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Sample records for early neoplastic changes12

  1. Early-enhancing non-neoplastic lesions on gadolinium-enhanced MRI of the liver

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    Kanematsu, M. E-mail: masa-gif@umin.ac.jp; Kondo, H.; Semelka, R.C.; Matsuo, M.; Goshima, S.; Hoshi, H.; Moriyama, N.; Itai, Y

    2003-10-01

    AIM: To assess the frequency, cause, and significance of early-enhancing, non-neoplastic (EN) lesions on gadolinium-enhanced magnetic resonance imaging (MRI) of the liver performed for the detection of malignant hepatic tumours. MATERIALS AND METHODS: From September 1997 to September 2000, we reviewed the images of 125 patients, suspected of having hepatic tumours, in whom (1) gadolinium-enhanced triphasic dynamic gradient-recalled-echo (GRE) imaging in addition to unenhanced T1- and T2-weighted MRI was performed, (2) conventional angiography and combination computed tomography (CT) hepatic arteriography and CT during arterial portography were performed within 2 weeks of the MRI, and (3) definitive surgery within 2 weeks of the MRI or follow-up study by means of intravenously contrast-enhanced CT or MRI in 10 months or more was performed. Angiographic studies were correlated to determine the underlying causes of the EN lesions. RESULTS: We found 78 EN lesions in 36 patients (29%), ranging in size from 4 and 50 mm (mean, 12.2 mm). From the MR reports, our radiologists had prospectively diagnosed EN lesions as probable malignant tumours in eight (10%), possible malignant tumours in 36 (46%), and probable non-neoplastic lesion in 34 (44%). EN lesions were found in 27 of 81 (33%) cirrhotic patients and in nine of 44 (20%) non-cirrhotic patients. Fifty-one EN lesions (65%) were located along the liver edge. The shape was circular in 42 (54%), oval in 14 (18%), irregular in 12 (15%), wedge-shaped in seven (9%), and fan-shaped in three (4%). Twenty EN lesions (26%) appeared slightly hyperintense on T2-weighted images. The causes were non-neoplastic arterio-portal shunting in 48 (62%), cystic venous drainage in four (5%), rib compression in four (5%), aberrant right gastric venous drainage in two (3%), and unknown in 20 (26%). CONCLUSION: Over half the number of EN lesions were caused by non-neoplastic arterio-portal shunting, occasionally showing slight hyperintensity on

  2. A human xenograft model for testing early events of epithelial neoplastic invasion

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    McCANDLESS, JOHN R.; CRESS, ANNE E.; RABINOVITZ, ISAAC; PAYNE, CLAIRE M.; BOWDEN, G. TIM; KNOX, J. DAVID; NAGLE, RAY B.

    2017-01-01

    We report on a model of human prostate tumor cell invasion using the SCID (severe combined immunodeficient) mouse diaphragm. Tumor cells were injected into SCID mice intraperitoneally and the diaphragms harvested three to five weeks later. Electron microscopy showed tumor cell penetration of the mesothelial cell layer and adhesion to the underlying basement membrane on the inferior surface of the mouse diaphragm, where colonies developed. Immunohistochemistry showed invasion by tumor cells through the basement membrane into the muscle of the diaphragm, presence of human tumor cells among the muscle cells and the presence of selected proteins on the invasion front of the tumor cells. Digital image analysis enabled quantitative comparison of events in the metastatic cascade by variants of the tumor cell line and evaluation of the effectiveness of a putative tumor inhibitor. Results suggest that the SCID mouse diaphragm model is a convenient, effective, easily oriented and reproducible in vivo model of the early events associated with human prostate tumor cell invasion. PMID:21533373

  3. Early and long-term results of combined cardiac surgery and neoplastic resection in patients with concomitant severe heart disease and neoplasms

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    FU Qiang; LI Quan-zheng; LIANG De-gang; RUAN Xin-hua; WANG Zan-xin; WEI Min-xin

    2011-01-01

    Background It is a surgical dilemma when patients present with both severe heart disease and neoplasms. The best surgical treatment remains controversial. This study aimed to analyze the early and long-term results of simultaneous surgical treatment of severe heart disease and neoplasms.Methods We reviewed the clinical records of 15 patients who underwent simultaneous neoplastic resection and cardiac surgery between September 2006 and January 2011. There were 5 male and 10 female patients. The mean age was (59.2±12.5) years and the mean left ventricular ejection fraction was (57.4±11.0)%. All patients were followed up completely for a period of 12 to 51 months (mean, (33.1±11.2) months).Results Fifteen patients underwent simultaneous cardiac surgery and neoplastic resection. Cardiac procedures consisted of off pump coronary artery bypass grafting (n=7), aortic valve replacement (n=3), mitral valve replacement (n=3), mitral valve replacement with coronary artery bypass grafting (n=1) and left atrial myxoma resection (n=1). Neoplastic resection consisted of lung cancer resection (n=5). colonic cancer resection (n=3), gallbladder resection (n=1), colonic cancer resection with gallbladder resection (n=1), hysterectomy (n=2), hysterectomy with bilateral salpingo-oophorectomy (n=2) and left ovariectomy (n=1). Pathological examination confirmed malignant disease in 10 patients and benign disease in 5 patients. There were no perioperative myocardial infarctions, stroke, pericardial tamponade, renal failure or hospital deaths. The most frequent complications were atrial fibrillation (33.3%), pneumonia (26.7%), low cardiac output syndrome (6.7%) and delayed healing of surgical wounds (6.7%). There was 1 late death 42 months after surgery for recurrent malignant disease. At 1 and 3 years, survival rates were 100% (Kaplan-Meier method).Conclusions Simultaneous cardiac surgery and neoplastic resection was not associated with increased early or late morbidity or mortality

  4. Chromosome 11 aneusomy in esophageal cancers and precancerous lesions-an early event in neoplastic transformation: An interphase fluorescence in situ hybridization study from south India

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    Vasavi Mohan; Shivani Ponnala; Hemakumar M Reddy; Radha Sistla; Rachel A Jesudasan; Yog Raj Ahuja; Qurratulain Hasan

    2007-01-01

    AIM: To detect aneusomic changes with respect to chromosome 11 copy number in esophageal precancers and cancers wherein the generation of cancer-specific phenotypes is believed to be associated with specific chromosomal aneuploidies.METHODS: We performed fluorescence in situ hybridization (FISH) on esophageal tissue paraffin sections to analyze changes in chromosome 11 copy number using apotome-generated images by optical sectioning microscopy. Sections were prepared from esophageal tumor tissue, tissues showing preneoplastic changes and histologically normal tissues (control)obtained from patients referred to the clinic for endoscopic evaluation.RESULTS: Our results demonstrated that aneusomy was seen in all the cancers and preneoplastic tissues, while none of the controls showed aneusomic cells. There was no increase in aneusomy from precancers to cancers.CONCLUSION: Our results suggest that evaluation of chromosome 11 aneusomy in esophageal tissue using FISH with an appropriate signal capture-analysis system, can be used as an ancillary molecular marker predictive of early neoplastic changes. Future studies can be directed towards the genes on chromosome 11,which may play a role in the neoplastic transformation of esophageal precancerous lesions to cancers.

  5. Management of neoplastic meningitis.

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    Roth, Patrick; Weller, Michael

    2015-06-01

    Leptomeningeal dissemination of tumor cells, also referred to as neoplastic meningitis, is most frequently seen in patients with late-stage cancer and mostly associated with a poor prognosis. Basically, neoplastic meningitis may affect all patients with a malignant tumor but is most common in patients affected by lung cancer, breast carcinoma, melanoma or hematologic neoplasms such as lymphoma and leukemia. Controlled clinical trials are largely lacking which results in various non-standardized treatment regimens. The presence of solid tumor manifestations in the CNS as well as the extracranial tumor load defines the most appropriate treatment approach. Radiation therapy, systemic chemotherapy and intrathecal treatment must be considered. For each patient, the individual situation needs to be carefully evaluated to determine the potential benefit as well as putative side effects associated with any therapy. A moderate survival benefit and particularly relief from pain and neurological deficits are the main treatment goals. Here, we summarize the management of patients with neoplastic meningitis and review the available treatment options.

  6. Non-neoplastic disorders of the esophagus

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    Hong, Min Ji; Kim, Young Tong [Dept. of Radiology, Soonchunhyang University College of Medicine, Cheonan Hospital, Cheonan (Korea, Republic of)

    2013-07-15

    Non-neoplastic disorders of the esophagus include esophagitis, esophageal diverticulum, esophageal injury, foreign body, fistulous formation between the esophagus and the surrounding structures and mucocele. Since these disorders have variable symptoms and radiologic findings, it needs to differentiated from other disorders other than esophageal diseases. Being knowledgeable of CT findings suggest that these disorders can help diagnose non-neoplastic disorders of the esophagus. The purpose of this pictorial essay is to review the CT appearance of non-neoplastic disorders of the esophagus.

  7. Capsule endoscopy in neoplastic diseases

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    Marco Pennazio; Emanuele Rondonotti; Roberto de Franchis

    2008-01-01

    Until recently,diagnosis and management of small-bowel tumors were delayed by the difficulty of access to the small bowel and the poor diagnostic capabilities of the available diagnostic techniques.An array of new methods has recently been developed,increasing the possibility of detecting these tumors at an earlier stage.Capsule endoscopy (CE) appears to be an ideal tool to recognize the presence of neoplastic lesions along this organ,since it is non-invasive and enables the entire small bowel to be visualized.Highquality images of the small-bowel mucosa may be captured and small and fiat lesions recognized,without exposure to radiation.Recent studies on a large population of patients undergoing CE have reported small-bowel tumor frequency only slightly above that reported in previous surgical series (range,1.6%-2.4%)and have also confirmed that the main clinical indication to CE in patients with small-bowel tumors is obscure gastrointestinal (GI) bleeding.The majority of tumors identified by CE are malignant;many were unsuspected and not found by other methods.However,it remains difficult to identify pathology and tumor type based on the lesion's endoscopic appearance.Despite its limitations,CE provides crucial information leading in most cases to changes in subsequent patient management.Whether the use of CE in combination with other new diagnostic (MRI or multidetector CT enterography) and therapeutic (Push-and-pull enteroscopy) techniques will lead to earlier diagnosis and treatment of these neoplasms,ultimately resulting in a survival advantage and in cost savings,remains to be determined through carefully-designed studies.

  8. Rare thyroid non-neoplastic diseases.

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    Lacka, Katarzyna; Maciejewski, Adam

    2015-01-01

    Rare diseases are usually defined as entities affecting less than 1 person per 2,000. About 7,000 different rare entities are distinguished and, among them, rare diseases of the thyroid gland. Although not frequent, they can be found in the everyday practice of endocrinologists and should be considered in differential diagnosis. Rare non-neoplastic thyroid diseases will be discussed. Congenital hypothyroidism's frequency is relatively high and its early treatment is of vital importance for neonatal psychomotor development; CH is caused primarily by thyroid dysgenesis (85%) or dyshormonogenesis (10-15%), although secondary defects - hypothalamic and pituitary - can also be found; up to 40% of cases diagnosed on neonatal screening are transient. Inherited abnormalities of thyroid hormone binding proteins (TBG, TBP and albumin) include alterations in their concentration or affinity for iodothyronines, this leads to laboratory test abnormalities, although usually with normal free hormones and clinical euthyroidism. Thyroid hormone resistance is most commonly found in THRB gene mutations and more rarely in THRA mutations; in some cases both genes are unchanged (non-TR RTH). Recently the term 'reduced sensitivity to thyroid hormones' was introduced, which encompass not only iodothyronine receptor defects but also their defective transmembrane transport or metabolism. Rare causes of hyperthyroidism are: activating mutations in TSHR or GNAS genes, pituitary adenomas, differentiated thyroid cancer or gestational trophoblastic disease; congenital hyperthyroidism cases are also seen, although less frequently than CH. Like other organs and tissues, the thyroid can be affected by different inflammatory and infectious processes, including tuberculosis and sarcoidosis. In most of the rare thyroid diseases genetic factors play a key role, many of them can be classified as monogenic disorders. Although there are still some limitations, progress has been made in our understanding of

  9. Neuro-ophthalmologic complications of neoplastic leptomeningeal disease.

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    Szatmáry, Gabriella

    2013-12-01

    Neoplastic leptomeningeal disease (NLD), which encompasses both primary and secondary leptomeningeal tumors, has a devastating impact on the life of cancer patients. The present diagnostic technical armamentarium is insufficient for early diagnosis of NLD. However, NLD may present with subtle neuro-ophthalmic features at a time of relatively small tumor burden, which gives the provider first encountering these patients the window of opportunity for early diagnosis and consequently improved life expectancy and quality of life of these patients. Therefore, familiarity with early, often subtle neuro-ophthalmic features is an essential tool for diagnosing these patients prior to the development of fixed deficits, which usually portend a dismal prognosis. Future evolving laboratory and neuroimaging technologies are expected to advance our understanding of underlying pathophysiology and early detection of NLD. This paper provides an up-to-date review and synthesis of the current literature with focus on neuro-ophthalmic features and their underlying pathophysiology.

  10. SUBCELLULAR LOCALIZATION OF BETA CATENIN IN COLORECTAL NON NEOPLASTIC AND NEOPLASTIC LESIONS

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    Diah Rini Handjari

    2011-12-01

    Full Text Available Loss of adenomatous polyposis coli (APC function is typically an early event in sporadic colorectal cancer (CRC pathogenesis. The key tumor suppressor function of the APC protein lies in its ability to destabilize free cytoplasmic beta catenin. This lead to the accumulation of nuclear beta catenin, and together with the DNA binding protein Tcf-4, function as a transcriptional activator. Accumulation of stabilized free β-catenin is considered as an early event and perhaps initiating the process in intestinal tumorigenesis. Neoplastic transformation in the CRC associated chronic colitis is considered similar to the adenoma-carcinoma sequence in sporadic CRC. The distinguish feature from the CRC-related colitis is the difference in time and frequency changes. Loss of APC function, regarded as the beginning of a very common event in sporadic CRC, but the CRC associated chronic colitis generally occurs at the end of thedysplasia-carcinoma sequence. This research was conducted to determine the subcellular location of beta catenin expression in chronic colitis, colorectal adenomas and carcinomas that were evaluated by immunohistochemical staining. It can be concluded that beta-catenin is a component that plays a role in the development of the CRC and the subcellular location of beta-catenin can describe its oncogenic activity.

  11. Neoplastic pericardial disease. Analysis of 26 patients

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    Helena Nogueira Soufen

    1999-01-01

    Full Text Available PURPOSE: To characterize patients with neoplastic pericardial disease diagnosed by clinical presentation, complementary test findings, and the histological type of tumor. METHODS: Twenty-six patients with neoplastic pericardial disease were retrospectively analyzed. RESULTS: Clinical manifestations and abnormalities in chest roentgenograms and electrocardiograms were frequent, but were not specific. Most patients underwent surgery. There was a high positivity of the pericardial biopsy when associated with the cytological analysis of the pericardial liquid used to determine the histological type of the tumor, particularly when the procedure was performed with the aid of pericardioscopy. CONCLUSION: The correct diagnosis of neoplastic pericardial disease involves suspicious but nonspecific findings during clinical examination and in screen tests. The suspicious findings must be confirmed through more invasive diagnostic approaches, in particular pericardioscopy with biopsy and cytological study.

  12. Total gastrectomy for non-neoplastic diseases

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    Bjorn, Niels; Ainsworth, Alan Patrick; Mortensen, Michael Bau

    2017-01-01

    Background: The aim of this study was to describe patients who had total gastrectomy for non-neoplastic diseases within a well-defined geographical area. Material and Methods: Retrospective study of patients who had gastrectomy for a non-neoplastic disease at the Department of Surgery, Odense...... University Hospital from 1 January 2005 to 31 December 2014. Results: A total of 268 gastrectomies were performed with the 10-year period. Of these, ten (4%) were done for non-neoplastic diseases. Two were men and eight women with a median age of 51 years (range 31 to 96 years). Six had emergency surgery...... and four were planned procedures. Four patients had no complications following surgery, whereas severe complications where seen in 6 patients, where anastomotic leakage occurred in 3 patients. Median length of postoperative stay was 21 days (range 6 to 98 days), and the 30-days and 90-days mortality was 1...

  13. Identification of the estrogen receptor GPER in neoplastic and non-neoplastic human testes

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    Maggiolini Marcello

    2011-10-01

    Full Text Available Abstract Background Estrogen signaling is mediated by estrogen receptor beta isoforms in normal and neoplastic human testes. Recently, a G-protein-coupled-receptor (GPER has been suggested as being involved in rapid responses to estrogens in different normal and tumor cells. Methods This study investigated the GPER expression in paraffin-embedded samples from non neoplastic and neoplastic human testes (sex-cord stromal and germ cell tumors by immunohistochemical and Western Blot analyses. Results In control testes, a positive GPER immunoreactivity was detected in Leydig and in Sertoli cells while all germ cells were immunonegative. Furthermore, neoplastic cells of the Sertoli cell tumor, Leydig cell tumor, seminoma and embryonal carcinoma samples were all immunopositive. The immunoblots of testis extracts confirmed the results. Conclusions These findings suggest that GPER could mediate estrogen signaling in both normal and transformed somatic cells of human testis, but they reveal a differential expression of the novel estrogen receptor in non neoplastic and neoplastic germ cells.

  14. Plasma sialic acid alterations in neoplastic diseases.

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    Dwivedi, C; Dixit, M; Kumar, S S; Reddy, H; Semenya, K A; Hardy, R E

    1987-01-01

    The several types of neoplastic transformations are accompanied by alterations in the composition of cell glycoproteins, which are major structural components of cell surfaces. One such observed alteration is in the level of sialic acid on the cell surface. In the present investigation, plasma sialic acid levels were measured in normal volunteers and neoplastic patients using thiobarbituric acid spectrophotometric methods. The mean plasma sialic acid level from 124 normal volunteers was 3.0 mumol/ml. The mean for 20 non-malignant patients was 3.2 mumol/ml. Such observed mean values of sialic acid were 3.7 mumol/ml in 64 breast cancer patients, 5.1 mumol/ml in 22 lung cancer patients, 4.1 mumol/ml in 20 colon patients, and 5.0 mumol/ml in 26 patients having ovarian, cervix, pancreas, prostate, thyroid, uterine, squamous cell, esophageal and endometrial cancers. Serial determinations of plasma sialic acid in 15 patients correlated well with the progression and regression of disease. These results indicate that plasma sialic acid levels are elevated over control levels in the different types of cancer patients studied. Assay of plasma sialic acid is not sensitive enough to be used for screening, but could be used as a prognostic determinant in a variety of neoplastic conditions.

  15. Differential expression of microRNAs in early-stage neoplastic transformation in the lungs of F344 rats chronically treated with the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

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    Kalscheuer, Stephen; Zhang, Xiaoxiao; Zeng, Yan; Upadhyaya, Pramod

    2008-12-01

    While numerous microRNAs (miRNAs) have been reported to alter their expression levels in human lung cancer tissues compared with normal tissues, the function of these miRNAs and their contribution to the long process of lung cancer development remains largely unknown. We applied a tobacco-specific carcinogen-induced cancer model to investigate the involvement of miRNAs in early lung cancer development, which could also provide information on potential, early biomarkers of lung cancers. Male F344 rats were first chronically treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a carcinogen present in tobacco products, for up to 20 weeks. The expression profiles of miRNAs in rat lungs were then determined. As measured by miRNA microarrays and confirmed by Northern blot and real-time polymerase chain reaction analyses, NNK treatment reduced the expression of a number of miRNAs, such as miR-101, miR-126*, miR-199 and miR-34. Significantly, these miRNAs overlap with previously published reports on altered miRNA expression in human lung cancer samples. These miRNAs might, therefore, represent early-response miRNAs that signify the molecular changes associated with pulmonary tumorigenesis. Moreover, we identified cytochrome P450 (CYP) 2A3, a critical enzyme in rat lungs that activates NNK to render it carcinogenic, as a potential target of miR-126*. NNK treatment in rats repressed miR-126* but induced CYP2A3 expression, a mechanism that may potentiate the oncogenic effects of NNK.

  16. Nosocomial Infections among Pediatric Patients with Neoplastic Diseases

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    Peninnah Oberdorfer; Natthida Pongwilairat; Washington, Charles H

    2009-01-01

    Background. Pediatric patients with neoplastic diseases are more likely to develop nosocomial infections (NIs). NIs may prolong their hospital stay, and increase morbidity and mortality. Objectives. The objectives of this study were to determine: (1) the incidence of NIs, (2) sites of NIs, (3) causal organisms, and (4) outcomes of NIs among pediatric patients with neoplastic diseases. Methods. This study was a prospective cohort study of pediatric patients with neoplastic diseases who were ad...

  17. Cancer related fatigue syndrome in neoplastic diseases

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    Magdalena Franc

    2014-12-01

    Full Text Available Fatigue is one of the most important factors which has a considerable influence on treatment and the life quality of oncological patients. The fatigue syndrome is often diagnosed during cancer treatment and this syndrome is not related to the physical effort. Cancer related fatigue is a patient’s subjective, psychologically, physically and emotionally based feeling. It is disproportionate to patient’s daily activity. The pathogenesis of this syndrome remains still unknown. However, on the basis of various questionnaires, it is possible to test the disease’s complex nature. Cancer related fatigue causes deterioration of patient’s life along with lower motivation to struggle with the disease. It is thought that the factor which increases the incidence of cancer related fatigue is a long-term use of drugs such as opioids, benzodiazepine, and medicines containing codeine, tranquilizers, anxiolytics and antidepressants. On the basis of the results, one can choose an appropriate treatment method for cancer related fatigue such as rehabilitation, psychotherapy or public assistance. A great number of patients consider excessive fatigue a typical concomitant symptom in neoplastic disease; therefore, they do not report it. It is of a paramount importance to make patients aware of the fact that cancer related fatigue is a serious disease which can be treated.

  18. Vitamins A and E in neoplastic disease.

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    Broccio, M; Dellarovere, F; Granata, A; Zirilli, A; Artemisia, A; Pirrone, G; Broccio, G

    1997-01-01

    Vitamins A and E play an important role against 'free radicals' (FRs). Their antioxidant action is evident in neoplastic disease (ND) that is known to have a FRs pathology. This finding has been supported by previous research showing increased lipid peroxidation of the erythrocyte membrane with increased permeability and higher hemoglobin susceptibility to oxidative stress. Connections exist between the two vitamins and FRs lipid peroxidation of the membranes. In order to study A and E vitamin behaviour in ND, they were assayed in the sera of 88 cancer patients versus 94 healthy subjects. In the 88 cancer cases, without considering variables such as age, sex and smoking habits, the average amount of vitamin A was 47.44+/-19.60 mu g/dl versus 71.77+/-18.30 in controls (P<0.0001). The average amount of vitamin E was 1144.42+/-507.45 in ND versus 1497.45+/-397.74 in controls (P<0.0001). The two vitamins were simultaneously assayed in the same serum by high pressure liquid chromatography. The method is rapid and gave exact and repeatable results. Reasons for vitamin decrease are discussed.

  19. Magnifying colonoscopy as a non-biopsy technique for differential diagnosis of non-neoplastic and neoplastic lesions

    Institute of Scientific and Technical Information of China (English)

    Shigeharu Kato; Kuang I Fu; Yasushi Sano; Takahiro Fujii; Yutaka Saito; Takahisa Matsuda; Ikuro Koba; Shigeaki Yoshida; Takahiro Fujimori

    2006-01-01

    AIM: To clarify whether mucosal crypt patterns observed with magnifying colonoscopy are feasible to distinguish non-neoplastic polyps from neoplastic polyps.METHODS: From June 1999 through March 2000, 180consecutive patients with 210 lesions diagnosed with a magnifying colonoscope (CF-200Z, Olympus Optical Co., Ltd., Tokyo, Japan) were enrolled. Magnification and chromoendoscopy with 0.2% indigo-carmine dye was applied to each lesion for mucosal crypt observation.Lesions showing types Ⅰ and Ⅱ crypt patterns were considered non-neoplastic and examined histologically by biopsy, whereas lesions showing types Ⅲ to Ⅴ crypt patterns were removed endoscopically or surgically.The correlation of endoscopic diagnosis and histologic diagnosis was then investigated.RESULTS: At endoscopy, 24 lesions showed a type Ⅰ or Ⅱ pit pattern, and 186 lesions showed type Ⅲ to Ⅴ pit patterns. With histologic examination, 26 lesions were diagnosed as non-neoplastic polyps, and 184lesions were diagnosed as neoplastic polyps. The overall diagnostic accuracy was 99.1% (208/210). The sensitivity and specificity were 92.3% (24/26) and 99.8%(184/186), respectively.CONCLUSION: Magnifying colonoscopy could be used as a non-biopsy technique for differentiating neoplastic and non-neoplastic polyps.

  20. CREB: A Key Regulator of Normal and Neoplastic Hematopoiesis

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    Salemiz Sandoval

    2009-01-01

    Full Text Available The cAMP response element-binding protein (CREB is a nuclear transcription factor downstream of cell surface receptors and mitogens that is critical for normal and neoplastic hematopoiesis. Previous work from our laboratory demonstrated that a majority of patients with acute myeloid leukemia (AML and acute lymphoid leukemia (ALL overexpress CREB in the bone marrow. To understand the role of CREB in leukemogenesis, we examined the biological effect of CREB overexpression on primary leukemia cells, leukemia cell lines, and CREB overexpressing transgenic mice. Our results demonstrated that CREB overexpression leads to an increase in cellular proliferation and survival. Furthermore, CREB transgenic mice develop a myeloproliferative disorder with aberrant myelopoiesis in both the bone marrow and spleen. Additional research from other groups has shown that the expression of the cAMP early inducible repressor (ICER, a CREB repressor, is also deregulated in leukemias. And, miR-34b, a microRNA that negative regulates CREB expression, is expressed at lower levels in myeloid leukemia cell lines compared to that of healthy bone marrow. Taken together, these data suggest that CREB plays a role in cellular transformation. The data also suggest that CREB-specific signaling pathways could possibly serve as potential targets for therapeutic intervention.

  1. STATISTICAL EVALUATION AND CORRELATIVE STUDY OF NEOPLASTIC AND NON-NEOPLASTIC LESIONS OF OESOPHAGUS

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    Kavitha Duraisamy

    2016-08-01

    Full Text Available BACKGROUND Oesophageal lesions once thought to be rare is nowadays being one of the common disorder affecting the people throughout the world. The clinical, endoscopic findings and histopathologic changes of oesophageal mucosa induced by Gastro-oesophageal Reflux Disease (GERD has been mainly focused and analysed. MATERIALS AND METHODS Patients presented with symptoms and signs of oesophageal lesions during January 2000 to September 2005 were included in this study. Upper gastrointestinal endoscopy was performed. Endoscopic changes were noted in the oesophagus and stomach. In oesophagectomy specimens, four longitudinal sections were taken, one including a portion of non-neoplastic mucosa proximal to tumour and another distal to the tumour. Sections taken from biopsy and resected specimens that were fixed in 10% buffered formalin were cut. The sections were stained with haematoxylin and eosin for evaluation of histopathologic features, Alcian blue (AB, Periodic Acid-Schiff stain (PAS to demonstrate metaplasia. OBSERVATION AND RESULTS This study covered a total of 323 cases, in which 277 were endoscopic biopsies and 46 were oesophagectomy specimens. In 277 endoscopic biopsies, 193 were males (69.68 and 84 were females (30.33%. There was increased incidence of oesophageal lesions observed. In the age group of 51-60, most of the patients in our study had complained of dysphagia (90.25% followed by loss of weight (70.04% and anorexia (54.87%. Among the 277 cases, 9 cases were Barrett’s (3.24%, 18 cases were diagnosed as adenocarcinoma (6.498%, 176 cases were diagnosed as squamous cell carcinomas (63.18%, 42 cases were squamous intraepithelial lesion (15.16%, 14 cases were interpreted as normal stratified squamous epithelium (5.05%, 14 cases were interpreted as only necrotic material/no tissue (5.05%. One case of basaloid squamous cell carcinoma, which is of poor prognosis was seen. One case of adenosquamous carcinoma characterised by mixed

  2. Multiphoton microscopy and microspectroscopy for diagnostics of inflammatory and neoplastic lung

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    Pavlova, Ina; Hume, Kelly R.; Yazinski, Stephanie A.; Flanders, James; Southard, Teresa L.; Weiss, Robert S.; Webb, Watt W.

    2012-03-01

    Limitations of current medical procedures for detecting early lung cancers inspire the need for new diagnostic imaging modalities for the direct microscopic visualization of lung nodules. Multiphoton microscopy (MPM) provides for subcellular resolution imaging of intrinsic fluorescence from unprocessed tissue with minimal optical attenuation and photodamage. We demonstrate that MPM detects morphological and spectral features of lung tissue and differentiates between normal, inflammatory and neoplastic lung. Ex vivo MPM imaging of intrinsic two-photon excited fluorescence was performed on mouse and canine neoplastic, inflammatory and tumor-free lung sites. Results showed that MPM detected microanatomical differences between tumor-free and neoplastic lung tissue similar to standard histopathology but without the need for tissue processing. Furthermore, inflammatory sites displayed a distinct red-shifted fluorescence compared to neoplasms in both mouse and canine lung, and adenocarcinomas displayed a less pronounced fluorescence emission in the 500 to 550 nm region compared to adenomas in mouse models of lung cancer. These spectral distinctions were also confirmed by two-photon excited fluorescence microspectroscopy. We demonstrate the feasibility of applying MPM imaging of intrinsic fluorescence for the differentiation of lung neoplasms, inflammatory and tumor-free lung, which motivates the application of multiphoton endoscopy for the in situ imaging of lung nodules.

  3. Annexin A3 is a mammary marker and a potential neoplastic breast cell therapeutic target.

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    Zeidan, Bashar; Jackson, Thomas R; Larkin, Samantha E T; Cutress, Ramsey I; Coulton, Gary R; Ashton-Key, Margaret; Murray, Nick; Packham, Graham; Gorgoulis, Vassilis; Garbis, Spiros D; Townsend, Paul A

    2015-08-28

    Breast cancers are the most common cancer-affecting women; critically the identification of novel biomarkers for improving early detection, stratification and differentiation from benign tumours is important for the reduction of morbidity and mortality.To identify and functionally characterise potential biomarkers, we used mass spectrometry (MS) to analyse serum samples representing control, benign breast disease (BBD) and invasive breast cancer (IDC) patients. Complementary and multidimensional proteomic approaches were used to identify and validate novel serum markers.Annexin A3 (ANX A3) was found to be differentially expressed amongst different breast pathologies. The diagnostic value of serum ANX A3 was subsequently validated by ELISA in an independent serum set representing the three groups. Here, ANX A3 was significantly upregulated in the benign disease group sera compared with other groups (P A3 was abundantly expressed in benign and to a lesser extent malignant neoplastic epithelium. Finally, we illustrated ANX A3 expression in cell culture lysates and conditioned media from neoplastic breast cell lines, and its role in neoplastic breast cell migration in vitro.This study confirms the novel role of ANX A3 as a mammary biomarker, regulator and therapeutic target.

  4. Nosocomial Infections among Pediatric Patients with Neoplastic Diseases

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    Peninnah Oberdorfer

    2009-01-01

    Full Text Available Background. Pediatric patients with neoplastic diseases are more likely to develop nosocomial infections (NIs. NIs may prolong their hospital stay, and increase morbidity and mortality. Objectives. The objectives of this study were to determine: (1 the incidence of NIs, (2 sites of NIs, (3 causal organisms, and (4 outcomes of NIs among pediatric patients with neoplastic diseases. Methods. This study was a prospective cohort study of pediatric patients with neoplastic diseases who were admitted to the Chiang Mai University Hospital, Thailand. Results. A total of 707 pediatric patients with neoplastic diseases were admitted. Forty-six episodes of NIs in 30 patients were reported (6.5 NIs/100 admission episodes and 7 NIs/1000 days of hospitalization. Patients with acute lymphoblastic leukemia had the highest number of NIs (41.3%. The most common causal organisms were gram-negative bacteria (47.1%. Patients who had undergone invasive procedures were more likely to develop NIs than those who had not (P<.05. The mortality rate of patients with NIs was 19.6%. Conclusion. Pediatric patients with neoplastic diseases are more likely to develop NIs after having undergone invasive procedures. Pediatricians should be aware of this and strictly follow infection control guidelines in order to reduce morbidity and mortality rates related to NIs.

  5. Nosocomial Infections among Pediatric Patients with Neoplastic Diseases.

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    Oberdorfer, Peninnah; Pongwilairat, Natthida; Washington, Charles H

    2009-01-01

    Background. Pediatric patients with neoplastic diseases are more likely to develop nosocomial infections (NIs). NIs may prolong their hospital stay, and increase morbidity and mortality. Objectives. The objectives of this study were to determine: (1) the incidence of NIs, (2) sites of NIs, (3) causal organisms, and (4) outcomes of NIs among pediatric patients with neoplastic diseases. Methods. This study was a prospective cohort study of pediatric patients with neoplastic diseases who were admitted to the Chiang Mai University Hospital, Thailand. Results. A total of 707 pediatric patients with neoplastic diseases were admitted. Forty-six episodes of NIs in 30 patients were reported (6.5 NIs/100 admission episodes and 7 NIs/1000 days of hospitalization). Patients with acute lymphoblastic leukemia had the highest number of NIs (41.3%). The most common causal organisms were gram-negative bacteria (47.1%). Patients who had undergone invasive procedures were more likely to develop NIs than those who had not (P < .05). The mortality rate of patients with NIs was 19.6%. Conclusion. Pediatric patients with neoplastic diseases are more likely to develop NIs after having undergone invasive procedures. Pediatricians should be aware of this and strictly follow infection control guidelines in order to reduce morbidity and mortality rates related to NIs.

  6. Results of screening in Lublin Province, Poland, for colorectal cancer and neoplastic polyps - the role of environmental factors

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    Halina Cichoż-Lach

    2017-03-01

    Full Text Available [b]Introduction and objective.[/b] Screening colonoscopy is a recommended tool, and the most sensitive and cost-effective method for reducing the incidence of colorectal cancer (CRC. [b]Objective.[/b] The purpose of the study was to present the results of a 5-year screening for early detection of CRC carried out among the population of the central-eastern regions of Poland, primarily in Lublin Province. [b]Materials and method. [/b]Screening colonoscopy was conducted in a group of 1,009 patients – 636 women and 373 men, aged 40–65 years. [b]Results.[/b] Neoplastic polyps were found in 275 patients, advanced adenomas in 49 patients and adenocarcinoma in 13. 70.55% of neoplastic polyps was located in the distal colon, 18.9% in the proximal part and 10.55% in both regions, advanced adenomas in 79.59%, 8.16% and 12.25%, respectively. Adenocarcinoma was located in the proximal colon in 2 cases and in the distal region in 11 cases. Neoplastic polyps and advanced adenomas occurred significantly more frequently in smokers than in non-smokers. Neoplastic polyps were found statistically more frequent in males than in females, among the overweight and obese patients, than in subjects with normal BMI, and more frequently in the group of urban, compared to rural patients. However, the frequency of advanced adenomas and CRC was not statistically different in those groups. The incidence of CRC was statistically more frequent in males than in females. Smoking and male gender were significant risk factors for developing neoplastic polyps. Male gender seemed to predispose to CRC. Obesity was found to favour advanced adenomas. [b]Conclusions.[/b] The results of screening found neoplastic polyps in every third person (mean who did not have any symptoms suggestive of colon pathology. Advanced adenomas were found in 5% of the examined and CRC was detected in 1.29% of participants. Smoking, male gender and overweight were significant risk factors for developing

  7. Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis

    Science.gov (United States)

    Bueso-Ramos, Carlos E.; Newberry, Kate J.; Knez, Liza; Post, Sean M.; Ahn, Jihae; Levine, Ross L.; Kantarjian, Hagop M.

    2016-01-01

    Primary myelofibrosis (PMF) is a fatal neoplastic disease characterized by clonal myeloproliferation and progressive bone marrow (BM) fibrosis thought to be induced by mesenchymal stromal cells stimulated by overproduced growth factors. However, tissue fibrosis in other diseases is associated with monocyte-derived fibrocytes. Therefore, we sought to determine whether fibrocytes play a role in the induction of BM fibrosis in PMF. In this study, we show that BM from patients with PMF harbors an abundance of clonal, neoplastic collagen- and fibronectin-producing fibrocytes. Immunodeficient mice transplanted with myelofibrosis patients’ BM cells developed a lethal myelofibrosis-like phenotype. Treatment of the xenograft mice with the fibrocyte inhibitor serum amyloid P (SAP; pentraxin-2) significantly prolonged survival and slowed the development of BM fibrosis. Collectively, our data suggest that neoplastic fibrocytes contribute to the induction of BM fibrosis in PMF, and inhibiting fibrocyte differentiation with SAP may interfere with this process. PMID:27481130

  8. Sequential Molecular and Cellular Events during Neoplastic Progression: A Mouse Syngeneic Ovarian Cancer Model

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    Paul C. Roberts

    2005-10-01

    Full Text Available Studies performed to identify early events of ovarian cancer and to establish molecular markers to support early detection and development of chemopreventive regimens have been hindered by a lack of adequate cell models. Taking advantage of the spontaneous transformation of mouse ovarian surface epithelial (MDSE cells in culture, we isolated and characterized distinct transitional stages of ovarian cancer as the cells progressed from a premalignant nontumorigenic phenotype to a highly aggressive malignant phenotype. Transitional stages were concurrent with progressive increases in proliferation, anchorage-independent growth capacity, in vivo tumor formation, and aneuploidy. During neoplastic progression, our ovarian cancer model underwent distinct remodeling of the actin cytoskeleton and focal adhesion complexes, concomitant with downregulation and/or aberrant subcellular localization of two tumor-suppressor proteins Ecadherin and connexin-43. In addition, we demonstrate that epigenetic silencing of E-cadherin through promoter methylation is associated with neoplastic progression of our ovarian cancer model. These results establish critical interactions between cellular cytoskeletal remodeling and epigenetic silencing events in the progression of ovarian cancer. Thus, our MDSE model provides an excellent tool to identify both cellularand molecular changes in the early and late stages of ovarian cancer, to evaluate their regulation, and to determine their significance in an immunocompetent in vivo environment.

  9. Use of Antihypertensive Drugs in Neoplastic Patients.

    Science.gov (United States)

    Rizzoni, Damiano; De Ciuceis, Carolina; Porteri, Enzo; Agabiti-Rosei, Claudia; Agabiti-Rosei, Enrico

    2017-06-01

    The introduction of Vascular Endothelial Growth Factor (VEGF) signaling pathway inhibitor treatment has highlighted the role of the baseline activity of the VEFG system for blood pressure regulation. VEGF signaling pathway is associated with hypertension and proteinuria. Activation of the endothelin system, endothelial dysfunction and capillary rarefaction are among the underlying mechanisms possibly explaining the rise in blood pressure and, to some extent, also the renal injury. The hypertension induced by VEGF signaling pathway inhibition is, usually, responsive to treatment. Recommendations about the management of cardiovascular toxicity in patients receiving VEGF signaling pathway inhibitors include a formal cardiovascular risk assessment before initiation of VEGF signaling pathway inhibitor treatment, active monitoring of blood pressure and cardiac toxicity throughout treatment, with more frequent monitoring during the first cycles of therapy, given that marked and unpredictable blood pressure rises can occur early after treatment with a VEGF signaling pathway inhibitor, and aggressive management of blood pressure elevations and early symptoms and signs of cardiac toxicity to prevent clinically limiting complications. In patients with preexisting hypertension, the blood pressure target for initiating VEGF signaling pathway inhibitor treatment should be <140/90 mmHg. Blockers of the renin-angiotensin system and calcium channel antagonists are among the drugs to be preferably used in these clinical conditions.

  10. Insight to neoplastic thyroid lesions by fine needle aspiration cytology

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    M Rangaswamy

    2013-01-01

    Conclusions: FNAC is a rapid, efficient, cost-effective, relatively painless procedure with a high diagnostic accuracy. It has high rate of sensitivity and positive predictive value in diagnosing thyroid neoplastic lesions. Hence, it is a valuable tool in the diagnosis and management of patients.

  11. Chromosomal abnormalities in non-neoplastic renal tissue

    NARCIS (Netherlands)

    vandenBerg, E; Dijkhuizen, T; Storkel, S; Molenaar, WM; deJong, B

    1995-01-01

    Chromosome aberrations were studied in short-term cultures of non-neoplastic renal tissue and tumor tissue in 60 patients, 41 male and 19 female, with renal cell cancer (RCC), and in normal renal parenchyma from two cases, one male and one female, at autopsy with non-kidney related disease. Cytogene

  12. Chromosomal abnormalities in non-neoplastic renal tissue

    NARCIS (Netherlands)

    vandenBerg, E; Dijkhuizen, T; Storkel, S; Molenaar, WM; deJong, B

    1995-01-01

    Chromosome aberrations were studied in short-term cultures of non-neoplastic renal tissue and tumor tissue in 60 patients, 41 male and 19 female, with renal cell cancer (RCC), and in normal renal parenchyma from two cases, one male and one female, at autopsy with non-kidney related disease. Cytogene

  13. New models of neoplastic progression in Barrett's oesophagus

    NARCIS (Netherlands)

    Pavlov, Kirill; Maley, Carlo C.

    2010-01-01

    Research in Barrett's oesophagus, and neoplastic progression to OAC (oesophageal adenocarcinoma), is hobbled by the lack of good pre-clinical models that capture the evolutionary dynamics of Barrett's cell populations. Current models trade off tractability for realism. Computational models are perha

  14. BM-derived cells randomly contribute to neoplastic and non-neoplastic epithelial tissues at low rates.

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    Soldini, D; Moreno, E; Martin, V; Gratwohl, A; Marone, C; Mazzucchelli, L

    2008-12-01

    Epithelial cancers can arise from BM-derived cells (BMCs) in animal models. We studied whether the same phenomenon can occur in humans. Biopsy specimens from carcinomas and healthy adjacent tissues were obtained from three women who had undergone allogeneic BMT from an HLA-matched brother. Complete donor hematopoietic chimerism was verified by cytogenetic analysis, RFLP analysis or by reverse transcription-PCR analysis. Biopsies were studied for the presence of the Y chromosome derived from BM-derived cells by combined FISH and immunohistochemical staining. In our studies, we showed that human epithelial neoplastic and adjacent non-neoplastic tissues incorporate the Y chromosome at low and comparable rates. The lack of enrichment in malignancies argues against the possibility that BM-derived cells represent a direct source of carcinomas, and we suggest that these cells randomly contribute to neoplastic and non-neoplastic epithelial cells. On the basis of the absence of a fusion karyotype, we favor a model in which the differentiation of BM-derived cells is largely determined by the microenvironment encountered.

  15. Neoplastic Disorders in 100 Patients with Adult Celiac Disease

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    HUGH J Freeman

    1996-01-01

    Full Text Available Previous reports have suggested that the incidence of some neoplastic disorders, particularly malignant lymphoma, is increased in patients with celiac disease. In this study, the type and number of neoplastic disorders detected in 100 consecutive celiac disease patients were explored. Sixty-five patients were initially diagnosed with celiac disease before, and 35 after, age 60 years. Ten elderly celiac patients had lymphoma or small intestinal adenocarcinoma. Although the overall incidence of malignant lymphoma was 8%, similar to that in other centres, the incidence in elderly celiac patients was 23% in this study. Celiac disease was detected before or after the diagnosis of lymphoma or small intestinal adenocarcinoma. In some patients, epithelial lymphocytosis was evident in the gastric, colonic or biliary tract epithelium. In addition, other immune-mediated disorders, dermatitis herpetiformis and autoimmune thyroiditis, were common. Finally, other malignant disorders of the esophagus, stomach and colon were not detected.

  16. Neoplastic transformation and tumorigenesis by the human protooncogene MYC

    Energy Technology Data Exchange (ETDEWEB)

    Ramsay, G.M.; Bishop, J.M. (Univ. of California, San Francisco (USA)); Moscovici, G.; Moscovici, C. (Univ. of Florida, Gainesville (USA))

    1990-03-01

    Damage to the protooncogene MYC has been implicated in the genesis of diverse human tumors, but the tumorigenic potential of the isolated gene has been disputed. Here the authors report the use of a retroviral vector to test the potency of human MYC for neoplastic transformation in avian cells. They found that sustained and abundant expression of MYC can transform both embryonic fibroblasts and hematopoietic cells and elicit granulocytic leukemias in chickens. Transformation by MYC is accompanied by changes in diverse aspects of cellular phenotype, including morphology, ability to grow in suspension, rate of proliferation, the structure of the cytoskeleton, and the composition of the extracellular matrix. Nevertheless, the biological potency of MYC is inherently constrained when compared to that of the retroviral oncogene v-myc. The findings enlarge on previous descriptions of neoplastic transformation by MYC and sustain the view that ungoverned expression of the gene can contribute to the genesis of human tumors.

  17. Neoplastic transformation and tumorigenesis by the human protooncogene MYC.

    Science.gov (United States)

    Ramsay, G M; Moscovici, G; Moscovici, C; Bishop, J M

    1990-01-01

    Damage to the protooncogene MYC has been implicated in the genesis of diverse human tumors, but the tumorigenic potential of the isolated gene has been disputed. Here we report the use of a retroviral vector to test the potency of human MYC for neoplastic transformation in avian cells. We found that sustained and abundant expression of MYC can transform both embryonic fibroblasts and hematopoietic cells and elicit granulocytic leukemias in chickens. Transformation by MYC is accompanied by changes in diverse aspects of cellular phenotype, including morphology, ability to grow in suspension, rate of proliferation, the structure of the cytoskeleton, and the composition of the extracellular matrix. Nevertheless, the biological potency of MYC is inherently constrained when compared to that of the retroviral oncogene v-myc. Our findings enlarge on previous descriptions of neoplastic transformation by MYC and sustain the view that ungoverned expression of the gene can contribute to the genesis of human tumors. Images PMID:2156260

  18. Microbial growth tests in anti-neoplastic injectable solutions.

    Science.gov (United States)

    Paris, Isabelle; Paci, Angelo; Rey, Jean-Baptiste; Bourget, Philippe

    2005-03-01

    The Institut Gustave-Roussy (IGR) Department of Clinical Pharmacy (DCP) ensures the annual preparation of about 30 000 therapeutic batches of anti-neoplastic agents. High performance thin-layer chromatography (HPTLC) allows postproduction quality control of these batches. Although the centralized chemotherapy manufacturing unit has been recently ISO 9001:2000 certified, it was considered to improve the quality level of manufactured batches even further. The viability of micro-organisms (bacteria and fungi) in appropriate sterile media containing various anti-neoplastic agents at therapeutic concentration was assessed to demonstrate the lack of contamination during our manufacturing process in the isolator. After 14 days of incubation in these media, the results show the absence of contamination of the manufactured batches. This leads us to conclude that using sterile drugs and sterile medical devices in a sterile isolator allows the manufacture of sterile therapeutic batches with excellent confidence.

  19. Non-neoplastic conditions presenting as soft-tissue tumours

    Energy Technology Data Exchange (ETDEWEB)

    Crundwell, N. [Royal National Orthopaedic Hospital, Stanmore, Middlesex (United Kingdom); O' Donnell, P. [Royal National Orthopaedic Hospital, Stanmore, Middlesex (United Kingdom); Saifuddin, A. [Royal National Orthopaedic Hospital, Stanmore, Middlesex (United Kingdom)]. E-mail: asif.saifuddin@rnoh.nhs.uk

    2007-01-15

    Review of referrals to our unit over the last 7 years showed that of approximately 750 cases referred as soft-tissue tumours, 132 were subsequently diagnosed as non-neoplastic lesions. The imaging characteristics of these lesions are presented to differentiate them from neoplasms. The most common diagnoses were myositis ossificans, ganglion cyst, abscess/infection, bursitis and synovitis. The imaging features of other rarer conditions will also be discussed.

  20. Cellular neoplastic transformation induced by 916 MHz microwave radiation.

    Science.gov (United States)

    Yang, Lei; Hao, Dongmei; Wang, Minglian; Zeng, Yi; Wu, Shuicai; Zeng, Yanjun

    2012-08-01

    There has been growing concern about the possibility of adverse health effects resulting from exposure to microwave radiations, such as those emitted by mobile phones. The purpose of this study was to investigate the cellular neoplastic transformation effects of electromagnetic fields. 916 MHz continuous microwave was employed in our study to simulate the electromagnetic radiation of mobile phone. NIH/3T3 cells were adopted in our experiment due to their sensitivity to carcinogen or cancer promoter in environment. They were divided randomly into one control group and three microwave groups. The three microwave groups were exposed to 916 MHz EMF for 2 h per day with power density of 10, 50, and 90 w/m(2), respectively, in which 10 w/m(2) was close to intensity near the antenna of mobile phone. The morphology and proliferation of NIH/3T3 cells were examined and furthermore soft agar culture and animal carcinogenesis assay were carried out to determine the neoplastic promotion. Our experiments showed NIH/3T3 cells changed in morphology and proliferation after 5-8 weeks exposure and formed clone in soft agar culture after another 3-4 weeks depending on the exposure intensity. In the animal carcinogenesis study, lumps developed on the back of SCID mice after being inoculated into exposed NIH/3T3 cells for more than 4 weeks. The results indicate that microwave radiation can promote neoplastic transformation of NIH/3T3cells.

  1. Angiogenic Signalling Pathways Altered in Gliomas: Selection Mechanisms for More Aggressive Neoplastic Subpopulations with Invasive Phenotype

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    Susana Bulnes

    2012-01-01

    Full Text Available The angiogenesis process is a key event for glioma survival, malignancy and growth. The start of angiogenesis is mediated by a cascade of intratumoural events: alteration of the microvasculature network; a hypoxic microenvironment; adaptation of neoplastic cells and synthesis of pro-angiogenic factors. Due to a chaotic blood flow, a consequence of an aberrant microvasculature, tissue hypoxia phenomena are induced. Hypoxia inducible factor 1 is a major regulator in glioma invasiveness and angiogenesis. Clones of neoplastic cells with stem cell characteristics are selected by HIF-1. These cells, called “glioma stem cells” induce the synthesis of vascular endothelial growth factor. This factor is a pivotal mediator of angiogenesis. To elucidate the role of these angiogenic mediators during glioma growth, we have used a rat endogenous glioma model. Gliomas induced by prenatal ENU administration allowed us to study angiogenic events from early to advanced tumour stages. Events such as microvascular aberrations, hypoxia, GSC selection and VEGF synthesis may be studied in depth. Our data showed that for the treatment of gliomas, developing anti-angiogenic therapies could be aimed at GSCs, HIF-1 or VEGF. The ENU-glioma model can be considered to be a useful option to check novel designs of these treatment strategies.

  2. Angiogenic Signalling Pathways Altered in Gliomas: Selection Mechanisms for More Aggressive Neoplastic Subpopulations with Invasive Phenotype

    Science.gov (United States)

    Bulnes, Susana; Bengoetxea, Harkaitz; Ortuzar, Naiara; Argandoña, Enrike G.; Garcia-Blanco, Álvaro; Rico-Barrio, Irantzu; Lafuente, José V.

    2012-01-01

    The angiogenesis process is a key event for glioma survival, malignancy and growth. The start of angiogenesis is mediated by a cascade of intratumoural events: alteration of the microvasculature network; a hypoxic microenvironment; adaptation of neoplastic cells and synthesis of pro-angiogenic factors. Due to a chaotic blood flow, a consequence of an aberrant microvasculature, tissue hypoxia phenomena are induced. Hypoxia inducible factor 1 is a major regulator in glioma invasiveness and angiogenesis. Clones of neoplastic cells with stem cell characteristics are selected by HIF-1. These cells, called “glioma stem cells” induce the synthesis of vascular endothelial growth factor. This factor is a pivotal mediator of angiogenesis. To elucidate the role of these angiogenic mediators during glioma growth, we have used a rat endogenous glioma model. Gliomas induced by prenatal ENU administration allowed us to study angiogenic events from early to advanced tumour stages. Events such as microvascular aberrations, hypoxia, GSC selection and VEGF synthesis may be studied in depth. Our data showed that for the treatment of gliomas, developing anti-angiogenic therapies could be aimed at GSCs, HIF-1 or VEGF. The ENU-glioma model can be considered to be a useful option to check novel designs of these treatment strategies. PMID:22852079

  3. A novel stem cell associated marker identified by monoclonal antibody HESC5:3 differentiates between neoplastic lesions in follicular thyroid neoplasms.

    Science.gov (United States)

    Heikkilä, Annukka; Fermér, Christian; Hagström, Jaana; Louhimo, Johanna; Mäenpää, Hanna; Siironen, Päivi; Heiskanen, Ilkka; Nilsson, Olle; Arola, Johanna; Haglund, Caj

    2015-07-01

    Follicular thyroid lesions are the bane of cytopathology. Differentiation between adenoma and carcinoma is impossible, and often these neoplasms are indistinguishable even from uninodular goitre. In other cancers as well, a theory of stem cells as the origin of cancer has been discussed in thyroid carcinogenesis. We aimed to examine a novel stem cell associated marker identified by monoclonal antibody HESC5:3 in follicular lesions in an attempt to find a marker for differential diagnosis in thyroid cytopathology. HESC5:3 was raised against and is specific for undifferentiated human embryonic stem cells. The epitope of this novel antibody is to be defined. Immunohistochemical expression of HESC5:3 was examined in clinical material comprised of follicular neoplasms (83 adenomas, 43 carcinomas) and non-neoplastic lesions (41 goitrous, 22 hyperplastic, 23 normal tissue specimens). Staining differed significantly between neoplastic and non-neoplastic lesions. Nuclear staining was increased in non-neoplastic cells, whereas in neoplastic cells expression was mainly cytoplasmic. There was no difference between benign and malignant lesions, suggesting a role in early tumourigenesis. In conclusion, the HESC5:3 epitope may be of benefit as a neoplasia marker in distinguishing between uninodular goitre and neoplasia. Characterization of the epitope would increase the interest in this promising new stem cell associated marker.

