially Expressed (CRNDE), a Novel Gene with Elevated Expression in Colorectal Adenomas and Adenocarcinomas

    PubMed Central

    Pedersen, Susanne K.; Brown, Glenn S.; Ho, Thu; Kassir, Zena; Moynihan, Audrey T.; Vizgoft, Emma K.; Dunne, Robert; Pimlott, Letitia; Young, Graeme P.; LaPointe, Lawrence C.; Molloy, Peter L.

    2011-01-01

    An uncharacterized gene locus (Chr16:hCG_1815491), now named colorectal neoplasia differentially expressed (gene symbol CRNDE), is activated early in colorectal neoplasia. The locus is unrelated to any known protein-coding gene. Microarray analysis of 454 tissue specimens (discovery) and 68 previously untested specimens (validation) showed elevated expression of CRNDE in >90% of colorectal adenomas and adenocarcinomas. These findings were confirmed and extended by exon microarray studies and RT-PCR assays. CRNDE transcription start sites were identified in CaCo2 and HCT116 cells by 5?-RACE. The major transcript isoforms in colorectal cancer (CRC) cell lines and colorectal tissue are CRNDE-a, -b, -d, -e, -f, -h, and -j. Except for CRNDE-d, the known CRNDE splice variants are upregulated in neoplastic colorectal tissue; expression levels for CRNDE-h alone demonstrate a sensitivity of 95% and specificity of 96% for adenoma versus normal tissue. A quantitative RT-PCR assay measuring CRNDE-h RNA levels in plasma was (with a threshold of 2–?Ct = 2.8) positive for 13 of 15 CRC patients (87%) but only 1 of 15 healthy individuals (7%). We conclude that individual CRNDE transcripts show promise as tissue and plasma biomarkers, potentially exhibiting high sensitivity and specificity for colorectal adenomas and cancers. PMID:22393467

  18. Arf Suppresses Hepatic Vascular Neoplasia in a Carcinogen-Exposed Murine Model

    PubMed Central

    Busch, Stephanie E; Gurley, Kay E; Moser, Russell D; Kemp, Christopher J

    2013-01-01

    Hepatic haemangiosarcoma is a deadly malignancy whose aetiology remains poorly understood. Inactivation of the CDKN2A locus, which houses the ARF and p16INK4a tumour suppressor genes, is a common event in haemangiosarcoma patients, but the precise role of ARF in vascular tumourigenesis is unknown. To determine the extent to which ARF suppresses vascular neoplasia, we examined the incidence of hepatic vascular lesions in Arf-deficient mice exposed to the carcinogen urethane (i.p. 1 mg/g). Loss of Arf resulted in elevated morbidity and increased the incidence of both haemangiomas and incipient haemangiosarcomas. Suppression of vascular lesion development by ARF was heavily dependent on both Arf gene-dosage and the genetic strain of the mouse. Trp53-deficient mice also developed hepatic vascular lesions after exposure to urethane, suggesting that ARF signals through a p53-dependent pathway to inhibit the development of hepatic haemangiosarcoma. Our findings provide strong evidence that inactivation of Arf is a causative event in vascular neoplasia and suggest that the ARF pathway may be a novel molecular target for therapeutic intervention in haemangiosarcoma patients. PMID:22430984

  19. Attribution of human papillomavirus types to cervical intraepithelial neoplasia and invasive cancers in Southern China.

    PubMed

    Chan, Paul K S; Cheung, Tak-Hong; Li, Wai-Hon; Yu, Mei Y; Chan, May Y M; Yim, So-Fan; Ho, Wendy C S; Yeung, Apple C M; Ho, King-Man; Ng, H K

    2012-08-01

    The attribution of individual human papillomavirus (HPV) types to cervical neoplasia, especially intraepithelial lesions, varies ethnogeographically. Population-specific data are required for vaccine cost-effectiveness assessment and type replacement monitoring. HPV was detected from 2,790 Chinese women (444 invasive cervical cancers [ICC], 772 cervical intraepithelial neoplasia [CIN] grade 3, 805 CIN2 and 769 CIN1. The attribution of each HPV type found in multiple-type infections was approximated by the fractional contribution approach. Multiple-type infection was common and correlated inversely with lesion severity (54.7% for CIN1, 48.7% for CIN2, 46.2% for CIN3, 27.5% for ICC). Vaccine-covered high-risk types (HPV16/18) attributed to 59.5% of squamous cell carcinoma, 78.6% of adenocarcinoma, 35.9% of CIN3, 18.4% of CIN2 and 7.4% of CIN1. Distinct features compared to worldwide were a higher attribution of HPV52 and HPV58, and a much lower attribution of HPV45. Inclusion of HPV52 and HPV58 in future vaccines would provide the highest marginal increase in coverage with 11.7% for squamous cell carcinoma, 14.4% for CIN3, 22.6% for CIN2 and 17.7% for CIN1. The attribution of HPV types in southern China is different from elsewhere, which should be considered in prioritizing HPV types for vaccine and screening assay development. PMID:21976212

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

    PubMed

    Vajen, Beate; Thomay, Kathrin; Schlegelberger, Brigitte

    2013-01-01

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

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

    PubMed

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

    2015-02-28

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

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

    PubMed Central

    Kim, Min Sung; Baek, In-Pyo; Lee, Sung Hak; Lee, Ah Won; Hur, Soo Young; Kim, Tae-Min; Lee, Sug Hyung; Chung, Yeun-Jun

    2015-01-01

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

  3. Gynecologic procedures: colposcopy, treatments for cervical intraepithelial neoplasia and endometrial assessment.

    PubMed

    Apgar, Barbara S; Kaufman, Amanda J; Bettcher, Catherine; Parker-Featherstone, Ebony

    2013-06-15

    Women who have abnormal Papanicolaou test results may undergo colposcopy to determine the biopsy site for histologic evaluation. Traditional grading systems do not accurately assess lesion severity because colposcopic impression alone is unreliable for diagnosis. The likelihood of finding cervical intraepithelial neoplasia grade 2 or higher increases when two or more cervical biopsies are performed. Excisional and ablative methods have similar treatment outcomes for the eradication of cervical intraepithelial neoplasia. However, diagnostic excisional methods, including loop electrosurgical excision procedure and cold knife conization, are associated with an increased risk of adverse obstetric outcomes, such as preterm labor and low birth weight. Methods of endometrial assessment have a high sensitivity for detecting endometrial carcinoma and benign causes of uterine bleeding without unnecessary procedures. Endometrial biopsy can reliably detect carcinoma involving a large portion of the endometrium, but is suboptimal for diagnosing focal lesions. A 3- to 4-mm cutoff for endometrial thickness on transvaginal ultrasonography yields the highest sensitivity to exclude endometrial carcinoma in postmenopausal women. Saline infusion sonohysteroscopy can differentiate globally thickened endometrium amenable to endometrial biopsy from focal abnormalities best assessed by hysteroscopy. Hysteroscopy with directed biopsy is the most sensitive and specific method of diagnosing endometrial carcinoma, other than hysterectomy. PMID:23939565

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

    NASA Astrophysics Data System (ADS)

    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

    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.

  5. Canine neoplasia

    PubMed Central

    Prier, J. E.; Brodey, R. S.

    1963-01-01

    The authors review current knowledge of spontaneous neoplasms in the dog. The prevalence of certain types of canine tumour has been studied, and comparisons have been made with the occurrence of similar neoplasms in man. Where there are appropriate analogies between the two species, the dog with spontaneous tumours can be used for studies that are not practicable in man. Nutritional and morphological studies have been done on cells cultured from canine tumours. Some consistency has been demonstrated in the morphology of cultures of different tumours of the same type. Nutritional studies with the transmissible venereal sarcoma of the dog have shown the cells to be subject to a growth-repressing effect by SH-containing amino-acids. Attempts to transmit tumours to other dogs or other species have generally been unsuccessful. A transplantable tumour developed in a mouse injected with non-cellular material from a canine thyroid carcinoma, but it is not certain that the tumour was induced. Cell-culture studies have shown that some tumours yield a factor that is cytopathogenic for normal cells, but none has been shown capable of inducing neoplasms in vivo. ImagesFIG. 3FIG. 4FIG. 5FIG. 1FIG. 2FIG. 6 PMID:14058226

  6. Shanxi Province Cervical Cancer Screening Study: A Cross-Sectional Comparative Trial of Multiple Techniques to Detect Cervical Neoplasia

    Microsoft Academic Search

    J. Belinson; Y. L. Qiao; R. Pretorius; W. H. Zhang; P. Elson; L. Li; Q. J. Pan; C. Fischer; A. Lorincz; D. Zahniser

    2001-01-01

    Objective. The aim of this study was to design a cervical cancer screening algorithm for the developing world that is highly sensitive for cervical intraepithelial neoplasia (CIN) II, III, and cancer and highly specific for CIN II and III, making it possible to ablate the transformation zone without histologic confirmation.Methods. In rural Shanxi Province, China, we examined 1997 women ages

  7. Detection of benign epithelia, prostatic intraepithelial neoplasia, and cancer regions in radical prostatectomy tissues using Raman spectroscopy

    Microsoft Academic Search

    Suneetha Devpura; Jagdish S. Thakur; Fazlul H. Sarkar; Wael A. Sakr; Vaman M. Naik; Ratna Naik

    2010-01-01

    We have studied benign epithelia (BE), prostatic intraepithelial neoplasia (PIN), adenocarcinoma, and cancerous tissues of different Gleason scores in human prostrate bulk tissues using Raman spectroscopy. The data shows two main differences in the Raman spectral features of BE, PIN and cancerous tissues: (i) A strong variations in the peak intensities, (ii) shift in certain peak positions. In order to

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

    Microsoft Academic Search

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

    1999-01-01

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

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

    E-print Network

    Mather, Ian

    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

  10. The frequency of bacterial and yeast infection in women with different grades of cervical intraepithelial neoplasia (CIN)

    Microsoft Academic Search

    Iztok Taka?

    1998-01-01

    Objective: To determine bacterial and yeast infection of the uterine cervix in women with different grades of cervical intraepithelial neoplasia (CIN). Study design: 578 patients with CIN were included in this study. In order to determine the presence of bacterial and yeast infection, a cervical swab was obtained before conization of the uterine cervix. After surgery and the definitive histology

  11. Assessment of haemic neoplasia in different soft shell clam Mya arenaria populations from eastern Canada by flow cytometry

    Microsoft Academic Search

    Maryse Delaporte; Stéphanie Synard; Julie Pariseau; Patricia McKenna; Réjean Tremblay; Jeffery Davidson; Franck C. J. Berthe

    2008-01-01

    Diagnosis of haemic neoplasia (HN) in the soft shell clam, Mya arenaria, is often achieved by hematocytology and histology. Since neoplastic cells display tetraploid DNA contents, haemocyte cell cycle analysis was developed for use as a diagnosis tool. The aim of this study was to assess the application of a flow cytometry procedure of cell cycle analysis established for the

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

    PubMed

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

    2015-05-01

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

  13. Oncogenic Kras activates a hematopoietic-to-epithelial IL-17 signaling axis in preinvasive pancreatic neoplasia

    PubMed Central

    McAllister, Florencia; Bailey, Jennifer M.; Alsina, Janivette; Nirschl, Christopher J.; Sharma, Rajni; Fan, Hongni; Rattigan, Yanique; Roeser, Jeffrey C.; Lankapalli, Rachana H.; Zhang, Hao; Jaffee, Elizabeth M.; Drake, Charles G.; Housseau, Franck; Maitra, Anirban; Kolls, Jay K.; Sears, Cynthia L.; Pardoll, Drew M.; Leach, Steven D.

    2014-01-01

    Summary Many human cancers are dramatically accelerated by chronic inflammation. However the specific cellular and molecular elements mediating this effect remain largely unknown. Using a murine model of pancreatic intraepithelial neoplasia (PanIN), we found that KrasG12D induces expression of functional IL-17 receptors on PanIN epithelial cells, and also stimulates infiltration of the pancreatic stroma by IL-17-producing immune cells. Both effects are augmented by associated chronic pancreatitis, resulting in functional in vivo changes in PanIN epithelial gene expression. Forced IL-17 overexpression dramatically accelerates PanIN initiation and progression, while inhibition of IL-17 signaling using genetic or pharmacologic techniques effectively prevents PanIN formation. Together, these studies suggest that a hematopoietic-to-epithelial IL-17 signaling axis is a potent and requisite driver of PanIN formation. PMID:24823639

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

    PubMed Central

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

    2012-01-01

    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

  15. [Combined endoscopic diagnostics with catheter confocal endomicroscopy for gastric neoplasia detection].

    PubMed

    Shuleshova, A G; Zav'ialov, M O; Ul'ianov, D N; Kanare?tseva, T D

    2014-01-01

    The analysis of combined endoscopic diagnostics with catheter confocal laser endomicroscopy (CCLE) for detection of gastric neoplasia in 103 patients is presented in the article. It was described the main principles of catheter confocal laser endomicroscopy by using of Cellvizio-system ("Mauna Kea Technologies", France). All patients underwent esophagogastroduodenoscopy before catheter confocal laser endomicroscopy. Such modes as HRE-endoscopy, NBI-endoscopy and Zoom-endoscopy were used. It was revealed different neoplastic changes of stomach mucous coat and early cancer forms of stomach in 185 cases. It was noted expediency and high informational content of CCLE which leads to detect the foci of intestinal metaplasia by colonic type, foci of dysplasia and early cancer of stomach mucous coat. The role of conventional morphological study for verification of changes detected with CCLE was shown. PMID:25327669

  16. Parasitic myomas after laparoscopic-assisted myomectomy in multiple endocrine neoplasia type 1.

    PubMed

    Takeda, Akihiro; Sakurai, Akihiro; Imoto, Sanae; Nakamura, Hiromi

    2013-05-01

    Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary disorder that develops multiple tumors arising from various endocrine organs, including the parathyroid gland, endocrine pancreas and pituitary gland. Although mesenchymal tumors can be an integral part of the syndrome, parasitic peritoneal myomas have never been described in an MEN1 patient. Seven years after laparoscopic-assisted myomectomy, parasitic peritoneal myomas were diagnosed in a 31-year-old woman with situs inversus totalis and previous history of parathyroid adenoma. Subsequently, MEN1 was clinically diagnosed by identification of endocrine pancreatic, adrenal and pituitary tumors. Genetic analysis revealed a heterozygous germline mutation in the splice donor sequence of intron 6 of the MEN1 gene. Although rare, parasitic peritoneal myomas could potentially be associated with MEN1 syndrome. PMID:23496674

  17. Minimally invasive techniques to decrease the impact of colorectal surgery for neoplasia.

    PubMed

    Saur, N M; Wexner, S D

    2015-08-01

    Minimally invasive colorectal surgery has evolved over the past few decades. Techniques currently in practice to decrease the impact of colorectal surgery for neoplasia include laparoscopy and its derivations, robotic surgery, transanal endoscopic surgery (TES), transanal total mesorectal excision (taTME), natural orifice specimen extraction (NOSE), needlescopic surgery, and advanced endoscopy. Many of the new techniques are variations of standard laparoscopy that aim to decrease the size of the incisions (needlescopic surgery), decrease the number of incisions (single-incision laparoscopic surgery, SILS), or eliminate the need for a specimen extraction incision (taTME). Each variation must be evaluated for safety and efficacy, especially in oncologic outcome. It is imperative that clinicians understand the role and limitation of each minimally-invasive technique. The goal moving forward should be to develop and sustain technology that is safe, effective, and offers superior clinical outcomes when compared to the current gold standards. PMID:25897590

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

    PubMed

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

    2011-08-15

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

  19. NON-MAMMALIAN FAT-1 GENE PREVENTS NEOPLASIA WHEN INTRODUCED TO A MOUSE HEPATOCARCINOGENESIS MODEL

    PubMed Central

    Griffitts, J.; Saunders, D.; Tesiram, Y.A.; Reid, G.E.; Salih, A.; Liu, S.; Lydic, T.A.; Busik, J.V.; Kang, J.X.; Towner, R.A.

    2010-01-01

    We investigated the effect of a non-mammalian omega-3 desaturase in a mouse hepatocarcinogenesis model. Mice containing double mutations (DM) in c-myc and TGF-? (transforming growth factor-?), leading to liver neoplasia, were crossed with mice containing omega-3 desaturase. MRI analysis of triple mutant (TM) mice showed the absence of neoplasia at all time points for 92% of mice in the study. Pathological changes of TM (TGF?/c-myc/fat-1) mouse liver tissue was similar to control mouse liver tissue. Magnetic resonance spectroscopy (MRS) measurements of unsaturated fatty acids found a significant difference (p<0.005) between DM and TM transgenic (Tg) mice at 34 and 40 weeks of age. HPLC analysis of mouse liver tissue revealed markedly decreased levels of omega-6 fatty acids in TM mice when compared to DM (TGF?/c-myc) and control (CD1) mice. Mass spectrometry (MS) analysis indicated significantly decreased 16:0/20:4 and 18:1/20:4 and elevated 16:0/22:6 fatty acyl groups in both GPCho and GPEtn, and elevated 16:0/20:5, 18:0/18:2, 18:0/18:1 and 18:0/22:6 in GPCho, within TM mice compared to DM mice. Total fatty acid analysis indicated a significant decrease in 18:1n9 in TM mice compared to DM mice. Western blot analysis of liver tissue showed a significant (p<0.05) decrease in NF-?B (nuclear factor- ?B) levels at 40 weeks of age in TM mice compared to DM mice. Microarray analysis of TM versus DM mice livers at 40 weeks revealed alterations in genes involved in cell cycle regulation, cell-to-cell signaling, p53 signaling, and arachidonic acid (20:4) metabolism. Endogenous omega-3 fatty acids were found to prevent HCC development in mice. PMID:20620224

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

    PubMed Central

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

    2013-01-01

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

  1. The association of uterine cervical microbiota with an increased risk for cervical intraepithelial neoplasia in Korea.

    PubMed

    Oh, H Y; Kim, B-S; Seo, S-S; Kong, J-S; Lee, J-K; Park, S-Y; Hong, K-M; Kim, H-K; Kim, M K

    2015-07-01

    Recent studies have suggested potential roles of the microbiome in cervicovaginal diseases. However, there has been no report on the cervical microbiome in cervical intraepithelial neoplasia (CIN). We aimed to identify the cervical microbiota of Korean women and assess the association between the cervical microbiota and CIN, and to determine the combined effect of the microbiota and human papillomavirus (HPV) on the risk of CIN. The cervical microbiota of 70 women with CIN and 50 control women was analysed using pyrosequencing based on the 16S rRNA gene. The associations between specific microbial patterns or abundance of specific microbiota and CIN risk were assessed using multivariate logistic regression, and the relative excess risk due to interaction (RERI) and the synergy index (S) were calculated. The phyla Firmicutes, Actinobacteria, Bacteroidetes, Proteobacteria, Tenericutes, Fusobacteria and TM7 were predominant in the microbiota and four distinct community types were observed in all women. A high score of the pattern characterized by predominance of Atopobium vaginae, Gardnerella vaginalis and Lactobacillus iners with a minority of Lactobacillus crispatus had a higher CIN risk (OR 5.80, 95% CI 1.73?19.4) and abundance of A. vaginae had a higher CIN risk (OR 6.63, 95% CI 1.61?27.2). The synergistic effect of a high score of this microbial pattern and oncogenic HPV was observed (OR 34.1, 95% CI 4.95?284.5; RERI/S, 15.9/1.93). A predominance of A. vaginae, G. vaginalis and L. iners with a concomitant paucity of L. crispatus in the cervical microbiota was associated with CIN risk, suggesting that bacterial dysbiosis and its combination with oncogenic HPV may be a risk factor for cervical neoplasia. PMID:25752224

  2. [The effect of rubomycin, mexidol and emoxypine on some metabolic indexes and the proccess of spontaneous metastasis under conditions of experimental neoplasia].

    PubMed

    Zor'kina, A V; Prosvirina, O N

    2007-01-01

    The effects of mexidol and emoxypine on some indexes of endotoxicosis and weighted characteristics of tumor carrier during experimental neoplasia have been studied under the conditions of therapy using antracycline antibiotic rubomycin. PMID:17402595

  3. Selective initiation and transmission of disseminated neoplasia in the soft shell clam Mya arenaria dependent on natural disease prevalence and animal size.

    PubMed

    Taraska, Norah G; Anne Böttger, S

    2013-01-01

    Disseminated neoplasia, a diffuse tumor of the hemolymph system, is one of the six most destructive diseases among bivalve mollusk populations, characterized by the development of abnormal, rounded blood cells that actively proliferate. Though the specific etiology of disseminated neoplasia in Mya arenaria remains undetermined, the involvement of viral pathogens and/or environmental pollutants has been suggested and considered. The current study used 5-bromodeoxyuridine (BrDU) known to induce the murine leukemia virus and filtered neoplastic hemolymph to initiate disseminated neoplasia in clams from different populations and size classes respectively. M. arenaria from three locations of different natural neoplasia occurrences were divided into a control and three experimental treatments and injected with 200 ?l of sterile filtered seawater or 50-200 ?g/ml BrDU respectively. In a concurrent experiment, animals from different size classes were injected with 2.5% total blood volume of 0.2 ?m filtered blood from a fully neoplastic animal. Animals were biopsied weekly and cell neoplasia development was counted and scored as 0-25, 26-50, 51-75 and 76-100% neoplastic hemocytes (stages 1-4) in 50 ?l samples. BrDU injection demonstrated that neoplasia development in M. arenaria was dose dependent on BrDU concentration. In addition, natural disease prevalence at the source location determined initiation of neoplasia induction, with animals from the area of the highest natural disease occurrence displaying fastest neoplasia development (p=0.0037). This could imply that depending on the natural disease occurrence, a potential infectious agent may remain dormant in normal (stage 1) individuals in higher concentrations until activated, i.e. through chemical injection or potentially stress. The size experiment demonstrated that only M. arenaria between 40 and 80 mm developed 26-100% neoplastic hemocytes when injected with filtered neoplastic hemolymph, indicating that individuals smaller than 20mm or larger than 80 mm were not or no longer susceptible to disease development. So far neoplasia studies have not considered natural disease prevalence or size involvement in neoplasia development and our results indicate that these should be future considerations in neoplasia examinations. PMID:23079141

  4. Risk for invasive and borderline epithelial ovarian neoplasias following use of hormonal contraceptives: the Norwegian–Swedish Women's Lifestyle and Health Cohort Study

    Microsoft Academic Search

    M Kumle; E Weiderpass; T Braaten; H-O Adami; E Lund

    2004-01-01

    The risk of ovarian epithelial neoplasia following use of hormonal contraceptives (HC) was examined in data from the Norwegian–Swedish Women's Lifestyle and Health cohort including 103 551 women aged 30–49 years in 1991–92. Follow-up through 2000 produced 214 incident cases of histologically confirmed epithelial ovarian neoplasias (135 invasive and 79 borderline cases). Using the Cox proportional hazard models, ever having

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

    PubMed Central

    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

    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

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

    PubMed Central

    1993-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  8. Analysis of ?-methylacyl-CoA racemase (P504S) expression in high-grade prostatic intraepithelial neoplasia

    Microsoft Academic Search

    Chin-Lee Wu; Ximing J Yang; Maria Tretiakova; Kurt T Patton; Elkan F Halpern; Bruce A Woda; Robert H Young; Zhong Jiang

    2004-01-01

    ?-methylacyl-CoA racemase (AMACR), also known as P504S, is a recently identified molecular marker for prostate cancer. The expression of AMACR\\/P504S has also been observed in high-grade prostatic intraepithelial neoplasia (PIN), a precursor lesion of prostate cancer. However, a detailed study focusing on the analysis of AMACR\\/P504S expression in high-grade PIN has not been performed. In this study, we analyzed AMACR\\/P504S

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

    PubMed

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

    2015-03-01

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

  10. Deregulated expression of insulin-like growth factor 1 in prostate epithelium leads to neoplasia in transgenic mice

    Microsoft Academic Search

    John Digiovanni; Kaoru Kiguchi; Anita Frijhoff; Eric Wilker; David K. Bol; Linda Beltrán; Samantha Moats; Angel Ramirez; José Jorcano; Claudio Conti

    2000-01-01

    Transgenic mice expressing human insulin-like growth factor 1 (IGF-1) in basal epithelial cells of prostate have been characterized. Transgene expression led to activation of the IGF-1 receptor and spontaneous tumorigenesis in prostate epithelium. Hyperplasia was evident in these mice by 2-3 months of age. Atypical hyperplasias and prostatic intraepithelial neoplasia were evident by 6-7 months of age. Well differentiated adenocarcinomas

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

    Microsoft Academic Search

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

    1993-01-01

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

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

    Microsoft Academic Search

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

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

  13. Multiphoton tomographic imaging: a potential optical biopsy tool for detecting gastrointestinal inflammation and neoplasia

    PubMed Central

    Makino, Tomoki; Jain, Manu; Montrose, David C.; Aggarwal, Amit; Sterling, Joshua; Bosworth, Brian P.; Milsom, Jeffrey W.; Robinson, Brian D.; Shevchuk, Maria M.; Kawaguchi, Kathy; Zhang, Ning; Brown, Christopher M.; Rivera, David R.; Williams, Wendy O.; Xu, Chris; Dannenberg, Andrew J.; Mukherjee, Sushmita

    2012-01-01

    Endoscopy is widely used to detect and remove premalignant lesions with the goal of preventing gastrointestinal (GI) cancers. Because current endoscopes do not provide cellular resolution, all suspicious lesions are biopsied and subjected to histological evaluation. Technologies that facilitate directed biopsies should decrease both procedure-related morbidity and cost. Here we explore the use of multiphoton microscopy (MPM), an optical biopsy tool that relies on intrinsic tissue emissions, to evaluate pathology in both experimental and human GI specimens, using hematoxylin and eosin (H&E)-stained sections from these tissues for comparison. After evaluating the entire normal mouse GI tract, MPM was used to investigate disease progression in mouse models of colitis and colorectal carcinogenesis. MPM provided sufficient histological detail to identify all relevant substructures in ex vivo normal GI tissue, visualize both acute and resolving stages of colitis, and show the progression of colorectal carcinogenesis. Next, ex vivo specimens from human subjects with celiac sprue, inflammatory bowel disease, and colorectal neoplasia were imaged by MPM. Finally, colonic mucosa in live anesthetized rats was imaged in vivo using a flexible endoscope prototype. In both animal models and human specimens, MPM images demonstrated a striking similarity to the results of H&E staining, as demonstrated by the 100% concordance achieved by the study pathologists’ diagnoses. In summary, MPM is a promising technique that accurately visualizes histology in fresh, unstained tissues. Our findings support the continued development of MPM as a technology to enhance the early detection of GI pathologies including premalignant lesions. PMID:22961775

  14. Metabolic Profiling, a Non-invasive Approach for the Detection of Experimental Colorectal Neoplasia

    PubMed Central

    Montrose, David C.; Zhou, Xi Kathy; Kopelovich, Levy; Yantiss, Rhonda K.; Karoly, Edward D.; Subbaramaiah, Kotha; Dannenberg, Andrew J.

    2012-01-01

    Colorectal cancer is the second leading cause of cancer-related deaths in the U.S. Although non-invasive stool-based screening tests are used for the early detection of colorectal neoplasia, concerns have been raised about their sensitivity and specificity. A metabolomics-based approach provides a potential non-invasive strategy to identify biomarkers of colorectal carcinogenesis including premalignant adenomas. Our primary objective was to determine whether a distinct metabolic profile could be found in both feces and plasma during experimental colorectal carcinogenesis. Feces, plasma as well as tumor tissue and normal colorectal mucosa were obtained from A/J mice at several time points following administration of azoxymethane or saline. UPLC/MS/MS and GC/MS were used to quantify metabolites in each of these matrices. Here we show that colorectal carcinogenesis was associated with significant metabolic alterations in both the feces and plasma, some of which overlap with metabolic changes in the tumor tissue. These consisted of 33 shared changes between feces and tumor, 14 shared changes between plasma and tumor and 3 shared changes across all 3 matrices. For example, elevated levels of sarcosine were found in both tumor and feces whereas increased levels of 2-hydroxyglutarate were found in both tumor and plasma. Collectively, these results provide evidence that metabolomics can be used to detect changes in feces and plasma during azoxymethane-induced colorectal carcinogenesis and thus provide a strong rationale for future studies in humans. PMID:22961778

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

    PubMed

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

    2002-09-01

    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

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

    PubMed

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

    2014-01-01

    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

  17. The incidence and histological characteristics of intratubular germ cell neoplasia in postpubertal cryptorchid testis

    PubMed Central

    Ryang, Seung Hoon; Jung, Jae Hung; Eom, Minseob; Song, Jae Mann; Chung, Hyun Chul; Chae, Yunbyung; Lee, Chang Min

    2015-01-01

    Purpose It is well known that testicular germ cell tumors arise with increased frequency in patients with cryptorchidism. In addition, intratubular germ cell neoplasia (ITGCN) is a precursor lesion to testicular germ cell tumor. Approximately 50% of patients with ITGCN will develop an invasive of testicular germ cell tumors within 5 years. Therefore, we evaluated that the incidence of ITGCN in postpubertal cryptorchidism. Materials and Methods Between January 2002 and August 2012, orchiectomy specimens from 31 postpubertalpatients (aged 12 or over) with cryptorchid testis were reviewed. The specimens were evaluated for ITGCN using immunohistochemical stains of placental-like alkaline phosphatase and Oct 3/4 with routine hematoxylin-eosin stain. Additionally, the degree of spermatogenesis was assessed using the Johnsen score. Results Mean age was 34 years (range, 17 to 74 years) at surgery. All patients were diagnosed as unilateral cryptorchidism. One patient (3.2%) of 20-year-old had ITGCN in surgical specimen with all positive markers. Histological assessment of spermatogenesis showed that mean Johnsen score was 3.42 (range, 1 to 9). Majority of patients (27 of 31) presented impaired spermatogenesis with low Johnsen score lesser than 5. Conclusions Considering the risk of malignancy and low spermatogenesis, we should perform immunohistochemical stains and discuss preventative orchiectomy for the postpubertal cryptorchidism.

  18. Fecal alpha 1-antitrypsin detection of colorectal neoplasia. An evaluation using HemoQuant.

    PubMed

    Moran, A; Robinson, M; Lawson, N; Stanley, J; Jones, A F; Hardcastle, J D

    1995-12-01

    Fecal alpha 1-antitrypsin measurement may be of value for the detection of colorectal neoplasia and is compared with the HemoQuant test in 119 subjects with either a screen-positive Hemoccult result (N = 78) or iron-deficiency anaemia (N = 41). Nineteen patients were found to have colorectal cancer, 35 had colorectal adenomatous polyps, 5 had inflammatory bowel disease, and 60 had no detected cause of occult blood loss. Of the cancer patients, 63% (12/19) were detected by fecal alpha 1-antitrypsin and 63% (12/19) by HemoQuant. Of the adenomas > 1 cm in diameter 33% (7/23) were detected by fecal alpha 1-antitrypsin and 26% (6/23) by HemoQuant. There was a poor correlation between fecal alpha 1-antitrypsin and HemoQuant results for colorectal cancers (r = 0.37, P > 0.05), and combining the tests, the sensitivity for colorectal cancer was increased to 84% (16/19). Fecal protein loss, as measured using alpha 1-antitrypsin, appears to involve largely different mechanisms from that of blood loss from colorectal cancers. PMID:8536506

  19. A study of anal intraepithelial neoplasia in HIV positive homosexual men

    PubMed Central

    Lacey, H. B.; Wilson, G. E.; Tilston, P.; Wilkins, E. G.; Bailey, A. S.; Corbitt, G.; Green, P. M.

    1999-01-01

    OBJECTIVES: To determine the prevalence of high grade anal intraepithelial neoplasia (HGAIN), the value of anal cytology in screening for HGAIN, and the characterisation of epidemiological factors and human papillomavirus (HPV) types. METHODS: Prospective cohort study of HIV positive homosexual men. Subjects were interviewed, underwent STD, anal cytological, and HPV screening at enrolment and at subsequent follow up visits with anoscopy and biopsy at the final visit. 57 enrolled, average CD4 count 273 x 10(6)/l (10-588); 41 completed the cytological surveillance over the follow up period (181 visits, average follow up 17 months), 38 of these had anoscopy and anal biopsy. RESULTS: Oncogenic HPV types were detected in 84% and high grade dyskaryosis in 10.5% (6/57) at enrollment. There was a 70% incidence of high grade dyskaryosis during follow up in patients with negative/warty or low grade dyskaryosis at enrollment. Anoscopy correlated with histology in high grade AIN lesions (sensitivity 91%, specificity 54%) and cytology was 78% sensitive (18/23) for HGAIN on biopsy. CONCLUSIONS: AIN and infection with multiple oncogenic HPV types are very common among immunosuppressed HIV positive homosexual men. Apparent progression from low to high grade cytological changes occurred over a short follow up period, with no cases of carcinoma. All 23 cases of HGAIN were predicted by cytology and/or anoscopy. Future studies focusing on the risk of progression to carcinoma are needed before applying anal cytology as a screening tool for AIN in this population. ??? PMID:10448395

  20. IMP3, a new biomarker to predict progression of cervical intraepithelial neoplasia into invasive cancer.

    PubMed

    Lu, Di; Yang, Xiaofang; Jiang, Naomi Y; Woda, Bruce A; Liu, Qin; Dresser, Karen; Mercurio, Arthur M; Rock, Kenneth L; Jiang, Zhong

    2011-11-01

    The expression of IMP3, an oncofetal protein, has been strongly associated with aggressive cancers. In this study, we investigated whether IMP3 can serve as a biomarker to predict invasive squamous cell carcinoma (SCC) in patients with cervical intraepithelial neoplasia (CIN) II and III. A total of 1249 patients with no dysplasia, CINs, or invasive SCC were studied for IMP3 expression. The 710 patients with CIN II and III in their cervical biopsies were further evaluated for invasive cancer-free survival analysis. The role of IMP3 in the regulation of cell proliferation and migration of HeLa cervical cancer cells was examined by modification of IMP3 expression with small interference RNA. Compared with CIN I or cervical tissues without dysplasia, IMP3 expression was significantly increased not only in invasive SCC but also most importantly in a subset of CIN III cases with concurrent invasive SCC. Importantly, invasive cancer was found only in patients with IMP3-positive CIN II and III, whereas no invasive cancer was detected in patients with IMP3-negative CIN II and III in their follow-up resections (P<0.0001). Reduction of IMP3 expression in cervical cancer cells significantly reduced cell migration without altering cell proliferation. IMP3 plays a critical role in the development of invasive SCC from cervical dysplasia. IMP3 can be used at the time of initial diagnosis of CIN to identify a group of patients with an increased chance of developing invasive cancer. PMID:21997684

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

    PubMed

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

    2014-08-01

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

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

    PubMed Central

    Potter, Michael

    1962-01-01

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

  3. Association of Dietary Vitamin D and Calcium With Genetic Polymorphisms in Colorectal Neoplasia

    PubMed Central

    Park, Yoon; Kim, Jeongseon

    2015-01-01

    The incidence trends of colorectal cancer have varied over time, and there is wide geographical variation across the world. Regarding colorectal cancer, diverse modifiable environmental or intrinsic risk factors have been investigated. This review summarizes the effects of both dietary intake of vitamin D and calcium in particular and diet-associated genetic factors on colorectal cancer risk. We searched the electronic database PubMed for articles published between January 2000 and March 2015. We reviewed case-control studies that included dietary factors, genetic polymorphisms, and gene-diet interactions in association with colorectal cancer risk. Overall, 21 studies were selected as eligible studies. These studies demonstrated that dietary consumption of vitamin D and calcium may decrease the risk of colorectal cancer or adenoma. Colorectal carcinogenesis was discussed in conjunction with dietary factors and mediating genetic factors. The epidemiological findings suggested that the gene-diet interactions may possibly alter the associations between dietary intake, genetic polymorphisms, and the risk of colorectal cancer. However, the reported effects of the same potential factors on colorectal cancer risk were inconsistent, depending on the study population and geographical location. This finding may imply the necessity of considering the environmental differences and genetic variations existing between individuals or specified populations. Therefore, further studies are required to investigate modifiable risk factors in diverse locations to derive useful implications for colorectal neoplasia.

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

    PubMed Central

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

    1998-01-01

    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

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

    USGS Publications Warehouse

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

    1998-01-01

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

  6. Is intraductal tubulopapillary neoplasia a new entity in the spectrum of familial pancreatic cancer syndrome?

    PubMed

    Del Chiaro, Marco; Mucelli, Raffaella Pozzi; Blomberg, John; Segersvärd, Ralf; Verbeke, Caroline

    2014-06-01

    We report on a 78-year old male with a positive family history for pancreatic cancer, who underwent total pancreatectomy for a suspected intraductal papillary mucinous neoplasm with extensive involvement of the main pancreatic duct and multiple branch ducts. The post operative course was uneventful. Macroscopic examination of the specimen revealed multiple solid non-mucinous tumour nodules throughout the main pancreatic duct and within multiple branch ducts. The microscopic appearance of the tumour, in particular its tubulopapillary growth pattern and immunohistochemical mucin profile (MUC1, MUC6 positive; MUC2, MUC5AC negative) were consistent with intraductal tubulopapillary neoplasia (ITPN) showing high-grade dysplasia. No evidence of stromal invasion was identified. To the best of our knowledge, this is the first report on ITPN in a high-risk patient based on a history of familial pancreatic cancer (FPC). The potential association between this entity and the spectrum of neoplastic lesions in FPC should be investigated with particular consideration of the lower biological aggressiveness of ITPN. PMID:24317685

  7. Multiphoton tomographic imaging: a potential optical biopsy tool for detecting gastrointestinal inflammation and neoplasia.

    PubMed

    Makino, Tomoki; Jain, Manu; Montrose, David C; Aggarwal, Amit; Sterling, Joshua; Bosworth, Brian P; Milsom, Jeffrey W; Robinson, Brian D; Shevchuk, Maria M; Kawaguchi, Kathy; Zhang, Ning; Brown, Christopher M; Rivera, David R; Williams, Wendy O; Xu, Chris; Dannenberg, Andrew J; Mukherjee, Sushmita

    2012-11-01

    Endoscopy is widely used to detect and remove premalignant lesions with the goal of preventing gastrointestinal (GI) cancers. Because current endoscopes do not provide cellular resolution, all suspicious lesions are biopsied and subjected to histologic evaluation. Technologies that facilitate directed biopsies should decrease both procedure-related morbidity and cost. Here we explore the use of multiphoton microscopy (MPM), an optical biopsy tool that relies on intrinsic tissue emissions, to evaluate pathology in both experimental and human GI specimens, using hematoxylin and eosin (H&E)-stained sections from these tissues for comparison. After evaluating the entire normal mouse GI tract, MPM was used to investigate disease progression in mouse models of colitis and colorectal carcinogenesis. MPM provided sufficient histologic detail to identify all relevant substructures in ex vivo normal GI tissue, visualize both acute and resolving stages of colitis, and show the progression of colorectal carcinogenesis. Next, ex vivo specimens from human subjects with celiac sprue, inflammatory bowel disease, and colorectal neoplasia were imaged by MPM. Finally, colonic mucosa in live anesthetized rats was imaged in vivo using a flexible endoscope prototype. In both animal models and human specimens, MPM images showed a striking similarity to the results of H&E staining, as shown by the 100% concordance achieved by the study pathologists' diagnoses. In summary, MPM is a promising technique that accurately visualizes histology in fresh, unstained tissues. Our findings support the continued development of MPM as a technology to enhance the early detection of GI pathologies including premalignant lesions. PMID:22961775

  8. Metabolic profiling, a noninvasive approach for the detection of experimental colorectal neoplasia.

    PubMed

    Montrose, David C; Zhou, Xi Kathy; Kopelovich, Levy; Yantiss, Rhonda K; Karoly, Edward D; Subbaramaiah, Kotha; Dannenberg, Andrew J

    2012-12-01

    Colorectal cancer is the second leading cause of cancer-related deaths in the United States. Although noninvasive stool-based screening tests are used for the early detection of colorectal neoplasia, concerns have been raised about their sensitivity and specificity. A metabolomics-based approach provides a potential noninvasive strategy to identify biomarkers of colorectal carcinogenesis including premalignant adenomas. Our primary objective was to determine whether a distinct metabolic profile could be found in both feces and plasma during experimental colorectal carcinogenesis. Feces, plasma as well as tumor tissue and normal colorectal mucosa were obtained from A/J mice at several time points following administration of azoxymethane or saline. Ultra-performance liquid chromatography tandem mass spectroscopy and gas chromatography mass spectroscopy were used to quantify metabolites in each of these matrices. Here, we show that colorectal carcinogenesis was associated with significant metabolic alterations in both the feces and plasma, some of which overlap with metabolic changes in the tumor tissue. These consisted of 33 shared changes between feces and tumor, 14 shared changes between plasma and tumor, and 3 shared changes across all 3 matrices. For example, elevated levels of sarcosine were found in both tumor and feces whereas increased levels of 2-hydroxyglutarate were found in both tumor and plasma. Collectively, these results provide evidence that metabolomics can be used to detect changes in feces and plasma during azoxymethane-induced colorectal carcinogenesis and thus provide a strong rationale for future studies in humans. PMID:22961778

  9. A Density Test for the Intraoperative Differentiation of Parathyroid Hyperplasia from Neoplasia

    PubMed Central

    Wang, Chiu-An; Rieder, Sidney V.