  4. Early

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    Kamel Abd Elaziz Mohamed

    2014-04-01

    Conclusion: Early PDT is recommended for patients who require prolonged tracheal intubation in the ICU as outcomes like the duration of mechanical ventilation length of ICU stay and hospital stay were significantly shorter in early tracheostomy.

  5. Albumin storage in neoplastic astroglial elements of gangliogliomas

    Science.gov (United States)

    Schmitz, Ann Kristin; Grote, Alexander; Raabe, Anna; Urbach, Horst; Friedman, Alon; von Lehe, Marec; Becker, Albert J.; Niehusmann, Pitt

    2013-01-01

    Purpose Low-grade neuroepithelial tumors are frequent neuropathological findings in patients with pharmacoresistant epilepsies. Little is known regarding epileptogenic mechanisms in this group of neoplasms with gangliogliomas (GG) as the most common entity. Presence of hemosiderin deposits in GG points to impairment of the blood-brain barrier (BBB). Therefore, we hypothesized a potential role of BBB dysfunction and astrocytic albumin uptake as potential epileptogenic factor in GG. Methods Prussian blue staining and fluorescent double-immunohistochemistry with antibodies against albumin, GFAP, CD34 and GLUT-1 were used to analyze hemosiderin deposits and astroglial albumin accumulation in tumor and adjacent pre-existing brain tissue of GG (n = 10) and several control groups, i.e. dysembryoplastic neuroepithelial tumors (DNT; n = 5), focal cortical dysplasia with balloon cells (FCD IIb; n = 10), astrocytomas WHO grade II (n = 5) and clear renal cell carcinoma brain metastases (RCCM, n = 6). Results Our results revealed strong hemosiderin deposits in GG. Intriguingly, we noted substantial albumin uptake exclusively in neoplastic glial cell components of GG and DNT, whereas no significant albumin was present in perilesional reactive astrocytes. Strikingly, we did not observe substantial albumin uptake in further controls. Conclusion Glial albumin uptake was restricted to long-term epilepsy associated, vasculature-containing tumors. Intratumoural BBB dysfunction in concert with subsequent accumulation of albumin by neoplastic glial cell elements represent a new putatively epileptogenic mechanism for long-term epilepsy-associated tumors. PMID:23182422

  6. Prognostic value of podoplanin expression in intratumoral stroma and neoplastic cells of uterine cervical carcinomas

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    Filomena M Carvalho

    2010-01-01

    Full Text Available OBJECTIVE: To investigate the clinicopathological significance of podoplanin expression in the intratumoral stroma and neoplastic cells of early stage uterine cervical cancer. MATERIALS AND METHODS: A total of 143 patients with clinical stage I and IIA uterine cervical carcinomas underwent surgery between 2000 and 2007. Clinicopathological data and slides associated with these cases were retrospectively reviewed. Immunodetection of podoplanin expression in histologic sections of tissue microarray blocks was performed using the monoclonal antibody D2-40. RESULTS: Expression of podoplanin was detected in neoplastic cells in 31/143 (21.6% cases, with 29/31 (93.5% of these cases diagnosed as squamous carcinoma. For all of the cases examined, the strongest signal for podoplanin expression was observed at the proliferating edge of the tumor nests. The rate of positive podoplanin expression for node-positive cases was lower than that of node-negative (18.9% vs. 22.6%, respectively. Furthermore, the rate of positive podoplanin expression in fatal cases was 10.5% vs. 21.6%, respectively. In 27/143 (18.8% cases, podoplanin expression was detected in fibroblasts of the intratumoral stroma, and this expression did not correlate with patient age, clinical stage, tumor size, histologic type, depth of infiltration, or vascular involvement. Moreover, expression of podoplanin in intratumoral stroma fibroblasts was only negatively associated with nodal metastasis. A greater number of fatal cases was observed among negative intratumoral stroma fibroblasts (15.5% vs. 3.7%, respectively, although this difference was not significant. CONCLUSIONS: These preliminary results suggest that podoplanin may have a role in host-tumor interactions and, as a result, may represent a favorable prognostic factor for squamous cervical carcinomas.

  7. FRA-1 protein overexpression is a feature of hyperplastic and neoplastic breast disorders

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    Di Bonito Maurizio

    2007-01-01

    Full Text Available Abstract Background Fos-related antigen 1 (FRA-1 is an immediate early gene encoding a member of AP-1 family of transcription factors involved in cell proliferation, differentiation, apoptosis, and other biological processes. fra-1 gene overexpression has an important role in the process of cellular transformation, and our previous studies suggest FRA-1 protein detection as a useful tool for the diagnosis of thyroid neoplasias. Here we investigate the expression of the FRA-1 protein in benign and malignant breast tissues by immunohistochemistry, Western blot, RT-PCR and qPCR analysis, to evaluate its possible help in the diagnosis and prognosis of breast neoplastic diseases. Methods We investigate the expression of the FRA-1 protein in 70 breast carcinomas and 30 benign breast diseases by immunohistochemistry, Western blot, RT-PCR and qPCR analysis. Results FRA-1 protein was present in all of the carcinoma samples with an intense staining in the nucleus. Positive staining was also found in most of fibroadenomas, but in this case the staining was present both in the nucleus and cytoplasm, and the number of positive cells was lower than in carcinomas. Similar results were obtained from the analysis of breast hyperplasias, with no differences in FRA-1 expression level between typical and atypical breast lesions; however the FRA-1 protein localization is mainly nuclear in the atypical hyperplasias. In situ breast carcinomas showed a pattern of FRA-1 protein expression very similar to that observed in atypical hyperplasias. Conversely, no FRA-1 protein was detectable in 6 normal breast tissue samples used as controls. RT-PCR and qPCR analysis confirmed these results. Similar results were obtained analysing FRA-1 expression in fine needle aspiration biopsy (FNAB samples. Conclusion The data shown here suggest that FRA-1 expression, including its intracellular localization, may be considered a useful marker for hyperplastic and neoplastic proliferative

  8. Clinical features of neoplastic pathological fracture in long bones

    Institute of Scientific and Technical Information of China (English)

    HU Yong-cheng; LUN Deng-xing; WANG Han

    2012-01-01

    Background Pathological fractures signify a potentially more aggressive subset of the original disease with higher misdiagnosis rates and inferior oncologic results.The purpose of the present study was to explore the clinical features of neoplastic pathological fracture in extremities.Methods From August 2002 to December 2010,a consecutive series of 139 patients suffering neoplastic pathological fracture were recruited,including 79 males and 60 females with a mean age of 31.3 years.Fractures were classified into five groups:tumor-like lesions (55),benign bone tumors (13),giant cell tumors (7),primary malignant bone tumors (28),and metastatic bone tumors (36).Based on their inducing forces,pathologic fractures were classified into four grades:spontaneous fracture,functional fracture,minor injury,and traumatic injury.Patients' age,fracture site,histological diagnoses,fracture forces,prodromes,and misdiagnosis were well reviewed.Kruskal-Wallis and x2 tests were used to compare forces and prodromes within different types of bone tumors.Results The highest pathologic fracture morbidity was 32.3% (45/139),which lay in the 11-20 year group,and 86.1%of metastatic tumors occurred in the 50-80 year group.The common sites of fractures were femur,humerus,and tibia.The fracture forces in benign bone tumors and tumor-like lesions are the strongest,followed by metastatic tumors and primary malignant bone tumors (Hc=80.980,P=0.000).Sixty-seven patients (48.2%) had local prodromes before pathologic fracture.The incidence rates of prodromes between primary malignant tumors and metastatic bone tumors had no significant difference (P=0.146),but they were all obviously higher than that of benign bone tumors and tumor-like lesions.Twenty patients experienced misdiagnosis.Conclusion Minor injury forces and local prodromes are clinical features of neoplastic pathologic fractures and they are also the critical factor avoiding misdiagnoses.

  9. Neoplastic transformation of breast epithelial cells by genotoxic stress

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    Raman Venu

    2010-06-01

    Full Text Available Abstract Background Exposure to genotoxic stresses such as radiation and tobacco smoke can cause increased cancer incidence rate as reflected in an in depth meta-analysis of data for women and breast cancer incidence. Published reports have indicated that exposures to low dose radiation and tobacco smoke are factors that contribute to the development of breast cancer. However, there is a scarcity of information on the combinatorial effects of low dose radiation and tobacco smoke on formation and progression of breast cancer. The combination of these two genotoxic insults can induce significant damage to the genetic material of the cells resulting in neoplastic transformation. Methods To study the effects of low dose ionizing radiation and tobacco smoke on breast cells, MCF 10A cells were treated either with radiation (Rad - 0.1 Gray or cigarette smoke condensate (Csc - 10 microgram/ml of medium or a combination of Rad + Csc. Following treatments, cells were analyzed for cell cycle distribution patterns and the ability to extrude the Hoechst 33342 dye. In addition, in vitro invasion and migration as well as mammosphere formation assays were performed. Finally, differential gene expression profiles were generated from the individual and combination treatment. Results Exposure of MCF 10A cells to the combination of radiation plus cigarette smoke condensate generated a neoplastic phenotype. The transformed phenotype promoted increased mammosphere numbers, altered cell cycle phases with a doubling of the population in S phase, and increased invasion and motility. Also, exclusion of Hoechst 33342 dye, a surrogate marker for increased ABC transporters, was observed, which indicates a possible increase in drug resistance. In addition, changes in gene expression include the up regulation of genes encoding proteins involved in metabolic pathways and inflammation. Conclusions The results indicate that when normal breast cells are exposed to low dose

  10. INSL-3 is expressed in human hyperplastic and neoplastic thyrocytes.

    Science.gov (United States)

    Hombach-Klonisch, Sabine; Hoang-Vu, Cuong; Kehlen, Astrid; Hinze, Raoul; Holzhausen, Hans-Jürgen; Weber, Ekkehard; Fischer, Bernd; Dralle, Henning; Klonisch, Thomas

    2003-05-01

    The insulin-like hormone INSL-3, also named relaxin-like factor (RLF) or Leydig-derived insulin-like peptide (LEY-IL), is expressed in various reproductive tissues and is regarded a marker of differentiation in human testicular Leydig cells. Recently, we have identified differential expression of human INSL-3 in neoplastic Leydig cells and mammary epithelial cells suggesting an involvement of INSL-3 in tumor biology. Here we have investigated the expression of INSL-3 in human thyroid carcinoma cell lines and in the human thyroid gland which has been shown to express transcripts for the G protein coupled INSL-3 receptor LGR8. When we determined the expression of INSL-3 in eight human thyroid carcinoma cell lines, a novel INSL-3 splice variant containing a 95 bp out-of-frame insertion at the beginning of exon II of the INSL-3 gene was discovered. Treatment of the human anaplastic thyroid carcinoma cell line 8505C with diethylstilbestrol (DES) caused a significant dose-dependent transcriptional down-regulation of INSL-3 and a marked up-regulation of LGR8. Employing in situ hybridization to detect INSL-3 transcripts and specific rabbit antisera against the INSL-3 proteins, both INSL-3 isoforms were detected in patients with Graves' disease (n=10), follicular carcinomas (FTC; n=12), papillary carcinomas (PTC; n=9) and undifferentiated anaplastic carcinomas (UTC; n=15). By contrast, thyrocytes of all 15 benign goiter tissues studied were devoid of both INSL-3 isoforms, mRNA and protein. Our data indicate that INSL-3 hormone is up-regulated in hyperplastic and neoplastic human thyrocytes suggesting that the INSL-3 isoforms may serve as additional markers for hyperplastic and neoplastic human thyrocytes. In the anaplastic thyroid carcinoma cell line 8505C, the regulation of both INSL-3 and LGR8 by estrogen may be the first indication of a novel hormonally responsive, auto-/paracrine INSL-3 LGR8 ligand receptor system active in human thyroid carcinoma cells.

  11. Adverse effects of thalidomide administration in patients with neoplastic diseases.

    Science.gov (United States)

    Dimopoulos, Meletios A; Eleutherakis-Papaiakovou, Vagelis

    2004-10-01

    Thalidomide, a glutamic acid derivative, was withdrawn from clinical use in 1962 due to its severe teratogenic effects. Its recent reinstitution in clinical practice was related to its benefits in leprosy and multiple myeloma. Moreover, the antiangiogenic and immunomodulatory properties of thalidomide have led to its evaluation in several malignant diseases, including myelofibrosis, renal cell cancer, prostate cancer, and Kaposi sarcoma. However, thalidomide use is associated with several side effects: somnolence and constipation are the most common, while deep vein thrombosis and peripheral neuropathy are the most serious. A combination of thalidomide with steroids or chemotherapy is being evaluated in several phase 2 studies. While it is not yet clear whether these combinations will enhance efficacy, they appear to increase the toxicity of thalidomide, and thalidomide analogs are being developed to minimize this toxicity. Ongoing studies will clarify the potential advantages of these agents in the treatment of neoplastic diseases.

  12. Autophagy process is associated with anti-neoplastic function

    Institute of Scientific and Technical Information of China (English)

    Chong Wang; Yachen Wang; Michael A. McNutt; Wei-Guo Zhu

    2011-01-01

    Autophagy is a highly conserved process of cellular degradation, which is present in yeast, plants, and mammals.Under normal physiological conditions, autophagy acts to maintain cellular homeostasis and regulate the turnover of organelles.In response to cellular stresses, autophagy prevents the accumulation of impaired proteins and organelles, which serves to inhibit carcinogenesis.On this basis,it is widely accepted that most tumor suppressors, such as beclin 1 associated proteins, forkhead box class O (FoxO)family proteins, multiple mammalian target of Rapamycin (mTOR) inactivators, and nuclear p53 play a role in indu cing autophagy.Here, we focus on how the process of autophagy is associated with anti-neoplastic function.

  13. Risk factors for neoplastic progression in Barrett's esophagus

    Institute of Scientific and Technical Information of China (English)

    Elizabeth F Wiseman; Yeng S Ang

    2011-01-01

    Barrett's esophagus (BE) confers a significant increasedrisk for development of esophageal adenocarcinoma (EAC), with the pathogenesis appearing to progress through a "metaplasia-dysplasia-carcinoma" (MDC) sequence. Many of the genetic insults driving this MDCsequence have recently been characterized, providing targets for candidate biomarkers with potential clinical utility to stratify risk in individual patients. Many clini-cal risk factors have been investigated, and associa-tions with a variety of genetic, specific gastrointestinaland other modifiable factors have been proposed in the literature. This review summarizes the current un-derstanding of the mechanisms involved in neoplastic progression of BE to EAC and critically appraises the relative roles and contributions of these putative risk factors from the published evidence currently available.

  14. Neoplastic meningitis as the presentation of occult primitive neuroectodermal tumors.

    Science.gov (United States)

    Jennings, M T; Slatkin, N; D'Angelo, M; Ketonen, L; Johnson, M D; Rosenblum, M; Creasy, J; Tulipan, N; Walker, R

    1993-10-01

    Seven children and young adults initially presented with subacute meningitis and/or increased intracranial pressure. The diagnosis of neoplastic meningitis secondary to a primitive neuroectodermal neoplasm was delayed by the absence of an obvious primary tumor. The neuroradiologic appearance was that of a basimeningeal infiltrative process, complicated by communicating hydrocephalus or "pseudotumor cerebri." Myelography was important in the diagnosis of disseminated meningeal malignancy in four cases. Cerebrospinal fluid cytologic diagnosis was insensitive but ultimately confirmed in five cases. All seven patients experienced progressive disease despite neuraxis radiotherapy and intensive chemotherapy; six have died. Systemic dissemination to bone and/or peritoneum occurred in three patients while on therapy. In two, a primary parenchymal brain or spinal cord tumor could not be identified at postmortem examination. The presentation of a primitive neuroectodermal tumor as subacute meningitis without an evident primary tumor heralds an aggressive and refractory neoplasm.

  15. Reversible posterior leukoencephalopathy syndrome and anti-neoplastic agents: a review

    Directory of Open Access Journals (Sweden)

    Farheen M. Shah-Khan

    2011-12-01

    Full Text Available Reversible Posterior Leukoencephalopathy Syndrome (RPLS is a well recognized entity with a variety of benign and malignant conditions. Recently it has been found to be associated with the use of anti-neoplastic agents including targeted therapies. RPLS occurs rapidly with the use of some drugs and more slowly with others. Combined therapies are associated with a more frequent and more rapid presentation. This review was based on a literature search for English Language articles concerning RPLS and chemotherapeutic agents published from June 1996 to March 2007. We used the PubMed database with keywords: “RPLS”, “Posterior reversible encephalopathy syndrome”, “(PRES”, “Chemotherapy” and “MRI”. This syndrome has classical Clinical-Radiologic features that are easy to recognize. Early recognition and withdrawal of the offending agent is all that is needed in most cases. This review highlights the features of the syndrome. It draws our attention to an entity which is being more frequently recognized and whose exact pathologic mechanisms need to be further studied. This syndrome is associated with the use of neurotoxic as well as non-neurotoxic agents and usually runs a benign course if there is an early diagnosis and management.

  16. Reversible posterior leukoencephalopathy syndrome and anti-neoplastic agents: a review

    Directory of Open Access Journals (Sweden)

    Farheen M. Shah-Khan

    2011-12-01

    Full Text Available Reversible Posterior Leukoencephalopathy Syndrome (RPLS is a well recognized entity with a variety of benign and malignant conditions. Recently it has been found to be associated with the use of anti-neoplastic agents including targeted therapies. RPLS occurs rapidly with the use of some drugs and more slowly with others. Combined therapies are associated with a more frequent and more rapid presentation. This review was based on a literature search for English Language articles concerning RPLS and chemotherapeutic agents published from June 1996 to March 2007. We used the PubMed database with keywords: “RPLS”, “Posterior reversible encephalopathy syndrome”, “(PRES”, “Chemotherapy” and “MRI”. This syndrome has classical Clinical-Radiologic features that are easy to recognize. Early recognition and withdrawal of the offending agent is all that is needed in most cases. This review highlights the features of the syndrome. It draws our attention to an entity which is being more frequently recognized and whose exact pathologic mechanisms need to be further studied. This syndrome is associated with the use of neurotoxic as well as non-neurotoxic agents and usually runs a benign course if there is an early diagnosis and management.

  17. Plasma lipid-bound sialic acid alterations in neoplastic diseases.

    Science.gov (United States)

    Dwivedi, C; Dixit, M; Hardy, R E

    1990-01-15

    Plasma lipid-bound sialic acid (LSA) was assayed in normal volunteers, patients with non-malignant diseases, and a variety of cancer patients. Mean plasma LSA in 50 normal volunteers, 16 patients with non-malignant diseases, 54 breast cancer, 17 lung cancer, 15 colon cancer, 7 ovarian cancer, 5 prostate cancer, 4 leukemia, 4 gastrointestinal, 3 thyroid cancer, 3 pancreas cancer and 2 adrenal cancer patients were 17.7, 23.2, 58, 85, 56.7, 46.2, 56.7, 53.3, 31.1, 33.2 and 119.5 mg/dl, respectively. None of the normal volunteers had elevated plasma LSA values. Plasma LSA level was not significantly different in male and female volunteers. Two out of 114 different cancer patients had plasma LSA levels within normal range exhibiting 98.2% sensitivity of the assay. Plasma LSA, which is relatively simple to assay, may be used as a tumor marker in wide variety of neoplastic diseases.

  18. Growth hormone is permissive for neoplastic colon growth.

    Science.gov (United States)

    Chesnokova, Vera; Zonis, Svetlana; Zhou, Cuiqi; Recouvreux, Maria Victoria; Ben-Shlomo, Anat; Araki, Takako; Barrett, Robert; Workman, Michael; Wawrowsky, Kolja; Ljubimov, Vladimir A; Uhart, Magdalena; Melmed, Shlomo

    2016-06-07

    Growth hormone (GH) excess in acromegaly is associated with increased precancerous colon polyps and soft tissue adenomas, whereas short-stature humans harboring an inactivating GH receptor mutation do not develop cancer. We show that locally expressed colon GH is abundant in conditions predisposing to colon cancer and in colon adenocarcinoma-associated stromal fibroblasts. Administration of a GH receptor (GHR) blocker in acromegaly patients induced colon p53 and adenomatous polyposis coli (APC), reversing progrowth GH signals. p53 was also induced in skin fibroblasts derived from short-statured humans with mutant GHR. GH-deficient prophet of pituitary-specific positive transcription factor 1 (Prop1)(-/-) mice exhibited induced colon p53 levels, and cross-breeding them with Apc(min+/-) mice that normally develop intestinal and colon tumors resulted in GH-deficient double mutants with markedly decreased tumor number and size. We also demonstrate that GH suppresses p53 and reduces apoptosis in human colon cell lines as well as in induced human pluripotent stem cell-derived intestinal organoids, and confirm in vivo that GH suppresses colon mucosal p53/p21. GH excess leads to decreased colon cell phosphatase and tensin homolog deleted on chromosome 10 (PTEN), increased cell survival with down-regulated APC, nuclear β-catenin accumulation, and increased epithelial-mesenchymal transition factors and colon cell motility. We propose that GH is a molecular component of the "field change" milieu permissive for neoplastic colon growth.

  19. Mechanisms of radiation-induced neoplastic cell transformation

    Energy Technology Data Exchange (ETDEWEB)

    Yang, T.C.H.; Tobias, C.A.

    1984-04-01

    Studies with cultured mammalian cells demonstrated clearly that radiation can transform cells directly and can enhance the cell transformation by oncogenic DNA viruses. In general, high-LET heavy-ion radiation can be more effective than X and gamma rays in inducing neoplastic cell transformation. Various experimental results indicate that radiation-induced DNA damage, most likely double-strand breaks, is important for both the initiation of cell transformation and for the enhancement of viral transformation. Some of the transformation and enhancement lesions can be repaired properly in the cell, and the amount of irrepairable lesions produced by a given dose depends on the quality of radiation. An inhibition of repair processes with chemical agents can increase the transformation frequency of cells exposed to radiation and/or oncogenic viruses, suggesting that repair mechanisms may play an important role in the radiation transformation. The progression of radiation-transformed cells appears to be a long and complicated process that can be modulated by some nonmutagenic chemical agents, e.g., DMSO. Normal cells can inhibit the expression of transforming properties of tumorigenic cells through an as yet unknown mechanism. The progression and expression of transformation may involve some epigenetic changes in the irradiated cells. 38 references, 15 figures, 1 table.

  20. Emperipolesis-like invasion of neoplastic lymphocytes into hepatocytes in feline T-cell lymphoma.

    Science.gov (United States)

    Suzuki, M; Kanae, Y; Kagawa, Y; Ano, N; Nomura, K; Ozaki, K; Narama, I

    2011-05-01

    Twelve cases of feline malignant lymphoma with emperipolesis-like invasion of neoplastic lymphocytes were examined microscopically, immunohistochemically and ultrastructurally. Intracytoplasmic invasion of neoplastic cells varied in severity between the cases, between hepatic lobules and between areas within the lobules. The number of infiltrating neoplastic cells ranged from one to several per hepatocyte. Neoplastic cells exhibited widely varying morphology from case-to-case and cell-to-cell within each case, and contained eosinophilic cytoplasmic granules in four cases. Immunohistochemical examination revealed that neoplastic cells in 11 of the 12 cases expressed one or both T-cell markers (CD3 and TIA-1). Diagnosis of T-cell lymphoma was also confirmed by assessment of clonality by polymerase chain reaction. Ultrastructural analysis revealed that the neoplastic lymphocytes were contained within an invagination of the cell membrane of the hepatocyte, rather than directly infiltrating into the cytoplasm of the cell. There was no evidence that the invasive neoplastic lymphocytes had a cytotoxic effect.

  1. Ultrasonography of small intestinal inflammatory and neoplastic diseases in dogs and cats.

    Science.gov (United States)

    Gaschen, Lorrie

    2011-03-01

    Ultrasonography, which has become a mainstay of diagnosing intestinal diseases in dogs and cats, is often one of the first diagnostic tools used to differentiate inflammatory from neoplastic infiltration of the small intestine. Although overlap in the sonographic appearances of inflammatory and neoplastic infiltration make a definitive diagnosis difficult, awareness of features of both diseases is important for the accurate interpretation of the sonographic findings. Full-thickness intestinal biopsy remains the gold standard for differentiating inflammatory from neoplastic disease of the small intestine.

  2. Imaging of demyelinating and neoplastic diseases of the spinal cord; Bildgebung bei demyelinisierenden und tumoroesen Erkrankungen des Rueckenmarks

    Energy Technology Data Exchange (ETDEWEB)

    Mueller-Mang, C. [Institut fuer CT und MRT Gaenserndorf, Gaenserndorf (Austria)

    2010-12-15

    The clinical symptoms of myelopathy are variable and non-specific. Demyelinating as well as neoplastic spinal cord diseases can cause paresthesia, progressive sensomotoric deficits and bowel and bladder dysfunction. Imaging of the spine, especially with magnetic resonance imaging (MRI), is an essential component in the diagnostic assessment of myelopathy and makes a substantial contribution to achieving the correct diagnosis. Although intramedullary neoplasms are far less common than demyelinating spinal cord diseases, radiologists should be familiar with the three most common entities, astrocytoma, ependymoma and hemangioblastoma, which represent over 70% of all spinal cord neoplasms. An early diagnosis and therapy is essential with neoplastic and demyelinating spinal cord diseases to hold residual neurological deficits as low as possible. (orig.) [German] Die klinische Symptomatik von Myelopathien ist aeusserst variabel und unspezifisch. Sowohl demyelinisierende als auch tumoroese Rueckenmarkerkrankungen koennen Paraesthesien, progrediente sensomotorische Ausfaelle und eine Sphinkterdysfunktion hervorrufen. Bildgebende Untersuchungen, und hier allen voran die MRT, sind ein unerlaesslicher Bestandteil zur Abklaerung von Myelopathien und tragen wesentlich zur korrekten Diagnose bei. Intramedullaere Tumoren sind zwar weitaus seltener als demyelinisierende Rueckenmarkerkrankungen, dennoch sollte der Radiologe mit den Bildmerkmalen der 3 haeufigsten Tumorarten, dem Astrozytom, Ependymom und Haemangioblastom vertraut sein, die ueber 70% aller Rueckenmarktumoren verursachen. Eine moeglichst fruehe Diagnostik und Therapie sind bei tumoroesen und demyelinisierenden Rueckenmarkerkrankungen essenziell, um bleibende neurologische Defizite moeglichst gering zu halten. (orig.)

  3. Protein p16 as a marker of dysplastic and neoplastic alterations in cervical epithelial cells

    Directory of Open Access Journals (Sweden)

    Spitkovsky Dimitry

    2004-08-01

    Full Text Available Abstract Background Cervical carcinomas are second most frequent type of women cancer. Success in diagnostics of this disease is due to the use of Pap-test (cytological smear analysis. However Pap-test gives significant portion of both false-positive and false-negative conclusions. Amendments of the diagnostic procedure are desirable. Aetiological role of papillomaviruses in cervical cancer is established while the role of cellular gene alterations in the course of tumor progression is less clear. Several research groups including us have recently named the protein p16INK4a as a possible diagnostic marker of cervical cancer. To evaluate whether the specificity of p16INK4a expression in dysplastic and neoplastic cervical epithelium is sufficient for such application we undertook a broader immunochistochemical registration of this protein with a highly p16INK4a-specific monoclonal antibody. Methods Paraffin-embedded samples of diagnostic biopsies and surgical materials were used. Control group included vaginal smears of healthy women and biopsy samples from patients with cervical ectopia. We examined 197 samples in total. Monoclonal antibody E6H4 (MTM Laboratories, Germany was used. Results In control samples we did not find any p16INK4a-positive cells. Overexpression of p16INK4a was detected in samples of cervical dysplasia (CINs and carcinomas. The portion of p16INK4a-positive samples increased in the row: CIN I – CIN II – CIN III – invasive carcinoma. For all stages the samples were found to be heterogeneous with respect to p16INK4a-expression. Every third of CINs III and one invasive squamous cell carcinoma (out of 21 analyzed were negative. Conclusions Overexpression of the protein p16INK4a is typical for dysplastic and neoplastic epithelium of cervix uteri. However p16INK4a-negative CINs and carcinomas do exist. All stages of CINs and carcinomas analyzed are heterogeneous with respect to p16INK4a expression. So p16INK4a-negativity is

  4. Low Dose Suppression of Neoplastic Transformation in Vitro

    Energy Technology Data Exchange (ETDEWEB)

    John Leslie Redpath

    2012-05-01

    This grant was to study the low dose suppression of neoplastic transformation in vitro and the shape of the dose-response curve at low doses and dose-rates of ionizing radiation. Previous findings had indicated a suppression of transformation at dose <10cGy of low-LET radiation when delivered at high dose-rate. The present study indicates that such suppression extends out to doses in excess of 100cGy when the dose (from I-125 photons) is delivered at dose-rates as low as 0.2 mGy/min and out to in excess of {approx}25cGy the highest dose studied at the very low dose-rate of 0.5 mGy/day. We also examined dose-rate effects for high energy protons (which are a low-LET radiation) and suppression was evident below {approx}10cGy for high dose-rate delivery and at least out to 50cGy for low dose-rate (20cGy/h) delivery. Finally, we also examined the effect of low doses of 1 GeV/n iron ions (a high-LET radiation) delivered at high dose-rate on transformation at low doses and found a suppression below {approx}10cGy that could be attributable to an adaptive response in bystander cells induced by the associated low-LET delta rays. These results have implications for cancer risk assessment at low doses.

  5. Non-neoplastic variants of the sternum detected on bone scintigrap

    Directory of Open Access Journals (Sweden)

    Yasser G. Abdelhafez

    2016-06-01

    Conclusion: Increased sternal uptake is significantly associated with CT structural abnormalities and knowledge of these non-neoplastic variants is essential for correct interpretation of SPECT/CT bone scans especially in patients with known cancers.

  6. Chondroblastoma and chondromyxoid fibroma : disentangling the neoplastic chondrogenesis of two rare cartilaginous tumours

    NARCIS (Netherlands)

    Romeo, Salvatore

    2010-01-01

    The scope of this study was to disentangle neoplastic chondrogenesis in two rare cartilaginous tumours: chondroblastoma and chondromyxoid fibroma. It was addressed: 1 The spectrum of phenotypic differentiation in chondroblastoma and chondromyxoid fibroma, 2 The signalling pathways driving chondrobla

  7. Hyaluronic Acid in Normal and Neoplastic Colorectal Tissue: Electrospray Ionization Mass Spectrometric and Fluor Metric Analysis

    Directory of Open Access Journals (Sweden)

    Ana Paula Cleto Marolla

    2016-01-01

    Conclusions: The expression of HA was found to be slightly lower in tumor tissue than in colorectal non-neoplastic mucosa, although this difference was not statistically significant. This finding probably influenced the lower expression of HA in tumor tissue than in colorectal non-neoplastic mucosa. Compared to normal tissues, HA levels are significantly increased in the tumor tissues unless they exhibit lymph node metastasis. Otherwise, the expression of HA in tumor tissue did not correlated with the other clinicopathological parameters.

  8. Factors that affect cancer patient compliance to oral anti-neoplastic therapy

    OpenAIRE

    Marques,Patrícia Andréa Crippa; Pierin, Angela Maria Geraldo

    2008-01-01

    OBJECTIVES: To identify factors that can affect compliance to treatment with neoplastic oral drugs in a group of cancer patients. METHODS: Interviews were performed on 61 patients diagnosed with cancer and under anti-neoplastic oral therapy in a private hospital. The interviews were carried out using instruments to assess compliance. RESULTS: Most patients (95%) reported the oral treatment was not difficult. The Morisky and Green Test were positive in 28% of the patients. Factors that may aff...

  9. Diffusion tensor imaging in inflammatory and neoplastic intramedullary spinal cord lesions: Focusing on fiber tracking

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyo Jin; Lee, Joon Woo; Lee, Eugene; Kim, Sung Gon; Kang, Yu Suhn; Ahn, Joong Mo; Kang, Heung Sik [Dept. of Radiology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

    2017-02-15

    Inflammatory and neoplastic intramedullary spinal cord lesions have overlapping clinical features, and it is occasionally difficult to distinguish one from the other on conventional magnetic resonance imaging. We aimed to compare diffusion tensor imaging findings between inflammatory and neoplastic intramedullary spinal cord lesions, with a specific focus on patterns of fiber tracking. Diffusion tensor imaging was performed in patients with either inflammatory or neoplastic intramedullary spinal cord lesions. The fiber tracking patterns (categorized as “intact,” “displaced,” or “interrupted”) were compared between these two groups. Eight patients were included in the study: 5 patients with pathologically or clinically confirmed inflammatory lesions and 3 patients with pathologically or clinically confirmed neoplastic lesions. Among the 5 patients with inflammatory lesions, 2 patients exhibited the displaced pattern and 3 patients exhibited the intact pattern. Among the 3 patients with neoplastic lesions, 1 patient exhibited the intact pattern, 1 patient exhibited the displaced pattern, and 1 patient exhibited the interrupted pattern. In this study, inflammatory and neoplastic intramedullary spinal cord lesions were not clearly differentiated by fiber tracking; both conditions can present with overlapping features such as displaced fibers. The exclusion of inflammatory conditions based on the presence of displaced fibers in fiber tracking images should be avoided.

  10. Recovery of uncommon bacteria from blood: association with neoplastic disease.

    Science.gov (United States)

    Beebe, J L; Koneman, E W

    1995-07-01

    bloodstream infections of Salmonella typhimurium and Capno-cytophaga canimorsus in Hodgkin's disease patients seems likely due to a particular mechanism which infection by these species is favored. The specific nature of these mechanisms remains to be determined. The recovery of any unusual bacterium from blood should warrant a careful consideration of the possibility of underlying disease, especially cancer. Microbiologists should advise clinicians of the unusual nature of the identified organism and provide the counsel that certain neoplastic processes, often accompanied by neutropenia, render the human host susceptible to invasion by almost any bacterium. The recovery of such organisms as C. septicum or S. bovis should prompt the clinician to aggressively seek to identify an occult neoplasm if one has not yet been diagnosed.

  11. Poly(ADP-ribosylation) and neoplastic transformation: effect of PARP inhibitors.

    Science.gov (United States)

    Donà, Francesca; Chiodi, Ilaria; Belgiovine, Cristina; Raineri, Tatiana; Ricotti, Roberta; Mondello, Chiara; Scovassi, Anna Ivana

    2013-01-01

    Poly(ADP-ribose) polymerases (PARPs) and poly(ADP-ribosylation) play essential roles in several biological processes, among which neoplastic transformation and telomere maintenance. In this paper, we review the poly(ADP-ribosylation) process together with the highly appealing use of PARP inhibitors for the treatment of cancer. In addition, we report our results concerning poly(ADP-ribosylation) in a cellular model system for neoplastic transformation developed in our laboratory. Here we show that PARP-1 and PARP-2 expression increases during neoplastic transformation, together with the basal levels of poly(ADP-ribosylation). Furthermore, we demonstrate a greater effect of the PARP inhibitor 3-aminobenzamide (3AB) on cellular viability in neoplastically transformed cells compared to normal fibroblasts and we show that prolonged 3AB administration to tumorigenic cells causes a decrease in telomere length. Taken together, our data support an active involvement of poly(ADP-ribosylation) in neoplastic transformation and telomere length maintenance and confirm the relevant role of poly(ADP-ribosylation) inhibition for the treatment of cancer.

  12. Extrathyroidal Implantation of Thyroid Hyperplastic/neoplastic Cells after Endoscopic Thyroid Surgery

    Institute of Scientific and Technical Information of China (English)

    Cao Xi; Xie-qun Xu; Tao Hong; Bing-lu Li; Wei Liu

    2014-01-01

    Objective To report a case of the implantation of thyroid hyperplastic or neoplastic tissue after endoscopic thyroidectomy and discuss this complication in aspects of prevalence, pathogenesis, protection, and therapies. Methods A systematic search of literature from the PubMed database was conducted for identifying eligible studies on implantation of thyroid hyperplastic or neoplastic cells after endoscopic thyroid surgery. Results Overall, 5 reported cases on patients suffering from endoscopic thyroid surgery with implantation of thyroid hyperplastic or neoplastic cells were included in the systematic review. Conclusions Unskilled surgeons, rough intraoperative surgical treatment, scarification or rupture of tumor, contamination of instruments, chimney effect, aerosolization of tumor cells may be associated with the implantation after endoscopic thyroidectomy. To minimize the risk of such complication, we should be more meticulous and strict the endoscopic surgery indications.

  13. A HISTOPATHOLOGICAL STUDY OF NEOPLASTIC LESIONS OF UTERINE CERVIX OF PERI AND POSTMENOPAUSAL WOMEN

    Directory of Open Access Journals (Sweden)

    Jogesh Kakati

    2017-03-01

    Full Text Available BACKGROUND Neoplastic lesions of uterine cervix is one of the most common malignant neoplasms in women. The tremendous success in giving a confirmed diagnosis of the disease by doing histopathological examination is of prime importance in giving the most appropriate treatment and to understand the prognosis. The aim of the study is to study the incidence and age-wise distribution of the neoplastic lesions of the uterine cervix in peri and postmenopausal women by doing histopathological examination of neoplastic lesions and by doing correlation of clinical findings with histopathological examination. MATERIALS AND METHODS The study included 803 cases of total cervical specimens, out of which 180 cases of neoplastic cervical lesions were found, out of which 150 cases were found in the peri and postmenopausal age groups, i.e. above 40 years of age. The study was done in Gauhati Medical College and Hospital, Guwahati, from the period 1 st June, 2013, to 1 st June, 2014. The specimens that were included in the study were punch biopsies, hysterectomies and polypectomies and cervical specimens were studied by doing histopathological examinations. RESULTS Out of the 150 cases of neoplastic lesions in the peri and postmenopausal women, the most common neoplastic lesion was cervical intraepithelial neoplasia, i.e. CIN (8.3% of the cervix, followed by malignant (5.6% and benign (4.7% lesions of the cervix in this study group of patients. CONCLUSION Histopathological examination of the cervix is an effective method of giving a confirmed diagnosis of all the noncancerous, precancerous and cancerous lesions of uterine cervix, which helps in giving the most appropriate treatment and also helps in understanding the prognosis.

  14. Hyaluronidases and hyaluronan synthases expression is inversely correlated with malignancy in lung/bronchial pre-neoplastic and neoplastic lesions, affecting prognosis

    Directory of Open Access Journals (Sweden)

    V.K. de Sá

    2015-11-01

    Full Text Available We collected a series of 136 lung/bronchial and 56 matched lung parenchyma tissue samples from patients who underwent lung/bronchial biopsies and presented invasive carcinoma after lung surgery. The lung/bronchial samples included basal cell hyperplasia, squamous metaplasia, moderate dysplasia, adenomatous hyperplasia, severe dysplasia, squamous cell carcinoma and adenocarcinoma. Matched lung parenchyma tissue samples included 25 squamous cell carcinomas and 31 adenocarcinomas. Immunohistochemistry was performed to analyze for the distribution of hyaluronidase (Hyal-1 and −3, and hyaluronan synthases (HAS-1, −2, and −3. Hyal-1 showed significantly higher expression in basal cell hyperplasia than in moderate dysplasia (P=0.01, atypical adenomatous hyperplasia (P=0.0001, or severe dysplasia (P=0.03. Lower expression of Hyal-3 was found in atypical adenomatous hyperplasia than in basal cell hyperplasia (P=0.01 or moderate dysplasia (P=0.02. HAS-2 was significantly higher in severe dysplasia (P=0.002 and in squamous metaplasia (P=0.04 compared with basal cell hyperplasia. HAS-3 was significantly expressed in basal cell hyperplasia compared with atypical adenomatous hyperplasia (P=0.05 and severe dysplasia (P=0.02. Lower expression of HAS-3 was found in severe dysplasia compared with squamous metaplasia (P=0.01 and moderate dysplasia (P=0.01. Epithelial Hyal-1 and −3 and HAS-1, −2, and −3 expressions were significantly higher in pre-neoplastic lesions than in neoplastic lesions. Comparative Cox multivariate analysis controlled by N stage and histologic tumor type showed that patients with high HAS-3 expression in pre-neoplastic cells obtained by lung/bronchial biopsy presented a significantly higher risk of death (HR=1.19; P=0.04. We concluded that localization of Hyal and HAS in lung/bronchial pre-neoplastic and neoplastic lesions was inversely related to malignancy, which implied that visualizing these factors could be a useful

  15. Malignant melanoma-The cradle of anti-neoplastic immunotherapy.

    Science.gov (United States)

    Koller, Kristian M; Wang, Wenge; Schell, Todd D; Cozza, Eugene M; Kokolus, Kathleen M; Neves, Rogerio I; Mackley, Heath B; Pameijer, Colette; Leung, Anna; Anderson, Bryan; Mallon, Carol A; Robertson, Gavin; Drabick, Joseph J

    2016-10-01

    One of the defining characteristics of the malignant phenotype is the ability to evade the host immune system. Immunotherapy as a treatment modality represents a new dawn in the way we think about the treatment of a variety of malignancies. The story of immunotherapy traces its roots to its relationship with malignant melanoma. In this article, we review the intertwined history of immunotherapy and melanoma, including the early significant history, a discussion on immune mechanisms, resistance, local and systemic immunotherapeutic modalities, and speculate on possible novel future treatment options. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. [X-ray computed tomography in non-neoplastic pathology of the larynx].

    Science.gov (United States)

    Vadalà, G; Di Guglielmo, L; Dore, R; Alerci, M; Santarelli, P; Pricca, P; Failoni, S; Di Giulio, G

    1984-10-01

    The authors describe the CT findings in 57 patients suffering from various non-neoplastic disease of the larynx: chronic laryngitis, pseudotumor, paralysis, post-traumatic lesions, laryngocele, cyst. CT is usefull in evaluating site and extension of the disease, as well as its relations with the surrounding tissues. The densitometric evaluation and the functional tests are important in differential diagnosis with malignant neoplasms.

  17. Cell cannibalism by malignant neoplastic cells: three cases in dogs and a literature review.

    Science.gov (United States)

    Meléndez-Lazo, Antonio; Cazzini, Paola; Camus, Melinda; Doria-Torra, Georgina; Marco Valle, Alberto Jesús; Solano-Gallego, Laia; Pastor, Josep

    2015-06-01

    Cell cannibalism refers to the engulfment of cells by nonprofessional phagocytic cells. Studies in human medicine have demonstrated a relationship between the presence of cell cannibalism by neoplastic cells and a poor outcome, and have shown a positive correlation with the presence of metastasis at the time of diagnosis. The biologic significance of cell cannibalism is unknown, but it is proposed that it may represent a novel mechanism of tumor immune evasion as a survival strategy in cases of unfavorable microenvironmental conditions. This report describes clinical and morphologic features of 3 cases of dogs with malignant neoplasia in which the presence of cellular cannibalism was observed in cytologic and histologic specimens. In the 1(st) case, a dog with a primary tonsillar squamous cell carcinoma with metastasis to retropharyngeal lymph nodes had neoplastic epithelial cells engulfing neutrophils noted in cytologic examination of the lymph nodes. In the 2(nd) case, neoplastic epithelial cells were seen engulfing each other in fine-needle aspirates from a primary mammary carcinoma with lung metastasis. In the 3(rd) case, poorly differentiated neoplastic mast cells from a recurrent, metastatic grade III mast cell tumor were observed cannibalizing eosinophils. A brief review of the literature describing known cell-into-cell relationships and the possible biologic significance and mechanisms involved in this phenomenon is provided. The relationship between cell cannibalism and distant metastasis should be explored in further studies, as it may prove to be a criterion of malignancy, as it is proposed in human medicine.

  18. HLA genes and other candidate genes involved in susceptibility for (pre)neoplastic cervical disease

    NARCIS (Netherlands)

    Zoodsma, M; Nolte, IM; Meerman, GJT; De Vries, EGE; Van Der Zee, AGJ

    2005-01-01

    This review focuses on common and genetic risk factors such as HLA and other genes that may be involved in susceptibility for (pre)neoplastic cervical disease. The goal of this review is the evaluation of polymorphisms that are either associated with cervical intraepithelial neoplasia (CIN) and/or c

  19. Multiparametric flow cytometry profiling of neoplastic plasma cells in multiple myeloma

    DEFF Research Database (Denmark)

    Johnsen, Hans E; Bøgsted, Martin; Klausen, Tobias W;

    2010-01-01

    The clinical impact of multiparametric flow cytometry (MFC) in multiple myeloma (MM) is still unclear and under evaluation. Further progress relies on multiparametric profiling of the neoplastic plasma cell (PC) compartment to provide an accurate image of the stage of differentiation. The primary...

  20. Immunohistochemical demonstration of lysozyme in normal, reactive and neoplastic cells of the mononuclear phagocyte system.

    Directory of Open Access Journals (Sweden)

    Motoi,Makoto

    1984-04-01

    Full Text Available Using the peroxidase antiperoxidase (PAP method, lysozyme (LZM was shown to exist in normal, reactive and neoplastic cells belonging to the mononuclear phagocyte system (MPS, but was not detected in histiocytosis X cells. Immunostaining for cytoplasmic LZM by the PAP method is useful for identification of mononuclear phagocytes and for diagnosis of the diseases in which these cells participate.

  1. Regulation of Notch signaling and endocytosis by the Lgl neoplastic tumor suppressor

    NARCIS (Netherlands)

    Portela, Marta; Parsons, Linda M.; Grzeschik, Nicola A.; Richardson, Helena E.

    2015-01-01

    The evolutionarily conserved neoplastic tumor suppressor protein, Lethal (2) giant larvae (Lgl), plays roles in cell polarity and tissue growth via regulation of the Hippo pathway. In our recent study, we showed that in the developing Drosophila eye epithelium, depletion of Lgl leads to increased li

  2. Interferons as Therapy for Viral and Neoplastic Diseases: From Panacea to Pariah to Paragon

    Directory of Open Access Journals (Sweden)

    Robert M. Friedman

    2009-12-01

    Full Text Available For more than 20 years after the excitement engendered by their discovery in 1957 as antiviral agents, there were no significant clinical uses of interferons; however, following their cloning they have been employed as effective treatment for several viral, autoimmune, and neoplastic diseases.

  3. HLA genes and other candidate genes involved in susceptibility for (pre)neoplastic cervical disease

    NARCIS (Netherlands)

    Zoodsma, M; Nolte, IM; Meerman, GJT; De Vries, EGE; Van Der Zee, AGJ

    2005-01-01

    This review focuses on common and genetic risk factors such as HLA and other genes that may be involved in susceptibility for (pre)neoplastic cervical disease. The goal of this review is the evaluation of polymorphisms that are either associated with cervical intraepithelial neoplasia (CIN) and/or c

  4. Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases

    DEFF Research Database (Denmark)

    Haycock, Philip C; Burgess, Stephen; Nounu, Aayah

    2017-01-01

    Importance: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. Objective: To conduct a Mendelian randomization study...

  5. Immunohistochemical expression of p16ink4a in inflammatory, preneoplastic and neoplastic cervical lesions

    Directory of Open Access Journals (Sweden)

    Gajanin Radoslav

    2015-01-01

    Full Text Available Introduction. High-risk human papilloma viruses play a main role in the development of cervical dysplasias and carcinomas. p16INK4a can be considered as a surrogate marker of active highrisk human papillomaviruses infection in dysplastic and neoplastic cells of the cervix. This study was aimed at determining the presence and level of p16INK4a expression in inflammatory, preneoplastic and neoplastic lesions of the cervix. Material and Methods. The study was performed on 109 samples of cervical biopsy. Cervical cancer was diagnosed in 36 patients, 34 patients had a preneoplastic change (dysplasia in stratified squamous cervix epithelium and a nonspecific inflammatory process was found in 39 patients. In all samples, immunohistochemical analysis using antibodies to p16INK4a was performed. Results. The expression of p16INK4a was verified in all cases of cervical cancer (100%, in 67.65% of dysplastic cervical lesions and in 38.5% of inflammatory lesions. A statistically highly significant difference was found in the presence and level of expression among neoplasic, dysplastic and inflammatory lesions of the cervix (χ² = 76.02, p < 0.001. The expression was more frequent and had a higher level in neoplastic and high grade dysplastic lesions compared to expression in inflammatory lesions and low grade dysplasias. Conclusion. The analysis of the presence of p16INK4a can differentiate non-neoplastic, high grade preneoplastic and neoplastic changes of the cervix. The use of p16INK4a in interpreting borderline lesions of the cervix can enable a rational therapeutic treatment of patients.

  6. Anti-neoplastic efficacy of Haimiding on gastric carcinoma and its mechanisms

    Institute of Scientific and Technical Information of China (English)

    Yu-Bin Ji; Shi-Yong Gao; Hong-Rui Ji; Qi Kong; Xiu-Juan Zhang; Bao-Feng Yang

    2004-01-01

    AIM: To study the anti-neoplastic effect of Haimiding and its mechanisms of action.METHODS: Experiments using MTT and colony formation were carried out to study thein vitro anti-neoplastic action of Haimiding, its in vivo anti-neoplastic action was studied by observing its effect on the weight of tumors in FC mice and S180, H22 tumor bearing mice, as well as their life spans.The effect of Haimiding on cell apoptosis and different stages of cell cycles in human gastric carcinoma cells were studied by flow cytometry. Its effect on [Ca2+]i of human gastric carcinoma cells and the source of Ca2+ during the change of [Ca2+]i were observed by confocal laser scanning technique.RESULTS: Haimiding showed a definite cytotoxicity to 8 human tumor cell lines, which was most prominent against BGC-823, Eca-109 and HCT-8 tumor cells. It also exhibited an obvious inhibition on colony formation of the above tumor cell lines, which was most prominent in Eca-109 tumor cells. It showed obvious inhibition on the growth of tumor in FC mice and S180 bearing mice as well as prolonged the life span of H22 bearing mice. It was able to induce apoptosis and elevate intracellular [Ca2+]i concentration of tumor cells.The source of Ca2+ came from both extracellular Ca2+ influx and intracellular Ca2+ release.CONCLUSION: Haimiding is composed of a TCM preparation and 5-flurouracil. Its anti-neoplastic potency is highly enhanced by synergism as compared with either one of its components. Its mechanisms of anti-neoplastic action can be attributed to its action to initiate apoptosis of tumor cells by opening the membrane calcium channel and inducing intracellular Ca2+ release to elevate [Ca2+]i of the tumor cells.

  7. Galectin-1 is a useful marker for detecting neoplastic squamous cells in oral cytology smears.

    Science.gov (United States)

    Noda, Yuri; Kondo, Yuko; Sakai, Manabu; Sato, Sunao; Kishino, Mitsunobu

    2016-06-01

    Cytologic diagnoses in the oral region are very difficult due to the small amount of cells in smears, which are also exposed to many stimulating factors and often show atypical changes. Galectin-1 (Gal1) is a β-galactoside binding protein that modulates tumor progression. Gal1 is very weakly expressed in normal cells, but is often overexpressed in neoplastic lesions. The aim of the present study was to determine whether it is possible to differentiate reactive changes from neoplastic changes in oral cytology smears based on the expression of Gal1. A total of 155 tissue biopsy specimens and 61 liquid-based cytology specimens were immunostained by an anti-Gal1 antibody, and Gal1 expression levels were subsequently evaluated. These samples consisted of oral squamous cell carcinomas, epithelial dysplasia, and oral mucosal diseases. The positive and negative expressions of Gal1 were examined in 37 specimens collected by scalpel and cytobrush biopsy. The sensitivity, specificity, and positive predictive value of Gal1 were also evaluated in smears. In tissue sections, the positive ratio of Gal1 in neoplastic lesions was high (72.3%). In cytology specimens, the positive ratio of Gal1 was higher in neoplastic lesions (79.0%) than in those negative for intraepithelial lesion or malignancy (22.2%). A correlation was found between immunocytochemical Gal1 expression and immunohistochemical Gal1 expression (P < .001). The sensitivity (75.0%), specificity (75.0%), and positive predictive value (91.3%) of Gal1 were also high in smears. In conclusion, Gal1 may be a useful marker for determining whether morphologic changes in cells are reactive or neoplastic.

  8. The eukaryotic translation elongation factor eEF1A2 induces neoplastic properties and mediates tumorigenic effects of ZNF217 in precursor cells of human ovarian carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Yu; Wong, Nicholas; Guan, Yinghui; Salamanca, Clara M.; Cheng, Jung Chien; Lee, Jonathan M.; Gray, Joe W.; Auersperg, Nelly

    2008-04-25

    Ovarian epithelial carcinomas (OEC) frequently exhibit amplifications at the 20q13 locus which is the site of several oncogenes, including the eukaryotic elongation factor EEF1A2 and the transcription factor ZNF217. We reported previously that overexpressed ZNF217 induces neoplastic characteristics in precursor cells of OEC. Unexpectedly, ZNF217, which is a transcriptional repressor, enhanced expression of eEF1A2. In this study, array comparative genomic hybridization, single nucleotide polymorphism and Affymetrix analysis of ZNF217-overexpressing cell lines confirmed consistently increased expression of eEF1A2 but not of other oncogenes, and revealed early changes in EEF1A2 gene copy numbers and increased expression at crisis during immortalization. We defined the influence of eEF1A2 overexpression on immortalized ovarian surface epithelial cells, and investigated interrelationships between effects of ZNF217 and eEF1A2 on cellular phenotypes. Lentivirally induced eEF1A2 overexpression caused delayed crisis, apoptosis resistance and increases in serum-independence, saturation densities, and anchorage independence. siRNA to eEF1A2 reversed apoptosis resistance and reduced anchorage independence in eEF1A2-overexpressing lines. Remarkably, siRNA to eEF1A2 was equally efficient in inhibiting both anchorage independence and resistance to apoptosis conferred by ZNF217 overexpression. Our data define neoplastic properties that are caused by eEF1A2 in nontumorigenic ovarian cancer precursor cells, and suggest that eEF1A2 plays a role in mediating ZNF217-induced neoplastic progression.

  9. Prevalence of human papillomavirus types in women with pre-neoplastic and neoplastic cervical lesions in the Federal District of Brazil

    Directory of Open Access Journals (Sweden)

    Geni NL Camara

    2003-10-01

    Full Text Available As a contribution to the public health authorities in planning prophylactic and therapeutic vaccine strategies, we describe the prevalence of human papillomavirus (HPV types in women presenting abnormal cytological results in Pap smear screening tests in the Federal District, Central Brazil. We studied 129 cervical scraping samples from women whose cytological tests showed either pre-neoplastic or neoplastic lesions. Amplification of HPV DNA was performed by polymerase chain reaction using consensus primers MY09 and MY11 followed by identification of isolates by restriction fragment length polymorphism. We detected HPV DNA in 62% of the samples, including HPV-16 in 43.8%, HPV-58 in 12.5%, HPV-31 in 10%, HPV-53 in 6.3%, each of HPV-18 and HPV-33 in 3.8% of the isolates. Other types (HPV-35, -52, -66, -CP8304, -6, -11, and -CP8061 were less frequent (= or < 2.5% each. The prevalence of HPV-58 was relatively higher in this population than in data in South America, but similar to results obtained in other studies in Latin America, Europe, and Eastern Asia. Case-control studies need to be carried out to establish the association between the prevalence of HPV types specially the less frequent high-risk types and cervical cancer.

  10. Euclidean and fractal geometry of microvascular networks in normal and neoplastic pituitary tissue.

    Science.gov (United States)

    Di Ieva, Antonio; Grizzi, Fabio; Gaetani, Paolo; Goglia, Umberto; Tschabitscher, Manfred; Mortini, Pietro; Rodriguez y Baena, Riccardo

    2008-07-01

    In geometrical terms, tumour vascularity is an exemplary anatomical system that irregularly fills a three-dimensional Euclidean space. This physical characteristic and the highly variable shapes of the vessels lead to considerable spatial and temporal heterogeneity in the delivery of oxygen, nutrients and drugs, and the removal of metabolites. Although these biological characteristics are well known, quantitative analyses of newly formed vessels in two-dimensional histological sections still fail to view their architecture as a non-Euclidean geometrical entity, thus leading to errors in visual interpretation and discordant results from different laboratories concerning the same tumour. We here review the literature concerning microvessel density estimates (a Euclidean-based approach quantifying vascularity in normal and neoplastic pituitary tissues) and compare the results. We also discuss the limitations of Euclidean quantitative analyses of vascularity and the helpfulness of a fractal geometry-based approach as a better means of quantifying normal and neoplastic pituitary microvasculature.

  11. Neoplastic leptomeningeal disease masquerading as central serous retinopathy. A case report.

    Science.gov (United States)

    Elaraoud, Ibrahim; Suleman, Hanif J; Cikatricis, Peter; Palmer, Helen

    2016-01-01

    A 69-year-old man became aware of people's speech being out of synch with their lip movements alongside persistent headaches, both of which progressively worsened. A few weeks later, he developed progressive and painless visual loss in one eye. Initial neurological evaluation, inflammatory markers and head computed tomography scan were normal. Ophthalmological examination and OCT scan revealed right macular subretinal fluid with choroidal indentation, which prompted urgent further investigations including head MRI revealing extensive leptomeningeal disease. The patient continued to deteriorate and deceased shortly afterwards. This is the first reported case of neoplastic leptomeningeal disease presenting with loss of vision due to choroidal metastasis with localised exudative retinal detachment. Diagnosing neoplastic leptomeningeal disease requires a high index of suspicion from the treating physician. Symptoms may be nonspecific and/or subtle. Combining cerebrospinal fluid cytology from lumbar puncture with contrast-enhanced magnetic resonance imaging of the brain is considered the optimal diagnostic approach.

  12. The role of gap junctions in inflammatory and neoplastic disorders (Review).

    Science.gov (United States)

    Wong, Pui; Laxton, Victoria; Srivastava, Saurabh; Chan, Yin Wah Fiona; Tse, Gary

    2017-03-01

    Gap junctions are intercellular channels made of connexin proteins, mediating both electrical and biochemical signals between cells. The ability of gap junction proteins to regulate immune responses, cell proliferation, migration, apoptosis and carcinogenesis makes them attractive therapeutic targets for treating inflammatory and neoplastic disorders in different organ systems. Alterations in gap junction profile and expression levels are observed in hyperproliferative skin disorders, lymphatic vessel diseases, inflammatory lung diseases, liver injury and neoplastic disorders. It is now recognized that the therapeutic effects mediated by traditional pharmacological agents are dependent upon gap junction communication and may even act by influencing gap junction expression or function. Novel strategies for modulating the function or expression of connexins, such as the use of synthetic mimetic peptides and siRNA technology are considered.

  13. Prevalence of Neoplastic Diseases in Pet Birds Referred for Surgical Procedures

    Directory of Open Access Journals (Sweden)

    Patrícia F. Castro

    2016-01-01

    Full Text Available Neoplastic disease is common in pet birds, particularly in psittacines, and treatment should be primarily aimed at tumor eradication. Nineteen cases of pet birds submitted to diagnostic and/or therapeutic surgical procedures due to neoplastic disease characterized by the presence of visible masses were retrospectively analyzed; affected species, types of neoplasms and respective locations, and outcomes of surgical procedures were determined. All birds undergoing surgery belonged to the order Psittaciformes; the Blue-fronted parrot (Amazona aestiva was the prevalent species. Lipoma was the most frequent neoplasm in the sample studied. Most neoplasms affected the integumentary system, particularly the pericloacal area. Tumor resection was the most common surgical procedure performed, with high resolution and low recurrence rates.

  14. Expression of adrenomedullin 2/intermedin in human adrenal tumors and attached non-neoplastic adrenal tissues.

    Science.gov (United States)

    Morimoto, Ryo; Satoh, Fumitoshi; Murakami, Osamu; Hirose, Takuo; Totsune, Kazuhito; Imai, Yutaka; Arai, Yoichi; Suzuki, Takashi; Sasano, Hironobu; Ito, Sadayoshi; Takahashi, Kazuhiro

    2008-07-01

    Adrenomedullin 2/intermedin (AM2/IMD) is a new member of calcitonin/calcitonin gene-related peptide family. AM is expressed in various tumors including adrenocortical tumors and modulates tumor growth. The AM2/IMD expression has not been studied, however, in adrenal tumors. The expression of AM2/IMD and AM was therefore studied in human adrenal tumors and attached non-neoplastic adrenal tissues by immunocytochemistry (ICC). Immunoreactive (IR)-AM2/IMD was measured by RIA. Furthermore, the expression of AM2/IMD and its receptor components, calcitonin receptor-like receptor (CRLR), and receptor activity-modifying proteins (RAMPs) 1, 2, and 3 mRNA in these tissues was studied by reverse transcription PCR (RT-PCR). ICC showed that AM2/IMD and AM immunoreactivities were localized in adrenocortical tumors and pheochromocytomas. AM2/IMD and AM immunoreactivities were detected in medulla of attached non-neoplastic tissues, while the degree of immunoreactivity for AM2/IMD and AM in cortices of attached adrenals was relatively weak or undetectable. RIA detected IR-AM2/IMD in adrenal tumors (0.414+/-0.12 to 0.786+/-0.27 pmol/g wet weight, mean+/-S.E.M.) and attached adrenal tissues (0.397+/-0.052 pmol/g wet weight). Reverse-phase high-performance liquid chromatography showed one broad peak eluted in the similar position to synthetic AM2/IMD with several minor peaks. RT-PCR showed expression of AM2/IMD, CRLR, and RAMP1, RAMP2, and RAMP3 mRNA in tissues of adrenal tumors and attached adrenal glands. In conclusion, AM2/IMD is expressed in human adrenal tumors and attached non-neoplastic adrenal tissues and may play (patho-)physiological roles in normal and neoplastic adrenals as an autocrine/paracrine regulator.

  15. Probiotics against neoplastic transformation of gastric mucosa: effects on cell proliferation and polyamine metabolism.

    Science.gov (United States)

    Russo, Francesco; Linsalata, Michele; Orlando, Antonella

    2014-10-07

    Gastric cancer is still the second leading cause of cancer death worldwide, accounting for about 10% of newly diagnosed neoplasms. In the last decades, an emerging role has been attributed to the relations between the intestinal microbiota and the onset of both gastrointestinal and non-gastrointestinal neoplasms. Thus, exogenous microbial administration of peculiar bacterial strains (probiotics) has been suggested as having a profound influence on multiple processes associated with a change in cancer risk. The internationally accepted definition of probiotics is live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. The possible effects on the gastrointestinal tract following probiotic administration have been investigated in vitro and in animal models, as well as in healthy volunteers and in patients suffering from different human gastrointestinal diseases. Although several evidences are available on the use of probiotics against the carcinogen Helicobacter pylori, little is still known about the potential cross-interactions among probiotics, the composition and quality of intestinal flora and the neoplastic transformation of gastric mucosa. In this connection, a significant role in cell proliferation is played by polyamines (putrescine, spermidine, and spermine). These small amines are required in both pre-neoplastic and neoplastic tissue to sustain the cell growth and the evidences here provided suggest that probiotics may act as antineoplastic agents in the stomach by affecting also the polyamine content and functions. This review will summarize data on the most widely recognized effects of probiotics against neoplastic transformation of gastric mucosa and in particular on their ability in modulating cell proliferation, paying attention to the polyamine metabolism.

  16. Meta-analysis of nasopharyngeal carcinoma microarray data explores mechanism of EBV-regulated neoplastic transformation

    OpenAIRE

    Liao ZhiJun; Zheng WenLing; Liang Shuang; Chen Xia; Shang Tao; Ma WenLi

    2008-01-01

    Abstract Background Epstein-Barr virus (EBV) presumably plays an important role in the pathogenesis of nasopharyngeal carcinoma (NPC), but the molecular mechanism of EBV-dependent neoplastic transformation is not well understood. The combination of bioinformatics with evidences from biological experiments paved a new way to gain more insights into the molecular mechanism of cancer. Results We profiled gene expression using a meta-analysis approach. Two sets of meta-genes were obtained. Meta-A...

  17. Meta-analysis of nasopharyngeal carcinoma microarray data explores mechanism of EBV-regulated neoplastic transformation

    OpenAIRE

    Chen, Xia; Liang, Shuang; ZHENG, WENLING; Liao, Zhijun; Shang, Tao; Ma, WenLi

    2008-01-01

    Background Epstein-Barr virus (EBV) presumably plays an important role in the pathogenesis of nasopharyngeal carcinoma (NPC), but the molecular mechanism of EBV-dependent neoplastic transformation is not well understood. The combination of bioinformatics with evidences from biological experiments paved a new way to gain more insights into the molecular mechanism of cancer. Results We profiled gene expression using a meta-analysis approach. Two sets of meta-genes were obtained. Meta-A genes we...

  18. Heritable, population-wide damage to cells as the driving force of neoplastic transformation.

    OpenAIRE

    Rubin, H.; A. Yao; Chow, M

    1995-01-01

    Prolonged incubation of NIH 3T3 cells under the growth constraint of confluence results in the death of some cells in a manner suggestive of apoptosis. Successive rounds of prolonged incubation at confluence of the surviving cells produce increasing neoplastic transformation in the form of increments in saturation density and transformed focus formation. Cells from the postconfluent cultures are given a recovery period of various lengths to remove the direct inhibitory effect of confluence be...

  19. [Para-neoplastic autoimmune multi-organ syndrome associated with follicular lymphoma: a case report and literature review].

    Science.gov (United States)

    Chen, D; Lin, C Y; Han, X; Chen, B; Lu, Z H; Chang, X Y; Duan, M H

    2016-12-14

    Objective: To broaden our knowledge of para-neoplastic autoimmune multi-organ syndrome (PAMS). Methods: A patient with PAMS associated with follicular lymphoma and bronchiolitis obliterans treated in our hospital was retrospectively analyzed and the clinical features of PAMS were reviewed. Results: A 49-year-old female patient suffered from painful ulcers in the oral cavity and vagina, dry cough and dyspnea. Imaging examinations suggested multiple lymph node enlargements. Inguinal lymph node biopsy revealed follicular lymphoma. Although the oral and vaginal ulcers went into remission with glucocorticoid and thalidomide therapy and follicular lymphoma gained partial remission with six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) chemotherapy, respiratory failure still progressed. Conclusion: PAMS should be considered in patients with unexplained oral mucosa ulcers and dyspnea, which didn't match with the chest image manifestations. Extensive work-up should be performed to find out the potential tumor after diagnosis of PAMS. Early diagnosis and complete removal of tumor were essential to PAMS treatment.

  20. Incidental neoplastics findings in paediatric {sup 99m}Tc-MDP bone scan patients with non-specific limp

    Energy Technology Data Exchange (ETDEWEB)

    Maddaford, S.; Morony, S. [Women`s and Children`s Hospital, North Adelaide, SA (Australia). Department of Nuclear Medicine

    1998-06-01

    Full text: A group of patients who attended the Department of Nuclear Medicine with non-specific limp/hip pain, for a {sup 99m}Tc-MDP bone scan, had incidental findings of diffuse neoplastic involvement. A variety of oncology patients attend the Department annually for a {sup 99m}Tc-MDP bone scan. These include patients with Ewing`s osteosarcoma, rhabdomyosarcoma, benign osteoid osteoma and neuroblastoma. We rarely see patients with leukemia. We found that of a number of patients with stage IV neuroblastoma 80% had presented to the Department with a non-specific limp/hip pain for investigation. The ESR in each case was either normal or raised, and previous radiological and ultrasound examination did not demonstrate any specific finding. The provisional diagnosis in each case was osteomyelitis or septic arthritis. In retrospect, a nuclear medicine {sup 99m}Tc-MDP bone scan was a clear advantage in assisting the diagnosis of neuroblastoma. A selection of these patient case studies is presented to demonstrate the value of the nuclear medicine bone scan incidental findings in the early diagnosis of neuroblastoma, and the subsequent monitoring and staging of this disease

  1. In-situ visualization and evaluation of neoplastic lesions of the human gastrointestinal tract using endoscopic optical coherence tomography

    Science.gov (United States)

    Rollins, Andrew M.; Westphal, Volker; Das, Ananya; Pfau, Patrick; Chak, Amitabh; Wong, Richard C. K.; Sivak, Michael J., Jr.; Izatt, Joseph A.

    2001-06-01

    Optical coherence tomography (OCT) is a novel biomedical imaging technique that uses low-coherence optical interferometry to obtain micron-scale resolution cross- sectional images of tissue microstructure noninvasively. OCT fills a valuable niche in imaging of tissue structure, providing subsurface imaging with high spatial resolution (on the order of 10 micrometers) and penetration depths of 1 - 2 mm with no contact or matching medium needed between the probe and the tissue. An OCT system for gastrointestinal (GI) endoscopy has been developed using a small-diameter rotary-scanning probe compatible with standard GI endoscopes and capable of imaging in real-time. To date more than 100 volunteers have been imaged during routine upper and lower endoscopic procedures. Results of imaging in normal organs have demonstrated visualization of morphological layers (epithelium, lamina propria, muscularis mucosa, submucosa, muscularis propria) and microscopic structures (glands, villi, crypts, vessels) in all endoscopically accessible GI organs. It has been observed in more than 30 patients that the EOCT appearance of Barrett's mucosa is clearly differentiable from normal gastric or esophageal mucosa. Furthermore, the EOCT appearance of dysplasia and neoplastic lesions, including adenocarcenoma in Barrett's and villous tumor in colon have been observed and are under investigation. Preliminary data indicate the potential of EOCT for routine clinical diagnostics in GI tissues, including early cancer detection and staging and detection of tumor margins.

  2. MOLECULAR MECHANISM OF SUPPRESSION OF NEOPLASTIC TRANSFORMATION BY LOW DOSES OF LOW LET RADIATION

    Energy Technology Data Exchange (ETDEWEB)

    J.LESIE REDPATH, PH.D.

    2011-03-29

    We are currently funded (9/01-8/04) by the DOE Low Dose Radiation Research Program to examine mechanisms underlying the suppression of neoplastic transformation in vitro by low doses of low LET radiation. For the new studies proposed under Notice 04-21, we intend to follow up on our observation that upregulation of DNA repair may be an important factor and that its importance is dose-dependent. The experimental system will be the human hybrid cell neoplastic transformation assay that we are currently using. We propose to test the following hypothesis: Down-regulation of DNA dsb repair will abrogate the low dose suppression of neoplastic transformation. Using the technique of RNA silencing, it is proposed to test the effect of down-regulation of the two major DNA dsb repair pathways, homologous recombination (HR) and non-homologous end-joining (NHEJ), on the dose response relationship for neoplastic transformation. Based on prior studies, we predict that this will result in abrogation of the suppressive effect at doses in the range 1 to 10 cGy, but not at lower doses. The proposed experiments will also help address the question as to which of the two DNA repair pathways may be the most important in causing suppression of transformation. HR is a pathway that is predominant in S and G2 phase cells and is known to be less error-prone than the NHEJ pathway that is predominant in G1 phase. We hypothesize that down-regulation of HR will result in the most effective abrogation of suppression. An important component of this study will be the determination of the how abrogation of DNA dsb repair impacts the spontaneous transformation frequency, presumably a consequence of endogeneous DNA damage. Experiments will be carried out using partially synchronized populations of cells enriched for G1 and S/G2 respectively. In addition to the endpoint of neoplastic transformation the impact of down-regulation of HR and NHEJ on the formation and disappearance of the DNA dsb marker

  3. Role of multiphasic multi-detector computed tomography (MDCT in the diagnosis and staging of solid neoplastic renal masses

    Directory of Open Access Journals (Sweden)

    Manal H. Wahba

    2015-03-01

    Conclusion: Multiphase multislice computed tomography combined with CT angiography and CT urography have a major role in solid renal neoplastic masses’ diagnosis, characterization and differentiating benign and malignant tumors.

  4. Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry.

    Science.gov (United States)

    Marolla, Ana Paula Cleto; Waisberg, Jaques; Saba, Gabriela Tognini; Waisberg, Daniel Reis; Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva

    2015-01-01

    To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student'st test. The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues.

  5. Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Marolla, Ana Paula Cleto [Universidade Federal de São Paulo, São Paulo, SP (Brazil); Waisberg, Jaques [Hospital do Servidor Público Estadual, São Paulo, SP (Brazil); Faculdade de Medicina do ABC, Santo André, SP (Brazil); Saba, Gabriela Tognini [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Waisberg, Daniel Reis [Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP (Brazil); Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva [Faculdade de Medicina do ABC, Santo André, SP (Brazil)

    2015-07-01

    To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student’s t test. The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues.

  6. Pitfalls of improperly procured adjacent non-neoplastic tissue for somatic mutation analysis using next-generation sequencing

    Directory of Open Access Journals (Sweden)

    Lei Wei

    2016-10-01

    Full Text Available Abstract Background The rapid adoption of next-generation sequencing provides an efficient system for detecting somatic alterations in neoplasms. The detection of such alterations requires a matched non-neoplastic sample for adequate filtering of non-somatic events such as germline polymorphisms. Non-neoplastic tissue adjacent to the excised neoplasm is often used for this purpose as it is simultaneously collected and generally contains the same tissue type as the neoplasm. Following NGS analysis, we and others have frequently observed low-level somatic mutations in these non-neoplastic tissues, which may impose additional challenges to somatic mutation detection as it complicates germline variant filtering. Methods We hypothesized that the low-level somatic mutation observed in non-neoplastic tissues may be entirely or partially caused by inadvertent contamination by neoplastic cells during the surgical pathology gross assessment or tissue procurement process. To test this hypothesis, we applied a systematic protocol designed to collect multiple grossly non-neoplastic tissues using different methods surrounding each single neoplasm. The procedure was applied in two breast cancer lumpectomy specimens. In each case, all samples were first sequenced by whole-exome sequencing to identify somatic mutations in the neoplasm and determine their presence in the adjacent non-neoplastic tissues. We then generated ultra-deep coverage using targeted sequencing to assess the levels of contamination in non-neoplastic tissue samples collected under different conditions. Results Contamination levels in non-neoplastic tissues ranged up to 3.5 and 20.9 % respectively in the two cases tested, with consistent pattern correlated with the manner of grossing and procurement. By carefully controlling the conditions of various steps during this process, we were able to eliminate any detectable contamination in both patients. Conclusion The results demonstrated that the

  7. Radiofrequency Kyphoplasty for the Treatment of Osteoporotic and Neoplastic Vertebral Body Fractures - Preliminary Experience and Clinical Results after 6 Months

    Directory of Open Access Journals (Sweden)

    Elgeti F

    2011-01-01

    Full Text Available Vertebroplasty and conventional kyphoplasty using a balloon or a stent are established methods for the treatment of painful osteoporotic or neoplastic vertebral compression fractures that are resistant to conservative medical treatment. Radiofrequency (RF kyphoplasty with ultra-high viscosity cement is an innovative method. It permits safe and effective treatment of painful osteoporotic and neoplastic vertebral compression fractures while preserving non-compromised cancellous bone.

  8. Differentiation of neoplastic from bland macroscopic portal vein thrombi using dual-energy spectral CT imaging: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Qian, Li Jun; Zhu, Jiong; Zhuang, Zhi Guo; Xu, Jian Rong [Shanghai Jiaotong University School of Medicine, Department of Radiology, Renji Hospital, Shanghai (China); Xia, Qiang [Shanghai Jiaotong University School of Medicine, Department of Hepatic Surgery, Renji Hospital, Shanghai (China); Cheng, Yu.Fan [Chang Gung University College of Medicine, Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung (China); Li, Jian Ying [GE Healthcare China, CT Imaging Research Center, Beijing (China)

    2012-10-15

    To assess the feasibility and value of dual-energy spectral computed tomography (DESCT) imaging for differentiating neoplastic from bland macroscopic portal vein (PV) thrombi. Computed tomography (CT) images of 44 patients with macroscopic PV thrombus (bland group, n = 16; neoplastic group, n = 28) were reviewed. Iodine-based material decomposition images in the portal venous phase were reconstructed to compare the iodine indices between groups, including thrombus iodine density (I{sub T}), thrombus-aorta iodine density ratio (I{sub T}/I{sub A}), and thrombus-PV iodine density ratio (I{sub T}/I{sub P}). Differential diagnostic performances of DESCT were calculated in the subgroup of 21 patients with histopathological evidence (bland group, n = 12; neoplastic group, n = 9). The iodine indices of the neoplastic group were significantly higher than those in the bland group (P < 0.001). A threshold I{sub T} of 1.14 mg/mL, I{sub T}/I{sub A} of 0.17, and I{sub T}/I{sub P} of 0.17 in the portal venous phase yielded 100 %, 88.9 %, and 100 % sensitivity, and 91.7 %, 91.7 %, and 83.3 % specificity, respectively, in differentiating neoplastic from bland PV thrombi. DESCT imaging with quantification of thrombus iodine density in the portal venous phase appears to be a promising new method for distinguishing neoplastic from bland macroscopic PV thrombi. (orig.)

  9. Clusterin expression in non-neoplastic adenohypophyses and pituitary adenomas: cytoplasmic clusterin localization in adenohypophysis is related to aging.

    Science.gov (United States)

    Ekici, A Işin Doğan; Eren, Bülent; Türkmen, Nursel; Comunoğlu, Nil; Fedakar, Recep

    2008-01-01

    Clusterin is a circulating multifunctional glycoprotein produced in several kinds of epithelial and neuronal cells. Clusterin is upregulated during different physiological and pathological states, such as senescence, type-2 diabetes mellitus, Alzheimer disease, and in various neoplasms. Herein, we investigated the immunohistochemical expression of clusterin in non-neoplastic adenohypophysis of human autopsy subjects and pituitary adenomas. We also investigated the association of clusterin increase with age in adenohypophysis of autopsy subjects. Immunohistochemically, clusterin was found positive in the cytoplasm of all adenoma cases, and in the cytoplasm of parenchymal cells, stellate cells, mixed cell follicles and in colloidal material inside of the follicles of non-neoplastic adenohypophysis as well. Clusterin expression in pituitary adenomas was found significantly higher than in non-neoplastic adenohypophyses. In addition, in non-neoplastic adenohypophysis, a significant increase in clusterin expression levels between young (or=61 years) subjects (p adenohypophysis. In conclusion, the present study demonstrated that clusterin expression was found in non-neoplastic adenohypophysis and in upregulated amounts in pituitary adenomas. This study also demonstrated that in non-neoplastic adenohypophyses, increase of clusterin positive cells; histopathological findings of calcification or presence colloidal material accumulation in large follicles were associated with age. To our knowledge, immunohistochemical localization of clusterin in pituitary adenomas was not reported previously.

  10. Miss rate of colorectal neoplastic polyps and risk factors for missed polyps in consecutive colonoscopies.

    Science.gov (United States)

    Kim, Nam Hee; Jung, Yoon Suk; Jeong, Woo Shin; Yang, Hyo-Joon; Park, Soo-Kyung; Choi, Kyuyong; Park, Dong Il

    2017-07-01

    Colonoscopic polypectomy is the best diagnostic and therapeutic tool to detect and prevent colorectal neoplasms. However, previous studies have reported that 17% to 28% of colorectal polyps are missed during colonoscopy. We investigated the miss rate of neoplastic polyps and the factors associated with missed polyps from quality-adjusted consecutive colonoscopies. We reviewed the medical records of patients who were found to have colorectal polyps at a medical examination center of the Kangbuk Samsung Hospital between March 2012 and February 2013. Patients who were referred to a single tertiary academic medical center and underwent colonoscopic polypectomy on the same day were enrolled in our study. The odds ratios (ORs) associated with polyp-related and patient-related factors were evaluated using logistic regression analyses. A total of 463 patients and 1,294 neoplastic polyps were analyzed. The miss rates for adenomas, advanced adenomas, and carcinomas were 24.1% (312/1,294), 1.2% (15/1,294), and 0% (0/1,294), respectively. Flat/sessile-shaped adenomas (adjusted OR, 3.62; 95% confidence interval [CI], 2.40-5.46) and smaller adenomas (adjusted OR, 5.63; 95% CI, 2.84- 11.15 for ≤5 mm; adjusted OR, 3.18; 95% CI, 1.60-6.30 for 6-9 mm, respectively) were more frequently missed than pedunculated/sub-pedunculated adenomas and larger adenomas. In patients with 2 or more polyps compared with only one detected (adjusted OR, 2.37; 95% CI, 1.55-3.61 for 2-4 polyps; adjusted OR, 11.52; 95% CI, 4.61-28.79 for ≥5 polyps, respectively) during the first endoscopy, the risk of missing an additional polyp was significantly higher. One-quarter of neoplastic polyps was missed during colonoscopy. We encourage endoscopists to detect smaller and flat or sessile polyps by using the optimal withdrawal technique.

  11. WT1 expression in salivary gland pleomorphic adenomas: a reliable marker of the neoplastic myoepithelium.

    Science.gov (United States)

    Langman, Gerald; Andrews, Claire L; Weissferdt, Annikka

    2011-02-01

    Pleomorphic adenoma is a benign salivary gland neoplasm with a diverse morphology. This is considered to be a function of the neoplastic myoepithelium, which shows histological and immunophenotypical variability. Wilms' tumor 1 gene (WT1) protein, involved in bidirectional mesenchymal-epithelial transition, has been detected by reverse transcription PCR in salivary gland tumors showing myoepithelial-epithelial differentiation. The aim of this study was to investigate the immunoreactivity of WT1 in pleomorphic adenomas and to compare the pattern of staining with p63 and calponin, two reliable markers of myoepithelial cells. A total of 31 cases of pleomorphic adenoma were selected. The myoepithelium was classified as myoepithelial-like (juxtatubular and spindled), modified myoepithelium (myxoid, chondroid and plasmacytoid) and transformed myoepithelium (solid epithelioid, squamous and basaloid cribriform). Immunohistochemistry for WT1, p63 and calponin was assessed in each myoepithelial component, as well as in nonneoplastic myoepithelial cells and inner tubular epithelial cells. There was no immunostaining of tubular epithelial cells by any of the markers. In contrast to p63 and calponin, WT1 did not react with normal myoepithelial cells. Cytoplasmic WT1 staining was present in all pleomorphic adenomas, and in 29 cases (94%), >50% of neoplastic myoepithelial cells were highlighted. p63 and calponin stained the myoepithelium in 30 tumors. In comparison, 50% of cells were positive in 21 (68%) and 9 (29%) cases of p63 and calponin, respectively. Staining with WT1 showed less variability across the spectrum of myoepithelial differentiation with the difference most marked in the transformed myoepithelium. WT1 is a sensitive marker of the neoplastic myoepithelial cell in pleomorphic adenomas. The role of this protein in influencing the mesenchymal-epithelial state of cells suggests that WT1 and the myoepithelial cell have an important role in the histogenesis of

  12. Clonal chromosome abnormalites found in three non-neoplastic proliferative brain lesions

    Directory of Open Access Journals (Sweden)

    Rainho Cláudia Aparecida

    1999-01-01

    Full Text Available Chromosome analysis was made of brain lesions from three patients which, according to classical histopathological criteria, did not contain tumor cells. In addition to normal cells, we identified abnormal karyotypes with clonal numerical and structural chromosome alterations in at least two independently originated primary cultures from each lesion. Our data suggest that chromosomal aberrations can exist in vivo in non-neoplastic lesions. Other abnormalities may be due to genetic instability manifested only in vitro (culture artifacts or may already have been present in brain tissue, reflecting previous chromosome damage (as a result of exposure to chemical treatment or enviromental clastogens.

  13. [Cancer procoagulant activity in serum and neoplastic tissue in cases of cervical and uterine carcinoma].

    Science.gov (United States)

    Szajda, Sławomir Dariusz; Jóźwik, Maciej; Jóźwik, Marcin; Zalewska, Beata; Panek, Grzegorz; Sulkowski, Stanisław; Skrzydlewski, Zdzisław

    2004-09-01

    Cancer procoagulant (CP) is a sulfhydryl proteinase thought to be synthesized mainly by neoplastic cells. Consequently, increased CP activity in blood serum was interpreted as being associated with the presence of a proliferative process in the host's body. To date, CP activity has not been systematically studied in cases of genital carcinoma. The present study is aimed at evaluation of CP activity in women with genital carcinoma. A case-controlled study backed up by histopathological examination. Peripheral blood was sampled preoperatively in a sterile manner from an antecubital vein, from 16 women with cervical carcinoma and 15 women with uterine carcinoma. Blood for the reference group of 12 healthy women was obtained in an identical manner after an overnight fast. The CP activity in serum was determined using the coagulative method according to Gordon and Benson, and was expressed as coagulation time in seconds (s). The CP activity in 10% tissue homogenates (in saline) of genital cancer was determined by the chromogenic method according to Colucci et al. The mean CP activity in serum of women with cervical carcinoma (78.28 +/- 15.25 s) and of women with uterine carcinoma (79.63 +/- 12.02 s) was significantly different (P < 0.0001) from the respective values found in healthy women (281.33 +/- 43.19 s). The CP activity in neoplastic tissue was 28.50 +/- 6.40 nmol pNa/mL for cervical carcinoma, and 28.31 +/- 3.92 nmol pNa/mL for uterine carcinoma, both values being significantly higher (P < 0.0009) than the activity found in the normal tissues. There was no established relationship between neoplastic CP activity and FIGO staging of the disease. This is the first study to demonstrate the concomitant presence of CP activity in serum and neoplastic tissue of women with genital carcinoma. These patients have decreased coagulation time and thus are likely to develop coagulation disturbances in the course of their cancer. There may be a role for CP as a tumor marker of

  14. Coexpression of intermediate filaments in normal and neoplastic human tissues: a reappraisal.

    Science.gov (United States)

    Coggi, G; Dell'Orto, P; Braidotti, P; Coggi, A; Viale, G

    1989-01-01

    The current view that coexpression of intermediate filaments (IFs) must be considered a bizarre and unpredictable phenomenon, which seriously jeopardizes the use of their localization in diagnostic applications, is critically reviewed in light of the evidence so far acquired by investigations in vivo and in vitro. A less dogmatic approach, which considers IF expression the result of a series of interactions between cells and their microenvironment instead of a function of their histogenesis, not only justifies the complex variety of coexpressions observed in normal and neoplastic tissues but also confirms the usefulness of IF expression in diagnostic applications and offers new opportunities for investigations, with special regard to immunoelectron microscopy.

  15. Low concentration of quercetin antagonizes the cytotoxic effects of anti-neoplastic drugs in ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Na Li

    Full Text Available OBJECTIVE: The role of Quercetin in ovarian cancer treatment remains controversial, and the mechanism is unknown. The aim of this study was to investigate the therapeutic effects of Quercetin in combination with Cisplatin and other anti-neoplastic drugs in ovarian cancer cells both in vitro and in vivo, along with the molecular mechanism of action. METHODS: Quercetin treatment at various concentrations was examined in combination with Cisplatin, taxol, Pirarubicin and 5-Fu in human epithelial ovarian cancer C13* and SKOV3 cells. CCK8 assay and Annexin V assay were for cell viability and apoptosis analysis, immunofluorescence assay, DCFDA staining and realtime PCR were used for reactive oxygen species (ROS-induced injury detection and endogenous antioxidant enzymes expression. Athymic BALB/c-nu nude mice were injected with C13*cells to obtain a xenograft model for in vivo studies. Immunohistochemical analysis was carried out to evaluate the ROS-induced injury and SOD1 activity of xenograft tumors. RESULTS: Contrary to the pro-apoptotic effect of high concentration (40 µM-100 µM of Quercetin, low concentrations (5 µM-30 µM of Quercetin resulted in varying degrees of attenuation of cytotoxicity of Cisplatin treatment when combined with Cisplatin. Similar anti-apoptotic effects were observed when Quercetin was combined with other anti-neoplastic agents: Taxol, Pirarubicin and 5-Fluorouracil (5-Fu. Low concentrations of Quercetin were observed to suppress ROS-induced injury, reduce intracellular ROS level and increase the expression of endogenous antioxidant enzymes, suggesting a ROS-mediated mechanism of attenuating anti-neoplastic drugs. In xenogeneic model, Quercetin led to a substantial reduction of therapeutic efficacy of Cisplatin along with enhancing the endogenous antioxidant enzyme expression and reducing ROS-induced damage in xenograft tumor tissue. CONCLUSION: Taken together, these data suggest that Quercetin at low concentrations

  16. Responsiveness of fetal rat brain cells to glia maturation factor during neoplastic transformation in cell culture

    DEFF Research Database (Denmark)

    Haugen, A; Laerum, O D; Bock, E

    1981-01-01

    The effect of partially purified extracts from adult pig brains containing a glia maturation protein factor (BE) has been investigated on neural cells during carcinogenesis. Pregnant BD IX-rats were given a single transplacental dose of the carcinogen ethylnitrosourea (EtNU) on the 18th day of ge...... on GFA-content was seen any longer, although some few weakly GFA positive cells could be observed in all permanent cell lines. Fetal rat brain cells therefore seem to become less responsive to this differentiation inducer during neoplastic transformation in cell culture....

  17. Effect of Octenisept antiseptic on bioburden of neoplastic ulcers in patients with advanced cancer.

    Science.gov (United States)

    Sopata, M; Ciupińska, M; Głowacka, A; Muszyński, Z; Tomaszewska, E

    2008-01-01

    To assess the effect of octenidine dihydrochloride (Octenisept, Schülke & Mayr) on the clinical condition and bacterial flora in neoplastic ulcers. Twenty-one patients with advanced cancer and neoplastic ulcers were included in the study. Octenisept-moistened gauze dressings were applied to the ulcers three times daily. The clinical and bacteriological status of the wounds were assessed at baseline and after three weeks of treatment. Thirty-three bacterial strains were cultured at baseline. After three weeks of treatment, the tests were repeated on 16 patients. Clinical observations confirmed an improvement in the clinical condition of the ulcers, characterised by a reduction in necrosis, exudate levels, erythema and oedema. According to the bacteriological assessment, Staphylococcus aureus, Staphylococcus epidermidis and Proteus mirabilis were eradicated from the wounds. Enterococcus faecalis persisted in two patients, Escherichia coli in one patient and Pseudomonas aeruginosa in another patient. Octenispet was an effective antimicrobial: Staphylococcus aureus and Proteus mirabilis were eradicated in all ulcers. After three weeks of treatment, none of the ulcers developed an infection and there was an improvement in their clinical condition.

  18. Neoplastic causes of nonacute facial paralysis: A review of 221 cases.

    Science.gov (United States)

    Leonetti, John P; Marzo, Sam J; Anderson, Douglas A; Sappington, Joshua M

    2016-09-01

    We conducted a retrospective review to assess the clinical presentation of patients with tumor-related nonacute complete peripheral facial weakness or an incomplete partial facial paresis and to provide an algorithm for the evaluation and management of these patients. Our study population was made up of 221 patients-131 females and 90 males, aged 14 to 79 years (mean: 49.7)-who had been referred to the Facial Nerve Disorders Clinic at our tertiary care academic medical center over a 23-year period with a documented neoplastic cause of facial paralysis. In addition to demographic data, we compiled information on clinical signs and symptoms, radiologic and pathologic findings, and surgical approaches. All patients exhibited gradual-onset facial weakness or facial twitching. Imaging identified an extratemporal tumor in 128 patients (58%), an intratemporal lesion in 55 patients (25%), and an intradural mass in 38 (17%). Almost all of the extratemporal tumors (99%) were malignant, while 91% of the intratemporal and intradural tumors were benign. A transtemporal surgical approach was used in the 93 intratemporal and intradural tumor resections, while the 128 extratemporal lesions required a parotidectomy with partial temporal bone dissection. The vast majority of patients (97%) underwent facial reanimation. We conclude that gradual-onset facial paralysis or twitching may occur as a result of a neoplastic invasion of the facial nerve along its course from the cerebellopontine angle to the parotid gland. We caution readers to beware of a diagnosis of "atypical Bell's palsy."

  19. Sites of inhibition of mitochondrial electron transport in macrophage-injured neoplastic cells.

    Science.gov (United States)

    Granger, D L; Lehninger, A L

    1982-11-01

    Previous work has shown that injury of neoplastic cells by cytotoxic macrophages (CM) in cell culture is accompanied by inhibition of mitochondrial respiration. We have investigated the nature of this inhibition by studying mitochondrial respiration in CM-injured leukemia L1210 cells permeabilized with digitonin. CM-induced injury affects the mitochondrial respiratory chain proper. Complex I (NADH-coenzyme Q reductase) and complex II (succinate-coenzyme Q reductase) are markedly inhibited. In addition a minor inhibition of cytochrome oxidase was found. Electron transport from alpha-glycerophosphate through the respiratory chain to oxygen is unaffected and permeabilized CM-injured L1210 cells oxidizing this substrate exhibit acceptor control. However, glycerophosphate shuttle activity was found not to occur within CM-injured or uninjured L1210 cells in culture hence, alpha-glycerophosphate is apparently unavailable for mitochondrial oxidation in the intact cell. It is concluded that the failure of respiration of intact neoplastic cells injured by CM is caused by the nearly complete inhibition of complexes I and II of the mitochondrial electron transport chain. The time courses of CM-induced electron transport inhibition and arrest of L1210 cell division are examined and the possible relationship between these phenomena is discussed.

  20. Relocalization of cell adhesion molecules during neoplastic transformation of human fibroblasts.

    Science.gov (United States)

    Belgiovine, Cristina; Chiodi, Ilaria; Mondello, Chiara

    2011-11-01

    Studying neoplastic transformation of telomerase immortalized human fibroblasts (cen3tel), we found that the transition from normal to tumorigenic cells was associated with the loss of growth contact inhibition, the acquisition of an epithelial-like morphology and a change in actin organization, from stress fibers to cortical bundles. We show here that these variations were paralleled by an increase in N-cadherin expression and relocalization of different adhesion molecules, such as N-cadherin, α-catenin, p-120 and β-catenin. These proteins presented a clear membrane localization in tumorigenic cells compared to a more diffuse, cytoplasmic distribution in primary fibroblasts and non-tumorigenic immortalized cells, suggesting that tumorigenic cells could form strong cell-cell contacts and cell contacts did not induce growth inhibition. The epithelial-like appearance of tumorigenic cells did not reflect a mesenchymal-epithelial transition; in fact, cen3tel cells expressed vimentin and did not express cytokeratins at all transformation stages. Moreover, they did not express epithelial proteins such as occluding and claudin-1. In contrast, ZO-1 showed higher levels and a more defined membrane localization in tumorigenic cells compared to non-tumorigenic cells; this confirms its role in adherens junction formation in mesenchymal cells and is in agreement with the strong cell-cell contact formation by neoplastically transformed cells. Finally, we found α-catenin and ZO-1 nuclear localization in non-transformed cells, suggestive of possible additional roles of these proteins besides cell junction formation.

  1. Taurolidine: a novel anti-neoplastic agent induces apoptosis of osteosarcoma cell lines.

    Science.gov (United States)

    Walters, Denise K; Muff, Roman; Langsam, Bettina; Gruber, Philipp; Born, Walter; Fuchs, Bruno

    2007-08-01

    Taurolidine, the active agent of Taurolin, is a broad spectrum anti-biotic that has been used for over 15 years for the treatment of severe surgical infections. Recently, taurolidine has been shown to possess anti-neoplastic properties in vitro and in vivo against a variety of cancers including ovarian, colon and prostate. In this study we assessed the cytotoxic activity of taurolidine against human osteosarcoma (OS) cell lines and normal human bone cells. Treatment with taurolidine inhibited the growth of all ten osteosarcoma cell lines tested and taurolidine was equally potent against cell lines with and without distinct genetic defects (i.e. p53, Rb). Moreover, taurolidine-induced growth inhibition was found to be associated with a dose dependent increase in the number of apoptotic cells and apoptosis was shown to be caspase-dependent. Taurolidine treatment was also found to inhibit adhesion of OS cell lines. Compared to OS cell lines, normal bone cells in primary culture were found to be less sensitive to the cytotoxic and anti-adhesive effects of taurolidine. These data indicate that taurolidine possesses potent anti-neoplastic activity against osteosarcoma cell lines and may have potential as a novel OS chemotherapeutic agent.

  2. A core of kinase-regulated interactomes defines the neoplastic MDSC lineage

    Science.gov (United States)

    Zudaire, Isabel; Liechtenstein, Therese; Arasanz, Hugo; Lozano, Teresa; Casares, Noelia; Chaikuad, Apirat; Knapp, Stefan; Guerrero-Setas, David; Escors, David; Kochan, Grazyna; Santamaría, Enrique

    2015-01-01

    Myeloid-derived suppressor cells (MDSCs) differentiate from bone marrow precursors, expand in cancer-bearing hosts and accelerate tumor progression. MDSCs have become attractive therapeutic targets, as their elimination strongly enhances anti-neoplastic treatments. Here, immature myeloid dendritic cells (DCs), MDSCs modeling tumor-infiltrating subsets or modeling non-cancerous (NC)-MDSCs were compared by in-depth quantitative proteomics. We found that neoplastic MDSCs differentially expressed a core of kinases which controlled lineage-specific (PI3K-AKT and SRC kinases) and cancer-induced (ERK and PKC kinases) protein interaction networks (interactomes). These kinases contributed to some extent to myeloid differentiation. However, only AKT and ERK specifically drove MDSC differentiation from myeloid precursors. Interfering with AKT and ERK with selective small molecule inhibitors or shRNAs selectively hampered MDSC differentiation and viability. Thus, we provide compelling evidence that MDSCs constitute a distinct myeloid lineage distinguished by a “kinase signature” and well-defined interactomes. Our results define new opportunities for the development of anti-cancer treatments targeting these tumor-promoting immune cells. PMID:26320174

  3. Two-staged operation on C2 neoplastic lesions: anterior excision and posterior stabilization.

    Science.gov (United States)

    Colak, Ahmet; Kutlay, Murat; Kibici, Kenan; Demircan, M Nusret; Akin, Osman N

    2004-07-01

    This retrospective study included eight consecutive cases with C2 vertebral body neoplastic lesions. The anterior retropharyngeal approach was used to remove the lesions and decompress the spinal cord. Spinal stabilization with occipitocervical plating in a second-stage operation makes the treatment more tolerable for patients. The object of this study was to determine the effectiveness of a two-stage operation strategy for these lesions. Eight patients were operated on via anterior retropharyngeal approach and then stabilized with occipitocervical plates posteriorly in a second sitting. All neck pain and all dysphagia problems resolved. Partial neurologic improvement was achieved in three out of four patients. No postoperative infection was seen. The retropharyngeal approach to the upper cervical spine and anterior foramen magnum lesions is an effective alternative to transoral surgery because of low complication rates. Neoplastic lesions in the upper cervical spine can safely and effectively be operated with this technique. The general medical status of patients with malignancies does not permit too long, time-consuming operations. Stabilization of the spine in a separate operation increases patient tolerability without any morbidity.

  4. The spectrum of oculocutaneous disease: Part II. Neoplastic and drug-related causes of oculocutaneous disease.

    Science.gov (United States)

    Day, Antoinette; Abramson, Amanda K; Patel, Mahir; Warren, Richard B; Menter, M Alan

    2014-05-01

    There are a multitude of diseases that commonly affect both the skin and the eye. Part II of this 2-part series reviews the oculocutaneous manifestations of neoplasms, both benign and malignant, and adverse drug reactions affecting the skin and the eye. Though rare, a number of neoplasms that primarily involve the skin, such as melanoma and basal cell carcinoma, can metastasize to the eye, leading to permanent damage if not properly treated. In addition, periocular neoplasms can irritate the conjunctiva and lid, reducing a patient's ability to see clearly. Neoplastic diseases, such as xeroderma pigmentosum, Sturge-Weber syndrome, and multiple myeloma, can also lead to permanent changes in the eye if not discovered and managed promptly. Furthermore, there are a multitude of drugs, including those commonly used by dermatologists, which can result in permanent damage to the eye. With proper knowledge of the ocular manifestations and treatment recommendations described in this 2-part series, dermatologists with the assistance of their ophthalmology colleagues can help avoid the complications, including permanent blindness, associated with infectious, inflammatory, genetic, neoplastic, and drug-related conditions. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  5. Extracellular matrix in tumours as a source of additional neoplastic lesions - a review

    Directory of Open Access Journals (Sweden)

    Madej Janusz A.

    2014-03-01

    Full Text Available The review describes the role of cells of extracellular matrix (ECM as a source of neoplastic outgrowths additional to the original tumour. The cells undergo a spontaneous transformation or stimulation by the original tumour through intercellular signals, e.g. through Shh protein (sonic hedgehog. Additionally, cells of an inflammatory infiltrate, which frequently accompany malignant tumours and particularly carcinomas, may regulate tumour cell behaviour. This is either by restricting tumour proliferation or, inversely, by induction and stimulation of the proliferation of another tumour cell type, e.g. mesenchymal cells. The latter type of tumour may involve formation of histologically differentiated stromal tumours (GIST, which probably originate from interstitial cells of Cajal in the alimentary tract. Occasionally, e.g. in gastric carcinoma, proliferation involves lymphoid follicles and lymphocytes of GALT (gut-associated lymphoid tissue, which gives rise to lymphoma. The process is preceded by the earlier stage of intestinal metaplasia, or is induced by gastritis alone. This is an example of primary involvement of inflammatory infiltrate cells in neoplastic progression. Despite the numerous histogenetic classifications of tumours (zygotoma benignum et zygotoma malignum, or mesenchymomata maligna et mesenchymomata benigna, currently in oncological diagnosis the view prevails that the direction of tumour differentiation and its degree of histologic malignancy (grading are more important factors than the histogenesis of the tumour.

  6. Immunoexpression of the COX-2, p53, and caspase-3 proteins in colorectal adenoma and non-neoplastic mucosa

    Science.gov (United States)

    Nogueira, Renan Brito; Pires, Andréa Rodrigues Cordovil; Soares, Thélia Maria Santos; Rodrigues, Simone Rabello de Souza; Campos, Mariane Antonieta Menino; Toloi, Giovanna Canato; Waisberg, Jaques

    2013-01-01

    ABSTRACT Objective: To analyze the immunoexpression of the COX-2, p53, and caspase-3 proteins in colorectal adenomas and non-neoplastic mucosa. Methods: 72 individuals were subjected to colonoscopy, which provided 50 samples of adenomas and 45 samples of non-neoplastic colorectal mucosa. The tissue samples were obtained via the tissue microarray technique and subjected to immunohistochemical analysis using primary anti-p53, anti-COX-2, and anti-caspase-3 antibodies. The positivity and intensity of the immunoreaction were classified. The analyzed variables were as follows: site of the adenomas in the colon, degree of dysplasia, size, and score of positivity and intensity of immunoexpression of the p-53, caspase-3, and COX-2 proteins. Results: The immunoexpression of mutated protein p53 was positive in 30 (60%) adenoma samples and negative in 20 (40%) adenoma samples. The immunoexpression of mutated protein p53 was negative in 39 (86.6%) samples and positive in 6 (13.3%) samples of the non-neoplastic colorectal mucosa (p<0.0001). Significant differences were seen between both the largest size (p=0.006) and the highest degree of dysplasia (p<0.0001) of the adenomas and the intensity of immunoexpression of mutated protein p53. The positivity and intensity of immunoexpression of COX-2 (p=0.14) and caspase-3 (p=0.23) showed no significant differences between the adenomas and the non-neoplastic colorectal mucosa. Conclusion: Mutated protein p53 was hyperexpressed in the adenomas compared with the non-neoplastic mucosa. Greater size and greater degree of dysplasia in the adenomas were associated with higher expression of mutated protein p53. The immunoexpression of COX-2 and caspase-3 in the adenomas did not exhibit a correlation with the anatomical-pathological features of the tumors and did not differ from the corresponding expression levels in the non-neoplastic mucosa. PMID:24488384

  7. The interleukin-6 receptor alpha-chain (CD126) is expressed by neoplastic but not normal plasma cells.

    Science.gov (United States)

    Rawstron, A C; Fenton, J A; Ashcroft, J; English, A; Jones, R A; Richards, S J; Pratt, G; Owen, R; Davies, F E; Child, J A; Jack, A S; Morgan, G

    2000-12-01

    Interleukin-6 (IL-6) is reported to be central to the pathogenesis of myeloma, inducing proliferation and inhibiting apoptosis in neoplastic plasma cells. Therefore, abrogating IL-6 signaling is of therapeutic interest, particularly with the development of humanized anti-IL-6 receptor (IL-6R) antibodies. The use of such antibodies clinically requires an understanding of IL-6R expression on neoplastic cells, particularly in the cycling fraction. IL-6R expression levels were determined on plasma cells from patients with myeloma (n = 93) and with monoclonal gammopathy of undetermined significance (MGUS) or plasmacytoma (n = 66) and compared with the levels found on normal plasma cells (n = 11). In addition, 4-color flow cytometry was used to assess the differential expression by stage of differentiation and cell cycle status of the neoplastic plasma cells. IL-6R alpha chain (CD126) was not detectable in normal plasma cells, but was expressed in approximately 90% of patients with myeloma. In all groups, the expression levels showed a normal distribution. In patients with MGUS or plasmacytoma, neoplastic plasma cells expressed significantly higher levels of CD126 compared with phenotypically normal plasma cells from the same marrow. VLA-5(-) "immature" plasma cells showed the highest levels of CD126 expression, but "mature" VLA-5(+) myeloma plasma cells also overexpressed CD126 when compared with normal subjects. This study demonstrates that CD126 expression is restricted to neoplastic plasma cells, with little or no detectable expression by normal cells. Stromal cells in the bone marrow microenvironment do not induce the overexpression because neoplastic cells express higher levels of CD126 than normal plasma cells from the same bone marrow in individuals with MGUS. (Blood. 2000;96:3880-3886)

  8. Most multifocal papillary thyroid carcinomas acquire genetic and morphotype diversity through subclonal evolution following the intra-glandular spread of the initial neoplastic clone.