    1978-01-01

    A simple, instant, and reliable test called the Density Test, based on the difference in density between the normal and the diseased parathyroid tissue, was performed intraoperatively in 73 patients with primary hyperparathyroidism. Whereas the normal parathyroid tissue floated, the diseased tissue invariably sank in a mannitol solution with a density range between 1.049 and 1.069. With the aid of this test, a diagnosis of adenoma was made in 66 patients and of primary hyperplasia in the remaining seven. In every case the diagnosis was subsequently confirmed. Forty-two of the 66 patients with an adenoma (64%) had a unilateral exploration of the neck. The Density Test saved these patients from an unnecessary contralateral exploration by the finding of an adenoma and a normal second gland in the same side of the neck. These data show that the Density Test is useful in the intraoperative diagnosis of a diseased from a normal parathyroid tissue. Tissue that sinks within the density range of 1.049 and 1.069 is without exception diseased and should therefore be either partially or completely excised even if the gland is of average size or only of slight enlargement. If it does not sink, it is virtually certain to be normal and should be spared. The Density Test provides a valuable clue in the differentiation of primary parathyroid hyperplasia from neoplasia. PMID:619801

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

    PubMed

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

    2015-03-01

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

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

    PubMed

    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

    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

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

    PubMed Central

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

    2014-01-01

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

  13. Thymic neuroendocrine carcinoma (carcinoid) in multiple endocrine neoplasia type 1 syndrome: the Italian series.

    PubMed

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

    2005-05-01

    Neuroendocrine tumors may occur in the setting of multiple endocrine neoplasia type 1 (MEN1) syndrome. Among these, a probably underestimated prevalence of well differentiated neuroendocrine thymic carcinoma (carcinoid), a neoplasm characterized by very aggressive behavior, has been described. We report characterization of the seven Italian cases in which this association occurred among a series of 221 MEN1 patients (41 sporadic and 180 familial cases; prevalence, 3.1%). All of the patients were male, and six of seven (85%) were heavy smokers. No associated hormonal hypersecretion was detected. The first diagnosis was between the second and fifth decades. Familial clusters were present in three of seven (42.8%). No genotype-phenotype correlation was found. All seven cases were associated with hyperparathyroidism. In one patient, prophylactic thymectomy revealed a small nodular lesion suggestive of a thymic carcinoid, providing evidence that preventive thymectomy might prevent additional growth of an occult thymic carcinoid. These findings confirm that thymic carcinoids are associated with a very high lethality, with a near-total prevalence in smoker males. Therefore, prophylactic thymectomy should be considered at neck surgery for primary hyperparathyroidism in MEN1 male patients, especially for smokers, and, due to the frequent familial clusters distribution of this pathology, in subjects with affected relatives presenting this feature. Thus, we recommend screening every patient affected with a neuroendocrine thymic neoplasm for MEN1 syndrome. PMID:15713725

  14. The Relationship between Hypomethylation and CpG Island Methylation in Colorectal Neoplasia

    PubMed Central

    Bariol, Carolyn; Suter, Catherine; Cheong, Kay; Ku, Su-Lyn; Meagher, Alan; Hawkins, Nicholas; Ward, Robyn

    2003-01-01

    Tumors are often characterized by an imbalance in cytosine methylation as manifested both by hypermethylation of CpG islands and by genome hypomethylation. These epigenetic changes were assessed in colorectal neoplasia to determine whether they arose through a common mechanism or indeed were distinct and unrelated phenomena. Fresh representative samples of adenomas, hyperplastic polyps, colorectal cancers, and normal mucosa were used in this study. Global methylation levels were measured by analyzing the methyl-accepting capacity of DNA. Methylation of p16, hMLH1, and MINT 1, 2, 12, and 31 were assessed by bisulfite polymerase chain reaction. Microsatellite status was determined by polymerase chain reaction using six markers and hMLH1 and proliferating cell nuclear antigen expression was assessed by immunohistochemistry. Normal colonic mucosa had a higher endogenous 5-methyl cytosine content than all proliferative lesions of the colon (P < 0.001). The extent of demethylation in hyperplastic polyps and adenomas was significantly related to its proliferative rate. Right-sided hyperplastic polyps were more likely to be methylated than adenomas (odds ratio, 2.3; confidence interval, 1.1 to 4.6). There was no relationship between the level of global hypomethylation and hypermethylation. Some hyperplastic colorectal polyps have a propensity to develop dense CpG island methylation. Hypermethylation and hypomethylation contribute separately to the process of carcinogenesis. PMID:12651628

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

    PubMed

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

    2012-03-01

    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

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

    SciTech Connect

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

    1988-06-01

    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.

  17. Genetic test in multiple endocrine neoplasia type 1 syndrome: An evolving story

    PubMed Central

    Marini, Francesca; Giusti, Francesca; Brandi, Maria Luisa

    2015-01-01

    Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited tumour syndrome expressing various endocrine and non-endocrine lesions and tumours. Since the identification of the causative gene, the oncosuppressor gene MEN1, in 1997, genetic testing has revealed an important approach for the early and differential diagnosis of the disease. The finding of a MEN1 mutation in a patient has important clinical implications for relatives since it allows very early disease diagnosis and identification of carriers, even before biochemical and/or clinical manifestation, permitting their inclusion in a specific program of surveillance and subsequent praecox therapy. Currently, genetic testing for MEN1 consists principally of the sequencing of coding regions and intron-exon junctions of the MEN1 gene. However, the recent acquisition of novel high throughput technologies will allow the design of innovative, accurate, complete and rapid genetic diagnosis. These new tools are able to increase the strength of the analysis and almost completely eliminate the possibility of false negative results. This review aims to give an overview on genetic testing of MEN1 syndrome, reporting the positive aspects of performing the analysis and the future perspectives for improving the performance of the test, as well as its application in clinical practice. PMID:25992327

  18. HPV-Based Screening, Triage, Treatment, and Followup Strategies in the Management of Cervical Intraepithelial Neoplasia

    PubMed Central

    Peralta-Zaragoza, Oscar; Deas, Jessica; Gómez-Cerón, Claudia; García-Suastegui, Wendy Argelia; Fierros-Zárate, Geny del Socorro; Jacobo-Herrera, Nadia Judith

    2013-01-01

    Cervical cancer is the second most common cause of death from cancer in women worldwide, and the development of new diagnostic, prognostic, and treatment strategies merits special attention. Many efforts have been made to design new drugs and develop immunotherapy and gene therapy strategies to treat cervical cancer. HPV genotyping has potentially valuable applications in triage of low-grade abnormal cervical cytology, assessment of prognosis and followup of cervical intraepithelial neoplasia, and in treatment strategies for invasive cervical cancer. It is known that during the development of cervical cancer associated with HPV infection, a cascade of abnormal events is induced, including disruption of cellular cycle control, alteration of gene expression, and deregulation of microRNA expression. Thus, the identification and subsequent functional evaluation of host proteins associated with HPV E6 and E7 oncoproteins may provide useful information in understanding cervical carcinogenesis, identifying cervical cancer molecular markers, and developing specific targeting strategies against tumor cells. Therefore, in this paper, we discuss the main diagnostic methods, management strategies, and followup of HPV-associated cervical lesions and review clinical trials applying gene therapy strategies against the development of cervical cancer. PMID:23690785

  19. Novel markers of gonadectomy-induced adrenocortical neoplasia in the mouse and ferret.

    PubMed

    Schillebeeckx, Maximiliaan; Pihlajoki, Marjut; Gretzinger, Elisabeth; Yang, Wei; Thol, Franziska; Hiller, Theresa; Löbs, Ann-Kathrin; Röhrig, Theresa; Schrade, Anja; Cochran, Rebecca; Jay, Patrick Y; Heikinheimo, Markku; Mitra, Robi D; Wilson, David B

    2015-01-01

    Gonadectomy (GDX) induces sex steroid-producing adrenocortical tumors in certain mouse strains and in the domestic ferret. Transcriptome analysis and DNA methylation mapping were used to identify novel genetic and epigenetic markers of GDX-induced adrenocortical neoplasia in female DBA/2J mice. Markers were validated using a combination of laser capture microdissection, quantitative RT-PCR, in situ hybridization, and immunohistochemistry. Microarray expression profiling of whole adrenal mRNA from ovariectomized vs. intact mice demonstrated selective upregulation of gonadal-like genes including Spinlw1 and Insl3 in GDX-induced adrenocortical tumors of the mouse. A complementary candidate gene approach identified Foxl2 as another gonadal-like marker expressed in GDX-induced neoplasms of the mouse and ferret. That both "male-specific" (Spinlw1) and "female-specific" (Foxl2) markers were identified is noteworthy and implies that the neoplasms exhibit mixed characteristics of male and female gonadal somatic cells. Genome-wide methylation analysis showed that two genes with hypomethylated promoters, Igfbp6 and Foxs1, are upregulated in GDX-induced adrenocortical neoplasms. These new genetic and epigenetic markers may prove useful for studies of steroidogenic cell development and for diagnostic testing. PMID:25289806

  20. Reverse transcriptase activity in tissues of the soft shell clam Mya arenaria affected with haemic neoplasia.

    PubMed

    AboElkhair, M; Synard, S; Siah, A; Pariseau, J; Davidson, J; Johnson, G; Greenwood, S J; Casey, J W; Berthe, F C J; Cepica, A

    2009-10-01

    Since all retroviruses possess reverse transcriptase (RT) enzyme, reverse transcriptase activity has been the main supportive evidence of retroviral etiology of haemic neoplasia (HN) in soft shell clams, Mya arenaria. The objective of the present study was to search for a putative retrovirus in various tissues of diseased clams following quantification of RT activity (biochemical indicator of retroviral infection). The clams were assessed by flow cytometry (FCM) for diagnosis of HN. RT activity was quantified by TaqMan-product enhanced reverse transcriptase (TM-PERT) assay in four different organs, gonad, gills, digestive gland, and mantle, at various stages of HN. The digestive gland, the organ with the highest RT activity, and haemocytes, the target cell of HN, were assessed by EM for presence of retroviruses. All organs were assessed by histology. The results of this study demonstrated that although all organs of healthy clams have some background RT activity, the activity observed in most of organs of diseased clams was significantly increased (p<0.05). An association was observed between the degree of neoplastic cell infiltration and the level of RT activity. Digestive gland showed the highest and most consistent RT activity in both healthy and diseased clams. No evidence for the existence of a retrovirus like particle was found by positive staining EM. The presence of RT activity without indications of retroviral particles in digestive gland and haemocytes suggests a probable endogenous source of RT. PMID:19632237

  1. Reverse transcriptase activity associated with haemic neoplasia in the soft-shell clam Mya arenaria.

    PubMed

    AboElkhair, M; Siah, A; Clark, K F; McKenna, P; Pariseau, J; Greenwood, S J; Berthe, F C J; Cepica, A

    2009-03-01

    Reverse transcriptase (RT) activity has been reported in bivalves affected by haemic neoplasia (HN). Since all retroviruses have RT, detection of RT activity was regarded as evidence for the retroviral etiology of HN. This study investigates the relationship between RT levels and the progress of HN as indicated by percentages of tetraploid cells in soft-shell clams Mya arenaria. The percentages of tetraploid cells were estimated by flow cytometry, and the RT levels were quantified using TaqMan product-enhanced RT (TM-PERT) assay. Results demonstrated that the amount of RT was positively correlated with the percentage of tetraploid cells circulating in clam haemolymph (R2 = 0.974, p < 0.001). Compared to HN-negative clams (<5% tetraploid cells), 2 stages with significantly elevated levels of RT activity were observed: the first stage at approximately 10 to approximately 20% tetraploid cells, and the second at approximately 30 to approximately 80% tetraploid cells (p < 0.01). These data support the well established fact from mammalian models that transformed cells express high levels of non-telomeric RT. The observed increase in RT levels at approximately 30% tetraploidy coincides with previously reported p53 gene expression. Taken together, this could indicate that using RT levels as an indicator of HN, > or = 30% tetraploidy is the stage at which the disease process undergoes a change, and perhaps becomes irreversible. PMID:19419007

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

    PubMed

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

    1998-11-30

    Disseminated neoplasia (DN), a proliferative cell disorder of the circulatory system of bivalves, was first reported in oysters in 1969. Since that time, the disease has been determined to be transmissible through water-borne exposure, but the etiological agent has not been unequivocally identified. In order to determine if a viral agent, possibly a retrovirus, could be the causative agent of DN, transmission experiments were performed, using both a cell-free filtrate and a sucrose gradient-purified preparation of a cell-free filtrate of DN positive materials. Additionally, a PCR-enhanced reverse transcriptase assay was used to determine if reverse transcriptase was present in tissues or hemolymph from DN positive soft shell clams Mya arenaria. DN was transmitted to healthy clams by injection with whole DN cells, but not with cell-free filtrates prepared from either tissues from DN positive clams, or DN cells. The cell-free preparations from DN-positive tissues and hemolymph having high levels of DN cells in circulation exhibited positive reactions in the PCR-enhanced reverse transcriptase assay. Cell-free preparations of of hemolymph from clams having low levels of DN (<0.1% of cells abnormal), hemocytes from normal soft shell clams, and normal soft shell clam tissues did not produce a positive reaction in the PCR enhanced reverse transcriptase assay. PMID:9925424

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

    PubMed

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

    2014-12-15

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2009-01-01

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

  6. Characterization of mutations in patients with multiple endocrine neoplasia type 1.

    PubMed Central

    Bassett, J H; Forbes, S A; Pannett, A A; Lloyd, S E; Christie, P T; Wooding, C; Harding, B; Besser, G M; Edwards, C R; Monson, J P; Sampson, J; Wass, J A; Wheeler, M H; Thakker, R V

    1998-01-01

    Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors of the parathyroids, pancreatic islets, and anterior pituitary. The MEN1 gene, on chromosome 11q13, has recently been cloned, and mutations have been identified. We have characterized such MEN1 mutations, assessed the reliability of SSCP analysis for the detection of these mutations, and estimated the age-related penetrance for MEN1. Sixty-three unrelated MEN1 kindreds (195 affected and 396 unaffected members) were investigated for mutations in the 2,790-bp coding region and splice sites, by SSCP and DNA sequence analysis. We identified 47 mutations (12 nonsense mutations, 21 deletions, 7 insertions, 1 donor splice-site mutation, and 6 missense mutations), that were scattered throughout the coding region, together with six polymorphisms that had heterozygosity frequencies of 2%-44%. More than 10% of the mutations arose de novo, and four mutation hot spots accounted for >25% of the mutations. SSCP was found to be a sensitive and specific mutational screening method that detected >85% of the mutations. Two hundred and one MEN1 mutant-gene carriers (155 affected and 46 unaffected) were identified, and these helped to define the age-related penetrance of MEN1 as 7%, 52%, 87%, 98%, 99%, and 100% at 10, 20, 30, 40, 50, and 60 years of age, respectively. These results provide the basis for a molecular-genetic screening approach that will supplement the clinical evaluation and genetic counseling of members of MEN1 families. PMID:9463336

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

    PubMed

    Canales, Norma Angélica Galicia; Marina, Vicente Madrid; Castro, Jorge Salmerón; Jiménez, Alfredo Antúnez; Mendoza-Hernández, Guillermo; McCARRON, Elizabeth Langley; Roman, Margarita Bahena; Castro-Romero, Julieta Ivone

    2014-08-01

    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

  8. [A Patient with Multiple Endocrine Neoplasia Type1(MEN1)Presenting with Hypoglycemic Attacks].

    PubMed

    Bando, Kazuhiko; Ebisutani, Daizo

    2015-05-01

    Here, we report the case of a woman with multiple endocrine neoplasia type 1(MEN1)who experienced hypoglycemic attacks. At the age of 59, she underwent parathyroid tumor resection for hyperparathyroidism. At the age of 65, she presented with dizziness at our hospital. Magnetic resonance imaging(MRI)revealed a left cerebellopontine(CP)angle tumor and a pituitary tumor. The CP angle tumor(acoustic neurionoma)was removed;the pituitary adenoma(prolactinoma)was managed by using bromocriptine. At the age of 77, she lost consciousness and was transferred to a local hospital. Her blood sugar level was 24mg/dL. Due to the frequent recurrence of hypoglycemic attacks, she was readmitted to our hospital. MRI revealed the almost complete removal of the acoustic tumor and that her pituitary gland was atrophied. Despite her baseline pituitary hormone levels being normal, we suspected panhypopituitarism and administered cortisol(15mg/day). As her hypoglycemia failed to improve, we performed a 75-g oral glucose tolerance test, and its result was not indicative of diabetes mellitus. Her pretest immunoreactive insulin(IRI)level was 6.8?U/mL;?IRI/?BS was 0.62, indicative of insulin hypersecretion. Contrast-enhanced abdominal computed tomography revealed multiple pancreatic tumors(insulinomas), and she underwent resection of the uncal tumor and pancreas body and tail. Her postoperative IRI level was normalized and she experienced no further hypoglycemic attacks. Based on her hyperparathyroidism, pancreatic tumor, and pituitary adenoma, we diagnosed her with MEN1. PMID:25926542

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

    PubMed Central

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

    1998-01-01

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

  10. Human papillomavirus genotype in cervical intraepithelial neoplasia grades 2 and 3 of Taiwanese women.

    PubMed

    Chao, Angel; Jao, Mei-Shan; Huang, Chu-Chun; Huang, Huei-Jean; Cheng, Hui-Hsin; Yang, Jung-Erh; Hsueh, Swei; Chen, Tse-Ching; Qiu, Jian-Tai; Lin, Cheng-Tao; Fu, Chang-Jui; Chou, Hung-Hsueh; Lai, Chyong-Huey

    2011-02-01

    We aimed to assess the distribution of human papillomavirus (HPV) genotypes in high-grade cervical lesions in Taiwan. The study included 1,086 paraffin-embedded, formaldehyde-fixed cervical intraepithelial neoplasia (CIN) 2/3 specimens. HPV genotyping was performed using polymerase chain reaction (PCR)-based methods. Multiple HPV types were validated by E6 type-specific PCR, direct sequencing and/or real-time PCR. HPV DNA was detected in 995 (91.6%) specimens, and multiple HPV types were identified in 192 (19.3%) samples. The leading HPV types were HPV16 (24%), HPV52 (20%), HPV58 (20%), HPV33 (13%), HPV31 (8%) and HPV18 (4.6%). Although the leading six types consisted of 87.6%, HPV16 or 18 comprised only 30.9%. The prevalence of different HPV types showed a significant association with age. In women older than 50 yr, HPV16 and 18 comprised 21.3% (83/389), while HPV52, 58 and 33 represented 55.5% (216/389). In women aged less than 50 yr, HPV16 and 18 comprised 32.1% (224/697, p < 0.0001), while HPV 52, 58 and 33 represented 47.9% (334/697, p = 0.02). The distribution of HPV genotypes was compared with previously reported findings for Taiwanese women with cervical cancer (CC). The overall HPV16 positivity rate was significantly higher in CC than in CIN 2/3 (odds ratio: 2.14, 95% CI: 1.91-2.40). In addition, HPV18, 39 and 45 were significantly overrepresented in CC, whereas HPV52, 58, 33, 31, 35, 51 and 53 were underrepresented. We concluded that an effective vaccine against the most common HPV types could prevent a significant proportion of cervical cancer cases that occur in Taiwan. PMID:20473874

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

    PubMed Central

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

    2014-01-01

    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

  12. Detection of superficial esophageal squamous cell neoplasia by chromoendoscopy-guided confocal laser endomicroscopy

    PubMed Central

    Huang, Jin; Yang, Yun-Sheng; Lu, Zhong-Sheng; Wang, Shuang-Fang; Yang, Jing; Yuan, Jing

    2015-01-01

    AIM: To evaluate the diagnostic potential of Lugol’s chromoendoscopy-guided confocal laser endomicroscopy (CLE) in detecting superficial esophageal squamous cell neoplasia (ESCN). METHODS: Between December 2008 and September 2010, a total of 52 patients were enrolled at the Chinese PLA General Hospital in Beijing, China. First, Lugol’s chromoendoscopy-guided CLE was performed in these patients and the CLE in vivo histological diagnosis was recorded. Then, chromoendoscopy-guided biopsy was performed in the same patients by another endoscopist who was blinded to the CLE findings. Based on the biopsy and CLE diagnosis, en bloc endoscopic resection was performed. The CLE in vivo diagnosis and the histological diagnosis of biopsy of ESCN were compared, using a histological examination of the endoscopic resection specimens as the standard reference. RESULTS: A total of 152 chromoendoscopy-guided biopsies were obtained from 56 lesions. In the 56 lesions of 52 patients, a total of 679 CLE images were obtained vs 152 corresponding biopsies. The sensitivity, specificity, negative predictive value and positive predictive value of chromoendoscopy-guided CLE compared with biopsy were 95.7% vs 82% (P < 0.05), 90% vs 70% (P < 0.05), 81.8% vs 46.7% (P < 0.05), and 97.8% vs 92.7% (P > 0.05), respectively. There was a significant improvement in sensitivity, specificity, negative predictive value, and accuracy when comparing chromoendoscopy-guided CLE with biopsy. CONCLUSION: Lugol’s chromoendoscopy-guided CLE is a real-time, non-invasive endoscopic diagnostic technology; the accuracy of the detection of superficial ESCN is equivalent to or may be superior to biopsy histology. PMID:26078575

  13. Proliferation Rates of Multiple Endocrine Neoplasia Type 1 (MEN1)-Associated Tumors

    PubMed Central

    Walls, Gerard V.; Reed, Anita A.C.; Jeyabalan, Jeshmi; Javid, Mahsa; Hill, Nathan R.; Harding, Brian

    2012-01-01

    Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the combined occurrence of parathyroid and adrenocortical tumors, and neuroendocrine tumors (NETs) of the pancreas and pituitary. The pancreatic NETs are predominantly gastrinomas and insulinomas, and the pituitary NETs are mostly prolactinomas and somatotrophinomas. We postulated that the different types of pancreatic and pituitary NETs may be partly due to differences in their proliferation rates, and we therefore assessed these in MEN1-associated tumors and gonadal tumors that developed in mice deleted for an Men1 allele (Men1+/?). To label proliferating cells in vivo, Men1+/? and wild-type (Men1+/+) mice were given 5-bromo-2-deoxyuridine (BrdU) in drinking water from 1–12 wk, and tissue sections were immunostained using anti-BrdU and hormone-specific antibodies. Proliferation in the tumors of Men1+/? mice was significantly (P < 0.001) increased when compared with the corresponding normal Men1+/+ tissues. Pancreatic, pituitary and adrenocortical proliferation fitted first- and second-order regression lines in Men1+/+ tissues and Men1+/? tumors, respectively, R2 = 0.999. Apoptosis was similar in Men1+/? pancreatic, pituitary, and parathyroid tumors when compared with corresponding normal tissues, decreased in Men1+/? adrenocortical tumors, but increased in Men1+/? gonadal tumors. Mathematical modeling of NET growth rates (proliferation minus apoptosis rates) predicted that in Men1+/? mice, only pancreatic ?-cells, pituitary lactotrophs and somatotrophs could develop into tumors within a murine lifespan. Thus, our studies demonstrate that Men1+/? tumors have low proliferation rates (<2%), second-order kinetics, and the higher occurrence of insulinomas, prolactinomas, and somatotrophinomas in MEN1 is consistent with a mathematical model for NET proliferation. PMID:23024266

  14. Conization Using an Electrosurgical Knife for Cervical Intraepithelial Neoplasia and Microinvasive Carcinoma

    PubMed Central

    Yang, Wentao; Xu, Xiaoli; Wu, Xiaohua; Wang, Huaying; Li, Ziting; Yang, Huijuan

    2015-01-01

    Objective The aim of the present study was to evaluate the incidences of margin involvement, disease relapse, and complications in patients who had undergone conization using an electrosurgical knife (EKC) for cervical intraepithelial neoplasia (CIN) or microinvasive carcinomas (micro-CAs). Materials and Methods A retrospective case series analysis was performed with a total of 1359 patients who underwent EKC in Fudan University Shanghai Cancer Center between June 2004 and July 2010. Results The median age of the patients was 39 years old (range: 19-72). Conization revealed the presence of CIN in 1113 (81.9%) patients, micro-CA in 72 (5.3%) patients and invasive carcinomas in 44 (3.2%) patients. The remaining 130 (9.6%) patients were free of diseases in the cone specimens. Positive surgical margins, or endocervical curettages (ECCs) were found in 90 (7.6%) patients with CINs or micro-CAs. Three factors were associated with positive margins and ECCs and included age (>50 years; odds ratio (OR), 3.0, P<0.01), postmenopausal status (OR, 3.1, P<0.01) and microinvasive disease (OR, 2.7, P<0.01). One thousand and eighty-nine (92.0%) patients were followed-up regularly for a median follow-up duration of 46 months (range: 24-106 months). Disease relapse was documented in 50 (4.6%) patients. Eighty-two (6.0%) cases experienced surgical complications that needed to be addressed, including early or late hemorrhages, infections, cervical stenosis, etc. Conclusions Our patients demonstrated that EKC was an alternative technique for diagnosis and treatment of CIN or micro-CAs with relatively low rate of recurrence and acceptable rate of complications. A randomized clinical trial is warranted to compare EKC, CKC and LEEP in the management of CIN or micro-CA. PMID:26153692

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

    PubMed

    Syrjänen, K J

    1987-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

    A 63-year-old female patient presented to a local physician with pain in her back and epigastric region. An abdominal computed tomography (CT) scan revealed a pancreatic tumor, and the patient was referred to our hospital. Multiple imaging studies that included ultrasonography (US), CT, MRI, and endoscopic US revealed a cystic lesion 3–4 cm in size with node-like projections in the body of the pancreas. The distal main pancreatic duct was also found to be dilated. Endoscopic retrograde pancreatography revealed an irregular stenosis of the main pancreatic duct proximal to the cystic lesion, and malignancy was suspected. The patient was preoperatively diagnosed with pancreatic ductal carcinoma concomitant with intraductal papillary mucinous carcinoma, and a distal pancreatectomy was performed. Rapid pathological diagnosis during surgery revealed positive surgical margins for pancreatic intraepithelial neoplasia (PanIN). Further resection was performed twice, her surgical margin was positive and total pancreatectomy was ultimately conducted. Histopathological findings revealed diffuse microinvasive cancerous lesions corresponding to PanIN-2 (moderate dysplasia) to PanIN-3 (carcinoma in situ) throughout the pancreas. PanIN involves microlesions of the ductal epithelium that may precede pancreatic cancer. Ascertaining changes in PanIN using images provided by diagnostic modalities such as CT and US is challenging. Ductal stenosis and distal cystic lesions resulting from atrophy and fibrosis of pancreatic tissue were noted around PanIN. Considering the possibility of PanIN, a precancerous lesion during differential diagnosis will help to improve early detection and prognosis for patients with pancreatic cancer. PMID:25762925

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

    PubMed Central

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

    2010-01-01

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

  19. Counselling in multiple endocrine neoplasia syndromes: from individual experience to general guidelines.

    PubMed

    Lips, C J; Höppener, J W; Van Nesselrooij, B P; Van der Luijt, R B

    2005-01-01

    Counselling of patients and closely related family members has to take a central place in management of hereditary diseases, like multiple endocrine neoplasia (MEN) syndromes including von Hippel-Lindau (VHL) disease. In the strategy of health care, preventive medicine such as periodic clinical examination of families at-risk needs a high priority, because in general it is assumed that continuity in attendance is cost-effective. Counselling has to be based on individual medical experience of the doctor, adjusted to common guidelines and the findings in the family. Information leaflets, appropriate outpatient departments and an extensive network of specialists will facilitate continuity in care. Flow diagrams involving practical guidelines for diagnosis, treatment and follow up need to be applicable and after adjustment, should be accepted generally. Specially trained paramedics for counselling are required as a network that will guarantee periodic clinical examination and secure optimal prevention. Such paramedics will coordinate nationwide multidisciplinary guidance, and organize preventive and emergency cure for these patients. They will be supervised by expert clinicians in the field, and collaborate with specialists for social and psychological issues, patient organizations and clinical genetic centres. All of these professionals are responsible together for providing patients with up to date clinical information (via newsletters, Internet, etc.). Recently, in the Netherlands, a project was initiated to guarantee continuity in care and study the delivery of care. In order to realize this plan, funding has to be provided in the current research programme. In a future system support has to be obtained on a continuous base, preferably by the government and health care insurers and supervised by the national institute for health care. PMID:15606378

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

    PubMed Central

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

    2012-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2011-08-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2010-12-01

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

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

    PubMed Central

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

    2010-01-01

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

  4. Combined use of vitamin D3 and metformin exhibits synergistic chemopreventive effects on colorectal neoplasia in rats and mice.

    PubMed

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

    2015-02-01

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

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

    USGS Publications Warehouse

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

    2009-01-01

    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.

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

    PubMed

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

    2014-08-01

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

  7. High-resolution endoscopy and endoscopic ultrasound for evaluation of early neoplasia in Barrett’s esophagus

    Microsoft Academic Search

    T. Thomas; D. Gilbert; P. V. Kaye; I. Penman; G. P. Aithal; Krish Ragunath

    2010-01-01

    Background  Endoscopic ultrasound (EUS) is useful for detecting depth of invasion and nodal involvement in patients with early Barrett’s\\u000a neoplasia (EBN), precluding endoscopic management. This study aimed to determine whether the lesion morphology of the EBN\\u000a shown on high-resolution endoscopy predicts EUS and histologic tumor stage.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Retrospective series from two tertiary referral centers were studied. Patients with EBN referred for EUS

  8. CT colonography with limited bowel preparation for the detection of colorectal neoplasia in an FOBT positive screening population

    Microsoft Academic Search

    Marjolein H. Liedenbaum; Ayso H. de Vries; Anne F. van Rijn; Helena M. Dekker; François E. J. A. Willemssen; Monique E. van Leerdam; Corine J. van Marrewijk; Paul Fockens; Shandra Bipat; Patrick M. M. Bossuyt; Evelien Dekker; Jaap Stoker

    2010-01-01

    Purpose  Aim was to evaluate the accuracy of computed tomography colonography (CTC) for detection of colorectal neoplasia in a Fecal\\u000a Occult Blood Test (FOBT) positive screening population.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  In three different institutions, consecutive FOBT positives underwent CTC after laxative free iodine tagging bowel preparation\\u000a followed by colonoscopy with segmental unblinding. Each CTC was read by two experienced observers. For CTC and for

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

    PubMed Central

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

    2011-01-01

    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

  10. Depth-sensitive optical spectroscopy for noninvasive diagnosis of oral neoplasia

    NASA Astrophysics Data System (ADS)

    Schwarz, Richard Alan

    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.

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

    PubMed

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

    2015-02-01

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

  12. Surgical versus medical treatment of ocular surface squamous neoplasia: A comparison of recurrences and complications

    PubMed Central

    Nanji, Afshan A.; Moon, Christina S.; Galor, Anat; Sein, Julia; Oellers, Patrick; Karp, Carol L.

    2014-01-01

    Purpose Treatment for ocular surface squamous neoplasia (OSSN) has historically been surgery, but non-surgical interventions are increasingly employed. Treatment with interferon is efficacious, but evidence is needed regarding recurrence and complication rates in comparison to surgery. The objective of this study is to compare the recurrence and complication rates of surgical versus interferon treatment for OSSN. Design A matched, case-control study. Participants Ninety eight patients with OSSN, 49 of whom were treated with interferon alpha 2b (IFN?2b) therapy and 49 of whom were treated with surgical intervention. Methods Patients with OSSN were treated with surgery versus IFN?2b therapy, either in topical or injection form. Median follow up after lesion resolution for the IFN?2b group was 21 months (range 0–173 months) and for the surgery group was 24 months (range 0.9–108 months). Main outcome measure The primary outcome measure for the study was the rate of recurrence of OSSN in each of the treatment groups. Recurrence rates were evaluated using Kaplan-Meier survival analysis. Results Mean patient age and gender were similar between the groups. There was a trend toward higher clinical American Joint Committee on Cancer tumor grade in the IFN?2b group. Despite this, the number of recurrences was equal at 3 per group. The one year recurrence rate was 5% in the surgery group versus 3% in the IFN?2b group (p=0.80). There was no statistically significant difference in the recurrence rate between the surgically and medically treated groups. Non-limbal location was a risk factor for recurrence (hazard ratio 8.96), in the entire study population. In patients treated successfully, the side effects of the two treatments were similar, with mild discomfort seen in the majority of patients in both groups. There was no limbal stem cell deficiency, symblephara, or diplopia noted in either group. Two patients were excluded from the IFN?2b group due to intolerance to the medication. Conclusion No difference in the recurrence rate of OSSN was found between surgical versus IFN?2b therapy. PMID:24411578

  13. Immunohistochemical expression of p16 and Ki-67 correlates with degree of anal intraepithelial neoplasia.

    PubMed

    Bean, Sarah M; Eltoum, Isam; Horton, Debra K; Whitlow, Leisa; Chhieng, David C

    2007-04-01

    Anal intraepithelial neoplasia (AIN) is a human papilloma virus related lesion. It has been shown that infection with high-risk human papilloma virus results in up-regulation of p16 and increased cellular proliferation. The objective of this study is to correlate p16 expression and cellular proliferation measured by Ki-67 staining with the degree of dysplasia in the anal canal and to determine the efficacy of these markers in diagnosing high-grade AIN. Seventy-five anal specimens from 55 patients (37 men; 18 women; mean age: 48 y; median: 44 y; range 25 to 96 y) were studied including 35 normal/reactive lesions, 23 low-grade AIN (AIN I and condyloma), and 17 high-grade AIN (AIN II and III). Immunostaining for p16 and Ki-67 was performed. Expression of p16 in AIN correlated with that of Ki-67 (P<0.001). High-grade AIN often demonstrated p16 staining in more than one-third of the thickness of the epithelium in a diffuse/continuous fashion. p16 expression in low-grade AIN was often restricted to the lower 1/3 of the epithelium and/or was focal and discontinuous. The expression of both p16 and Ki-67 correlated with the degree of dysplasia (P<0.01). When positive p16 staining was defined as the presence of diffuse/continuous staining in more than one-third of the thickness of epithelium, the sensitivity, specificity, and accuracy of p16 as a marker for diagnosing high-grade AIN were 76%, 86%, and 84%, respectively. When positive Ki-67 staining was defined as the presence of nuclear staining in more than 25% of the cells in more than one-third of the thickness of epithelium, the sensitivity, specificity, and accuracy of Ki-67 as a marker for diagnosing high-grade AIN were 71%, 84%, and 83% respectively. Both p16 and Ki-67 are reliable markers for diagnosing high-grade AIN. PMID:17414102

  14. Entrevista con Vicente Leñero

    E-print Network

    Day, Stuart A.

    2004-01-01

    también en la vida profesional de Leñero. Poco después de este acontecimiento algunos de los ex-colaboradorcs de Excélsior, dirigidos nuevamen te por Julio Scherer y con Leñero como vocal, forman una agencia de noticias que empieza con dos máquinas... de la primera edición de Proceso, Leñero decide ignorar este incidente para hacerlo materia de su novela testimonial Los periodistas, al mismo tiempo que lo instituye en travesura para no sucumbir ante el miedo. Su formación periodística, combinada...

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

    PubMed Central

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

    2014-01-01

    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

  16. LYMPHOID NEOPLASIA Pharmaceutical inhibition of glycogen synthetase kinase-3 reduces multiple

    E-print Network

    Hammerton, James

    osteoclastogenesis and inhibits differentiation of mesenchymal stem cells/marrow stromal cells (MSCs), presumptive- esis in mesenchymal stem/progenitor cells, irrespective of the extracellular con- centration of Wnt Hospital, Texas A&M Health Science Center, Temple, TX Multiple myeloma (MM) is a malignancy of plasma cells

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

    Microsoft Academic Search

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

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

  18. Circumferential EMR and complete removal of Barrett's epithelium: A new approach to management of Barrett's esophagus containing high-grade intraepithelial neoplasia and intramucosal carcinoma

    Microsoft Academic Search

    Stefan Seewald; Thawatchai Akaraviputh; Uwe Seitz; Boris Brand; Stefan Groth; Gerardo Mendoza; Xikun He; Frank Thonke; Manfred Stolte; Soeren Schroeder; Nib Soehendra

    2003-01-01

    Background: There is no study of circumferential EMR in patients with Barrett's esophagus containing early stage malignant lesions. This study investigated the effectiveness and safety of circumferential EMR by using a simple snare technique without cap. Method: Patients with Barrett's esophagus containing multifocal high-grade intraepithelial neoplasia or intramucosal cancer, and patients with endoscopically nonidentifiable early stage malignant mucosal changes incidentally

  19. High-grade prostatic intraepithelial neoplasia and atypical small acinar proliferation on initial 21-core extended biopsy scheme: incidence and implications for patient care and surveillance

    E-print Network

    Paris-Sud XI, Université de

    [4,5,6]. The prostate cancer detection rate on repeated biopsy after initial diagnosis of HGPIN ; high grade intraepithelial neoplasia ; prostate cancer ; saturation biopsy 1 inserm-00423056,version1 and to determine the prostate cancer detection rate in the repeated biopsy. METHODS: Between 2002 and 2008, 2

  20. 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...