    Science.gov (United States)

    Jovanovic, L; Delahunt, B; McIver, B; Eberhardt, N L; Grebe, S K G

    2008-06-01

    Papillary thyroid carcinoma (PTC) is frequently multifocal (mPTC), with synchronous tumour foci often showing varied morphology. The genetic mechanisms underlying the development of multiple and histologically diverse tumour foci remain uncertain. Different tumour foci might develop either through intrathyroidal dissemination of a single malignant clone, with morphotype differentiation occurring as a result of subclonal progression, or they may stem from independent transformational events involving multiple progenitor clones. To determine the clonal derivation of multiple tumour foci and to map their clonal relationships and genetic progression in mPTC, we evaluated genome-wide allelic imbalances (AI) and BRAF V600E mutation status in 55 synchronous tumour foci from 18 mPTC patients. For apparently monoclonal tumours, we calculated the probabilities of monoclonal derivation and used phylogenetic analysis to model clonal evolution. Genome-wide allelotyping and BRAF mutation analysis showed genetic alterations consistent with monoclonal origin in 83% of cases, mostly with evidence of subclonal evolution. BRAF V600E mutations were early events during clonal evolution of most, but not all cases. MPTC with morphologically diverse tumour foci also arose through monoclonal derivation in 75% of cases, demonstrating that morphotype-determining genetic changes can be acquired during clonal diversification, subsequent to the spread of the original malignant progenitor clone. In 17% of patients, discordant AI or BRAF V600E profiles implied that mPTCs can occasionally develop from distinct transformation events. This study suggests that mPTC originates usually from neoplastic transformation and subsequent intrathyroidal spread of a single malignant progenitor clone. Clonal progression and morphotype differentiation occur through progressive acquisition of genetic alterations subsequent to the initial intra-glandular spread. In monoclonal BRAF V600E-positive mPTCs, BRAF V600E

  9. Experimental study on anti-neoplastic activity of epigallocatechin-3-gallate to digestive tract carcinomas

    Institute of Scientific and Technical Information of China (English)

    RAN Zhi-hua; ZOU Jian; XIAO Shu-dong

    2005-01-01

    Background Epigallocatechin-3-gallate (EGCG) has been demonstrated to have anti-neoplastic activity, but the effective concentration of EGCG and its possible mechanisms are uncertain. The study on the killing effects of EGCG on different digestive tract cancer cell lines can find target sites of its anti-neoplastic effect and provide a theoretical basis for its clinical application in the treatment of cancers. Methods Methyl thiazolyl tetrazolium (MTT) analysis was made to detect the differential sensitivities of eight digestive tract cancer cell lines to EGCG. The effect of EGCG on cell cycle distribution of sensitive cancer cell line was measured by flow cytometry. By polymerase chain reaction (PCR)-enzyme linked immunosorbent assay (ELISA) protocol, the influence of EGCG on telomerase activity of sensitive cancer cell line was also investigated. RT-PCR method was employed to detect the influence of EGCG on the expressions of hTERT, c-myc, p53 and mad1 genes in sensitive cancer cell line. Results EGCG exhibited dose-dependent killing effects on all eight disgestive tract cancer cell lines. The 50% inhibitory concentration (IC50) of SW1116, MKN45, BGC823, SGC7901, AGS, MKN28, HGC27 and LoVo cells were 51.7 μmol/L, 55.9 μmol/L, 68.5 μmol/L, 79.1 μmol/L, 83.8 μmol/L, 119.8 μmol/L, 183.2 μmol/L and 194.6 μmol/L, respectively. There were no apparent changes in cell cycle distribution of sensitive cancer cell line MKN45 48 hours after incubating with three different concentrations of EGCG compared with the controls. It was found that EGCG could suppress the telomerase activity of MKN45 cells, and the effects were dose- and time-dependent. After EGCG administration, the expression of hTERT and c-myc genes in MKN45 cells was decreased, that of the mad1 gene increased, and that of the p53 gene unchanged. Conclusions EGCG has dose-dependent killing effects on different digestive tract cancer cell lines. Administration of EGCG has no obvious effect on cell cycle

  10. Validation of coded aperture coherent scatter spectral imaging for normal and neoplastic breast tissues via surgical pathology

    Science.gov (United States)

    Morris, R. E.; Albanese, K. E.; Lakshmanan, M. N.; McCall, S. J.; Greenberg, J. A.; Kapadia, A. J.

    2016-03-01

    This study intends to validate the sensitivity and specificity of coded aperture coherent scatter spectral imaging (CACSSI) by comparison to standard histological preparation and pathologic analysis methods used to differentiate normal and neoplastic breast tissues. A composite overlay of the CACSSI rendered image and pathologist interpreted stained sections validate the ability of CACSSI to differentiate normal and neoplastic breast structures ex-vivo. Via comparison to pathologist annotated slides, the CACSSI system may be further optimized to maximize sensitivity and specificity for differentiation of breast carcinomas.

  11. Review Article: The Role of Molecular Pathological Epidemiology in the Study of Neoplastic and Non-neoplastic Diseases in the Era of Precision Medicine.

    Science.gov (United States)

    Ogino, Shuji; Nishihara, Reiko; VanderWeele, Tyler J; Wang, Molin; Nishi, Akihiro; Lochhead, Paul; Qian, Zhi Rong; Zhang, Xuehong; Wu, Kana; Nan, Hongmei; Yoshida, Kazuki; Milner, Danny A; Chan, Andrew T; Field, Alison E; Camargo, Carlos A; Williams, Michelle A; Giovannucci, Edward L

    2016-07-01

    Molecular pathology diagnostics to subclassify diseases based on pathogenesis are increasingly common in clinical translational medicine. Molecular pathological epidemiology (MPE) is an integrative transdisciplinary science based on the unique disease principle and the disease continuum theory. While it has been most commonly applied to research on breast, lung, and colorectal cancers, MPE can investigate etiologic heterogeneity in non-neoplastic diseases, such as cardiovascular diseases, obesity, diabetes mellitus, drug toxicity, and immunity-related and infectious diseases. This science can enhance causal inference by linking putative etiologic factors to specific molecular biomarkers as outcomes. Technological advances increasingly enable analyses of various -omics, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics, microbiome, immunomics, interactomics, etc. Challenges in MPE include sample size limitations (depending on availability of biospecimens or biomedical/radiological imaging), need for rigorous validation of molecular assays and study findings, and paucities of interdisciplinary experts, education programs, international forums, and standardized guidelines. To address these challenges, there are ongoing efforts such as multidisciplinary consortium pooling projects, the International Molecular Pathological Epidemiology Meeting Series, and the Strengthening the Reporting of Observational Studies in Epidemiology-MPE guideline project. Efforts should be made to build biorepository and biobank networks, and worldwide population-based MPE databases. These activities match with the purposes of the Big Data to Knowledge (BD2K), Genetic Associations and Mechanisms in Oncology (GAME-ON), and Precision Medicine Initiatives of the United States National Institute of Health. Given advances in biotechnology, bioinformatics, and computational/systems biology, there are wide open opportunities in MPE to contribute to public

  12. [Computerized tomography guided biopsy in the diagnosis of neoplastic and inflammatory lesions of the pelvis].

    Science.gov (United States)

    Rimondi, E; Busacca, M; Moio, A; Molinari, M; Nigrisoli, M; Trentani, F; Trentani, P; Tigani, D

    2001-01-01

    To assess the efficacy of percutaneous CT-guided biopsy in the diagnosis and therapeutic planning of neoplastic and flogistic diseases of the pelvis. From July 1990 to December 1999 193 patients (113 males, 80 females: mean age 49, standard deviation 16) were submitted to CT-guided percutaneous biopsy of the pelvic region; 117 biopsies (61%) were performed at iliac, pubic and ischial segments and 76 (39%) at sacral region; 107 patients were admitted to the hospital and 86 were in clinic. Needles were 8 G (4 mm), 10 to 15 cm long. Approach to pelvic lesions was performed according to the specific site. Lesions of the lateral pelvic region have always been approached through the lateral surgical incision according to Enneking. Lesions of the posterior pelvic region have always been approached by the introduction of the needle along the posterior surgical incision according to Enneking. Lesions of the anterior region have always been approached through the anterior surgical incision according to Enneking. From July 1990 to May 1997 pelvic percutaneous biopsies have been carried out with a CT Sytec 3000. From May 1997 to December 1999 the device was replaced by a High Speed CTi. The introduction of spiral CT allowed reduction of performance mean time from 45 minutes (standard deviation 15) to 30 minutes (standard deviation 10). In 154 patients (80%) we observed a neoplastic, inflammatory or not classified degeneration. In 8 patients (4%) the retrieved material ended to be inadequate for a diagnosis. In 31 patients (16%) no disease was revealed at the histological examination. Such patients with negative histological examination have been kept under clinical and radiological control in the following period in order to verify the manifestation or the presence of an alteration previously not observed. On 31-3-2000 none of them had been submitted to a new percutaneous biopsy of the pelvic region. The overall mean accuracy has been 96% considering the negative patients as

  13. The Role of miRNAs as Key Regulators in the Neoplastic Microenvironment

    Directory of Open Access Journals (Sweden)

    K. K. Wentz-Hunter

    2011-01-01

    Full Text Available The neoplastic microenvironment has been recognized to play a critical role in the development of cancer. Although a large body of evidence has established the importance of the cancer microenvironment, the manners of crosstalk between it and the cancer cells still remains unclear. Emerging mechanisms of communication include microRNAs (miRNAs. miRNAs are small noncoding RNA molecules that are involved in the posttranscriptional regulation of mRNA. Both intracellular and circulating miRNAs are differentially expressed in cancer and some of these alterations have been correlated with clinical patient outcomes. The role of miRNAs in the tumor microenvironment has only recently become a focus of research, however. In this paper, we discuss the influence of miRNAs on the tumor microenvironment as it relates to cancer progression. We conclude that miRNAs are a critical component in understanding invasion and metastasis of cancer cells.

  14. Diagnostic ultrasound is unable to enhance the rate of neoplastic transformation in cultured mammalian cells.

    Science.gov (United States)

    Tolsma, S S; Madsen, E L; Chmiel, J; Martin, A O; Bouck, N P

    1991-11-01

    The ability of diagnostic pulsed ultrasound to induce heritable genetic damage of the type that could result in neoplasia was assayed using BHK21/cl 13 hamster cells or normal human fibroblasts as targets. Using an exposure apparatus carefully designed to minimize beam attenuation and reflection, cavitation, and heating, cells were exposed from 20 seconds to 40 minutes either to clinical machines operating at maximum power, or to a highly focused nonclinical transducer at 2900 W/cm2, or to 200 shocks from a lithotripter. No evidence of an increase in the frequency of neoplastically transformed BHK cells or in the frequency of mutant human cells was seen over those found in matched sham-exposed controls.

  15. Neoplastic transformation of a human prostate epithelial cell line by the v-Ki-ras oncogene.

    Science.gov (United States)

    Parda, D S; Thraves, P J; Kuettel, M R; Lee, M S; Arnstein, P; Kaighn, M E; Rhim, J S; Dritschilo, A

    1993-01-01

    Investigations of mechanisms of human prostate carcinogenesis are limited by the unavailability of a suitable in vitro model system. We have demonstrated that an immortal, but nontumorigenic, human epithelial cell line (267B1) established from fetal prostate tissue can be malignantly transformed by a biological carcinogen, and can serve as a useful model for investigations of the progression steps of carcinogenesis. Activated Ki-ras was introduced into 267B1 cells by infection with the Kirsten murine sarcoma virus. Morphological alterations and anchorage-independent growth were observed; when cells were injected into nude mice, poorly differentiated adenocarcinomas developed. These findings represent the first evidence of malignant transformation of human prostate epithelial cells in culture, and support a role for Ki-ras activation in a multistep process for prostate neoplastic transformation.

  16. Neoplastic diseases of the spermatic cord: an overview of pathological features, evaluation, and management

    Science.gov (United States)

    Dagur, Gautam; Gandhi, Jason; Kapadia, Kailash; Inam, Rafid; Smith, Noel L.; Joshi, Gargi

    2017-01-01

    Extracellular tumors found with the spermatic cord, known as neoplasms, are usually identified to be benign. However, the accurate and timely diagnosis of spermatic cord masses is highly crucial, especially when most results are often overlooked or unclear. In this review, we discuss the anatomy and embryology of the spermatic cord. Upon rooting these fundamental concepts, we discuss an array of benign and malignant neoplastic tumors, including their origin, pathological features, clinical evaluation and management, as well as other case-specific characteristics of unique presentation. Many of these neoplasms are based on local neurological, vascular, muscular, bone, soft tissue, or lymphatic origin, while others have metastasized from particular areas of the body. PMID:28217455

  17. Bioactive substances with anti-neoplastic efficacy from marine invertebrates: Porifera and Coelenterata

    Science.gov (United States)

    Sima, Peter; Vetvicka, Vaclav

    2011-01-01

    An ever increasing demand for new lead compounds in the pharmaceutical industry has led scientists to search for natural bioactive products. Based on this extensive research, marine invertebrates now represent a rich source of novel substances with significant anti-neoplastic activities. As the current approach of synthesizing new and chemically modifying old drugs seems to have slowed down, and the identification of new anticancer drugs is not too promising, a new approach is clearly needed. The objective of this review is to present up-to-date data on these newer compounds. Based on the data summarized in this short review, it is clear that marine invertebrates represent an extremely important source of compounds with potential anti-cancer effects. Considering that we tested only a tiny number of Porifera and Coelenterata, the best is yet to come. PMID:22087433

  18. The origin of pre-neoplastic metaplasia in the stomach: Chief cells emerge from the Mist

    Energy Technology Data Exchange (ETDEWEB)

    Goldenring, James R., E-mail: jim.goldenring@vanderbilt.edu [Nashville Department of Veterans Affairs Medical Center, Nashville, TN (United States); Departments of Surgery and Cell and Developmental Biology, Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, TN (United States); Nam, Ki Taek [Nashville Department of Veterans Affairs Medical Center, Nashville, TN (United States); Departments of Surgery and Cell and Developmental Biology, Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, TN (United States); Mills, Jason C. [Divison of Gastroenterology, Departments of Medicine, Pathology, and Developmental Biology, Washington University School of Medicine, St. Louis, MO (United States)

    2011-11-15

    The digestive-enzyme secreting, gastric epithelial chief (zymogenic) cell is remarkable and underappreciated. Here, we discuss how all available evidence suggests that mature chief cells in the adult, mammalian stomach are postmitotic, slowly turning over cells that arise via a relatively long-lived progenitor, the mucous neck cell, The differentiation of chief cells from neck cells does not involve cell division, and the neck cell has its own distinct pattern of gene expression and putative physiological function. Thus, the ontogeny of the normal chief cell lineage exemplifies transdifferentiation. Furthermore, under pathophysiogical loss of acid-secreting parietal cell, the chief cell lineage can itself trasndifferentiate into a mucous cell metaplasia designated Spasmolytic Polypeptide Expressing Metaplasia (SPEM). Especially in the presence of inflammation, this metaplastic lineage can regain proliferative capacity and, in humans may also further differentiate into intestinal metaplasia. The results indicate that gastric fundic lineages display remarkable plasticity in both physiological ontogeny and pathophysiological pre-neoplastic metaplasia.

  19. GRAPEVINE HABITUATION: UNDERSTANDING OF FACTORS THAT ONTRIBUTE TO SOMACLONAL VARIATION AND NEOPLASTIC TRANSFORMATION

    Directory of Open Access Journals (Sweden)

    I. Baumgartnerová

    2008-09-01

    Full Text Available A type of heritable cellular change, known as habituation, occurs spontaneously in plant tissue and cell culture. It is the acquired ability of a population of cells to grow and divide independently of exogenously supplied growth regulators. An imbalance in phytohormones in the media, particularly auxins and cytokinins, is an important source of stress and has been linked to hyperhydricity, somaclonal variation, recalcitrance and habituation. All of these abnormalities are potentially very costly to the plant breeding industry. Moreover, habituation as a tumorous and/or neoplastic transformation state that is interchangeable with a normal state in plant cell. This requires a better understanding of factors that contribute to these phenomena. Here we used a computational prediction method based on the known protein structural interactions to analyze grapevine large-scale protein-protein interaction rules within and among complete genomes such as yeast, fly, worm, Arabidopsis, and human and their HTP (high-throughput method maps. These studies may help to elucidate the molecular mechanisms of neoplastic phenomena in plants and perhaps in animals. We found fundamental differences among eukaryotic interactomes. We confirmed that all the predicted protein family interactomes (the full set of protein family interactions within a proteome of 6 species are scale-free networks, and they share a small core network comprising 16 protein families related to indispensable cellular functions involved predominantly in the pathogenesis, apoptosis and plant tumorigenesis, as well. Molecular evidence is presented that suggests that grapevine cells that have become habituated for one or more essential factors results from heritable alterations in the pattern of gene expression and that it can, therefore, be used as a model for study of cell differentiation. Moreover, the overall significance of these findings to the plant and in a some instantion also the animal

  20. MicroRNAs involved in neoplastic transformation of liver cancer stem cells

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    Wang Xinchuan

    2010-12-01

    Full Text Available Abstract Background The existence of cancer stem cells in hepatocellular carcinoma (HCC has been verified by characterizing side population (SP cells based on efflux of Hoechst 33342 dye from stem cells. Recent advances in microRNA (miRNA biology have revealed that miRNAs play an important role in embryonic development and tumorigenesis. However, it is still unclear which miRNAs participate in the neoplastic transformation of liver cancer stem cells (LCSCs during hepatocarcinogenesis. Methods To identify the unique set of miRNAs differentially regulated in LCSCs, we applied SP sorting to primary cultures of F344 rat HCC cancer cells treated with diethylnitrosamine (DEN and normal syngenic fetal liver cells, and the stem-like characteristics of SP cells were verified through detecting expression of CD90.1, AFP and CK-7. Global miRNA expression profiles of two groups of SP cells were screened through microarray platform. Results A total of 68 miRNAs, including miR-10b, miR-21, miR-470*, miR-34c-3p, and let-7i*, were identified as overexpressed in SP of HCC cells compared to fetal liver cells. Ten miRNAs were underexpressed, including miR-200a* and miR-148b*. These miRNAs were validated using stem-loop real-time reverse transcriptase polymerase chain reaction (RT-PCR. Conclusions Our results suggest that LCSCs may have a distinct miRNA expression fingerprint during hepatocarcinogenesis. Dissecting these relationships will provide a new understanding of the function of miRNA in the process of neoplastic transformation of LCSCs.

  1. Expression of proto-oncogene Fra-1 in human neoplastic breast tissues

    Institute of Scientific and Technical Information of China (English)

    Yuhua Song; Jing Wang; Xiaoyun Yu; Santai Song; Zefei Jiang

    2012-01-01

    Objective: Invasion and metastasis are the most significant and intrinsic biological characteristics of cancers, also which are main factors of malignant tumor causing treatment failure and death. Recent studies have found that Fra-1 plays an important role on cell migration, invasion, and maintaining malignant phenotype of transformed cells. But there are few studies about the expression and location of Fra-1 in breast tissues and cells being reported This study just aims to discuss the expression and location of transcription factor Fra-1 in benign and malignant human breast tissues. Methods: The expression of Fra-1 was investigated by immunohistochemistry in neoplastic breast diseases ranging from benign fibroadenoma to very aggressive undifferentiated carcinoma. The correlations of Fra-1 expression with other indicators of breast carcinoma prognosis (ER, PR and ErbB2 receptors) were analyzed. Results: All neoplastic breast tissues, either benign or malignant breast tissues, were nuclear immunoreactive for Fra-1-recognizing antibody. In 85% of benign tumors (17/20), the immunoreactive for Fra-1-recognizing antibody as exclusively restricted to the nuclei. In three cases (3/20,15%), focal unequivocal cytoplas-mic staining was also exhibited. Strong positive nuclear staining for Fra-1 was easily seen in all types of breast carcinomas. However the nuclear/cytoplasmic concomitant immunoreactivity was observed in all types of breast carcinomas. A clear shift in Fra-1 immunoreactivity, from an exclusively nuclear to a simultaneous nuclear and cytoplasmic localization was noticed in 90.2% (37/41) of breast carcinomas. No inverse relationship between Fra-1 and ER and PR protein levels was noticed in malignant tumors. The relative expression level of Fra-1 was not correlated with the expression of ErbB2. Conclusion: The overall expression, pattern and intensity of Fra-1 proteins were correlated with breast oncogenesis. Overexpression of Fra-1, leading to a persistent

  2. Neoplastic Meningitis: How MRI and CSF Cytology Are Influenced by CSF Cell Count and Tumor Type

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    P. Prömmel

    2013-01-01

    Full Text Available Background. Although CSF cytology and MRI are standard methods to diagnose neoplastic meningitis (NM, this complication of neoplastic disease remains difficult to detect. We therefore reevaluated the sensitivity of gadolinium (GD-enhanced MRI and cerebrospinal-fluid (CSF-cytology and the relevance of tumor type and CSF cell count. Methods. We retrospectively identified 111 cases of NM diagnosed in our CSF laboratory since 1990 with complete documentation of both MRI and CSF cytology. 37 had haematological and 74 solid neoplasms. CSF cell counts were increased in 74 and normal in 37 patients. Results. In hematological neoplasms, MRI was positive in 49% and CSF cytology in 97%. In solid tumors, the sensitivity of MRI was 80% and of cytology 78%. With normal CSF cell counts, MRI was positive in 59% (50% hematological, 72% solid malignancies and CSF cytology in 76% (92% in hematological, 68% in solid neoplasms. In cases of elevated cell counts, the sensitivity of MRI was 72% (50% for hematological, 83% for solid malignancies and of CSF cytology 91% (100% for haematological and 85% for solid neoplasms. 91% of cytologically positive cases were diagnosed at first and another 7% at second lumbar puncture. Routine protein analyses had a low sensitivity in detecting NM. Conclusions. The high overall sensitivity of MRI was only confirmed for NM from solid tumors and for elevated CSF cell counts. With normal cell counts and haematological neoplasms, CSF-cytology was superior to MRI. None of the analysed routine CSF proteins had an acceptable sensitivity and specificity in detecting leptomeningeal disease.

  3. Adenocarcinoma of the rete testis with prominent papillary structure and clear neoplastic cells: Morphologic and immunohistochemical findings and differential diagnosis

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    Pei-Wen Huang

    2015-01-01

    Full Text Available Adenocarcinoma of the rete testis is rare, and its etiology is unknown. The definite diagnosis merely depends on the exclusion of other tumors and histological features. We first describe a 38-year-old man with a carcinoma arising in the rete testis. The tumor was characterized by clear neoplastic cells and branching papillary growth. Focal stromal invasion and transition of normal rete epithelium to neoplastic cells were seen. The neoplastic cells were positive for epithelial membrane antigen, Ber-Ep4, vimentin, renal cell carcinoma marker, and CD10, while negative for Wilms′ tumor 1, thyroid transcription factor-1, estrogen receptor, prostate specific antigen, placental alkaline phosphate, CD117, and alpha-1-fetoprotein. According to the above features, we diagnosed this tumor as adenocarcinoma of the rete testis. To our best knowledge, this is the first reported case of adenocarcinoma of the rete testis with prominently papillary structure and clear neoplastic cells. The rarity of adenocarcinoma of the rete testis and the unique features in our case cause diagnostic pitfalls. A complete clinicopathological study and thorough differential diagnosis are crucial for the correct result.

  4. Mechanisms underlying the adaptive response against spontaneous neoplastic transformation induced by low doses of low LET radiation - Final Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    John Leslie Redpath

    2007-01-17

    The objective of the research was to examine mechanisms underlying the suppressive effects of low doses (<10 cGy) of low-LET radiation on the endpoint of neoplastic transformation in vitro. The findings indicated a role for upregulation of DNA repair but not of antioxidants.

  5. EFFECTS OF p53 OVEREXPRESSION ON NEOPLASTIC CELL MITOSIS AND APOPTOSIS IN NASOPHARYNGEAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To investigate the p53 overexpression and its correlation withneoplastic cell mitosis and apoptosis in 43 nasopharyngeal carcinomas (NPCs). Methods: Forty-three pretreated NPC biopsy samples were randomly collected in the year 1997 for this study. p53 overexpression was detected by LSAB immunohistochemistry using DO-7 primary antibody. Mitotic figures were counted on H&E stained slides, and apoptotic cells on TUNEL-stained slides by use of in-situ cell death detection kit. Both of mitotic and apoptotic cells were quantitated by cell numbers per one high power field (5′ 40) averagely in terms of mitotic index (MI) and TUNEL index (TI), respectively. To compare the mean MIs of two groups categorized by different percentages of positive p53 positive cells found in NPC specimens was taken for the purpose of designating the criterion of p53 overexpression. And then, the correlation of p53 overexpression with MI and TI was made by statistical analysis. Results: Because statistically significant difference appeared at the criterion of 20%, the p53 overexpression of NPC was defined as≥20% of positive cells found. The p53 overexpression thus could be detected in 37 out of 43 NPCs, reaching 86.05% (37/43). The mean MI (1.87± 1.78/HPF) of 37 NPCs with p53 overexpression was significantly higher than that (0.76± 0.63/HPF) of 6 NPCs without p53 overexpression, the P value being <0.05. However, there was no statistical difference between the mean TI (24.50± 26.66HPF) of 37 NPCs with p53 overexpression and TI (23.17± 25.30/HPF) of 6 NPCs without p53 overexpression. Conclusions: p53 overexpression of NPC could be designated by ≥20% of positive neoplastic cells found in pretreated NPC specimens, and the rate of which reached 86.05% (37/43). The overexpressed p53 could enhance cell proliferative activity in pretreated NPCs represented by increasing of MI, but showed no effect on neoplastic cell apoptosis.

  6. Spontaneous proliferative and neoplastic lesions in thyroid and parathyroid glands of nondomestic felids.

    Science.gov (United States)

    Pope, Jenny P; Steeil, James; Ramsay, Edward C; Reel, Danielle; Newman, Shelley J

    2017-01-01

    Based on microscopic and immunohistochemical characterization, we documented spontaneous proliferative and neoplastic lesions in the thyroid and parathyroid glands of nondomestic felids. Ten animals (4 leopards, 3 tigers, and 3 cougars), all with a previous diagnosis of thyroid neoplasia were identified from the University of Tennessee College of Veterinary Medicine database. The mean age of affected animals was 15.9 y. Twelve neoplasms were identified; 2 animals had 2 concurrent neoplasms. After immunohistochemical characterization using a panel of chromogranin A, thyroglobulin, and calcitonin, 7 of the former thyroid neoplasms were diagnosed as thyroid adenomas, 1 was diagnosed as a thyroid carcinoma, and 4 were diagnosed as parathyroid adenomas. No thyroid medullary neoplasms (C-cell tumors) were diagnosed in the current study. Most of the diagnosed neoplasms were benign (11 of 12), and metastasis was not documented in the single carcinoma. Only 2 animals were suspected to have functional neoplasms (1 thyroid adenoma and 1 parathyroid adenoma), based on associated tissue lesions or serum biochemistry. Other documented lesions in the thyroid and parathyroid glands included thyroid nodular hyperplasia ( n = 7), parathyroid hyperplasia associated with chronic renal disease ( n = 2), a thyroid abscess, and a branchial cyst. Parathyroid adenomas were more commonly diagnosed than expected in comparison with domestic cats. We demonstrated that an immunohistochemistry panel for thyroglobulin, calcitonin, and chromogranin A can be used to differentiate neoplasms of thyroid from parathyroid origin in nondomestic felids.

  7. Rejection of normal and neoplastic hemopoietic cells by lethally irradiated mice

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    Afifi, M.S.H.

    1985-01-01

    The objective of this study was to investigate the mechanisms of rejection of normal and neoplastic hemopoietic cells by lethally irradiated mice, in part by investigating the hypothesis that two or more cell types are involved in recognition and rejection of hemopoietic cells. Interferon (IFN) was used as a tool for investigating such mechanisms. IFN alpha/beta stimulated the rejection of normal hemopoietic marrow cell grafts in Fl hybrid and in allogeneic host mice but did not affect the growth of cells in syngeneic mice. IFN alpha/beta was effective in hosts pretreated with silica but not in hosts pretreated with cyclophosphamide (Cy) or with anti-asialoGMI serum. Rabbit anti-IFN alpha/beta, but not anti-IFN gamma, serum inhibited genetic resistance to bone marrow cells. These results indicated that IFN alpha/beta was acting indirectly during the rejection of normal hemopoietic cells. It is proposed that four events occur in succession: a host cell recognizes the hemopoietic histocompatibility (Hh) antigens expressed on the surface of incompatible stem cells; this recognition leads to secretion of IFN; IFN activates natural killer (NK) cells; NK cells lyse donor stem cells. Silica interrupts one or both of the first two events. i.e., recognition and/or interrupts one or both of the first two events, i.e. recognition and/or IGN secretion.

  8. Cytopathology of neoplastic meningitis: A series of 66 cases from a tertiary care center

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    Gurdeep Singh

    2013-01-01

    Full Text Available Background: Neoplastic meningitis (NM is a condition characterized by leptomeningeal involvement by metastatic carcinoma. Detection of exfoliated malignant cells in cerebrospinal fluid (CSF due to meningeal metastasis is frequently associated with diverse neurologic presentations. Materials and Methods: In this retrospective study of all cases of NM diagnosed in CSF samples over a 20-year period at a tertiary care referral center, the cytomorphologic features were reviewed. Results: Sixty six cases of NM were identified of which 36 already had an established diagnosis of malignancy while in 30 patients, there was no previously known tumor. The most common known primary in the former group was breast followed by ovary. Single cell pattern, cellular cannibalism, moderate cytoplasm and rounded nuclei were seen in breast and lung tumors. Papillary architecture and cytoplasmic vacuolation were seen in the ovarian primaries. Melanin pigment was seen in malignant melanoma. Conclusion: CSF cytology is an important tool for diagnosis of NM. Cytomorphologic features helped in diagnosis and for prediction of the primary site. Correct identification of this condition is important as it has therapeutic and prognostic implications.

  9. miR-200 family expression is downregulated upon neoplastic progression of Barrett's esophagus

    Institute of Scientific and Technical Information of China (English)

    Cameron M Smith; David I Watson; Mary P Leong; George C Mayne; Michael Z Michael; Bas PL Wijnhoven; Damian J Hussey

    2011-01-01

    AIM:To investigate miR-200 family expression in Barrett's epithelium,gastric and duodenal epithelia,and esophageal adenocarcinoma. METHODS:Real-time reverse transcriptase-polymerase chain reaction was used to measure miR-200,ZEB1 and ZEB2 expression.Ingenuity Pathway Analysis of miR-200 targets was used to predict biological outcomes. RESULTS:Barrett's epithelium expressed lower levels of miR-141 and miR-200c than did gastric and duodenal epithelia (P < 0.001).In silico analysis indicated roles for the miR-200 family in molecular pathways that distinguish Barrett's epithelium from gastric and duodenal epithelia,and which control apoptosis and proliferation. All miR-200 members were downregulated in adenocarcinoma (P < 0.02),and miR-200c expression was also downregulated in non-invasive epithelium adjacent to adenocarcinoma (P < 0.02).The expression of all miR-200 members was lower in Barrett's epithelium derived high-grade dysplastic cell lines than in a cell line derived from benign Barrett's epithelium.We observed significant inverse correlations between miR-200 family expression and ZEB1 and ZEB2 expression in Barrett's epithelium and esophageal adenocarcinoma (P < 0.05). CONCLUSION:miR-200 expression might contribute to the anti-apoptotic and proliferative phenotype of Barrett's epithelium and regulate key neoplastic processes in this epithelium.

  10. Neoplastic transformation of cells by soluble but not particulate forms of metals used in orthopaedic implants.

    Science.gov (United States)

    Doran, A; Law, F C; Allen, M J; Rushton, N

    1998-01-01

    Recent developments in cell culture techniques have made it possible to study the cellular mechanisms involved in carcinogenesis and to apply these methods as screening tools in vitro. This study investigated and compared the ability of the metals most commonly used in orthopedic implants to induce toxicity and neoplastic transformation in the C3H10T1/2 mouse fibroblast cell line. Eight metals (cobalt, chromium, nickel, iron, molybdenum, aluminium, vanadium and titanium) and their alloys (stainless steel, cobalt-chrome alloy and titanium alloy) were tested, both as soluble salts and as solid particles. There were marked differences between the various metals in terms of both toxicity and transforming ability. Significant increases in the incidence of cell transformation were seen with soluble forms of cobalt, chromium, nickel and molybdenum but not with iron, aluminium, vanadium or titanium. For most of the metals. transforming ability was directly related to toxicity, although this correlation did not hold for either molybdenum or vanadium. The physical form of the metal was critically important in determining its effects, and transformation occurred only with soluble metal salts.

  11. Hierarchies and causal relationships in interpretative models of the neoplastic process.

    Science.gov (United States)

    Bertolaso, Marta

    2011-01-01

    The aim of this paper is to present a critical analysis of the kind of biological systems identified in the main explanatory theories of cancer (i.e. Somatic Mutation Theory and Tissue Organization Field Theory) and how references to the hierarchical organization of these biological systems are used in their explanatory arguments. I will discuss these aspects in terms of the isolation of the "locus of control" (Bechtel and Richardson 2010); that is, the point at which decisions are made shaping the explanatory endeavour. In fact, the current view of the neoplastic process, not as a static circumstance but as an evolving molecular and cellular process, makes it evident that the choice of the right level of analysis is not self-evident. This focus clarifies some epistemological reasons for the divergence between reductionist and organicist accounts and seems to suggest that the basis for distinctions among causal relationships that scientists sometimes make can be found in the hierarchical character of complex biological systems. I will argue that these different causal relationships reflect different levels of epistemic concern.

  12. Phytic acid (IP6), novel broad spectrum anti-neoplastic agent: a systematic review.

    Science.gov (United States)

    Fox, C H; Eberl, M

    2002-12-01

    Phytic acid or IP6 has been extensively studied in animals and is being promoted as an anti-cancer agent in health food stores. It is naturally found in legumes, wheat bran, and soy foods. It is believed to be the active ingredient that gives these substances their cancer fighting abilities. Proposed mechanisms of action include gene alteration, enhanced immunity, and anti-oxidant properties. A Medline search from 1966 to May 2002 using the keywords phytic acid and cancer, and limiting the search to the subheadings of therapeutic uses, prevention, and adverse effects revealed 28 studies. These studies were included in the review. A great majority of the studies were done in animals and showed that phytic acid had anti-neoplastic properties in breast, colon, liver, leukemia, prostate, sarcomas, and skin cancer. There were no human studies. Side effects included chelation of multivalent cations, and an increase in bladder and renal papillomas. This increase in papilloma formation only occurred with the sodium salt of phytic acid. It did not occur with either the potassium or magnesium salts. There is a large body of animal evidence to show that phytic acid may have a role in both the prevention and treatment of many forms of cancer. There is clearly enough evidence to justify the initiation of Phase I and Phase II clinical trials in humans.

  13. Radiographer involvement with stent insertion to palliate symptomatic dysphagia resulting from neoplastic obstruction

    Energy Technology Data Exchange (ETDEWEB)

    Law, R.L. [Department of Radiology, Frenchay Hospital, Bristol, BS16 1LE (United Kingdom)], E-mail: robert.law@nbt.nhs.uk

    2008-02-15

    Self-expanding metal stent (SEMS) insertion is recognized as an effective palliative treatment for patients with symptomatic dysphagia resulting from inoperable neoplastic occlusion. This paper reviews radiographer involvement in the fluoroscopic deployment of SEMS. One hundred and fifty-eight SEMS were passed in 136 consecutive patients. Radiographers were responsible for the barium swallow and subsequent passage of an oro-gastric wire across the strictured lumen. One hundred and twenty-seven guide wire insertions under fluoroscopic control transgressed the tumour lumen at first attempt. Nine (6.6%) guide wire insertions were unsuccessful at first attempt however two patients (2.7%) had successful second attempts at fluoroscopically guided wire insertion. Five patients went on to have a joint endoscopic/fluoroscopic SEMS procedure, three were successful, two failed. Due to poor health it was decided not to proceed with further intervention with two other patients. With an overall success rate of 96%, a joint radiographer/clinician approach to guide wire insertion and subsequent SEMS deployment using fluoroscopy alone is a safe, time- and cost-effective procedure.

  14. Ultrasonographic Differentiation Between Nodular Hyperplasia and Neoplastic Follicular-Patterned Lesions of the Thyroid Gland.

    Science.gov (United States)

    Song, Yong Sub; Kim, Ji-Hoon; Na, Dong Gyu; Min, Hye Sook; Won, Jae-Kyung; Yun, Tae Jin; Choi, Seung Hong; Sohn, Chul-Ho

    2016-08-01

    We evaluate the gray-scale ultrasonographic characteristics that differentiate between nodular hyperplasia (NH) and neoplastic follicular-patterned lesions (NFPLs) of the thyroid gland. Ultrasonographic features of 750 patients with 832 thyroid nodules (NH, n = 361; or NFPLs, follicular adenoma, n = 123; follicular carcinoma, n = 159; and follicular variant papillary carcinoma, n = 189) were analyzed. Except for echogenicity, over two-thirds of the cases of NH and NFPLs share the ultrasonographic characteristics of solid internal content, a well-defined smooth margin and round-to-ovoid shape. Independent predictors for NH were non-solid internal content (sensitivity 27.1%, specificity 90.2%), isoechogenicity (sensitivity 69.5%, specificity 63.5%) and an ill-defined margin (sensitivity 18.8%, specificity 94.5%). Independent predictors for NFPLs were hypoechogenicity (sensitivity 60.5%, specificity 70.4%), marked hypoechogenicity (sensitivity 2.8%, specificity 99.4%) and taller-than-wide shape (sensitivity 6.6%, specificity 98.1%). Although NH and NFPLs commonly share ultrasonographic characteristics, non-solid internal content and ill-defined margin are specific to NH and marked hypoechogenicity and taller-than-wide shape are specific to NFPLs.

  15. Automatic segmentation of histological structures in normal and neoplastic mammary gland tissue sections

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez-Gonzalez, Rodrigo; Deschamps, Thomas; Idica, Adam K.; Malladi, Ravi; Ortiz de Solorzano, Carlos

    2003-01-18

    In this paper we present a scheme for real time segmentation of histological structures in microscopic images of normal and neoplastic mammary gland sections. Paraffin embedded or frozen tissue blocks are sliced, and sections are stained with hematoxylin and eosin (H&E). The sections are then imaged using conventional bright field microscopy. The background of the images is corrected by arithmetic manipulation using a ''phantom.'' Then we use the fast marching method with a speed function that depends on the brightness gradient of the image to obtain a preliminary approximation to the boundaries of the structures of interest within a region of interest (ROI) of the entire section manually selected by the user. We use the result of the fast marching method as the initial condition for the level set motion equation. We run this last method for a few steps and obtain the final result of the segmentation. These results can be connected from section to section to build a three-dimensional reconstruction of the entire tissue block that we are studying.

  16. Dose protraction studies with low- and high-LET radiations on neoplastic cell transformation in vitro

    Science.gov (United States)

    Yang, Tracy Chui-Hsu; Craise, Laurie M.; Tobias, Cornelius A.; Mei, Man-Tong

    1986-01-01

    The effects of the low- and high-LET radiation (by X-rays, Co-60, and heavy ions) on the transformation of neoplastic cells were studied using cultured C3H10T1/2 mouse embryo cells. The transformed colonies in the confluent cell monolayers were recognized as focuses composed of highly polar fibroblastic multilayered criss-cross arrays of densely stained cells. For the low-LET radiation, there was a decrease in cell killing and cell transformation frequency when cells were irradiated with fractionated doses and at a low dose rate, indicating that cultured mammalian cells can repair both subtransformation and potential transformation lesions. No sparing effect, however, was found for the high-LET radiation. An enhancement of cell transformation was observed for low-dose/rate argon (400 MeV/u; 120 keV/micron) and iron particles (600 MeV/u; 200 keV/micron). The molecular mechanism for this enhancement effect is not known.

  17. Inferring compositional style in the neo-plastic paintings of Piet Mondrian by machine learning

    Science.gov (United States)

    Andrzejewski, David; Stork, David G.; Zhu, Xiaojin; Spronk, Ron

    2010-02-01

    We trained generative models and decision tree classifiers with positive and negative examples of the neo-plastic works of Piet Mondrian to infer his compositional principles, to generate "faux" works, and to explore the possibility of computer-based aids in authentication and attribution studies. Unlike previous computer work on this and other artists, we used "earlier state" works-intermediate versions of works created by Mondrian revealed through x-radiography and infra-red reflectography-when training our classifiers. Such intermediate state works provide a great deal of information to a classifier as they differ only slightly from the final works. We used methods from machine learning such as leave-one-out cross validation. Our decision tree classifier had accuracy of roughly 70% in recognizing the genuine works of Mondrian versus computer-generated replicas with similar statistical properties. Our trained classifier reveals implicit compositional principles underlying Mondrian's works, for instance the relative visual "weights" of the four colors (red, yellow, blue and black) he used in his rectangles. We used our trained generative model to generate "faux" Mondrians, which informally possess some of the compositional attributes of genuine works by this artist.

  18. Osteogenic tumour in Australopithecus sediba: Earliest hominin evidence for neoplastic disease

    Directory of Open Access Journals (Sweden)

    Patrick S. Randolph-Quinney

    2016-07-01

    Full Text Available We describe the earliest evidence for neoplastic disease in the hominin lineage. This is reported from the type specimen of the extinct hominin Australopithecus sediba from Malapa, South Africa, dated to 1.98 million years ago. The affected individual was male and developmentally equivalent to a human child of 12 to 13 years of age. A penetrating lytic lesion affected the sixth thoracic vertebra. The lesion was macroscopically evaluated and internally imaged through phase-contrast X-ray synchrotron microtomography. A comprehensive differential diagnosis was undertaken based on gross- and micro-morphology of the lesion, leading to a probable diagnosis of osteoid osteoma. These neoplasms are solitary, benign, osteoid and bone-forming tumours, formed from well-vascularised connective tissue within which there is active production of osteoid and woven bone. Tumours of any kind are rare in archaeological populations, and are all but unknown in the hominin record, highlighting the importance of this discovery. The presence of this disease at Malapa predates the earliest evidence of malignant neoplasia in the hominin fossil record by perhaps 200 000 years.

  19. Detection of HPV-induced cervical (pre) neoplastic lesions: a tissue microarray (TMA) study.

    Science.gov (United States)

    Arafa, Mohammad; Boniver, Jacques; Delvenne, Philippe

    2008-10-01

    The aim of this study was to evaluate the usefulness of a panel of biomarkers in the characterization of human papillomavirus (HPV)-induced cervical lesions. Management of these lesions depends on their histologic confirmation. Misinterpretation especially for benign mimics results in a significant diagnostic disagreement. For these reasons, a continuous effort is still needed to discover surrogate markers, which could support the final diagnosis. Archival biopsies of normal ectocervical and endocervical tissues, squamous metaplasia, cervical intraepithelial neoplasia (CIN), squamous cell carcinoma, adenocarcinoma in situ, and adenocarcinoma were retrieved to perform a tissue microarray (TMA). A panel of markers was tested on the TMA obtained slides by in situ hybridization (HPV DNA) and immunohistochemistry (p16, involucrin, Ki-67, and HPV L1 proteins). The sensitivity to detect high-risk HPV DNA increased with lesion's severity. In situ hybridization signals suggesting integrated viral physical status predominated in CIN II/III, squamous cell carcinoma, and glandular (pre) neoplastic lesions. The p16 and Ki-67 protein expression increased from CIN I to CIN III and to infiltrative lesions. Involucrin positivity was better appreciated in well-differentiated diagnostic entities (ectocervix, mature metaplasia, and CIN I). HPV L1 antibody detected the viral capsid protein in a low proportion of CIN I and II. In conclusion, using a panel of cervical biomarkers improves the final reporting of various HPV-induced epithelial lesions. Carefully constructed TMA with single spots of 1-mm diameter are powerful tools, which have a high reliability in representing full tissue sections.

  20. Imaging the cranial nerves: part II: primary and secondary neoplastic conditions and neurovascular conflicts

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Alexandra [Instituto Portugues de Oncologia Francisco Gentil- Centro de Lisboa, Radiology Department, Lisboa Codex (Portugal); Casselman, Jan [A. Z. St Jan Brugge and A. Z. St Augustinus Antwerpen Hospitals, Department of Radiology, Antwerp (Belgium)

    2007-09-15

    There have been unprecedented improvements in cross-sectional imaging in the last decades. The emergence of volumetric CT, higher field MR scanners and higher resolution MR sequences is largely responsible for the increasing diagnostic yield of imaging in patients presenting with cranial nerve deficits. The introduction of parallel MR imaging in combination with small surface coils allows the depiction of submillimetric nerves and nerve branches, and volumetric CT and MR imaging is able to provide high quality multiplanar and curved reconstructions that can follow the often complex course of cranial nerves. Seeking the cause of a cranial nerve deficit is a common indication for imaging, and it is not uncommon that radiologists are the first specialists to see a patient with a cranial neuropathy. To increase the diagnostic yield of imaging, high-resolution studies with smaller fields of view are required. To keep imaging studies within a reasonable time frame, it is mandatory to tailor the study according to neuro-topographic testing. This review article focuses on the contribution of current imaging techniques in the depiction of primary and secondary neoplastic conditions affecting the cranial nerves as well as on neurovascular conflicts, an increasingly recognized cause of cranial neuralgias. (orig.)

  1. Dose protraction studies with low- and high-LET radiations on neoplastic cell transformation in vitro

    Science.gov (United States)

    Yang, Tracy Chui-Hsu; Craise, Laurie M.; Tobias, Cornelius A.; Mei, Man-Tong

    1986-01-01

    The effects of the low- and high-LET radiation (by X-rays, Co-60, and heavy ions) on the transformation of neoplastic cells were studied using cultured C3H10T1/2 mouse embryo cells. The transformed colonies in the confluent cell monolayers were recognized as focuses composed of highly polar fibroblastic multilayered criss-cross arrays of densely stained cells. For the low-LET radiation, there was a decrease in cell killing and cell transformation frequency when cells were irradiated with fractionated doses and at a low dose rate, indicating that cultured mammalian cells can repair both subtransformation and potential transformation lesions. No sparing effect, however, was found for the high-LET radiation. An enhancement of cell transformation was observed for low-dose/rate argon (400 MeV/u; 120 keV/micron) and iron particles (600 MeV/u; 200 keV/micron). The molecular mechanism for this enhancement effect is not known.

  2. Micro-Raman spectroscopy Detects Individual Neoplastic and Normal Hematopoietic Cells

    Energy Technology Data Exchange (ETDEWEB)

    Chan, J W; Taylor, D; Zwerdling, T; Lane, S M; Ihara, K; Huser, T

    2005-01-18

    Current methods for identifying neoplastic cells and discerning them from their normal counterparts are often non-specific, slow, biologically perturbing, or a combination, thereof. Here, we show that single-cell micro-Raman spectroscopy averts these shortcomings and can be used to discriminate between unfixed normal human lymphocytes and transformed Jurkat and Raji lymphocyte cell lines based on their biomolecular Raman signatures. We demonstrate that single-cell Raman spectra provide a highly reproducible biomolecular fingerprint of each cell type. Characteristic peaks, mostly due to different DNA and protein concentrations, allow for discerning normal lymphocytes from transformed lymphocytes with high confidence (p << 0.05). Spectra are also compared and analyzed by principal component analysis (PCA) to demonstrate that normal and transformed cells form distinct clusters that can be defined using just two principal components. The method is shown to have a sensitivity of 98.3% for cancer detection, with 97.2% of the cells being correctly classified as belonging to the normal or transformed type. These results demonstrate the potential application of confocal micro-Raman spectroscopy as a clinical tool for single cell cancer detection based on intrinsic biomolecular signatures, therefore eliminating the need for exogenous fluorescent labeling.

  3. Drug/Nutrients Interaction in Neoplastic Patients Requiring Nutritional Support. Practical Advice with Special Focusing on Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Ilaria Uomo

    2008-07-01

    Full Text Available Malnutrition and cachexia are frequent complaints in neoplastic disease [1, 2]. Nutritional support and pain treatment still remain the main treatment option for the majority of patients with cancer, particularly for those affected by pancreatic cancer who very often present an advanced stage of the disease at moment of first diagnosis [3, 4, 5]. Therefore, in their clinical practice, physicians are faced with the need for parenteral or enteral nutrition and with the contemporary requirement of several drugs capable of interfering with the components of the nutritional admixture. Different drawbacks may arise from these drug/nutrient interactions, nullifying the pharmacological effect and/or the nutritional value [6]. The aim of this review is to summarize possible drug/nutrient interaction in neoplastic patients, particularly in those with pancreatic cancer, during external food supplementation.

  4. The pilot study assessing efficacy and versatility of novel therapy for neoplastic ulceration: clinical and microbiological aspects.

    Science.gov (United States)

    Sopata, Maciej; Tomaszewska, Elżbieta; Muszyński, Zygmunt; Ciupińska, Maria; Kotlińska-Lemieszek, Aleksandra

    2013-08-01

    Neoplastic ulcers are chronic and, most often, irreversible lesions caused by proliferation of tumor cells infiltrating and damaging skin tissues. The treatment of neoplastic ulcers is a very difficult and time-consuming process. So, is very important to find methods of controlling this type of chronic wounds. To evaluate the efficiency of monitored treatment of neoplastic ulcers by means of providing moist wound environment dressings and antiseptic to the group of patients with an advanced stage of tumor, with particular focus on the impact of the treatment applied on the clinical condition of the ulcers; to evaluate the impact of the treatment applied on the dynamics of bacterial flora in neoplastic ulcers, with particular focus on the presence of alarm pathogens; to conduct a risk analysis of the occurrence of local and systemic complications during treatment. This was a prospective pilot clinical study of 30 patients with malignant ulcers, 13 male and 17 female aged from 24 to 92 years treated with octenidine antiseptic and dressing set for 3 weeks. The wounds were clinically assessed for the changes of amount of necrotic tissue, exudate level and type, malodour and pain level during treatment. At the baseline and after 3 weeks of treatment, the wounds were swabbed for microbiological assessment. The used scheme of treatment is efficient and brings clinical improvement in all treated ulcers. During the 3-week treatment, reduction of necrotic tissue, decrease in the level of exudate, pain and malodour was observed in all patients (p octenidine against Gram(-) and Gram(+) bacteria was observed. The use of octenidine dihydrochloride correlated with a progressing eradication of multiresistant strains and alarm pathogens (p < 0.001). No serious adverse effects or significant symptoms of intolerance of the applied treatment were observed.

  5. Drug/Nutrients Interaction in Neoplastic Patients Requiring Nutritional Support. Practical Advice with Special Focusing on Pancreatic Cancer

    OpenAIRE

    Ilaria Uomo; Adele Savoia

    2008-01-01

    Malnutrition and cachexia are frequent complaints in neoplastic disease [1, 2]. Nutritional support and pain treatment still remain the main treatment option for the majority of patients with cancer, particularly for those affected by pancreatic cancer who very often present an advanced stage of the disease at moment of first diagnosis [3, 4, 5]. Therefore, in their clinical practice, physicians are faced with the need for parenteral or enteral nutrition and with the contemporary requirement ...

  6. Althaea rosea Cavanil and Plantago major L. suppress neoplastic cell transformation through the inhibition of epidermal growth factor receptor kinase.

    Science.gov (United States)

    Choi, Eun-Sun; Cho, Sung-Dae; Shin, Ji-Ae; Kwon, Ki Han; Cho, Nam-Pyo; Shim, Jung-Hyun

    2012-10-01

    For thousands of years in Asia, Althaea rosea Cavanil (ARC) and Plantago major L. (PML) have been used as powerful non-toxic therapeutic agents that inhibit inflammation. However, the anticancer mechanisms and molecular targets of ARC and PML are poorly understood, particularly in epidermal growth factor (EGF)-induced neoplastic cell transformation. The aim of this study was to evaluate the chemopreventive effects and mechanisms of the methanol extracts from ARC (MARC) and PML (MPML) in EGF-induced neoplastic cell transformation of JB6 P+ mouse epidermal cells using an MTS assay, anchorage-independent cell transformation assay and western blotting. Our results showed that MARC and MPML significantly suppressed neoplastic cell transformation by inhibiting the kinase activity of the EGF receptor (EGFR). The activation of EGFR by EGF was suppressed by MARC and MPML treatment in EGFR(+/+) cells, but not in EGFR(-/-) cells. In addition, MARC and MPML inhibited EGF-induced cell proliferation in EGFR-expressing murine embryonic fibroblasts (EGFR(+/+)). These results strongly indicate that EGFR targeting by MARC and MPML may be a good strategy for chemopreventive or chemotherapeutic applications.

  7. Neoplastic Meningitis from Solid Tumors: A Prospective Clinical Study in Lombardia and a Literature Review on Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    A. Silvani

    2013-01-01

    Full Text Available Neoplastic dissemination to the leptomeninges is an increasingly common occurrence in patients with both haematological and solid tumors arising outside the central nervous system. Both refinement of diagnostic techniques (Magnetic resonance imaging and increased survival in patients treated with targeted therapies for systemic tumors account for this increased frequency. Cerebrospinal fluid cytological analysis and MRI confirm clinical diagnosis based on multifocal central nervous system signs/symptoms in a patient with known malignancy. Overall survival in patients with leptomeningeal neoplastic dissemination from solid tumors is short, rarely exceeding 3-4 months. However, selected patients may benefit from aggressive therapies, Apart from symptomatic treatment, intrathecal chemotherapy is used, with both free (methotrexate, Thiotepa, AraC and liposomal antitumor agents (liposomal AraC. Palliative radiotherapy is indicated only in cases of symptomatic bulky disease, surgery is limited to positioning of Ommaya recervoirs or C5F shunting. We report clinical data on a cohort of 26 prospectively followed patients with neoplastic leptomeningitis followed in Lombardia, Italy, in 2011. Prognostic factors and pattern of care are reported.

  8. Microvesicles as a potential biomarker of neoplastic diseases and their role in development and progression of neoplasm.

    Science.gov (United States)

    Kajdos, Magdalena; Janas, Łukasz; Kolasa-Zwierzchowska, Dorota; Wilczyński, Jacek R; Stetkiewicz, Tomasz

    2015-12-01

    Neoplastic diseases together with cardiovascular diseases are the most frequent causes of death in the Polish population. Cancers of reproductive organs with breast cancer are responsible for the highest morbidity and mortality in women suffering from neoplasm diseases. Asymptomatic dynamics of the development of a neoplasm and no deviations from the normal level of laboratory results contribute to the fact that malignant diseases are diagnosed too late. The aim of modern medicine is to diagnose cancer at the earliest stage, however, there is no sufficiently sensitive and specific biomarker which can be used for diagnostic, prognostic and therapeutic purposes. Cellular interactions play the main role in the development, angiogenesis and invasiveness of a tumor. Recent research suggests the possibility of microvesicles (MVs) involvement in communication between cells. The MVs ability to fuse with various cells is used in cell-to-cell contact. Microvesicles cargo may include growth factors, their receptors, protease, adhesion molecules, signaling molecules and the sequence of DNA, mRNA, and micro-RNA. Larger quantities of MVs released from neoplastic cells affect both the local environment and systematic range causing metastases and progression. The research on molecular mechanisms of MVs' release and the presence of characteristic oncogenes in blood of patients with neoplasms is being carried out. Confirmation of MVs presence in patients' serum can potentially serve as useful information for therapeutic purposes and as the biomarker of a neoplastic disease.

  9. Neoplastic lesions of the temporomandibular joint (TMJ): diagnosis, differential diagnosis and intervention; Neoplasien des Temporomandibulargelenks (TMG). Diagnostik, Differenzialdiagnostik und Intervention

    Energy Technology Data Exchange (ETDEWEB)

    Vogl, T.J.; Abolmaali, N.; Schedel, H.; Bergh, B. [Frankfurt Univ. (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie; Maeurer, J. [Radiologische Praxis am Prinzregentenplatz, Muenchen (Germany)

    2001-09-01

    Purpose. To evaluate the effectiveness of diagnostic and interventional radiological techniques for neoplastic lesions of the temporomandibular joint (TMJ). Material and methods. Modern diagnosis of the TMJ is based on the clinical use of conventional X-ray techniques, computed tomography (CT), magnetic resonance imaging (MRI) and interventional techniques like biopsies, vascular occlusion and ablation. Results. Conventional X-ray still forms the basic diagnostic procedure applied in open and closed mouth position. CT improves the diagnostic information and serves as the standard diagnostical instrument for cartaliganeous or osseous neoplastic lesions. MRI evaluates soft tissue infiltration in multiplanar techniques and high spatial resolution. Interventional vascular and ablative techniques improve the treatment of neoplastic disorders. (orig.) [German] Zielsetzung. Vorstellung der Wertigkeit bildgebender Verfahren fuer die diagnostische und interventionelle Radiologie des Temporomandibulargelenks (TMG). Material und Methodik. Die moderne Radiologie des TMG basiert auf dem Einsatz der konventionellen Roentgendiagnostik, der Computertomographie (CT) und der Magnetresonanztomographie (MRT), sowie interventioneller Verfahren wie der Biopsie, vaskulaerer Embolisationsverfahren und tumorablativer Verfahren. Ergebnisse. Als Basisdiagnostik dient die konventionelle Diagnostik in offener und geschlossener Mundposition der Erfassung von Funktionsstoerungen sowie ossaerer Destruktionen. Die CT erweitert das diagnostische Spektrum und verbessert die Differenzialdiagnostik fuer ossifizierende Prozesse. Der Einsatz der MRT erlaubt die Erfassung der Weichteilinfiltration sowie der Gelenkstrukturen. Vaskulaere interventionelle Verfahren dienen der praetherapeutischen Okklusion bzw. der palliativen Tumortherapie in Form der okklusiven Embolisation, der Chemoembolisation, oder auch der Tumorablation. (orig.)

  10. Biological Characteristics of Caspase-14 and Its Expression in Neoplastic Diseases in the View of Translational Medicine

    Institute of Scientific and Technical Information of China (English)

    LIU Kang-sheng; LYU Juan; LI Ping; ZHONG Tian-ying

    2016-01-01

    Caspase-14, a member of caspase family, only exists in mammals. As the most divergent member in the family of mammalian caspases, caspase-14 displays a variety of unique characteristics. It is expressed in a limited number of tissues and has the shortest amino acid sequence within the caspase protein family. At present, it has been found that caspase-14 is functionally different from the inlfammatory reaction group of typical caspase family members. It exerts a certain effect in the promotion of ifnal differentiation of epidermal cells and hydration of stratum corneum so as to maintain the steady state of skin barrier. In recent years, caspase-14 expression has been discovered in neoplastic diseases. Translational medicine integrates experimental research results and clinical guidance into the optimal implementation criteria for promoting the prediction, prevention and treatment of diseases. Via human genomics and molecular biology, translational medicine offers a possibility of screening molecular markers so that it can be used to diagnose the neoplastic diseases. In this article, the biological characteristics and substrates of caspase-14 as well as its expression in embryonic period and neoplastic diseases were reviewed.

  11. Compton scattering spectrum as a source of information of normal and neoplastic breast tissues' composition

    Energy Technology Data Exchange (ETDEWEB)

    Antoniassi, M.; Conceicao, A.L.C. [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, 14040-901 Sao Paulo (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.br [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, 14040-901 Sao Paulo (Brazil)

    2012-07-15

    In this work we measured X-ray scatter spectra from normal and neoplastic breast tissues using photon energy of 17.44 keV and a scattering angle of 90 Degree-Sign , in order to study the shape (FWHM) of the Compton peaks. The obtained results for FWHM were discussed in terms of composition and histological characteristics of each tissue type. The statistical analysis shows that the distribution of FWHM of normal adipose breast tissue clearly differs from all other investigated tissues. Comparison between experimental values of FWHM and effective atomic number revealed a strong correlation between them, showing that the FWHM values can be used to provide information about elemental composition of the tissues. - Highlights: Black-Right-Pointing-Pointer X-ray scatter spectra from normal and neoplastic breast tissues were measured. Black-Right-Pointing-Pointer Shape (FWHM) of Compton peak was related with elemental composition and characteristics of each tissue type. Black-Right-Pointing-Pointer A statistical hypothesis test showed clear differences between normal and neoplastic breast tissues. Black-Right-Pointing-Pointer There is a strong correlation between experimental values of FWHM and effective atomic number. Black-Right-Pointing-Pointer Shape (FWHM) of Compton peak can be used to provide information about elemental composition of the tissues.

  12. Pre-neoplastic lesion, mucin-depleted foci, reveals de novo high-grade dysplasia in rat colon carcinogenesis.

    Science.gov (United States)

    Cui, Changxu; Takamatsu, Reika; Doguchi, Hiroshi; Matsuzaki, Akiko; Saio, Masanao; Yoshimi, Naoki

    2012-05-01

    Aberrant crypt foci (ACF) and mucin-depleted foci (MDF) have recently been recognized as pre-neoplastic lesions in the colon of carcinogen-treated rodents. In the present study, we analyzed the sequential development of ACF and MDF histopathologically in the colon of rats from 5 to 40 weeks after DMH treatment. The numbers of ACF per colon increased over time during the experiment, and were much higher than the number in tumors, while the number of MDF per colon remained unchanged from the early stage (the 5th week after carcinogen exposure), and approximate to those in tumors. The incidence of ACF, which was much higher than that of tumors, also increased gradually in a time-dependent manner. The incidence of MDF, however, was similar to that of tumors and did not change significantly during the whole experiment. No lesion as dysplasia with high-grade (DHG) or adenocarcinoma (AC) were found in any large ACF from the 5th to 40th week histopathologically, whereas all of the large MDF showed DHG or AC features. Even at 5 weeks, MDF showed features of DHG. We classified these into two forms of MDF: flat and protruded MDF. At 40 weeks, the number of flat MDF per colon decreased significantly compared with that at 20 weeks (pMDF per colon increased (pMDF lesion decreased but that of AC increased remarkably. In conclusion, MDF may develop into cancer through the so-called 'de novo cancer' pathway.

  13. Psidium guajava L. anti-neoplastic effects: induction of apoptosis and cell differentiation.

    Science.gov (United States)

    Bontempo, P; Doto, A; Miceli, M; Mita, L; Benedetti, R; Nebbioso, A; Veglione, M; Rigano, D; Cioffi, M; Sica, V; Molinari, A M; Altucci, L

    2012-02-01

    Curative properties of medicinal plants such as Psidium guajava L. (Myrtaceae) have often been indicated by epidemiological studies on populations in which these fruits are consumed daily. However, complete characterization of the active principles responsible for this ability has never been performed. Here, we have characterized P. guajava's anti-cancer potential and identified the parts of the fruit involved in its anti-neoplastic action. We studied morphology of our cells, cell cycle characteristics and apoptosis and performed immunostaining, differentiation and western blot analyses. We report that the P. guajava extract exerted anti-cancer control on both haematological and solid neoplasias. P. guajava extract's anti-tumour properties were found to be tightly bound to induction of apoptosis and differentiation. Use of ex vivo myeloid leukaemia blasts corroborated that P. guajava was able to induce cell death but did not exhibit anti-cancer effects on all malignant cells investigated, indicating selective activity against certain types of tumour. Analyses of P. guajava pulp, peel and seeds identified the pulp as being the most relevant component for causing cell cycle arrest and apoptosis, whereas peel was responsible for causing cell differentiation. P. guajava itself and its pulp-derived extract were found to induce apoptosis accompanied by caspase activation and p16, p21, Fas ligand (FASL TNF super-family, member 6), Bcl-2-associated agonist of cell death (BAD) and tumour necrosis factor receptor super-family, member 10b (DR5), overexpression. Our findings showed that P. guajava L. extract was able to exert anti-cancer activity on cultures in vitro and ex vivo, supporting the hypothesis of its anti malignant pro-apoptotic modulation. © 2011 Blackwell Publishing Ltd.

  14. DUAL ION EXPOSURE VS. SPLIT-DOSE EXPOSURES IN HUMAN CELL NEOPLASTIC TRANSFORMATION.

    Energy Technology Data Exchange (ETDEWEB)

    BENNETT, P.V.; CUTTER, N.C.; SUTHERLAND, B.M.

    2006-06-05

    Since radiation fields of space contain many-fold more protons than high atomic number, high energy (HZE) particles, cells in astronaut crews will experience on average several proton hits before an HZE hit. Thus radiation regimes of proton exposure before HZE particle exposure simulate space radiation exposure, and measurement of the frequency of neoplastic transformation of human primary cells to anchorage-independent growth simulates in initial step in cancer induction. Previously our group found that exposure to 20 cGy 1 GeV/n protons followed within about 1 hr by a HZE ion (20 cGy 1 GeV/n Fe or Ti ions) hit gave about a 3-fold increase in transformation frequency ([1]). To provide insight into the H-HZE induced increased transformation frequencies, we asked if split doses of the same ion gave similar increased transformation frequencies. However, the data show that the split dose of 20 cGy plus 20 cGy of either H or HZE ions gave about the same effect as the 40 cGy uninterrupted dose, quite different from the effect of the mixed ion H + HZE irradiation. We also asked if lower proton doses than 20 cGy followed 15 minutes later by 20 cGy of HZE ions gave greater than additive transformation frequencies. Substantial increases in transformation levels were observed for all proton doses tested, including 1 cGy. These results point to the signal importance of protons in affecting the effect of space radiation on human cells.

  15. Androgen receptor expression in normal, hyperplastic and neoplastic hepatoid glands in the dog.

    Science.gov (United States)

    Pisani, G; Millanta, F; Lorenzi, D; Vannozzi, I; Poli, A

    2006-10-01

    Neoplasms of the perianal glands are common in the dog, particularly in the male. The occurrence of these tumours appears to be hormone related and castration, without excision of the tumour, has sometimes resulted in regression of the tumour. The aim of this study was to investigate the expression of androgen receptors (AR) in normal, hyperplastic and neoplastic hepatoid glands in the dog. Thirty-one samples of canine hepatoid gland tissues were investigated. The lesions, classified according to WHO criteria, were comprised of 19 hyperplastic tissues, 10 benign lesions (2 hepatoid gland epithelioma and 8 hepatoid adenomas), and 19 carcinomas. Five samples from normal hepatoid glands were also investigated. The AR expression was evaluated by immunohistochemistry using a streptavidin-biotin peroxidase method. The immunoexpression was scored by two pathologists as the percentage of positive nuclei. The intensity of staining was also considered. AR expression was detected in all normal and abnormal glands. However, in hyperplastic tissues the percentage of positive nuclei was significantly higher than in normal tissue and especially in reserve basaloid cells. A similar increase in the percent of positive nuclei was also observed in hepatoid epitheliomas, while in hepatoid adenoma the percent of AR-immunolabelling was only slightly increased compared to normal tissue. In hepatoid carcinomas the percent of AR-positive cells was similar to that observed in benign tumours. The grade of differentiation of hepatoid carcinomas did not affect AR expression. These results demonstrate that increased AR expression is maintained throughout perianal gland cancer progression and that hepatoid gland carcinomas still express AR. Although further studies may be required to evaluate the hormonal background of these diseases, dogs bearing those carcinomas might benefit from castration or anti hormonal therapy.

  16. Estrogens and Insulin-Like Growth Factor 1 Modulate Neoplastic Cell Growth in Human Cholangiocarcinoma

    Science.gov (United States)

    Alvaro, Domenico; Barbaro, Barbara; Franchitto, Antonio; Onori, Paolo; Glaser, Shannon S.; Alpini, Gianfranco; Francis, Heather; Marucci, Luca; Sterpetti, Paola; Ginanni-Corradini, Stefano; Onetti Muda, Andrea; Dostal, David E.; De Santis, Adriano; Attili, Adolfo F.; Benedetti, Antonio; Gaudio, Eugenio

    2006-01-01

    We investigated the expression of estrogen receptors (ERs), insulin-like growth factor 1 (IGF-1), and IGF-1R (receptor) in human cholangiocarcinoma and cholangiocarcinoma cell lines (HuH-28, TFK-1, Mz-ChA-1), evaluating the role of estrogens and IGF-1 in the modulation of neoplastic cell growth. ER-α, ER-β, IGF-1, and IGF-1R were expressed (immunohistochemistry) in all biopsies (18 of 18) of intrahepatic cholangiocarcinoma. ER-α was expressed (Western blot) only by the HuH-28 cell line (intrahepatic cholangiocarcinoma), whereas ER-β, IGF-1, and IGF-1R were expressed in the three cell lines examined. In serum-deprived HuH-28 cells, serum readmission induced stimulation of cell proliferation that was inhibited by ER and IGF-1R antagonists. 17β-Estradiol and IGF-1 stimulated proliferation of HuH-28 cells to a similar extent to that of MCF7 (breast cancer) but greater than that of TFK-1 and Mz-ChA-1, inhibiting apoptosis and exerting additive effects. These effects of 17β-estradiol and IGF-1 were associated with enhanced protein expression of ER-α, phosphorylated (p)-ERK1/2 and pAKT but with decreased expression of ER-β. Finally, transfection of IGF-1R anti-sense oligonucleotides in HuH-28 cells markedly decreased cell proliferation. In conclusion, human intrahepatic cholangiocarcinomas express receptors for estrogens and IGF-1, which cooperate in the modulation of cell growth and apoptosis. Modulation of ER and IGF-1R could represent a strategy for the management of cholangiocarcinoma. PMID:16936263

  17. Health status in older hospitalized patients with cancer or non-neoplastic chronic diseases

    Directory of Open Access Journals (Sweden)

    Corica Francesco

    2005-08-01

    Full Text Available Abstract Background Whether cancer is more disabling than other highly prevalent chronic diseases in the elderly is not well understood, and represents the objective of the present study. Methods We used data from the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA study, a large collaborative observational study based in community and university hospitals located throughout Italy. Our series consisted of three groups of patients with non-neoplastic chronic disease (congestive heart failure, CHF, N = 832; diabetes mellitus, N = 939; chronic obstructive pulmonary disease, COPD, N = 399, and three groups of patients with cancer (solid tumors without metastasis, N = 813; solid tumors with metastasis, N = 259; leukemia/lymphoma, N = 326. Functional capabilities were ascertained using the activities of daily living (ADL scale, and categorical variables for dependency in at least 1 ADL or dependency in 3 or more ADLs were considered in the analysis. Cognitive status was evaluated by the 10-items Hodgkinson Abbreviated Mental Test (AMT. Results Cognitive impairment was more prevalent in patients with CHF (28.0% or COPD (25.8% than in those with cancer (solid tumors = 22.9%; leukemia/lymphoma = 19.6%; metastatic cancer = 22.8%. Dependency in at least 1 ADL was highly prevalent in patients with metastatic cancer (31.3% vs. 24% for patients with CHF and 22.4% for those with non-metastatic solid tumors, p Conclusion Cancer should not be considered as an ineluctable cause of severe cognitive and physical impairment, at least not more than other chronic conditions highly prevalent in older people, such as CHF and diabetes mellitus.

  18. Neoplastic human embryonic stem cells as a model of radiation resistance of human cancer stem cells.

    Science.gov (United States)

    Dingwall, Steve; Lee, Jung Bok; Guezguez, Borhane; Fiebig, Aline; McNicol, Jamie; Boreham, Douglas; Collins, Tony J; Bhatia, Mick

    2015-09-08

    Studies have implicated that a small sub-population of cells within a tumour, termed cancer stem cells (CSCs), have an enhanced capacity for tumour formation in multiple cancers and may be responsible for recurrence of the disease after treatment, including radiation. Although comparisons have been made between CSCs and bulk-tumour, the more important comparison with respect to therapy is between tumour-sustaining CSC versus normal stem cells that maintain the healthy tissue. However, the absence of normal known counterparts for many CSCs has made it difficult to compare the radiation responses of CSCs with the normal stem cells required for post-radiotherapy tissue regeneration and the maintenance of tissue homeostasis. Here we demonstrate that transformed human embryonic stem cells (t-hESCs), showing features of neoplastic progression produce tumours resistant to radiation relative to their normal counterpart upon injection into immune compromised mice. We reveal that t-hESCs have a reduced capacity for radiation induced cell death via apoptosis and exhibit altered cell cycle arrest relative to hESCs in vitro. t-hESCs have an increased expression of BclXL in comparison to their normal counterparts and re-sensitization of t-hESCs to radiation upon addition of BH3-only mimetic ABT737, suggesting that overexpression of BclXL underpins t-hESC radiation insensitivity. Using this novel discovery platform to investigate radiation resistance in human CSCs, our study indicates that chemotherapy targeting Bcl2-family members may prove to be an adjuvant to radiotherapy capable of targeting CSCs.

  19. Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study.

    Science.gov (United States)

    Haycock, Philip C; Burgess, Stephen; Nounu, Aayah; Zheng, Jie; Okoli, George N; Bowden, Jack; Wade, Kaitlin Hazel; Timpson, Nicholas J; Evans, David M; Willeit, Peter; Aviv, Abraham; Gaunt, Tom R; Hemani, Gibran; Mangino, Massimo; Ellis, Hayley Patricia; Kurian, Kathreena M; Pooley, Karen A; Eeles, Rosalind A; Lee, Jeffrey E; Fang, Shenying; Chen, Wei V; Law, Matthew H; Bowdler, Lisa M; Iles, Mark M; Yang, Qiong; Worrall, Bradford B; Markus, Hugh Stephen; Hung, Rayjean J; Amos, Chris I; Spurdle, Amanda B; Thompson, Deborah J; O'Mara, Tracy A; Wolpin, Brian; Amundadottir, Laufey; Stolzenberg-Solomon, Rachael; Trichopoulou, Antonia; Onland-Moret, N Charlotte; Lund, Eiliv; Duell, Eric J; Canzian, Federico; Severi, Gianluca; Overvad, Kim; Gunter, Marc J; Tumino, Rosario; Svenson, Ulrika; van Rij, Andre; Baas, Annette F; Bown, Matthew J; Samani, Nilesh J; van t'Hof, Femke N G; Tromp, Gerard; Jones, Gregory T; Kuivaniemi, Helena; Elmore, James R; Johansson, Mattias; Mckay, James; Scelo, Ghislaine; Carreras-Torres, Robert; Gaborieau, Valerie; Brennan, Paul; Bracci, Paige M; Neale, Rachel E; Olson, Sara H; Gallinger, Steven; Li, Donghui; Petersen, Gloria M; Risch, Harvey A; Klein, Alison P; Han, Jiali; Abnet, Christian C; Freedman, Neal D; Taylor, Philip R; Maris, John M; Aben, Katja K; Kiemeney, Lambertus A; Vermeulen, Sita H; Wiencke, John K; Walsh, Kyle M; Wrensch, Margaret; Rice, Terri; Turnbull, Clare; Litchfield, Kevin; Paternoster, Lavinia; Standl, Marie; Abecasis, Gonçalo R; SanGiovanni, John Paul; Li, Yong; Mijatovic, Vladan; Sapkota, Yadav; Low, Siew-Kee; Zondervan, Krina T; Montgomery, Grant W; Nyholt, Dale R; van Heel, David A; Hunt, Karen; Arking, Dan E; Ashar, Foram N; Sotoodehnia, Nona; Woo, Daniel; Rosand, Jonathan; Comeau, Mary E; Brown, W Mark; Silverman, Edwin K; Hokanson, John E; Cho, Michael H; Hui, Jennie; Ferreira, Manuel A; Thompson, Philip J; Morrison, Alanna C; Felix, Janine F; Smith, Nicholas L; Christiano, Angela M; Petukhova, Lynn; Betz, Regina C; Fan, Xing; Zhang, Xuejun; Zhu, Caihong; Langefeld, Carl D; Thompson, Susan D; Wang, Feijie; Lin, Xu; Schwartz, David A; Fingerlin, Tasha; Rotter, Jerome I; Cotch, Mary Frances; Jensen, Richard A; Munz, Matthias; Dommisch, Henrik; Schaefer, Arne S; Han, Fang; Ollila, Hanna M; Hillary, Ryan P; Albagha, Omar; Ralston, Stuart H; Zeng, Chenjie; Zheng, Wei; Shu, Xiao-Ou; Reis, Andre; Uebe, Steffen; Hüffmeier, Ulrike; Kawamura, Yoshiya; Otowa, Takeshi; Sasaki, Tsukasa; Hibberd, Martin Lloyd; Davila, Sonia; Xie, Gang; Siminovitch, Katherine; Bei, Jin-Xin; Zeng, Yi-Xin; Försti, Asta; Chen, Bowang; Landi, Stefano; Franke, Andre; Fischer, Annegret; Ellinghaus, David; Flores, Carlos; Noth, Imre; Ma, Shwu-Fan; Foo, Jia Nee; Liu, Jianjun; Kim, Jong-Won; Cox, David G; Delattre, Olivier; Mirabeau, Olivier; Skibola, Christine F; Tang, Clara S; Garcia-Barcelo, Merce; Chang, Kai-Ping; Su, Wen-Hui; Chang, Yu-Sun; Martin, Nicholas G; Gordon, Scott; Wade, Tracey D; Lee, Chaeyoung; Kubo, Michiaki; Cha, Pei-Chieng; Nakamura, Yusuke; Levy, Daniel; Kimura, Masayuki; Hwang, Shih-Jen; Hunt, Steven; Spector, Tim; Soranzo, Nicole; Manichaikul, Ani W; Barr, R Graham; Kahali, Bratati; Speliotes, Elizabeth; Yerges-Armstrong, Laura M; Cheng, Ching-Yu; Jonas, Jost B; Wong, Tien Yin; Fogh, Isabella; Lin, Kuang; Powell, John F; Rice, Kenneth; Relton, Caroline L; Martin, Richard M; Davey Smith, George

    2017-05-01

    The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. Genomewide association studies (GWAS) published up to January 15, 2015. GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of

  20. Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non-Neoplastic Prostate Tissue

    Science.gov (United States)

    2016-12-01

    Award Number: W81XWH-11-1-0744 TITLE: Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated...with Cancer in Non-Neoplastic Prostate Tissue PRINCIPAL INVESTIGATOR: Farhad Kosari, Ph.D. CONTRACTING ORGANIZATION: Mayo Clinic Rochester, MN...Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non- Neoplastic Prostate Tissue 5b. GRANT NUMBER 10623678 5c

  1. Difference of the Nuclear Green Light Intensity between Papillary Carcinoma Cells Showing Clear Nuclei and Non-neoplastic Follicular Epithelia in Papillary Thyroid Carcinoma

    Science.gov (United States)

    Lee, Hyekyung; Baek, Tae Hwa; Park, Meeja; Lee, Seung Yun; Son, Hyun Jin; Kang, Dong Wook; Kim, Joo Heon; Kim, Soo Young

    2016-01-01

    Background There is subjective disagreement regarding nuclear clearing in papillary thyroid carcinoma. In this study, using digital instruments, we were able to quantify many ambiguous pathologic features and use numeric data to express our findings. Methods We examined 30 papillary thyroid carcinomas. For each case, we selected representative cancer cells showing clear nuclei and surrounding non-neoplastic follicular epithelial cells and evaluated objective values of green light intensity (GLI) for quantitative analysis of nuclear clearing in papillary thyroid carcinoma. Results From 16,274 GLI values from 600 cancer cell nuclei and 13,752 GLI values from 596 non-neoplastic follicular epithelial nuclei, we found a high correlation of 94.9% between GLI and clear nuclei. GLI between the cancer group showing clear nuclei and non-neoplastic follicular epithelia was statistically significant. The overall average level of GLI in the cancer group was over two times higher than the non-neoplastic group despite a wide range of GLI. On a polygonal line graph, there was a fluctuating unique difference between both the cancer and non-neoplastic groups in each patient, which was comparable to the microscopic findings. Conclusions Nuclear GLI could be a useful factor for discriminating between carcinoma cells showing clear nuclei and non-neoplastic follicular epithelia in papillary thyroid carcinoma. PMID:27550048

  2. RET/PTC1-Driven Neoplastic Transformation and Proinvasive Phenotype of Human Thyrocytes Involve Met Induction and β-Catenin Nuclear Translocation

    Directory of Open Access Journals (Sweden)

    Giuliana Cassinelli

    2009-01-01

    Full Text Available Activation of the RET gene by chromosomal rearrangements generating RET/PTC oncogenes is a frequent, early, and causative event in papillary thyroid carcinoma (PTC. We have previously shown that, in human primary thyrocytes, RET/PTC1 induces a transcriptional program including the MET proto-oncogene. In PTCs, β-catenin is frequently mislocated to the cytoplasm nucleus. We investigated the interplay between Ret/ptc1 signaling and Met in regulating the proinvasive phenotype and β-catenin localization in cellular models of human PTC. Here, we show that Met protein is expressed and is constitutively active in human thyrocytes exogenously expressing RET/PTC1 as well as a mutant (Y451F devoid of the main Ret/ptc1 multidocking site. Both in transformed thyrocytes and in the human PTC cell line TPC-1, Ret/ptc1-Y451-dependent signaling and Met cooperated to promote a proinvasive phenotype. Accordingly, gene/functional silencing of either RET/PTC1 or MET abrogated early branching morphogenesis in TPC-1 cells. The same effect was obtained by blocking the common downstream effector Akt. Y451 of Ret/ptc1 was required to promote proliferation and nuclear translocation of β-catenin, suggesting that these oncogene-driven effects are Met-independent. Pharmacologic inhibition of Ret/ptc1 and Met tyrosine kinases by the multitarget small molecule RPI-1 blocked cell proliferation and invasive ability and dislocated β-catenin from the nucleus. Altogether, these results support that Ret/ptc1 cross talks with Met at transcriptional and signaling levels and promotes β-catenin transcriptional activity to drive thyrocyte neoplastic transformation. Such molecular network, promoting disease initiation and acquisition of a proinvasive phenotype, highlights new options to design multitarget therapeutic strategies for PTCs.

  3. Effects of p53 overexpression on neoplastic cell pro-liferation and apoptosis in thymic carcinoma

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To investigate p53 overexpression and its correlation with neoplastic cell proliferation and apoptosis in 20 thymic carcinomas. Methods: 20 surgical samples of thymic carcinoma were collected randomly during the past 15 years in the Guangzhou area. Immunohistochemical staining was performed using LSAB method with anti-p53 monoclonal antibody (DO-7) and proliferating cell nuclear antigen (clone PC 10) as primary antibodies. The p53 index was indicated by the number of p53 positive cells among 100 carcinoma cells. More than 25 percentage of p53 positive cells found in tissue sections was recognized as p53 overexpression. Carcinoma cell proliferation activity was assayed by PCNA index (PI), and apoptosis degree was evaluated by TUNEL (TdT-mediated dUTP-X nick end labeling) index (TI) using Boehringer Mannheim In Situ Death Detection Kit. Results: P53 positive cells could be found in vast majority of thymic carcinomas (19/20) and the overexpression rate reached 35% (7/20). The median PI (40%) of 7 cases with p53 overexpression was higher than that (31%) of 13 cases without p53 overexpression, but there was no statistical significance that existed between these two data (P>0.05). The median TI (0.5/HPF) of 7 p53 overexpression cases was much lower than that (4.5/HPF) of 13 non-overexpression cases, and there was a significant difference statistically (P<0.05). Conclusion: p53 expression was a frequent finding in thymic carcinoma cells, and the p53 overexpression which might represent p53 inactivation or gene mutation was often involved in thymic carcino-genesis. The median PCNA index of p53 overexpression group was higher than that of non-overexpression group though there existed no statistical difference. This indicates that the inhibiting function of p53 on cell proliferation seemed lost in p53 overexpressed thymic carcinomas. It is worthy to be specially mentioned that the inducing function of p53 on cell apoptosis was markedly lost in p53 overexpressed thymic

  4. Heterogeneous nuclear expression of the promyelocytic leukemia (PML) protein in normal and neoplastic human tissues.

    Science.gov (United States)

    Gambacorta, M.; Flenghi, L.; Fagioli, M.; Pileri, S.; Leoncini, L.; Bigerna, B.; Pacini, R.; Tanci, L. N.; Pasqualucci, L.; Ascani, S.; Mencarelli, A.; Liso, A.; Pelicci, P. G.; Falini, B.

    1996-01-01

    The RING-finger promyelocytic leukemia (PML) protein is the product of the PML gene that fuses with the retinoic acid receptor-alpha gene in the t(15; 17) translocation of acute promyelocytic leukemia. Wild-type PML localizes in the nucleus with a typical speckled pattern that is a consequence of the concentration of the protein within discrete subnuclear domains known as nuclear bodies. Delocalization of PML from nuclear bodies has been documented in acute promyelocytic leukemia cells and suggested to contribute to leukemogenesis. In an attempt to get new insights into the function of the wild-type PML protein and to investigate whether it displays an altered expression pattern in neoplasms other than acute promyelocytic leukemia, we stained a large number of normal and neoplastic human tissues with a new murine monoclonal antibody (PG-M3) directed against the amino-terminal region of PML. As the PG-M3 epitope is partially resistant to fixatives, only cells that overexpress PML are detected by the antibody in microwave-heated paraffin sections. Among normal tissues, PML was characteristically up-regulated in activated epithelioid histiocytes and fibroblasts in a variety of pathological conditions, columnar epithelium in small active thyroid follicles, well differentiated foamy cells in the center of sebaceous glands, and hypersecretory endometria (Arias-Stella). Interferons, the PML of which is a primary target gene, and estrogens are likely to represent some of the cytokines and/or hormones that may be involved in the up-regulation of PML under these circumstances. In keeping with this concept, we found that PML is frequently overexpressed in Hodgkin and Reed-Sternberg cells of Hodgkin's disease, a tumor of cytokine-producing cells. Among solid tumors, overexpression of PML was frequently found in carcinomas of larynx and thyroid (papillary), epithelial thymomas, and Kaposi's sarcoma, whereas carcinomas of the lung, thyroid (follicular), breast, and colon were

  5. Hormone Receptor Expression Analyses in Neoplastic and Non-Neoplastic Canine Mammary Tissue by a Bead Based Multiplex Branched DNA Assay: A Gene Expression Study in Fresh Frozen and Formalin-Fixed, Paraffin-Embedded Samples.

    Science.gov (United States)

    Mohr, Annika; Lüder Ripoli, Florenza; Hammer, Susanne Conradine; Willenbrock, Saskia; Hewicker-Trautwein, Marion; Kiełbowicz, Zdzisław; Murua Escobar, Hugo; Nolte, Ingo

    2016-01-01

    Immunohistochemistry (IHC) is currently considered the method of choice for steroid hormone receptor status evaluation in human breast cancer and, therefore, it is commonly utilized for assessing canine mammary tumors. In case of low hormone receptor expression, IHC is limited and thus is complemented by molecular analyses. In the present study, a multiplex bDNA assay was evaluated as a method for hormone receptor gene expression detection in canine mammary tissues. Estrogen receptor (ESR1), progesterone receptor (PGR), prolactin receptor (PRLR) and growth hormone receptor (GHR) gene expressions were evaluated in neoplastic and non-neoplastic canine mammary tissues. A set of 119 fresh frozen and 180 formalin-fixed, paraffin-embedded (FFPE) was comparatively analyzed and used for assay evaluation. Furthermore, a possible association between the hormone receptor expression in different histological subtypes of canine malignant mammary tumors and the castration status, breed and invasive growth of the tumor were analyzed. The multiplex bDNA assay proved to be more sensitive for fresh frozen specimens. Hormone receptor expression found was significantly decreased in malignant mammary tumors in comparison to non-neoplastic tissue and benign mammary tumors. Among the histological subtypes the lowest gene expression levels of ESR1, PGR and PRLR were found in solid, anaplastic and ductal carcinomas. In summary, the evaluation showed that the measurement of hormone receptors with the multiplex bDNA assay represents a practicable method for obtaining detailed quantitative information about gene expression in canine mammary tissue for future studies. Still, comparison with IHC or quantitative real-time PCR is needed for further validation of the present method.

  6. Some growth factors in neoplastic tissues of brain tumors of different histological structure

    Directory of Open Access Journals (Sweden)

    O. I. Kit

    2016-01-01

    -β1 (BenderMedSystem, Austria.Results. We have found both common and distinctive features in the content of growth factors in neoplastic tissues of different histological structure and corresponding peritumoral areas. Common metabolic features of glioblastomas, brain metastases and meningiomas include various increase in the level of VEGF-A, VEGF-R1, VEGF-C, IFR-1, IFR-2 and VEGF-C/VEGF-R3 index ratio. Differences included the fact that the level of VEGF-R3 and TGF-β1 did not increase in the benign tumor, while the level of EGF and VEGF-A/VEGF-R1 index ratio were below the control values in contrast to the values of malignant tumors.Conclusions• In the neoplastic tissues of glioblastomas and peritumoral area there is a strong positive correlation between the level of VEGF-A with the level of EGF, IGF-1, IGF-II and TGF-β1.• In the metastatic tissue there is a strong positive correlation between the level of VEGF-A with the level of EGF, IGF-1, IGF-II and TGF-β1. However, correlations had a different nature in the peritumoral zone tissues near to metastases: there was a strong positive correlation of VEGF-A level with TGF-β1 only, while there was a strong negative correlation with the level of IGF-1 and IGF-II, there were no correlations with EGF level.• In meningioma tissues VEGF-A levels correlated only with the level of insulin-like growth factors: there was a strong positive correlation with IGF-1 and IGF-II, correlation has been found with the level of EGF and TGF-β1.• In descending order VEGF-C was detected in glioblastoma tissue, in metastatic tumors, meningiomas, peritumoral zones of glioblastomas and metastases. However, in all of these samples the level of the studied factor significantly exceeded the value in intact brain tissue. VEGFR-3 level was elevated in glioblastoma tissue only. 

  7. Observation of radiation-specific damage in human cells exposed to depleted uranium: dicentric frequency and neoplastic transformation as endpoints.

    Science.gov (United States)

    Miller, A C; Xu, J; Stewart, M; Brooks, K; Hodge, S; Shi, L; Page, N; McClain, D

    2002-01-01

    Depleted uranium (DU) is a dense heavy metal used primarily in military applications. Published data from our laboratory have demonstrated that DU exposure in vitro to immortalised human osteoblast cells (HOS) is both neoplastically transforming and genotoxic. DU possesses both a radiological (alpha-particle) and chemical (metal) component. Since DU has a low specific activity in comparison to natural uranium, it is not considered to be a significant radiological hazard. The potential contribution of radiation to DU-induced biological effects is unknown and the involvement of radiation in DU-induced biological effects could have significant implications for current risk estimates for internalised DU exposure. Two approaches were used to address this question. The frequency of dicentrics was measured in HOS cells following DU exposure in vitro. Data demonstrated that DU exposure (50 microM, 24 h) induced a significant elevation in dicentric frequency in vitro in contrast to incubation with the heavy metals, nickel and tungsten which did not increase dicentric frequency above background levels. Using the same concentration (50 microM) of three uranyl nitrate compounds that have different uranium isotopic concentrations and therefore, different specific activities, the effect on neoplastic transformation in vitro was examined. HOS cells were exposed to one of three-uranyl nitrate compounds (238U-uranyl nitrate, specific activity 0.33 microCi.g-1; DU-uranyl nitrate, specific activity 0.44 microCi.g-1; and 235U-uranyl nitrate, specific activity 2.2 microCi.g-1) delivered at a concentration of 50 microM for 24 h. Results showed, at equal uranium concentration, there was a specific activity dependent increase in neoplastic transformation frequency. Taken together these data suggest that radiation can play a role in DU-induced biological effects in vitro.

  8. Observation of radiation-specific damage in human cells exposed to depleted uranium: dicentric frequency and neoplastic transformation as endpoints

    Energy Technology Data Exchange (ETDEWEB)

    Miller, A.C.; Xu, J.; Stewart, M.; Brooks, K.; Hodge, S.; Shi, L.; Page, M.; McClain, D

    2002-07-01

    Depleted uranium (DU) is a dense heavy metal used primarily in military applications. Published data from our laboratory have demonstrated that DU exposure in vitro to immortalised human osteoblast cells (HOS) is both neoplastically transforming and genotoxic. DU possesses both a radiological (alpha-particle) and chemical (metal) component. Since DU has a low specific activity in comparison to natural uranium, it is not considered to be a significant radiological hazard. The potential contribution of radiation to DU-induced biological effects is unknown and the involvement of radiation in DU-induced biological effects could have significant implication for current risk estimates for internalised DU exposure. Two approaches were used to address this question. The frequency of dicentrics was measured in HOS cells following DU exposure in vitro. Data demonstrated that DU exposure (50 {mu}M, 24h) induced a significant elevation in dicentric frequency in vitro in contrast to incubation with the heavy metals, nickel and tungsten which did not increase dicentric frequency above background levels. Using the same concentration (50 {mu}M) of three uranyl nitrate compounds that have different uranium isotopic concentrations and therefore, different specific activities, the effect on neoplastic transformation in vitro was examined. HOS cells were exposed to one of three-uranyl nitrate compounds ({sup 238}U-uranyl nitrate, specific activity 0.33 {mu}Ci.g{sup -1}: DU-uranyl nitrate, specific activity 0.44 {mu}Ci.g{sup -1}: and {sup 235}U-uranyl nitrate, specific activity 2.2 {mu}Ci.g{sup -1}) delivered at a concentration of 50 {mu}M for 24 h. Results showed, at equal uranium concentration, there was a specific activity dependent increase in neoplastic transformation frequency. Taken together these data suggest that radiation can play a role in DU-induced biological effects in vitro. (author)

  9. Prenatal exposure to BPA alters the epigenome of the rat mammary gland and increases the propensity to neoplastic development.

    Directory of Open Access Journals (Sweden)

    Eugen Dhimolea

    Full Text Available Exposure to environmental estrogens (xenoestrogens may play a causal role in the increased breast cancer incidence which has been observed in Europe and the US over the last 50 years. The xenoestrogen bisphenol A (BPA leaches from plastic food/beverage containers and dental materials. Fetal exposure to BPA induces preneoplastic and neoplastic lesions in the adult rat mammary gland. Previous results suggest that BPA acts through the estrogen receptors which are detected exclusively in the mesenchyme during the exposure period by directly altering gene expression, leading to alterations of the reciprocal interactions between mesenchyme and epithelium. This initiates a long sequence of altered morphogenetic events leading to neoplastic transformation. Additionally, BPA induces epigenetic changes in some tissues. To explore this mechanism in the mammary gland, Wistar-Furth rats were exposed subcutaneously via osmotic pumps to vehicle or 250 µg BPA/kg BW/day, a dose that induced ductal carcinomas in situ. Females exposed from gestational day 9 to postnatal day (PND 1 were sacrificed at PND4, PND21 and at first estrus after PND50. Genomic DNA (gDNA was isolated from the mammary tissue and immuno-precipitated using anti-5-methylcytosine antibodies. Detection and quantification of gDNA methylation status using the Nimblegen ChIP array revealed 7412 differentially methylated gDNA segments (out of 58207 segments, with the majority of changes occurring at PND21. Transcriptomal analysis revealed that the majority of gene expression differences between BPA- and vehicle-treated animals were observed later (PND50. BPA exposure resulted in higher levels of pro-activation histone H3K4 trimethylation at the transcriptional initiation site of the alpha-lactalbumin gene at PND4, concomitantly enhancing mRNA expression of this gene. These results show that fetal BPA exposure triggers changes in the postnatal and adult mammary gland epigenome and alters gene

  10. Selenium, selenoenzymes, oxidative stress and risk of neoplastic progression from Barrett's esophagus: results from biomarkers and genetic variants.

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    Yumie Takata

    Full Text Available Clinical trials have suggested a protective effect of selenium supplementation on the risk of esophageal cancer, which may be mediated through the antioxidant activity of selenoenzymes. We investigated whether serum selenium concentrations, selenoenzyme activity, oxidative stress and genetic variation in selenoenzymes were associated with the risk of neoplastic progression to esophageal adenocarcinoma (EA and two intermediate endpoints, aneuploidy and tetraploidy. In this prospective cohort study, during an average follow-up of 7.3 years, 47 EA cases, 41 aneuploidy cases and 51 tetraploidy cases accrued among 361 participants from the Seattle Barrett's Esophagus Research Study who were free of EA at the time of blood draw and had at least one follow-up visit. Development to EA was assessed histologically and aneuploidy and tetraploidy by DNA content flow cytometry. Serum selenium concentrations were measured using atomic absorption spectrometry, activity of glutathione peroxidase (GPX 1 and GPX3 by substrate-specific coupled test procedures, selenoprotein P (SEPP1 concentrations and protein carbonyl content by ELISA method and malondialdehyde concentrations by HPLC. Genetic variants in GPX1-4 and SEPP1 were genotyped. Serum selenium was not associated with the risk of neoplastic progression to EA, aneuploidy or tetraploidy (P for trend = 0.25 to 0.85. SEPP1 concentrations were positively associated with the risk of EA [hazard ratio (HR = 3.95, 95% confidence intervals (CI = 1.42-10.97 comparing the third tertile with the first] and with aneuploidy (HR = 6.53, 95% CI = 1.31-32.58, but not selenoenzyme activity or oxidative stress markers. No genetic variants, overall, were associated with the risk of neoplastic progression to EA (global p = 0.12-0.69. Our results do not support a protective effect of selenium on risk of neoplastic progression to EA. Our study is the first to report positive associations of plasma SEPP1

  11. Renal cell carcinoma and synchronous thyroid metastasis with neoplastic thrombosis of the internal jugular vein: report of a case.

    Science.gov (United States)

    Matei, Deliu-Victor; Brescia, Antonio; Nordio, Andrea; Spinelli, Matteo Giulio; Melegari, Sara; Cozzi, Gabriele; Andrioli, Massimiliano; Salvatori, Pietro

    2011-12-01

    A case of thyroid metastasis of a renal clear cell carcinoma is presented. The fine-needle aspiration cytology pointed out the primary tumor origin. The patient underwent robot-assisted radical nephrectomy and contextual thyroidectomy. During the operative procedure, a neoplastic thrombus extending from the thyroid metastasis and protruding into the internal jugular vein was found. As a result, thrombectomy and ligation of the internal jugular vein were required. In cases of single synchronous thyroid metastases form RCC, radical surgery should be advisable. Robotic approach allows to associate major surgery procedures, as nephrectomy, with radical metastasectomy.

  12. The Relationship between Brown Adipose Tissue Activity and Neoplastic Status: an 18F-FDG PET/CT Study in the Tropics

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    Huang Yung-Cheng

    2011-12-01

    Full Text Available Abstract Background Brown adipose tissue (BAT has thermogenic potential. For its activation, cold exposure is considered a critical factor though other determinants have also been reported. The purpose of this study was to assess the relationship between neoplastic status and BAT activity by 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG positron emission tomography/computed tomography (PET/CT in people living in the tropics, where the influence of outdoor temperature was low. Methods 18F-FDG PET/CT scans were reviewed and the total metabolic activity (TMA of identified activated BAT quantified. The distribution and TMA of activated BAT were compared between patients with and without a cancer history. The neoplastic status of patients was scored according to their cancer history and 18F-FDG PET/CT findings. We evaluated the relationships between the TMA of BAT and neoplastic status along with other factors: age, body mass index, fasting blood sugar, gender, and outdoor temperature. Results Thirty of 1740 patients had activated BAT. Those with a cancer history had wider BAT distribution (p = 0.043 and a higher TMA (p = 0.028 than those without. A higher neoplastic status score was associated with a higher average TMA. Multivariate analyses showed that neoplastic status was the only factor significantly associated with the TMA of activated BAT (p = 0.016. Conclusions Neoplastic status is a critical determinant of BAT activity in patients living in the tropics. More active neoplastic status was associated with more vigorous TMA of BAT.

  13. P-glycoprotein--implications of metabolism of neoplastic cells and cancer therapy.

    Science.gov (United States)

    Breier, Albert; Barancík, Miroslav; Sulová, Zdenka; Uhrík, Branislav

    2005-09-01

    Multidrug resistance (MDR) of neoplastic tissues is a major obstacle in cancer chemotherapy. The predominant cause of MDR is the overexpression and drug transport activity of P-glycoprotein (P-gp, a product of the MDR gene). P-gp is a member of the ATP binding cassette (ABC) transporters family, with broad substrate specificity for several substances including anticancer drugs, linear and cyclic peptides, inhibitors of HIV protease, and several other substances. The development of P-gp-mediated MDR is often associated with several changes in cell structure and metabolism of resistant cells. In the present review are discussed the relations between glucosylceramide synthase activity, Pregnane X receptor and development of P-gp mediated MDR phenotype. Attention is also focused on the changes in protein kinase systems (mitogen-activated protein kinases, protein kinase C, Akt kinase) that are associated with the development of MDR phenotype and to the possible role of these kinase cascades in modulation of P-gp expression and function. The overexpression of P-gp may be associated with changes in metabolism of sugars as well as energy production. Structural and ultrastructural characteristics of multidrug resistant cells expressing P-gp are typical for cells engaged in a metabolically demanding process of protein synthesis and transport. P-gp mediated MDR phenotype is often also associated with alterations in cytoskeletal elements, microtubule and mitochondria distribution, Golgi apparatus, chromatin texture, vacuoles and caveolae formation. The current review also aims at bringing some state-of-the-art information on interactions of P-glycoprotein with various substances. To capture and transport the numerous unrelated substances, P-gp should contain site(s) able to bind compounds with a molecular weight of several hundreds and comprising hydrophobic and/or base regions that are protonated under physiological conditions. Drug binding sites that are able to recognize

  14. Optic Neuritis as Isolated Manifestation of Leptomeningeal Carcinomatosis: A Case Report and Systematic Review of Ocular Manifestations of Neoplastic Meningitis

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    Silvia Lanfranconi

    2013-01-01

    Full Text Available Introduction. Leptomeningeal carcinomatosis occurs in about 5% of cancer patients. Ocular involvement is a common clinical manifestation and often the presenting clinical feature. Materials and Methods. We report the case of a 52-year old lady with optic neuritis as isolated manifestation of neoplastic meningitis and a review of ocular involvement in neoplastic meningitis. Ocular symptoms were the presenting clinical feature in 34 patients (83% out of 41 included in our review, the unique manifestation of meningeal carcinomatosis in 3 patients (7%. Visual loss was the presenting clinical manifestation in 17 patients (50% and was the most common ocular symptom (70%. Other ocular signs were diplopia, ptosis, papilledema, anisocoria, exophthalmos, orbital pain, scotomas, hemianopsia, and nystagmus. Associated clinical symptoms were headache, altered consciousness, meningism, limb weakness, ataxia, dizziness, seizures, and other cranial nerves involvement. All patients except five underwent CSF examination which was normal in 1 patient, pleocytosis was found in 11 patients, increased protein levels were observed in 16 patients, and decreased glucose levels were found in 8 patients. Cytology was positive in 29 patients (76%. Conclusion. Meningeal carcinomatosis should be considered in patients with ocular symptoms even in the absence of other suggestive clinical symptoms.

  15. Activated Hepatic Stellate Cells Induce Tumor Progression of Neoplastic Hepatocytes in a TGF-β Dependent Fashion

    Science.gov (United States)

    MIKULA, M.; PROELL, V.; FISCHER, A.N.M.; MIKULITS, W.

    2010-01-01

    The development of hepatocellular carcinomas from malignant hepatocytes is frequently associated with intra- and peritumoral accumulation of connective tissue arising from activated hepatic stellate cells. For both tumorigenesis and hepatic fibrogenesis, transforming growth factor (TGF)-β signaling executes key roles and therefore is considered as a hallmark of these pathological events. By employing cellular transplantation we show that the interaction of neoplastic MIM-R hepatocytes with the tumor microenvironment, containing either activated hepatic stellate cells (M1-4HSCs) or myofibroblasts derived thereof (M-HTs), induces progression in malignancy. Cotransplantation of MIM-R hepatocytes with M-HTs yielded strongest MIM-R generated tumor formation accompanied by nuclear localization of Smad2/3 as well as of β-catenin. Genetic interference with TGF-β signaling by gain of antagonistic Smad7 in MIM-R hepatocytes diminished epithelial dedifferentiation and tumor progression upon interaction with M1-4HSCs or M-HTs. Further analysis showed that tumors harboring disrupted Smad signaling are devoid of nuclear β-catenin accumulation, indicating a crosstalk between TGF-β and β-catenin signaling. Together, these data demonstrate that activated HSCs and myofibroblasts directly govern hepatocarcinogenesis in a TGF-β dependent fashion by inducing autocrine TGF-β signaling and nuclear β-catenin accumulation in neoplastic hepatocytes. These results indicate that intervention with TGF-β signaling is highly promising in liver cancer therapy. PMID:16883581

  16. Autophagy-deficiency in hepatic progenitor cells leads to the defects of stemness and enhances susceptibility to neoplastic transformation.

    Science.gov (United States)

    Xue, Feng; Hu, Lei; Ge, Ruiliang; Yang, Lixue; Liu, Kai; Li, Yunyun; Sun, Yanfu; Wang, Kui

    2016-02-01

    Autophagy is a highly conserved and lysosome-dependent degradation process which assists in cell survival and tissue homeostasis. Although previous reports have shown that deletion of the essential autophagy gene disturbs stem cell maintenance in some cell types such as hematopoietic and neural cells, it remains unclear how autophagy-deficiency influences hepatic progenitor cells (HPCs). Here we report that Atg5-deficiency in HPCs delays HPC-mediated rat liver regeneration in vivo. In vitro researches further demonstrate that loss of autophagy decreases the abilities of colony and spheroid formations, and disrupts the induction of hepatic differentiation in HPCs. Meanwhile, autophagy-deficiency increases the accumulations of damaged mitochondria and mitochondrial reactive oxygen species (mtROS) and suppresses homologous recombination (HR) pathway of DNA damage repair in HPCs. Moreover, in both diethylnitrosamine (DEN) and CCl4 models, autophagy-deficiency accelerates neoplastic transformation of HPCs. In conclusion, these findings demonstrate that autophagy contributes to stemness maintenance and reduces susceptibility to neoplastic transformation in HPCs.

  17. A high throughput screen identifies Nefopam as targeting cell proliferation in β-catenin driven neoplastic and reactive fibroproliferative disorders.

    Directory of Open Access Journals (Sweden)

    Raymond Poon

    Full Text Available Fibroproliferative disorders include neoplastic and reactive processes (e.g. desmoid tumor and hypertrophic scars. They are characterized by activation of β-catenin signaling, and effective pharmacologic approaches are lacking. Here we undertook a high throughput screen using human desmoid tumor cell cultures to identify agents that would inhibit cell viability in tumor cells but not normal fibroblasts. Agents were then tested in additional cell cultures for an effect on cell proliferation, apoptosis, and β-catenin protein level. Ultimately they were tested in Apc1638N mice, which develop desmoid tumors, as well as in wild type mice subjected to full thickness skin wounds. The screen identified Neofopam, as an agent that inhibited cell numbers to 42% of baseline in cell cultures from β-catenin driven fibroproliferative disorders. Nefopam decreased cell proliferation and β-catenin protein level to 50% of baseline in these same cell cultures. The half maximal effective concentration in-vitro was 0.5 uM and there was a plateau in the effect after 48 hours of treatment. Nefopam caused a 45% decline in tumor number, 33% decline in tumor volume, and a 40% decline in scar size when tested in mice. There was also a 50% decline in β-catenin level in-vivo. Nefopam targets β-catenin protein level in mesenchymal cells in-vitro and in-vivo, and may be an effective therapy for neoplastic and reactive processes driven by β-catenin mediated signaling.

  18. Modifications of glycosphingolipid profile and synthesis in normal rat fibroblasts and in syngeneic neoplastic cells at different subculture stages.

    Science.gov (United States)

    Colombo, I; Sottocornola, E; Moretti, S; Meloni, M A; Pippia, P; Berra, B

    2000-05-31

    Glycosphingolipids are plasma membrane macromolecules involved in diversified recognition functions on the cell surface resulting in modulation of cell adhesion and differentiation. As the in vitro cellular system of the neoplastic cell line SGS/4A and syngeneic normal fibroblasts (FG) represents a useful tool for studies on molecular mechanisms regulating cell adhesion, neoplastic transformation and cellular ageing, we studied the changes of glycosphingolipid and of the enzymes involved in their metabolism in both cultured cells at different subculture stages. The FG subculture progression induces a drastic decrease of total glycosphingolipid content with consistent alterations in the molecular composition. In particular, a significant decrease of GM(3), a slight increase of GD(1a), the disappearance of 'b'-series gangliosides and the drastic reduction of triosylceramides were observed. On the contrary, the increasing number of SGS/4A subcultures, characterized by a specific and different glycosphingolipid composition as compared with FG cells, does not cause modifications. Although glycosyltransferase activity levels quite well parallel the glycosphingolipid patterns and can account for the noted variations, the mRNA expression analysis of two glycosyltransferases suggests that the in vitro cell ageing of normal rat fibroblasts causes drastic changes in the glycosphingolipid profile through the regulation, at either the transcriptional or post-translational level, of some biosynthetic enzymes.

  19. Increased frequency of spontaneous neoplastic transformation in progeny of bystander cells from cultures exposed to densely ionizing radiation.