  1. 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

    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

    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

  2. Large duct type invasive adenocarcinoma of the pancreas with microcystic and papillary patterns: a potential microscopic mimic of non-invasive ductal neoplasia

    Microsoft Academic Search

    Pelin Bagci; Aleodor A Andea; Olca Basturk; Kee-Taek Jang; Ipek Erbarut; Volkan Adsay

    2012-01-01

    A morphological variant of pancreatic ductal adenocarcinoma forming large ductal elements, large duct type ductal adenocarcinoma, is documented and its clinicopathological features are studied. These tumors may have microcystic and papillary growth patterns that closely mimic the non-invasive cystic and papillary pancreatic tumors such as: intraductal papillary-mucinous neoplasia, including the oncocytic variant, mucinous cystic neoplasms, and ducts involved by pancreatic

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

    E-print Network

    Dove, William

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

  4. Potential link between exposure to fungicides chlorothalonil and mancozeb and haemic neoplasia development in the soft-shell clam Mya arenaria: A laboratory experiment

    Microsoft Academic Search

    Julie Pariseau; Richard Saint-Louis; Maryse Delaporte; Mohammed Abo El Khair; Patricia McKenna; Réjean Tremblay; T. Jeffrey Davidson; Emilien Pelletier; Franck C. J. Berthe

    2009-01-01

    The aetiology of haemic neoplasia (HN) is unknown, so far but many causative factors are suggested such as viral, pollution and genetics. The aim of this study was to determine if, under chronic exposure, two major pesticides (chlorothalonil and mancozeb) which are used in potato production could induce HN in soft-shell clams (Mya arenaria). Short-term experiments with acute exposure were

  5. A pilot study of the endomicroscopic assessment of tumor extension in Barrett’s esophagus–associated neoplasia before endoscopic resection

    PubMed Central

    Dolak, Werner; Mesteri, Ildiko; Asari, Reza; Preusser, Matthias; Tribl, Barbara; Wrba, Friedrich; Schoppmann, Sebastian F.; Hejna, Michael; Trauner, Michael; Häfner, Michael; Püspök, Andreas

    2015-01-01

    Background and study aims: Barrett’s esophagus (BE)?–?associated neoplasia can be treated endoscopically, but accurate assessment before intervention is challenging. This study aimed to investigate the role of confocal laser endomicroscopy (CLE) as an adjunct in the endoscopic treatment of BE-associated neoplasia by assessing lateral tumor and subsquamous tumor (SST) extension. Patients and methods: In the context of a prospective, single-arm pilot clinical trial, patients referred for endoscopic resection of BE-associated neoplasia (high grade dysplasia and esophageal adenocarcinoma) underwent high definition, white light endoscopy with narrow-band imaging (NBI). Then, CLE mapping of suspected neoplastic lesions was performed by another endoscopist, partially blinded to the previous findings, before the patients underwent endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD), depending on lesion size and anticipated histology. Results: In 7 of 38 patients (18?%), CLE revealed additional neoplastic tissue compared with prior white light endoscopy and NBI: 2 concomitant lesions, 2 cases of lateral tumor extension within the Barrett’s epithelium, and 3 cases of previously undetected SST extension. Overall, en bloc resection (tumor-free lateral margin) was achieved in 28 of 34 neoplastic lesions (82?%), and complete resection (tumor-free lateral and basal margins) in 21 of 34 neoplastic lesions (62?%). Conclusions: CLE-assisted endoscopic resection of BE-associated neoplasia was safe and effective in this study, as proved by a high additional diagnostic yield of CLE (including visualization of occult SST extension) and a favorable rate of en bloc resection. The clinical value of CLE for assisting endoscopic therapy of BE-associated neoplasia deserves further evaluation in randomized controlled trials.

  6. Detection of benign epithelia, prostatic intraepithelial neoplasia, and cancer regions in radical prostatectomy tissues using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Devpura, Suneetha; Thakur, Jagdish S.; Sarkar, Fazlul H.; Sakr, Wael A.; Naik, Vaman M.; Naik, Ratna

    2010-03-01

    We have studied benign epithelia (BE), prostatic intraepithelial neoplasia (PIN), adenocarcinoma, and cancerous tissues of different Gleason scores in human prostrate bulk tissues using Raman spectroscopy. The data shows two main differences in the Raman spectral features of BE, PIN and cancerous tissues: (i) A strong variations in the peak intensities, (ii) shift in certain peak positions. In order to quantify these variations, Raman data were analyzed using chemometric methods of principal component analysis (PCA) and discriminant function analysis (DFA). The PCA and DFA clearly separated the data into three main distinct pathological groups representing BE, PIN and cancer. Similarly the analysis of different Gleason scores shows that the data can be categorized into three distinct groups representing Gleason score 6, 7, and 8. The results demonstrate that Raman spectroscopy can be used to distinguish different stages of the prostrate cancer.

  7. Adenovirus-mediated suppression of HMGI(Y) protein synthesis as potential therapy of human malignant neoplasias

    PubMed Central

    Scala, Stefania; Portella, Giuseppe; Fedele, Monica; Chiappetta, Gennaro; Fusco, Alfredo

    2000-01-01

    High mobility group I (HMGI) proteins are overexpressed in several human malignant tumors. We previously demonstrated that inhibition of HMGI synthesis prevents thyroid cell transformation. Here, we report that an adenovirus carrying the HMGI(Y) gene in an antisense orientation (Ad-Yas) induced programmed cell death of two human thyroid anaplastic carcinoma cell lines (ARO and FB-1), but not normal thyroid cells. The Ad-Yas virus led to death of lung, colon, and breast carcinoma cells. A control adenovirus carrying the lacZ gene did not inhibit the growth of either normal or neoplastic cells. Ad-Yas treatment of tumors induced in athymic mice by ARO cells caused a drastic reduction in tumor size. Therefore, suppression of HMGI(Y) protein synthesis by an HMGI(Y) antisense adenoviral vector may be a useful treatment strategy in a variety of human malignant neoplasias, in which HMGI(Y) gene overexpression is a general event. PMID:10759549

  8. Detection of benign epithelia, prostatic intraepithelial neoplasia, and cancer regions in radical prostatectomy tissues using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Devpura, Suneetha; Thakur, Jagdish S.; Naik, Ratna; Sarkar, Fazlul H.; Sakr, Wael A.; Naik, Vaman M.

    2010-04-01

    In this study we have investigated Benign Epithelia (BE), Prostatic Intraepithelial Neoplasia (PIN), adenocarcinoma, and different Gleason scores in human prostate bulk tissues using Raman spectroscopy. A careful investigation of the data shows that two main differences in the Raman spectral features of BE, PIN, and cancerous tissues: (i) a strong variations in the band intensities of certain bands, (ii) shift in certain band positions. In order to quantify these variations, Raman data were further analyzed using chemometric methods of Principal Component Analysis (PCA) and Discriminant Function Analysis (DFA). The PCA and DFA clearly separated the data into three main distinct pathological groups representing BE, PIN, and cancerous state in tissue. Similarly the analysis of the Raman data of tissues with different Gleason scores shows that the data can be categorized into three distinct groups representing Gleason scores 6, 7, and 8. The results of this study demonstrate that Raman spectroscopy can diagnose different stages of the prostate cancer.

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

    SciTech Connect

    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

    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.

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

    PubMed Central

    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

    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

  11. Human papillomavirus type 16 E6/E7-specific cytotoxic T lymphocytes in women with cervical neoplasia.

    PubMed

    Bontkes, H J; de Gruijl, T D; van den Muysenberg, A J; Verheijen, R H; Stukart, M J; Meijer, C J; Scheper, R J; Stacey, S N; Duggan-Keen, M F; Stern, P L; Man, S; Borysiewicz, L K; Walboomers, J M

    2000-10-01

    Infection with oncogenic human papillomavirus (HPV) types is associated with the development of cervical neoplasia (CIN). The E6 and E7 oncoproteins are constitutively expressed in these lesions and are therefore putative targets for the immune response against HPV. The relation between HPV 16-specific memory cytotoxic T-cell precursor (mCTLp) activity to both oncoproteins and the natural course of cervical dysplasia was analyzed in 38 patients participating in a nonintervention cohort study of women with CIN and 11 HPV 16-positive cervical carcinoma patients. In a cross-sectional study at the end of follow-up prior to biopsy, 8 of 20 patients with a persistent HPV 16 infection had specific mCTLp against at least one of the two oncoproteins. By contrast, no specific mCTLp activity was detected in 11 HPV-negative patients or in 7 patients who had cleared an HPV 16 infection at the end of follow-up. However, 5 of 11 cervical carcinoma patients showed mCTLp activity against the E7 protein only. This study demonstrates that HPV 16 oncogene-specific mCTLp are present in women with HPV 16-positive CIN prior to any intervention. Since HPV-specific mCTLp were detected predominantly in women with high-grade lesions or invasive cervical carcinoma and not in women who cleared the virus, the role of naturally occurring mCTLp in the protection against HPV-associated cervical neoplasia remains to be established. PMID:10962445

  12. Comparative Analysis of Clinical Factors Associated with Ocular Surface Squamous Neoplasia in HIV Infected and Non HIV Patients

    PubMed Central

    Khaitan, Isha A.

    2015-01-01

    Introduction Ocular surface squamous neoplasia (OSSN) refers to a spectrum of conjunctival and corneal epithelial disease ranging from dysplasia to invasive carcinoma. HIV infection is an important risk factor postulated for the development of disease Aim To compare and to find out any statistically significant difference in patient demographics, clinical features and pathological findings in HIV infected and non-HIV infected histologically proven cases of ocular surface squamous neoplasia (OSSN). Materials and Methods In the present retrospective case study, data from indoor case records and ocular pathology records of histologically proven cases of OSSN was obtained. The data was then tabulated under various clinicopathological headings in HIV affected and non HIV affected groups. A chi-square test was applied to compare data of two groups and look for any significant difference between two groups. A p-value less than 0.05 was considered significant. Results Amongst the total of 48 patients, 11 were HIV positive and 37 were HIV negative. Age of the patients ranged from 14-66 years in HIV and 22-66 years in non HIV group with a preponderance of younger age patients in HIV positive group. 54.5% patients with lesion having base more than 5mm were observed at the time of presentation in HIV positive population as compared to 21.6% in non HIV cases. Feeder vessels were seen in all HIV patients and a significantly greater degree of fornicial involvement was noted in comparison with non-HIV group. Histopathological analysis showed 63.63% of cases to be of invasive carcinoma amongst the HIV positive group and 54.05% of invasive carcinoma in non HIV group. Conclusion Younger age and aggressive looking tumour at presentation should caution ophthalmologist to look for an undiagnosed HIV infection in OSSN patients.

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

    PubMed

    Agaimy, Abbas

    2014-11-01

    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

  14. ELEVATED EXPRESSION OF CANCER-ASSOCIATED PROLIFERATING CELL NUCLEAR ANTIGEN IN HIGH-GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA AND PROSTATE CANCER

    PubMed Central

    Wang, Xiaoyan; Hickey, Robert J.; Malkas, Linda H.; Koch, Michael O.; Li, Lang; Zhang, Shaobo; Sandusky, George E.; Grignon, David J; Eble, John N.; Cheng, Liang

    2011-01-01

    Background Proliferating-cell nuclear antigen (PCNA) plays an important role in DNA replication and repair. The expression and potential utility of this marker in prostatic neoplasia is uncertain. With the development of this new caPCNA selective antibody, we explored the potential utility of this marker in prostate cancer. Methods Using a traditional primary Fab2? rabbit anti-caPCNA antibody-HRP conjugated secondary anti-Fab2? antibody format, the expression of the caPCNA was analyzed in prostate tissue from 89 radical prostatectomy specimens. The caPCNA expression was correlated with clinicopathologic characteristics. Results The fraction of cells staining positively with caPCNA antibody in prostatic adenocarcinoma (mean, 23%) was significantly higher than that in benign prostatic epithelium (mean, 2%; p < 0.001) or high-grade prostatic intraepithelial neoplasia (PIN) (mean, 6%; p < 0.05). Moreover, the intensity of caPCNA expression in prostatic adenocarcinoma (mean, 2.9) was significantly higher than that in benign prostatic tissue (mean, 0.7; p < 0.001) or high-grade PIN (mean, 2.0; p < 0.001). Benign prostatic epithelium showed only minimal or negative reactivity. There was significant correlation between the percentage of caPCNA expression and primary Gleason grade (p = 0.01), and with Gleason score (p = 0.02). Adenocarcinomas with positive vascular invasion had a significantly higher percentage of cells staining with caPCNA antibody (p < 0.0001) and a higher intensity of caPCNA expression (p = 0.04). Conclusions Our data indicate that increased expression of the cancer-associated isoform of PCNA is common in prostatic adenocarcinoma and its precursor and may be a useful biomarker. PMID:21031434

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

    PubMed

    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

    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

  16. First-line chemotherapy in low-risk gestational trophoblastic neoplasia

    PubMed Central

    Alazzam, Mo’iad; Tidy, John; Hancock, Barry W; Osborne, Raymond; Lawrie, Theresa A

    2014-01-01

    Background This is an update of a Cochrane review that was first published in Issue 1, 2009. Gestational trophoblastic neoplasia (GTN) is a rare but curable disease arising in the fetal chorion during pregnancy. Most women with low-risk GTN will be cured by evacuation of the uterus with or without single-agent chemotherapy. However, chemotherapy regimens vary between treatment centres worldwide and the comparable benefits and risks of these different regimens are unclear. Objectives To determine the efficacy and safety of first-line chemotherapy in the treatment of low-risk GTN. Search methods In September 2008, we electronically searched the Cochrane Gynaecological Cancer Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL Issue 3, 2008), MEDLINE and EMBASE. In addition, we searched online trial registers, conference proceedings and reference lists of identified studies. We re-ran these searches in February 2012 for this updated review. Selection criteria For the original review, we included randomised controlled trials (RCTs), quasi-RCTs and non-RCTs that compared first-line chemotherapy for the treatment of low-risk GTN. For this updated version of the review, we included only RCTs. Data collection and analysis Two review authors independently assessed studies for inclusion and extracted data to a pre-designed data extraction form. Meta-analysis was performed by pooling the risk ratio (RR) of individual trials. Main results We included five moderate to high quality RCTs (517 women) in the updated review. These studies all compared methotrexate with dactinomycin. Three studies compared weekly intramuscular (IM) methotrexate with bi-weekly pulsed intravenous (IV) dactinomycin (393 women), one study compared five-day IM methotrexate with bi-weekly pulsed IV dactinomycin (75 women) and one study compared eight-day IM methotrexate-folinic acid (MTX-FA) with five-day IV dactinomycin (49 women). Overall, dactinomycin was associated with significantly higher rates of primary cure than methotrexate (five studies, 513 women; RR 0.64, 95% Confidence Interval (CI) 0.54 to 0.76). Methotrexate was associated with significantly more treatment failure than dactinomycin (five studies, 513 women; RR 3.81, 95% CI 1.64 to 8.86). We consider this evidence to be of a moderate quality. There was no significant difference between the two groups with respect to nausea (four studies, 466 women; RR 0.61, 95% CI 0.29 to 1.26) or any of the other individual side-effects reported, although data for all of these outcomes were insufficient and too heterogeneous to be conclusive. No severe adverse effects (SAEs) occurred in either group in three out of the five included studies and there was no significant difference in SAEs between the groups overall (five studies, 515 women; RR 0.35, 95% CI 0.08 to 1.66; I2 = 60%), however, there was a trend towards fewer SAEs in the methotrexate group. We considered this evidence to be of a low quality due to substantial heterogeneity and low consistency in the occurrence/reporting of SAEs between trials. Authors’ conclusions Dactinomycin is more likely to achieve a primary cure in women with low-risk GTN, and less likely to result in treatment failure, compared with methotrexate. There is limited evidence relating to side-effects, however, the pulsed dactinomycin regimen does not appear to be associated with significantly more side-effects than the low-dose methotrexate regimen and therefore should compare favourably to the five- and eight-day methotrexate regimens in this regard. We consider pulsed dactinomycin to have a better cure rate than, and a side-effect profile at least equivalent to, methotrexate when used for first-line treatment of low-risk GTN. Data from a large ongoing trial of pulsed dactinomycin compared with five- and eight-day methotrexate regimens is likely to have an important impact on our confidence in these findings. PMID:22786502

  17. Entrevista con Sergio Vodanovic

    E-print Network

    Agosin, Marjorie

    1984-04-01

    de pionero dentro del teatro chileno contemporáneo. Este es el tema de la entrevista cuyas preguntas fueron contestadas directamente por Vodanovic y transcritas en la misma manera como aparecen en el texto. ¿Cómo ves tú el teatro chileno desde el... remora de los teatros que antes eran líderes, de los teatros universitarios que, en general, se mantienen dentro de una posición de dar obras clásicas u obras de teatros universal, y con mucho temor respecto al teatro chileno. ¿ Tú crees que el público...

  18. Entrevista con Santiago García

    E-print Network

    Baycroft, Bernard

    1982-04-01

    muchas resistencias que había entre la gente de tea tro a este fenómeno de la creación colectiva, que aparece compitiendo con el autor y entrando al terreno de la creatividad artística. ¿Cómo es esto diferente a la práctica del Teatro Experimental de... teatral que nosotros estamos produciendo porque el tener este pú blico y un campo de experimentación tan fecundo como es ése de los sectores populares, más avanzados, más revolucionarios, más progresistas de nuestro país, garantizaría ya la...

  19. Entrevista con Enrique Buenaventura

    E-print Network

    Dí ez, Luys A.

    1981-04-01

    el individuo; entrañable y sencillo, conversador penetrante y muy ameno. Y fue en esta capacidad, aprovechando una falla en la programación, que una tarde le acompañamos a ver A Chorus Line, el musical de Bennett, que le iba a interesar... todavía muestran las huellas de los terribles bombardeos e incendios, con las paredes acribilladas por todas partes. Y luego las historias que iba contando todo el mundo, tantas que en realidad sería muy difícil escoger. Yo he seleccionado unas pocas y...

  20. Targeting Human Papillomavirus to Reduce the Burden of Cervical, Vulvar and Vaginal Cancer and Pre-Invasive Neoplasia: Establishing the Baseline for Surveillance

    PubMed Central

    Nygård, Mari; Hansen, Bo Terning; Dillner, Joakim; Munk, Christian; Oddsson, Kristján; Tryggvadottir, Laufey; Hortlund, Maria; Liaw, Kai-Li; Dasbach, Erik J.; Kjær, Susanne Krüger

    2014-01-01

    Background Infection with high-risk human papillomavirus (HPV) is causally related to cervical, vulvar and vaginal pre-invasive neoplasias and cancers. Highly effective vaccines against HPV types 16/18 have been available since 2006, and are currently used in many countries in combination with cervical cancer screening to control the burden of cervical cancer. We estimated the overall and age-specific incidence rate (IR) of cervical, vulvar and vaginal cancer and pre-invasive neoplasia in Denmark, Iceland, Norway and Sweden in 2004–2006, prior to the availability of HPV vaccines, in order to establish a baseline for surveillance. We also estimated the population attributable fraction to determine roughly the expected effect of HPV16/18 vaccination on the incidence of these diseases. Methods Information on incident cervical, vulvar and vaginal cancers and high-grade pre-invasive neoplasias was obtained from high-quality national population-based registries. A literature review was conducted to define the fraction of these lesions attributable to HPV16/18, i.e., those that could be prevented by HPV vaccination. Results Among the four countries, the age-standardised IR/105 of cervical, vaginal and vulvar cancer ranged from 8.4–13.8, 1.3–3.1 and 0.2–0.6, respectively. The risk for cervical cancer was highest in women aged 30–39, while vulvar and vaginal cancers were most common in women aged 70+. Age-standardised IR/105 of cervical, vulvar and vaginal pre-invasive neoplasia ranged between 138.8?183.2, 2.5?8.8 and 0.5?1.3, respectively. Women aged 20?29 had the highest risk for cervical pre-invasive neoplasia, while vulvar and vaginal pre-invasive neoplasia peaked in women aged 40?49 and 60?69, respectively. Over 50% of the observed 47,820 incident invasive and pre-invasive cancer cases in 2004?2006 can be attributed to HPV16/18. Conclusion In the four countries, vaccination against HPV 16/18 could prevent approximately 8500 cases of gynecological cancer and pre-cancer annually. Population-based cancer and vaccination registries are essential to assess the predicted public health effects of HPV vaccination. PMID:24505474

  1. Crnica ornitolgica con las citas

    E-print Network

    Carrete, Martina

    Crónica ornitológica con las citas más relevantes del año 2000 Estudio de la avifauna de las balsas seguimiento que ha realizado a la avifauna del paraje. · La crónica ornitológica del año 2000, con las

  2. Entrevista con Wilberto Cantón

    E-print Network

    Vé lez, Joseph F.

    1979-10-01

    FALL 1979 71 Entrevista con Wilberto Cantón JOSEPH F. VÉLEZ Señor Cantón, ¿quisiera usted decirme donde y cuándo nació?1 Nací en la ciudad de Mérida, Yucatán, el día 15 de julio de 1925. ¿Puede usted ahora decirnos un poco de su educación... primaria, secundaria y universitaria, ya haya sido en México o en el extranjero? Sí. Yo hice mis primeros estudios allá en la ciudad de Mérida y, posterior mente, vine a México, y aquí cursé el bachillerato y mi profesión, que es de abogado. Terminé...

  3. Use of confocal laser endomicroscopy to assess the adequacy of endoscopic treatment of gastrointestinal neoplasia: a systematic review and meta-analysis.

    PubMed

    Ypsilantis, Efthymios; Pissas, Dimitrios; Papagrigoriadis, Savvas; Haji, Amyn

    2015-02-01

    Evaluation of the adequacy of endoscopic mucosal resection (EMR) of gastrointestinal lesions remains challenging by use of conventional endoscopy. Confocal laser endomicroscopy (CLE) is a novel imaging technique, designed to provide in vivo histology, and facilitate diagnosis with real-time intervention. We undertook a systematic review of the available literature, exploring the role of CLE in assuring completeness of EMR of gastrointestinal lesions. The number of pertinent studies is very limited, including only 1 randomized controlled study and 2 prospective comparative case series. Per-lesion meta-analysis showed that the sensitivity of CLE for detection of residual neoplasia was 91% (95% confidence interval, 82.5%-96%) with specificity of 69% (95% confidence interval, 61%-77%), with significant heterogeneity noted in all outcomes. In conclusion, the evidence underpinning the usefulness of CLE in ensuring adequate EMR of gastrointestinal neoplasia is currently very weak, with limited promising results related to gastric and colorectal polyp resections. PMID:24910941

  4. Hexose uptake in 7,12-dimethylbenz(a)anthracene-preexposed rat tracheal epithelial cells during the progression of neoplasia

    SciTech Connect

    Wasilenko, W.J.; Marchok, A.C.

    1984-07-01

    Hexose uptake during the progression of neoplasia in rat tracheal epithelial cells was studied by measuring the uptake of 2-deoxy(/sup 3/H)glucose (2-dGlc) in nontumorigenic (C-18) and tumorigenic (T-8, 1000-WT) rat tracheal epithelial cell lines with varying degrees of cell association as well as in: (a) normal primary cell cultures (NPC) derived from explants of nonexposed tracheas; (b) selected primary cell cultures (SPC) generated from explants of 7,12-dimethylbenz(a)anthracene-treated tracheal implants; and (c) primary tumor cell cultures (TPC) derived from explants of 7,12-dimethylbenz(a)anthracene-induced tracheal carcinomas. The latter two groups represented cells from earlier and late states in the progression of neoplasia, respectively, and each displayed an in vitro growth advantage that allowed for their survival and growth in medium devoid of supplements of pyruvate and insulin. This property was used in this study to select the carcinogen-altered cells from neighboring normal cells. Uptake of 2-dGlc per ..mu..g of DNA was similar in subconfluent cultures of all cell lines. At confluency, uptake per ..mu..g of DNA was reduced markedly (>3-fold) in C-18 cells but it was reduced only 1.3-fold in T-8 cells and 1.6-fold in 1000-WT cells. Hexose uptake was further reduced in T-8 and 1000-WT cell cultures generated as outgrowths from explants of denuded tracheas bearing a reestablished epithelium from each cell line. Under these conditions, T-8 cells retained higher 2-dGlc uptake than did C-18, but uptake by 1000-WT was lower, indicating that tissue-like cell associations have a profound effect on hexose uptake in these epithelial cells. Results were generally similar when uptake was expressed per mg of protein although, in several instances, the interpretation of uptake data was affected by differences in the protein content between cultures. 46 references, 1 figure, 7 tables.

  5. Frequency of Occult High-Grade Squamous Intraepithelial Neoplasia and Invasive Cancer Within Anal Condylomata in Men Who Have Sex With Men

    PubMed Central

    Schlecht, Hans P.; Fugelso, Dana K.; Murphy, Ryan K.; Wagner, Katiri T.; Doweiko, John P.; Proper, JoAnn; Dezube, Bruce J.; Panther, Lori A.

    2015-01-01

    Human papillomavirus causes anal condylomata, high-grade intraepithelial neoplasia (HGAIN), and squamous cell cancer (SCCA). We found HGAIN or SCCA in 75/159 (47%) HIV-seropositive and 42/160 (26%) HIV-seronegative men who have sex with men (MSM) with anal condylomata meriting surgery (p<0.0001, chi-square). Anal condylomata in MSM often harbor HGAIN and SCCA. PMID:20482370

  6. The Induction of Hepatocellular Neoplasia by Trichloroacetic Acid Administered in the Drinking Water of the Male B6C3F1 Mouse

    Microsoft Academic Search

    Anthony B. DeAngelo; F. Bernard Daniel; Diana M. Wong; Michael H. George

    2008-01-01

    The prevalence (percent of animals with a tumor) and multiplicity (number of tumors per animal) of hepatocellular neoplasia in the male B6C3F1 mouse exposed to trichloroacetic acid (TCA) in the drinking water were determined. Male mice were exposed to 0.05, 0.5, and 5 g\\/L TCA for 60 wk (Study 1), to 4.5 g\\/L TCA for 104 wk (Study 2) and

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

    Microsoft Academic Search

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

    2011-01-01

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

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

    Microsoft Academic Search

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

    2001-01-01

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

  9. Immunological Responses in Women with Human Papillomavirus Type 16 (HPV16)Associated Anogenital Intraepithelial Neoplasia Induced by Heterologous Prime-Boost HPV16 Oncogene Vaccination

    Microsoft Academic Search

    Lucy J. C. Smyth; Mariette I. E. van Poelgeest; Emma J. Davidson; Kitty M. C. Kwappenberg; Debbie Burt; Peter Sehr; Michael Pawlita; Julian K. Hickling; Alison N. Fiander; Amanda Tristram; Henry C. Kitchener; Rienk Offringa; Peter L. Stern; Sjoerd H. van der Burg

    Purpose: The purpose is to study the immunogenicity of heterologous prime-boost human papillomavirus (HPV) on- cogene vaccination in patients with anogenital intraepithe- lial neoplasia (AGIN). Experimental Design: Twenty-nine women with high- grade AGIN received three i.m. doses of TA-CIN (HPV-16 L2\\/E6\\/E7 protein) at four weekly intervals followed by a single dermal scarification of vaccinia HPV-16\\/18 E6\\/E7 and were followed up

  10. Immunological and Clinical Responses in Women with Vulval Intraepithelial Neoplasia Vaccinated with a Vaccinia Virus Encoding Human Papillomavirus 16\\/18 Oncoproteins1

    Microsoft Academic Search

    Emma J. Davidson; Christopher M. Boswell; Peter Sehr; Michael Pawlita; Anne E. Tomlinson; Rhona J. McVey; Jennifer Dobson; C. Roberts; Julian Hickling; Henry C. Kitchener; Peter L. Stern

    2003-01-01

    This study assessed the immunological and clinical responses of women with human papillomavirus (HPV) 16-associated high-grade vulval intra- epithelial neoplasia (VIN) vaccinated with TA-HPV, a recombinant vac- cinia virus encoding modified HPV 16 and 18 E6 and E7. Eighteen women with HPV 16-positive high-grade VIN were vaccinated with TA-HPV. The extent of their baseline disease was compared after 24 weeks

  11. EMR is not inferior to ESD for early Barrett’s and EGJ neoplasia: An extensive review on outcome, recurrence and complication rates

    PubMed Central

    Komeda, Yoriaki; Bruno, Marco; Koch, Arjun

    2014-01-01

    Background and study aims In recent years, it has been reported that early Barrett’s and esophagogastric junction (EGJ) neoplasia can be effectively and safely treated using endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Multiband mucosectomy (MBM) appears to be the safest EMR method. The aim of this systematic review is to assess the safety and efficacy of MBM compared with ESD for the treatment of early neoplasia in Barrett’s or at the EGJ. Methods A literature review of studies published up to May 2013 on EMR and ESD for early Barrett’s esophagus (BE) neoplasia and adenocarcinoma at the EGJ was performed through MEDLINE, EMBASE and the Cochrane Library. Results on outcome parameters such as number of curative resections, complications and procedure times are compared and reported. Results A total of 16 studies met the inclusion criteria for analysis in this study. There were no significant differences in recurrence rates when comparing EMR (10/380, 2.6?%) to ESD (1/333, 0.7?%) (OR 8.55; 95?%CI, 0.91?–?80.0, P?=?0.06). All recurrences after EMR were treated with additional endoscopic resection. The risks of delayed bleeding, perforation and stricture rates in both groups were similar. The procedure was considerably less time-consuming in the EMR group (mean time 36.7?min, 95?%CI, 34.5?–?38.9) than in the ESD group (mean time 83.3?min, 95?%CI, 57.4?–?109.2). Conclusions The MBM technique for EMR is as effective as ESD when comparing outcomes related to recurrence and complication rates for the treatment of early Barrett’s or EGJ neoplasia. The MBM technique is considerably less time-consuming.

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

    Microsoft Academic Search

    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

    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

  13. Outcome of unexpected adnexal neoplasia discovered during risk reduction salpingo-oophorectomy in women with germ-line BRCA1 or BRCA2 mutations

    PubMed Central

    Conner, James R.; Meserve, Emily; Pizer, Ellen; Garber, Judy; Roh, Michael; Urban, Nicole; Drescher, Charles; Quade, Bradley J.; Muto, Michael; Howitt, Brooke E.; Pearlman, Mark D.; Berkowitz, Ross S.; Horowitz, Neil; Crum, Christopher P.; Feltmate, Colleen

    2014-01-01

    Purpose This study computed the risk of clinically silent adnexal neoplasia in women with germ-line BRCA1 or BRCA2 mutations (BRCAm+) and determined recurrence risk. Methods We analyzed risk reduction salpingo-oophorectomies (RRSOs) from 349 BRCAm+ women processed by the SEE-FIM protocol and addressed recurrence rates for 29 neoplasms from three institutions. Results Nineteen neoplasms (5.4%) were identified at one institution, 9.2% of BRCA1 and 3.4% of BRCA2 mutation-positive women. Fourteen had a high-grade tubal intraepithelial neoplasm (HGTIN, 74%). Mean age (54.4) was higher than the BRCAm+ cohort without neoplasia (47.8) and frequency increased with age (p<0.001). Twenty-nine BRCA m+ patients with neoplasia from three institutions were followed for a median of 5 years (1–8 yrs.). One of 11 with HGTIN alone (9%) recurred at 4 years, in contrast to 3 of 18 with invasion or involvement of other sites (16.7%). All but two, are currently alive. Among the 29 patients in the three institution cohort, mean ages for HGTIN and advanced disease were 49.2 and 57.7 (p = 0.027). Conclusions Adnexal neoplasia is present in 5–6% of RRSOs, is more common in women with BRCA1 mutations, and recurs in 9% of women with HGTIN alone. The lag in time from diagnosis of the HGTIN to pelvic recurrence (4 years) and differences in mean age between HGTIN and advanced disease (8.5 years) suggest an interval of several years from the onset of HGTIN until pelvic cancer develops. However, some neoplasms occur in the absence of HGTIN. PMID:24333842

  14. Human papillomavirus detection in cervical intraepithelial neoplasia by the second-generation hybrid capture microplate test, comparing two different cervical specimen collection methods

    Microsoft Academic Search

    Ingo Nindl; Attila Lörincz; Iwona Mielzynska; Ulrich Petry; Siegfried Baur; Reinhard Kirchmayr; Wolfgang Michels; Achim Schneider

    1998-01-01

    Background: The second generation Hybrid Capture microplate-based human papillomavirus (HPV) test (HC II) was examined to determine its sensitivity for identification of cervical intraepithelial neoplasia (CIN) by two different cervical specimen collection methods.Objectives: A cohort of 115 women with a mean age of 34.6 years (SD 9.1), referred to colposcopy with a history of abnormal cytology, was studied to compare

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

    Microsoft Academic Search

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

    2005-01-01

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

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

    Microsoft Academic Search

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

    2010-01-01

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

  17. Phase 1 study of HPV16-specific immunotherapy with E6E7 fusion protein and ISCOMATRIX™ adjuvant in women with cervical intraepithelial neoplasia

    Microsoft Academic Search

    Ian H. Frazer; Michael Quinn; Jim L. Nicklin; Jeffrey Tan; Lew C. Perrin; Peng Ng; Vivienne M. O’Connor; Olivia White; Ngaire Wendt; Juliet Martin; Jayne M. Crowley; Stirling J. Edwards; Andrew W. McKenzie; Susan V. Mitchell; Darryl W. Maher; Martin J. Pearse; Russell L. Basser

    2004-01-01

    Purpose: Persistent infection of cervical epithelium with “high risk” human papillomavirus (HPV) results in cervical intraepithelial neoplasia (CIN) from which squamous cancer of the cervix can arise. A study was undertaken to evaluate the safety and immunogenicity of an HPV16 immunotherapeutic consisting of a mixture of HPV16 E6E7 fusion protein and ISCOMATRIX™ adjuvant (HPV16 Immunotherapeutic) for patients with CIN.

  18. Prevalence of Different Subtypes of Serrated Polyps and Risk of Synchronous Advanced Colorectal Neoplasia in Average-Risk Population Undergoing First-Time Colonoscopy

    Microsoft Academic Search

    Andrea Buda; Manuela De Bona; Isabella Dotti; Pierluca Piselli; Eva Zabeo; Renzo Barbazza; Angelo Bellumat; Flavio Valiante; Ermanno Nardon; Chris S Probert; Massimo Pignatelli; Giorgio Stanta; Giacomo Carlo Sturniolo; Michele De Boni

    2012-01-01

    OBJECTIVES:A growing body of evidence indicates that patients with sessile serrated adenoma\\/polyp (SSA\\/P) and traditional serrated adenoma (TSA) are at risk for subsequent malignancy. Despite increasing knowledge on histological categorization of serrated polyps (SPs) data are lacking on the actual prevalence and the association of each SP subtype with advanced colorectal neoplasia.METHODS:We prospectively determined the prevalence of different SP subtypes

  19. Nam Con Son Basin

    SciTech Connect

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

    1994-07-01

    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.

  20. Residual disease and risk factors in patients with high-grade cervical intraepithelial neoplasia and positive margins after initial conization

    PubMed Central

    Fu, Yunfeng; Chen, Chen; Feng, Suwen; Cheng, Xiaodong; Wang, Xinyu; Xie, Xing; Lü, Weiguo

    2015-01-01

    Background The purpose of this study was to determine the clinicopathologic predictors of residual disease in patients with high-grade cervical intraepithelial neoplasia (CIN) and margin involvement after initial conization. Methods Data from 145 patients who underwent subsequent surgery for high-grade CIN with positive margins were retrospectively analyzed. Results After subsequent surgery, residual disease was diagnosed in 47 (34.2%) patients, of whom five had invasive cervical carcinoma, 31 had CIN 3, nine had CIN 2, and two had CIN 1. Multivariate analysis revealed that only age ?35 years (P=0.033), major abnormal cytology (P=0.002), and pre-cone high-risk human papillomavirus load ?300 relative light units (P=0.011) were significant factors associated with residual disease. Conclusion Age ?35 years, major abnormal cytology, and pre-cone high-risk human papillomavirus load ?300 relative light units were the only significant factors predicting post-cone residual disease. Appropriate application of these predictive factors may avoid delayed treatment and overtreatment.

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

    PubMed

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

    2014-01-01

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

  2. Helper T Lymphocyte Response in the Peripheral Blood of Patients with Intraepithelial Neoplasia Submitted to Immunotherapy with Pegylated Interferon-?

    PubMed Central

    Michelin, Márcia Antoniazi; Montes, Letícia; Nomelini, Rosekeila Simões; Trovó, Marco Aurélio; Murta, Eddie Fernando Candido

    2015-01-01

    Immunotherapy in cancer patients is a very promising treatment and the development of new protocols and the study of the mechanisms of regression is imperative. The objective of this study was to evaluate the production of cytokines in helper T (CD4+) lymphocytes during immunotherapy with pegylated IFN-? in patients with cervical intraepithelial neoplasia (CIN). We conducted a prospective study with 17 patients with CIN II-III using immunotherapy with pegylated IFN-? subcutaneouly weekly, and using flow cytometry we evaluated the peripheric CD4+ T lymphocytes. The results show that in the regression group the patients presented a significant increase in the amount of IFN-? during the entire immunotherapy, compared with the group without a response. The amount of CD4+ T lymphocytes positive for IL-2, IL-4, IL-10 and TGF-? is significantly lower in patients with good clinical response. The results also demonstrate that patients with regression have a higher amount of intracellular TNF-? in CD4+ T lymphocytes before the start of treatment. Analyzing these data sets, it can be concluded that immunotherapy is a viable clinical treatment for patients with high-grade CIN and that the regression is dependent on the change in the immune response to a Th1 pattern. PMID:25764160

  3. Changes in methylation pattern of albumin and alpha-fetoprotein genes in developing rat liver and neoplasia.

    PubMed Central

    Vedel, M; Gomez-Garcia, M; Sala, M; Sala-Trepat, J M

    1983-01-01

    To determine whether methylation changes in specific DNA sequences of the albumin and AFP genes are implicated in the modulation of transcriptional activity during rat liver development and neoplasia we have analysed the methylation pattern of C-C-G-G sequences within these genes in DNA isolated from fetal and adult hepatocytes, from adult kidney and from a clonal hepatoma cell line which produces AFP but no albumin. We have assayed for methylation of the internal cytosine of this sequence by using the restriction enzyme isoschizomers HpaII and MspI. 32P-labelled cloned cDNA probes were used to reveal the albumin and AFP gene containing fragments. Genomic subclones of the albumin gene were also utilized as molecular probes to measure quantitatively the level of methylation of 6 specific sites within the albumin gene in the different DNA samples. The results indicate that methylation changes at the sites analysed are not responsible for the changes in gene activity during rat liver development. Further they demonstrate that: 1) extensively methylated genes can be actively transcribed; 2) prominent changes in methylation of specific genes during normal development are not necessarily related to alterations in gene activity. Images PMID:6191280

  4. Analysis of Families with Lynch Syndrome Complicated by Advanced Serrated Neoplasia: The Importance of Pathology Review and Pedigree Analysis

    PubMed Central

    Walsh, Michael D; Buchanan, Daniel D; Walters, Rhiannon; Roberts, Aedan; Arnold, Sven; McKeone, Diane; Clendenning, Mark; Ruszkiewicz, Andrew R; Jenkins, Mark A; Hopper, John L; Goldblatt, Jack; George, Jillian; Suthers, Graeme K; Phillips, Kerry; Young, Graeme P; Macrae, Finlay; Drini, Musa; Woods, Michael O; Parry, Susan; Jass, Jeremy R; Young, Joanne P

    2009-01-01

    The identification of Lynch syndrome has been greatly assisted by the advent of tumour immunohistochemistry (IHC) for mismatch repair (MMR) proteins, and by the recognition of the role of acquired somatic BRAF mutation in sporadic MMR-deficient colorectal cancer (CRC). However, somatic BRAF mutation may also be present in the tumours in families with a predisposition to develop serrated polyps in the colorectum. In a subgroup of affected members in these families, CRCs emerge which demonstrate clear evidence of MMR deficiency with absent MLH1 staining and high-level microsatellite instability (MSI). This may result in these families being erroneously classified as Lynch syndrome or, conversely, an individual is considered “sporadic” due to the presence of a somatic BRAF mutation in a tumour. In this report, we describe two Lynch syndrome families who demonstrated several such inconsistencies. In one family, IHC deficiency of both MSH2 and MLH1 was demonstrated in tumours from different affected family members, presenting a confusing diagnostic picture. In the second family, MLH1 loss was observed in the lesions of both MLH1 mutation carriers and those who showed normal MLH1 germline sequence. Both families had Lynch syndrome complicated by an independently segregating serrated neoplasia phenotype, suggesting that in families such as these, tumour and germline studies of several key members, rather than of a single proband, are indicated to clarify the spectrum of risk. PMID:19241144

  5. A probabilistic approach to segmentation and classification of neoplasia in uterine cervix images using color and geometric features

    NASA Astrophysics Data System (ADS)

    Srinivasan, Yeshwanth; Hernes, Dana; Tulpule, Bhakti; Yang, Shuyu; Guo, Jiangling; Mitra, Sunanda; Yagneswaran, Sriraja; Nutter, Brian; Jeronimo, Jose; Phillips, Benny; Long, Rodney; Ferris, Daron

    2005-04-01

    Automated segmentation and classification of diagnostic markers in medical imagery are challenging tasks. Numerous algorithms for segmentation and classification based on statistical approaches of varying complexity are found in the literature. However, the design of an efficient and automated algorithm for precise classification of desired diagnostic markers is extremely image-specific. The National Library of Medicine (NLM), in collaboration with the National Cancer Institute (NCI), is creating an archive of 60,000 digitized color images of the uterine cervix. NLM is developing tools for the analysis and dissemination of these images over the Web for the study of visual features correlated with precancerous neoplasia and cancer. To enable indexing of images of the cervix, it is essential to develop algorithms for the segmentation of regions of interest, such as acetowhitened regions, and automatic identification and classification of regions exhibiting mosaicism and punctation. Success of such algorithms depends, primarily, on the selection of relevant features representing the region of interest. We present color and geometric features based statistical classification and segmentation algorithms yielding excellent identification of the regions of interest. The distinct classification of the mosaic regions from the non-mosaic ones has been obtained by clustering multiple geometric and color features of the segmented sections using various morphological and statistical approaches. Such automated classification methodologies will facilitate content-based image retrieval from the digital archive of uterine cervix and have the potential of developing an image based screening tool for cervical cancer.