    Directory of Open Access Journals (Sweden)

    Manuela Buonanno

    Full Text Available An increased risk of carcinogenesis caused by exposure to space radiation during prolonged space travel is a limiting factor for human space exploration. Typically, astronauts are exposed to low fluences of ionizing particles that target only a few cells in a tissue at any one time. The propagation of stressful effects from irradiated to neighboring bystander cells and their transmission to progeny cells would be of importance in estimates of the health risks of exposure to space radiation. With relevance to the risk of carcinogenesis, we investigated, in model C3H 10T½ mouse embryo fibroblasts (MEFs, modulation of the spontaneous frequency of neoplastic transformation in the progeny of bystander MEFs that had been in co-culture 10 population doublings earlier with MEFs exposed to moderate doses of densely ionizing iron ions (1 GeV/nucleon or sparsely ionizing protons (1 GeV. An increase (P<0.05 in neoplastic transformation frequency, likely mediated by intercellular communication through gap junctions, was observed in the progeny of bystander cells that had been in co-culture with cells irradiated with iron ions, but not with protons.

  20. Detection of a complement-derived chemotactic factor for tumor cells in human inflammatory and neoplastic effusions.

    Science.gov (United States)

    Orr, F. W.; Delikatny, E. J.; Mokashi, S.; Krepart, G. V.; Stiver, H. G.

    1983-01-01

    A chemotactic factor for neoplastic cells can be generated in vitro by incubating human C5 or C5a with leukocytic or pancreatic lysosomal enzymes and is also detectable in experimental inflammatory exudates. The authors therefore sought evidence for the existence of this factor in human effusions. Using the Boyden chamber assay, they detected chemotactic activity for MB-MDA-231 human breast carcinoma cells and Walker ascites tumor cells in human inflammatory and neoplastic exudates, including ascites, pleural effusions, synovial fluids and cerebrospinal fluids. Chemotactic activity was not found in transudates, normal cerebrospinal fluid, or normal serum. Human ovarian adenocarcinoma cells from one of the effusions migrated toward autologous ascites and towards the C5-derived chemotactic factor that had been prepared in vitro. In gel filtration the chemotactic factor behaved generally as a molecule having a molecular weight of approximately 6000 daltons. The activity was blocked after incubation with antiserums directed against C5 but not by antiserums directed against C3 or C4. In vitro, chemotactic activity for tumor cells could be generated by incubating extracts of exudate cells with autologous plasma or with purified C5. The authors conclude that a chemotactic factor for tumor cells can be formed in human effusions and that this factor has properties similar to those of a previously described C5-derived chemotactic factor. PMID:6185003

  1. Association of urothelial carcinoma of the renal pelvis with papillary and medullary thyroid carcinomas. A new sporadic neoplastic syndrome?

    Science.gov (United States)

    Albores-Saavedra, Jorge; Dorantes-Heredia, Rita; Chablé-Montero, Fredy; Córdova-Ramón, Juan Carlos; Henson, Donald E

    2014-10-01

    We describe 2 adult women (72 and 54 years), 1 with a low-grade noninvasive papillary urothelial carcinoma of the renal pelvis, who 14 years later developed a papillary carcinoma in 1 thyroid lobe and a medullary carcinoma in the contralateral lobe. Both neoplasms were similar in size and appeared symmetrical. Despite its small size, the medullary carcinoma metastasized in multiple cervical lymph nodes. The second patient had a high-grade invasive papillary urothelial carcinoma of the renal pelvis that infiltrated the renal parenchyma and metastasized in one of the lungs. Five months later, a papillary carcinoma was discovered in the thyroid gland. The 2 papillary thyroid carcinomas were of the follicular variant. Adjacent to 1 papillary carcinoma, there was a dominant nodule of a colloid and adenomatous goiter. The medullary carcinoma contained stromal amyloid and was immunoreactive for calcitonin and carcinoembryonic antigen. There was no C-cell hyperplasia (medullary carcinoma in situ). The 2 patients are alive, 1 is living with pulmonary metastasis from the high-grade urothelial carcinoma. Twelve cases of this neoplastic association were registered in the Survey, Epidemiology, and End Results Program from 1980 to 2009. We believe that the combination of these unusual neoplasms in the same patient may represent a new sporadic neoplastic syndrome.

  2. Study of electron densities of normal and neoplastic human breast tissues by Compton scattering using synchrotron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Antoniassi, M.; Conceicao, A.L.C. [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto-Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.br [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto-Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo (Brazil)

    2012-07-15

    Electron densities of 33 samples of normal (adipose and fibroglangular) and neoplastic (benign and malignant) human breast tissues were determined through Compton scattering data using a monochromatic synchrotron radiation source and an energy dispersive detector. The area of Compton peaks was used to determine the electron densities of the samples. Adipose tissue exhibits the lowest values of electron density whereas malignant tissue the highest. The relationship with their histology was discussed. Comparison with previous results showed differences smaller than 4%. - Highlights: Black-Right-Pointing-Pointer Electron density of normal and neoplastic breast tissues was measured using Compton scattering. Black-Right-Pointing-Pointer Monochromatic synchrotron radiation was used to obtain the Compton scattering data. Black-Right-Pointing-Pointer The area of Compton peaks was used to determine the electron densities of samples. Black-Right-Pointing-Pointer Adipose tissue shows the lowest electron density values whereas the malignant tissue the highest. Black-Right-Pointing-Pointer Comparison with previous results showed differences smaller than 4%.

  3. Gene Expression Analysis for the Identification of Genes Involved in Early Tumour Development

    Science.gov (United States)

    Forte, Stefano; Scarpulla, Salvatore; Lagana, Alessandro; Memeo, Lorenzo; Gulisano, Massimo

    Prostatic tissues can undergo to cancer insurgence and prostate cancer is one of the most common types of malignancies affecting adult men in the United States. Primary adenocarcinoma of the seminal vesi-cles (SVCA) is a very rare neoplasm with only 48 histologically confirmed cases reported in the European and United States literature. Prostatic tissues, seminal vesicles and epididymis belongs all to the same microenvironment, shows a very close morphology and share the same embryological origin. Despite these common features the rate of cancer occurrence is very different. The understanding of molecular differences between non neoplastic prostatic tissues and non neoplastic epididymis or seminal vesicles may suggest potential mechanisms of resistance to tumour occurrence. The comparison of expression patterns of non neoplastic prostatic and seminal vesicles tissues to identify differentially expressed genes can help researchers in the identification of biological actors involved in the early stages of the tumour development.

  4. Hyperspectral imaging of neoplastic progression in a mouse model of oral carcinogenesis

    Science.gov (United States)

    Lu, Guolan; Qin, Xulei; Wang, Dongsheng; Muller, Susan; Zhang, Hongzheng; Chen, Amy; Chen, Zhuo Georgia; Fei, Baowei

    2016-03-01

    Hyperspectral imaging (HSI) is an emerging modality for medical applications and holds great potential for noninvasive early detection of cancer. It has been reported that early cancer detection can improve the survival and quality of life of head and neck cancer patients. In this paper, we explored the possibility of differentiating between premalignant lesions and healthy tongue tissue using hyperspectral imaging in a chemical induced oral cancer animal model. We proposed a novel classification algorithm for cancer detection using hyperspectral images. The method detected the dysplastic tissue with an average area under the curve (AUC) of 0.89. The hyperspectral imaging and classification technique may provide a new tool for oral cancer detection.

  5. Cell-block procedure in endoscopic ultrasound-guided-fine-needle-aspiration of gastrointestinal solid neoplastic lesions

    Institute of Scientific and Technical Information of China (English)

    Antonio; Ieni; Valeria; Barresi; Paolo; Todaro; Rosario; Alberto; Caruso; Giovanni; Tuccari

    2015-01-01

    In the present review we have analyzed the clinical applications of endoscopic ultrasound-guided-fineneedle-aspiration(EUS-FNA) and the methodological aspects obtained by cell-block procedure(CBP) in the diagnostic approach to the gastrointestinal neoplastic pathology. CBP showed numerous advantages in comparison to the cytologic routine smears; in particular, better preservation of cell architecture, achievement of routine haematoxylin-eosin staining equivalent to histological slides and possibility to perform immunohistochemistry or molecular analyses represented the most evident reasons to choose this method. Moreover, by this approach, the differential diagnosis of solid gastrointestinal neoplasias may be more easily achieved and the background of contaminant nonneoplastic gastrointestinal avoided. Finally, biological samples collected by EUS-FNA CBP-assisted should be investigated in order to identify and quantify further potential molecular markers.

  6. The antibacterial substance taurolidine exhibits anti-neoplastic action based on a mixed type of programmed cell death.

    Science.gov (United States)

    Stendel, Ruediger; Biefer, Hector Rodriguez Cetina; Dékány, Gabriela Marta; Kubota, Hisashi; Münz, Christian; Wang, Sheng; Mohler, Hanns; Yonekawa, Yasuhiro; Frei, Karl

    2009-02-01

    The antibacterial amino-acid derivative taurolidine (TAU) has been recently shown to exhibit anti-neoplastic activity based on a mechanism, which is still unknown in detail. Cytotoxicity and clonogenic assays were performed and the impact of apoptosis modulators, a radical scavenger, autophagy inhibitors, silencing of apoptosis inducing actor (AIF) and cytochrome-c (Cyt-C) by siRNA, and knockdown of autophagy related genes were evaluated in vitro. The intracellular ATP-content, release of AIF and Cyt-C, and DNA-laddering were investigated. This study could demonstrate cell killing, inhibition of proliferation, and inhibition or prevention of colony formation in human glioma cell lines and ex vivo glioblastoma cells after incubation with TAU. This effect is based on the induction of a mixed type of programmed cell death with the main preference of autophagy, and involvement of senescence, necroptosis and necrosis. This mechanism of action may open a new approach for therapeutic intervention.

  7. Formation of Shc-Grb2 complexes is necessary to induce neoplastic transformation by overexpression of Shc proteins

    DEFF Research Database (Denmark)

    Salcini, A E; McGlade, J; Pelicci, G

    1994-01-01

    of Grb2 to Shc proteins requires phosphorylation of Shc at Tyr317, which lies within the high affinity binding motif for the Grb2 SH2 domain, pYVNV, where Asn at the +2 position is crucial for complex formation. In vivo, Tyr317 is the major, but not the only, site for Shc phosphorylation, and is the sole...... is implicated in the regulation of Ras, suggesting that Shc is involved in the intracellular transmission of growth signals from activated tyrosine kinases to Ras. Overexpression of Shc proteins in cultured fibroblasts induces a transformed phenotype. We now report that, in vitro, the high affinity binding...... Shc high affinity binding site for Grb2. Mutant Shc proteins with substitution of the Tyr317 by Phe lose the capacity to be highly phosphorylated on tyrosine upon growth factor receptor activation, to bind Grb2 and to induce neoplastic transformation. In contrast, Shc proteins that have an extensive...

  8. A Tumor Surveillance Model: A Non-Coding RNA Senses Neoplastic Cells and Its Protein Partner Signals Cell Death

    Directory of Open Access Journals (Sweden)

    Yong Sun Lee

    2012-10-01

    Full Text Available nc886 (= pre-miR-886 or vtRNA2-1 is a non-coding RNA that has been recently identified as a natural repressor for the activity of PKR (Protein Kinase R. The suppression of nc886 activates PKR and thereby provokes a cell death pathway. When combined with the fact that nc886 is suppressed in a wide range of cancer cells, the nc886-PKR relationship suggests a tumor surveillance model. When neoplastic cells develop and nc886 decreases therein, PKR is released from nc886 and becomes the active phosphorylated form, which initiates an apoptotic cascade to eliminate those cells. The nc886-PKR pathway is distinct from conventional mechanisms, such as the immune surveillance hypothesis or intrinsic mechanisms that check/proofread the genomic integrity, and thus represents a novel example of tumor surveillance.

  9. Mycalamide A Shows Cytotoxic Properties and Prevents EGF-Induced Neoplastic Transformation through Inhibition of Nuclear Factors

    Science.gov (United States)

    Dyshlovoy, Sergey A.; Fedorov, Sergey N.; Kalinovsky, Anatoly I.; Shubina, Larisa K.; Bokemeyer, Carsten; Stonik, Valentin A.; Honecker, Friedemann

    2012-01-01

    Mycalamide A, a marine natural compound previously isolated from sponges, is known as a protein synthesis inhibitor with potent antitumor activity. However, the ability of this compound to prevent malignant transformation of cells has never been examined before. Here, for the first time, we report the isolation of mycalamide A from ascidian Polysincraton sp. as well as investigation of its cancer preventive properties. In murine JB6 Cl41 P+ cells, mycalamide A inhibited epidermal growth factor (EGF)-induced neoplastic transformation, and induced apoptosis at subnanomolar or nanomolar concentrations. The compound inhibited transcriptional activity of the oncogenic nuclear factors AP-1 and NF-κB, a potential mechanism of its cancer preventive properties. Induction of phosphorylation of the kinases MAPK p38, JNK, and ERK was also observed at high concentrations of mycalamide A. The drug shows promising potential for both cancer-prevention and cytotoxic therapy and should be further developed. PMID:22822368

  10. In Situ Nuclear Morphology Measurements Using Light Scattering as Biomarkers of Neoplastic Change in Animal Models of Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Adam Wax

    2008-01-01

    Full Text Available Light scattering spectroscopy measurements can be used to determine the structure of tissue samples. Through refined data acquisition and signal processing techniques, quantitative nuclear morphology measurements may be obtained from light scattering data. These data have been used primarily as a biomarker of neoplastic change in a wide range of settings. Here, we review the application of light scattering to assessing the health status of tissues drawn from animal models of carcinogenesis, in particular, the rat esophagus and the golden Syrian hamster trachea carcinogenesis models. In addition, we present results from ex vivo human tissues to demonstrate the relevance of the use of animal models which are excellent surrogates for several human cancers. These models provide the opportunity to develop biomarkers and test chemopreventive and therapy strategies before application in humans.

  11. Three-dimensional lithographically-defined organotypic tissue arrays for quantitative analysis of morphogenesis and neoplastic progression

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, Celeste M.; Inman, Jamie L.; Bissell, Mina J.

    2008-02-13

    Here we describe a simple micromolding method to construct three-dimensional arrays of organotypic epithelial tissue structures that approximate in vivo histology. An elastomeric stamp containing an array of posts of defined geometry and spacing is used to mold microscale cavities into the surface of type I collagen gels. Epithelial cells are seeded into the cavities and covered with a second layer of collagen. The cells reorganize into hollow tissues corresponding to the geometry of the cavities. Patterned tissue arrays can be produced in 3-4 h and will undergo morphogenesis over the following one to three days. The protocol can easily be adapted to study a variety of tissues and aspects of normal and neoplastic development.

  12. Polyubiquitinated proteins, proteasome, and glycogen characterize the particle-rich cytoplasmic structure (PaCS) of neoplastic and fetal cells.

    Science.gov (United States)

    Necchi, Vittorio; Sommi, Patrizia; Vitali, Agostina; Vanoli, Alessandro; Savoia, Anna; Ricci, Vittorio; Solcia, Enrico

    2014-05-01

    A particle-rich cytoplasmic structure (PaCS) concentrating ubiquitin-proteasome system (UPS) components and barrel-like particles in clear, cytoskeleton- and organelle-free areas has recently been described in some neoplasms and in genetic or infectious diseases at risk of neoplasia. Ultrastructurally similar particulate cytoplasmic structures, interpreted as glycogen deposits, have previously been reported in clear-cell neoplasms and some fetal tissues. It remains to be investigated whether the two structures are the same, colocalize UPS components and polysaccharides, and have a role in highly proliferative cells such as fetal and neoplastic cells. We used immunogold electron microscopy and confocal immunofluorescence microscopy to examine human and mouse fetal tissues and human neoplasms. Fetal and neoplastic cells both showed colocalization of polyubiquitinated proteins, 19S and 20S proteasomes, and polysaccharides, both glycogen and chondroitin sulfate, inside cytoplasmic structures showing all distinctive features of PaCSs. Poorly demarcated and/or hybrid (ribosomes admixed) UPS- and glycogen-enriched areas, likely stages in PaCS development, were also seen in some fetal cells, with special reference to those, like primary alveolar pulmonary cells or pancreatic centroacinar cells, having a crucial role in organogenesis. UPS- and glycogen-rich PaCSs developed extensively in clear-cell neoplasms of the kidney, ovary, pancreas, and other organs, as well as, in infantile, development-related tumors replicating fetal patterns, such as choroid plexus papilloma. UPS-mediated, ATP-dependent proteolysis and its potential energy source, glycogen metabolism, may have a crucial, synergic role in embryo-/organogenesis and carcinogenesis.

  13. Postulating a dermal pathway for exposure to anti-neoplastic drugs among hospital workers. Applying a conceptual model to the results of three workplace surveys

    NARCIS (Netherlands)

    Kromhout, H.; Hoek, F.; Uitterhoeve, R.; Huijbers, R.; Overmars, R.F.; Anzion, R.; Vermeulen, R.

    2000-01-01

    Dermal exposure to anti-neoplastic drugs has been suggested as a potentially important route of exposure of hospital workers. Three small-scale workplace surveys were carried out in several hospitals focusing on contamination by leakage from IV infusion systems; contamination by spilled urine of

  14. Postulating a dermal pathway for exposure to anti-neoplastic drugs among hospital workers. Applying a conceptual model to the results of three workplace surveys

    NARCIS (Netherlands)

    Kromhout, H.; Hoek, F.; Uitterhoeve, R.; Huijbers, R.; Overmars, R.F.; Anzion, R.; Vermeulen, R.

    2000-01-01

    Dermal exposure to anti-neoplastic drugs has been suggested as a potentially important route of exposure of hospital workers. Three small-scale workplace surveys were carried out in several hospitals focusing on contamination by leakage from IV infusion systems; contamination by spilled urine of pat

  15. Effect of cisplatin exposure on platinum accumulation and growth inhibition in human neoplastic and normal squamous epithelial cells of the mucosa of the upper-aerodigestive tract

    NARCIS (Netherlands)

    Braakhuis, B.J.M.; Welters, M.J.P.; Cloos, J.; Pankras, J.E.; Smeets, S.J.; Fichtinger-Schepman, A.-M.J.

    1999-01-01

    The aim of the present study was to investigate how normal head and neck epithelial cells (NHNEC) respond to cisplatin compared to their neoplastic counterparts with respect to intracellular platinum (Pt) levels and growth inhibition. A colorimetric assay was used to assess growth inhibition after e

  16. Telomerase activity as a biomarker for (pre)neoplastic cervical disease in scrapings and frozen sections from patients with abnormal cervical smear

    NARCIS (Netherlands)

    Wisman, GBA; Hollema, H; de Jong, S; ter Schegget, J; Tjong-A-Hung, SP; Ruiters, MHJ; Krans, M; de Vries, EGE; van der Zee, AGJ

    1998-01-01

    Purpose: To evaluate the diagnostic value of semiquantitative telomerase activity assessment in cervical scrapings together with human papillomavirus (HPV) typing for detection of (pre)neoplastic cervical lesions and to compare telomerase activity in cervical scrapings and frozen specimens from the

  17. The pan-Bcl-2 blocker obatoclax promotes the expression of Puma, Noxa, and Bim mRNA and induces apoptosis in neoplastic mast cells.

    Science.gov (United States)

    Peter, Barbara; Cerny-Reiterer, Sabine; Hadzijusufovic, Emir; Schuch, Karina; Stefanzl, Gabriele; Eisenwort, Gregor; Gleixner, Karoline V; Hoermann, Gregor; Mayerhofer, Matthias; Kundi, Michael; Baumgartner, Sigrid; Sperr, Wolfgang R; Pickl, Winfried F; Willmann, Michael; Valent, Peter

    2014-01-01

    Advanced SM is an incurable neoplasm with short survival time. So far, no effective therapy is available for these patients. We and others have shown recently that neoplastic MC in ASM and MCL express antiapoptotic Mcl-1, Bcl-2, and Bcl-xL. In this study, we examined the effects of the pan-Bcl-2 family blocker obatoclax (GX015-070) on primary neoplastic MC, the human MC leukemia cell line HMC-1, and the canine mastocytoma cell line C2. Obatoclax was found to inhibit proliferation in primary human neoplastic MC (IC₅₀: 0.057 μM), in HMC-1.2 cells expressing KIT D816V (IC₅₀: 0.72 μM), and in HMC-1.1 cells lacking KIT D816V (IC₅₀: 0.09 μM), as well as in C2 cells (IC₅₀: 0.74 μM). The growth-inhibitory effects of obatoclax in HMC-1 cells were accompanied by an increase in expression of Puma, Noxa, and Bim mRNA, as well as by apoptosis, as evidenced by microscopy, TUNEL assay, and caspase cleavage. Viral-mediated overexpression of Mcl-1, Bcl-xL, or Bcl-2 in HMC-1 cells was found to introduce partial resistance against apoptosis-inducing effects of obatoclax. We were also able to show that obatoclax synergizes with several other antineoplastic drugs, including dasatinib, midostaurin, and bortezomib, in producing apoptosis and/or growth arrest in neoplastic MC. Together, obatoclax exerts major growth-inhibitory effects on neoplastic MC and potentiates the antineoplastic activity of other targeted drugs. Whether these drug effects can be translated to application in patients with advanced SM remains to be determined.

  18. Critical Function of PRDM2 in the Neoplastic Growth of Testicular Germ Cell Tumors

    Directory of Open Access Journals (Sweden)

    Erika Di Zazzo

    2016-12-01

    Full Text Available Testicular germ cell tumors (TGCTs derive from primordial germ cells. Their maturation is blocked at different stages, reflecting histological tumor subtypes. A common genetic alteration in TGCT is a deletion of the chromosome 1 short arm, where the PRDM2 gene, belonging to the Positive Regulatory domain gene (PRDM family, is located. Expression of PRDM2 gene is shifted in different human tumors, where the expression of the two principal protein forms coded by PRDM2 gene, RIZ1 and RIZ2, is frequently unbalanced. Therefore, PRDM2 is actually considered a candidate tumor suppressor gene in different types of cancer. Although recent studies have demonstrated that PRDM gene family members have a pivotal role during the early stages of testicular development, no information are actually available on the involvement of these genes in TGCTs. In this article we show by qRT-PCR analysis that PRDM2 expression level is modulated by proliferation and differentiation agents such as estradiol, whose exposure during fetal life is probably an important risk factor for TGCTs development in adulthood. Furthermore in normal and cancer germ cell lines, PRDM2 binds estradiol receptor α (ERα and influences proliferation, survival and apoptosis, as previously reported using MCF-7 breast cancer cell line, suggesting a potential tumor-suppressor role in TGCT formation.

  19. Progress of Neoplastic Fever: Diagnosis and Treatment%肿瘤性发热的诊治进展

    Institute of Scientific and Technical Information of China (English)

    陈衍智

    2012-01-01

    Fever occurs frequently in cancer patients, thus, it is very important to determine the etiology of fever in cancer patients.Neoplastic fever ( NF ) is a paraneoplastic syndrome caused by cancer itself, although the pathophysiology of NF remains uncertain.Research aimed at elucidating the mechanisms involved suggests the possible role of inflammatory cytokines that are released by cancer cells. Other mechanisms include tumor necrosis, which may be associated with the release of pyrogens from dead tissue. NF is a diagnosis of exclusion, that is, it can be suspected only after excluding identifiable etiologies. The naproxen test can be used to aid in the differentiation of NF from non-neoplastic fever. Once the diagnosis is established, disease-specific palliative chemotherapy and surgery may control NF, wherein naproxen and other anti-inflammatory agents can be effective for symptom palliation. The efficacy of the treatment was from 82% to 90%. However, if naproxen is used, the potential benefit of symptomatic palliation should be weighed against possible side effects like gastritis and gastrointestinal bleeding, as well as additional relative contraindications, such as cardiac,renal, and hepatic dysfunction.%肿瘤性发热是指由肿瘤本身所引起的发热,其发生的病理生理机制仍不清楚,可能与肿瘤细胞分泌的致热原有关,也可能与肿瘤坏死物质吸收有关.肿瘤性发热的诊断实际上是一个排除性诊断,即对发热的患者进行详尽的评估,如病史以及必要的理化检查,并排除其他原因的发热后,才考虑诊断为肿瘤性发热.非甾体抗炎药如萘普生有助于区别肿瘤性发热和非肿瘤性发热.一旦确诊为肿瘤性发热,包括手术、化疗在内的抗肿瘤治疗手段均有助于控制肿瘤性发热,萘普生及其他的非甾体抗炎药可以有效地缓解和控制肿瘤性发热,有效率为82%~90%,若长期使用,可出现胃炎以及胃肠道出血的风险.

  20. Quantitative evaluation of DNA methylation patterns for ALVE and TVB genes in a neoplastic disease susceptible and resistant chicken model.

    Directory of Open Access Journals (Sweden)

    Ying Yu

    Full Text Available Chicken endogenous viruses, ALVE (Avian Leukosis Virus subgroup E, are inherited as LTR (long terminal repeat retrotransposons, which are negatively correlated with disease resistance, and any changes in DNA methylation may contribute to the susceptibility to neoplastic disease. The relationship between ALVE methylation status and neoplastic disease in the chicken is undefined. White Leghorn inbred lines 7(2 and 6(3 at the ADOL have been respectively selected for resistance and susceptibility to tumors that are induced by avian viruses. In this study, the DNA methylation patterns of 3 approximately 6 CpG sites of four conserved regions in ALVE, including one unique region in ALVE1, the promoter region in the TVB (tumor virus receptor of ALV subgroup B, D and E locus, were analyzed in the two lines using pyrosequencing methods in four tissues, i.e., liver, spleen, blood and hypothalamus. A significant CpG hypermethylation level was seen in line 7(2 in all four tissues, e.g., 91.86 +/- 1.63% for ALVE region2 in blood, whereas the same region was hemimethylated (46.16 +/- 2.56% in line 6(3. CpG methylation contents of the ALVE regions were significantly lower in line 6(3 than in line 7(2 in all tissues (P < 0.01 except the ALVE region 3/4 in liver. RNA expressions of ALVE regions 2 and 3 (PPT-U3 were significantly higher in line 6(3 than in line 7(2 (P < 0.01. The methylation levels of six recombinant congenic strains (RCSs closely resembled to the background line 6(3 in ALVE-region 2, which imply the methylation pattern of ALVE-region 2 may be a biomarker in resistant disease breeding. The methylation level of the promoter region in the TVB was significantly different in blood (P < 0.05 and hypothalamus (P < 0.0001, respectively. Our data disclosed a hypermethylation pattern of ALVE that may be relevant for resistance against ALV induced tumors in chickens.

  1. Neoplastic and stromal cells contribute to an extracellular matrix gene expression profile defining a breast cancer subtype likely to progress.

    Directory of Open Access Journals (Sweden)

    Tiziana Triulzi

    Full Text Available We recently showed that differential expression of extracellular matrix (ECM genes delineates four subgroups of breast carcinomas (ECM1, -2, -3- and -4 with different clinical outcome. To further investigate the characteristics of ECM signature and its impact on tumor progression, we conducted unsupervised clustering analyses in 6 additional independent datasets of invasive breast tumors from different platforms for a total of 643 samples. Use of four different clustering algorithms identified ECM3 tumors as an independent group in all datasets tested. ECM3 showed a homogeneous gene pattern, consisting of 58 genes encoding 43 structural ECM proteins. From 26 to 41% of the cases were ECM3-enriched, and analysis of datasets relevant to gene expression in neoplastic or corresponding stromal cells showed that both stromal and breast carcinoma cells can coordinately express ECM3 genes. In in vitro experiments, β-estradiol induced ECM3 gene production in ER-positive breast carcinoma cell lines, whereas TGFβ induced upregulation of the genes leading to ECM3 gene classification, especially in ER-negative breast carcinoma cells and in fibroblasts. Multivariate analysis of distant metastasis-free survival in untreated breast tumor patients revealed a significant interaction between ECM3 and histological grade (p = 0.001. Cox models, estimated separately in grade I-II and grade III tumors, indicated a highly significant association between ECM3 and worse survival probability only in grade III tumors (HR = 3.0, 95% CI = 1.3-7.0, p = 0.0098. Gene Set Enrichment analysis of ECM3 compared to non-ECM3 tumors revealed significant enrichment of epithelial-mesenchymal transition (EMT genes in both grade I-II and grade III subsets of ECM3 tumors. Thus, ECM3 is a robust cluster that identifies breast carcinomas with EMT features but with accelerated metastatic potential only in the undifferentiated (grade III phenotype. These findings support the

  2. The role of dynamic susceptibility contrast-enhanced perfusion MR imaging in differentiating between infectious and neoplastic focal brain lesions: results from a cohort of 100 consecutive patients.

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    Valdeci Hélio Floriano

    Full Text Available BACKGROUND AND PURPOSE: Differentiating between infectious and neoplastic focal brain lesions that are detected by conventional structural magnetic resonance imaging (MRI may be a challenge in routine practice. Brain perfusion-weighted MRI (PWI may be employed as a complementary non-invasive tool, providing relevant data on hemodynamic parameters, such as the degree of angiogenesis of lesions. We aimed to employ dynamic susceptibility contrast-enhanced perfusion MR imaging (DSC-MRI to differentiate between infectious and neoplastic brain lesions by investigating brain microcirculation changes. MATERIALS AND METHODS: DSC-MRI perfusion studies of one hundred consecutive patients with non-cortical neoplastic (n = 54 and infectious (n = 46 lesions were retrospectively assessed. MRI examinations were performed using a 1.5-T scanner. A preload of paramagnetic contrast agent (gadolinium was administered 30 seconds before acquisition of dynamic images, followed by a standard dose 10 seconds after starting imaging acquisitions. The relative cerebral blood volume (rCBV values were determined by calculating the regional cerebral blood volume in the solid areas of lesions, normalized to that of the contralateral normal-appearing white matter. Discriminant analyses were performed to determine the cutoff point of rCBV values that would allow the differentiation of neoplastic from infectious lesions and to assess the corresponding diagnostic performance of rCBV when using this cutoff value. RESULTS: Neoplastic lesions had higher rCBV values (4.28±2.11 than infectious lesions (0.63±0.49 (p<0.001. When using an rCBV value <1.3 as the parameter to define infectious lesions, the sensitivity of the method was 97.8% and the specificity was 92.6%, with a positive predictive value of 91.8%, a negative predictive value of 98.0%, and an accuracy of 95.0%. CONCLUSION: PWI is a useful complementary tool in distinguishing between infectious and neoplastic brain

  3. Chronic Trichuris muris infection causes neoplastic change in the intestine and exacerbates tumour formation in APC min/+ mice.

    Directory of Open Access Journals (Sweden)

    Kelly S Hayes

    2017-06-01

    Full Text Available Incidences of infection-related cancers are on the rise in developing countries where the prevalence of intestinal nematode worm infections are also high. Trichuris muris (T. muris is a murine gut-dwelling nematode that is the direct model for human T. trichiura, one of the major soil-transmitted helminth infections of humans. In order to assess whether chronic infection with T. muris does indeed influence the development of cancer hallmarks, both wild type mice and colon cancer model (APC min/+ mice were infected with this parasite. Parasite infection in wild type mice led to the development of neoplastic change similar to that seen in mice that had been treated with the carcinogen azoxymethane. Additionally, both chronic and acute infection in the APCmin/+ mice led to an enhanced tumour development that was distinct to the site of infection suggesting systemic control. By blocking the parasite induced T regulatory response in these mice, the increase in the number of tumours following infection was abrogated. Thus T. muris infection alone causes an increase in gut pathologies that are known to be markers of cancer but also increases the incidence of tumour formation in a colon cancer model. The influence of parasitic worm infection on the development of cancer may therefore be significant.

  4. Chronic Trichuris muris infection causes neoplastic change in the intestine and exacerbates tumour formation in APC min/+ mice.

    Science.gov (United States)

    Hayes, Kelly S; Cliffe, Laura J; Bancroft, Alison J; Forman, Simon P; Thompson, Seona; Booth, Cath; Grencis, Richard K

    2017-06-01

    Incidences of infection-related cancers are on the rise in developing countries where the prevalence of intestinal nematode worm infections are also high. Trichuris muris (T. muris) is a murine gut-dwelling nematode that is the direct model for human T. trichiura, one of the major soil-transmitted helminth infections of humans. In order to assess whether chronic infection with T. muris does indeed influence the development of cancer hallmarks, both wild type mice and colon cancer model (APC min/+) mice were infected with this parasite. Parasite infection in wild type mice led to the development of neoplastic change similar to that seen in mice that had been treated with the carcinogen azoxymethane. Additionally, both chronic and acute infection in the APCmin/+ mice led to an enhanced tumour development that was distinct to the site of infection suggesting systemic control. By blocking the parasite induced T regulatory response in these mice, the increase in the number of tumours following infection was abrogated. Thus T. muris infection alone causes an increase in gut pathologies that are known to be markers of cancer but also increases the incidence of tumour formation in a colon cancer model. The influence of parasitic worm infection on the development of cancer may therefore be significant.

  5. Fatal cases of Theileria annulata infection in calves in Portugal associated with neoplastic-like lymphoid cell proliferation

    Science.gov (United States)

    Orvalho, João; Leitão, Alexandre; Pereira, Isadora; Malta, Manuel; Mariano, Isabel; Carvalho, Tânia; Baptista, Rui; Shiels, Brian R.; Peleteiro, Maria C.

    2010-01-01

    This study was carried out to investigate fifteen cases of acute lethal infection of calves (≤ 4 months of age) by the protozoan parasite Theileria (T.) annulata in the south of Portugal. Calves developed multifocal to coalescent nodular skin lesions, similar to multicentric malignant lymphoma. Infestation with ticks (genus Hyalomma) was intense. Theileria was seen in blood and lymph node smears, and T. annulata infection was confirmed by isolation of schizont-transformed cells and sequencing of hypervariable region 4 of the 18S rRNA gene. At necropsy, hemorrhagic nodules or nodules with a hemorrhagic halo were seen, particularly in the skin, subcutaneous tissue, skeletal and cardiac muscles, pharynx, trachea and intestinal serosa. Histologically, nodules were formed by large, round, lymphoblastoid neoplastic-like cells. Immunohistochemistry (IHC) identified these cells as mostly CD3 positive T lymphocytes and MAC387 positive macrophages. A marker for B lymphocytes (CD79αcy) labeled very few cells. T. annulata infected cells in these nodules were also identified by IHC through the use of two monoclonal antibodies (1C7 and 1C12) which are diagnostic for the parasite. It was concluded that the pathological changes observed in the different organs and tissues were caused by proliferation of schizont-infected macrophages, which subsequently stimulate a severe uncontrolled proliferation of uninfected T lymphocytes. PMID:20195062

  6. Telomere length in non-neoplastic colonic mucosa in ulcerative colitis (UC) and its relationship to the severe clinical phenotypes.

    Science.gov (United States)

    Tahara, Tomomitsu; Shibata, Tomoyuki; Okubo, Masaaki; Kawamura, Tomohiko; Sumi, Kazuya; Ishizuka, Takamitsu; Nakamura, Masakatsu; Nagasaka, Mitsuo; Nakagawa, Yoshihito; Ohmiya, Naoki; Arisawa, Tomiyasu; Hirata, Ichiro

    2015-08-01

    Telomere shortening occurs with human aging in many organs and tissues and is accelerated by rapid cell turnover and oxidative injury. To clarify the clinical importance of telomere shortening in colonic mucosa in ulcerative colitis (UC), we measured average telomere length using quantitative real-time PCR in non-neoplastic colonic mucosa in UC patients and assessed its relationship to various clinical subtypes. Relative telomere length in genomic DNA was measured in colonic biopsies obtained from rectal inflammatory mucosa from 86 UC patients as well as paired non-inflammatory proximal colonic mucosae from 10 patients. Data were correlated with various clinical phenotypes. In paired samples, average relative telomere length of rectal inflammatory mucosa was shortened compared to normal appearing proximal colon in eight out of ten cases (p = 0.01). Telomere length shortening was significantly associated with more severe Mayo endoscopic subscore (p telomere length was significantly shortened in the same phenotypes than the others (p = 0.003). Telomere shortening is associated with more severe clinical phenotypes of UC, reflecting severe inflammatory state in the colonic mucosa.

  7. Expression of ZFX gene correlated with the central features of the neoplastic phenotype in human brain tumors with distinct phenotypes.

    Science.gov (United States)

    Afzali, Azita; Emadi-Baygi, Modjtaba; Nikpour, Parvaneh; Nazemroaya, Fatemehe; Kheirollahi, Majid

    2015-01-01

    The zinc finger transcription factor zinc finger protein, X-linked (ZFX) acts as an important director of self-renewal in several stem cell types. Moreover, ZFX expression abnormally increases in various cancers and relates to tumor grade. We performed this study, to examine its role in the pathogenesis of astrocytoma and meningioma. We used real-time reverse transcription polymerase chain reaction method for evaluation of ZFX expression in 25 astrocytoma tumoral tissue and 25 meningioma tumoral tissues with different WHO grades. Furthermore, the association of gene expression with various clinic-pathological characteristics was examined. We found that there is a significant association between gene expression and different tumor grades, the presence or absence of invasion, forming and nonforming of glomeruloid vessels, the age over or under 50 and the presence or absence of calcification in astrocytomas. This is the first report that shows that ZFX was directly correlated with the central features of the neoplastic phenotype, including the growth of cancer cells, angiogenesis, and invasion. Regarding all the above-mentioned studies, it is highly plausible that silencing the expression of ZFX gene in gliomas has a major role in the therapeutic interventions of the disease in future.

  8. Concanavalin A: A potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis for cancer therapeutics

    Energy Technology Data Exchange (ETDEWEB)

    Li, Wen-wen; Yu, Jia-ying; Xu, Huai-long [School of Life Sciences and State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610064 (China); Bao, Jin-ku, E-mail: jinkubao@yahoo.com [School of Life Sciences and State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610064 (China)

    2011-10-22

    Highlights: {yields} ConA induces cancer cell death targeting apoptosis and autophagy. {yields} ConA inhibits cancer cell angiogenesis. {yields} ConA is utilized in pre-clinical and clinical trials. -- Abstract: Concanavalin A (ConA), a Ca{sup 2+}/Mn{sup 2+}-dependent and mannose/glucose-binding legume lectin, has drawn a rising attention for its remarkable anti-proliferative and anti-tumor activities to a variety of cancer cells. ConA induces programmed cell death via mitochondria-mediated, P73-Foxo1a-Bim apoptosis and BNIP3-mediated mitochondrial autophagy. Through IKK-NF-{kappa}B-COX-2, SHP-2-MEK-1-ERK, and SHP-2-Ras-ERK anti-angiogenic pathways, ConA would inhibit cancer cell survival. In addition, ConA stimulates cell immunity and generates an immune memory, resisting to the same genotypic tumor. These biological findings shed light on new perspectives of ConA as a potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis in pre-clinical or clinical trials for cancer therapeutics.

  9. American College of Medical Genetics and Genomics technical standards and guidelines: microarray analysis for chromosome abnormalities in neoplastic disorders.

    Science.gov (United States)

    Cooley, Linda D; Lebo, Matthew; Li, Marilyn M; Slovak, Marilyn L; Wolff, Daynna J

    2013-06-01

    Microarray methodologies, to include array comparative genomic hybridization and single-nucleotide polymorphism-based arrays, are innovative methods that provide genomic data. These data should be correlated with the results from the standard methods, chromosome and/or fluorescence in situ hybridization, to ascertain and characterize the genomic aberrations of neoplastic disorders, both liquid and solid tumors. Over the past several decades, standard methods have led to an accumulation of genetic information specific to many neoplasms. This specificity is now used for the diagnosis and classification of neoplasms. Cooperative studies have revealed numerous correlations between particular genetic aberrations and therapeutic outcomes. Molecular investigation of chromosomal abnormalities identified by standard methods has led to discovery of genes, and gene function and dysfunction. This knowledge has led to improved therapeutics and, in some disorders, targeted therapies. Data gained from the higher-resolution microarray methodologies will enhance our knowledge of the genomics of specific disorders, leading to more effective therapeutic strategies. To assist clinical laboratories in validation of the methods, their consistent use, and interpretation and reporting of results from these microarray methodologies, the American College of Medical Genetics and Genomics has developed the following professional standard and guidelines.

  10. Antioxidants impair anti-tumoral effects of Vorinostat, but not anti-neoplastic effects of Vorinostat and caspase-8 downregulation.

    Science.gov (United States)

    Bergadà, Laura; Yeramian, Andree; Sorolla, Annabel; Matias-Guiu, Xavier; Dolcet, Xavier

    2014-01-01

    We have recently demonstrated that histone deacetylase inhibitor, Vorinostat, applied as a single therapy or in combination with caspase-8 downregulation exhibits high anti-tumoral activity on endometrial carcinoma cell lines. In the present study, we have assessed the signalling processes underlying anti-tumoral effects of Vorinostat. Increasing evidence suggests that reactive oxygen species are responsible for histone deacetylase inhibitor-induced cell killing. We have found that Vorinostat induces formation of reactive oxygen species and DNA damage. To investigate the role of oxidative stress as anti-neoplastic mechanism, we have evaluated the effects of different antioxidants (Bha, Nac and Tiron) on endometrial carcinoma cell line Ishikawa treated with Vorinostat. We show that Bha, Nac and Tiron markedly inhibited the cytotoxic effects of Vorinostat, increasing cell viability in vitro. We found that all three antioxidants did not inhibited accumulation of acetyl Histone H4, so that antioxidants did not inhibit Vorinostat activity. Finally, we have evaluated the effects of antioxidants on anti-tumoral activity of Vorinostat as monotherapy or in combination with caspase-8 downregulation in vivo. Interestingly, antioxidants blocked the reduction of tumour growth caused by Vorinostat, but they were unable to inhibit anti-tumoral activity of Vorinostat plus caspase-8 inhibition.

  11. Antioxidants impair anti-tumoral effects of Vorinostat, but not anti-neoplastic effects of Vorinostat and caspase-8 downregulation.

    Directory of Open Access Journals (Sweden)

    Laura Bergadà

    Full Text Available We have recently demonstrated that histone deacetylase inhibitor, Vorinostat, applied as a single therapy or in combination with caspase-8 downregulation exhibits high anti-tumoral activity on endometrial carcinoma cell lines. In the present study, we have assessed the signalling processes underlying anti-tumoral effects of Vorinostat. Increasing evidence suggests that reactive oxygen species are responsible for histone deacetylase inhibitor-induced cell killing. We have found that Vorinostat induces formation of reactive oxygen species and DNA damage. To investigate the role of oxidative stress as anti-neoplastic mechanism, we have evaluated the effects of different antioxidants (Bha, Nac and Tiron on endometrial carcinoma cell line Ishikawa treated with Vorinostat. We show that Bha, Nac and Tiron markedly inhibited the cytotoxic effects of Vorinostat, increasing cell viability in vitro. We found that all three antioxidants did not inhibited accumulation of acetyl Histone H4, so that antioxidants did not inhibit Vorinostat activity. Finally, we have evaluated the effects of antioxidants on anti-tumoral activity of Vorinostat as monotherapy or in combination with caspase-8 downregulation in vivo. Interestingly, antioxidants blocked the reduction of tumour growth caused by Vorinostat, but they were unable to inhibit anti-tumoral activity of Vorinostat plus caspase-8 inhibition.

  12. Mesenchymal Tumors Can Derive from Ng2/Cspg4-Expressing Pericytes with β-Catenin Modulating the Neoplastic Phenotype

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    Shingo Sato

    2016-07-01

    Full Text Available The cell of origin for most mesenchymal tumors is unclear. One cell type that contributes to this lineages is the pericyte, a cell expressing Ng2/Cspg4. Using lineage tracing, we demonstrated that bone and soft tissue sarcomas driven by the deletion of the Trp53 tumor suppressor, or desmoid tumors driven by a mutation in Apc, can derive from cells expressing Ng2/Cspg4. Deletion of the Trp53 tumor suppressor gene in these cells resulted in the bone and soft tissue sarcomas that closely resemble human sarcomas, while stabilizing β-catenin in this same cell type caused desmoid tumors. Comparing expression between Ng2/Cspg4-expressing pericytes lacking Trp53 and sarcomas that arose from deletion of Trp53 showed inhibition of β-catenin signaling in the sarcomas. Activation of β-catenin inhibited the formation and growth of sarcomas. Thus, pericytes can be a cell of origin for mesenchymal tumors, and β-catenin dysregulation plays an important role in the neoplastic phenotype.

  13. Mesenchymal Tumors Can Derive from Ng2/Cspg4-Expressing Pericytes with β-Catenin Modulating the Neoplastic Phenotype.

    Science.gov (United States)

    Sato, Shingo; Tang, Yuning J; Wei, Qingxia; Hirata, Makoto; Weng, Angela; Han, Ilkyu; Okawa, Atsushi; Takeda, Shu; Whetstone, Heather; Nadesan, Puvindran; Kirsch, David G; Wunder, Jay S; Alman, Benjamin A

    2016-07-26

    The cell of origin for most mesenchymal tumors is unclear. One cell type that contributes to this lineages is the pericyte, a cell expressing Ng2/Cspg4. Using lineage tracing, we demonstrated that bone and soft tissue sarcomas driven by the deletion of the Trp53 tumor suppressor, or desmoid tumors driven by a mutation in Apc, can derive from cells expressing Ng2/Cspg4. Deletion of the Trp53 tumor suppressor gene in these cells resulted in the bone and soft tissue sarcomas that closely resemble human sarcomas, while stabilizing β-catenin in this same cell type caused desmoid tumors. Comparing expression between Ng2/Cspg4-expressing pericytes lacking Trp53 and sarcomas that arose from deletion of Trp53 showed inhibition of β-catenin signaling in the sarcomas. Activation of β-catenin inhibited the formation and growth of sarcomas. Thus, pericytes can be a cell of origin for mesenchymal tumors, and β-catenin dysregulation plays an important role in the neoplastic phenotype.

  14. Histopathological and Immunohistochemical Characterization of Methyl Eugenol-induced Nonneoplastic and Neoplastic Neuroendocrine Cell Lesions in Glandular Stomach of Rats.

    Science.gov (United States)

    Janardhan, Kyathanahalli S; Rebolloso, Yvette; Hurlburt, Geoffrey; Olson, David; Lyght, Otis; Clayton, Natasha P; Gruebbel, Margarita; Picut, Catherine; Shackelford, Cynthia; Herbert, Ronald A

    2015-07-01

    Methyl eugenol induces neuroendocrine (NE) cell hyperplasia and tumors in F344/N rat stomach. Detailed histopathological and immunohistochemical (IHC) characterization of these tumors has not been previously reported. The objective of this study was to fill that data gap. Archived slides and paraffin blocks were retrieved from the National Toxicology Program Archives. NE hyperplasias and tumors were stained with chromogranin A, synaptophysin, amylase, gastrin, H(+)/K(+) adenosine triphosphatase (ATPase), pepsinogen, somatostatin, and cytokeratin 18 (CK18) antibodies. Many of the rats had gastric mucosal atrophy, due to loss of chief and parietal cells. The hyperplasias and tumors were confined to fundic stomach, and females were more affected than the males. Hyperplasia of NE cells was not observed in the pyloric region. Approximately one-third of the females with malignant NE tumors had areas of pancreatic acinar differentiation. The rate of metastasis was 21%, with liver being the most common site of metastasis. Immunohistochemically, the hyperplasias and tumors stained consistently with chromogranin A and synaptophysin. Neoplastic cells were also positive for amylase and CK18 and negative for gastrin, somatostatin, H(+)/K(+) ATPase, and pepsinogen. Metastatic neoplasms histologically similar to the primary neoplasm stained positively for chromogranin A and synaptophysin. Based on the histopathological and IHC features, the neoplasms appear to arise from enterochromaffin-like cells.

  15. Spectrum of mucin-producing neoplastic conditions of the abdomen and pelvis: Cross-sectional imaging evaluation

    Institute of Scientific and Technical Information of China (English)

    Nam Kyung Lee; Suk Kim; Hyun Sung Kim; Tae Yong Jeon; Gwang Ha Kim; Dong Uk Kim; Do Youn Park; Tae Un Kim; Dae Hwan Kang

    2011-01-01

    Various mucin-producing neoplasms originate in differ-ent abdominal and pelvic organs. Mucinous neoplasms differ from non-mucinous neoplasms because of the differences in clinical outcome and imaging appear-ance. Mucinous carcinoma, in which at least 50% of the tumor is composed of large pools of extracellular mucin and columns of malignant cells, is associated with a worse prognosis. Signet ring cell carcinoma is characterized by large intracytoplasmic mucin vacuoles that expand in the malignant cells with the nucleus displaced to the periphery. Its prognosis is also gener-ally poor. In contrast, intraductal papillary mucinous neoplasm of the bile duct and pancreas, which is characterized by proliferation of ductal epithelium and variable mucin production, has a better prognosis than other malignancies in the pancreaticobiliary tree. Im-aging modalities play a critical role in differentiating mucinous from non-mucinous neoplasms. Due to high water content, mucin has a similar appearance to wa-ter on ultrasound (US), computed tomography (CT), and magnetic resonance imaging, except when thick and proteinaceous, and then it tends to be hypoechoic with fine internal echoes or have complex echogenicity on US, hyperdense on CT, and hyperintense on T1- and hypointense on T2-weighted images, compared to water. Therefore, knowledge of characteristic mucin imaging features is helpful to diagnose various mucin-producing neoplastic conditions and to facilitate appro-priate treatment.

  16. Regulation of Hippo signaling by Jun kinase signaling during compensatory cell proliferation and regeneration, and in neoplastic tumors.

    Science.gov (United States)

    Sun, Gongping; Irvine, Kenneth D

    2011-02-01

    When cells undergo apoptosis, they can stimulate the proliferation of nearby cells, a process referred to as compensatory cell proliferation. The stimulation of proliferation in response to tissue damage or removal is also central to epimorphic regeneration. The Hippo signaling pathway has emerged as an important regulator of growth during normal development and oncogenesis from Drosophila to humans. Here we show that induction of apoptosis in the Drosophila wing imaginal disc stimulates activation of the Hippo pathway transcription factor Yorkie in surviving and nearby cells, and that Yorkie is required for the ability of the wing to regenerate after genetic ablation of the wing primordia. Induction of apoptosis activates Yorkie through the Jun kinase pathway, and direct activation of Jun kinase signaling also promotes Yorkie activation in the wing disc. We also show that depletion of neoplastic tumor suppressor genes, including lethal giant larvae and discs large, or activation of aPKC, activates Yorkie through Jun kinase signaling, and that Jun kinase activation is necessary, but not sufficient, for the disruption of apical-basal polarity associated with loss of lethal giant larvae. Our observations identify Jnk signaling as a modulator of Hippo pathway activity in wing imaginal discs, and implicate Yorkie activation in compensatory cell proliferation and disc regeneration.

  17. Antioxidants Impair Anti-Tumoral Effects of Vorinostat, but Not Anti-Neoplastic Effects of Vorinostat and Caspase-8 Downregulation

    Science.gov (United States)

    Bergadà, Laura; Yeramian, Andree; Sorolla, Annabel

    2014-01-01

    We have recently demonstrated that histone deacetylase inhibitor, Vorinostat, applied as a single therapy or in combination with caspase-8 downregulation exhibits high anti-tumoral activity on endometrial carcinoma cell lines. In the present study, we have assessed the signalling processes underlying anti-tumoral effects of Vorinostat. Increasing evidence suggests that reactive oxygen species are responsible for histone deacetylase inhibitor-induced cell killing. We have found that Vorinostat induces formation of reactive oxygen species and DNA damage. To investigate the role of oxidative stress as anti-neoplastic mechanism, we have evaluated the effects of different antioxidants (Bha, Nac and Tiron) on endometrial carcinoma cell line Ishikawa treated with Vorinostat. We show that Bha, Nac and Tiron markedly inhibited the cytotoxic effects of Vorinostat, increasing cell viability in vitro. We found that all three antioxidants did not inhibited accumulation of acetyl Histone H4, so that antioxidants did not inhibit Vorinostat activity. Finally, we have evaluated the effects of antioxidants on anti-tumoral activity of Vorinostat as monotherapy or in combination with caspase-8 downregulation in vivo. Interestingly, antioxidants blocked the reduction of tumour growth caused by Vorinostat, but they were unable to inhibit anti-tumoral activity of Vorinostat plus caspase-8 inhibition. PMID:24651472

  18. MYC through miR-17-92 Suppresses Specific Target Genes to Maintain Survival, Autonomous Proliferation, and a Neoplastic State

    KAUST Repository

    Li, Yulin

    2014-08-01

    The MYC oncogene regulates gene expression through multiple mechanisms, and its overexpression culminates in tumorigenesis. MYC inactivation reverses turmorigenesis through the loss of distinguishing features of cancer, including autonomous proliferation and survival. Here we report that MYC via miR-17-92 maintains a neoplastic state through the suppression of chromatin regulatory genes Sin3b, Hbp1, Suv420h1, and Btg1, as well as the apoptosis regulator Bim. The enforced expression of miR-17-92 prevents MYC suppression from inducing proliferative arrest, senescence, and apoptosis and abrogates sustained tumor regression. Knockdown of the five miR-17-92 target genes blocks senescence and apoptosis while it modestly delays proliferative arrest, thus partially recapitulating miR-17-92 function. We conclude that MYC, via miR-17-92, maintains a neoplastic state by suppressing specific target genes.

  19. Three-Dimensional Printing as an Interdisciplinary Communication Tool: Preparing for Removal of a Giant Renal Tumor and Atrium Neoplastic Mass.

    Science.gov (United States)

    Golab, Adam; Slojewski, Marcin; Brykczynski, Miroslaw; Lukowiak, Magdalena; Boehlke, Marek; Matias, Daniel; Smektala, Tomasz

    2016-08-22

    Three-dimensional (3D) printing involves preparing 3D objects from a digital model. These models can be used to plan and practice surgery. We used 3D printing to plan for a rare complicated surgery involving the removal of a renal tumor and neoplastic mass, which reached the heart atrium. A printed kidney model was an essential element of communication for physicians with different specializations.

  20. Delivery of granulocyte-macrophage colony-stimulating factor in bioadhesive hydrogel stimulates migration of dendritic cells in models human papillomavirus-associated (pre)neoplastic epithelial lesions

    OpenAIRE

    Hubert, Pascale; Evrard, Brigitte; Maillard, Catherine; Franzen-Detrooz, E.; Delattre, Luc; Foidart, Jean-Michel; Noël, Agnès; Boniver, Jacques; Delvenne, Philippe

    2004-01-01

    Because of the central role of dendritic cells and/or Langerhans cells(DC/LC) in the induction of cellular immune responses, pharmacological agents that modulate the recruitment of these cells might have a clinical interest. The present study was designed to evaluate the capacity of several pharmaceutical formulations to topically deliver granulocyte-macrophage colony-stimulating factor (GM-CSF) on human papillomavirus (HPV)-associated genital (pre)neoplastic lesions. The formulations were ev...

  1. Differentiation of osteoporotic and neoplastic vertebral fractures by chemical shift {l_brace}in-phase and out-of phase{r_brace} MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ragab, Yasser [Radiology Department, Faculty of Medicine, Cairo University (Egypt); Radiology Department, Dr Erfan and Bagedo General Hospital (Saudi Arabia)], E-mail: yragab61@hotmail.com; Emad, Yasser [Rheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University (Egypt); Rheumatology and Rehabilitation Department, Dr Erfan and Bagedo General Hospital (Saudi Arabia)], E-mail: yasseremad68@yahoo.com; Gheita, Tamer [Rheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University (Egypt)], E-mail: gheitamer@yahoo.com; Mansour, Maged [Oncology Department, Faculty of Medicine, Cairo University (Egypt); Oncology Department, Dr Erfan and Bagedo General Hospital (Saudi Arabia)], E-mail: magedmansour@yahoo.com; Abou-Zeid, A. [Public Health Department, Faculty of Medicine, Cairo University, Cairo (Egypt)], E-mail: alaabouzeid@yahoo.com; Ferrari, Serge [Division of Bone Diseases, Department of Rehabilitation and Geriatrics, and WHO, Collaborating Center for Osteoporosis Prevention, Geneva University Hospital (Switzerland)], E-mail: serge.ferrari@medecine.unige.ch; Rasker, Johannes J. [Rheumatologist University of Twente, Enschede (Netherlands)], E-mail: j.j.rasker@utwente.nl

    2009-10-15

    Objective: The objective of this study was to establish the cut-off value of the signal intensity drop on chemical shift magnetic resonance imaging (MRI) with appropriate sensitivity and specificity to differentiate osteoporotic from neoplastic wedging of the spine. Patients and methods: All patients with wedging of vertebral bodies were included consecutively between February 2006 and January 2007. A chemical shift MRI was performed and signal intensity after (in-phase and out-phase) images were obtained. A DXA was performed in all. Results: A total of 40 patients were included, 20 with osteoporotic wedging (group 1) and 20 neoplastic (group 2). They were 21 males and 19 females. Acute vertebral collapse was observed in 15 patients in group 1 and subacute collapse in another 5 patients, while in group 2, 11 patients showed acute collapse and 9 patients (45%) showed subacute vertebral collapse. On the chemical shift MRI a substantial reduction in signal intensity was found in all lesions in both groups. The proportional changes observed in signal intensity of bone marrow lesions on in-phase compared with out-of-phase images showed significant differences in both groups (P < 0.05). At a cut-off value of 35%, the observed sensitivity of out-of-phase images was 95%, specificity was 100%, positive predictive value was 100% and negative predictive value was 95.2%. Conclusion: A chemical shift MRI is useful in order to differentiate patients with vertebral collapse due to underlying osteoporosis or neoplastic process.

  2. CLINICO - PATHOLOGICAL STUDY OF NON - NEOPLASTIC LESIONS IN SINO - NASAL CAVITY OF PATIENTS ATTENDING CIMS, BILASPUR (C. G.: A RETROSPECTIVE STUDY

    Directory of Open Access Journals (Sweden)

    Arya

    2015-10-01

    Full Text Available INTRODUCTION : The present study examined the patterns of sinonasal masses in biopsies received in department of pathology of Govt. CIMS, Bilaspur which is a tertiary care hospital of central eastern region of India and represents a tribal belt. During the study period, 91 biopsied reported were retrieved from the records and results analyzed. OBJECTIVE : This study is designed to find out patterns of benign lesions of nasal mass in patients attending Chhattisgarh Institute of Medical Sciences (CIMS, a teaching institute in Bilaspur Chhattisgarh. MATERIAL AND METHODS : 91 nasal biopsy records of March 2003 to August 2015 were reviewed. All the biopsy samples of patients were received and studied in department of pathology. RESULTS AND OBSERVATIONS : Average age of subjects reported as non - neoplastic lesions is found 19.69 years with standard deviation of 9.44, ranging from 6 to 47 years. Among 75 non - neoplastic lesions, 63 (84.00% reported as rhinosporidiosis, 10(13.33% non - specific inflammatory po lyp and 2 were (2.67% tuberculosis. CONCLUSION : Rhinosporidiosis encountered as most common non - neoplastic lesion and most patients affected were in younger age groups. The study concluded with the exceptionally higher prevalence of rhinosporidiosis obser ved in this region

  3. Differences in modifications of cytoplasmic free Ca2+ concentration and 86Rb+ influx in human neoplastic B cells by antibodies to mu- relative to delta-Ig heavy chains.

    Science.gov (United States)

    Heikkilä, R; Ruud, E; Funderud, S; Godal, T

    1985-01-01

    Cytoplasmic free Ca2+ concentration and influx of 86Rb+ (K+ analogue) were determined during the first minutes after stimulation of neoplastic human B cells and B cell lines by antibodies to surface Ig. The Ca2+ concentration increased in the great majority of samples (41 of 48). All of four B cell lines also responded, providing formal evidence that accessory cells are not required for this early, surface Ig-mediated event. Antibodies to delta as well as mu, heavy chains (anti-delta and anti-mu) could induce both Ca2+ and 86Rb+ responses. 86Rb+ responders were found within the group of Ca2+ responders, but no quantitative relation was observed between the two responses. In cells expressing both sIgM and sIgD, antibodies to delta heavy chains were more potent than those to mu heavy chains in inducing Ca2+ responses, whereas the opposite pattern was seen with regard to 86Rb+ responses. These results demonstrate that sIgM and sIgD can deliver different biochemical signals to the cell. PMID:3921300

  4. In vitro cytotoxicity of Selol-loaded magnetic nanocapsules against neoplastic cell lines under AC magnetic field activation

    Science.gov (United States)

    Falqueiro, A. M.; Siqueira-Moura, M. P.; Jardim, D. R.; Primo, F. L.; Morais, P. C.; Mosiniewicz-Szablewska, E.; Suchocki, P.; Tedesco, A. C.

    2012-04-01

    The goals of this study are to evaluate invitro compatibility of magnetic nanomaterials and their therapeutic potential against cancer cells. Highly stable ionic magnetic fluid sample (maghemite, γ-Fe2O3) and Selol were incorporated into polymeric nanocapsules by nanoprecipitation method. The cytotoxic effect of Selol-loaded magnetic nanocapsules was assessed on murine melanoma (B16-F10) and oral squamous cell carcinoma (OSCC) cell lines following AC magnetic field application. The influence of different nanocapsules on cell viability was investigated by colorimetric MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. In the absence of AC magnetic field Selol-loaded magnetic nanocapsules, containing 100 µg/mL Selol plus 5 × 1012 particle/mL, showed antitumoral activity of about 50% on B16-F10 melanoma cells while OSCC carcinoma cells demonstrated drug resistance at all concentrations of Selol and magnetic fluid (range of 100-500 µg/mL Selol and 5 × 1012-2.5 × 1013 particle/mL). On the other hand, under AC applied fields (1 MHz and 40 Oe amplitude) B16-F10 cell viability was reduced down to 40.5% (±3.33) at the highest concentration of nanoencapsulated Selol. The major effect, however, was observed on OSCC cells since the cell viability drops down to about 33.3% (±0.38) under application of AC magnetic field. These findings clearly indicate that the Selol-loaded magnetic nanocapsules present different toxic effects on neoplastic cell lines. Further, the cytotoxic effect was maximized under AC magnetic field application on OSCC, which emphasizes the effectiveness of the magnetohyperthermia approach.

  5. Anti free radical action of calcium antagonists and H1 and H2 receptors antagonists in neoplastic disease.

    Science.gov (United States)

    della Rovere, F; Broccio, M; Granata, A; Zirilli, A; Brugnano, L; Artemisia, A; Broccio, G

    1996-01-01

    The blood of the subjects suffering from Neoplastic Disease (ND) shows phenomena of membrane peroxidation due to the presence of Free Radicals (FRs), in a quantity much greater than the one observed in the blood of healthy subjects. This can be detected either by calculating the time necessary for the formation of "Heinz bodies" (Hbs), (p < 0.00001) after oxidative stress of the blood in vitro with acetylphenylidrazine (APH), or by calculating the methemoglobin (metHb) quantity that forms after the same treatment (P < 0.00001). The statistical analyses we carried out showed that metHb formation was not affected by age, sex, smoking habits, red blood cell number, Hb, Ht or tumor staging. In this study, by using equal parameters of investigation, we noted that the blood of the subjects with ND who were previously treated with calcium-antagonists drugs and with antagonists of H1 and H2 receptors, gave results completely superimposable on the results obtained from healthy subjects, implying that the treatment had avoided the increase of FRs. Therefore we concluded that calcium-antagonists and the antagonists of the H1 and H2 receptors behave as antioxidant substances, having decreased the FRs damaging activity on the cellular membranes, thus controlling, although to a limited degree, the pejorative evolution of the disease. It is also important to remember that investigations into the ND, even possible screenings, must take into account the above said data, submitting the subjects under investigation to a pharmacological wash out, particularly with those substances which, are considered to be scavengers of FRs. Some of these substances are investigated in this work.

  6. Mechanisms underlying the adaptive response against spontaneous neoplastic transformation induced by low doses of low LET radiation, Final Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    J. Leslie Redpath, Ph.D.

    2006-01-23

    The goal of this project was to investigate mechanisms underlying the adaptive response seen following exposure of HeLa x skin fibroblast human hybrid cells to low doses of low LET radiation. It was proposed to investigate the contributions of three possible mechanisms. These were: 1. Upregulation of cellular antioxidant status. 2. Upregulation of DNA repair. 3. Upregulation of gap junction intracellular communication. We have completed the study of the role of upregulation of reduced glutathione (GSH) as a possible mechanism underlying our observed suppression of transformation frequency at low radiation doses. We have also completed our study of the possible role of upregulation of DNA repair in the observed adaptive response against neoplastic transformation. We concluded that upregulation of DNA repair may be more important in modulating transformation at the higher dose. A manuscript describing the above studies has been submitted published in Carcinogenesis 24:1961-1965, 2003. Finally, we have completed two studies of the possible role of upregulation of gap junction intercellular communication (GJIC) in modulating transformation frequency at low doses of low LET radiation. This research was published in Radiation Research 162:646-654, 2004. In order to optimize the opportunity for GJIC, we then carried out a study where confluent cultures were irradiated. The results indicated, that while the degree of low dose suppression was somewhat reduced compared to that seen for subconfluent cultures, it was not completely absent. This research has been submitted for publication. Our research program was of sufficient interest to generate two invited reviews, and five invited presentations.

  7. Enzymic capacities of purine de Novo and salvage pathways for nucleotide synthesis in normal and neoplastic tissues.

    Science.gov (United States)

    Natsumeda, Y; Prajda, N; Donohue, J P; Glover, J L; Weber, G

    1984-06-01

    amidophosphoribosyltransferase. The purine phosphoribosyltransferase activities were also higher than that of amidophosphoribosyltransferase in Lewis lung carcinoma (8.2- to 32-fold), human renal cell carcinoma (3.5- to 22-fold), and hepatocellular carcinoma (3.4- to 30-fold). The high activities and the high affinity to PRPP of the purine phosphoribosyltransferases might explain the lack of linkage of the behavior of these enzymic activities with proliferation in normal, regenerating, differentiating, or neoplastic tissues. In contrast, the specific activity of the amidophosphoribosyltransferase, which is lower than that of the salvage enzymes, is linked with transformation as it is increased in all examined tumors.4

  8. Systematic review of the relation between smokeless tobacco and non-neoplastic oral diseases in Europe and the United States

    Directory of Open Access Journals (Sweden)

    Weitkunat Rolf

    2008-05-01

    Full Text Available Abstract Background How smokeless tobacco contributes to non-neoplastic oral diseases is unclear. It certainly increases risk of oral mucosal lesions, but reviewers disagree as to other conditions. In some areas, especially South-East Asia, risk is difficult to quantify due to the many products, compositions (including non-tobacco ingredients, and usage practices involved. This review considers studies from Europe (in practice mainly Scandinavia and from the USA. Methods Experimental and epidemiological studies published in 1963–2007 were identified that related risk of oral lesions to smokeless tobacco use. Data were assessed separately for oral mucosal lesions, periodontal and gingival diseases, dental caries and tooth loss, and oral pain. Results Oral mucosal lesions: Thirty-three epidemiological studies consistently show a strong dose-related effect of current snuff on oral mucosal lesion prevalence. In Scandinavia, users have a near 100% prevalence of a characteristic "snuff-induced lesion", but prevalence of the varied lesions reported in the USA is lower. Associations with chewing tobacco are weaker. The lack of clear association with former use suggests reversibility following cessation, consistent with experimental studies showing rapid lesion regression on quitting. Periodontal and gingival diseases: Two of four studies report a significant association of snuff with attachment loss and four out of eight with gingival recession. Snuff is not clearly related to gingivitis or periodontal diseases. Limited evidence suggests chewing tobacco is unrelated to periodontal or gingival diseases. Tooth loss: Swedish studies show no association with snuff, but one US study reported an association with snuff, and another with chewing tobacco. Dental caries: Evidence from nine studies suggests a possible relationship with use of smokeless tobacco, particularly chewing tobacco, and the risk of dental caries. Oral pain: Limited evidence precludes any

  9. Development in treatment of vulvar intraepithelial non-neoplastic lesions%外阴上皮内非瘤样变治疗进展

    Institute of Scientific and Technical Information of China (English)

    闫星妹; 任红莲; 何淑莹

    2009-01-01

    外阴上皮内非瘤样病变是一组慢性疾病,根据1987年国际外阴疾病研究协会与国际妇科病理学家协会共同制定的新外阴皮肤疾病分类法,外阴上皮内非瘤样病变分为外阴鳞状上皮增生、外阴硬化性苔癣及其他皮肤病.因其病因不明确,临床上许多治疗方法虽能暂时控制其症状,但复发率较高.故临床医师正努力探索各种方法以提高患者的治愈率,降低复发率.该文就外阴上皮内非瘤样变治疗进展作以综述.%Vulvar intraepithelial non-neoplastic lesion is a chronic inflammatory disease of skin and mucosa in vulva. According to new classification of vular dermopathy formulated by International Vulvar Disease Research Association and International Gynecologist-pathologist Association in 1987, vulvar intraepithelial non-neoplastic lesions are classified into vulvar squamous cell hyperplasia and vulvar lichen sclerosus and other vulvar dermoses. Because etiology of the disease is unclear till now, there is no optimal therapy for it. Although many therapies can control symptoms of the disease temporarily, the recurrence rate is hight in clinic.In this paper, we summarized development in therapies of vular intraepithelial non-neoplastic lesions.

  10. Neoplastic transformation in C3H 10T(1/2) cells after exposure to 835.62 MHz FDMA and 847.74 MHz CDMA radiations.

    Science.gov (United States)

    Roti Roti JL; Malyapa, R S; Bisht, K S; Ahern, E W; Moros, E G; Pickard, W F; Straube, W L

    2001-01-01

    The effect of radiofrequency (RF) radiation in the cellular phone communication range (835.62 MHz frequency division multiple access, FDMA; 847.74 MHz code division multiple access, CDMA) on neoplastic transformation frequency was measured using the in vitro C3H 10T(1/2) cell transformation assay system. To determine if 835.62 MHz FDMA or 847.74 MHz CDMA radiations have any genotoxic effects that induce neoplastic transformation, C3H 10T(1/2) cells were exposed at 37 degrees C to either of the above radiations [each at a specific absorption rate (SAR) of 0.6 W/kg] or sham-exposed at the same time for 7 days. After the culture medium was changed, the cultures were transferred to incubators and refed with fresh growth medium every 7 days. After 42 days, the cells were fixed and stained with Giemsa, and transformed foci were scored. To determine if exposure to 835.62 MHz FDMA or 847.74 MHz CDMA radiation has any epigenetic effects that can promote neoplastic transformation, cells were first exposed to 4.5 Gy of X rays to induce the transformation process and then exposed to the above radiations (SAR = 0.6 W/kg) in temperature-controlled irradiators with weekly refeeding for 42 days. After both the 7-day RF exposure and the 42-day RF exposure after X irradiation, no statistically significant differences in the transformation frequencies were observed between incubator controls, the sham-exposed (maintained in irradiators without power to the antenna), and the 835.62 MHz FDMA or 847.74 MHz CDMA-exposed groups.

  11. A composite neoplastic lesion of the vulva with mixed features of fibroadenoma and hidradenoma papilliferum combined with pseudoangiomatous stromal hyperplasia containing multinucleated giant cells.

    Science.gov (United States)

    Konstantinova, Anastasia M; Kacerovska, Denisa; Michal, Michal; Kazakov, Dmitry V

    2014-10-01

    Anogenital mammary-like glands (AGMLG) are nowadays considered a normal component of the anogenital area. Lesions affecting AGMLG are similar to those seen in breast. We present a case of a complex neoplastic lesion of the AGMLG with mixed features of fibroadenoma and hidradenoma papilliferum combined with pseudoangiomatous stromal hyperplasia. Multinucleated cells were detected in the pseudoangiomatous stromal hyperplasia areas as seen in some patients with neurofibromatosis type 1. The neoplasm is similar to rare mammary composite neoplasms that feature simultaneously patterns of a fibroepithelial neoplasms and intraductal papilloma.

  12. A novel role for mixed-lineage kinase-like mitogen-activated protein triple kinase alpha in neoplastic cell transformation and tumor development.

    Science.gov (United States)

    Cho, Yong-Yeon; Bode, Ann M; Mizuno, Hideya; Choi, Bu Young; Choi, Hong Seok; Dong, Zigang

    2004-06-01

    Previously, no member of the mixed-lineage kinase (MLK) protein family was known to function as an oncogene. Here, we demonstrate that MLK-like mitogen-activated protein triple kinase (MLTK)-alpha, a member of the MLK family, induced neoplastic cell transformation and tumorigenesis in athymic nude mice. Introduction of small interference RNA (siRNA)-MLTK-alpha into MLTK-alpha-overexpressing cells dramatically suppressed cell transformation. Nuclear accumulation of the pHisG-MLTK-alpha fusion protein was observed after epidermal growth factor or 12-O-tetradecanoylphorbol-13-acetate treatment. Phosphorylation of downstream mitogen-activated protein kinase-targeted transcription factors including c-Myc, Elk-1, c-Jun, and activating transcription factor (ATF) 2 was also differentially enhanced in MLTK-alpha-overexpressing cells exposed to epidermal growth factor or 12-O-tetradecanoylphorbol-13-acetate stimulation compared with cells expressing mock vector or siRNA-MLTK-alpha. Very importantly, MLTK-alpha-overexpressing cells formed fibrosarcomas when injected s.c. into athymic nude mice, whereas almost no tumor formation was observed in mice that received injections of mock or siRNA-MLTK-alpha stably transfected cells. These results are the first to indicate that MLTK-alpha plays a key role in neoplastic cell transformation and cancer development.

  13. Neoplastic transformation of BALB/3T3 cells and cell cycle of HL-60 cells are inhibited by mango (Mangifera indica L.) juice and mango juice extracts.

    Science.gov (United States)

    Percival, Susan S; Talcott, Stephen T; Chin, Sherry T; Mallak, Anne C; Lounds-Singleton, Angela; Pettit-Moore, Jennifer

    2006-05-01

    The mango, Mangifera indica L., is a fruit with high levels of phytochemicals, suggesting that it might have chemopreventative properties. In this study, whole mango juice and juice extracts were screened for antioxidant and anticancer activity. Antioxidant activity of the mango juice and juice extracts was measured by 3 standard in vitro methods. The results of the 3 methods were in general agreement, although different radicals were measured in each. Anticancer activity was measured by examining the effect on cell cycle kinetics and the ability to inhibit chemically induced neoplastic transformation of mammalian cell lines. Incubation of HL-60 cells with whole mango juice and mango juice fractions resulted in an inhibition of the cell cycle in the G(0)/G(1) phase. A fraction of the eluted mango juice with low peroxyl radical scavenging ability was most effective in arresting cells in the G(0)/G(1) phase. Whole mango juice was effective in reducing the number of transformed foci in the neoplastic transformation assay in a dose-dependent manner. These techniques provide valuable screening tools for health benefits derived from mango phytochemicals.

  14. Experimental Evidence of ω-3 Polyunsaturated Fatty Acid Modulation of Inflammatory Cytokines and Bioactive Lipid Mediators: Their Potential Role in Inflammatory, Neurodegenerative, and Neoplastic Diseases

    Directory of Open Access Journals (Sweden)

    Gabriella Calviello

    2013-01-01

    Full Text Available A large body of evidence has emerged over the past years to show the critical role played by inflammation in the pathogenesis of several diseases including some cardiovascular, neoplastic, and neurodegenerative diseases, previously not considered inflammation-related. The anti-inflammatory action of ω-3 polyunsaturated fatty acids (PUFAs, as well as their potential healthy effects against the development and progression of the same diseases, has been widely studied by our and others’ laboratories. As a result, a rethinking is taking place on the possible mechanisms underlying the beneficial effects of ω-3 PUFAs against these disorders, and, in particular, on the influence that they may exert on the molecular pathways involved in inflammatory process, including the production of inflammatory cytokines and lipid mediators active in the resolving phase of inflammation. In the present review we will summarize and discuss the current knowledge regarding the modulating effects of ω-3 PUFAs on the production of inflammatory cytokines and proresolving or protective lipid mediators in the context of inflammatory, metabolic, neurodegenerative, and neoplastic diseases.

  15. Local immunosuppression induced by high viral load of human papillomavirus: characterization of cellular phenotypes producing interleukin-10 in cervical neoplastic lesions.

    Science.gov (United States)

    Prata, Thiago Theodoro Martins; Bonin, Camila Mareti; Ferreira, Alda Maria Teixeira; Padovani, Cacilda Tezelli Junqueira; Fernandes, Carlos Eurico dos Santos; Machado, Ana Paula; Tozetti, Inês Aparecida

    2015-09-01

    A specific immune response to human papillomavirus (HPV) in the cervical microenvironment plays a key role in eradicating infection and eliminating mutated cells. However, high-risk HPVs modulate immune cells to create an immunosuppressive microenvironment, and induce these immune cells to produce interleukin 10 (IL-10). This production of IL-10, in conjunction with HPV infection, contributes to the appearance of cervical neoplastic lesions. We sought to characterize the IL-10-producing cellular phenotype, and investigate the influence of host and HPV factors upon the induction of an immunosuppressive microenvironment. Immunohistochemical analysis demonstrated an increase in IL-10 production by keratinocytes, macrophages and Langerhans cells in high-grade cervical lesions and cervical cancer. This increase was more pronounced in patients older than 30 years, and was also correlated with high viral load, and infection with a single HPV type, particularly high-risk HPVs. Our results indicate the existence of a highly immunosuppressive microenvironment composed of different IL-10-producing cellular phenotypes in cervical cancer samples, and samples classified as high-grade cervical lesions (cervical intraepithelial neoplasia stages II and III). The immunosuppressive microenvironment that developed for these different cellular phenotypes favours viral persistence and neoplastic progression.

  16. Correlation between standardized uptake value and apparent diffusion coefficient of neoplastic lesions evaluated with whole-body simultaneous hybrid PET/MRI.

    Science.gov (United States)

    Rakheja, Rajan; Chandarana, Hersh; DeMello, Linda; Jackson, Kimberly; Geppert, Christian; Faul, David; Glielmi, Christopher; Friedman, Kent P

    2013-11-01

    The purpose of this study was to assess the correlation between standardized uptake value (SUV) and apparent diffusion coefficient (ADC) of neoplastic lesions in the use of a simultaneous PET/MRI hybrid system. Twenty-four patients with known primary malignancies underwent FDG PET/CT. They then underwent whole-body PET/MRI. Diffusion-weighted imaging was performed with free breathing and a single-shot spin-echo echo-planar imaging sequence with b values of 0, 350, and 750 s/mm(2). Regions of interest were manually drawn along the contours of neoplastic lesions larger than 1 cm, which were clearly identified on PET and diffusion-weighted images. Maximum SUV (SUVmax) on PET/MRI and PET/CT images, mean SUV (SUVmean), minimum ADC (ADCmin), and mean ADC (ADCmean) were recorded on PET/MR images for each FDG-avid neoplastic soft-tissue lesion with a maximum of three lesions per patient. Pearson correlation coefficient was used to asses the following relations: SUVmax versus ADCmin on PET/MR and PET/CT images, SUVmean versus ADCmean, and ratio of SUVmax to mean liver SUV (SUV ratio) versus ADCmin. A subanalysis of patients with progressive disease versus partial treatment response was performed with the ratio of SUVmax to ADCmin for the most metabolically active lesion. Sixty-nine neoplastic lesions (52 nonosseous lesions, 17 bone metastatic lesions) were evaluated. The mean SUVmax from PET/MRI was 7.0 ± 6.0; SUVmean, 5.6 ± 4.6; mean ADCmin, 1.10 ± 0.58; and mean ADCmean, 1.48 ± 0.72. A significant inverse Pearson correlation coefficient was found between PET/MRI SUVmax and ADCmin (r = -0.21, p = 0.04), between SUVmean and ADCmean (r = -0.18, p = 0.07), and between SUV ratio and ADCmin (r = -0.27, p = 0.01). A similar inverse Pearson correlation coefficient was found between the PET/CT SUVmax and ADCmin. Twenty of 24 patients had previously undergone PET/CT; five patients had a partial treatment response, and six had progressive disease according to Response Evaluation

  17. Biomarkers for Early Detection of Malignant Mesothelioma: Diagnostic and Therapeutic Application

    Directory of Open Access Journals (Sweden)

    Marco Tomasetti

    2010-04-01

    Full Text Available Malignant mesothelioma (MM is a rare and aggressive tumour of the serosal cavities linked to asbestos exposure. Improved detection methods for diagnosing this type of neoplastic disease are essential for an early and reliable diagnosis and treatment. Thus, focus has been placed on finding tumour markers for the non-invasive detection of MM. Recently, some blood biomarkers have been described as potential indicators of early and advanced MM cancers. The identification of tumour biomarkers alone or in combination could greatly facilitate the surveillance procedure for cohorts of subjects exposed to asbestos, a common phenomenon in several areas of western countries.

  18. El Instituto Nacional de Enfermedades Neoplásicas en el control del cáncer en el Perú The role of the National Institute of Neoplastic Diseases in the control of cancer in Peru

    Directory of Open Access Journals (Sweden)

    Miriam Rosario Salazar

    2013-03-01

    Full Text Available La incidencia estimada de cáncer en el Perú es de 150 casos x 100 000 habitantes. Este ocupa el segundo lugar de las causas mortalidad a nivel nacional y se estima que el 75% de los casos se diagnostican en etapa avanzada y principalmente en Lima. En ese contexto, el Instituto Nacional de Enfermedades Neoplásicas (INEN ha promovido la descentralización de la atención oncológica con la creación de los institutos regionales de enfermedades neoplásicas, las unidades oncológicas y los preventorios. Asimismo ha diseñado, desarrollado e implementado el Programa Presupuestal de Prevención y Control de Cáncer, por lo que desde el año 2011, más de 7000 establecimientos del país asignan recursos para la prevención, promoción y detección precoz de los cánceres más frecuentes en el Perú. Con el financiamiento del seguro estatal, se integraron los ejes estratégicos básicos para una atención integral del cáncer en la población de menores recursos. De esta manera y dentro de una política de estado integradora y articulada con el sector salud, nace el Plan Nacional para la Atención Integral del Cáncer y el Mejoramiento del Acceso a los Servicios Oncológicos en el Perú, denominado “Plan Esperanza”. En este artículo, desarrollamos el papel que viene cumpliendo el INEN en el control del cáncer como problema de salud pública, destacando la importancia del Programa Estratégico Presupuestal de Prevención y Control del Cáncer y de su papel en el “Plan Esperanza”With a mortality rate that constitutes the second nationwide, the estimated incidence of cancer in Peru is 150 cases x 100 000 inhabitants. Around 75% of the cases are diagnosed at an advanced stage and mainly in Lima. In this context, the National Institute of Neoplastic Diseases (INEN has promoted the decentralization of oncological care creating regional institutes of neoplastic diseases, oncological units and prevention centers. In addition, INEN has designed

  19. Pubertal bisphenol A exposure alters murine mammary stem cell function leading to early neoplasia in regenerated glands.

    Science.gov (United States)

    Wang, Danhan; Gao, Hui; Bandyopadhyay, Abhik; Wu, Anqi; Yeh, I-Tien; Chen, Yidong; Zou, Yi; Huang, Changjiang; Walter, Christi A; Dong, Qiaoxiang; Sun, Lu-Zhe

    2014-04-01

    Perinatal exposure to bisphenol A (BPA) has been shown to cause aberrant mammary gland morphogenesis and mammary neoplastic transformation. Yet, the underlying mechanism is poorly understood. We tested the hypothesis that mammary glands exposed to BPA during a susceptible window may lead to its susceptibility to tumorigenesis through a stem cell-mediated mechanism. We exposed 21-day-old Balb/c mice to BPA by gavage (25 μg/kg/d) during puberty for 3 weeks, and a subset of animals were further challenged with one oral dose (30 mg/kg) of 7,12-dimethylbenz(a)anthracene (DMBA) at 2 months of age. Primary mammary cells were isolated at 6 weeks, and 2 and 4 months of age for murine mammary stem cell (MaSC) quantification and function analysis. Pubertal exposure to the low-dose BPA increased lateral branches and hyperplasia in adult mammary glands and caused an acute increase of MaSC in 6-week-old glands and a delayed increase of luminal progenitors in 4-month-old adult gland. Most importantly, pubertal BPA exposure altered the function of MaSC from different age groups, causing early neoplastic lesions in their regenerated glands similar to those induced by DMBA exposure, which indicates that MaSCs are susceptible to BPA-induced transformation. Deep sequencing analysis on MaSC-enriched mammospheres identified a set of aberrantly expressed genes associated with early neoplastic lesions in patients with human breast cancer. Thus, our study for the first time shows that pubertal BPA exposure altered MaSC gene expression and function such that they induced early neoplastic transformation.

  20. Estudio de las lesiones neoplásicas metacrónicas en el carcinoma colorrectal Study of colorectal metachronous neoplastic lesions

    Directory of Open Access Journals (Sweden)

    A. Borda

    2009-12-01

    Full Text Available Fundamento. Analizar la frecuencia y las características de las lesiones neoplásicas metacrónicas, carcinomas y adenomas, tras la resección de un cáncer colo-rectal (CCR. Pacientes y métodos. Revisamos 382 CCR operados y seguidos mediante colonoscopias completas en dos hospitales de nuestra comunidad. Analizamos las lesiones metacrónicas registradas valorando su localización, momento del diagnóstico, histología, número y tamaño. Estudiamos la frecuencia de adenomas de aparición precoz (12 meses, comparando su tamaño con respecto al resto de lesiones. Resultados. La mediana de seguimiento fue de 48 meses (12-112, con 2,74±1,47 colonoscopias/caso. Diagnosticamos 7 cánceres metacrónicos (1,8%, 4 de ellos en estadio I. La mediana de tiempo hasta su diagnóstico fue de 24 meses (13-54. Registramos adenomas metacrónicos en 162 casos (42,4%, sin diferencias entre los dos hospitales: 42,1% vs. 43,8% (p=0,88. Un 6,3% de los pacientes presentaron adenomas avanzados. En 164 casos en que el primer control se efectuó a los 12 meses, la incidencia de adenomas fue del 24%. Los adenomas fueron mayoritariamente únicos (60,8% y menores de 5 mm (68,5%. En un 55,5% de los casos con pólipos, alguno tenía una localización proximal. El diagnóstico se realizó en la 1ª exploración (56,2%, 2ª (27,8% ó 3ª (9%. La mediana de tiempo hasta el diagnóstico fue de 21 meses (12-112 para el adenoma simple y de 35 (12-112 para el avanzado. Conclusiones. Nuestro seguimiento permitió aplicar un tratamiento teóricamente curativo en la mayoría de los carcinomas metacrónicos diagnosticados. La alta incidencia de adenomas y su frecuente localización proximal hacen necesario un seguimiento con colonoscopias completas, que debería iniciarse al año de la operación y podría pasar a ser menos estricto tras tres exploraciones consecutivas sin pólipos.Background. To analyse the frequency and characteristics of metachronous neoplastic lesions, carcinomas

  1. Early clerkships

    NARCIS (Netherlands)

    Kamalski, Digna M. A.; Ter Braak, Edith W. M. T.; Ten Cate, Olle Th. J.; Borleffs, Jan C. C.

    2007-01-01

    Background: Early clinical experience is being introduced in innovative, vertically integrated undergraduate medical curricula. While in many cases, this early clinical experience is limited to the presence of patients during lectures, in Utrecht students gain 'hands on' experience of daily clinical

  2. Curcumol induces apoptosis in SPC-A-1 human lung adenocarcinoma cells and displays anti-neoplastic effects in tumor bearing mice.

    Science.gov (United States)

    Tang, Qi-Ling; Guo, Ji-Quan; Wang, Qi-You; Lin, Hai-Shu; Yang, Zhou-Ping; Peng, Tong; Pan, Xue-Diao; Liu, Bing; Wang, Su-Jun; Zang, Lin-Quan

    2015-01-01

    Curcumol is a sesquiterpene originally isolated from curcuma rhizomes, a component of herbal remedies commonly used in oriental medicine. Its beneficial pharmacological activities have attract significant interest recently. In this study, anti-cancer activity of curcumol was examined with both in vitro and in vivo models. It was found that curcumol exhibited time- and concentration-dependent anti-proliferative effects in SPC-A-1 human lung adenocarcinoma cells with cell cycle arrest in the G0/G1 phase while apoptosis-induction was also confirmed with flow cytometry and morphological analyses. Interestingly, curcumol did not display growth inhibition in MRC-5 human embryonic lung fibroblasts, suggesting the anti-proliferative effects of curcumol were specific to cancer cells. Anti-neoplastic effects of curcumol were also confirmed in tumor bearing mice. Curcumol (60 mg/kg daily) significantly reduced tumor size without causing notable toxicity. In conclusion, curcumol appears a favorable anti-cancer candidate for further development.

  3. Uncaria tomentosa exerts extensive anti-neoplastic effects against the Walker-256 tumour by modulating oxidative stress and not by alkaloid activity.

    Directory of Open Access Journals (Sweden)

    Arturo Alejandro Dreifuss

    Full Text Available This study aimed to compare the anti-neoplastic effects of an Uncaria tomentosa (UT brute hydroethanolic (BHE extract with those of two fractions derived from it. These fractions are choroformic (CHCl3 and n-butanolic (BuOH, rich in pentacyclic oxindole alkaloids (POA and antioxidant substances, respectively. The cancer model was the subcutaneous inoculation of Walker-256 tumour cells in the pelvic limb of male Wistar rat. Subsequently to the inoculation, gavage with BHE extract (50 mg.kg(-1 or its fractions (as per the yield of the fractioning process or vehicle (Control was performed during 14 days. Baseline values, corresponding to individuals without tumour or treatment with UT, were also included. After treatment, tumour volume and mass, plasma biochemistry, oxidative stress in liver and tumour, TNF-α level in liver and tumour homogenates, and survival rates were analysed. Both the BHE extract and its BuOH fraction successfully reduced tumour weight and volume, and modulated anti-oxidant systems. The hepatic TNF-α level indicated a greater effect from the BHE extract as compared to its BuOH fraction. Importantly, both the BHE extract and its BuOH fraction increased the survival time of the tumour-bearing animals. Inversely, the CHCl3 fraction was ineffective. These data represent an in vivo demonstration of the importance of the modulation of oxidative stress as part of the anti-neoplastic activity of UT, as well as constitute evidence of the lack of activity of isolated POAs in the primary tumour of this tumour lineage. These effects are possibly resulting from a synergic combination of substances, most of them with antioxidant properties.

  4. Uncaria tomentosa exerts extensive anti-neoplastic effects against the Walker-256 tumour by modulating oxidative stress and not by alkaloid activity.

    Science.gov (United States)

    Dreifuss, Arturo Alejandro; Bastos-Pereira, Amanda Leite; Fabossi, Isabella Aviles; Lívero, Francislaine Aparecida Dos Reis; Stolf, Aline Maria; Alves de Souza, Carlos Eduardo; Gomes, Liana de Oliveira; Constantin, Rodrigo Polimeni; Furman, Aline Emmer Ferreira; Strapasson, Regiane Lauriano Batista; Teixeira, Simone; Zampronio, Aleksander Roberto; Muscará, Marcelo Nicolás; Stefanello, Maria Elida Alves; Acco, Alexandra

    2013-01-01

    This study aimed to compare the anti-neoplastic effects of an Uncaria tomentosa (UT) brute hydroethanolic (BHE) extract with those of two fractions derived from it. These fractions are choroformic (CHCl3) and n-butanolic (BuOH), rich in pentacyclic oxindole alkaloids (POA) and antioxidant substances, respectively. The cancer model was the subcutaneous inoculation of Walker-256 tumour cells in the pelvic limb of male Wistar rat. Subsequently to the inoculation, gavage with BHE extract (50 mg.kg(-1)) or its fractions (as per the yield of the fractioning process) or vehicle (Control) was performed during 14 days. Baseline values, corresponding to individuals without tumour or treatment with UT, were also included. After treatment, tumour volume and mass, plasma biochemistry, oxidative stress in liver and tumour, TNF-α level in liver and tumour homogenates, and survival rates were analysed. Both the BHE extract and its BuOH fraction successfully reduced tumour weight and volume, and modulated anti-oxidant systems. The hepatic TNF-α level indicated a greater effect from the BHE extract as compared to its BuOH fraction. Importantly, both the BHE extract and its BuOH fraction increased the survival time of the tumour-bearing animals. Inversely, the CHCl3 fraction was ineffective. These data represent an in vivo demonstration of the importance of the modulation of oxidative stress as part of the anti-neoplastic activity of UT, as well as constitute evidence of the lack of activity of isolated POAs in the primary tumour of this tumour lineage. These effects are possibly resulting from a synergic combination of substances, most of them with antioxidant properties.

  5. CD56(bright)perforin(low) noncytotoxic human NK cells are abundant in both healthy and neoplastic solid tissues and recirculate to secondary lymphoid organs via afferent lymph.

    Science.gov (United States)

    Carrega, Paolo; Bonaccorsi, Irene; Di Carlo, Emma; Morandi, Barbara; Paul, Petra; Rizzello, Valeria; Cipollone, Giuseppe; Navarra, Giuseppe; Mingari, Maria Cristina; Moretta, Lorenzo; Ferlazzo, Guido

    2014-04-15

    As limited information is available regarding the distribution and trafficking of NK cells among solid organs, we have analyzed a wide array of tissues derived from different human compartments. NK cells were widely distributed in most solid tissues, although their amount varied significantly depending on the tissue/organ analyzed. Interestingly, the distribution appeared to be subset specific, as some tissues were preferentially populated by CD56(bright)perforin(low) NK cells, with others by the CD56(dim)perforin(high) cytotoxic counterpart. Nevertheless, most tissues were highly enriched in CD56(bright)perforin(low) cells, and the distribution of NK subsets appeared in accordance with tissue gene expression of chemotactic factors, for which receptors are differently represented in the two subsets. Remarkably, chemokine expression pattern of tissues was modified after neoplastic transformation. As a result, although the total amount of NK cells infiltrating the tissues did not significantly change upon malignant transformation, the relative proportion of NK subsets infiltrating the tissues was different, with a trend toward a tumor-infiltrating NK population enriched in noncytotoxic cells. Besides solid tissues, CD56(bright)perforin(low) NK cells were also detected in seroma fluids, which represents an accrual of human afferent lymph, indicating that they may leave peripheral solid tissues and recirculate to secondary lymphoid organs via lymphatic vessels. Our results provide a comprehensive mapping of NK cells in human tissues, demonstrating that discrete NK subsets populate and recirculate through most human tissues and that organ-specific chemokine expression patterns might affect their distribution. In this context, chemokine switch upon neoplastic transformation might represent a novel mechanism of tumor immune escape.

  6. MicroRNA-19a/b mediates grape seed procyanidin extract-induced anti-neoplastic effects against lung cancer.

    Science.gov (United States)

    Mao, Jenny T; Xue, Bingye; Smoake, Jane; Lu, Qing-Yi; Park, Heesung; Henning, Susanne M; Burns, Windie; Bernabei, Alvise; Elashoff, David; Serio, Kenneth J; Massie, Larry

    2016-08-01

    Oncomirs are microRNAs (miRNA) associated with carcinogenesis and malignant transformation. They have emerged as potential molecular targets for anti-cancer therapy. We hypothesize that grape seed procyanidin extract (GSE) exerts antineoplastic effects through modulations of oncomirs and their downstream targets. We found that GSE significantly down-regulated oncomirs miR-19a and -19b in a variety of lung neoplastic cells. GSE also increased mRNA and protein levels of insulin-like growth factor II receptor (IGF-2R) and phosphatase and tensin homolog (PTEN), both predicted targets of miR-19a and -19b. Furthermore, GSE significantly increased PTEN activity and decreased AKT phosphorylation in A549 cells. Transfection of miR-19a and -19b mimics reversed the up-regulations of IGF2R and PTEN gene expression and abrogated the GSE induced anti-proliferative response. Additionally, oral administration of leucoselect phytosome, comprised of standardized grape seed oligomeric procyanidins complexed with soy phospholipids, to athymic nude mice via gavage, significantly down-regulated miR-19a, -19b and the miR-17-92 cluster host gene (MIR17HG) expressions, increased IGF-2R, PTEN, decreased phosphorylated-AKT in A549 xenograft tumors, and markedly inhibited tumor growth. To confirm the absorption of orally administered GSE, plasma procyanidin B1 levels, between 60 and 90 min after gavage of leucoselect phytosome (400 mg/kg), were measured by LC/MS at week 2 and 8 of treatment; the estimated concentration that was associated with 50% growth inhibition (IC50) (1.3 μg/mL) in vitro was much higher than the IC50 (0.032-0.13 μg/ml) observed in vivo. Our findings reveal novel antineoplastic mechanisms by GSE and support the clinical translation of leucoselect phytosome as an anti-neoplastic and chemopreventive agent for lung cancer. Published by Elsevier Inc.

  7. Dietary polyacetylenes, falcarinol and falcarindiol, isolated from carrots prevents the formation of neoplastic lesions in the colon of azoxymethane-induced rats.

    Science.gov (United States)

    Kobaek-Larsen, Morten; El-Houri, Rime B; Christensen, Lars P; Al-Najami, Issam; Fretté, Xavier; Baatrup, Gunnar

    2017-03-22

    Falcarinol (FaOH) and falcarindiol (FaDOH) are found in many food plants of the Apiaceae family. Carrots are a major dietary source of these polyacetylenes. Feeding azoxymethane (AOM)-induced rats with carrots and purified FaOH have previously been shown to inhibit neoplastic transformations in the colon. FaOH and FaDOH have also shown to have a synergistic effect in vitro, resulting in a significant increased cytotoxic activity. Based on these findings the antineoplastic effect of FaOH and FaDOH (purity > 99%) was investigated in the AOM-induced rat model. Twenty rats received rat diet containing 7 μg FaOH per g feed and 7 μg FaDOH per g feed and 20 rats were controls receiving only rat diet. Then carcinogenesis was induced in all 40 rats with the carcinogen AOM. All animals received the designated diet for 2 weeks before AOM induction and continued on the designated diet throughout the experiment. Rats were euthanized 18 weeks after the first AOM injection and macroscopic polyp/cancers were measured, harvested and stained for histology. The difference in sizes of aberrant crypt foci (ACF) were analysed in a Wilcoxon rank sum test, in which the median number of small ACF was 218 in controls and 145 in polyacetylene treated rats (P < 0.001). Fifteen control rats and 8 treated rats had macroscopic tumors (P = 0.027). The number of tumors larger than 3 mm were 6 and 1 in control and treated rats, respectively (P = 0.032). In conclusion dietary supplements with FaOH and FaDOH reduced the number of neoplastic lesions as well as the growth rate of the polyps suggesting a preventive effect of FaOH and FaDOH on the development of colorectal cancer.

  8. Inflammatory cues acting on the adult intestinal stem cells and the early onset of cancer (review).

    Science.gov (United States)

    De Lerma Barbaro, A; Perletti, G; Bonapace, I M; Monti, E

    2014-09-01

    The observation that cancer often arises at sites of chronic inflammation has prompted the idea that carcinogenesis and inflammation are deeply interwoven. In fact, the current literature highlights a role for chronic inflammation in virtually all the steps of carcinogenesis, including tumor initiation, promotion and progression. The aim of the present article is to review the current literature on the involvement of chronic inflammation in the initiation step and in the very early phases of tumorigenesis, in a type of cancer where adult stem cells are assumed to be the cells of origin of neoplasia. Since the gastrointestinal tract is regarded as the best-established model system to address the liaison between chronic inflammation and neoplasia, the focus of this article will be on intestinal cancer. In fact, the anatomy of the intestinal epithelial lining is uniquely suited to study adult stem cells in their niche, and the bowel crypt is an ideal developmental biology system, as proliferation, differentiation and cell migration are all distributed linearly along the long axis of the crypt. Moreover, crypt stem cells are regarded today as the most likely targets of neoplastic transformation in bowel cancer. More specifically, the present review addresses the molecular mechanisms whereby a state of chronic inflammation could trigger the neoplastic process in the intestine, focusing on the generation of inflammatory cues evoking enhanced proliferation in cells not initiated but at risk of neoplastic transformation because of their stemness. Novel experimental approaches, based on triggering an inflammatory stimulus in the neighbourhood of adult intestinal stem cells, are warranted to address some as yet unanswered questions. A possible approach, the targeted transgenesis of Paneth cells, may be aimed at 'hijacking' the crypt stem cell niche from a status characterized by the maintenance of homeostasis to local chronic inflammation, with the prospect of initiating

  9. Early literacy

    DEFF Research Database (Denmark)

    Jensen, Anders Skriver

    2012-01-01

    This paper discusses findings from the Danish contribution to the EASE project, a European research project running from 2008 to 2010 on early literacy in relation to the transition from childcare to school. It explores a holistic, inclusive approach to early literacy that resists a narrow...... and schools. The paper also draws on Gee’s (2001, 2003, 2004, 2008) sociocultural approach to literacy, and Honneth’s (2003, 2006) concept of recognition. Emphasizing participation and recognition as key elements, it claims that stakeholders in early liter- acy must pay attention to how diverse early literacy...... opportunities empower children, especially when these opportunities are employed in a project-based learning environ- ment in which each child is able to contribute to the shared literacy events....

  10. 消化道浅表性瘤变的巴黎分型(更新版)%Update on the Paris Classification of Superficial Neoplastic lesions in the Digestive Tract

    Institute of Scientific and Technical Information of China (English)

    Endoscopic Classification Review Group

    2011-01-01

    Background and Study Aims:Neoplastic lesions in the digestive-tract mucosa are termed “superficial” when the depth of invasion is limited to the mucosa and submucosa.The endoscopic appearance has a predictive value for invasion into the submucosa,which is critical for the risk of nodal metastases.

  11. The RBE of 3.4 MeV alpha-particles and 0.565 MeV neutrons relative to 60Co gamma-rays for neoplastic transformation of human hybrid cells and the impact of culture conditions.

    Science.gov (United States)

    Frankenberg-Schwager, M; Spieren, S; Pralle, E; Giesen, U; Brede, H J; Thiemig, M; Frankenberg, D

    2010-01-01

    The neoplastic transformation of human hybrid CGL1 cells is affected by perturbations from external influences such as serum batch and concentration, the number of medium changes during the 21-day expression period and cell seeding density. Nevertheless, for doses up to 1.5 Gy, published transformation frequencies for low linear energy transfer (LET) radiations (gamma-rays, MeV electrons or photons) are in good agreement, whereas for higher doses larger variations are reported. The (60)Co gamma-ray data here for doses up to 1.5 Gy, using a low-yield serum batch and only one medium change, are in agreement with published frequencies of neoplastic transformation of human hybrid cells. For 3.4 MeV alpha-particles (LET = 124 keV/mum) and 0.565 MeV monoenergetic neutrons relative to low doses of (60)Co gamma-rays, a maximum relative biological effectiveness (RBE(M)) of 2.8 +/- 0.2 and 1.5 +/- 0.2, respectively, was calculated. Surprisingly, at higher doses of (60)Co gamma-rays lower frequencies of neoplastic transformation were observed. This non-monotonic dose relationship for neoplastic transformation by (60)Co gamma-rays is likely due to the lack of a G2/M arrest observed at low doses resulting in higher transformation frequencies per dose, whereas the lower frequencies per dose observed for higher doses are likely related to the induction of a G2/M arrest.

  12. High milk consumption does not affect prostate tumor progression in two mouse models of benign and neoplastic lesions.

    Directory of Open Access Journals (Sweden)

    Sophie Bernichtein

    Full Text Available Epidemiological studies that have investigated whether dairy (mainly milk diets are associated with prostate cancer risk have led to controversial conclusions. In addition, no existing study clearly evaluated the effects of dairy/milk diets on prostate tumor progression, which is clinically highly relevant in view of the millions of men presenting with prostate pathologies worldwide, including benign prostate hyperplasia (BPH or high-grade prostatic intraepithelial neoplasia (HGPIN. We report here a unique interventional animal study to address this issue. We used two mouse models of fully penetrant genetically-induced prostate tumorigenesis that were investigated at the stages of benign hyperplasia (probasin-Prl mice, Pb-Prl or pre-cancerous PIN lesions (KIMAP mice. Mice were fed high milk diets (skim or whole for 15 to 27 weeks of time depending on the kinetics of prostate tumor development in each model. Prostate tumor progression was assessed by tissue histopathology examination, epithelial proliferation, stromal inflammation and fibrosis, tumor invasiveness potency and expression of various tumor markers relevant for each model (c-Fes, Gprc6a, activated Stat5 and p63. Our results show that high milk consumption (either skim or whole did not promote progression of existing prostate tumors when assessed at early stages of tumorigenesis (hyperplasia and neoplasia. For some parameters, and depending on milk type, milk regimen could even exhibit slight protective effects towards prostate tumor progression by decreasing the expression of tumor-related markers like Ki-67 and Gprc6a. In conclusion, our study suggests that regular milk consumption should not be considered detrimental for patients presenting with early-stage prostate tumors.

  13. Pilot Study on Clinical Effectiveness of Autofluorescence Imaging for Early Gastric Cancer Diagnosis by Less Experienced Endoscopists

    Directory of Open Access Journals (Sweden)

    Kazuhiro Tada

    2011-01-01

    Full Text Available This study aimed to assess and compare effectiveness of Autofluorescence imaging (AFI in diagnosis of early gastric cancer (EGC between experienced and less experienced endoscopists. Fifty selected images (20 neoplastic lesions and 30 benign lesions/areas of both white light endoscopy (WLE and AFI were blindly reviewed by two groups; first consisted of five experienced endoscopists and second included five less experienced endoscopists. Sensitivity, specificity, and accuracy were 70%, 78%, and 75%, respectively, for AFI and 81%, 76%, and 78%, respectively, for WLE in the experienced group. In the less experienced group, sensitivity, specificity and accuracy were 80%, 81% and 80%, respectively, for AFI and 65%, 77%, and 72%, respectively, for WLE. Interobserver variability for the less experienced group was better with AFI than WLE. AFI improved sensitivity of endoscopic diagnosis of neoplastic lesions by less experienced endoscopists, and its use could beneficially enhance the clinical effectiveness of EGC screening.

  14. A color discriminating broad range cell staining technology for early detection of cell transformation

    Directory of Open Access Journals (Sweden)

    Sagiv Idit

    2009-01-01

    Full Text Available Background: Advanced diagnostic tools stand today at the heart of successful cancer treatment. CellDetect® is a new histochemical staining technology that enables color discrimination between normal cells and a wide variety of neoplastic tissues. Using this technology, normal cells are colored blue/green, while neoplastic cells color red. This tinctorial difference coincides with clear morphological visualization properties, mainly in tissue samples. Here we show that the CellDetect® technology can be deployed to distinguish normal cells from transformed cells and most significantly detect cells in their early pre-cancerous transformed state. Materials and Methods: In tissue culture, we studied the ability of the CellDetect® technology to color discriminate foci in a number of two stage transformation systems as well as in a well defined cellular model for cervical cancer development, using HPV16 transformed keratinocytes. Results: In all these cellular systems, the CellDetect® technology was able to sensitively show that all transformed cells, including pre-cancerous HPV 16 transformed cells, are colored red, whereas normal cells are colored blue/green. The staining technology was able to pick up: (i early transformation events in the form of small type 1 foci (non-invasive, not piled up small, with parallel alignment of cells, and (ii early HPV16 transformed cells, even prior to their ability to form colonies in soft agar. The study shows the utility of the CellDetect® technology in early detection of transformation events.