  6. Can photodynamic therapy be the preferred treatment option for anal intraepithelial neoplasia? Initial results of a pilot study.

    PubMed

    Welbourn, Hannah; Duthie, Graeme; Powell, John; Moghissi, Keyvan

    2014-03-01

    Anal intra-epithelial neoplasia (AIN) is a pre-malignant condition, which over time may progress to invasive anal squamous cell carcinoma. There is no standard treatment for AIN, but one of the therapeutic options available is photodynamic therapy (PDT). There are very few published studies of the efficacy of PDT, but it has been shown to produce downgrading of high-grade dysplasia in the anal region. The aim of the study was to evaluate the role of PDT in the treatment of AIN. Fifteen patients who received anal PDT between 2004 and 2013 were identified; twelve of these had AIN, two had intra-epithelial adenocarcinoma and one had dysplasia with high-risk human papillomavirus. After a median follow-up of nineteen months, ten of these have had at least one follow-up with aceto-white staining. Six of these ten patients had a complete response to PDT, although three subsequently had some recurrence. Three further patients had a partial response to PDT. There were no major therapeutic complications. Our findings suggest that PDT is a safe and feasible treatment option for AIN, associated with reasonable response rates and relatively little morbidity. Further research into the efficacy of PDT for AIN is required. PMID:24280437

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

    PubMed

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

    2011-12-01

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

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

    PubMed Central

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

    2011-01-01

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

  9. T-cell responses to human papillomavirus type 16 among women with different grades of cervical neoplasia

    PubMed Central

    Steele, J C; Mann, C H; Rookes, S; Rollason, T; Murphy, D; Freeth, M G; Gallimore, P H; Roberts, S

    2005-01-01

    Infection with high-risk genital human papillomavirus (HPV) types is a major risk factor for the development of cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma. The design of effective immunotherapies requires a greater understanding of how HPV-specific T-cell responses are involved in disease clearance and/or progression. Here, we have investigated T-cell responses to five HPV16 proteins (E6, E7, E4, L1 and L2) in women with CIN or cervical carcinoma directly ex vivo. T-cell responses were observed in the majority (78%) of samples. The frequency of CD4+ responders was far lower among those with progressive disease, indicating that the CD4+ T-cell response might be important in HPV clearance. CD8+ reactivity to E6 peptides was dominant across all disease grades, inferring that E6-specific CD8+ T cells are not vitally involved in disease clearance. T-cell responses were demonstrated in the majority (80%) of cervical cancer patients, but are obviously ineffective. Our study reveals significant differences in HPV16 immunity during progressive CIN. We conclude that the HPV-specific CD4+ T-cell response should be an important consideration in immunotherapy design, which should aim to target preinvasive disease. PMID:15986031

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

    PubMed

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

    2014-01-01

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

  11. Lack of detection of a putative retrovirus associated with haemic neoplasia in the soft shell clam Mya arenaria.

    PubMed

    AboElkhair, M; Iwamoto, T; Clark, K F; McKenna, P; Siah, A; Greenwood, S J; Berthe, F C J; Casey, J W; Cepica, A

    2012-01-01

    Haemic neoplasia (HN) is a leukemia-like disease that affects at least 20 species of marine bivalves including soft shell clam, Mya arenaria. Since the disease was discovered in 1969, the etiology remains unknown. A retroviral etiology has been suggested based on the detection of reverse transcriptase activity and electron microscopic observation of retroviral-like particles using negative staining. To date, however no virus isolate and no retroviral sequence from HN has been obtained. Moreover, transmission of the disease by cell-free filtrate from affected clams has not been reproduced. In the current study, we reinvestigated the association of HN with a putative retrovirus. Sucrose gradient centrifugation followed by assessment of reverse transcriptase activity, electrophoretic analysis of protein and RNA, and electron microscopic examinations of fractions corresponding to retroviral density were employed. Detection of retroviral pol sequences using degenerate RT-PCR approaches was also attempted. Our results showed visible bands at the expected density of retrovirus in HN-positive and HN-negative clam tissues and both with reverse transcriptase activity. Electron microscopy, RNA analysis, protein analysis, and PCR systems targeting the pol gene of retroviruses did not however provide clear evidence supporting presence of a retrovirus. We point out that the retrovirus etiology of HN of Mya arenaria proposed some 25 years ago should be reconsidered in the absence of a virus isolate or virus sequences. PMID:22036985

  12. Cervical metastases of glucagonoma in a patient with multiple endocrine neoplasia type 1: report of a case.

    PubMed

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

    2008-01-01

    Multiple endocrine neoplasia type 1 (MEN 1) is a syndrome characterized by tumors of the parathyroid glands, pancreatic islet cells, duodenum, and pituitary gland. We report a case of cervical metastases of glucagonoma with MEN 1. The patient was a 34-year-old woman admitted to our hospital with epigastric pain. Her medical history included two resections of prolactinoma and two upper GI hemorrhages secondary to duodenal ulcers. Computed tomography (CT) showed two hypervascular lesions in the tail of the pancreas and cervical ultrasound showed multiple hypoechogenic ovoid images in the neck. A cervical CT scan confirmed two 15-mm lymph nodes in the left cervical region and 111In-DOTATOC imaging showed focal abnormal somatostatin expression in the pancreatic tail and the cervical nodes. The patient had asymptomatic hypoglycemic episodes, with blood sugar levels as low as 30 mg/dl, which raised our suspicion of MEN 1 associated with pancreatic insulinoma. Thus, we performed a distal pancreatectomy with bilateral cervical dissection and parathyroid gland resection. Histopathological examination revealed 12 pancreatic tumors as well as metastases in four cervical lymph nodes. The resected parathyroid glands had normal structure, suggesting parathyroid hyperplasia. A follow-up CT scan, 18 months after surgery, showed new tumors in the head of the pancreas and in the duodenal wall. A pancreatoduodenectomy was performed and histopathological examination revealed nine nonfunctioning endocrine tumors in the pancreas, one tumor in the duodenal wall, and metastases in two peripancreatic lymph nodes. The patient recovered well and remains asymptomatic. PMID:19039643

  13. Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial

    PubMed Central

    2010-01-01

    Objectives To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata). Design Data from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II)). The trials were to be 4 years in length, and the results reported are from final study data of 42 months’ follow-up. Setting Primary care centres and university or hospital associated health centres in 24 countries and territories around the world. Participants 17?622 women aged 16-26 years enrolled between December 2001 and May 2003. Major exclusion criteria were lifetime number of sexual partners (>4), history of abnormal cervical smear test results, and pregnancy. Intervention Three doses of quadrivalent HPV vaccine (for serotypes 6, 11, 16, and 18) or placebo at day 1, month 2, and month 6. Main outcome measures Vaccine efficacy against cervical, vulvar, and vaginal intraepithelial neoplasia grade I and condyloma in a per protocol susceptible population that included subjects who received all three vaccine doses, tested negative for the relevant vaccine HPV types at day 1 and remained negative through month 7, and had no major protocol violations. Intention to treat, generally HPV naive, and unrestricted susceptible populations were also studied. Results In the per protocol susceptible population, vaccine efficacy against lesions related to the HPV types in the vaccine was 96% for cervical intraepithelial neoplasia grade I (95% confidence interval 91% to 98%), 100% for both vulvar and vaginal intraepithelial neoplasia grade I (95% CIs 74% to 100%, 64% to 100% respectively), and 99% for condyloma (96% to 100%). Vaccine efficacy against any lesion (regardless of HPV type) in the generally naive population was 30% (17% to 41%), 75% (22% to 94%), and 48% (10% to 71%) for cervical, vulvar, and vaginal intraepithelial neoplasia grade I, respectively, and 83% (74% to 89%) for condyloma. Conclusions Quadrivalent HPV vaccine provided sustained protection against low grade lesions attributable to vaccine HPV types (6, 11, 16, and 18) and a substantial reduction in the burden of these diseases through 42 months of follow-up. Trial registrations NCT00092521 and NCT00092534. PMID:20647284

  14. VEGF elicits epithelial-mesenchymal transition (EMT) in prostate intraepithelial neoplasia (PIN)-like cells via an autocrine loop

    SciTech Connect

    Gonzalez-Moreno, Oscar [Laboratory of Novel Therapeutic Targets, Division of Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Avda. Pio XII, 55, 31008 Pamplona (Spain)] [Laboratory of Novel Therapeutic Targets, Division of Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Avda. Pio XII, 55, 31008 Pamplona (Spain); Lecanda, Jon [Digna Biotech, and Department of Biochemistry, University of Navarra, Pamplona (Spain)] [Digna Biotech, and Department of Biochemistry, University of Navarra, Pamplona (Spain); Green, Jeffrey E. [Laboratory of Cancer Biology and Genetics, NCI, NIH, Bethesda , MD (United States)] [Laboratory of Cancer Biology and Genetics, NCI, NIH, Bethesda , MD (United States); Segura, Victor [Unit of Proteomics, Genomics and Bioinformatics, CIMA, University of Navarra, Pamplona (Spain)] [Unit of Proteomics, Genomics and Bioinformatics, CIMA, University of Navarra, Pamplona (Spain); Catena, Raul; Serrano, Diego [Laboratory of Novel Therapeutic Targets, Division of Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Avda. Pio XII, 55, 31008 Pamplona (Spain)] [Laboratory of Novel Therapeutic Targets, Division of Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Avda. Pio XII, 55, 31008 Pamplona (Spain); Calvo, Alfonso, E-mail: acalvo@unav.es [Laboratory of Novel Therapeutic Targets, Division of Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Avda. Pio XII, 55, 31008 Pamplona (Spain)] [Laboratory of Novel Therapeutic Targets, Division of Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Avda. Pio XII, 55, 31008 Pamplona (Spain)

    2010-02-15

    Vascular endothelial growth factor (VEGF) is overexpressed during the transition from prostate intraepithelial neoplasia (PIN) to invasive carcinoma. We have mimicked such a process in vitro using the PIN-like C3(1)/Tag-derived Pr-111 cell line, which expresses low levels of VEGF and exhibits very low tumorigenicity in vivo. Elevated expression of VEGF164 in Pr-111 cells led to a significant increase in tumorigenicity, invasiveness, proliferation rates and angiogenesis. Moreover, VEGF164 induced strong changes in cell morphology and cell transcriptome through an autocrine mechanism, with changes in TGF-beta1- and cytoskeleton-related pathways, among others. Further analysis of VEGF-overexpressing Pr-111 cells or following exogenous addition of recombinant VEGF shows acquisition of epithelial-mesenchymal transition (EMT) features, with an increased expression of mesenchymal markers, such as N-cadherin, Snail1, Snail2 (Slug) and vimentin, and a decrease in E-cadherin. Administration of VEGF led to changes in TGF-beta1 signaling, including reduction of Smad7 (TGF-beta inhibitory Smad), increase in TGF-betaR-II, and translocation of phospho-Smad3 to the nucleus. Our results suggest that increased expression of VEGF in malignant cells during the transition from PIN to invasive carcinoma leads to EMT through an autocrine loop, which would promote tumor cell invasion and motility. Therapeutic blockade of VEGF/TGF-beta1 in PIN lesions might impair not only tumor angiogenesis, but also the early dissemination of malignant cells outside the epithelial layer.

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

    PubMed

    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

    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

  16. High Fat, High Calorie Diet Promotes Early Pancreatic Neoplasia in the Conditional KrasG12D Mouse Model

    PubMed Central

    Dawson, David W.; Hertzer, Kathleen; Moro, Aune; Donald, Graham; Chang, Hui-Hua; Go, Vay Liang; Pandol, Steven J.; Lugea, Aurelia; Gukovskaya, Anna S.; Li, Gang; Hines, Oscar J.; Rozengurt, Enrique; Eibl, Guido

    2013-01-01

    There is epidemiologic evidence that obesity increases the risk of cancers. Several underlying mechanisms, including inflammation and insulin resistance, are proposed. However, the driving mechanisms in pancreatic cancer are poorly understood. The goal of the present study was to develop a model of diet-induced obesity and pancreatic cancer development in a state-of-the-art mouse model, which resembles important clinical features of human obesity, e.g. weight gain and metabolic disturbances. Offspring of Pdx-1-Cre and LSL-KrasG12D mice were allocated to either a diet high in fats and calories (HFCD; ~4,535 kcal/kg; 40% of calories from fats) or control diet (CD; ~3,725 kcal/kg; 12% of calories from fats) for 3 months. Compared to control animals, mice fed the HFCD significantly gained more weight and developed hyperinsulinemia, hyperglycemia, hyperleptinemia, and elevated levels of IGF-1. The pancreas of HFCD-fed animals showed robust signs of inflammation with increased numbers of infiltrating inflammatory cells (macrophages and T-cells), elevated levels of several cytokines and chemokines, increased stromal fibrosis, and more advanced PanIN lesions. Our results demonstrate that a diet high in fats and calories leads to obesity and metabolic disturbances similar to humans and accelerates early pancreatic neoplasia in the conditional KrasG12D mouse model. This model and findings will provide the basis for more robust studies attempting to unravel the mechanisms underlying the cancer-promoting properties of obesity as well as to evaluate dietary- and chemo-preventive strategies targeting obesity-associated pancreatic cancer development. PMID:23943783

  17. Distribution of genital human papillomavirus (HPV) genotypes in Croatian women with cervical intraepithelial neoplasia (CIN)--a pilot study.

    PubMed

    Roksandi?-Krizan, Ivana; Bosnjak, Zinka; Peri?, Magdalena; Durkin, Ivona; Atali?, Vlasta Zuji?; Vukovi?, Dubravka

    2013-12-01

    Genital infection with high-risk human papillomavirus (HR HPV) associates with increased risk of developing precancerous lesions, such as cervical intraepithelial neoplasia (CIN). The objective of this pilot study conducted in north-east Croatia was to determine the prevalence of HPV genital infection in women with abnormal cervical cytology and to determine its association with their age and HPV genotype(s). From March 2009 to December 2011, cervical swabs from 100 women were analysed for HR HPV infection (AMPLICOR HPV Test, Roche Diagnostics) and genotyped for high risk (HR), intermediate (IR) and low risk (LR) HPVs (Linear Array HPV Genotyping Test, Roche Diagnostics). The most prevalent HR genotypes in women with CIN were HPV 16 (27.6%), HPV 31 (11.8%), HPV 51 and HPV 52 (10.2% each). The most prevalent IR genotypes were HPV 66 (30%) and HPV 62 (23.3%). The most prevalent LR genotype was HPV 6 (20.3%). Women between 21 and 25 years of age showed the highest rate of HPV infection (44.2%). Moreover, women younger than 35 years showed a significant association (p < 0.01) and positive correlation (r = 0.67; p < 0.05) between HR HPV infection and CIN stages 1 and 2. Multiple HPV infections were found in almost half of the women. This is the first study that analysed the prevalence of genital infection with HR/IR/LR HPVs in women with CIN from north-east Croatia. Despite the preliminary nature of this pilot study, the lower prevalence of some HR HPVs (HPV18) and the higher prevalence of other HR HPVs (HPVs 51, 52 and 31) may imply the necessity for the development of more targeted anti-HPV vaccines or other strategies for more efficient protection against oncogenic HPV infection in women from our region. PMID:24611331

  18. Trisomy of the Dscr1 gene suppresses early progression of pancreatic intraepithelial neoplasia driven by oncogenic Kras

    SciTech Connect

    Lee, Jang Choon; Shin, Jimin; Baek, Kwan-Hyuck, E-mail: khbaek@skku.edu

    2013-10-11

    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.

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

    PubMed

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

    2001-01-15

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

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

    PubMed Central

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

    2014-01-01

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

  1. Mapk Signaling Is Required for Dedifferentiation of Acinar Cells and Development of Pancreatic Intraepithelial Neoplasia in Mice

    PubMed Central

    Collins, Meredith A.; Yan, Wei; Sebolt–Leopold, Judith S.; di Magliano, Marina Pasca

    2014-01-01

    BACKGROUND & AIMS Kras signaling via mitogen-activated protein kinase (MAPK) is highly up-regulated in pancreatic cancer cells. We investigated whether Mapk signaling is required for the initiation and maintenance of pancreatic carcinogenesis in mice. METHODS We studied the formation and maintenance of pancreatic intraepithelial neoplasia (Pan-INs) inp48Cre; TetO-KrasG12D; Rosa26rtTa-IRES-EGFP (iKras*) mice and LSL-KrasG12D mice bred with p48Cre mice (KC mice). Mice were given oral PD325901, which is a small-molecule inhibitor of Mek1 and Mek2 (factors in the Mapk signaling pathway), along with injections of cerulein to induce pancreatitis. Other mice were given PD325901 only after Pan-INs developed. Pancreatic tissues were collected and evaluated using histologic, immunohistochemical, immunofluorescence, and electron microscopy analyses. Acinar cells were isolated from the tissues and the effects of Mek1 and 2 inhibitors were assessed. RESULTS PD325901 prevented PanIN formation, but not pancreatitis, in iKras* and KC mice. In iKras* or KC mice given PD325901 at 5 weeks after PanINs developed, PanINs regressed and acinar tissue regenerated. The regression occurred through differentiation of the PanIN cells to acini, accompanied by re-expression of the acinar transcription factor Mist1. CONCLUSIONS In iKras* and KC mice, Mapk signaling is required for the initiation and maintenance of pancreatic cancer precursor lesions. Mapk signaling promotes formation of PanINs by enabling dedifferentiation of acinar cells into duct-like cells that are susceptible to transformation. PMID:24315826

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

    PubMed

    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

    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

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

    PubMed Central

    2012-01-01

    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

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

    PubMed Central

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

    2010-01-01

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

  5. CT colonography with limited bowel preparation for the detection of colorectal neoplasia in an FOBT positive screening population

    PubMed Central

    de Vries, Ayso H.; van Rijn, Anne F.; Dekker, Helena M.; Willemssen, François E. J. A.; van Leerdam, Monique E.; van Marrewijk, Corine J.; Fockens, Paul; Bipat, Shandra; Bossuyt, Patrick M. M.; Dekker, Evelien; Stoker, Jaap

    2009-01-01

    Purpose Aim was to evaluate the accuracy of computed tomography colonography (CTC) for detection of colorectal neoplasia in a Fecal Occult Blood Test (FOBT) positive screening population. Methods In three different institutions, consecutive FOBT positives underwent CTC after laxative free iodine tagging bowel preparation followed by colonoscopy with segmental unblinding. Each CTC was read by two experienced observers. For CTC and for colonoscopy the per-polyp sensitivity and per-patient sensitivity and specificity were calculated for detection of carcinomas, advanced adenomas, and adenomas. Results In total 22 of 302 included FOBT positive participants had a carcinoma (7%) and 137 had an adenoma or carcinoma ?10 mm (45%). CTC sensitivity for carcinoma was 95% with one rectal carcinoma as false negative finding. CTC sensitivity for advanced adenomas was 92% (95% CI: 88–96) vs. 96% (95% CI: 93–99) for colonoscopy (P = 0.26). For adenomas and carcinomas ?10 mm the CTC per-polyp sensitivity was 93% (95% CI: 89–97) vs. 97% (95% CI: 94–99) for colonoscopy (P = 0.17). The per-patient sensitivity for the detection of adenomas and carcinomas ?10 mm was 95% (95% CI: 91–99) for CTC vs. 99% (95% CI: 98–100) for colonoscopy (P = 0.07), while the per-patient specificity was 90% (95% CI: 86–95) and 96% (95% CI: 94–99), respectively (P < 0.001). Conclusion CTC with limited bowel preparation performed in an FOBT positive screening population has high diagnostic accuracy for the detection of adenomas and carcinomas and a sensitivity similar to that of colonoscopy for relevant lesions. PMID:19888629

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

    PubMed

    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

    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

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

    PubMed Central

    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

    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

  8. Assessment of haemic neoplasia in different soft shell clam Mya arenaria populations from eastern Canada by flow cytometry.

    PubMed

    Delaporte, Maryse; Synard, Stéphanie; Pariseau, Julie; McKenna, Patricia; Tremblay, Réjean; Davidson, Jeffery; Berthe, Franck C J

    2008-06-01

    Diagnosis of haemic neoplasia (HN) in the soft shell clam, Mya arenaria, is often achieved by hematocytology and histology. Since neoplastic cells display tetraploid DNA contents, haemocyte cell cycle analysis was developed for use as a diagnosis tool. The aim of this study was to assess the application of a flow cytometry procedure of cell cycle analysis established for the common cockle, to clams and to evaluate different thresholds of value for the percentage of tetraploid cells for establishing HN disease status of individual clams and clam populations. HN status of six clam populations from eastern Canada was determined. Results of the present study demonstrate a flow cytometry procedure to be useful for HN diagnosis in clams. Individual clams were considered to be affected by HN when presenting at least 20% of haemocytes in S-4N phase; and negative when presenting less that 5% of haemocytes in S-4N phase. As discussed in this paper, intermediate cases represent uncertain diagnoses including either false-negative or false-positive clams, which are difficult to discriminate. At a population level, an additional threshold of 15% for the mean intensity of the disease is proposed, which means having in the population several individual clams presenting more than 20% of their haemocytes in S-4N phase. Based on these thresholds of value, only one population was considered as free of HN disease, and one population was unequivocally affected by HN. For the four other clam populations, further investigations are needed toward development and use of specific and objective biomarkers of HN. PMID:18241883

  9. Relaciones trigonometricas Operaciones con logaritmos

    E-print Network

    Relaciones trigonom´etricas Operaciones con logaritmos Funciones elementales y sus gr´aficas Gr´aficas de funciones elementales L´imites Continuidad Tema 1: Repaso de conocimientos previos. Funciones´etricas Operaciones con logaritmos Funciones elementales y sus gr´aficas Gr´aficas de funciones elementales L

  10. LA PRÁCTICA EDUCATIVA CON DISCAPACITADOS

    Microsoft Academic Search

    Eduardo Ullate Rada

    2010-01-01

    La práctica educativa con discapacitados suponía un reto para mí. Con la realización del curso de monitor de tiempo libre me vi obligado a realizar unas prácticas educativas que no sabía en qué lugar y ciudad iba a realizarlas. Tras una larga meditación decidí explorar un “nuevo mundo”, el de la educación de personas discapacitadas.

  11. Planificación Neuroquirúrgica con Software Osirix

    PubMed Central

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

    2014-01-01

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

  12. Prevalence of HPV infection and cervical intraepithelial neoplasia and attitudes towards HPV vaccination among Chinese women aged 18–25 in Jiangsu Province

    Microsoft Academic Search

    Shang-ying Hu; Ying Hong; Fang-hui Zhao; Adam K. Lewkowitz; Feng Chen; Wen-hua Zhang; Qin-jing Pan; Xun Zhang; Cindy Fei; Hui Li; You-lin Qiao

    2011-01-01

    Objective  Few data are available on the epidemiology of HPV and cervical cancer among Chinese women younger than 25 years old. This\\u000a study aimed to estimate the HPV infection rate and the prevalence of cervical intraepithelial neoplasia (CIN) in women aged\\u000a 18–25, as well as their knowledge of and attitudes towards HPV vaccination.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  A population-based cervical cancer screening study was conducted

  13. Risk of preterm delivery with increasing depth of excision for cervical intraepithelial neoplasia in England: nested case-control study

    PubMed Central

    Castanon, Alejandra; Landy, Rebecca; Brocklehurst, Peter; Evans, Heather; Peebles, Donald; Singh, Naveena; Walker, Patrick; Patnick, Julietta

    2014-01-01

    Objective To determine the association between depth of excision of cervical intraepithelial neoplasia and risk of preterm birth. Design Case-control study nested in record linkage cohort study. Setting 12 hospitals in England. Participants From a cohort of 11?471 women with at least one histological sample taken at colposcopy and a live singleton birth (before or after colposcopy), 1313 women with a preterm birth (20-36 weeks) were identified and frequency matched on maternal age at delivery, parity, and study site to 1313 women with term births (38-42 weeks). Main outcome measures Risk of preterm birth and very/extreme preterm birth by depth of excisional treatment of the cervical transformation zone. Results After exclusions, 768 preterm births (cases) and 830 term births after colposcopy remained. The risk of preterm birth was no greater in women with a previous small (<10 mm) excision (absolute risk 7.5%, 95% confidence interval 6.0% to 8.9%) than in women with a diagnostic punch biopsy (7.2%, 5.9% to 8.5%). Women with a medium (10-14 mm) (absolute risk 9.6%; relative risk 1.28, 0.98 to 1.68), large (15-19 mm) (15.3%; 2.04, 1.41 to 2.96), or very large (?20 mm) excision (18.0%; 2.40, 1.53 to 3.75) had a higher risk of preterm delivery than those with small excision. The same pattern was seen in 161 women with very/extremely preterm births (20-31 weeks) and with increasing volume excised. Most births were conceived more than three years after colposcopy, and the risk of preterm delivery did not seem to depend on time from excision to conception. Conclusions The risk of preterm birth is at most minimally affected by a small excision. Larger excisions, particularly over 15 mm or 2.66 cm3, are associated with a doubling of the risk of both preterm and very preterm births. The risk does not decrease with increasing time from excision to conception. Efforts should be made to excise the entire lesion while preserving as much healthy cervical tissue as possible. Close obstetric monitoring is warranted for women who have large excisions of the cervical transformation zone. PMID:25378384

  14. Differential expression of cytokeratin mRNA and protein in normal prostate, prostatic intraepithelial neoplasia, and invasive carcinoma.

    PubMed Central

    Yang, Y.; Hao, J.; Liu, X.; Dalkin, B.; Nagle, R. B.

    1997-01-01

    The expression of cytokeratin (CK) mRNA for CK5, -8, -14, -16, and -19 was investigated in normal prostate, prostatic intraepithelial neoplasia (PIN) lesions, and invasive carcinoma using in situ hybridization. Protein localization was carried out in adjacent sections using immunohistochemistry and correlated with mRNA expression. Snap-frozen human prostate samples including 22 examples of normal glands, 20 cases of PIN lesions, and 12 cases of invasive carcinoma were examined. CK5 and -14 mRNA and protein were prominently expressed only in the basal cells of normal glands and PIN lesions. CK14 mRNA was absent in the luminal cells of the most of the PIN lesions but was seen at a low level in some PIN lesions. CK14 protein was not detected in any PIN lesion, suggesting that, if the cell that makes up the PIN lesions is derived from a basal cell, CK14 translation is depressed although a low level of CK14 mRNA may persist. CK8 mRNA and protein were constitutively expressed in all epithelia of normal and abnormal prostate tissues. CK19 mRNA and protein were persistently expressed in both basal and luminal cells of the tubular portion of normal glands as well as PIN lesions, but were expressed heterogeneously in both basal and luminal cells of normal alveoli. CK16 mRNA was expressed in a similar pattern as CK19, but CK16 protein was not detected either in normal or in abnormal prostate tissues. In conclusion, the expression of CK19 in PIN lesions is similar to its tubular expression and would support an origin of PIN lesions from this structure rather than the alveolar portion of the glands. The similar cytokeratin expression between PIN lesions and invasive carcinoma further supports the concept that PIN is a precursor lesion of invasive carcinoma. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:9033282

  15. Comparison of seven tests for high-grade cervical intraepithelial neoplasia in women with abnormal smears: the Predictors 2 study.

    PubMed

    Szarewski, Anne; Mesher, David; Cadman, Louise; Austin, Janet; Ashdown-Barr, Lesley; Ho, Linda; Terry, George; Liddle, Stuart; Young, Martin; Stoler, Mark; McCarthy, Julie; Wright, Corrina; Bergeron, Christine; Soutter, W P; Lyons, Deirdre; Cuzick, Jack

    2012-06-01

    High-risk human papillomavirus (HPV) DNA/RNA testing provides higher sensitivity but lower specificity than cytology for the identification of high-grade cervical intraepithelial neoplasia (CIN). Several new HPV tests are now available for this purpose, and a direct comparison of their properties is needed. Seven tests were evaluated with samples in liquid PreservCyt transport medium from 1,099 women referred for colposcopy: the Hybrid Capture 2 (Qiagen), Cobas (Roche), PreTect HPV-Proofer (NorChip), Aptima HPV (Gen-Probe), and Abbott RealTime assays, the BD HPV test, and CINtec p16(INK4a) cytology (mtm laboratories) immunocytochemistry. Sensitivity, specificity, and positive predictive value (PPV) were based on the worst histology found on either the biopsy or the treatment specimen after central review. Three hundred fifty-nine women (32.7%) had CIN grade 2+ (CIN2+), with 224 (20.4%) having CIN3+. For detection of CIN2+, Hybrid Capture 2 had 96.3% sensitivity, 19.5% specificity, and 37.4% PPV. Cobas had 95.2% sensitivity, 24.0% specificity, and 37.6% PPV. The BD HPV test had 95.0% sensitivity, 24.2% specificity, and 37.8% PPV. Abbott RealTime had 93.3% sensitivity, 27.3% specificity, and 38.2% PPV. Aptima had 95.3% sensitivity, 28.8% specificity, and 39.3% PPV. PreTect HPV-Proofer had 74.1% sensitivity, 70.8% specificity, and 55.4% PPV. CINtec p16(INK4a) cytology had 85.7% sensitivity, 54.7% specificity, and 49.1% PPV. Cytology of a specimen taken at colposcopy (mild dyskaryosis or worse) had 88.9% sensitivity, 58.1% specificity, and 50.7% PPV. Our study confirms that, in a referral setting, HPV testing by a number of different tests provides high sensitivity for high-grade disease. Further work is needed to confirm these findings in a routine screening setting. PMID:22422852

  16. The genetic defect in multiple endocrine neoplasia type 2A maps next to the centromere of chromosome 10

    PubMed Central

    Wu, Jingshi; Carson, Nancy L.; Myers, Shirley; Pakstis, Andrew J.; Kidd, Judith R.; Castiglione, Carmela M.; Anderson, Linda; Hoyle, L. Suzanne; Genel, Myron; Verdy, Maurice; Jackson, Charles E.; Simpson, Nancy E.; Kidd, Kenneth K.

    1990-01-01

    Multiple endocrine neoplasia type 2A (MEN2A) is a rare cancer syndrome that is inherited in an apparently autosomal dominant fashion. Previous linkage studies had assigned the MEN2A locus to chromosome 10 in the pericentromeric region. We recently have described several new easily scorable RFLPs for the chromosome 10–specific alpha satellite DNA (the D10Z1) locus that is known, on the basis of previous in situ hybridization experiments, to lie at the centromere. We report here tight linkage between MEN2A and D10Z1, as demonstrated by a maximum lod score of 12.02 at the recombination frequency of zero (1-lod-unit support interval 0–4 cM), indicating that the genetic defect in MEN2A lies in the immediate vicinity of the centromere. By means of a set of ordered polymorphic DNA markers from the pericentromeric region, multipoint as well as pairwise linkage analyses place the MEN2A locus at the middle of a small region (?11 cM) bracketing the centromere with FNRB (at 10p11.2) and RBP3 (at 10q11.2) on either side, providing further support for the centromeric location of the MEN2A locus. Marked sex difference in recombination frequencies exists in this pericentromeric region: significantly (P < .01) more female than male crossovers were observed across all of the adjacent intervals D10S24–FNRB, FNRB–D10Z1, and D10Z1–RBP3. However, a sex difference was not seen in the 7-cM interval from RBP3 to D10S5, suggesting that large variation in the sex difference in recombination can occur over small chromosomal regions. Proper clinical application of these DNA markers in genetic counseling to determine the genotypes at the disease locus for those at-risk members in informative afflicted families must therefore take into account the implications imposed by the large and highly significant sex effect on recombination in the MEN2A region. PMID:1968709

  17. Studies of lectin binding to the human cervix uteri: II. Cervical intraepithelial neoplasia and invasive squamous carcinoma

    Microsoft Academic Search

    Paul Byrne; Ann Williams; Terence Rollason

    1989-01-01

    Summary  The cell surface carbohydrate profile of formalin-fixed paraffin-embedded tissue sections of neoplastic cervical squamous epithelium was evaluated using lectins ofBauhinia purpurea (BPA),Canavalin ensiformis (Con A),Griffonia simplicifolia I (GS I),Griffonia simplicifolia II (GS II),Maclura pomifera (MPA),Archis hypogaea (PNA),Glycine max (SBA),Ulex europaeus I (UEA I) andTriticum vulgaris (WGA). Three lectins (BPA, Con A and PNA) showed a similar pattern of staining in

  18. Una entrevista con Emilio Carballido.

    E-print Network

    Vé lez, Joseph F.

    1973-10-01

    FALL 1973 17 Una entrevista con Emilio Carballido JOSEPH F. VÉLEZ V. Señor Carballido, ¿podría decirme cuándo comenzó a interesarse en escribir? C. Fui un niño precoz que escribió mucho desde muy chamaquito. V. ¿Qué escribió primero: poesía... han presentado aquí? C. Todavía no. Pero parece que el teatro de Fuentes no es realista, y está más bien emparentado con otras corrientes. El teatro de Leñero tiende a ser teatro documental. El tuerto es rey, de Fuentes, tiene, parece...

  19. Neurologic abnormalities as the predominant signs of neoplasia of the nasal cavity in dogs and cats: seven cases (1973-1986).

    PubMed

    Smith, M O; Turrel, J M; Bailey, C S; Cain, G R

    1989-07-15

    Neurologic abnormalities were the predominant historic and physical findings in 5 dogs and 2 cats with primary nasal cavity tumors that had invaded the cranial vault. Seizures, behavior changes, and obtundation were the most common signs. Other neurologic signs included paresis, ataxia, circling, visual deficit, and proprioceptive deficit. Although 1 dog and 2 cats had historic findings of mild respiratory disease, no physical abnormalities related to the respiratory tract were found in any of the 7 animals. Nasal cavity neoplasia was suggested by radiographic and computed tomographic studies and was confirmed histopathologically in each case. The nasal tumor types in the 5 dogs were epidermoid carcinoma (n = 1), adenocarcinoma (n = 2), solid carcinoma (n = 1), and anaplastic chondrosarcoma (n = 1). An esthesioneuroblastoma was found in each cat. Radiation therapy was effective for 3 months in palliating the clinical signs in the 2 dogs in which it was used. Neoplasia of the nasal cavity should be considered in the differential diagnosis for animals with neurologic signs suggestive of cerebral disorders. PMID:2768045

  20. Regular Article MYELOID NEOPLASIA

    E-print Network

    von Andrian, Ulrich H.

    -selectin. Whereas vascular cell adhesion molecule-1 and P-selectin were not required, deficiency of E curative treatment of CML but is limited by graft-versus-host disease and donor availability. Autologous, avoids graft-versus-host disease and has been used extensively for treatment of CML, lym- phoma

  1. Asbestos exposure and neoplasia

    SciTech Connect

    Selikoff, I.J.; Churg, J.; Hammond, E.C.

    1984-07-06

    Builiding trades insulation workers have relatively light, intermittent, exposure to asbestos. Of 632 insulation workers, who entered the trade before 1943 and were traced through 1962, forty-five died of cancer of the lung or pleura, whereas only 6.6 such deaths were expected. Three of the pleural tumors were mesotheliomas; there was also one peritoneal mesothelioma. Four mesotheliomas in a total of 255 deaths is an exceedingly high incidence for such a rare tumor. In addition, an unexpectedly large number of men died of cancer of the stomach, colon, or rectum (29 compared with 9.4 expected). Other cancers were not increased; 20.5 were expected, 21 occurred. Twelve men died of asbestosis. This landmark article appeared originally in this journal 188:22-26, 1964.

  2. Evolution of Glomerular Filtration Rate, Renal Injury Markers, Anemia, and Angiotensin Blockers Use After Change From Calcineurin Inhibitors to Sirolimus in Transplant Patients With Neoplasia Versus Chronic Allograft Nephropathy

    Microsoft Academic Search

    E. Luna; I. Cerezo; R. Macias; J. Villa; C. Martinez; J. Cubero; R. Martinez; F. Ferreira; C. García

    2011-01-01

    BackgroundThe change from calcineurin inhibitors (CNI) to sirolimus (SRL) is a safe alternative in transplant patients with neoplasia (NEO) whereas the results of conversion for chronic allograft nephropathy (CAN) are controversial, depending on the histologic score, degree of proteinuria, and glomerular filtration rate (GFR). Our aim in this study was to compare GFR, proteinuria, albuminuria, blood pressure (BP) effects, and

  3. Cryospray ablation using pressurized CO2 for ablation of Barrett’s esophagus with early neoplasia: early termination of a prospective series

    PubMed Central

    Verbeek, Romy E.; Vleggaar, Frank P.; ten Kate, Fiebo J.; van Baal, Jantine W. P. M.; Siersema, Peter D.

    2015-01-01

    Background: Cryotherapy is a relatively novel ablation modality for the endoscopic ablation of Barrett’s esophagus (BE). Data on the use of pressurized carbon dioxide (CO2) gas for cryoablation are scarce. Study aim: To determine the efficacy and safety of cryospray ablation using pressurized CO2 gas in the treatment of BE with early neoplasia. Methods: In this prospective single center case series, we aimed to include 30 patients with BE and early neoplasia. Nodular neoplastic lesions were treated with endoscopic mucosal resection (EMR). Residual BE mucosa was treated with cryospray ablation every 4 weeks until the complete BE segment was eliminated or up to seven treatment sessions. If no reduction of the BE segment was observed after two subsequent treatment sessions, cryoablation was terminated. Patients were contacted at days 1 and 4 post-treatment to evaluate the level of discomfort. Endoscopic and histologic follow-up evaluations were performed up to 24 months post-treatment. Results: After the inclusion of 10 patients, insufficient effect of cryoablation was observed, resulting in early termination of the study. In total, seven patients with intramucosal carcinoma (IMC) and three with high grade dysplasia (HGD) were included. Prior EMR was performed in nine patients. A median of 2.5 (IQR 2.0?–?4.0) cryoablation sessions were performed. At 6 months of follow-up, complete eradication of intestinal metaplasia was observed in 11?% (1?/9; one patient died, not treatment or disease related) of the patients and complete eradication of dysplasia in 44?% (4?/9). In three patients, HGD or IMC was detected during follow-up, and was endoscopically treated. Apart from a gastric perforation as a result of gastric distension caused by CO2 gas during the first treatment, cryospray treatments were well tolerated. Conclusion: After a short learning curve, cryoablation using CO2 gas was found to be a safe and well tolerated treatment modality. However, in our experience, the efficacy of CO2 cryoablation combined with EMR for nodular lesions is disappointing for the treatment of BE associated neoplasia.

  4. Zinc finger arrays binding human papillomavirus types 16 and 18 genomic DNA: precursors of gene-therapeutics for in-situ reversal of associated cervical neoplasia

    PubMed Central

    2012-01-01

    Background Human papillomavirus (HPV) types 16 and 18 are the high-risk, sexually transmitted infectious causes of most cervical intraepithelial neoplasias (CIN) or cancers. While efficacious vaccines to reduce the sexual acquisition of these high-risk HPVs have recently been introduced, no virus-targeted therapies exist for those already exposed and infected. Considering the oncogenic role of the transforming (E6 and E7) genes of high-risk HPVs in the slow pathogenesis of cervical cancer, we hypothesize that timely disruption or abolition of HPV genome expression within pre-cancerous lesions identified at screening may reverse neoplasia. We aimed to derive model zinc finger nucleases (ZFNs) for mutagenesis of the genomes of two high-risk HPV (types 16 & 18). Methods and results Using ZiFiT software and the complete genomes of HPV types16 and 18, we computationally generated the consensus amino acid sequences of the DNA-binding domains (F1, F2, & F3) of (i) 296 & 327 contextually unpaired (or single) three zinc-finger arrays (sZFAs) and (ii) 9 & 13 contextually paired (left and right) three- zinc-finger arrays (pZFAs) that bind genomic DNA of HPV-types 16 and 18 respectively, inclusive of the E7 gene (s/pZFAHpV/E7). In the absence of contextually paired three-zinc-finger arrays (pZFAs) that bind DNA corresponding to the genomic context of the E6 gene of either HPV type, we derived the DNA binding domains of another set of 9 & 14 contextually unpaired E6 gene-binding ZFAs (sZFAE6) to aid the future quest for paired ZFAs to target E6 gene sequences in both HPV types studied (pZFAE6). This paper presents models for (i) synthesis of hybrid ZFNs that cleave within the genomic DNA of either HPV type, by linking the gene sequences of the DNA-cleavage domain of the FokI endonuclease FN to the gene sequences of a member of the paired-HPV-binding ZFAs (pZFAHpV/E7?+?FN), and (ii) delivery of the same into precancerous lesions using HPV-derived viral plasmids or vectors. Conclusions With further optimization, these model ZFNs offer the opportunity to induce target-mutagenesis and gene-therapeutic reversal of cervical neoplasia associated with HPV types 16 & 18. PMID:22840184

  5. Single-tube multiplex PCR using type-specific E6/E7 primers and capillary electrophoresis genotypes 21 human papillomaviruses in neoplasia

    PubMed Central

    2011-01-01

    Background Human papillomavirus (HPV) E6/E7 type-specific oncogenes are required for cervical carcinogenesis. Current PCR protocols for genotyping high-risk HPV in cervical screening are not standardized and usually use consensus primers targeting HPV capsid genes, which are often deleted in neoplasia. PCR fragments are detected using specialized equipment and extra steps, including probe hybridization or primer extension. In published papers, analytical sensitivity is typically compared with a different protocol on the same sample set. A single-tube multiplex PCR containing type-specific primers was developed to target the E6/E7 genes of two low-risk and 19 high-risk genotypes (HPV6, 11 and 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 70, 73 and 82) and the resulting short fragments were directly genotyped by high-resolution fluorescence capillary electrophoresis. Results The method was validated using long oligonucleotide templates, plasmid clones and 207 clinical samples of DNA from liquid-based cytology, fresh and formalin-fixed specimens and FTA Microcards® imprinted with cut tumor surfaces, swabbed cervical cancers or ejected aspirates from nodal metastases of head and neck carcinomas. Between one and five long oligonucleotide targets per sample were detected without false calls. Each of the 21 genotypes was detected in the clinical sample set with up to five types simultaneously detected in individual specimens. All 101 significant cervical neoplasias (CIN 2 and above), except one adenocarcinoma, contained E6/E7 genes. The resulting genotype distribution accorded with the national pattern with HPV16 and 18 accounting for 69% of tumors. Rare HPV types 70 and 73 were present as the sole genotype in one carcinoma each. One cervical SCC contained DNA from HPV6 and 11 only. Six of twelve oropharyngeal cancer metastases and three neck metastases of unknown origin bore E6/E7 DNA; all but one were HPV16. One neck aspirate contained atypical squames with HPV26. Analytical sensitivity in dilute plasmid mixes was variable. Conclusions A primer-rich PCR readily detects the E6/E7 oncogenes of 21 HPV types in cellular and fixed tissue specimens. The method is straightforward, robust and reproducible and avoids post-PCR enzymatic and hybridization steps while detecting HPV with high clinical sensitivity in significant HPV-related neoplasia regardless of specimen type. PMID:21241508

  6. Programando con Igualdad Similar Estricta

    Microsoft Academic Search

    Ginés Moreno; Vicente Pascual

    Resumen En los últimos años, hemos sido testigos del importante papel que la lógica difusa o borrosa (fuzzy logic) ha jugado en el desarrollo de sofisticadas aplicaciones software en campos tan diversos como los sistemas expertos, inteligencia artificial, control industrial, medicina, etc. Con el objetivo de facilitar el desarrollo de tales aplicaciones, mucho más recientemente ha surgido el interés por

  7. Cefalea con criterios de alarma

    Microsoft Academic Search

    Nuria Martínez Sánchez; Antonio Palasí Franco; Luis Miguel Martínez Sánchez

    2010-01-01

    La alta prevalencia de cefalea en la población general hace que sea uno de los principales motivos de consulta neurológica en Atención Primaria tanto para el médico de familia como para el neurólogo. Pese a que la mayoría de las consultas están motivadas por cefaleas primarias (migraña y cefalea tensional son, con mucho, las cefaleas más prevalentes) hay que tener

  8. An efficient strategy for gene mapping using multipoint linkage analysis: exclusion of the multiple endocrine neoplasia 2A (MEN2A) locus from chromosome 13.

    PubMed Central

    Farrer, L A; Goodfellow, P J; Lamarche, C M; Franjkovic, I; Myers, S; White, B N; Holden, J J; Kidd, J R; Simpson, N E; Kidd, K K

    1987-01-01

    Members of four families in which multiple endocrine neoplasia type 2A (MEN-2A) is segregating were typed for seven DNA markers and one red cell enzyme marker on chromosome 13. Close linkage was excluded between the MEN2A locus and each marker locus tested. By means of multipoint analysis and the genetic map of chromosome 13 developed by Leppert et al., MEN2A was excluded from any position between the most proximal marker locus (D13S6) and the most distal marker locus (D13S3) and from within 12 cMorgans outside these two loci, respectively. However, the support of exclusion within an interval was diminished under the assumption of a substantially larger genetic map in females. The strategy of multipoint analysis, which excluded between 1.5 and 2.0 times more chromosome 13 than did two-point analysis, demonstrates the utility of linkage maps in mapping disease genes. PMID:2883889

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

    PubMed

    Zhang, William Weiben; Feng, Zhenqing; Narod, Steven A

    2014-09-01

    Cruciferous vegetables belong to the plant family that has flowers with four equal-sized petals in the pattern of a crucifer cross. These vegetables are an abundant source of dietary phytochemicals, including glucosinolates and their hydrolysis products such as indole-3-carbinol (I3C) and 3,3'-diindolylmethane (DIM). By 2013, the total number of natural glucosinolates that have been documented is estimated to be 132. Recently, cruciferous vegetable intake has garnered great interest for its multiple health benefits such as anticancer, antiviral infections, human sex hormone regulation, and its therapeutic and preventive effects on prostate cancer and high grade prostatic intraepithelial neoplasia (HGPIN). DIM is a hydrolysis product of glucosinolates and has been used in various trials. This review is to provide an insight into the latest developments of DIM in treating or preventing both prostate cancer and HGPIN. PMID:25332705

  10. High grade anal intraepithelial neoplasia among HIV-1-infected men screening for a multi-center clinical trial of a human papillomavirus vaccine

    PubMed Central

    Wilkin, Timothy; Lee, Jeannette Y.; Lensing, Shelly Y.; Stier, Elizabeth A.; Goldstone, Stephen E.; Berry, J. Michael; Jay, Naomi; Aboulafia, David M.; Einstein, Mark H.; Saah, Alfred; Mitsuyasu, Ronald T.; Palefsky, Joel M.

    2013-01-01

    Purpose High-grade anal intraepithelial neoplasia (HGAIN) is the precursor lesion to invasive anal cancer. HPV vaccination holds great promise for preventing anal cancer. Methods We examined 235 HIV-1-infected men screening for participation in a multi-site clinical trial of a quadrivalent HPV vaccine. All participants had anal swabs obtained for HPV testing and cytology, and high resolution anoscopy with biopsies of visible lesions to assess for HGAIN. Results HPV 16 and 18 were detected in 23% and 10%, respectively; abnormal anal cytology was found in 56% and HGAIN in 30%. HGAIN prevalence was significantly higher in those with HPV 16 detection compared to those without (38% vs. 17%, P=.01). Use of antiretroviral therapy, nadir and current CD4+ cell count were not associated with abnormal anal cytology or HGAIN. Conclusion HGAIN is highly prevalent in HIV-infected men. Further studies are needed on treatment and prevention of HGAIN. PMID:23611828

  11. Prevalence of genotype-specific human papillomavirus infection and cervical neoplasia in Taiwan: a community-based survey of 10,602 women.

    PubMed

    Chen, Hui-Chi; You, San-Lin; Hsieh, Chang-Yao; Schiffman, Mark; Lin, Ching-Yu; Pan, Mei-Hung; Chou, Yi-Chun; Liaw, Kai-Li; Hsing, Ann W; Chen, Chien-Jen

    2011-03-01

    Human papillomavirus (HPV) causes cervical neoplasia; but limited data are available from Asia. We conducted a large-scale community-based cohort study in Taiwan to estimate prevalence of genotype-specific HPV infection and cervical neoplasia. Following written informed consent, cervical cells for cytology and HPV testing were collected from 11,923 participants (aged 30-65 years old, mean 46.3) in 1991-1992. Genotyping was performed using MY11/GP6+ PCR-based HPV Blot (EasyChip) for 39 HPV types. The overall HPV prevalence was 16.2% for 10,602 eligible participants, and 13.8% for 10,190 cytologically normal participants. The most common carcinogenic types were HPV52 (2.5%), HPV16 (2.0%), HPV56 (1.8%), HPV18 (1.6%), HPV33 (1.2%), HPV58 (1.3%) and HPV39 (1.0%). Among the 56 prevalent invasive and in situ cases, HPV16 (48.2%) was most common, followed by HPV58 (25.0%), HPV52 (19.6%), HPV31 (8.9%), HPV33 (8.9%) and HPV18 (3.6%). HPV16 and HPV58 caused cytological HSIL+ at younger ages than HPV52. Approximately half of the cervical cancer cases and high-grade precursors in Taiwan could be prevented by prophylactic vaccines against HPV16 and HPV18 infection. Up to 40% more could be prevented by targeting HPV58, HPV52, HPV33 and HPV31, arguing for the introduction of vaccines including more types. PMID:20853317

  12. One year of sitagliptin treatment protects against islet amyloid-associated ?-cell loss and does not induce pancreatitis or pancreatic neoplasia in mice

    PubMed Central

    Aston-Mourney, Kathryn; Subramanian, Shoba L.; Zraika, Sakeneh; Samarasekera, Thanya; Meier, Daniel T.; Goldstein, Lynn C.

    2013-01-01

    The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin is an attractive therapy for diabetes, as it increases insulin release and may preserve ?-cell mass. However, sitagliptin also increases ?-cell release of human islet amyloid polypeptide (hIAPP), the peptide component of islet amyloid, which is cosecreted with insulin. Thus, sitagliptin treatment may promote islet amyloid formation and its associated ?-cell toxicity. Conversely, metformin treatment decreases islet amyloid formation by decreasing ?-cell secretory demand and could therefore offset sitagliptin's potential proamyloidogenic effects. Sitagliptin treatment has also been reported to be detrimental to the exocrine pancreas. We investigated whether long-term sitagliptin treatment, alone or with metformin, increased islet amyloid deposition and ?-cell toxicity and induced pancreatic ductal proliferation, pancreatitis, and/or pancreatic metaplasia/neoplasia. hIAPP transgenic and nontransgenic littermates were followed for 1 yr on no treatment, sitagliptin, metformin, or the combination. Islet amyloid deposition, ?-cell mass, insulin release, and measures of exocrine pancreas pathology were determined. Relative to untreated mice, sitagliptin treatment did not increase amyloid deposition, despite increasing hIAPP release, and prevented amyloid-induced ?-cell loss. Metformin treatment alone or with sitagliptin decreased islet amyloid deposition to a similar extent vs untreated mice. Ductal proliferation was not altered among treatment groups, and no evidence of pancreatitis, ductal metaplasia, or neoplasia were observed. Therefore, long-term sitagliptin treatment stimulates ?-cell secretion without increasing amyloid formation and protects against amyloid-induced ?-cell loss. This suggests a novel effect of sitagliptin to protect the ?-cell in type 2 diabetes that appears to occur without adverse effects on the exocrine pancreas. PMID:23736544

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

    PubMed

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

    2013-01-14

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

  14. todasuvida: Las personas con diabetes son ms

    E-print Network

    diabetes Controlesu todasuvida: Las personas con diabetes son más propensas a padecer de enfermedades del corazón que quienes no tienen diabetes. Boletín 631 D Las personas con diabetes tienen mayor- res relacionados con la diabetes, como derrame cerebral, mala circulación en las piernas y pies e

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

    PubMed Central

    2010-01-01

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

  16. Polymorphisms in genes involved in folate metabolism modify the association of dietary and circulating folate and vitamin B-6 with cervical neoplasia.

    PubMed

    Tomita, Luciana Y; D'Almeida, Vania; Villa, Luisa L; Franco, Eduardo L; Cardoso, Marly A

    2013-12-01

    High folate intake has been suggested as an important factor in cancer prevention; however, previous studies on the relation among folate intake, serum folate, and plasma homocysteine (hcy) are controversial. We conducted a hospital-based, case-control study in Brazil investigating associations between dietary and circulating vitamins B-6 and B-12 and folate, hcy, genotypes of folate-metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR C677T, A1298C), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR A2756G), methionine synthase reductase (MTRR A66G), and reduced folate carrier (RFC1 G80A) and risk of cervical intraepithelial neoplasia (CIN) grades 1 (CIN1), 2 (CIN2), and 3 (CIN3). The study was composed by 453 controls, 140 CIN1, 126 CIN2, and 231 CIN3. We investigated the joint effects of genetic variants of folate-related genes using genetic risk scores (GRSs) by summing the number of risk alleles for CIN1 and CIN2+ (CIN2 and CIN3 cases). The OR (95% CI) for CIN1 and CIN2+ per each risk allele were 1.29 (1.01, 1.65) and 1.22 (1.01, 1.46), respectively. An association between folate intake and CIN2+ was observed only after stratification according to GRS: crude OR (95% CI) for lower folate intake and GRS ? 4 was 1.67 (0.92, 3.04) (P-trend < 0.001) compared with higher folate intake (above the median) and GRS ? 3. The CIN2+ risk of lower serum vitamin B-6 and GRS ? 4 was 2.14 (0.92, 5.02) (P-trend = 0.05) and lower serum folate (below the median) and GRS ? 4 was 0.49 (0.20, 1.17) (P-trend = 0.05) after adjustment for confounding variables and human papillomavirus infection. Our data suggest that polymorphisms in genes related to folate metabolism modify the association of dietary and circulating folate and vitamin B-6 with cervical neoplasia. PMID:24089416

  17. Potential link between exposure to fungicides chlorothalonil and mancozeb and haemic neoplasia development in the soft-shell clam Mya arenaria: a laboratory experiment.

    PubMed

    Pariseau, Julie; Saint-Louis, Richard; Delaporte, Maryse; El Khair, Mohammed Abo; McKenna, Patricia; Tremblay, Réjean; Davidson, T Jeffrey; Pelletier, Emilien; Berthe, Franck C J

    2009-04-01

    The aetiology of haemic neoplasia (HN) is unknown, so far but many causative factors are suggested such as viral, pollution and genetics. The aim of this study was to determine if, under chronic exposure, two major pesticides (chlorothalonil and mancozeb) which are used in potato production could induce HN in soft-shell clams (Mya arenaria). Short-term experiments with acute exposure were also performed. Clams were collected from an epizootic site (North River, PEI) and from a site free of the disease (Magdalen Islands, Quebec). The tetraploid level of haemocytes was assessed by flow cytometry for each clam to determine the HN status. The bioaccumulation of pesticides in tissues was quantified by gas chromatography/mass spectrometry (GC/MS) for chlorothalonil while mancozeb and manganese were quantified by inductively coupled plasma-mass spectrometer (ICP/MS). Long term exposure to fungicide Bravo 500((R)) did not induce high tetraploid levels on negative calm from North River and the analysis of the digestive gland and the mantle did not reveal any detectable level of chlorothalonil. In the Manzate 200 DF((R)), some clams revealed high level of tetraploid cells but no difference were observed between the treatments and the control. The analysis of the digestive gland and the mantle for manganese did not highlight any significant difference in tissue concentration (p=0.05). For the acute exposure, chlorothalonil analysis showed that the active ingredient is distributed between four chlorinated compounds: 99.5% for chlorothalonil isomers, 0.4% for pentachlorothalonil and 0.1% for trichlorothalonil isomers. For a 72 h experiment, the accumulation was within 4h; the higher tissue concentration of chlorothalonil was 59.2 microg g(-1) in the mantle after 48 h, following by a decrease to an undetectable level at the end. For the manganese, the accumulation was detected after 4h; the higher tissue concentration was 48.8 microg g(-1) in the mantle after 24h and, over the following 48 h, the accumulation decreased until the end of the trial. Based on the data, the accumulation of these fungicides seems to be transitory. Chlorothalonil and mancozeb are both oxidative-stress promoters and could have induced cell dysfunction while in the tissue. Study on the effect of these fungicides on the p53 protein system is an example of strategy that would provide information on cellular events promoting neoplasia. PMID:19157463

  18. Analysis of E6 variants of human papillomavirus type 33, 52 and 58 in Japanese women with cervical intraepithelial neoplasia\\/cervical cancer in relation to their oncogenic potential

    Microsoft Academic Search

    Cui Yong Xin; Koji Matsumoto; Hiroyuki Yoshikawa; Toshiharu Yasugi; Takashi Onda; Shunsuke Nakagawa; Manabu Yamada; Shiro Nozawa; Souei Sekiya; Yasuo Hirai; Kenji Shiromizu; Tomoyuki Fujii; Yuji Taketani

    2001-01-01

    The variation of the E6 region of human papillomavirus type 16 (HPV16) is associated with a high risk for cervical carcinogenesis. To see whether the same is the case with HPV33, 52 and 58, known to have high homology with HPV16, we analyzed the E6 sequence variation of these HPVs in 107 Japanese women with cervical intraepithelial neoplasia (CIN) or

  19. Comparison of GP5+\\/6+PCR and SPF10-line blot assays for detection of high-risk human papillomavirus in samples from women with normal cytology results who develop grade 3 cervical intraepithelial neoplasia

    Microsoft Academic Search

    A. T. Hesselink; M. A. P. C. van Ham; D. A. M. Heideman; Z. M. A. Groothuismink; L. Rozendaal; J. Berkhof; F. J. van Kemenade; L. A. F. G. Massuger; W. J. G. Melchers; C. J. L. M. Meijer; P. J. L. M. Snijders

    2008-01-01

    Using a case control approach, we performed a two-way comparison study between GP5+\\/6+-PCR and HPV SPF(10)-Line Blot 25 (SPF(10)) assays for detection of 14 types of high-risk human papillomavirus (hrHPV) in samples from women with normal cytology results who had or developed grade 3 cervical intraepithelial neoplasia (CIN 3). Samples were pooled from two cohorts, i.e., women participating in population-based

  20. Phase I\\/II trial of immunogenicity of a human papillomavirus (HPV) type 16 E7 protein–based vaccine in women with oncogenic HPV-positive cervical intraepithelial neoplasia

    Microsoft Academic Search

    Sophie Hallez; Philippe Simon; Frédéric Maudoux; Jean Doyen; Jean-Christophe Noël; Aude Beliard; Xavier Capelle; Frédéric Buxant; Isabelle Fayt; Anne-Cécile Lagrost; Pascale Hubert; Colette Gerday; Arsène Burny; Jacques Boniver; Jean-Michel Foidart; Philippe Delvenne; Nathalie Jacobs

    2004-01-01

    Purpose: Infection with oncogenic human papillomavirus (HPV) and HPV-16 in particular is a leading cause of anogenital neoplasia. High-grade intraepithelial lesions require treatment because of their potential to progress to invasive cancer. Numerous preclinical studies have demonstrated the therapeutic potential of E7-directed vaccination strategies in mice tumour models. In the present study, we tested the immunogenicity of a fusion protein

  1. Effect of TA-CIN (HPV 16 L2E6E7) booster immunisation in vulval intraepithelial neoplasia patients previously vaccinated with TA-HPV (vaccinia virus encoding HPV 16\\/18 E6E7)

    Microsoft Academic Search

    E. J Davidson; R. L Faulkner; P Sehr; M Pawlita; L. J. C Smyth; D. J Burt; A. E Tomlinson; J Hickling; H. C Kitchener; P. L Stern

    2004-01-01

    Heterologous prime-boost vaccination schedules employing TA-HPV, a vaccinia virus encoding HPV 16\\/18 E6 and E7, in combination with TA-CIN, an HPV 16 L2E6E7 fusion protein, may offer advantages over the use of either agent alone for the immunotherapy of human papillomavirus (HPV) type 16-associated vulval intraepithelial neoplasia (VIN). In the present study, 10 women with HPV 16-positive high grade VIN,

  2. Regression of Cervical Intraepithelial Neoplasia and Loss of Human Papillomavirus (HPV) Infection Is Associated with Cell-mediated Immune Responses to an HPV Type 16 E7 Peptide1

    Microsoft Academic Search

    Anna S. Kadish; Patrick Timmins; Yuexian Wang; Gloria Y. F. Ho; Robert D. Burk; John Ketz; Seymour L. Romney; Anne Johnson; Ruth Angeletti; Maria Abadi

    Most human papillomavirus (HPV)-associated cervical intraepithelial neoplasia (CIN) lesions in normal women regress spontaneously, but a small number persist and may progress to invasive cancer. To evaluate the role of immunity to HPV and the outcome of CIN and associated HPV infection, we examined cell-mediated immune (CMI) responses to HPV 16 E6 and E7 peptides. One hundred thirty-six women with

  3. Genetic mapping studies of 40 loci and 23 cosmids in chromosome 11p13-11g13, and exclusion of ?-calpain as the multiple endocrine neoplasia type 1 gene

    Microsoft Academic Search

    J. T. Pang; S. E. Lloyd; C. Wooding; B. Farren; B. Pottinger; B. Harding; S. E. A. Leigh; M. A. Pook; R. V. Thakker; F. J. Benham; G. T. Gillett; R. T. Taggart

    1996-01-01

    Forty loci (16 polymorphic and 24 non-polymorphic) together with 23 cosmids isolated from a chromosome 11-specific library\\u000a were used to construct a detailed genetic map of 11p13-11g13. The map was constructed by using a panel of 13 somatic cell\\u000a hybrids that sub-divided this region into 19 intervals, a meiotic mapping panel of 33 multiple endocrine neoplasia type 1\\u000a (MEN1) families

  4. Clinical data and characterization of the liver conditional mouse model exclude neoplasia as a non-neurological manifestation associated with Friedreich's ataxia.

    PubMed

    Martelli, Alain; Friedman, Lisa S; Reutenauer, Laurence; Messaddeq, Nadia; Perlman, Susan L; Lynch, David R; Fedosov, Kathrin; Schulz, Jörg B; Pandolfo, Massimo; Puccio, Hélène

    2012-11-01

    Friedreich's ataxia (FRDA) is the most common hereditary ataxia in the caucasian population and is characterized by a mixed spinocerebellar and sensory ataxia, hypertrophic cardiomyopathy and increased incidence of diabetes. FRDA is caused by impaired expression of the FXN gene coding for the mitochondrial protein frataxin. During the past ten years, the development of mouse models of FRDA has allowed better understanding of the pathophysiology of the disease. Among the mouse models of FRDA, the liver conditional mouse model pointed to a tumor suppressor activity of frataxin leading to the hypothesis that individuals with FRDA might be predisposed to cancer. In the present work, we investigated the presence and the incidence of neoplasia in the largest FRDA patient cohorts from the USA, Australia and Europe. As no predisposition to cancer could be observed in both cohorts, we revisited the phenotype of the liver conditional mouse model. Our results show that frataxin-deficient livers developed early mitochondriopathy, iron-sulfur cluster deficits and intramitochondrial dense deposits, classical hallmarks observed in frataxin-deficient tissues and cells. With age, a minority of mice developed structures similar to the ones previously associated with tumor formation. However, these peripheral structures contained dying, frataxin-deficient hepatocytes, whereas the inner liver structure was composed of a pool of frataxin-positive cells, due to inefficient Cre-mediated recombination of the Fxn gene, that contributed to regeneration of a functional liver. Together, our data demonstrate that frataxin deficiency and tumorigenesis are not associated. PMID:22736457

  5. The impact of commercial rodent diets on the induction of tumours and flat aberrant crypt foci in the intestine of multiple intestinal neoplasia mice.

    PubMed

    Svendsen, Camilla; Alexander, Jan; Paulsen, Jan Erik; Knutsen, Helle K; Hjertholm, Hege; Brantsæter, Anne Lise; Husøy, Trine

    2012-07-01

    A large variation in spontaneous tumour development in the multiple intestinal neoplasia (Min) mouse model between laboratories has been reported. The composition of the diet might be an important factor. We examined the impact of five commercial rodent diets: the natural ingredient breeding diet Harlan Teklad 2018 (HT), the purified breeding diet AIN93G, the natural ingredient maintenance diet RM1, and the purified maintenance diets AIN93M and AIN76A, on the spontaneous intestinal tumorigenesis in the Min mouse model. The Min mice were fed one of two breeding diets during gestation and until four weeks of age, thereafter one of the three maintenance diets. Min mice bred on the breeding diet HT had significantly higher numbers and incidences of tumours in the colon, but fewer tumours in the small intestine than the breeding diet AIN93G. The maintenance diet RM1 gave a significantly higher number of small intestinal and colonic tumours and precancerous lesions called flat aberrant crypt foci (ACF) compared with the maintenance diets AIN93M and AIN76A. These findings show the importance of defining the type of diet used in experimental intestinal carcinogenesis studies, and that the diet should be taken into consideration when comparing results from different studies with Min mice. PMID:22522416

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

    SciTech Connect

    Marsh, D.J.; Andrew, S.; Richardson, A.L. [Royal North Shore Hospital, St. Leonards (Australia)] [Royal North Shore Hospital, St. Leonards (Australia); [Univ. of Sydney, New South Wales (Australia)] [and others

    1994-09-15

    Multiple endocrine neoplasia type 2A (MEN2A) and familial medullary thyroid carcinoma (FMTC) are autosomal dominant inherited cancer syndromes with incomplete penetrance. Following the identification of mutations in the RET proto-oncogene that segregate with the disease phenotype in MEN2A, MEN2B, and FMTC, genetic screening of individuals with mutations in RET may be performed. The authors have employed restriction endonuclease digestion of polymerase chain reaction products as an alternative to sequence analysis for rapid identification of mutant gene carriers in families in which MEN2A and RMTC are segregating. Twenty-one Australasian MEN2A and FMTC families have been screened for mutations in a cysteine-rich region of the RET proto-oncogene. Seven independent mutations were identified in key individuals in 16 of these families. The authors have identified a mutation in codon 620, 2053 T {r_arrow}C (Cys620Arg), and two mutations in codon 634 of exon 11 of RET, 2095 T {r_arrow} C (Cys634Arg) and 2096 G {r_arrow} A (Cys634Tyr), all three of which were present in both MEN2A and FMTC families. 7 refs., 1 fig., 1 tab.

  7. The tumor microenvironment: possible role of integrins and the extracellular matrix in tumor biological behavior of intratubular germ cell neoplasia and testicular seminomas.

    PubMed Central

    Timmer, A.; Oosterhuis, J. W.; Schraffordt Koops, H.; Sleijfer, D. T.; Szabo, B. G.; Timens, W.

    1994-01-01

    In the present study, we examined the distribution of integrin subunits and extracellular matrix proteins in normal testis, intratubular germ cell neoplasia (ITGCN), and primary and metastatic seminomas. Compared to normal testis in ITGCN, Sertoli cells showed increased expression of alpha 3, alpha 6, and beta 1 integrin subunits. Malignant intratubular germ cells stained for alpha 3, alpha 6, and beta 1 integrin subunits. Progression of ITGCN to invasive seminoma was associated with loss of alpha 3 integrin subunit expression by tumor cells. Consequent to this loss, it can be speculated that the strong expression on ITGCN may be related to the noninvasive character of the lesion as is also known from other noninvasive tumors. All tumors showed a strong expression of alpha 6 and beta 1 integrin subunits. The alpha 5 integrin subunit was weakly expressed in primary seminomas in all stages. No differences were observed in integrin expression between primary and metastatic tumors. The distribution of extracellular matrix proteins was heterogeneous and revealed clear architectural differences between seminomas that may reflect different stages of tumor stroma formation. To our knowledge, the results presented in this study provide the first information on the possible role of tumor-extracellular matrix interactions in the biological behavior of ITGCN and testicular seminomas. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8178927

  8. Epidermolytic hyperkeratosis of the vulva associated with basal cell carcinoma in a patient with vaginal condyloma acuminatum and vaginal intraepithelial neoplasia harboring HPV, type 42.

    PubMed

    Kacerovská, Denisa; Michal, Michal; Kašpírková, Jana; Kazakov, Dmitry V

    2014-04-01

    The occurrence of basal cell carcinoma (BCC) of the vulva is rare. We report the case of a 79-year-old woman with a medical history of intravaginal condyloma acuminatum and vaginal intraepithelial neoplasia 3 (VaIN 3) who presented with a solitary whitish lesion sized 8x5 mm with a central desquamation located on the right labium majus. Histopathologic examination revealed a typical superficial and nodular BCC. Additionally, there were multiple remarkable foci of epidermolytic hyperkeratosis (EH). These foci both merged with superficial BCC or were sharply demarcated from the tumor. Retrospective molecular-biological examination of all the available material revealed HPV type 42 in both condyloma acuminatum and VaIN 3 specimen but not in the BCC associated with EH. To our best knowledge, involvement of the lower female genitalia by EH is a rare finding with six cases published to date. Awareness of EH in this location and its distinction is important because it may be potentially misinterpreted as a viral condyloma. PMID:24758505

  9. Sulla termodinamica dei materiali con memoria

    Microsoft Academic Search

    Dario Graffi

    1974-01-01

    Sunto  Si espone limitandosi, per semplicità, ai corpi solidi con deformazioni infinitesime, la teoria di Coleman sulla termodinamica\\u000a dei materiali con memoria. Si considerano poi, in particolare, i corpi viscoelastici lineari e identificata l'energia libera\\u000a con l'energia potenziale interna di Volterra, si deducono, dalla termodinamica, proprietà dei coefficenti di memoria, finora\\u000a ammesse come intuitive e si ottiene una rapida dimostrazione del

  10. Anal high-risk human papillomavirus infection and high-grade anal intraepithelial neoplasia detected in women and heterosexual men infected with human immunodeficiency virus

    PubMed Central

    Gandra, Sumanth; Azar, Aline; Wessolossky, Mireya

    2015-01-01

    Background Although anal high-risk human papillomavirus (HR-HPV) infection and anal cytological abnormalities are highly prevalent among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM), there are insufficient data on these abnormalities among HIV-infected heterosexual men (HSM) and women. In this study, we evaluated the prevalence of anal HR-HPV, cytological abnormalities, and performance of these screening tests in detecting high-grade anal intraepithelial neoplasia (AIN2+) among our cohort of HIV-infected MSM and non-MSM (HSM and women). Methods A single-center, retrospective cohort study was conducted with HIV-infected individuals who underwent anal cancer screening with anal cytology and HR-HPV testing from January 2011 to January 31, 2013. Results Screening of 221 HIV-infected individuals for both HR-HPV and anal cytology showed the presence of HR-HPV in 54% (abnormal anal cytology 48%) of MSM, 28% (abnormal anal cytology 28%) of HSM, and 27% (abnormal anal cytology 34%) of women. Among 117 (53%) individuals with abnormal results (HR-HPV-positive and/or cytology was atypical squamous cells of undetermined significance or above), 67 underwent high resolution anoscopy. Of these 67 individuals, 22 individuals had AIN2+ (17 MSM, four women, and one HSM). HR-HPV correlated better with AIN2+ than with anal cytology on biopsy in both MSM (r=0.29 versus r=0.10; P=0.05 versus P=0.49) and non-MSM (r=0.36 versus r=?0.34; P=0.08 versus P=0.09). Conclusion Given the presence of AIN2+ in screened HIV-infected HSM and women, routine anal cancer screening in all HIV-infected individuals should be considered. HR-HPV merits further evaluation for anal cancer screening among non-MSM. PMID:25670914

  11. HPV16 L1 and L2 DNA methylation predicts high-grade cervical intraepithelial neoplasia in women with mildly abnormal cervical cytology

    PubMed Central

    Lorincz, Attila T; Brentnall, Adam R; Vasiljevi?, Nataša; Scibior-Bentkowska, Dorota; Castanon, Alejandra; Fiander, Alison; Powell, Ned; Tristram, Amanda; Cuzick, Jack; Sasieni, Peter

    2013-01-01

    DNA methylation changes in human papillomavirus type 16 (HPV16) DNA are common and might be important for identifying women at increased risk of cervical cancer. Using recently published data from Costa Rica we developed a classification score to differentiate women with cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3) from those with no evident high-grade lesions. Here, we aim to investigate the performance of the score using data from the UK. Exfoliated cervical cells at baseline and 6-months follow-up were analyzed in 84 women selected from a randomized clinical trial of women undergoing surveillance for low-grade cytology. Selection of women for the methylation study was based on detectable HPV16 in the baseline sample. Purified DNA was bisulfite converted, amplified and pyrosequenced at selected CpG sites in the viral genome (URR, E6, L1 and L2), with blinding of laboratory personnel to the clinical data. The primary measure was a predefined score combining the mean methylation in L1 and any methylation in L2. At the second follow-up visit, 73/84 (87%) women were HPV16 positive and of these 25 had a histopathological diagnosis of CIN2/3. The score was significantly associated with CIN2/3 (area under curve = 0.74, p = 0.002). For a cutoff with 92% sensitivity, colposcopy could have been avoided in 40% (95% CI 27–54%) of HPV16 positive women without CIN2/3; positive predictive value was 44% (32–58%) and negative predictive value was 90% (71–97%). We conclude that quantitative DNA methylation assays could help to improve triage among HPV16 positive women. PMID:23335178

  12. Risk Factors for Cervical Intraepithelial Neoplasia in HIV-Infected Women on Antiretroviral Treatment in Côte d'Ivoire, West Africa

    PubMed Central

    Jaquet, Antoine; Horo, Apollinaire; Ekouevi, Didier K.; Toure, Badian; Coffie, Patrick A.; Effi, Benjamin; Lenaud, Severin; Messou, Eugene; Minga, Albert; Sasco, Annie J.; Dabis, François

    2014-01-01

    Background Facing the dual burden of invasive cervical cancer and HIV in sub-Saharan Africa, the identification of preventable determinants of Cervical Intraepithelial Neoplasia (CIN) in HIV-infected women is of paramount importance. Methods A cervical cancer screening based on visual inspection methods was proposed to HIV-infected women in care in Abidjan, Côte d'Ivoire. Positively screened women were referred for a colposcopy to a gynaecologist who performed directed biopsies. Results Of the 2,998 HIV-infected women enrolled, 132 (4.4%) CIN of any grade (CIN+) were identified. Women had been followed-up for a median duration of three years [IQR: 1–5] and 76% were on antiretroviral treatment (ART). Their median most recent CD4 count was 452 [IQR: 301–621] cells/mm3. In multivariate analysis, CIN+ was associated with a most recent CD4 count >350 cells/mm3 (OR: 0.3; 95% CI: 0.2–0.6) or ?200–350 cells/mm3 (OR 0.6; 95% CI 0.4–1.0) (Ref: <200 cells/mm3 CD4) (p<10?4). Conclusions The presence of CIN+ is less common among HIV-infected women with limited or no immune deficiency. Despite the potential impact of immunological recovery on the reduction of premalignant cervical lesions through the use of ART, cervical cancer prevention, including screening and vaccination remains a priority in West Africa while ART is rolled-out. PMID:24595037

  13. Identification of five novel germline mutations of the MEN1 gene in Japanese multiple endocrine neoplasia type 1 (MEN1) families.

    PubMed Central

    Sato, M; Matsubara, S; Miyauchi, A; Ohye, H; Imachi, H; Murao, K; Takahara, J

    1998-01-01

    Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by tumours of the parathyroid glands, the anterior pituitary, and endocrine pancreas. The MEN1 gene has recently been cloned and germline mutations have been identified in MEN1 patients in the United States, Canada, and Europe. We examined MEN1 gene mutations in MEN1 and MEN1 related cases in eight unrelated Japanese families. These families include five familial MEN1 (FMEN1), two sporadic MEN1 (SMEN1), and one familial hyperparathyroidism (FHP). Direct sequence analysis of the protein coding regions was carried out in all the probands. We identified six different heterozygous mutations in the coding region, of which five were novel, including one missense mutation (E45G) in both FMEN1 and SMEN1, three deletions (569del, 711del, and 1350del3) in FMEN1 and FHP, and two nonsense mutations (R29X and Y312X) in FMEN1 and SMEN1. Only one of these mutations (Y312X) has previously been reported. One proband with FMEN1 had no mutation in the entire exon sequence including the 5' and 3' untranslated regions. A restriction digestion analysis of 19 relatives from the five families showed a close correlation between the existence of the MEN1 gene mutation and disease onset. Four different polymorphisms, including two novel ones, were identified. These findings imply that a diversity of MEN1 gene mutations exists in Japanese MEN1 and MEN1 related disease, suggesting that analysis of the entire coding region of the MEN1 gene is required for genetic counselling in Japan. Images PMID:9832038

  14. Dipeptidase 1 (DPEP1) is a marker for the transition from low-grade to high-grade intraepithelial neoplasia and an adverse prognostic factor in colorectal cancer

    PubMed Central

    Eisenach, P A; Soeth, E; Röder, C; Klöppel, G; Tepel, J; Kalthoff, H; Sipos, B

    2013-01-01

    Background: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Improvements in the understanding of its molecular mechanism and the characterisation of CRC-specific biomarkers facilitating early detection are considered to increase overall survival. Methods: A meta-analysis of microarray and Serial Analysis of Gene Expression (SAGE) has been performed to identify differentially regulated genes in CRC. Dipeptidase 1 (DPEP1/MDP/RDP) and Syntenin-2 (SDCBP2/SITAC18) were found to be differentially expressed in tumour tissue compared with normal mucosa. Expression of DPEP1 was assessed in a validation set of 87 normal mucosa samples, 20 hyperplastic polyps, 46 CR adenomas with low- and high-grade intraepithelial neoplasia (IEN) and 217 well-documented CRCs by immunohistochemistry and partially by immunoblotting and real-time PCR. Results: Expression of DPEP1 was specifically increased in human CRC tissue samples compared with normal mucosa (P<0.0001, Mann–Whitney U-test), showing a striking upregulation in high-grade compared with low-grade IEN. Furthermore, high DPEP1 expression was found to strongly correlate with histological stage (P<0.0001, chi-square test) as well as localisation (P<0.0001, chi-square test) and has been recognised as an independent adverse prognostic factor, showing significant prognostic values with an ROC (receiver operating characteristic)-AUC of 0.9230. Conclusion: Dipeptidase 1 has been identified as an excellent marker of high-grade IEN and CRC, and may thus be applied for screening of early neoplastic lesions and for prognostic stratification. PMID:23839495

  15. Low prostate concentration of lycopene is associated with development of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia.

    PubMed

    Mariani, Simone; Lionetto, Luana; Cavallari, Michele; Tubaro, Andrea; Rasio, Debora; De Nunzio, Cosimo; Hong, Gena M; Borro, Marina; Simmaco, Maurizio

    2014-01-01

    Prostate cancer (PC) is a frequent male malignancy and represents the second most diagnosed cancer in men. Since pre-cancerous lesions, i.e., the high-grade prostatic intraepithelial neoplasia (HGPIN), can be detected years before progression to PC, early diagnosis and chemoprevention are targeted strategies to reduce PC rates. Animal studies have shown that lycopene, a carotenoid contained in tomatoes, is a promising candidate for the chemoprevention of PC. However, its efficacy in humans remains controversial. The present study aimed to investigate the relevance of plasma and prostate concentration of lycopene after a lycopene-enriched diet in patients diagnosed with HGPIN. Thirty-two patients diagnosed with HGPIN were administered a lycopene-enriched diet (20-25 mg/day of lycopene; through 30 g/day of triple concentrated tomato paste) for 6 months. A 6-month follow-up prostate biopsy assessed progression to PC. Patients were classified into three groups according to the histopathological features of the 6-month follow-up biopsy results: prostatitis; HGPIN and PC. PSA and plasma lycopene levels were measured before and after the dietary lycopene supplementation. Prostatic lycopene concentration was only assessed after the supplementation diet. Only prostatic lycopene concentration showed significant differences between the three groups (p = 0.03). Prostatic lycopene concentration below a 1 ng/mg threshold was associated with PC at 6-month follow-up biopsy (p = 0.003). We observed no overall benefits from a 6-month lycopene supplementation, as the rate of HGPIN progression to PC in our population (9/32, 28%) was similar to rates reported in the literature. Baseline PSA levels also showed no significant changes after a lycopene-enriched diet. Our findings point to prostatic lycopene concentration as a promising biomarker of PC. Further prospective longitudinal studies are needed to assess the prognostic role of prostatic lycopene in PC. PMID:24451130

  16. Low Prostate Concentration of Lycopene Is Associated with Development of Prostate Cancer in Patients with High-Grade Prostatic Intraepithelial Neoplasia

    PubMed Central

    Mariani, Simone; Lionetto, Luana; Cavallari, Michele; Tubaro, Andrea; Rasio, Debora; De Nunzio, Cosimo; Hong, Gena M.; Borro, Marina; Simmaco, Maurizio

    2014-01-01

    Prostate cancer (PC) is a frequent male malignancy and represents the second most diagnosed cancer in men. Since pre-cancerous lesions, i.e., the high-grade prostatic intraepithelial neoplasia (HGPIN), can be detected years before progression to PC, early diagnosis and chemoprevention are targeted strategies to reduce PC rates. Animal studies have shown that lycopene, a carotenoid contained in tomatoes, is a promising candidate for the chemoprevention of PC. However, its efficacy in humans remains controversial. The present study aimed to investigate the relevance of plasma and prostate concentration of lycopene after a lycopene-enriched diet in patients diagnosed with HGPIN. Thirty-two patients diagnosed with HGPIN were administered a lycopene-enriched diet (20–25 mg/day of lycopene; through 30 g/day of triple concentrated tomato paste) for 6 months. A 6-month follow-up prostate biopsy assessed progression to PC. Patients were classified into three groups according to the histopathological features of the 6-month follow-up biopsy results: prostatitis; HGPIN and PC. PSA and plasma lycopene levels were measured before and after the dietary lycopene supplementation. Prostatic lycopene concentration was only assessed after the supplementation diet. Only prostatic lycopene concentration showed significant differences between the three groups (p = 0.03). Prostatic lycopene concentration below a 1 ng/mg threshold was associated with PC at 6-month follow-up biopsy (p = 0.003). We observed no overall benefits from a 6-month lycopene supplementation, as the rate of HGPIN progression to PC in our population (9/32, 28%) was similar to rates reported in the literature. Baseline PSA levels also showed no significant changes after a lycopene-enriched diet. Our findings point to prostatic lycopene concentration as a promising biomarker of PC. Further prospective longitudinal studies are needed to assess the prognostic role of prostatic lycopene in PC. PMID:24451130

  17. Credentialing of DNA methylation assays for human genes as diagnostic biomarkers of cervical intraepithelial neoplasia in high-risk HPV positive women

    PubMed Central

    Vasiljevi?, Nataša; Scibior-Bentkowska, Dorota; Brentnall, Adam R.; Cuzick, Jack; Lorincz, Attila T.

    2014-01-01

    Objective Testing for high risk human papillomavirus (HR-HPV) is increasing; however due to limitations in specificity there remains a need for better triage tests. Research efforts have focused recently on methylation of human genes which show promise as diagnostic classifiers. Methods Methylation of 26 genes: APC, CADM1, CCND2, CDH13, CDKN2A, CTNNB1, DAPK1, DPYS, EDNRB, EPB41L3, ESR1, GSTP1, HIN1, JAM3, LMX1, MAL, MDR1, PAX1, PTGS2, RARB, RASSF1, SLIT2, SOX1, SPARC, TERT and TWIST1 was measured by pyrosequencing in cytology specimens from a pilot set of women with normal or cervical intraepithelial neoplasia grade 3 (CIN3) histology. Six genes were selected for testing in Predictors 1, a colposcopy referral study comprising 799 women. The three genes EPB41L3, DPYS and MAL were further tested in a second colposcopy referral study, Predictors 2, comprising 884 women. Results The six genes selected from the pilot: EPB41L3, EDNRB, LMX1, DPYS, MAL and CADM1 showed significantly elevated methylation in CIN2 and CIN3 (CIN2/3) versus ?CIN1 in Predictors 1 (p < 0.01). Highest methylation was observed in cancer tissues. EPB41L3 methylation was the best single classifier of CIN2/3 in both HR-HPV positive (p < 0.0001) and negative samples (p = 0.02). Logistic regression modeling showed that other genes did not add significantly to EPB41L3 and in Predictors 2, its classifier value was validated with AUC 0.69 (95% CI 0.65–0.73). Conclusion Several methylated genes show promise for detecting CIN2/3 of which EPB41L3 seems the best. Methylated human gene biomarkers used in combination may be clinically useful for triage of women with HR-HPV infections. PMID:24508839

  18. High-fat, high-calorie diet promotes early pancreatic neoplasia in the conditional KrasG12D mouse model.

    PubMed

    Dawson, David W; Hertzer, Kathleen; Moro, Aune; Donald, Graham; Chang, Hui-Hua; Go, Vay Liang; Pandol, Steven J; Lugea, Aurelia; Gukovskaya, Anna S; Li, Gang; Hines, Oscar J; Rozengurt, Enrique; Eibl, Guido

    2013-10-01

    There is epidemiologic evidence that obesity increases the risk of cancers. Several underlying mechanisms, including inflammation and insulin resistance, are proposed. However, the driving mechanisms in pancreatic cancer are poorly understood. The goal of the present study was to develop a model of diet-induced obesity and pancreatic cancer development in a state-of-the-art mouse model, which resembles important clinical features of human obesity, for example, weight gain and metabolic disturbances. Offspring of Pdx-1-Cre and LSL-KrasG12D mice were allocated to either a high-fat, high-calorie diet (HFCD; ?4,535 kcal/kg; 40% of calories from fats) or control diet (?3,725 kcal/kg; 12% of calories from fats) for 3 months. Compared with control animals, mice fed with the HFCD significantly gained more weight and developed hyperinsulinemia, hyperglycemia, hyperleptinemia, and elevated levels of insulin-like growth factor I (IGF-I). The pancreas of HFCD-fed animals showed robust signs of inflammation with increased numbers of infiltrating inflammatory cells (macrophages and T cells), elevated levels of several cytokines and chemokines, increased stromal fibrosis, and more advanced PanIN lesions. Our results show that a diet high in fats and calories leads to obesity and metabolic disturbances similar to humans and accelerates early pancreatic neoplasia in the conditional KrasG12D mouse model. This model and findings will provide the basis for more robust studies attempting to unravel the mechanisms underlying the cancer-promoting properties of obesity, as well as to evaluate dietary- and chemopreventive strategies targeting obesity-associated pancreatic cancer development. PMID:23943783

  19. Discrimination of grade 2 and 3 cervical intraepithelial neoplasia by means of analysis of water soluble proteins recovered from cervical biopsies

    PubMed Central

    2011-01-01

    Background Cervical intraepithelial neoplasia (CIN) grades 2 and 3 are usually grouped and treated in the same way as "high grade", in spite of their different risk to cancer progression and spontaneous regression rates. CIN2-3 is usually diagnosed in formaldehyde-fixed paraffin embedded (FFPE) punch biopsies. This procedure virtually eliminates the availability of water-soluble proteins which could have diagnostic and prognostic value. Aim To investigate whether a water-soluble protein-saving biopsy processing method followed by a proteomic analysis of supernatant samples using LC-MS/MS (LTQ Orbitrap) can be used to distinguish between CIN2 and CIN3. Methods Fresh cervical punch biopsies from 20 women were incubated in RPMI1640 medium for 24 hours at 4°C for protein extraction and subsequently subjected to standard FFPE processing. P16 and Ki67-supported histologic consensus review CIN grade (CIN2, n = 10, CIN3, n = 10) was assessed by independent gynecological pathologists. The biopsy supernatants were depleted of 7 high abundance proteins prior to uni-dimensional LC-MS/MS analysis for protein identifications. Results The age of the patients ranged from 25-40 years (median 29.7), and mean protein concentration was 0.81 mg/ml (range 0.55 - 1.14). After application of multistep identification criteria, 114 proteins were identified, including proteins like vimentin, actin, transthyretin, apolipoprotein A-1, Heat Shock protein beta 1, vitamin D binding protein and different cytokeratins. The identified proteins are annotated to metabolic processes (36%), signal transduction (27%), cell cycle processes (15%) and trafficking/transport (9%). Using binary logistic regression, Cytokeratin 2 was found to have the strongest independent discriminatory power resulting in 90% overall correct classification. Conclusions 114 proteins were identified in supernatants from fresh cervical biopsies and many differed between CIN2 and 3. Cytokeratin 2 is the strongest discriminator with 90% overall correct classifications. PMID:21711556

  20. Predictors of persistent cytologic abnormalities after treatment of cervical intraepithelial neoplasia in Soweto, South Africa: a cohort study in a HIV high prevalence population

    PubMed Central

    Adam, Yasmin; van Gelderen, Cyril J; de Bruyn, Guy; McIntyre, James A; Turton, Diane A; Martinson, Neil A

    2008-01-01

    Background In the presence of both HIV infection and cervical intraepithelial neoplasia (CIN), the risk of cancer development despite treatment may be greater. We investigated clinical predictors of persistent cytological abnormalities in women who had had a large loop excision of the transformation zone (LLETZ). Methods Women with high grade squamous intraepithelial lesions or worse (HSIL), less severe abnormalities which persisted and any abnormality in women who are HIV-infected, were referred to the colposcopy clinic. HIV infection was ascertained by self-report. A LLETZ was performed on all patients with HSIL or higher on Papanicolaou (Pap) smear or colposcopy, LSIL or higher in patients who are HIV-infected, where the colposcopy is inadequate, and when there was a discrepancy between colposcopy and cytology by one or more grades. Women with abnormal follow-up smears were compared to those with normal smears. We examined the association between abnormal follow-up smears and demographic and clinical predictors using logistic regression Results The median time between LLETZ and first follow-up Pap smear was rather short at 122 days. Persistent cytological abnormalities occurred in 49% of our patients after LLETZ. Predictors of persistence included the presence of disease at both margins and HIV infection. Among the latter, disease at the excision margins and CD4+ cell count were important predictors. In these women, disease at the endocervical margin, both margins, and disease only at the ectocervical margin were associated with increased odds of persistent abnormalities on follow-up cervical smear. Conclusion We showed extremely high risk of cytological abnormality at follow-up after treatment more so in patients with incomplete excision and in the presence of immunocompromise. It remains uncertain whether recurrent CIN is a surrogate marker for invasive cervical cancer. PMID:18657270

  1. Ultrasonographic evaluation of parathyroid hyperplasia in multiple endocrine neoplasia type 1: Positive correlation between parathyroid volume and circulating parathyroid hormone concentration.

    PubMed

    Tamiya, Hiroyuki; Miyakawa, Megumi; Takeshita, Akira; Miura, Daishu; Takeuchi, Yasuhiro

    2014-09-17

    There are few reports on parathyroid ultrasonography of multiple endocrine neoplasia type 1 (MEN1). This study investigated the ultrasonographic features of parathyroid glands in 10 patients with MEN1 who underwent preoperative neck ultrasonography and parathyroidectomy between 2006 and 2010 at Toranomon Hospital. We retrospectively analyzed clinical features, laboratory and ultrasonographic data, and pathological diagnosis. A total of 38 parathyroid glands were surgically removed (three to five glands from each patient). All removed parathyroids were pathologically diagnosed as hyperplasia. Seven cases (70.0 %) had adenomatous thyroid nodules. Twenty-five enlarged parathyroid glands (65.8 %) were detected by preoperative ultrasonography with a detection rate of 81.8 % (9/11) and 59.3 % (16/27) for patients without and with adenomatous nodules, respectively. Total parathyroid gland weight and potentially predictable total parathyroid volume by preoperative ultrasonography were significantly correlated with preoperative serum intact parathyroid hormone (iPTH) concentration (R = 0.97, P < 0.001 and R = 0.96, P < 0.001, respectively). The equation used for prediction of the total volume by ultrasonography was 15 × iPTH (pg/ml) - 1,000 and that for total weight was 20 × iPTH (pg/ml) - 1,400. Although adenomatous nodules often coexisted with MEN1 and made identification of enlarged parathyroid glands by ultrasonography difficult, the positive correlation between the predictable parathyroid volume by ultrasonography and serum iPTH suggests that their measurement is useful in the preoperative detection and localization of enlarged parathyroid glands in patients with MEN1. Furthermore, the presence of parathyroid glands that should be resected can be predicted before surgery using the equation proposed here. PMID:25227285

  2. Comparison of Onclarity Human Papillomavirus (HPV) Assay with Hybrid Capture II HPV DNA Assay for Detection of Cervical Intraepithelial Neoplasia Grade 2 and 3 Lesions.

    PubMed

    Bottari, F; Sideri, M; Gulmini, C; Igidbashian, S; Tricca, A; Casadio, C; Carinelli, S; Boveri, S; Ejegod, D; Bonde, J; Sandri, M T

    2015-07-01

    Analytical and clinical performance validation is essential before introduction of a new human papillomavirus (HPV) assay into clinical practice. This study compares the new BD Onclarity HPV assay, which detects E6/E7 DNA from 14 high-risk HPV types, to the Hybrid Capture II (HC2) HPV DNA test, to concurrent cytology and histology results, in order to evaluate its performance in detecting high-grade cervical lesions. A population of 567 women, including 325 with ?ASCUS (where ASCUS stands for atypical cells of undetermined significance) and any HC2 result and 242 with both negative cytology and negative HC2 results, were prospectively enrolled for the study. The overall agreement between Onclarity and HC2 was 94.6% (95% confidence intervals [CI], 92.3% to 96.2%). In this population with a high prevalence of disease, the relative sensitivities (versus adjudicated cervical intraepithelial neoplasia grades 2 and 3 [CIN2+] histology endpoints) of the Onclarity and HC2 tests were 95.2% (95% CI, 90.7% to 97.5%) and 96.9% (95% CI, 92.9% to 98.7%), respectively, and the relative specificities were 50.3% (95% CI, 43.2% to 57.4%) for BD and 40.8% (95% CI, 33.9%, 48.1%) for HC2. These results indicate that the BD Onclarity HPV assay has sensitivity comparable to that of the HC2 assay, with a trend to an increased specificity. Moreover, as Onclarity gives the chance to discriminate between the different genotypes, we calculated the genotype prevalence and the absolute risk of CIN2+: HPV 16 was the most prevalent genotype (19.8%) with an absolute risk of CIN2+ of 77.1%. PMID:25903574

  3. p53, erbB-2 and K-ras gene alterations are rare in spontaneous and plutonium-239-induced canine lung neoplasia

    SciTech Connect

    Tierney, L.A.; Hahn, F.F.; Lechner, J.F. [Inhalation Toxicology Research Inst., Albuquerque, NM (United States)

    1996-02-01

    Inhalation of high-linear energy transfer radiation in the form of radon progeny is a suspected cause of human lung cancer. To gain insight into the types of genetic derangements caused by this type of radiation, lung tumors from beagle dogs exposed to {sup 239}PuO{sub 2} and those arising in animals with no known carcinogen exposure were examined for evidence of aberrations in genes known to be altered in lung tumors. Altered expression of the p53 tumor suppressor gene and proto-oncogene erbB-2 proteins (p185{sup erbB2}) was evaluated by immunohistochemical analysis of 117 tumors representing different histological types in exposed (n = 80) and unexposed (n = 37) animals. Twenty-eight tumors were analyzed for K-ras proto-oncogene mutations by polymerase chain reaction amplification and direct sequencing. Fourteen percent (16/116) of all lung neoplasms showed elevated nuclear accumulation of p53 protein. Regardless of exposure history, adenosquamous and squamous cell cancers comprised 94% of all tumors with p53 abnormalities. Eighteen percent (21/117) of all tumors had evidence of erbB-2 protein overexpression. K-ras mutations were not detected in codons 12, 13 or 61 of tumors from unexposed (n = 9) or plutonium-exposed dogs (n = 19). These data indicate that p53 and K-ras gene abnormalities as a result of missense mutation are infrequent events in spontaneous and {sup 239}PuO{sub 2}-induced lung neoplasia in this colony of beagle dogs. Alternative mechanisms of gene alteration may be involved in canine pulmonary carcinogenesis. 45 refs., 3 figs., 2 tabs.

  4. Safety and efficacy of topical Cidofovir to treat high-grade perianal and vulvar intraepithelial neoplasia in HIV-positive men and women

    PubMed Central

    STIER, Elizabeth A; GOLDSTONE, Stephen E.; EINSTEIN, Mark H.; JAY, Naomi; BERRY, J. Michael; WILKIN, Timothy; LEE, Jeannette Y.; DARRAGH, Teresa M.; DA COSTA, Maria; PANTHER, Lori; ABOULAFIA, David; PALEFSKY, Joel M.

    2013-01-01

    Objective To evaluate the safety and efficacy of topical cidofovir for treatment of high-grade squamous perianal and vulvar intraepithelial neoplasia (PAIN and VIN) lesions in HIV-positive individuals. Design Phase IIa prospective multicenter trial conducted at eight clinical sites through the AIDS Malignancy Consortium (AMC) Methods HIV-positive patients with biopsy-proven high-grade PAIN that was ? 3 cm2 were enrolled. PAIN biopsy specimens were assessed for HPV using PCR and type-specific HPV probing. Subjects applied 1% topical cidofovir to PAIN and VIN (if present) for 6 two-week cycles. Results were designated as complete response (CR), partial response (PR) (> 50% reduction in size), stable disease (SD), or progressive disease (PD). Results Twenty-four men and 9 women (8 with high-grade VIN as well) were enrolled. Mean age was 44 years, mean CD4+ count was 412 cells/?l. HPV DNA (most commonly HPV16) was detected in all pre-treatment study specimens. Twenty six (79%) subjects completed treatment per protocol—CR: 5 (15%); PR: 12 (36%), SD: 7 (21%); PD: 2 (6%) (1 with a superficially invasive cancer and 1 with new area of high-grade PAIN). Treatment was well tolerated with most common adverse events being mild to moderate affecting lesional skin: pain/burning/irritation (25 subjects) and ulceration (13 subjects). Conclusions Topical cidofovir had 51% efficacy in the short-term treatment of high-grade PAIN and VIN with acceptable toxicity in HIV-positive individuals. Randomized control studies with more prolonged treatment courses and longer follow-up to assess the durability of the response are needed. PMID:23032420

  5. Modeling Dynamic Domains with ConGolog

    Microsoft Academic Search

    Yves Lespérance; Todd G. Kelley; John Mylopoulos; Eric S. K. Yu

    1999-01-01

    In this paper, we describe the process specification language ConGolog and show how it can be used to model business processes for requirements analysis. In ConGolog, the effects of actions in a dynamic domain are spec- ified in a logical framework. This supports modeling even in the absence of complete information. The behavior of agents in the domain is specified

  6. ProteoCon kit Handbook www.geba.org ProteoCon Kit

    E-print Network

    Lebendiker, Mario

    The ProteoCon kit technology ................................................................3 Mini bottle 2 bottles Buffer WBD2 (washing buffer) 30 ml 60 ml ProteoConN kit 10 units 20 units Proteo. Limitations on Product use The ProteoCon kits were developed designed and are being sold for resear

  7. Tensión postraumática relacionada con el cáncer (PDQ®)

    Cancer.gov

    Resumen de información revisada por expertos acerca de la tensión postraumática y síntomas relacionados en los pacientes con cáncer, sobrevivientes del cáncer y miembros de la familia. Se discuten la evaluación y tratamiento de estos síntomas.

  8. Case–control study of HLA-G promoter methylation status, HPV infection and cervical neoplasia in Curitiba, Brazil: a pilot analysis

    PubMed Central

    2012-01-01

    Background The causal association between persistent human papillomavirus (HPV) infection and cervical cancer has been established, but the mechanisms that favor HPV persistence in cervical cells are still unknown. The diminished capability of the immune system to control and resolve HPV infection is one of several hypotheses. The tolerogenic protein HLA-G has shown aberrant expression in a variety of cancers, which has been suggested as a mechanism for tumor escape from immunosurveillance. In the present study we evaluate the role of epigenetic modification (promoter de-methylation) of the HLA-G gene on susceptibility to HPV infection and development of high-grade cervical lesions. Methods A case–control study was carried out in Curitiba, Brazil, between February and June 2010. A total of 789 women aged 15–47 years were recruited: 510 controls with normal cervical cytology, and 279 cases with histologically confirmed cervical intraepithelial neoplasia grade 2 (CIN2, N?=?150) or grade 3 (CIN3, N?=?129). All women were administered a questionnaire by interview, which collected information on demographic and lifestyle factors, and a cervical sample was collected. HPV DNA detection was performed by GP5+/GP6+ primer-mediated PCR. HPV-positive samples were genotyped by multiplex PCR. A pilot analysis of HLA-G promoter methylation was carried out in a subset of the study population (96 cases and 76 controls) by pyrosequencing. HLA-G methylation and HPV infection status of cases and controls were compared, and confounding factors were computed by t Student and non-parametric Wilcoxon tests. Comparison of HLA-G methylation between cases and controls was assessed by the Bonferroni correction. The association of HLA-G methylation with CIN2/3 was evaluated by logistic regression. Results HPV prevalence was 19.6% in controls and 94.3% in CIN2/3 cases. HPV16, 31, 33, 35 and 18 were the most prevalent types. Methylation analysis of seven CpGs in the HLA-G promoter did not reveal any spontaneous de-methylation events in CIN2/3 cases (mean proportion of methylation: 75.8%) with respect to controls (mean 73.7%; odds ratio 1.01, 95% confidence interval 0.96, 1.07). Conclusions This study did not support the hypothesis that spontaneous de-methylation events in the HLA-G promoter play a primary role in promoting escape from immunosurveillance in the development of precancerous cervical lesions. PMID:23265140

  9. Simultaneous occurrence of multiple neoplasms and hyperplasias in the adrenal and thyroid gland of the horse resembling multiple endocrine neoplasia syndrome: case report and retrospective identification of additional cases.

    PubMed

    De Cock, H E; MacLachlan, N J

    1999-11-01

    Neoplastic and hyperplastic disorders that affect multiple endocrine tissues in a single individual are well described in humans but less so in domestic animals. Multiple endocrine neoplasia (MEN) in humans is a genetically determined syndrome characterized by the appearance of benign or malignant proliferations within two or more endocrine glands. The primary endocrine tumors that are characteristic of MEN arise from cells that share the capacity for amine precursor uptake and decarboxylation. Here we describe the case of a 22-year-old Thoroughbred mare that died during an unattended parturition and subsequently was presented for necropsy at the University of California, Davis, Veterinary Medical Teaching Hospital. A C-cell (medullary) thyroid adenoma, pheochromocytoma, and multicentric bilateral nodular hyperplasia of the adrenal medulla were present, findings that are remarkably similar to those of human MEN syndrome. Mortality during pregnancy in women with undiagnosed pheochromocytoma is high (approximately 50%), typically because of hypertension and/or hemorrhage associated with catecholamine release from the tumor. Similarly, the mare in this report died of hemorrhage subsequent to parturition. A retrospective evaluation of endocrine tumors in horses that underwent necropsy at the Veterinary Medical Teaching Hospital from 1987 to 1997 was undertaken to identify additional possible cases of MEN in horses. Data from this retrospective evaluation suggest that coexistence of hyperplasias and neoplasias of the thyroid and adrenal glands, similar to MEN syndrome of humans, also occurs with some frequency in the horse. PMID:10568452

  10. Irradiation induced salivary gland neoplasia

    SciTech Connect

    Sener, S.F.; Scanlon, E.F.

    1980-03-01

    Twenty-six patients with a prior history of irradiation for benign conditions of the head and neck and salivary gland abnormalities are reported. All the patients had preoperative physical findings suggestive of tumor, not glandular infection. Forty-six per cent of the patients had one carcinoma and 11% had two carcinomas within the irradiated field. Eight of the 11 malignant tumors in these 26 patients were in the parotid gland. The nonmalignant salivary changes were similar to those previously reported in glands receiving therapeutic irradiation for carcinoma.

  11. Stem Cells in Intraepithelial Neoplasia

    Microsoft Academic Search

    Nicholas A. Wright

    \\u000a Tumours are thought to contain a subpopulation of self-renewing stem cells, the so-called cancer stem cells, which maintain the tumour. Moreover, tumours themselves are thought to arise from organ-specific stem cells. In epithelia, transformation of these cells leads to spread of a mutated stem cell clone through the epithelial sheet, leading to the development of a pre-invasive lesion. Barrett’s oesophagus

  12. Multiple Endocrine Neoplasia Type I

    MedlinePLUS

    ... using medical, or nonsurgical, treatments. According to this school of thought, pancreatic surgery has serious complications, so ... tumor or cure a hormone excess state. Another school advocates early surgery, perhaps when a tumor grows ...

  13. MTHFR POLYMORPHISMS AND COLORECTAL NEOPLASIA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Folate is essential for the synthesis, repair and methylation of DNA. Aberrations in folate metabolism can modify our risk for cancer. Folate depletion alters DNA methylation patterns and increases DNA uracil-content and the frequency of DNA breaks. These DNA aberrations are involved in the etiology...

  14. Urachal neoplasia: a case report

    PubMed Central

    da Cruz, Célio Lúcio Palha; Fernandes, Gabriel Lacerda; Natal, Marcelo Ricardo Canuto; Taveira, Thales Roberto Teixeira; Bicalho, Patrícia Amaral; de Brito, Yanna Quitéria Iida Pimentel

    2014-01-01

    Diseases of urachal remnants are uncommon and generally located on the junction of the urachal remnant with the bladder dome. In most cases such diseases correspond to mucinous adenocarcinomas and present hematuria as their most common clinical finding. The authors report the case of a 62-year-old female patient undergoing follow-up due to macroscopic hematuria for three years. Ultrasonography and computed tomography findings are described. PMID:25741124

  15. Genomic Landscapes of Pancreatic Neoplasia

    PubMed Central

    Wood, Laura D.; Hruban, Ralph H.

    2015-01-01

    Pancreatic cancer is a deadly disease with a dismal prognosis. However, recent advances in sequencing and bioinformatic technology have led to the systematic characterization of the genomes of all major tumor types in the pancreas. This characterization has revealed the unique genomic landscape of each tumor type. This knowledge will pave the way for improved diagnostic and therapeutic approaches to pancreatic tumors that take advantage of the genetic alterations in these neoplasms. PMID:25812653

  16. Epidemiological Trends in Pancreatic Neoplasias

    Microsoft Academic Search

    Babette Simon; Hartmut Printz

    2001-01-01

    Primary prevention is the most effective approach to reduce the incidence of pancreatic cancer. Epidemiological studies have contributed to the identification of risk factors for pancreatic cancer, suggesting an association with age, various medical conditions, environmental and lifestyle risk factors, and occupational and genetic conditions. Age is the strongest risk factor. The most consistently identified environmental risk factor is smoking,

  17. Early lesions in lymphoid neoplasia

    PubMed Central

    Fend, Falko; Cabecadas, José; Gaulard, Philippe; Jaffe, Elaine S.; Kluin, Philip; Kuzu, Isinsu; Peterson, LoAnn; Wotherspoon, Andrew; Sundström, Christer

    2013-01-01

    The increasing use of immunophenotypic and molecular techniques on lymphoid tissue samples without obvious involvement by malignant lymphoma has resulted in the increased detection of “early” lymphoid proliferations, which show some, but not all the criteria necessary for a diagnosis of malignant lymphoma. In most instances, these are incidental findings in asymptomatic individuals, and their biological behaviour is uncertain. In order to better characterize these premalignant conditions and to establish diagnostic criteria, a joint workshop of the European Association for Haematopathology and the Society of Hematopathology was held in Uppsala, Sweden, in September 2010. The panel reviewed and discussed more than 130 submitted cases and reached consensus diagnoses. Cases representing the nodal equivalent of monoclonal B-cell lymphocytosis (MBL) were discussed, as well as the “in situ” counterparts of follicular lymphoma (FL) and mantle cell lymphoma (MCL), topics that also stimulated discussions concerning the best terminology for these lesions. The workshop also addressed the borderland between reactive hyperplasia, and clonal proliferations such as pediatric marginal zone lymphoma and pediatric FL, which may have very limited capacity for progression. Virus-driven lymphoproliferations in the grey zone between reactive lesions and manifest malignant lymphoma were covered. Finally, early manifestations of T-cell lymphoma, both nodal and extranodal, and their mimics were addressed. This workshop report summarizes the most important conclusions concerning diagnostic features, as well as proposals for terminology and classification of early lymphoproliferations and tries to give some practical guidelines for diagnosis and reporting. PMID:24307917

  18. Genesis of Pancreatic Ductal Neoplasia

    Microsoft Academic Search

    Barbara A. Centeno; Gregory M. Springett

    \\u000a Pancreatic cancer is the fourth overall leading cause of cancer death in both genders, even though it is not among the most\\u000a frequent. Early detection and targeted therapeutic options, which can be obtained through a better understanding of the cellular\\u000a and molecular processes which lead to the development of pancreatic carcinoma, are key to improving the outcome of this highly

  19. LA MAESTRA EN CIENCIAS (NEUROBIOLOGA), Con el objetivo de formar profesionales con conocimientos slidos de los

    E-print Network

    Islas, León

    LA MAESTRÍA EN CIENCIAS (NEUROBIOLOGÍA), Con el objetivo de formar profesionales con conocimientos, neurociencias, psicobiología, física, matemáticas, estadística y metodología de la ciencia, a presentar su Nacional de Posgrado de Calidad del Consejo Nacional de Ciencia y Tecnología en categoría: COMPETENTE

  20. Too Many Minas Spoil The Con

    E-print Network

    2007-02-13

    and in livejournal, I suddenly got the urge to go to a con again. The thought of a proper anime con, with people dressing up and showing videos and panels and discussions about the series and even about writing fanfiction, well, I thought that you must be involved...'t write proper porn. There's more to it than just the penis. I mean, erotica. Not porn. Um, sorry. That was just the first day. Day two had the writing panels and the surprise guest standing in for H.P Lovecraft (I mean, everyone knew that it was a...

  1. Management of patients and subjects at risk for multiple endocrine neoplasia type 1: MEN 1. GENEM 1. Groupe d'Etude des Néoplasies Endocriniennes Multiples de type 1.

    PubMed

    Chanson, P; Cadiot, G; Murat, A

    1997-01-01

    Multiple endocrine neoplasia type 1 (MEN 1) is characterized by the combined occurrence, to variable degree, of hyperparathyroidism (HPT) (85.7% of cases according to the French Registry of GENEM 1), tumors of the endocrine pancreas (49.6%), pituitary adenomas (38.4%) and, less frequently, adrenal tumors (9.6%) and neuroendocrine tumors (5.8%). Currently, diagnosis of MEN 1 is done in the fourth decade of life, but familial screening (using genetic tools whose diagnostic accuracy approaches 100%) has lowered the age of diagnosis. Screening for MEN 1 in a patient harboring an apparently sporadic tumor will depend on the endocrine gland involved. Extensive screening for MEN 1 in the presence of HPT will be conducted only when the familial history is suggestive, when parathyroid glands are hyperplastic or when multiple parathyroid adenomas have been found at surgery. All patients with an endocrine pancreas tumor need to be investigated for the presence of other endocrine lesions of MEN 1. Extensive screening for MEN 1 is only recommended when a patient with a pituitary tumor or an adrenal tumor has a familial history suggestive of MEN 1. Otherwise regular measurement of blood calcium and PTH levels seem sufficient. Extensive screening for endocrine lesions when MEN 1 is suspected involves hormone measurements and imaging procedures. For the diagnosis of HPT, calcemia and PTH 1-84 must be measured. In the absence of clinical symptoms, basal measurement of serum gastrin, glucose, insulin, glucagon, VIP, somatostatin and pancreatic polypeptide levels are combined with abdominal ultrasonography. When symptoms suggest the Zollinger-Ellison syndrome, the secretin stimulation test is recommended. The diagnosis of a pituitary tumor is made by pituitary imaging and selected hormone assays (mainly PRL). To detect an adrenal tumor, CT scan is recommended, combined with serum potassium, urinary free cortisol and androgen measurement. When the diagnosis of MEN 1 is made, clinical and hormonal follow-up (once a year) and imaging surveillance (every 3-5 years) may be sufficient to detect new other endocrinopathies (unless suggestive clinical symptoms arise). Surgical management of each endocrine lesion must be done by skilled surgeons according to therapeutic protocols which have been discussed in detail. Genetic screening is an integral part of familial screening which may be conducted in collateral and in the offspring of MEN 1 patients. Obviously ethical principles (informed consent, etc.) must be respected. As it is now possible to detect presymptomatic gene carriers with a high degree of accuracy, follow-up is needed to make appropriate management decisions. The marked anxiety provoked by screening in an overtly asymptomatic healthy subject must not be underestimated. Conversely, a negative genetic diagnosis helps to reassure the subject and avoid repetitive and costly follow-up. PMID:9167954

  2. CON Advising Academic Year 2013-2014

    E-print Network

    Carter, John

    in achieving the learning outcomes, ensuring student academic success, and planning to achieve the studentsCON Advising Academic Year 2013-2014 Advisors: Rita Tower Kelly Fanning Office: Garrand 403 Garrand students to make decisions about their academic, personal and professional pathways, and to encourage

  3. Diagramas de Voronoi con funciones temporales \\Lambda

    E-print Network

    Palop del Río, Belén

    Diagramas de Voronoi con funciones temporales \\Lambda Ferran Hurtado, Bel'en Palop, Vera Sacrist'etricas. En este trabajo se describen los diagramas de Voronoi dados por funciones temporales surgidas al introducir en el plano una red de transporte. Dichas funciones pueden dar lugar a bisectores que no forman un

  4. Google Scholar: the pros and the cons

    Microsoft Academic Search

    Péter Jacsó

    2005-01-01

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

  5. Teorías sobre cobertura con contratos de futuro

    Microsoft Academic Search

    Vicent Aragó Manzana

    2009-01-01

    En este trabajo se presenta una revisión de las principales teorías sobre cobertura con contratos de futuro y de los distintos métodos de estimación utilizados para determinar el ratio de cobertura óptimo. La aproximación a la cobertura más utilizada en la literatura especializada es la basada en el modelo de la teoría de carteras. No obstante, debido a sus hipótesis

  6. VANET Routing Protocols: Pros and Cons

    E-print Network

    Paul, Bijan; Bikas, Md Abu Naser

    2012-01-01

    VANET (Vehicular Ad-hoc Network) is a new technology which has taken enormous attention in the recent years. Due to rapid topology changing and frequent disconnection makes it difficult to design an efficient routing protocol for routing data among vehicles, called V2V or vehicle to vehicle communication and vehicle to road side infrastructure, called V2I. The existing routing protocols for VANET are not efficient to meet every traffic scenarios. Thus design of an efficient routing protocol has taken significant attention. So, it is very necessary to identify the pros and cons of routing protocols which can be used for further improvement or development of any new routing protocol. This paper presents the pros and cons of VANET routing protocols for inter vehicle communication.

  7. Somatic cell nuclear transfer: pros and cons.

    PubMed

    Sumer, Huseyin; Liu, Jun; Tat, Pollyanna; Heffernan, Corey; Jones, Karen L; Verma, Paul J

    2009-01-01

    Even though the technique of mammalian SCNT is just over a decade old it has already resulted in numerous significant advances. Despite the recent advances in the reprogramming field, SCNT remains the bench-mark for the generation of both genetically unmodified autologous pluripotent stem cells for transplantation and for the production of cloned animals. In this review we will discuss the pros and cons of SCNT, drawing comparisons with other reprogramming methods. PMID:20232594

  8. Too Many Minas Spoil The Con 

    E-print Network

    2007-02-13

    1 12:08 pm February 13th, 2007 vuirneen A semi-private email to Mina de Malfois Is anyone familiar with the writings of mina_de_malfois? I wrote this email to her, based entirely on her Minaverse, between... midnight and two am last night and I just wanted someone to check it before I send it to her. Too Many Minas Spoil The Con Dear Mina, I'm not quite sure how to start this letter. I feel as though I've failed a test of some kind and that if I only...

  9. Connector Generator (ConGen) Table of contents

    E-print Network

    Connector Generator (ConGen) Table of contents 1 Overview of Con of ConGen Software connectors are typically used in component-based engineering to model and realize component interconnections. Connectors play an important role both at design time, when they allow

  10. Combinando multiples discretizadores para aprendizaje de reglas evolutivo con enfoque

    E-print Network

    Bacardit, Jaume

    resultados de las pruebas realizadas con diversos dominios muestran que se consigue obtener un sistema clasi sistemas GABIL [3] y XCS [4] respectivamente. Para tratar con problemas con atributos reales una de las representaciones del conocimiento clasicas de este tipo de sistemas. Un buen algorit­ mo de discretizacion tiene

  11. Análisis comparado de los contratos marco para operaciones con derivados

    Microsoft Academic Search

    Iván Eduardo Rozo; Lina Maria Contreras; Laura Maria Gallego

    2010-01-01

    En teoría, las operaciones con derivados son instrumentos financieros cuyo propósito es cubrir los riesgos sobre los flujos a recibir, no obstante un contrato de esta naturaleza que presente vacíos o no cuente con provisiones suficientes, puede generar riesgos adicionales y costos de transacción aún mayores a los que se intentaba mitigar inicialmente. De acuerdo con lo anterior, este documento

  12. Energy Star program benefits Con Edison

    SciTech Connect

    NONE

    1995-05-01

    Impressed with savings in energy costs achieved after upgrading the lighting and air conditioning systems at its Manhattan headquarters, Home Box Office (HBO) wanted to do more, James Flock, vice president for computer and office systems, contacted Con Edison Co. of New York in March 1991 to determine what the company could do to save money by reducing energy consumed by personal computers. Arthur Kressner, Con Edison Research and Development manager contacted industry organizations and manufacturers for advice, but was told only to shut off computers at night and on weekends. Kressner arranged a series of meetings with IBM and the Electric Power Research Institute (EPRI) to discuss the issue, then approached the U.S. Environmental Protection Agency (EPA), which was designing a program to promote the introduction and use of energy-efficient office equipment. In 1992, the EPA announced the Energy Star program for PCs, enabling manufacturers to display the Energy Star logo on machines meeting program criteria, including the ability to enter a sleep mode in which neither the computer nor monitor consume more than 30 W or electricity. Industry experts estimate national energy consumption by office equipment could double by the year 2000, but Energy Star equipment is expected to improve efficiency and help maintain electric loads.

  13. Tiene familiares con Alzheimer? La Escuela de Medicina del Recinto de Ciencias Mdicas en colaboracin con la Universidad de Columbia

    E-print Network

    Quirk, Gregory J.

    ¿Tiene familiares con Alzheimer? 25/1/2008 La Escuela de Medicina del Recinto de Ciencias Médicas más con Alzheimer para participar de un estudio genético. La investigación pretende encontrar genes que se encuentren relacionados a la enfermedad de Alzheimer con el propósito de aprender más sobre las

  14. Progression of cervical intraepithelial neoplasia to cervical cancer: interactions of cytochrome P450 CYP2D6 EM and glutathione s-transferase GSTM1 null genotypes and cigarette smoking.

    PubMed Central

    Warwick, A. P.; Redman, C. W.; Jones, P. W.; Fryer, A. A.; Gilford, J.; Alldersea, J.; Strange, R. C.

    1994-01-01

    The factors that determine progression of cervical intraepithelial neoplasia (CIN) to squamous cell carcinoma (SCC) are unknown. Cigarette smoking is an independent risk factor for cervical neoplasia, suggesting that polymorphism at detoxicating enzyme loci such as cytochrome P450 CYP2D6 and glutathione S-transferase GSTM1 may determine susceptibility to these cancers. We have studied the frequencies of genotypes at these loci in women suffering low-grade CIN, high-grade CIN and SCC. A non-cancer control group was provided by women with normal cervical histology suffering menorrhagia. Comparison of the frequency distributions of the CYP2D6 PM, HET and EM genotypes (G-->A transition at intron 3/exon 4 and base pair deletion in exon 5) revealed no significant differences between the menorrhagia and SCC groups. Frequency distributions in the menorrhagia group, however, were significantly different (P < 0.04) from those in the low- and high-grade CIN groups. Thus, the proportion of EM was significantly larger (P < 0.03) and of HET generally lower. We found that the frequency of GSTM1 null in the menorrhagia and case groups was not significantly different. Interactive effects of enzyme genotypes with cigarette smoking were studied by comparing the multinomial frequency distributions of CYP2D6 EM/GSTM1 null/smoking over mutually exclusive categories. These showed no significant differences between the menorrhagia group and SCC or low-grade CIN groups. The frequency distribution in high-grade CIN, however, was significantly different to that in the menorrhagia group and in both SCC and low-grade CIN groups. This study was identified, for the first time, an inherited characteristic in women with high-grade CIN who appear to be at reduced risk of SCC. Thus, women with CYP2D6 EM who smoke have increased susceptibility to high-grade CIN but are less likely to progress to SCC, possibly because they effectively detoxify an unidentified chemical involved in mediating disease progression. PMID:7917923

  15. Web Spoofing: An Internet Con Game

    NSDL National Science Digital Library

    Balfanz, Dirk .

    1996-01-01

    The Safe Internet Programming group at the Princeton University Department of Computer Science in 1996 published a paper on the practice known as "web spoofing," through which an attacker intervenes between an end-user browsing the Web and real Web sites. The attacker sets up a shadow copy of the Web, and as users request pages from sites they will receive pages from the attacker's site instead. This process also enables attackers to gather data (possibly credit card numbers, etc.) submitted through bogus web forms. The nine-page paper describes how the con game works and suggests remedies. The article is available in PostScript, compressed PostScript, Microsoft Word, and zipped Microsoft Word format. Unfortunately, it is not available online as HTML.

  16. Recent developments in human biomonitoring: non-invasive assessment of target tissue dose and effects of pneumotoxic metals

    PubMed Central

    Mutti, A.; Corradi, M.

    2006-01-01

    Summary Tobacco smoke and polluted environments substantially increase the lung burden of pneumotoxic chemicals, particularly pneumotoxic metallic elements. To achieve a better understanding of the early events between exposure to inhaled toxicants and the onset of adverse effects on the lung, the characterization of dose at the target organ would be extremely useful. Exhaled breath condensate (EBC), obtained by cooling exhaled air under conditions of spontaneous breathing, is a novel technique that could provide a non-invasive assessment of pulmonary pathobiology. Considering that EBC is water practically free of interfering solutes, it represents an ideal biological matrix for elemental characterization. Published data show that several toxic metals and trace elements are detectable in EBC, raising the possibility of using this medium to quantify the lung tissue dose of pneumotoxic substances. This novel approach may represent a significant advance over the analysis of alternative media (blood, serum, urine, hair), which are not as reliable (owing to interfering substances in the complex matrix) and reflect systemic rather than lung (target tissue) levels of both toxic metals and essential trace elements. Data obtained among workers occupationally exposed to either hard metals or chromium (VI) and in smokers with or without chronic obstructive pulmonary disease (COPD) are reviewed to show that – together with biomarkers of exposure – EBC also allows the simultaneous quantification of biomarkers of effect directly sampled from the epithelial lining fluid, thus providing novel insights on both kinetic and dynamic aspects of metal toxicology. Riassunto «Recenti sviluppi nel biomonitoraggio umano: valutazione non invasiva della dose a livello dell’organo bersaglio e degli effetti pneumotossici». L’esposizione cronica a fumo di tabacco ed ad altri inquinati ambientali determina un accumulo polmonare di sostanze pneumotossiche, soprattutto metalli. Allo scopo di ottenere una migliore comprensione dei meccanismi attraverso i quali i tossici inalati inducono un danno polmonare, la valutazione della dose a livello dell’organo bersaglio, in questo caso il polmone, potrebbe essere molto utile. Il condensato dell’aria espirata (CAE) è un fluido ottenuto raffreddando l’aria esalata durante la respirazione a volume corrente ed è una nuova tecnica che può fornire una valutazione della patobiologia polmonare. Il CAE è formato quasi completamente da acqua, quindi rappresenta una matrice biologica ideale per la determinazione d’elementi metallici. Dati presenti in letteratura dimostrano come nel CAE si possono dosare vari metalli tossici ed elementi di transizione, permettendo quindi di proporre questa matrice per la quantificazione della dose al bersaglio di sostanze pneumotossiche. La quantificazione della dose al bersaglio consente di avere informazioni aggiuntive rispetto a quelle ottenute con i tradizionali metodi di monitoraggio biologico in lavoratori esposti, che generalmente consentono di stimare la dose sistemica, ma non l’esposizione delle vie respiratorie ad inquinanti aerodispersi né la frazione trattenuta nel polmone, verosimilmente implicata nella patologia infiammatoria e degenerativa a livello polmonare. In questa breve rassegna sono discussi i dati ottenuti in lavoratori professionalmente esposti a metalli duri ed in fumatori con o senza bronco-pneumopatica cronica ostruttiva (BPCO), per mostrare come il CAE – oltre agli indicatori di esposizione – consente di valutare indicatori di effetto campionati direttamente dal film che riveste le vie respiratorie, fornendo quindi nuovi spunti per meglio comprendere sia gli aspetti cinetici che quelli dinamici della tossicologia dei metalli. PMID:17017350

  17. Detection of a small molecular species of human chorionic gonadotropin in the urine of patients with carcinoma of the cervix and cervical intraepithelial neoplasia: comparison with other assays for human chorionic gonadotropin and its fragments.

    PubMed

    Norman, R J; Buck, R H; Aktar, B; Mayet, N; Moodley, J

    1990-05-01

    A low-molecular-weight glycoprotein containing sequences of the beta subunit of human chorionic gonadotropin (hCG) has been found in the urine of patients with carcinoma of the cervix using an immunoradiometric assay. This fragment has chromatographic and immunological identity with hCG beta core. This molecule was present in 52 to 77% of all patients with invasive disease, while between 11 and 27% of patients with cervical intraepithelial neoplasia (CIN) also exhibited significant hCG beta-core immunoactivity. Few patients had either a positive assay for intact hCG or a positive assay directed at an epitope on the beta subunit (beta-hCG radioimmunoassay) in serum. However, between 17 and 40% of patients with invasive disease were positive for free beta-subunit immunoactivity in the blood. The origin of the beta-core immunoactivity in the urine is uncertain; while tumor production cannot be excluded, it is possible that the molecule originates from renal metabolism of small quantities of the beta subunit of hCG. Regardless of the source of the molecule, hCG beta core is a far more sensitive marker of hCG production by tumors than is serum hCG. PMID:2344970

  18. Incidence of therapy-related myeloid neoplasia after initial therapy for chronic lymphocytic leukemia with fludarabine-cyclophosphamide versus fludarabine: long-term follow-up of US Intergroup Study E2997

    PubMed Central

    Neuberg, Donna; Flinn, Ian W.; Grever, Michael R.; Lazarus, Hillard M.; Rowe, Jacob M.; Dewald, Gordon; Bennett, John M.; Paietta, Elisabeth M.; Byrd, John C.; Hussein, Mohamad A.; Appelbaum, Frederick R.; Larson, Richard A.; Litzow, Mark R.; Tallman, Martin S.

    2011-01-01

    Chemotherapy-related myeloid neoplasia (t-MN) is a significant late toxicity concern after cancer therapy. In the randomized intergroup phase 3 E2997 trial, initial therapy of chronic lymphocytic leukemia with fludarabine plus cyclophosphamide (FC) compared with fludarabine alone yielded higher complete and overall response rates and longer progression-free, but not overall, survival. Here, we report t-MN incidence in 278 patients enrolled in E2997 with a median 6.4-year follow-up. Thirteen cases (4.7%) of t-MN occurred at a median of 5 years from initial therapy for chronic lymphocytic leukemia, 9 after FC and 4 after fludarabine alone. By cumulative incidence methodology, rates of t-MN at 7 years were 8.2% after FC and 4.6% after fludarabine alone (P = .09). Seven of the 9 cases of t-MN after FC occurred without additional therapy. Abnormalities involving chromosomes 5 or 7 were found in 10 cases, which suggests alkylator involvement. These data suggest that FC may induce more t-MN than fludarabine alone. PMID:21803850

  19. ConChord: Cooperative SDSI Certificate Storage and Name Resolution

    Microsoft Academic Search

    Sameer Ajmani; Dwaine E. Clarke; Chuang-hue Moh; Steven Richman

    2002-01-01

    We present ConChord, a large-scale certicate distribution system built on a peer-to-peer distributed hash table. ConChord provides load-balanced storage while eliminating many of the administrative dif- culties of traditional, hierarchical server architectures. ConChord is specically designed to support SDSI, a fully-decentralized public key infrastructure that allows principals to dene local names and link their namespaces to delegate trust. We discuss

  20. A ConA-like lectin from Dioclea guianensis Benth. has antifungal activity against Colletotrichum gloeosporioides, unlike its homologues, ConM and ConA.

    PubMed

    Araújo-Filho, José H; Vasconcelos, Ilka M; Martins-Miranda, Aparecida S; Gondim, Darcy M F; Oliveira, José T A

    2010-04-14

    This study reports on the antifungal activity of Dgui, a ConA-like lectin from Dioclea guianensis seeds. Dgui inhibited conidial germination but not mycelial growth of Colletotrichum gloeosporioides. The lectins ConA and ConM from Canavalia ensiformis and Canavalia maritima, respectively, share high levels of amino acid sequence similarity (>84%) with Dgui and have the same specificity toward glucose/mannose but had no effect on the fungus. Fluorescence microscopy showed that both Dgui and ConM bind to C. gloeosporioides ungerminated conidia. However, Dgui did not bind to C. gloeosporioides germinated conidia and germ tubes and was not inhibitory to mycelial growth. Because only Dgui inhibited germination of the fungus, C. gloeosporioides conidia might have surface-specific germination targets recognized by Dgui but not by its homologues, ConM and ConA. Therefore, Dgui is a candidate for biotechnological approaches for improving the resistance of various nutritionally and commercially important crops that are affected by C. gloeosporioides. PMID:20201549

  1. Breath Analysis Science at PittCon 2012, Orlando, Florida

    EPA Science Inventory

    Breath analysis science was featured in three organized sessions at this year?s Pittsburgh Conference and Exposition, or ?PittCon 2012? (http://www.pittcon.org/). As described in previous meeting reports, PittCon is one of the largest international conferences for analytical chem...

  2. -okfl ^ ORNL/CON-172 Linear Harmonic Analysis of Free-

    E-print Network

    Oak Ridge National Laboratory

    -okfl ^ ORNL/CON-172 OAK RIDGE NATIONAL LABORATORY Linear Harmonic Analysis of Free- Piston. #12;ORNL/CON-172 Engineering Technology Division* LINEAR HARMONIC ANALYSIS OF FREE-PISTON STIRLING/dynamic problem that is associated with a free-piston Stirling engine (FPSE). The governing equations

  3. VARIABILIDAD DE UN DIFRASISMO MAYA : EMPAREJAMIENTOS CON CH'AB

    E-print Network

    Boyer, Edmond

    VARIABILIDAD DE UN DIFRASISMO MAYA : EMPAREJAMIENTOS CON CH'AB JEAN-MICHEL HOPPAN* Y EMILIE por el análisis de la literatura maya previa al período de la conquista española1 aparece en forma de, propio de los mayas, consiste en el emparejamiento de un glifo que se lee ch'ab con otro que se lee ak

  4. Clave de determinacin de los Heliconiinae con rayas anaranjadas

    E-print Network

    Joron, Mathieu

    : mathieu.joron@ed.ac.uk 1. a. Abdomen con puntos amarillos y gruesos en los costados (intrasegmentales..............................................................................2 2. a. Abdomen con anillos intersegmentales amarillos........................Heliconius xanthocles relativamente pequeña, abdomen no muy largo. Ciertas razas no tienen color anaranjado en la cara dorsal

  5. Clinical Implication of p16, Ki-67, and Proliferating Cell Nuclear Antigen Expression in Cervical Neoplasia: Improvement of Diagnostic Accuracy for High-grade Squamous Intraepithelial Lesion and Prediction of Resection Margin Involvement on Conization Specimen

    PubMed Central

    Kim, Tae Hun; Han, Jee Hye; Shin, Eun; Noh, Jae Hong; Kim, Hee Seung; Song, Yong Sang

    2015-01-01

    Background: Cervical intraepithelial neoplasia (CIN) grading is subjective and affected by substantial rates of discordance among pathologists. Although the use of p16INK4a (p16) staining has been proven to improve diagnostic accuracy for high-grade squamous intraepithelial lesion (HSIL), the clinical evidence for use of Ki-67 and proliferating cell nuclear antigen (PCNA) is insufficient to make an independent recommendation for use, alone or in combination. The primary objective was to evaluate clinical utility of Ki-67 and PCNA in combination with p16 in diagnosing HSIL. Also, we assessed the correlation between expressions of three biomarkers and resection margin status of conization specimen. Methods: The expressions of p16, Ki-67, and PCNA were evaluated by immunohistochemical methods in 149 cervical tissues encompassing 17 negative lesion, 31 CIN 1, 25 CIN 2, 41 CIN 3, and 35 invasive squamous cell carcinoma. The immunohistochemical staining results were classified into four grades: 0, 1+, 2+ and 3+. Results: The expression of three biomarkers was positively associated with CIN grade. Ki-67 immunostaining did not increase the accuracy of HSIL diagnosis when combined with p16 immunostaining compared with p16 immunostaining alone. In contrast, combining the staining results for p16 and PCNA (p16 = 3+ and PCNA ?2+) increased its specificity (66.7% vs. 75.0%, P = 0.031) without decrease of its sensitivity (98.7% vs. 98.7%) for diagnosis of CIN 3 and more sever lesion. Subgroup analysis for conization specimen with CIN 2 and CIN 3 showed that positive Ki-67 immunostaining was an independent risk factor for predicting resection margin positivity (odds ratio = 6.52, 95% confidence interval 1.07–39.64). Conclusions: We found that the combined use of p16 and PCNA immunostaining enhanced diagnostic accuracy for HSIL. Positive Ki-67 immunostaining was associated with incomplete excision. PMID:25853106

  6. The pros and cons of plant estrogens for menopause.

    PubMed

    Bedell, Sarah; Nachtigall, Margaret; Naftolin, Frederick

    2014-01-01

    Concerns pertaining to the risk of estrogen exposure through HT have prompted an increase in the use of natural alternatives. Phytoestrogens may provide postmenopausal women with a practical alternative and many women have already begun to utilize phytoestrogen supplements. However, research regarding the efficacy of phytoestrogens as a hormone therapy alternative has been previously pessimistic or questionable at best. This review scrutinizes the most current research regarding the efficacy of three types of phytoestrogens, isoflavones, lignans and coumestans, and their specific effect on the reduction of climacteric symptoms, specifically vasomotor symptoms, vaginal atrophy, insomnia and osteoporosis. A discussion of the research pertaining to the relative safety of each phytoestrogen in terms of breast and endometrial health is also included. Overall, current research demonstrates that phytoestrogens are effective in reducing the intensity of hot flushes, and some phytoestrogen combinations result in a decreased frequency. Certain phytoestrogens have also been shown to decrease vaginal atrophy, improve sleep and cognition, and positively affect bone health. Even though initial research was generally unconvincing, the more recent evidence reviewed here is rather positive. In terms of safety and reports of adverse reactions, trials have not shown an increase in breast cancer risk or increase in endometrial hyperplasia following phytoestrogen use, but trials explicitly designed to find neoplasia have not been reported. Moreover, unlike hormone therapy, lignans may not increase clotting risk in postmenopausal women, thus supplements may serve as a treatment option for patients who have contraindications to hormone therapy. Phytoestrogens may provide a safe and partially effective alternative to HT. However, because research regarding phytoestrogens is relatively new, pharmaco-vigilence is still required, as these products are not yet FDA-approved. This article is part of a Special Issue entitled 'Phytoestrogens'. PMID:23270754

  7. iCons, 2011 Alzheimers and Aluminum: Lesson Plan

    E-print Network

    Auerbach, Scott M.

    © iCons, 2011 Alzheimers and Aluminum: Lesson Plan Handouts to explore mechanistic link between Alzheimer's and aluminum 5. Brief proposal expanding Points to Aluminum's Link With Alzheimer's Disease" from 1989. Provide handout

  8. Each year Minnesota Agricultural Experiment Station scientists con-

    E-print Network

    Minnesota, University of

    October. Plots at Rosemount and Roseau had hail at mid-season, which reduced yields. Tables 1 to 4 provide, Rosemount, Stewart, Wabun and Waseca. Tables 15 to 17 present SCN infor- mation from greenhouse tests con

  9. ConFunc - functional annotation in the twilight zone

    Microsoft Academic Search

    Mark N. Wass; Michael J. E. Sternberg

    2008-01-01

    Motivation: The success of genome sequencing has resulted in many protein sequences without functional annotation. We present ConFunc, an automated Gene Ontology (GO)-based protein function prediction approach, which uses conserved residues to generate sequence profiles to infer function. ConFunc split sets of sequences identified by PSI-BLAST into sub-alignments according to their GO annotations. Conserved residues are identified for each GO

  10. Breath analysis science at PittCon 2012, Orlando, Florida

    Microsoft Academic Search

    Joachim D Pleil; Matthew A Stiegel; Tzipporah M Kormos; Jon R Sobus

    2012-01-01

    BackgroundBreath analysis science was featured in three organized sessions at this year's Pittsburgh Conference and Exposition, or 'PittCon 2012' (http:\\/\\/www.pittcon.org\\/). As described in previous meeting reports, PittCon is one of the largest international conferences for analytical chemistry and instrumentation, typically attracting about 20 000 attendees and 1000 commercial exhibitors (Pleil 2010, 2011). This year the conference was held in Orlando,

  11. Crystal structure of a lectin from Canavalia maritima (ConM) in complex with trehalose and maltose reveals relevant mutation in ConA-like lectins

    Microsoft Academic Search

    Plínio Delatorre; Bruno A. M. Rocha; Carlos A. A. Gadelha; Tatiane Santi-Gadelha; João B. Cajazeiras; Emmanuel P. Souza; Kyria S. Nascimento; Valder N. Freire; Alexandre H. Sampaio; Walter F. Azevedo; Benildo S. Cavada

    2006-01-01

    The crystal structure of Canavalia maritima lectin (ConM) complexed with trehalose and maltose revealed relevant point mutations in ConA-like lectins. ConM with the disaccharides and other ConA-like lectins complexed with carbohydrates demonstrated significant differences in the position of H-bonds. The main difference in the ConM structure is the replacement of Pro202 by Ser202, a residue that promotes the approximation of

  12. Polymerase chain reaction and deoxyribonucleic acid-sequencing based study on distribution of human papillomavirus 16/18 among histopathological types of cervical intra-epithelial neoplasia and primary invasive cervical carcinoma: A scenario in North Bengal, India

    PubMed Central

    Ghosh, Prithwijit; Ghosh, Damayanti Das; Majumdar (Giri), Amita; Sengupta, Sharmila; Das, Chandana; Mukhopadhyay, Indranil

    2014-01-01

    Introduction: Human papillomavirus (HPV) types 16/18 are reportedly most common in cervical cancer (CaCx) with geographical variation of genotypes. HPV16 predominates both in squamous cell carcinoma (SCC) and adenocarcinoma in India, contrary to reported global predominance of HPV18 in the latter. Our study was aimed to determine the occurrence of HPV16/18 among histopathological types of cervical intra-epithelial neoplasia (CIN) and invasive CaCx from North Bengal, India and to identify any major deviation from the known Indian scenario of distribution of HPV16/18 genotypes in cases of SCC and adenocarcinoma. Materials and Methods: This was a retrospective, cross-sectional, case-only type of study, in which 40 cases were histopathologically diagnosed as CIN/CaCx, on which polymerase chain reaction (PCR), deoxyribonucleic acid (DNA)-sequencing and bioinformatics by basic search local alignment tool were performed for HPV-genotyping. Statistical Analysis: The distribution of HPV genotypes among cases of SCC and adenocarcinoma was compared by Fisher's exact-test. Results: HPV was detected in 97.5% (39/40) cases. HPV16-infected cases (32/39; 82.05%) predominated over HPV18-infected ones (7/39; 17.95%). However, HPV18-only infection was significantly (P = 0.0045, one-sided Fisher's exact test) more among adenocarcinoma (3/4; 75%) than SCC (2/26; 7.69%) contrary to HPV16-only infection (SCC = 24/26, 92.31%; adenocarcinoma = 1/4; 25%) whereas both CIN3 cases were HPV16-positive. Conclusion: Predominance of HPV18 over HPV16 in cases of adenocarcinoma in this region was contrasting to that of earlier Indian studies suggesting research on HPV18 related cervical carcinogenesis. PCR and DNA-sequencing could prove to be highly effective tools in HPV detection and genotyping. The study reported HPV16/18 infection in almost 98% of the cases, the knowledge about which might prove useful in future population based studies on HPV genotyping and designing of appropriate HPV-vaccines for this region. PMID:24672201

  13. Association between MTHFR C677T, MTHFR A1298C and MS A2756G polymorphisms and risk of cervical intraepithelial neoplasia II/III and cervical cancer: a meta-analysis.

    PubMed

    Zhu, Jie; Wu, Lei; Kohlmeier, Martin; Ye, Fangli; Cai, Wei

    2013-09-01

    Numerous case-control studies on the association between polymorphisms of key genes involved in methionine remethylation [methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS)] and the susceptibility of cervical intraepithelial neoplasia (CIN) and cervical cancer have provided inconclusive results. The aim of the present meta-analysis was to determine the effects of two MTHFR (C677T and A1298C) and one MS gene polymorphism (A2756G) on the risk of CIN II/III or cervical cancer. Relevant data were retrieved following a systematic search in PubMed, Web of Science, MEDLINE and Wanfang Data up to November 2012. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated from eligible studies by meta-analysis with subgroup analyses stratified by ethnicity. A total of 13 studies with 1,936 cases and 2,858 controls were included in the present meta?analysis. An increased risk of cervical cancer was found in Asian women with the MTHFR 677T allele (TT vs. CC: OR=1.41, 95% CI=1.07?1.86, P=0.01; TT vs. CC+CT: OR=1.38, 95% CI=1.08-1.75, P=0.008), while a decreased risk was observed in Caucasian women (TT vs. CC: OR=0.65, 95% CI=0.45-0.93, P=0.02; TT+CT vs. CC: OR=0.7, 95% CI=0.58-0.86, P=0.0005). No effects of MTHFR C677T polymorphism on CIN II/III risk and MTHFR A1298C or MS A2756G polymorphisms on cervical cancer risk were detected. The sensitivity analysis suggested stability of this meta-analysis and no publication bias was detected. The MTHFR 677T allele may enhance the risk of cervical cancer in the Asian female population and play a protective role in Caucasian females. However, limited association is suggested between MTHFR A1298C and MS A2756G polymorphisms with cervical tumorigenesis. PMID:23864153

  14. PROPUESTA DEL PROGRAMA Este grupo cuenta con 30 personas con un fin comun, el aporte al desarrollo de

    E-print Network

    de la matem´atica, en particular de los sistemas din´amicos en el Uruguay. Se ha separado la parte´ian particicipado de la pr´actica de la matem´atica en el Uruguay con un grupo de j´ovenes estudiantes que hab actividad, este grupo se ha consolidado como el mayor grupo de estudio de la matem´atica en el Uruguay, con

  15. Mechanisms of Obesity-induced Gastrointestinal Neoplasia

    PubMed Central

    Eusebi, Leonardo H.; Ricciardiello, Luigi; Patidar, Kavish; Sanyal, Arun J.

    2014-01-01

    Obesity is among the fastest growing diseases worldwide; treatment is inadequate and associated disorders, including gastrointestinal cancers, have high morbidity and mortality. An increased understanding of the mechanisms of obesity-induced carcinogenesis is required to develop methods to prevent or treat these cancers. We review the mechanisms of obesity-associated colorectal, esophageal, gastric, and pancreatic cancers and potential treatment strategies. PMID:24315827

  16. [Frantz tumor: a pancreatic pseudopapillary solid neoplasia].

    PubMed

    Llatas, Juan; Palomino, Américo; Frisancho, Oscar

    2011-01-01

    We report a case of solid and papillary epithelial neoplasm of the pancreas in a 35-year-old female. She presented with epigastric pain and weight loss, these symptoms developed 3 months before. Physical examination revealed mild pain on deep palpation of mesogastrium, without palpable abdominal mass; rest of the examination was normal. The laboratory data showed hemoglobin 13.3 gr/dl; WBC, platelets, blood coagulation test, blood biochemistry, electrolytes, liver function test were normals. Urine test: 14-16 leukocytes per field, urocultive negative, Ca 19.9: 21.2 (0-37). Her serology for hydatic cyst (arc V and inmunoblot) was negative.Abdominal ultrasound showed between body and tail of the pancreas a solid hypoechoic image. In abdominal CT was detected in the body of the pancreas the presence of two hypodense lesions with average density of 25 UH and mediate 50 and 22 mm in diameter. The nuclear magnetic resonance imaging identified the body of the pancreas, bilobed cyst of 45 and 25 mm in diameter, with isointensity in T1, hyperintensity in T2, unchanged after fat saturation, with peripheral contrast enhancement. Operation findings showed a cystic tumor in the body of pancreas without signs of infiltration to other organs. Therefore, distal pancreatectomy and splenectomy were carried out. The tumor was 60 x 46 x 35 mm and a half oval, encapsulated, irregular consistency, which the court left necrotic-looking material flow. The study showed the pattern typical hyalinized perivascular pseudopapillary with stroma, in immunohistochemical studies positive immunoreactivity was observed in cyclin D1 and progesterone receptor, also were positive for vimentin, enolase neuronoespecífica and CD-56. The proliferation index assessed by Ki-67 was less than 1% in tumor cells. The solid pseudopapillary neoplasm of the pancreas is a low-grade malignancy, relatively rare, representing between 0.9 and 2.7% of all pancreatic malignancies. It mainly affects young women (89% of cases), with a mean age at diagnosis of 28 years. Most have specific symptoms related to intra-abdominal mass and more than one third are usually discovered incidentally. PMID:21544157

  17. Mechanisms of obesity-induced gastrointestinal neoplasia.

    PubMed

    Alemán, José O; Eusebi, Leonardo H; Ricciardiello, Luigi; Patidar, Kavish; Sanyal, Arun J; Holt, Peter R

    2014-02-01

    Obesity is among the fastest growing diseases worldwide; treatment is inadequate, and associated disorders, including gastrointestinal cancers, have high morbidity and mortality. An increased understanding of the mechanisms of obesity-induced carcinogenesis is required to develop methods to prevent or treat these cancers. In this report, we review the mechanisms of obesity-associated colorectal, esophageal, gastric, and pancreatic cancers and potential treatment strategies. PMID:24315827

  18. INDUCED AND SPONTANEOUS NEOPLASIA IN ZEBRAFISH.

    EPA Science Inventory

    To address the potential of zebrafish as a cancer model, it is important to determine the susceptibility of zebrafish to tumors, and to compare zebrafish tumors with human tumors. To determine whether the commonly-used germ line mutagen, ethylnitrosourea (ENU) induces tumors, we ...

  19. Spectral karyotyping (SKY) in hematological neoplasia

    NASA Astrophysics Data System (ADS)

    Preiss, Birgitte S.; Pedersen, Rikke K.; Kerndrup, Gitte B.

    2001-07-01

    From November 1, 1997 till November 1, 2000 we have investigated 204 cases of acute myeloid leukemia (AML) (nequals95), acute lymphatic leukemia (ALL) (nequals40), myelodysplastic syndrome (MDS) (nequals11), chronic myeloid leukemia (CML) (nequals9), chronic lymphatic leukemia (CLL) (nequals4) and non-Hodgkin lymphoma (NHL) (nequals45) cytogenetically, using G-band analysis and spectral karyotyping (SKY). By SKY we were able to detect the abnormal clones in all cases but 9. In the G-band preparations these cases showed very few abnormal mitoses. The SKY either extended or confirmed the G-band findings in 94% of those with an abnormal karyotype. Cryptic translocations (translocations not suspected from the G-band karyotype) were found in 71 cases (26 AML, 9 ALL, 5 MDS, 2 CLL and 29 NHL). We find SKY a powerful adjuvant diagnostic tool that does not compromise one of the advantages of karyotyping techniques, the analysis of the entire genome which, in contrast to molecular biological techniques, still leave the possibility to get mroe answers than questions posed.

  20. REMBRANDT - Repository for Molecular Brain Neoplasia Data

    Cancer.gov

    REMBRANDT data portal will be retired on or after June 1st, 2015. All data currently hosted in REMBRANDT, including microarray gene expression, copy number, and clinical data, has been migrated to the Georgetown Database of Cancer GDOC, a knowledge discovery platform that will allow continued support for the community's efforts to mine these data. Click here for more information about REMBRANDT retirement.

  1. REMBRANDT - Repository for Molecular Brain Neoplasia Data

    Cancer.gov

    A monitor resolution of greater than 800x600 is highly recommended. To view the online tutorials you may need to install the Flash Plug-in for your browser. Please click the "Flash Player" logo to go to the Macromedia website to download this free plug-in.

  2. A Clinical Perspective on Gastric Neuroendocrine Neoplasia

    Microsoft Academic Search

    Ben Lawrence; Mark Kidd; Bernhard Svejda; Irvin Modlin

    2011-01-01

    The incidence of gastric neuroendocrine tumors (NETs) has increased exponentially based on widespread use of endoscopy and\\u000a a greater pathological awareness of the condition. A key concern is the potential association with hypergastrinemia induced\\u000a by proton pump inhibitor administration. Previous confusion regarding diagnosis and therapy has been diminished by a series\\u000a of international consensus statements defining the biology and management

  3. Laser immunotherapy of canine and feline neoplasia

    NASA Astrophysics Data System (ADS)

    Woods, J. P.; Bartels, Kenneth E.; Davidson, Ellen B.; Ritchey, Jerry W.; Lehenbauer, Terry W.; Nordquist, Robert E.; Chen, Wei R.

    1998-07-01

    The major cause of treatment failure in human and veterinary cancer patients is tumor invasion and metastasis. The inability of local therapy (surgery, radiation, photodynamic therapy) to eradicate a metastatic cancer presents a challenge in the therapy of residual or micrometastatic disease. Because of its local therapy limitations, chromophore-enhanced selective photothermal laser treatment has been augmented with a superimposed laser-induced systemic photobiological reaction, laser immunotherapy. Laser immunotherapy is a novel cancer treatment consisting of: (1) a laser in the infrared wavelength range (i.e. 805 nm solid state laser); (2) a photosensitizer of the corresponding absorption peak [i.e. indocyanine green (ICG)]; and (3) an immunoadjuvant [i.e. glycated chitosan gel (GCG)]. The intratumor injection of the photosensitizer (ICG) and immunoadjuvant (GCG) solution is followed by noninvasive laser irradiation. The laser energy causes tumor cell destruction by photothermal interaction to reduce the tumor burden and at the same time exposes tumor antigens. The immunoadjuvant concomitantly stimulates the host to mount a systemic anti-tumor immune response against the remaining cells of the tumor and to induce a long-term, tumor-specific immunity. This study investigates the feasibility of utilizing laser immunotherapy as an adjunctive therapy for the control of feline fibrosarcoma in future.

  4. Inflammatory bowel disease and neoplasia in children.

    PubMed

    Rufo, Paul A

    2014-01-01

    Advances in our understanding of the pathophysiology of ulcerative colitis and Crohn's disease have led to the widespread use of increasingly potent immunosuppressive therapies. This has greatly benefited the majority of patients with inflammatory bowel disease (IBD) and has resulted in improved overall clinical outcomes and quality of life. However, a growing body of data now indicates that long-term use of these agents may at the same time place patients at risk for a number of adverse effects, including colorectal and skin cancer, as well as lymphoma. Children and adolescents may be at particular cumulative risk for the development of these malignancies as a result of their young age at diagnosis, often increased disease extent and severity, and greater lifetime exposure to immunosuppressive agents. More recent epidemiologic studies are now identifying specific genetic and treatment-related factors that may place patients at increased risk for the development of IBD-related cancer. Improved understanding of these risk factors should contribute to a more rational approach to the pharmacologic management of children and young adults with IBD. Similarly, clinicians will be better able to counsel patients about the risks and benefits associated with specific therapies and develop improved monitoring guidelines to reduce the incidence of these rare but often severe oncologic complications. PMID:24969294

  5. Endocrinopathies in Survivors of Childhood Neoplasia

    PubMed Central

    Barnes, Nicole; Chemaitilly, Wassim

    2014-01-01

    Advancements in cancer treatments have increased the number of survivors of childhood cancers. Endocrinopathies are common complications following cancer therapy and may occur decades later. The objective of the current review is to address the main endocrine abnormalities detected in childhood cancer survivors including disorders of the hypothalamic-pituitary axis, thyroid, puberty, gonads, bone, body composition, and glucose metabolism. PMID:25295241

  6. Intestinal cancer : linking infection, inflammation and neoplasia

    E-print Network

    Sohn, Jane Joo-hee, 1976-

    2005-01-01

    Cancer is a leading cause of death in the world. Much work has been done to study the role of inflammation in carcinogenesis. One hypothesis suggests that inflammation causes oxidative stress that induces damage to cellular ...

  7. Genetics Home Reference: Multiple endocrine neoplasia

    MedlinePLUS

    ... the body's network of hormone-producing glands (the endocrine system). Hormones are chemical messengers that travel through the ... benign ; calcium ; cancer ; carcinoma ; cell ; cell division ; DNA ; endocrine system ; familial ; gene ; hormone ; hyperparathyroidism ; hypertension ; inherit ; inheritance ; inherited ; ...

  8. Blond Blintz Bulletin Special Zebra-Con Edition 1

    E-print Network

    Multiple Contributors

    1979-01-01

    CON REPOR by Paulie Gi lmore Zebra Con Has hel d at t he Helrose Park Hol iday Inn . July 21. 28, and 29. and ~ras attended by about 60 of t he 65 people scheduled to come. ~re als Here proudly .... upported by 35 others. I suppose should take...'s over for now. Time to go ome ,:r .t .: GHOST CRIES by Febra Jean Ulch [i J]otty llil]ierison It was a quiet and peaceful place, nob like a park-than a cenetery' A s,nrff-ero;o "t=oapf"'rpful;;h;A ,i.-C*ripf"d ,gravesi.*- . Thpre wgre...

  9. Dia internacional de la dona Exposicin "Trabajo social con las mujeres" Pgina 1 de 2

    E-print Network

    Escolano, Francisco

    al.]. El apoyo social de mujeres solas con responsabilidad familiar: un estudio con madres usuariasDia internacional de la dona ­ Exposición "Trabajo social con las mujeres" Página 1 de 2 SELECCIÓN DE LIBROS PARA LA EXPOSICIÓN "TRABAJO SOCIAL CON LAS MUJERES" Alemán Bracho, Carmen, García Serrano

  10. Una gua de navegacin para las familias de Wisconsin con nios y

    E-print Network

    Wisconsin at Madison, University of

    Una guía de navegación para las familias de Wisconsin con niños y jóvenes con necesidades especiales de salud y discapacidades. GUÍA DE RECURSOS #12;#12;1 GUÍA DE RECURSOS Una guía de navegación para las familias de Wisconsin con niños y jóvenes con necesidades especiales de salud y discapacidades

  11. Detail of conning tower atop the submarine. Note the wire ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail of conning tower atop the submarine. Note the wire rope wrapped around the base of the tower, which may have been used in an attempt to pull the submarine offshore. - Sub Marine Explorer, Located along the beach of Isla San Telmo, Pearl Islands, Isla San Telmo, Former Panama Canal Zone, CZ

  12. FUNCIONES CONTINUAS CON MAXIMOS LOCALES DENSOS GODOFREDO IOMMI

    E-print Network

    Iommi, Godofredo

    FUNCIONES CONTINUAS CON M´AXIMOS LOCALES DENSOS GODOFREDO IOMMI Abstract. En estas notas estudiaremos la clase de funciones continuas que poseen m´aximos estrictos locales en un conjunto denso. Siguiendo el trabajo de Posey y Vaughan construiremos un ejemplo expl´icito de una funci´on que pertenece

  13. Cómo hacer las gestiones con su plan de salud

    Cancer.gov

    Hay formas de saber si su plan de salud cubre los costos de atención médica de rutina durante un estudio clínico. Esta información puede servirle para saber con quién comunicarse para solicitar ayuda, preguntas que puede hacer y la información que debe recoger y guardar si decide participar en un estudio clínico.

  14. On Invariant Con guration of a Three-Fingered Grasp

    E-print Network

    Payandeh, Shahram

    using screw theory and inner product spaces. The results are shown to present themselves as an elegant advantage of the grasp con guration and the screw geometry. However, their method did not take advantage of the fundamental coordinate free property of screw systems and it was rather an algebraic approach. Various methods

  15. Real-time Coastal Observation Network (ReCON)

    E-print Network

    Real-time Coastal Observation Network (ReCON) The need for development of regional coastal. High bandwidth, wireless Ethernet-based system. Real-time, secure data access. Universal sensor real-time whole water column observations of physical, chemical, and biological variables. The Re

  16. performances, lectures, demonstra-tions, and workshops exploring con-

    E-print Network

    Miranda, Eduardo Reck

    promoted three major concerts in three different spaces. The opening event brought together the jazz of Frances Lynch, one of the few international singers to have worked closely with composers of electro- acoustic music. Her dramatic and most commited performances con- tinue to inspire many composers, not least

  17. Desarrollo costero y conservacin marina en armona con las personas

    E-print Network

    Richner, Heinz

    también explotan los recursos del mar pero que no se preocupan por el desarrollo sostenible. LaDesarrollo costero y conservación marina en armonía con las personas Los debates sobre la conservación marino costera El desarrollo y conservación de las costas de Costa Rica es concebido de formas

  18. 2006 Annual Report TAble of ConTenTS

    E-print Network

    Security Management and Assistance Security Testing and Metrics Security Technology Security Research, tests, and validation programs to promote, measure, and validate security in systems and services. WeComputer Security Division 2006 Annual Report #12;TAble of ConTenTS Welcome Letter Division

  19. Preserving con dentiality when sharing medical database the Cellsecu system

    E-print Network

    Chen, Sheng-Wei

    named Cellsecu that maintains not only the anonymity but also the con dentiality of each cell identi ers, such as name, address, and phone numbers. Simply removing all the explicit iden- ti ers, the existence of such database would enable researchers to track certain diseases as well as to patients

  20. Stochastic Con nement of Rossby Waves by Fluctuating Eastward Flows

    E-print Network

    Monahan, Adam Hugh

    Stochastic Con#12;nement of Rossby Waves by Fluctuating Eastward Flows Adam Hugh Monahan, Lionel axis - the so-called beta e#11;ect [20]. These planetary, or Rossby, waves have played an important of stationary Rossby waves on zonally- inhomogeneous ows such as the climatological boreal winter 300 mb ow

  1. con Diabetes Su diabetes s se puede controlar!

    E-print Network

    Do Well, Be Well con Diabetes ¡Su diabetes sí se puede controlar! Educational programs of the Texas, and the County Commissioners Courts of Texas Cooperating. to develop diabetes self-care skills, to improve eating habits and maintain good nutrition, to increase physical activity, to prevent diabetes complications

  2. L' ABUSO DI FARMACI NEL PAZIENTE CON CEFALEA: POSSIBILI INDICATORI

    Microsoft Academic Search

    PAOLA BROGGI; SANDRO IANNACCONE; LILIANA NOVELLA; STEFANO CLERICI; ANDREA FOSSATI; LUCIO SARNO

    L'abuso di farmaci tra le persone affette da disturbi cefalalgici rappresenta un problema di notevole rilevanza clinica, sia per il Medico di Medicina Generale (MMG), che frequentemente rappresenta il primo e unico inter- faccia con il paziente cefalalgico, sia per lo specialista Neurologo, che viene chiamato alla gestione di quadri clinici talora complessi. L'assunzione eccessiva o non congrua di alcuni

  3. Precisión de las velocidades radiales obtenidas con el REOSC

    NASA Astrophysics Data System (ADS)

    González, J. F.; Lapasset, E.

    Complementando una línea de trabajo iniciada con anterioridad discutimos la estabilidad del espectrógrafo REOSC de CASLEO en DC para la medición de velocidades radiales en base al análisis de observaciones realizadas en enero y abril de 1997. En esas oportunidades obtuvimos 26 espectros de estrellas patrones y 27 espectros de 3 estrellas usadas como estrellas de referencia en nuestro programa de cúmulos abiertos. Además tomamos 26 espectros de crepúsculo con el telescopio en posiciones cubriendo el rango H=-4,+4 y ? =-90,+30. Mediante correlaciones cruzadas derivamos la velocidad de 19 órdenes en cada uno de estos espectros. En base a un análisis estadístico de los datos obtenidos discutimos la contribución de los distintos factores que afectan a la dispersión de lectura observada. En particular, la flexión del instrumento no introduciría errores significativos cuando se observa con masas de aire menores que 2.0. La dispersión de los valores de velocidad medidos para espectros de alta relación S/N de una misma estrella resultó del orden de 0.5 km/s. La comparación con los valores de velocidad publicados por distintos autores para las estrellas patrones no permite distinguir ninguna diferencia sistemática apreciable de las velocidades de CASLEO, siendo la media cuadrática de los residuos del orden de 1.0 km/s.

  4. Null alleles for salivary Concanavalin A-binding (Con A) and Po proteins at PRB2 and PRB4 loci

    Microsoft Academic Search

    E. A. Azen; E. Amberger

    1994-01-01

    Six closely linked PRP (proline-rich protein) genes code for many salivary PRPs which show frequent null variants especially. The Con polymorphism includes the different sized Con 1 and Con 2 proteins and the null Con 0 form. N-terminal amino acid sequences (60 aa) were determined on Con 1 and Con 2 proteins. From comparison of the protein sequences with those

  5. Expandiendo los límites del teatro: Una entrevista con Astrid Hadad

    E-print Network

    Alzate, Gastó n

    1997-04-01

    SPRING 1997 153 Expandiendo los límites del teatro: Una entrevista con Astrid Hadad Gastón Álzate Astrid Hadad, nacida en Chetumal, Quintana Roo (México) y de padres libaneses, es hoy en día una de las artistas más significativas dentro de un... consolidado un espacio propio. Esto se puede apreciar en el trabajo desarrollado por Jesusa Rodríguez, Liliana Felipe y la misma Astrid Hadad. Es importante anotar que existe un buen número de artistas que ha venido desarrollando trabajos paralelos, como es...

  6. Vibrational and rotational relaxation in a CON2 laser

    Microsoft Academic Search

    R. Charneau; F. Legay; N. Legay-Sommaire; G. Taieb

    1975-01-01

    A double-resonance method inside the optical cavity of a CO-N2 laser has been used to study vibrational and rotational relaxation processes in the amplifying medium. Measurements of rotational relaxation of CO are in agreement with the work of other authors. Measurements of the V-V exchange rates between two molecules in a high vibrational state (v approximately equal to 10) suggest

  7. Segundo Catálogo Estelar del Hemisferio Sur con Astrolabio Fotoeléctrico PAII

    NASA Astrophysics Data System (ADS)

    Manrique, W. T.; Podestá, R. C.; Alonso, E.; Actis, E. V.; Pacheco, A. M.; Bustos, G.; Lizhi, L.; Zezhi, W.; Fanmiao, Z.; Hongqi, W.; Perdomo, R.

    Recordamos que entre el Observatorio Astronómico ``Félix Aguilar'', el Observatorio Astronómico de Beijing y el Observatorio Astronómico de La Plata, se ha convenido en desarrollar un Proyecto de Investigación conjunto, para la observación sistemática de estrellas en el Hemisferio Sur, con el objeto de la elaboración de un Catálogo Estelar Global utilizando un Astrolabio Fotoeléctrico PAII del Observatorio de Beijing, que ha sido usado con éxito en la República de China. En este trabajo se presenta el Segundo Catálogo Estelar del Hemisferio Sur, derivado de las observaciones realizadas con el PAII instalado en el OAFA, durante el períiodo Febrero de 1992 a Marzo de 1997. En este lapso se han observado mas de 400000 pasajes estelares, obteniéndose las correcciones ? ? y ? ? de 5241 estrellas del FK4, FK5, FK5 Ext., SRS, CAMC y GC. Las precisiones medias son del orden de ± 3,2 ms en ascensión recta y ±0."057 en declinación. Rango de magnitudes : 2,0 a 11,5 Rango de declinaciones : -3o a -60o Epoca Media : 1994.9 Se analizan los residuos en función de la magnitud y tipo espectral, correcciones de grupo y frecuencia de distribución ? ? y ? ?.

  8. Crystal structure of a lectin from Canavalia maritima (ConM) in complex with trehalose and maltose reveals relevant mutation in ConA-like lectins.

    PubMed

    Delatorre, Plínio; Rocha, Bruno A M; Gadelha, Carlos A A; Santi-Gadelha, Tatiane; Cajazeiras, João B; Souza, Emmanuel P; Nascimento, Kyria S; Freire, Valder N; Sampaio, Alexandre H; Azevedo, Walter F; Cavada, Benildo S

    2006-06-01

    The crystal structure of Canavalia maritima lectin (ConM) complexed with trehalose and maltose revealed relevant point mutations in ConA-like lectins. ConM with the disaccharides and other ConA-like lectins complexed with carbohydrates demonstrated significant differences in the position of H-bonds. The main difference in the ConM structure is the replacement of Pro202 by Ser202, a residue that promotes the approximation of Tyr12 to the carbohydrate-binding site. The O-6' of the second glucose ring in maltose interacts with Tyr12, while in trehalose the interaction is established by the O-2' and Tyr12, explaining the higher affinity of ConM for disaccharides compared to monosaccharides. PMID:16677825

  9. Aspectos relacionados con la sexualidad y la reproducción –para profesionales de salud (PDQ®)

    Cancer.gov

    Resumen de información revisada por expertos acerca de los factores que pueden afectar el funcionamiento sexual de las personas con cáncer. Se discuten además temas sobre la fecundidad relacionados con el tratamiento del cáncer.

  10. IZ-CON: an intelligent zone controller for building systems operation

    E-print Network

    Mahdavi, A.; Schub, M.

    2012-01-01

    This paper describes the concept of an intelligent zone controller (IZ-CON) for integrated operation of building systems. IZ-CON is intended to deploy a predictive control methodology with embedded simulation capability. Thereby, the scalability...

  11. IZ-CON: an intelligent zone controller for building systems operation 

    E-print Network

    Mahdavi, A.; Schub, M.

    2012-01-01

    This paper describes the concept of an intelligent zone controller (IZ-CON) for integrated operation of building systems. IZ-CON is intended to deploy a predictive control methodology with embedded simulation capability. Thereby, the scalability...

  12. El teatro como reflexión colectiva: Conversación con Sergio Corrieri

    E-print Network

    Luzuriaga, Gerardo

    1983-04-01

    gente del Escambray se nos queja. Uno de los aspectos más interesantes, a mi modo de ver, de la experiencia del Teatro Escambray es que todo este proceso se ha ido haciendo sobre la marcha, ha ido surgiendo, como tú decías hace poco, de la práctica... grandes rasgos, por supuesto. Por nuestra convivencia en la zona y por los multiples canales naturales que eso nos brinda, nosotros estamos actualizados de la problemática. Aparte, con el tiempo, el Escambray ha ido perdiendo artistas particulares en el...

  13. Apoyo a Estudios Geodinamicos con GPS en Guatemala

    NASA Astrophysics Data System (ADS)

    Robles, V. R.

    2013-05-01

    El Instituto Geografico Nacional de Guatemala implemento 17 estaciones GNSS en el año 2009, como un proyecto de credito mixto de donacion de equipamiento del Gobierno de Suiza, el cual, este equipamiento de estaciones CORS GNSS es un sistema de recepción y transmisión de datos crudos GPS RInex que utiliza la tecnologia Spider Web de Leica, asi mismo este sistema esta sirviendo para el espablecimiento de un marco geodesico nacional de coordenadas geodesicas oficiales, el cual se calculan u obtienen las velocidades en tiempos temporales programados de las 17 Estaciones CORS. La infraestructura del marco geodesico de Guatemala esta sirviendo de base para las aplicaciones de estudios geodinamicos como el monitoreo de del desplazamiento de las placas tectonicas por medio de un estudio que se inicio en el año de 1999, llamado medicion con GPS el sistema de Fallas de los rios Polochic Motagua de Guatemala, tambien para un estudio que se implemento para deformación de corteza terrestre local en un Volcan Activo de Guatemala llamado Pacaya. Para el estudio de medicion con GPS en el sistema de falla de los Rios del polochic Motagua se implementaron 16 puntos para medir con GPS de dos frecuencias en el año de 1999, el cual, tres puntos son estaciones geodesicas CORS IGS llamados GUAT, ELEN y HUEH, despues en el año de 2003 se hizo otra medicion en un total de 20 puntos, que permitió calcular las velocidades de desplazamieinto de los puntos en mención, usando como referencia el modelo NUVEL 1A de DeMets de la placa de Norteamerica. Este estudio fue en cooperación internacional por la universidad de Nice de Francia y el IGNde Francia. Para el estudio del monitoreo con GPS del volcan activo de Guatemala, se implementaron cuatro puntos al rededor del volcan, el cual, se realizan cuatro mediciones al año, que permiten determinar axialmente la distancias entre los puntos, y rebisar estadisticamente cual es el comportamiento de las distancias en funcion del tiempo, si existen diferencias graduales crecientes o decrecientes, que nos da un indicativo del desplazamiento de la corteza terrestre al rededor del volcan.

  14. Las espirales de Fibonacci podran estar relacionadas con la tensin 26/04/2007 Astroseti

    E-print Network

    Zexian, Cao

    Las espirales de Fibonacci podrían estar relacionadas con la tensión 26/04/2007 Astroseti Las espirales de Fibonacci podrían estar relacionadas con la tensión. La serie de Fibonacci ­ en la cual cada tensión" para crear espirales con la serie de Fibonacci en microestructuras que crecen en laboratorio

  15. Information Loss in Coarse Graining of Polymer Con gurations via Contact

    E-print Network

    - duced description of this system can be based [7, 10, 13, 14] on associating to each polymer con#12Information Loss in Coarse Graining of Polymer Con#12;gurations via Contact Matrices Patrik L description of the con- #12;guration ! of a linear chain (polymer or random walk) on Z n : C ij (!) = 1 when

  16. Trastorno por déficit de atención con hiperactividad: orientaciones psicoeducativas para los padres

    Microsoft Academic Search

    López Villalobos; S. Alberola López; José Antonio López Villalobos

    2008-01-01

    Resumen Se exponen orientaciones psicoeducativas para padres de niños con trastorno por déficit de atención con hiperactividad (TDAH), basadas en criterios empíricos, teóricos y clínicos, abor- dando las siguientes dimensiones: ambiente familiar, modelado, refuerzo de conducta, normas, autonomía y autoestima, aprender a pensar y saber esperar, atención, relación con compañeros, grupo familiar, adolescencia y una reflexión sobre el tratamiento. Palabras

  17. Sepsis por Salmonella enteritidis en una paciente con lupus eritematoso sistémico

    Microsoft Academic Search

    Carlos Alberto Cañas; Gustavo Adolfo Ospina; María Elena Ochoa; Juan Diego Vélez

    Resumen Presentamos el caso clínico de una paciente de 28 años de edad con Lupus Eritematoso Sistémico (LES), con compromiso a nivel neurológico central, riñón y sistema hematológico, con tratamiento cró- nico de esteroides y desnutrición avanzada, quien desarrolla sepsis por Salmonella enteritidis, germen aislado en muestras tomadas en lavado bronco alveolar, sangre y materia fecal. Presentó un absce- so

  18. Accesibilidad para personas con debilidad motriz ASIC 18 de noviembre de 2010 Pg. 1 de 7

    E-print Network

    Fernández de Córdoba, Pedro

    Accesibilidad para personas con debilidad motriz Windows XP ASIC ­ 18 de noviembre de 2010 Pág. 1: · Pulse T Utilizando el ratón #12;Accesibilidad para personas con debilidad motriz Windows XP ASIC ­ 18 de)... #12;Accesibilidad para personas con debilidad motriz Windows XP ASIC ­ 18 de noviembre de 2010 Pág. 3

  19. Accesibilidad para personas con debilidad visual ASIC 18 de noviembre de 2010 Pg. 1 de 6

    E-print Network

    Fernández de Córdoba, Pedro

    Accesibilidad para personas con debilidad visual Windows XP ASIC ­ 18 de noviembre de 2010 Pág. 1: · Pulse T #12;Accesibilidad para personas con debilidad visual Windows XP ASIC ­ 18 de noviembre de 2010 seleccionando las opciones adecuadas). #12;Accesibilidad para personas con debilidad visual Windows XP ASIC ­ 18

  20. Accesibilidad para personas con debilidad auditiva ASIC 18 de noviembre de 2010 Pg. 1 de 8

    E-print Network

    Fernández de Córdoba, Pedro

    Accesibilidad para personas con debilidad auditiva Windows 7 ASIC ­ 18 de noviembre de 2010 Pág. 1 sonidos. #12;Accesibilidad para personas con debilidad auditiva Windows 7 ASIC ­ 18 de noviembre de 2010 con debilidad auditiva Windows 7 ASIC ­ 18 de noviembre de 2010 Pág. 3 de 8 -Figura 1-Centro de

  1. COMPARACIÓN ENTRE LA TERAPIA CONVENCIONAL ODONTOLÓGICA Y SU USO COMBINADO CON LA FISIOTERAPIA Y LA OSTEOPATÍA, EN PACIENTES CON DISFUNCIÓN TEMPOROMANDÍBULAR. \\

    Microsoft Academic Search

    Graciela Carvallo; Maria Fasanella; Sofia Caricote

    RESUMEN Dado que la disfunción temporomandibular es una patología que cursa frecuentemente con, dolor y limitación en la apertura bucal los pacientes afectados reducen su calidad de vida desde el punto de vista social, laboral y familiar. La presente investigación tiene como propósito evaluar comparativamente los alcances terapéuticos entre el tratamiento odontológico convencional y el uso combinado de éste, con

  2. Do Well, Be Well with Diabetes 2013 1 Formulario de Registro para Personas con Diabetes Formulario de Registro para Personas con Diabetes 2013

    E-print Network

    Do Well, Be Well with Diabetes ­ 2013 1 Formulario de Registro para Personas con Diabetes Formulario de Registro para Personas con Diabetes ­ 2013 Si usted NO TIENE diabetes, por favor NO LLENE este sobre diabetes en el Condado de _______________. D. El código postal en mi casa es __ __ __ __ __. E

  3. Do Well, Be Well with Diabetes 2013 1 Formulario de Conclusin para Personas con Diabetes Formulario de Conclusin para Personas con Diabetes 201

    E-print Network

    Do Well, Be Well with Diabetes ­ 2013 1 Formulario de Conclusión para Personas con Diabetes Formulario de Conclusión para Personas con Diabetes ­ 201 Si usted NO TIENE diabetes, por favor NO LLENE este últimos cuatro números de mi número telefónico son __ __ __ __. C. Marque todas las clases sobre diabetes

  4. Amino Acid Synthesis from CO-N2 and CO-N2-H2 Gas Mixtures Via Complex Organic Compounds

    NASA Astrophysics Data System (ADS)

    Miyakawa, S.; Kobayashi, K.; Sawaoka, A. B.

    1999-01-01

    Reaction among hydrogen cyanide (HCN), formaldehyde (H2CO) and ammonia (NH3) are generally considered an important reaction in amino acid synthesis by electric discharge. Precursors of glycine and aspartic acid were, however, synthesized by adding water to metastable complex compounds produced by quenching a CO-N2 high-temperature plasma. In order to investigate effects of water remaining in an experimental vacuum chamber, optical emission spectroscopic and mass spectrometric measurements were conducted with CO-N2 and CO-N2-H2 gas mixtures. Although residual hydrogen atoms were detected in the CO-N2 experiment, the amount of them was much less than that in the CO-N2-H2 experiment

  5. [Modern tribology in total hip arthroplasty: pros and cons].

    PubMed

    Gómez-García, F

    2014-01-01

    The wear products and adverse reactions that occur on bearing surfaces represent one of the greatest challenges in prosthetic replacements, as the latter experience increasing demands due to the large number of young and older adult patients that have a long life expectancy and remarkable activity. The purpose of this review is to analyze the pros and cons of the new advances in the bearing components of the articular surfaces of current total hip arthroplasties. We also discuss the strategies used historically, their problems, results and the surgeon's role in prescribing the tribologic couple that best fits each patient's needs. We conclude with practical recommendations for the prescription and management of the latest articular couples for total hip arthroplasty. PMID:26021098

  6. Obtención de perfiles teóricos de elementos metálicos con velocidades macroscópicas

    NASA Astrophysics Data System (ADS)

    Cirigliano, D.; Costa, A.; Rovira, M.

    El propósito de este trabajo es poder establecer -a partir de la modelización de perfiles de distintas especies- patrones de comparación observacional que permitan caracterizar los fenómenos físicos que están presentes en las estructuras que se observan. Para ello se resuelven las ecuaciones de equilibrio de ionización para un determinado átomo y una atmósfera de parámetros determinados. A partir de ello se definen las poblaciones para los distintos grados de ionización. Considerando distintas configuraciones e intensidades de flujos de masa se deducen la función fuente, el espesor óptico y se calculan los perfiles de las distintas líneas. Se obtuvieron perfiles teóricos de líneas del CII, CIV y del OIV para flujos entrante, saliente y pasante. La forma del perfil, las intensidades relativas entre los distintos flujos y el corrimiento Doppler da cuenta de una caracterización teórica a partir de la cual se comparará con observaciones.

  7. Neogene sequence stratigraphy, Nam Con Son Basin, offshore Vietnam

    SciTech Connect

    McMillen, K.J. [Beaver Creek Tech. Co., Mason, TX (United States); Do Van Luu; Lee, E.K.; Hong, S.S. [PEDCO, Ho Chi Minh City (Viet Nam)

    1996-12-31

    An integrated well log, biostratigraphic, and seismic stratigraphic study of Miocene to Recent deltaic sediments deposited in the Nam Con Son Basin offshore from southern Vietnam shows the influence of eustacy and tectonics on sequence development. Sediments consist of Oligocene non-marine rift-basin fill (Cau Formation), early to middle Miocene tide-dominated delta plain to delta front sediments (TB 1.5 to TB 2.5, Due and Thong Formations), and late Miocene to Recent marine shelf sediments (TB. 2.6 to TB 3.1 0, Mang Cau, Nam Con Son, and Bien Dong Formations). Eustacy controlled the timing of key surfaces and sand distribution in the tectonically-quiet early Miocene. Tectonic effects on middle to late Miocene sequence development consist of thick transgressive systems tracts due to basin-wide subsidence and transgression, sand distribution in the basin center, and carbonate sedimentation on isolated fault blocks within the basin. Third-order sequence boundaries (SB) are identified by spore peaks, sand stacking patterns, and channel incision. In the basin center, widespread shale beds with coal occur above sequence boundaries followed by transgressive sandstone units. These TST sandstones merge toward the basin margin where they lie on older HST sandstones. Maximum flooding surfaces (MFS) have abundant marine microfossils and mangrove pollen, a change in sand stacking pattern, and often a strong seismic reflection with downlap. Fourth-order genetic-type sequences are also interpreted. The MFS is the easiest marker to identify and correlate on well logs. Fourth-order SB occur within these genetic units but are harder to identify and correlate.

  8. Neogene sequence stratigraphy, Nam Con Son Basin, offshore Vietnam

    SciTech Connect

    McMillen, K.J. (Beaver Creek Tech. Co., Mason, TX (United States)); Do Van Luu; Lee, E.K.; Hong, S.S. (PEDCO, Ho Chi Minh City (Viet Nam))

    1996-01-01

    An integrated well log, biostratigraphic, and seismic stratigraphic study of Miocene to Recent deltaic sediments deposited in the Nam Con Son Basin offshore from southern Vietnam shows the influence of eustacy and tectonics on sequence development. Sediments consist of Oligocene non-marine rift-basin fill (Cau Formation), early to middle Miocene tide-dominated delta plain to delta front sediments (TB 1.5 to TB 2.5, Due and Thong Formations), and late Miocene to Recent marine shelf sediments (TB. 2.6 to TB 3.1 0, Mang Cau, Nam Con Son, and Bien Dong Formations). Eustacy controlled the timing of key surfaces and sand distribution in the tectonically-quiet early Miocene. Tectonic effects on middle to late Miocene sequence development consist of thick transgressive systems tracts due to basin-wide subsidence and transgression, sand distribution in the basin center, and carbonate sedimentation on isolated fault blocks within the basin. Third-order sequence boundaries (SB) are identified by spore peaks, sand stacking patterns, and channel incision. In the basin center, widespread shale beds with coal occur above sequence boundaries followed by transgressive sandstone units. These TST sandstones merge toward the basin margin where they lie on older HST sandstones. Maximum flooding surfaces (MFS) have abundant marine microfossils and mangrove pollen, a change in sand stacking pattern, and often a strong seismic reflection with downlap. Fourth-order genetic-type sequences are also interpreted. The MFS is the easiest marker to identify and correlate on well logs. Fourth-order SB occur within these genetic units but are harder to identify and correlate.

  9. Con A-induced suppressor cells in children with acute lymphoblastic leukaemia.

    PubMed Central

    Eibl, M; Krepler, P; Schmidmeier, W; Zielinski, C; Winterleitner, H

    1980-01-01

    The function of Con A stimulation was investigated in patients with ALL in remission and in patients with ALL in the acute phase of the disease as compared to healthy controls. Suppression of the Con A response brought about by autologous Con A-activated cells was significantly lower in ALL patients in remission (mean value 29.33%) and in the acute phase (mean value 10%) than in the controls (mean value 64.86%). Suppression of the Con A stimulation of control lymphocytes by Con A-activated homologous cells of ALL patients had a mean value of 51.65%. This was significantly higher than the suppression obtained by the same ALL cells in the autologous system and of the same order of magnitude as the suppression obtained by control Con A-activated cells on control Con A stimulation (57.67%). Suppression of the Con a response of ALL lymphocytes produced by control Con A-activated cells was 23.17% and comparable to healthy controls. These results demonstrate that the function of Con A-induced suppression is significantly lower in ALL patients. They further indicate that at least two cell types are involved in this kind of suppression in humans. PMID:6448114

  10. Range Con: a management evaluation system for assessing sucess of selected range improvement practices

    E-print Network

    Ekblad, Steven Linn

    1989-01-01

    Knowledge Representation Procedure. Knowledge Acquisition Procedure. Validation Procedure. 12 15 20 Modeling Qualitative Judgement. 22 TABLE OF CONTENTS Continued DEVELOPMENT OF RANGE CON. Phase 1 ? Prototype Phase 2 ? Prototype. Range Con... System Planning Model 2. Range Con knowledge acquisition and knowledge- base flow chart development procedure. 17 3. Algorithm for combination of rule certainty factors in inexact reasoning model (adapted from Buchanan and Shortliffe 1985) 24 4...

  11. Pros, Cons, and Alternatives to Weight Based Cost Estimating

    NASA Technical Reports Server (NTRS)

    Joyner, Claude R.; Lauriem, Jonathan R.; Levack, Daniel H.; Zapata, Edgar

    2011-01-01

    Many cost estimating tools use weight as a major parameter in projecting the cost. This is often combined with modifying factors such as complexity, technical maturity of design, environment of operation, etc. to increase the fidelity of the estimate. For a set of conceptual designs, all meeting the same requirements, increased weight can be a major driver in increased cost. However, once a design is fixed, increased weight generally decreases cost, while decreased weight generally increases cost - and the relationship is not linear. Alternative approaches to estimating cost without using weight (except perhaps for materials costs) have been attempted to try to produce a tool usable throughout the design process - from concept studies through development. This paper will address the pros and cons of using weight based models for cost estimating, using liquid rocket engines as the example. It will then examine approaches that minimize the impct of weight based cost estimating. The Rocket Engine- Cost Model (RECM) is an attribute based model developed internally by Pratt & Whitney Rocketdyne for NASA. RECM will be presented primarily to show a successful method to use design and programmatic parameters instead of weight to estimate both design and development costs and production costs. An operations model developed by KSC, the Launch and Landing Effects Ground Operations model (LLEGO), will also be discussed.

  12. Non Invasive Biomedical Analysis. Breath Networking Session at PittCon 2011, Atlanta, Georgia Non Invasive Biomedical Analysis. Breath Networking Session at PittCon 2011, Atlanta, Georgia

    Microsoft Academic Search

    Joachim D. Pleil

    2011-01-01

    Background This was the second year that our breath colleagues organized a networking session at the Pittsburgh Conference and Exposition, or 'PittCon' (www.pittcon.org\\/). This time it was called 'Non Invasive Biomedical Analysis' to broaden the scope a bit, but the primary focus remained on exhaled breath diagnostics. As reported last year in the Journal of Breath Research, PittCon continues to

  13. MEETING REPORT Breath Biomarkers Networking Sessions at PittCon 2010, Orlando, Florida Breath Biomarkers Networking Sessions at PittCon 2010, Orlando, Florida

    Microsoft Academic Search

    Joachim D. Pleil

    2010-01-01

    The Pittsburgh Conference and Exposition, or 'PittCon' (www.pittcon.org\\/), is one of the largest international conferences for analytical chemistry and instrumentation, typically attracting about 25 000 attendees and 1000 commercial exhibitors. PittCon began in 1950 as a small spectroscopy and analytical chemistry gathering and, as the name implies, originated in Pittsburgh, PA. The conference has outgrown its humble beginnings and is

  14. Un programa innovador busca ayudar a las personas que cuidan a pacientes con cáncer

    Cancer.gov

    Los familiares proporcionan la gran mayoría de los cuidados de las personas con cáncer. Un programa educativo del City of Hope Cancer Center ofrece a los profesionales de salud la información y las herramientas necesarias para ayudar a los familiares a saber cómo cuidarse a si mismos y a sus seres queridos con cáncer.

  15. EL RAZONAMIENTO PROPORCIONAL EN ALUMNOS DE 7º GRADO CON DIFERENTES EXPERIENCIAS CURRICULARES 1

    Microsoft Academic Search

    David Ben-Chaim; James Fey; William Fitzgerald; Catherine Benedetto; Jane Miller

    Se presentaron problemas contextualizados que envuelven números racionales y razonamiento proporcional a alumnos de 7° con diferentes experiencias curriculares. Hay fuerte evidencia de que los estudiantes en la reforma curricular, quienes son estimulados a construir sus propios conceptos y procedimientos de proporcionalidad a través de trabajo colaborativo de resolución de problemas, tuvieron un mejor desempeño que los estudiantes con un

  16. Control contextual en el aprendizaje de números para un niño con discapacidad intelectual

    Microsoft Academic Search

    Francisco J. Alós

    2007-01-01

    El objetivo de este estudio fue la enseñanza de la discriminación «igual» y «diferente» en números. Se describe un experimento efectuado con un niño de siete años con discapacidad intelectual. El proble- ma fue analizado desde la perspectiva del control contextual. El procedimiento de aprendizaje consis- tió en la enseñanza explícita de una discriminación condicional de segundo orden y se

  17. Per: Chirapaq celebra 25 aos con un foro sobre "Derechos de los Pueblos Indgenas"

    E-print Network

    Islas, León

    Perú: Chirapaq celebra 25 años con un foro sobre "Derechos de los Pueblos Indígenas celebrará su 25 aniversario con el foro público internacional: "Derechos de los Pueblos Indígenas: Avances y la Nación Cree, ex parlamentario y miembro del Mecanismo de Expertos sobre los Derechos de los

  18. Table of ConTenTs -Temp 2 Message from the President

    E-print Network

    Indiana University

    Cial RepoRT 2009­10 Table of ConTenTs 2 Message from the President 6 Message from the Vice President#12;#12;1 Table of ConTenTs -Temp 2 Message from the President 7 Message from the Vice President and Chief Financial Officer 9 Independent Auditors' Report 10 Management's Discussion and Analysis 18

  19. La salud en personas con discapacidad intelectual en España: estudio europeo POMONA-II

    PubMed Central

    Martínez-Leal, Rafael; Salvador-Carulla, Luis; Gutiérrez-Colosía, Mencía Ruiz; Nadal, Margarida; Novell-Alsina, Ramón; Martorell, Almudena; González-Gordón, Rodrigo G.; Mérida-Gutiérrez, M. Reyes; Ángel, Silvia; Milagrosa-Tejonero, Luisa; Rodríguez, Alicia; García-Gutiérrez, Juan C.; Pérez-Vicente, Amado; García-Ibáñez, José; Aguilera-Inés, Francisco

    2011-01-01

    Introducción Estudios internacionales demuestran que existe un patrón diferenciado de salud y una disparidad en la atención sanitaria entre personas con discapacidad intelectual (DI) y población general. Objetivo Obtener datos sobre el estado de salud de las personas con DI y compararlos con datos de población general. Pacientes y métodos Se utilizó el conjunto de indicadores de salud P15 en una muestra de 111 sujetos con DI. Los datos de salud encontrados se compararon según el tipo de residencia de los sujetos y se utilizó la Encuesta Nacional de Salud 2006 para comparar estos datos con los de la población general. Resultados La muestra con DI presentó 25 veces más casos de epilepsia y el doble de obesidad. Un 20% presentó dolor bucal, y existió una alta presencia de problemas sensoriales, de movilidad y psicosis. Sin embargo, encontramos una baja presencia de patologías como la diabetes, la hipertensión, la osteoartritis y la osteoporosis. También presentaron una menor participación en programas de prevención y promoción de la salud, un mayor número de ingresos hospitalarios y un uso menor de los servicios de urgencia. Conclusiones El patrón de salud de las personas con DI difiere del de la población general, y éstas realizan un uso distinto de los servicios sanitarios. Es importante el desarrollo de programas de promoción de salud y de formación profesional específicamente diseñados para la atención de personas con DI, así como la implementación de encuestas de salud que incluyan datos sobre esta población. PMID:21948011

  20. Resolution of Con icts Involving Many Aircraft via Semide nite Programming

    E-print Network

    Feron, Eric

    Resolution of Con icts Involving Many Aircraft via Semide nite Programming E. Frazzoli Z.-H. Mao y J.-H. Oh z E. Feron x April, 1999 Abstract Aircraft con ict detection and resolution is currently question: Given a set of airborne aircraft and their intended trajectories, what control strategy should

  1. CPR: A Con guration Pro ling Tool Srihari Cadambiand Seth Copen Goldsteiny

    E-print Network

    Goldstein, Seth Copen

    CPR: A Con guration Pro ling Tool Srihari Cadambiand Seth Copen Goldsteiny Carnegie Mellon tool CPR and show how it can be used to aid compiler designers, FPGA architects and in the con- struction of a macro-generator libraries. CPR uses subgraph matching to identify the parts of an ap

  2. Meeting Report: Breath Biomarkers Networking Sessions at PittCon 2010, Orlando, Florida

    EPA Science Inventory

    The Pittsburgh Conference and Exposition, or "PittCon" (www.pittcon.org/), is one of the largest international conferences for analytical chemistry and instrumentation typically attracting about 25,000 attendees and 1,000 commercial exhibitors. PittCon began in 1950 as a small sp...

  3. Teorías y doctrina sobre las relaciones del derecho con la economía

    Microsoft Academic Search

    William Leguizamón Acosta

    2004-01-01

    A partir de la conformación definitiva de la Economía como ciencia autónoma; hecho sucedido a partir de la obra de ADAM SMITH “sobre la naturaleza y riqueza de las Naciones” se ha venido discutiendo con intensidad sobre las estrechas relaciones que esta disciplina mantiene con el Derecho. Algunos abordan el tema bajo condiciones de dominio de una ciencia sobre la

  4. Resolving con icts in collaborative human-computer interaction (extended abstract)

    E-print Network

    Resolving con icts in collaborative human-computer interaction (extended abstract) Robert St. Amant softwareagentsand human agents. Our discus- sion is drawn mainly from research in human-computer interaction (HCI in autonomous agents research. Managing con icts in human-computer interaction poses a set of challenges beyond

  5. conStruction MAnAgeMent College of Rural and Community Development

    E-print Network

    Hartman, Chris

    conStruction MAnAgeMent College of Rural and Community Development Community and Technical College The construction management program meets growing needs in the con- struction industry by training entry-level construction managers and by providing continuing education for construction employees. Construction managers

  6. Taller de espacios de Banach Reticulos de Banach con la propiedad de Kato

    E-print Network

    Taller de espacios de Banach Reticulos de Banach con la propiedad de Kato Resumen: Se estudian retículos de Banach y espacios de funciones de reordenamiento invariante E con la propiedad de que las Estructura de Espacios de Banach (MTM2012-31286) Francisco L. Hernández UCM #12;

  7. Diventa Social Media Trainer Aumenta le tue possibilit occupazionali con competenze Web 2.0 e

    E-print Network

    Robbiano, Lorenzo

    Diventa Social Media Trainer · Aumenta le tue possibilità occupazionali con competenze Web 2.0 e marketing. Perché partecipare: · Riceverai una Formazione per diventare un Social Media Trainer formative, aiutando un membro dello staff aziendale a familiarizzare con gli strumenti Social Media. Questo

  8. On the Formal Veri cation of the TCAS Con ict Resolution Algorithms 1

    E-print Network

    Lynch, Nancy

    On the Formal Veri cation of the TCAS Con ict Resolution Algorithms 1 John Lygeros and Nancy Lynch 02139 lygeros, lynch@lcs.mit.edu Abstract TCAS is an on-board protocol for detecting con icts between aircraft and providing resolution advisories to the pilots. Because of its safety-critical role the TCAS

  9. Enhanced ballistic performance of conned multi-layered ceramic targets against long rod penetrators through

    E-print Network

    Espinosa, Horacio D.

    Enhanced ballistic performance of con®ned multi-layered ceramic targets against long rod Science Ltd. All rights reserved. Keywords: Ballistic penetration; Damage; Fragmentation; Interferometry is one of the most important material properties that in¯uence its ballistic performance and motivated

  10. Accesibilidad para personas con debilidad motriz ASIC 18 de noviembre de 2010 Pg. 1 de 17

    E-print Network

    Fernández de Córdoba, Pedro

    Accesibilidad para personas con debilidad motriz Windows 7 ASIC ­ 18 de noviembre de 2010 Pág. 1 de;Accesibilidad para personas con debilidad motriz Windows 7 ASIC ­ 18 de noviembre de 2010 Pág. 2 de 17 Windows 7 ASIC ­ 18 de noviembre de 2010 Pág. 3 de 17 Figura 1-Centro de accesibilidad -Figura 2-Teclado

  11. Accesibilidad para personas con debilidad auditiva ASIC 18 de noviembre de 2010 Pg. 1 de 4

    E-print Network

    Fernández de Córdoba, Pedro

    Accesibilidad para personas con debilidad auditiva Windows XP ASIC ­ 18 de noviembre de 2010 Pág. 1 debilidad auditiva Windows XP ASIC ­ 18 de noviembre de 2010 Pág. 2 de 4 Utilizando el ratón 3 En el cuadro). Utilizando el ratón #12;Accesibilidad para personas con debilidad auditiva Windows XP ASIC ­ 18 de noviembre

  12. Accesibilidad para personas con debilidad visual ASIC 18 de noviembre de 2010 Pg. 1 de 12

    E-print Network

    Fernández de Córdoba, Pedro

    Accesibilidad para personas con debilidad visual Windows 7 ASIC ­ 18 de noviembre de 2010 Pág. 1 de accesibilidad haga Intro sobre la Lupa : #12;Accesibilidad para personas con debilidad visual Windows 7 ASIC Windows 7 ASIC ­ 18 de noviembre de 2010 Pág. 3 de 12 Ctrl+Alt+R Tecla del logotipo de Windows +Esc

  13. 9/26/2014 Recargar el iPhone con aire ser posible? | Informacion Celulares [VC] http://viciodeciudad.com.ar/recargar-el-iphone-con-aire-sera-posible/celulares-informacion/ 1/3

    E-print Network

    Chiao, Jung-Chih

    9/26/2014 ¿Recargar el iPhone con aire será posible? | Informacion Celulares [VC] http://viciodeciudad.com.ar/recargar-el-iphone-con-aire-sera-posible/celulares-informacion/ 1/3 INFORMACIONCELULARES ocupan hoy en día. Hablamos de un nuevo prototipo de sistema de carga para el iPhone, con el que se

  14. ConSurf 2010: calculating evolutionary conservation in sequence and structure of proteins and nucleic acids

    PubMed Central

    Ashkenazy, Haim; Erez, Elana; Martz, Eric; Pupko, Tal; Ben-Tal, Nir

    2010-01-01

    It is informative to detect highly conserved positions in proteins and nucleic acid sequence/structure since they are often indicative of structural and/or functional importance. ConSurf (http://consurf.tau.ac.il) and ConSeq (http://conseq.tau.ac.il) are two well-established web servers for calculating the evolutionary conservation of amino acid positions in proteins using an empirical Bayesian inference, starting from protein structure and sequence, respectively. Here, we present the new version of the ConSurf web server that combines the two independent servers, providing an easier and more intuitive step-by-step interface, while offering the user more flexibility during the process. In addition, the new version of ConSurf calculates the evolutionary rates for nucleic acid sequences. The new version is freely available at: http://consurf.tau.ac.il/. PMID:20478830

  15. Titolo Breve descrizione N. tirocini Titolo studio Conoscenze specifiche Comunicazione con interventi

    E-print Network

    Robbiano, Lorenzo

    progetto "Genova Smart City per i giovani" iniziato nel 2012 con l'obiettivo di diffondere il modello di percorso, collaborando inoltre nei 3 progetti europei Smart Cities and Communities "Transform" - "R2 Cities

  16. Qu sucede con esta imagen? Crculo las diez cosas mal en la

    E-print Network

    limpio #12;¿Qué sucede con esta imagen? -"Servir comida segura" Clave 1. Caliente explotación por debajo lugar en la tabla que no se han eliminado 6. Un alimento no tiene sus propios utensilios de servir en el

  17. Tensión postraumática relacionada con el cáncer–para profesionales de salud (PDQ®)

    Cancer.gov

    Resumen de información revisada por expertos acerca de la tensión postraumática y síntomas relacionados en los pacientes con cáncer, sobrevivientes del cáncer y miembros de la familia. Se discuten la evaluación y tratamiento de estos síntomas.

  18. Courses: Economics (ECON) Page 291Sonoma State University 2010-2011 Catalog eCOn 321 lABOr eCOnOMiCS (4)

    E-print Network

    Ravikumar, B.

    history, market structure, labor laws, gender and race, education and training, and collective bargaining, consumers, labor and government. Topics include: constitutional law, administrative law, regulation of monopoly and competition, labor law and international law. Prerequisite: ECON 204 or 205. eCOn 403 Se

  19. Estudio de los NIH señala una relación de la tomografía computarizada (TC) en la infancia con leucemia y con cáncer de cerebro más tarde

    Cancer.gov

    Niños y adultos jóvenes a quienes se les hicieron exploraciones muchas veces con tomografía computarizada (TC), una herramienta de diagnóstico de uso frecuente, tienen un riesgo ligeramente mayor de padecer leucemia y tumores cerebrales en la década posterior a su primera tomografía.

  20. NSF funds iCons and HCC interdisciplinary renewable energy labs The campus' Integrated Concentration in Science (iCons) program and

    E-print Network

    Auerbach, Scott M.

    NSF funds iCons and HCC interdisciplinary renewable energy labs The campus' Integrated Foundation (NSF) funding. These new courses will provide undergraduate students the opportunity will use the NSF award to purchase equipment and develop teaching strategies for their parallel renewable