  15. Inhibition of aberrant proliferation and induction of apoptosis in pre-neoplastic human mammary epithelial cells by natural phytochemicals.

    Science.gov (United States)

    Katdare, M; Osborne, M P; Telang, N T

    1998-01-01

    Aberrant proliferation and modulated apoptosis leading to impaired cellular homeostasis represent crucial early events in the multi-step carcinogenic process. Regulation of these perturbed biomarkers may predict efficacious prevention of cancer development. Present experiments on non-cancerous human mammary epithelial 184-B5 cells were designed to examine whether i) exposure to suspect environmental human carcinogen Benzo (a) pyrene (BP) alters the status of cell proliferation and apoptosis and ii) BP-induced alterations are modulated in response to select natural phytochemicals that inhibit rodent mammary tumorigenesis. Flow cytometric analysis, cellular immunoreactivity to proliferation specific and apoptosis specific gene products and anchorage-dependent colony formation represented quantitative endpoints. Cruciferous glucosinolate indole-3-carbinol (I3C), tea polyphenol (-) epigallo catechin gallate (EGCC) and soy isoflavone genistein (GEN) represented the chemopreventive test compounds. A single 24 h exposure to 39 lM BP resulted in a 50% decrease (P=0.02) in the ratio of quiescent (Q=G0) to proliferative (P=S + M) population in part due to increase in aberrantly proliferative cells. The BP-initiated cells also exhibited an 87.8% inhibition (P=0. 0001) in confluency-associated apoptosis and a concomitant decrease in cellular immunoreactivity to wild-type p53. Simultaneous treatment of cultures with BP + I3C, BP + EGCG and BP + GEN resulted in a 1.8- to 3.4-fold increase (Pp53 immunoreactivity (Pp53 dependent apoptosis.

  16. Routine experimental system for defining conditions used in photodynamic therapy and fluorescence photodetection of (non-) neoplastic epithelia

    Science.gov (United States)

    Lange, Norbert; Vaucher, Laurent; Marti, Alexandre; Etter, Anne-Lise; Gerber, Patrick; van den Bergh, Hubert; Jichlinski, Patrice; Kucera, Pavel

    2001-04-01

    A common method to induce enhanced short-term endogenous porphyrin synthesis and accumulation in cell is the topical, systemic application of 5-aminolevulinic acid or one of its derivatives. This circumvents the intravenous administration of photosensitizers normally used for photodynamic therapy (PDT) of fluorescence photodetection. However, in the majority of potential medical indications, optimal conditions with respect to the porphyrin precursor or its pharmaceutical formulation have not yet been found. Due to ethical restrictions and animal right directives, the number of available test objects is limited. Hence, definition and use of nonanimal test methods are needed. Tissue and organ cultures are a promising approach in replacing cost intensive animal models in early stages of drug development. In this paper, we present a tissue culture, which can among others be used routinely to answer specific questions emerging in the field of photodynamic therapy and fluorescence photodetection. This technique uses mucosae excised from sheep paranasal sinuses or pig bladder, which is cultured under controlled conditions. It allows quasiquantative testing of different protoporphyrin IX precursors with respect to dose-response curves and pharmacokinetics, as well as the evaluation of different incubation conditions and/or different drug formulations. Furthermore, this approach, when combined with the use of electron microscopy and fluorescence-based methods, can be used to quantitatively determine the therapeutic outcome following protoporphyrin IX-mediated PDT.

  17. Active vitamin D potentiates the anti-neoplastic effects of calcium in the colon: A cross talk through the calcium-sensing receptor.

    Science.gov (United States)

    Aggarwal, Abhishek; Höbaus, Julia; Tennakoon, Samawansha; Prinz-Wohlgenannt, Maximilian; Graça, João; Price, Sally A; Heffeter, Petra; Berger, Walter; Baumgartner-Parzer, Sabina; Kállay, Enikö

    2016-01-01

    Epidemiological studies suggest an inverse correlation between dietary calcium (Ca(2+)) and vitamin D intake and the risk of colorectal cancer (CRC). It has been shown in vitro that the active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25-D3) can upregulate expression of the calcium-sensing receptor (CaSR). In the colon, CaSR has been suggested to regulate proliferation of colonocytes. However, during tumorigenesis colonic CaSR expression is downregulated and we hypothesized that the loss of CaSR could influence the anti-tumorigenic effects of Ca(2+) and vitamin D. Our aim was to assess the impact of CaSR expression and function on the anti-neoplastic effects of 1,25-D3 in colon cancer cell lines. We demonstrated that in the healthy colon of mice, high vitamin D diet (2500 IU/kg diet) increased expression of differentiation and apoptosis markers, decreased expression of proliferation markers and significantly upregulated CaSR mRNA expression, compared with low vitamin D diet (100 IU/kg diet). To determine the role of CaSR in this process, we transfected Caco2-15 and HT29 CRC cells with wild type CaSR (CaSR-WT) or a dominant negative CaSR mutant (CaSR-DN) and treated them with 1,25-D3 alone, or in combination with CaSR activators (Ca(2+) and NPS R-568). 1,25-D3 enhanced the anti-proliferative effects of Ca(2+) and induced differentiation and apoptosis only in cells with a functional CaSR, which were further enhanced in the presence of NPS R-568, a positive allosteric modulator of CaSR. The mutant CaSR inhibited the anti-tumorigenic effects of 1,25-D3 suggesting that the anti-neoplastic effects of 1,25-D3 are, at least in part, mediated by the CaSR. Taken together, our data provides molecular evidence to support the epidemiological observation that both, vitamin D and calcium are needed for protection against malignant transformation of the colon and that their effect is modulated by the presence of a functional CaSR. This article is part of a Special Issue

  18. MO-F-CAMPUS-I-04: Characterization of Fan Beam Coded Aperture Coherent Scatter Spectral Imaging Methods for Differentiation of Normal and Neoplastic Breast Structures

    Energy Technology Data Exchange (ETDEWEB)

    Morris, R; Albanese, K; Lakshmanan, M; Greenberg, J; Kapadia, A [Duke University Medical Center, Durham, NC, Carl E Ravin Advanced Imaging Laboratories, Durham, NC (United States)

    2015-06-15

    Purpose: This study intends to characterize the spectral and spatial resolution limits of various fan beam geometries for differentiation of normal and neoplastic breast structures via coded aperture coherent scatter spectral imaging techniques. In previous studies, pencil beam raster scanning methods using coherent scatter computed tomography and selected volume tomography have yielded excellent results for tumor discrimination. However, these methods don’t readily conform to clinical constraints; primarily prolonged scan times and excessive dose to the patient. Here, we refine a fan beam coded aperture coherent scatter imaging system to characterize the tradeoffs between dose, scan time and image quality for breast tumor discrimination. Methods: An X-ray tube (125kVp, 400mAs) illuminated the sample with collimated fan beams of varying widths (3mm to 25mm). Scatter data was collected via two linear-array energy-sensitive detectors oriented parallel and perpendicular to the beam plane. An iterative reconstruction algorithm yields images of the sample’s spatial distribution and respective spectral data for each location. To model in-vivo tumor analysis, surgically resected breast tumor samples were used in conjunction with lard, which has a form factor comparable to adipose (fat). Results: Quantitative analysis with current setup geometry indicated optimal performance for beams up to 10mm wide, with wider beams producing poorer spatial resolution. Scan time for a fixed volume was reduced by a factor of 6 when scanned with a 10mm fan beam compared to a 1.5mm pencil beam. Conclusion: The study demonstrates the utility of fan beam coherent scatter spectral imaging for differentiation of normal and neoplastic breast tissues has successfully reduced dose and scan times whilst sufficiently preserving spectral and spatial resolution. Future work to alter the coded aperture and detector geometries could potentially allow the use of even wider fans, thereby making coded

  19. Mesenchymal stromal cells (MSC) from JAK2+ myeloproliferative neoplasms differ from normal MSC and contribute to the maintenance of neoplastic hematopoiesis

    Science.gov (United States)

    Sánchez-Abarca, Luis Ignacio; Rosón-Burgo, Beatriz; Redondo, Alba; Rico, Ana; Preciado, Silvia; Ortega, Rebeca; Rodríguez, Concepción; Muntión, Sandra; Hernández-Hernández, Ángel; De Las Rivas, Javier; González, Marcos; González Porras, José Ramón; del Cañizo, Consuelo; Sánchez-Guijo, Fermín

    2017-01-01

    There is evidence of continuous bidirectional cross-talk between malignant cells and bone marrow-derived mesenchymal stromal cells (BM-MSC), which favors the emergence and progression of myeloproliferative neoplastic (MPN) diseases. In the current work we have compared the function and gene expression profile of BM-MSC from healthy donors (HD-MSC) and patients with MPN (JAK2V617F), showing no differences in the morphology, proliferation and differentiation capacity between both groups. However, BM-MSC from MPN expressed higher mean fluorescence intensity (MIF) of CD73, CD44 and CD90, whereas CD105 was lower when compared to controls. Gene expression profile of BM-MSC showed a total of 169 genes that were differentially expressed in BM-MSC from MPN patients compared to HD-MSC. In addition, we studied the ability of BM-MSC to support the growth and survival of hematopoietic stem/progenitor cells (HSPC), showing a significant increase in the number of CFU-GM colonies when MPN-HSPC were co-cultured with MPN-MSC. Furthermore, MPN-MSC showed alteration in the expression of genes associated to the maintenance of hematopoiesis, with an overexpression of SPP1 and NF-kB, and a downregulation of ANGPT1 and THPO. Our results suggest that BM-MSC from JAK2+ patients differ from their normal counterparts and favor the maintenance of malignant clonal hematopoietic cells. PMID:28796790

  20. [Outbreak of methicillin-resistant Staphylococcus aureus (MRSA) infection or colonization among patients with neoplastic disease: a clinico-epidemiological study of 11 cases].

    Science.gov (United States)

    Sakai, C; Satoh, Y; Ohkusu, K; Kumagai, K; Ishii, A

    2001-11-01

    MRSA infection or colonization developed in eleven patients with neoplastic disease including malignant lymphoma (5 cases), soft tissue sarcoma (2 cases), acute myeloblastic leukemia (one), myelodysplastic syndrome (one), multiple myeloma (one), and mesothelioma (one) at our ward from October to December 1999. The infections were pneumonia (six cases), enteritis (three), bacteremia (one), and wound infection (one). Ten of 11 cases received antimicrobial agent (s) during one month before isolation of MRSA, suggesting selection of MRSA. Five cases improved and survived, but six cases died of infection. At the isolation of MRSA, the neutrophil count (NC) of the alive cases was 1, 500/microliter or more but the NC of five cases who died was less than 1,000/microliter, especially less than 100/microliter in three cases who had just received a cancer chemotherapy. Pulsed-field gel electrophoresis, performed in 9 cases, showed an identical DNA-pattern of MRSA in 7 cases, indicating a nosocomial infection. Our method to prevent spread of MRSA targeting solely the patients with MRSA infection was obviously unsatisfactory. We should target also the cases of MRSA colonization and make an effort to wash hands more vigorously. Furthermore, radical reformation such as increasing single sick-rooms drastically and increasing the number of nursing staff is also required.

  1. Telomere length in non-neoplastic gastric mucosa and its relationship to H. pylori infection, degree of gastritis, and NSAID use.

    Science.gov (United States)

    Tahara, Tomomitsu; Shibata, Tomoyuki; Kawamura, Tomohiko; Ishizuka, Takamitsu; Okubo, Masaaki; Nagasaka, Mitsuo; Nakagawa, Yoshihito; Arisawa, Tomiyasu; Ohmiya, Naoki; Hirata, Ichiro

    2016-02-01

    Telomere shortening occurs with human aging in many organs and tissues and is accelerated by rapid cell turnover and oxidative injury. We measured average telomere length using quantitative real-time PCR in non-neoplastic gastric mucosa and assessed its relationship to H. pylori-related gastritis, DNA methylation, ulcer disease, and nonsteroidal anti-inflammatory drug (NSAID) usage. Gastric biopsies were obtained from 151 cancer-free subjects including 49 chronic NSAID users and 102 nonusers. Relative telomere length in genomic DNA was measured by real-time PCR. H. pylori infection status, histological severity of gastritis, and serum pepsinogens (PGs) were also investigated. E-cadherin (CDH1) methylation status was determined by methylation-specific PCR (MSP). Average relative telomere length of H. pylori-infected subjects was significantly shortened when compared to H. pylori-negative subjects (p = 0.002) and was closely associated with all histological parameter of gastritis (all p values gastritis and CDH1 methylation status. Also, telomere shortening is accelerated by NSAID usage especially in H. pylori-negative subjects.

  2. Case of polycythemia vera with unusual organizing pneumonia mimicking the clinical features of military tuberculosis and possibly caused by the involvement of neoplastic megakaryocytes.

    Science.gov (United States)

    Kimura, Yoshizo; Imamura, Yutaka; Higaki, Koichi; Ohno, Yuju; Hashiguchi, Namiko; Seki, Rituko; Okamura, Takashi; Arakawa, Fumiko; Kiyasu, Junichi; Takeuchi, Masanori; Miyoshi, Hiroaki; Yoshida, Maki; Nakamura, Yukihiko; Niino, Daisuke; Sugita, Yasuo; Ohshima, Koichi

    2011-08-01

    Polycythemia vera (PV) is a clonal myeloproliferative neoplasm (MPN) of hematopoietic stem cells. Although the management of MPN patients generally focuses on the prevention of thromboembolic events caused by hypercoagulability, it is true that the patients with hematological malignancy often suffer from pulmonary diseases with atypical radiological patterns. We present here a 56-year-old woman with PV harboring a JAK2(V617F) mutation that had a diffuse reticulonodular pattern on chest radiography and was initially suspected of having military tuberculosis. Pathological assessment of a video-assisted thoracoscopic surgery lung biopsy revealed that the lesions were in fact organizing pneumonia (OP). Interestingly, pulmonary extramedullary hematopoiesis with a diffuse plugging of the alveolar blood capillaries by numerous atypical megakaryocytes was also observed around the granulation components. The histological findings of our case of unusual OP suggest that local activated neoplastic megakaryocytes and platelets played an important role in the development of spreading fibrotic lesions. JAK2 mutation or the preleukemic phase of MPN may accelerate the activation of megakaryocytes and result in the proliferative process of fibrosis.

  3. Behavior of some enzymatic systems to the action of the cytostatic active EGlCP glucanic biopreparation upon HeLa neoplastic cells

    Directory of Open Access Journals (Sweden)

    Daniela Gherghel

    2010-02-01

    Full Text Available Interference of an autochthonous cytostatic active EGlCP glucanic biopreparation (in dose of 1.5 mg/mL with the activity of some key enzymes, involved in the development of active transmembranary transport, of the intermediary and energetic metabolism, as well as in cellular answer to the oxidative stress, of HeLa neoplastic cells has been investigated. The study revealed: the intensification of the membranary Na+-K+-ATP-ase, of the cellular Mg2+-ATP-ase, of the superoxide dismutase activities; the operating level attenuation of the of catalase, peroxidase, glutathion peroxidase, lactate dehydrogenase, alkaline phosphatase, acid phosphatase; the diminution of the malondialdehyde content. This functional interference with some cell enzymatic biomolecules has also induced the perturbation of the diverse membrane and metabolic processes, which was incompatible with the survival of HeLa tumoral cells The modulations of the cellular enzymatic equipment activity can be the consequences of the glucanic components direct (with the molecules of the miscellaneous enzymes or indirect interactions ( with membrane or genetic apparatus with some cell, subcell and molecular structures, implicated in the control and regulation of the biosynthesis and activity of the enzymatic biomolecules. The central element, which induces this enzymatic imbalance, appears to be the excess generation of the free radicals in the tumoral cells’ metabolism aggressed by glucanic constituents.

  4. A highly efficient tumor-infiltrating MDSC differentiation system for discovery of anti-neoplastic targets, which circumvents the need for tumor establishment in mice

    Science.gov (United States)

    Liechtenstein, Therese; Perez-Janices, Noemi; Gato, Maria; Caliendo, Fabio; Kochan, Grazyna; Blanco-Luquin, Idoia; Van der Jeught, Kevin; Arce, Frederick; Guerrero-Setas, David; Fernandez-Irigoyen, Joaquin; Santamaria, Enrique; Breckpot, Karine; Escors, David

    2014-01-01

    Myeloid-derived suppressor cells (MDSCs) exhibit potent immunosuppressive activities in cancer. MDSCs infiltrate tumors and strongly inhibit cancer-specific cytotoxic T cells. Their mechanism of differentiation and identification of MDSC-specific therapeutic targets are major areas of interest. We have devised a highly efficient and rapid method to produce very large numbers of melanoma-infiltrating MDSCs ex vivo without inducing tumors in mice. These MDSCs were used to study their differentiation, immunosuppressive activities and were compared to non-neoplastic counterparts and conventional dendritic cells using unbiased systems biology approaches. Differentially activated/deactivated pathways caused by cell type differences and by the melanoma tumor environment were identified. MDSCs increased the expression of trafficking receptors to sites of inflammation, endocytosis, changed lipid metabolism, and up-regulated detoxification pathways such as the expression of P450 reductase. These studies uncovered more than 60 potential novel therapeutic targets. As a proof of principle, we demonstrate that P450 reductase is the target of pro-drugs such as Paclitaxel, which depletes MDSCs following chemotherapy in animal models of melanoma and in human patients. Conversely, P450 reductase protects MDSCs against the cytotoxic actions of other chemotherapy drugs such as Irinotecan, which is ineffective for the treatment of melanoma. PMID:25151659

  5. Tumor Destruction and In Situ Delivery of Antigen Presenting Cells Promote Anti-Neoplastic Immune Responses: Implications for the Immunotherapy of Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Manfredi AA

    2004-07-01

    Full Text Available Antigen presenting cells (APCs activate helper and cytotoxic T cells specific for antigens expressed by tissue cells, including neoplastic cells. This event occurs after the antigen transfer from tissue cells to APC, and is referred to as "cross-presentation". The number and the state of activation of APC in the tumor control the outcome of cross-presentation, including the establishment of protective immune responses. Cell death favors cross-presentation. Cancer cells normally die, either spontaneously or as a consequence of targeted therapies. The transfer of tumor antigens from dying tumor cells to APCs in vivo, exploiting the cross-presentation pathway, has the potential of yielding novel immunotherapeutic strategies. Their success will depend on at least two factors: the induction of synchronized cell death in the tumor, and the recruitment of activated dendritic cells in the tumor. Under normal conditions, pancreatic cancer represents a privileged environment; its profound chemoresistance reflects limited apoptosis after chemotherapy. Moreover, it usually contains only a few cells endowed with APC function. Endoscopic ultrasonography offers attractive possibilities of circumventing this privilege, including the delivery of ultrasound, radiofrequency or radiation in order to destroy the tumor and the delivery in situ of autologous APC or appropriate chemotactic signals. In general, loco-regional approaches offer the possibility of using the tumor of each patient as a complex antigen source, thus limiting the risk of tumor escape and reducing the need for extensive ex vivo handling of the neoplasm and of the patient APCs.

  6. Clinical Observation on the Treatment of Male Neoplastic Anemia with Yixuesheng Capsule(益血生胶囊) Combined with Recombination Human Erythropoietin

    Institute of Scientific and Technical Information of China (English)

    CHENG Zhi; WU Jia-li; CHEN Jun-fa

    2009-01-01

    Objective: To explore the efficacy and mechanism of Yixuesheng capsule (益血生胶囊, YXS) combined with recombination human erythropoietin (RHE) in treating male neoplastic anemia (NA). Methods: Sixty-five patients were randomized into two groups, the 33 patients in the treated group treated with a combined therapy of YXS and RHE, and the 32 in the control group treated with RHE alone, all for 12 weeks. Related clinical indexes, including hemoglobin (Hgb), red blood cell (RBC), hematocrit (HMC), testosterone (T), estradiol (E) arid prolactin (PRL), were measured before and after treatment. Results: After treatment, Hgb in the treated group and the control group was 108±5 g/L and 104±8 g/L respectively, showing marked improvement as compared with that before treatment (P<0.01), and the improvement in the former was more significant than that in the latter (P<0.05). Further, the level of T was also increased in the treated group after treatment (P<0.05), and showed a significant difference from that of the control group (P<0.05). Conclusions: YXS capsule combined with RHE shows a better therapeutic effect in treating NA than that of RHE alone, and the effect might be through stimulation by YXS of erythropoiesis which could promote the secretion of testosterone.

  7. Genetic and epigenetic aberrations of p16 in feline primary neoplastic diseases and tumor cell lines of lymphoid and non-lymphoid origins.

    Science.gov (United States)

    Mochizuki, H; Fujiwara-Igarashi, A; Sato, M; Goto-Koshino, Y; Ohno, K; Tsujimoto, H

    2017-01-01

    The p16 gene acts as a tumor suppressor by regulating the cell cycle and is frequently inactivated in human and canine cancers. The aim of this study was to characterize genetic and epigenetic alterations of the p16 in feline lymphoid and non-lymphoid malignancies, using 74 primary tumors and 11 tumor cell lines. Cloning of feline p16 and subsequent sequence analysis revealed 11 germline sequence polymorphisms in control cats. Bisulfite sequencing analysis of the p16 promoter region in a feline lymphoma cell line revealed that promoter methylation was associated with decreased mRNA expression. Treatment with a demethylating agent restored mRNA expression of the silenced p16. PCR amplification and sequencing analysis detected homozygous loss (five tumors, 6.7%) and a missense mutation (one tumor, 1.4%) in the 74 primary tumors analyzed. Methylation-specific PCR analysis revealed promoter methylation in 10 primary tumors (14%). Promoter methylation was frequent in B cell lymphoid tumors (7/21 tumors, 33%). These genetic and epigenetic alterations were also observed in lymphoma and mammary gland carcinoma cell lines, but not detected in non-neoplastic control specimens. These data indicate that molecular alterations of the p16 locus may be involved in the development of specific types of feline cancer, and warrant further studies to evaluate the clinical value of this evolutionarily-conserved molecular alteration in feline cancers.

  8. Identification of differential anti-neoplastic activity of copper bis(thiosemicarbazones) that is mediated by intracellular reactive oxygen species generation and lysosomal membrane permeabilization.

    Science.gov (United States)

    Stefani, Christian; Al-Eisawi, Zaynab; Jansson, Patric J; Kalinowski, Danuta S; Richardson, Des R

    2015-11-01

    Bis(thiosemicarbazones) and their copper (Cu) complexes possess unique anti-neoplastic properties. However, their mechanism of action remains unclear. We examined the structure-activity relationships of twelve bis(thiosemicarbazones) to elucidate factors regarding their anti-cancer efficacy. Importantly, the alkyl substitutions at the diimine position of the ligand backbone resulted in two distinct groups, namely, unsubstituted/monosubstituted and disubstituted bis(thiosemicarbazones). This alkyl substitution pattern governed their: (1) Cu(II/I) redox potentials; (2) ability to induce cellular (64)Cu release; (3) lipophilicity; and (4) anti-proliferative activity. The potent anti-cancer Cu complex of the unsubstituted bis(thiosemicarbazone) analog, glyoxal bis(4-methyl-3-thiosemicarbazone) (GTSM), generated intracellular reactive oxygen species (ROS), which was attenuated by Cu sequestration by a non-toxic Cu chelator, tetrathiomolybdate, and the anti-oxidant, N-acetyl-l-cysteine. Fluorescence microscopy suggested that the anti-cancer activity of Cu(GTSM) was due, in part, to lysosomal membrane permeabilization (LMP). For the first time, this investigation highlights the role of ROS and LMP in the anti-cancer activity of bis(thiosemicarbazones).

  9. Leptin acts on neoplastic behavior and expression levels of genes related to hypoxia, angiogenesis, and invasiveness in oral squamous cell carcinoma.

    Science.gov (United States)

    Sobrinho Santos, Eliane Macedo; Guimarães, Talita Antunes; Santos, Hércules Otacílio; Cangussu, Lilian Mendes Borborema; de Jesus, Sabrina Ferreira; Fraga, Carlos Alberto de Carvalho; Cardoso, Claudio Marcelo; Santos, Sérgio Henrique Souza; de Paula, Alfredo Maurício Batista; Gomez, Ricardo Santiago; Guimarães, André Luiz Sena; Farias, Lucyana Conceição

    2017-05-01

    Leptin, one of the main hormones controlling energy homeostasis, has been associated with different cancer types. In oral cancer, its effect is not well understood. We investigated, through in vitro and in vivo assays, whether leptin can affect the neoplastic behavior of oral squamous cell carcinoma. Expression of genes possibly linked to the leptin pathway was assessed in leptin-treated oral squamous cell carcinoma cells and also in tissue samples of oral squamous cell carcinoma and oral mucosa, including leptin, leptin receptor, hypoxia-inducible factor 1-alpha, E-cadherin, matrix metalloproteinase-2, matrix metalloproteinase-9, Col1A1, Ki67, and mir-210. Leptin treatment favored higher rates of cell proliferation and migration, and reduced apoptosis. Accordingly, leptin-treated oral squamous cell carcinoma cells show decreased messenger RNA caspase-3 expression, and increased levels of E-cadherin, Col1A1, matrix metalloproteinase-2, matrix metalloproteinase-9, and mir-210. In tissue samples, hypoxia-inducible factor 1-alpha messenger RNA and protein expression of leptin and leptin receptor were high in oral squamous cell carcinoma cases. Serum leptin levels were increased in first clinical stages of the disease. In animal model, oral squamous cell carcinoma-induced mice show higher leptin receptor expression, and serum leptin level was increased in dysplasia group. Our findings suggest that leptin seems to exert an effect on oral squamous cell carcinoma cells behavior and also on molecular markers related to cell proliferation, migration, and tumor angiogenesis.

  10. Isolation, purification, culture and characterisation of myoepithelial cells from normal and neoplastic canine mammary glands using a magnetic-activated cell sorting separation system.

    Science.gov (United States)

    Sánchez-Céspedes, R; Maniscalco, L; Iussich, S; Martignani, E; Guil-Luna, S; De Maria, R; Martín de Las Mulas, J; Millán, Y

    2013-08-01

    Mammary gland tumours, the most common malignant neoplasm in bitches, often display myoepithelial (ME) cell proliferation. The aim of this study was to isolate, purify, culture and characterise ME cells from normal and neoplastic canine mammary glands. Monodispersed cells from three normal canine mammary glands and five canine mammary tumours were incubated with an anti-Thy1 antibody and isolated by magnetic-activated cell sorting (MACS). Cells isolated from two normal glands (cell lines CmME-N1 and CmME-N2) and four tumours (cell lines CmME-K1 from a complex carcinoma, CmME-K2 from a simple tubulopapillary carcinoma, and CmME-K3 and CmME-K4 from two carcinomas within benign tumours) were cultured in supplemented DMEM/F12 media for 40days. Cell purity was >90%. Tumour-derived ME cell lines exhibited heterogeneous morphology, growth patterns and immunocytochemical expression of cytokeratins, whereas cell lines from normal glands retained their morphology and levels of cytokeratin expression during culture. Cell lines from normal glands and carcinomas within benign tumours grew more slowly than those from simple and complex carcinomas. This methodology has the potential to be used for in vitro analysis of the role of ME cells in the growth and progression of canine mammary tumours.

  11. Early blindness and coma during intrathecal chemotherapy for meningeal carcinomatosis.

    Science.gov (United States)

    Boogerd, W; Moffie, D; Smets, L A

    1990-02-01

    A 35-year-old woman was treated with intraventricular methotrexate (MTX) with a total dose of 70 mg followed by cytosine arabinoside (Ara-C) with a total dose of 80 mg for meningeal metastasis of breast carcinoma. Radiation therapy was not given. Despite a response of the meningeal tumor the patient developed in the third week of MTX treatment a progressive visual loss and loss of consciousness which worsened during subsequent Ara-C treatment and led to death within 3 weeks. Postmortem examination revealed only minimal neoplastic infiltration of the meninges. Multiple foci of axonal degeneration and demyelination were found in the optic nerves and chiasm, the superficial layers of the brainstem, and spinal cord and to some extent in other cranial nerves and spinal nerve roots. The possible causes of this previously unreported early complication are discussed.

  12. PDZ-binding kinase/T-LAK cell-originated protein kinase is a target of the fucoidan from brown alga Fucus evanescens in the prevention of EGF-induced neoplastic cell transformation and colon cancer growth.

    Science.gov (United States)

    Vishchuk, Olesia S; Sun, Huimin; Wang, Zhe; Ermakova, Svetlana P; Xiao, JuanJuan; Lu, Tao; Xue, PeiPei; Zvyagintseva, Tatyana N; Xiong, Hua; Shao, Chen; Yan, Wei; Duan, Qiuhong; Zhu, Feng

    2016-04-05

    The fucoidan with high anticancer activity was isolated from brown alga Fucus evanescens. The compound effectively prevented EGF-induced neoplastic cell transformation through inhibition of TOPK/ERK1/2/MSK 1 signaling axis. In vitro studies showed that the fucoidan attenuated mitogen-activated protein kinases downstream signaling in a colon cancer cells with different expression level of TOPK, resulting in growth inhibition. The fucoidan exerts its effects by directly interacting with TOPK kinase in vitro and ex vivo and inhibits its kinase activity. In xenograft animal model, oral administration of the fucoidan suppressed HCT 116 colon tumor growth. The phosphorylation of TOPK downstream signaling molecules in tumor tissues was also inhibited by the fucoidan. Taken together, our findings support the cancer preventive efficacy of the fucoidan through its targeting of TOPK for the prevention of neoplastic cell transformation and progression of colon carcinomas in vitro and ex vivo.

  13. Para neoplastic syndromes: Usefulness of {sup 18}F-fluoro-deoxy-glucose (F.D.G.) positron emission tomography (PET); Syndromes paraneoplasiques: interet de la tomographie par emission de positons (TEP) au {sup 18}F-fluoro-deoxyglucose (FDG)

    Energy Technology Data Exchange (ETDEWEB)

    Banayan, S.; Janier, M.; Guillerma-Zucchi, N.; Billotey, C. [Hopital Edouard-Herriot, Service de Medecine Nucleaire, 69 - Lyon (France); Ninet, J. [Hopital Edouard-Herriot, Service de Medecine Interne, 69 - Lyon (France); Delmas, P. [Hopital Edouard-Herriot, Service de Rhumatologie, 69 - Lyon (France); Thivolet, C. [Hopital Edouard-Herriot, Service d' Endocrinologie, 69 - Lyon (France); Pellet, O. [Centre Hospitalier de Lyon-Sud, Service de Medecine Nucleaire, 69 (France)

    2008-05-15

    Background We evaluated the performance of {sup 18}F-fluorodeoxyglucose ({sup 18}F.D.G.) positron emission tomography (PET) in the diagnosis of underlying malignancy in cases of suspected para neoplastic syndrome (P.S.). Methods {sup 18}F.D.G.-PET was performed in 31 patients, clinically suspected to have P.S.. The P.S. were 34, among which 12 neurological diseases, eight endocrine, seven rheumatological, one dermatological and six vascular. We compared computed tomography (CT), iodine-enhanced most of the time, and {sup 18}F.D.G.-PET reports to clinicians definitive conclusion at the end of the work-up and a follow-up period of, at least, two months. Results We obtained a histological diagnosis of cancer for ten patients, but could only identify the primary site of malignancy for nine of them. {sup 18}F.D.G.-PET showed six primary sites among which three were not seen on CT. CT disclosed four primary sites, among which one was not seen on {sup 18}F.D.G.-PET. In one case, {sup 18}F.D.G.-PET disclosed regional lymph node metastases whereas these were not identified by CT. Eleven non-neoplastic causes were evidenced, among which {sup 18}F.D.G.-PET played a major role in three cases. Ten causes were still undetermined at the end of the study. Conclusion Whole-body {sup 18}F.D.G.-PET study plays an important role in the identification of underlying malignancy in clinically suspected para neoplastic syndromes; either by identifying the primary tumor or by directing biopsy of metastases. Furthermore, it can identify non-neoplastic causes. (authors)

  14. Delivery of Granulocyte-Macrophage Colony-Stimulating Factor in Bioadhesive Hydrogel Stimulates Migration of Dendritic Cells in Models of Human Papillomavirus-Associated (Pre)Neoplastic Epithelial Lesions

    OpenAIRE

    Hubert, Pascale; Evrard, Brigitte; Maillard, Catherine; Franzen-Detrooz, Elizabeth; Delattre, Luc; Foidart, Jean-Michel; Noël, Agnes; Boniver, Jacques; Delvenne, Philippe

    2004-01-01

    Because of the central role of dendritic cells and/or Langerhans cells(DC/LC) in the induction of cellular immune responses, pharmacological agents that modulate the recruitment of these cells might have a clinical interest. The present study was designed to evaluate the capacity of several pharmaceutical formulations to topically deliver granulocyte-macrophage colony-stimulating factor (GM-CSF) on human papillomavirus (HPV)-associated genital (pre)neoplastic lesions. The formulations were ev...

  15. Delivery of granulocyte-macrophage colony-stimulating factor in bioadhesive hydrogel stimulates migration of dendritic cells in models of human papillomavirus-associated (pre)neoplastic epithelial lesions.

    Science.gov (United States)

    Hubert, Pascale; Evrard, Brigitte; Maillard, Catherine; Franzen-Detrooz, Elizabeth; Delattre, Luc; Foidart, Jean-Michel; Noël, Agnes; Boniver, Jacques; Delvenne, Philippe

    2004-11-01

    Because of the central role of dendritic cells and/or Langerhans cells(DC/LC) in the induction of cellular immune responses, pharmacological agents that modulate the recruitment of these cells might have a clinical interest. The present study was designed to evaluate the capacity of several pharmaceutical formulations to topically deliver granulocyte-macrophage colony-stimulating factor (GM-CSF) on human papillomavirus (HPV)-associated genital (pre)neoplastic lesions. The formulations were evaluated for their bioactivity and for their potential to recruit DC in organotypic cultures of HPV-transformed keratinocytes. We found that a bioadhesive polycarbophil gel (Noveon) at pH 5.5 is able to maintain the bioactivity of GM-CSF at 4 or 37 degrees C for at least 7 days, whereas a decreased activity of GM-CSF was observed when the molecule is included in other polymer gels. GM-CSF incorporated in the polycarbophil gel was also a potent factor in enhancing the colonization of DC into organotypic cultures of HPV-transformed keratinocytes since the infiltration of DC in the in vitro-formed (pre)neoplastic epithelium was very low under basal conditions and dramatically increased in the presence of GM-CSF gel. We next demonstrated that GM-CSF incorporated in polycarbophil gel induces the recruitment of human DC in a human (pre)neoplastic epithelium grafted into NOD/SCID mice. The efficacy of GM-CSF in this formulation was equivalent to that observed with liquid GM-CSF. These results suggest that GM-CSF incorporated in polycarbophil gel could play an important role in the recruitment of DC/LC in mucosal surfaces and be useful as a new immunotherapeutic approach for genital HPV-associated (pre)neoplastic lesions.

  16. Molecular markers of cancer in cartilaginous fish: immunocytochemical study of PCNA, p-53, myc and ras expression in neoplastic and hyperplastic tissues from free ranging blue sharks, Prionace glauca (L.).

    Science.gov (United States)

    Borucinska, J D; Schmidt, B; Tolisano, J; Woodward, D

    2008-02-01

    Archival formalin-fixed tissues from wild-caught adult blue sharks, Prionace glauca (L.), were used for immunocytochemical detection of proliferating cell nuclear antigen (PCNA), two oncoproteins from the oncogenes c-myc and pan-ras, and a protein product from the tumour suppressor gene p-53. All sharks were caught during summer months between 2000 and 2006 by recreational fishermen off the USA coast in the northwestern Atlantic. The sharks were necropsied on landing and selected organ samples were collected into elasmobranch formalin and processed for paraffin embedding and light microscopy. Paraffin-embedded sections from collected tissue were both stained with haematoxylin and eosin and processed by immunocytochemical techniques using antibodies raised against the PCNA, p-ras, c-myc and p-53 proteins. The lesions examined in this study included two well differentiated adenomatous gastric polyps, a testicular capsular mesothelioma, a gingival fibropapilloma with elements of ameloblastoma, three liver tumours, two pericardial fibropapillomas and six cases of proliferative serositis (pericarditis and peritonitis). Normal and hyperplastic tissues from blue sharks, and human neoplastic tissues served as negative and positive controls, respectively. We detected upregulation of PCNA in many neoplastic, one dysplastic and in some hyperplastic lesions, and positive p-ras and c-myc signals in some of the neoplastic lesions. None of the examined tissues showed positive p-53 signalling. This is the first literature report on immunocytochemical detection of molecular markers of cancer in sharks and in fish of the class Chondrichthyes.

  17. In multiple myeloma, only a single stage of neoplastic plasma cell differentiation can be identified by VLA-5 and CD45 expression.

    Science.gov (United States)

    Rawstron, A C; Barrans, S L; Blythe, D; English, A; Richards, S J; Fenton, J A; Davies, F E; Child, J A; Jack, A S; Morgan, G J

    2001-06-01

    The nature of the proliferating fraction in myeloma is still not known and understanding the characteristics of this fraction is central to the development of effective novel therapies. However, myeloma plasma cells typically show a very low rate of proliferation and this complicates accurate analysis. Although the level of CD45 and/or VLA-5 has been reported to identify proliferating 'precursor' plasma cells, there are discrepancies between these studies. We have therefore used a rigorous sequential gating strategy to simultaneously analyse cycle status and immunophenotype with respect to CD45, VLA-5 and a range of other integrin molecules. In 11 presentation myeloma patients, the proliferative fraction was distributed evenly between CD45+ and CD45- cells, however, cycling plasma cells were consistently VLA-5-. There was close correlation between the expression of VLA-5 and a range of other integrin molecules (CD11a, CD11c, CD103), as well as the immunoglobulin-associated molecules CD79a/b (Spearman, n = 10, P < 0.0001). In short-term culture, cells that were initially VLA-5-showed increasing VLA-5 expression with time. However, simultaneous analysis of the DNA-binding dye 7-amino-actinomycin D demonstrated that this was not as a result of differentiation, as VLA-5+ plasma cells were all non-viable. This was confirmed in freshly explanted plasma cells from nine patients. Discrete stages of plasma cell differentiation could not be distinguished by the level of CD45 or VLA-5 expression. The results indicate that there is a single stage of plasma cell differentiation, with the phenotype CD38+CD138+VLA-5-. These findings support the hypothesis that neoplastic bone marrow plasma cells represent an independent, self-replenishing population.

  18. Anti-HBs profiles in children treated for neoplastic disease who had been vaccinated against hepatitis B postnatally or as infants.

    Science.gov (United States)

    Koltan, S; Koltan, A; Wysocki, M; Debski, R; Styczynski, J

    2005-05-01

    Children with cancer are a risk group for hepatitis B virus (HBV) infection. In Poland, the initiation of a national HBV vaccination programme in neonates and infants in 1995 has contributed to the prevention of HBV infection in children treated for neoplastic diseases. The objective of this study was to analyse the anti-HBs pattern and occurrence of HBV infections in children with cancer who had been vaccinated during infancy. The study included 96 children divided into three groups: Group A, children who had received a full vaccination course with an initial level of anti-HBs >/=100 IU/L; Group B, children who had received a full vaccination course with anti-HBs anti-HBs after the full vaccination programme was found in 80.5% of children after three months, 74.2% after six months, 61.5% after 12 months and 78.6% after 18 months. Among children who produced antibodies, a slow decrease in the level of anti-HBs was observed. It was still protective during follow-up in Group A, but occasionally fell below 100 IU/L in Group B. In Group C, five of 11 subjects had a protective level of anti-HBs throughout follow-up. Of 28 children who showed the presence of HBsAg during follow-up, 23 eradicated the virus. In children with cancer vaccinated against HBV according to the vaccination schedule, the immune response maintains a protective level of anti-HBs in more than 60% of cases, despite immunosuppression.

  19. Expression of von Hippel-Lindau tumor suppressor and tumor-associated carbonic anhydrases Ⅸ and Ⅻ in normal and neoplastic colorectal mucosa

    Institute of Scientific and Technical Information of China (English)

    Antti J. Kivela; Abdul Waheed; William S. Sly; Hannu Rajaniemi; Silvia Pastorekova; Jaromir Pastorek; Seppo Parkkila; Juha Saarnio; Tuomo J. Karttunen; Jyrki Kivela; Anna-Kaisa Parkkila; Maria Bartosova; Vojtech Mucha; Michal Novak

    2005-01-01

    AIM: To analyze possible relationships between CA Ⅸ/ CA Ⅻ and pVHL expression in normal and neoplastic colorectal mucosa.METHODS: Immunohistochemical staining of 42 tissue specimens obtained from 17 cancer patients was performed to evaluate the distribution and semi-quantitatively assess the levels of CA Ⅸ, CA Ⅻ and pVHL. VHL mRNAs from 14fresh-frozen tumors was amplified by RT-PCR and subjected to sequencing. CA9 and CA12 mRNA levels were analyzed by semi-quantitative RT-PCR in comparison with VEGF as an indicator of hypoxia that uncouples the pVHL control.RESULTS: Tumor tissues were associated with a borderline increase of CA Ⅸ staining signal and slight but significant decrease of CA Ⅻ immunoreactivity, whereas no association was found for pVHL. Sequence analysis of RT-PCR-amplified VHL mRNAs revealed no deletions/ mutations, suggesting that they were VHL-competent. We did not observe any correlation between pVHL andCA Ⅸ/CA Ⅻ proteins as well as between VEGF and CA9mRNAs, but the tumor-associated changes in mRNA levels of VEGF and CA12showed a significant inverse relationship. CONCLUSION: Our results indicate that CA9 and CA12 are regulated by different intratumoral factors and that lack of apparent relationship between the levels of CA Ⅸ/CA Ⅻ and pVHL cannot be fully assigned to uncoupling of negative regulatory function of pVHL by tumor hypoxia signified by induced VEGF transcription. The interplay between the functional pVHL and CA Ⅸ/CA Ⅻ in colorectal tumors seems rather complex and is not evident merely at the expression levels.

  20. Cutaneous neoplastic lesions of equids in the central United States and Canada: 3,351 biopsy specimens from 3,272 equids (2000-2010).

    Science.gov (United States)

    Schaffer, Paula A; Wobeser, Bruce; Martin, Laura E R; Dennis, Michelle M; Duncan, Colleen G

    2013-01-01

    To identify epidemiological trends in cutaneous neoplasms affecting equids in central North America and compare them with previously reported trends. Retrospective case series. 3,351 cutaneous biopsy specimens from 3,272 equids with a neoplastic diagnosis. Diagnostic reports from 2 diagnostic laboratories (Colorado State University and Prairie Diagnostic Services Inc) were reviewed for frequency of specific lesions and epidemiological trends. Variables included in analyses (if known) were age, sex, breed, geographic location, date of diagnosis, location of neoplasm on the body, and presence or absence of ulceration. Sarcoid, squamous cell carcinoma (SCC), and melanoma were the 3 most common tumors diagnosed. Tumors associated with UV radiation (SCC, SCC in situ, hemangioma, hemangiosarcoma) were 2.3 (95% confidence interval [CI], 1.8 to 3.0) times as common in biopsy specimens received by Colorado State University than in specimens received by Prairie Diagnostic Services Inc. Appaloosa horses and American Paint horses, respectively, were 7.2 (95% CI, 5.6 to 9.2) and 4.4 (95% CI, 3.6 to 5.4) times as likely as other breeds to have tumors associated with UV radiation. Thoroughbreds were predisposed to cutaneous lymphoma, whereas Arabians were more likely to have melanomas. Draft and pony breeds were 3.1 (95% CI, 1.9 to 5.1) times as likely as other breeds to have benign soft tissue tumors. Morgans and pony breeds more commonly had basal cell tumors. Tumors in the perianal region were significantly more likely to be SCC or melanoma while tumors on the limbs were more likely to be giant cell tumor of soft parts. Signalment, anatomic location of the mass, and geographic location of the horse can be used to help equine practitioners formulate differential diagnoses for cutaneous masses. Further research is necessary to identify the biological basis for the development of many equine cutaneous neoplasms.

  1. Actinic keratosis associated with squamous and basal cell carcinomas: an evaluation of neoplastic progression by a standardized AgNOR analysis

    Directory of Open Access Journals (Sweden)

    G Giuffrè

    2009-08-01

    Full Text Available In an attempt to investigate the neoplastic progression in different stages of actinic keratosis (AK, a standardized AgNOR analysis was performed in 94 cases of AK, 35 of which were associated with squamous cell carcinoma (SCC or basal cell carcinoma (BCC, and in 31 cases of SCC and 22 cases of BCC. The cases were subdivided into low- and high- AgNOR-expressing (AgNOR status AK by using the mean area of AgNORs per cell (NORA value (3.996 ?m2 as the cut-off. In AK samples, a progressive increase of the mean NORA value from Stage I to Stage IV was encountered. In addition, a significantly higher mean NORA value was found in the AK cases associated with SCC, in comparison to those without SCC; by contrast, no significant differences in the mean NORA value were noted between AK cases with or without BCC. A highly significant association between a high AgNOR quantity and the coexistence of SCC was encountered in AK; no association was appreciable between the AgNOR quantity and the co-occurrence of BCC. Moreover, when the co-existence of SCC in AK was considered as the reference point, the AK cases associated with SCC mostly (95.5% presented a high AgNOR quantity (high sensitivity, but only 57.6% of cases without SCC displayed a low AgNOR quantity (low specificity. Additionally, our data document that the standardised AgNOR analysis represents a strong negative predictor for the association between SCC and AK. Indeed, a low AgNOR quantity mostly is associated with AK cases without SCC.

  2. Increased cycling cell numbers and stem cell associated proteins as potential biomarkers for high grade human papillomavirus+ve pre-neoplastic cervical disease.

    Directory of Open Access Journals (Sweden)

    Maurice Canham

    Full Text Available High risk (oncogenic human papillomavirus (HPV infection causes cervical cancer. Infections are common but most clear naturally. Persistent infection can progress to cancer. Pre-neoplastic disease (cervical intraepithelial neoplasia/CIN is classified by histology (CIN1-3 according to severity. Cervical abnormalities are screened for by cytology and/or detection of high risk HPV but both methods are imperfect for prediction of which women need treatment. There is a need to understand the host virus interactions that lead to different disease outcomes and to develop biomarker tests for accurate triage of infected women. As cancer is increasingly presumed to develop from proliferative, tumour initiating, cancer stem cells (CSCs, and as other oncogenic viruses induce stem cell associated gene expression, we evaluated whether presence of mRNA (detected by qRT-PCR or proteins (detected by flow cytometry and antibody based proteomic microarray from stem cell associated genes and/or increased cell proliferation (detected by flow cytometry could be detected in well-characterised, routinely collected cervical samples from high risk HPV+ve women. Both cytology and histology results were available for most samples with moderate to high grade abnormality. We found that stem cell associated proteins including human chorionic gonadotropin, the oncogene TP63 and the transcription factor SOX2 were upregulated in samples from women with CIN3 and that the stem cell related, cell surface, protein podocalyxin was detectable on cells in samples from a subset of women with CIN3. SOX2, TP63 and human gonadotrophin mRNAs were upregulated in high grade disease. Immunohistochemistry showed that SOX2 and TP63 proteins clearly delineated tumour cells in invasive squamous cervical cancer. Samples from women with CIN3 showed increased proliferating cells. We believe that these markers may be of use to develop triage tests for women with high grade cervical abnormality to

  3. Effects of a probiotic soy product and physical exercise on formation of pre-neoplastic lesions in rat colons in a short-term model of carcinogenic

    Directory of Open Access Journals (Sweden)

    Rossi Elizeu A

    2009-08-01

    Full Text Available Abstract Purpose In this study the influence of moderate or intense physical exercise, alone or in combination with the consumption of a soya product fermented with Enterococcus faecium, on the development of colon cancer induced chemically in rats with 1,2-dimethylhydrazine (DMH, was investigated. Methods Eighty male Wistar SPF rats were randomly allocated to 8 groups (n = 10. One week after the start of the program of product ingestion and/or physical activity, all animals except the controls (group I were injected subcutaneously with 50 mg/kg b.w. of 1,2-dimethylhydrazine (DMH. This procedure was repeated at the end of the second week. At the end of the 6-week experiment, all the animals were euthanized; the colons were removed and numbers of ACF was estimated. Results Twenty-four days after the induction of pre-neoplastic lesions, it was evident that the formation of ACF was not significantly reduced by the ingestion of the fermented product, by intense or moderate physical activity or by a combination of these factors, in comparison with the positive control group of rats (p Conclusion The results reported in this article show that consumption of the fermented soy product described here and the practice of physical exercise (intense or moderate were incapable, separately or combined, of inhibiting the formation of ACF in DMH-induced rats. The intense physical exercise led to an increased number of foci in the colons of these rats and, probably, to greater susceptibility to colorectal cancer.

  4. Inhibition of Neoplastic Transformation and Chemically-Induced Skin Hyperplasia in Mice by Traditional Chinese Medicinal Formula Si-Wu-Tang

    Science.gov (United States)

    Liu, Mandy M.; Huang, Kevin M.; Yeung, Steven; Chang, Andy; Zhang, Suhui; Mei, Nan; Parsa, Cyrus; Orlando, Robert; Huang, Ying

    2017-01-01

    Exploring traditional medicines may lead to the development of low-cost and non-toxic cancer preventive agents. Si-Wu-Tang (SWT), comprising the combination of four herbs, Rehmanniae, Angelica, Chuanxiong, and Paeoniae, is one of the most popular traditional Chinese medicines for women’s diseases. In our previous studies, the antioxidant Nrf2 pathways were strongly induced by SWT in vitro and in vivo. Since Nrf2 activation has been associated with anticarcinogenic effects, the purpose of this study is to evaluate SWT’s activity of cancer prevention. In the Ames test, SWT demonstrated an antimutagenic activity against mutagenicity induced by the chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). In JB6 P+ cells, a non-cancerous murine epidermal model for studying tumor promotion, SWT inhibited epidermal growth factor (EGF)-induced neoplastic transformation. The luciferase reporter gene assays demonstrated that SWT suppressed EGF-induced AP-1 and TNF-α-induced NF-κB activation, which are essential factors involved in skin carcinogenesis. In a DMBA-induced skin hyperplasia assay in ‘Sensitivity to Carcinogenesis’ (SENCAR) mice, both topical and oral SWT inhibited DMBA-induced epidermal hyperplasia, expression of the proliferation marker Proliferating cell nuclear antigen (PCNA), and H-ras mutations. These findings demonstrate, for the first time, that SWT prevents tumor promoter and chemical-induced carcinogenesis in vitro and in vivo, partly by inhibiting DNA damage and blocking the activation of AP-1 and NF-κB. PMID:28335476

  5. Early Astronomy

    Science.gov (United States)

    Thurston, Hugh

    The earliest investigations that can be called scientific are concerned with the sky: they are the beginnings of astronomy. Many early civilizations produced astronomical texts, and several cultures that left no written records left monuments and artifacts-ranging from rock paintings to Stonehenge-that show a clear interest in astronomy. Civilizations in China, Mesopotamia, India and Greece had highly developed astronomies, and the astronomy of the Mayas was by no means negligible. Greek astronomy, as developed by the medieval Arab philosophers, evolved into the astronomy of Copernicus. This displaced the earth from the central stationary position that almost all earlier astronomies had assumed. Soon thereafter, in the first decades of the seventeenth century, Kepler found the true shape of the planetary orbits and Galileo introduced the telescope for astronomical observations.

  6. Factors that affect cancer patient compliance to oral anti-neoplastic therapy Factores que influyen en la adhesión de pacientes con cáncer a la terapia antineoplásica oral Fatores que influenciam a adesão de pacientes com câncer à terapia antineoplásica oral

    OpenAIRE

    Patrícia Andréa Crippa Marques; Angela Maria Geraldo Pierin

    2008-01-01

    OBJECTIVES: To identify factors that can affect compliance to treatment with neoplastic oral drugs in a group of cancer patients. METHODS: Interviews were performed on 61 patients diagnosed with cancer and under anti-neoplastic oral therapy in a private hospital. The interviews were carried out using instruments to assess compliance. RESULTS: Most patients (95%) reported the oral treatment was not difficult. The Morisky and Green Test were positive in 28% of the patients. Factors that may aff...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. Phase- and size-adjusted CT cut-off for differentiating neoplastic lesions from normal colon in contrast-enhanced CT colonography

    Energy Technology Data Exchange (ETDEWEB)

    Luboldt, W. [University Hospital Frankfurt, Department of Radiology, Frankfurt (Germany); Multiorgan Screening Foundation, Frankfurt (Germany); University Hospital Essen, Clinic of Angiology, Essen (Germany); Kroll, M.; Wetter, A.; Vogl, T.J. [University Hospital Frankfurt, Department of Radiology, Frankfurt (Germany); Toussaint, T.L. [Multiorgan Screening Foundation, Frankfurt (Germany); Hoepffner, N. [University Hospital Frankfurt, Department of Internal Medicine, Frankfurt (Germany); Holzer, K. [University Hospital Frankfurt, Department of Visceral and Vascular Surgery, Frankfurt (Germany); Kluge, A. [Kerckhoff Heart Center, Department of Radiology, Bad Nauheim (Germany)

    2004-12-01

    A computed tomography (CT) cut-off for differentiating neoplastic lesions (polyps/carcinoma) from normal colon in contrast-enhanced CT colonography (CTC) relating to the contrast phase and lesion size is determined. CT values of 64 colonic lesions (27 polyps <10 mm, 13 polyps {>=}10 mm, 24 carcinomas) were determined by region-of-interest (ROI) measurements in 38 patients who underwent contrast-enhanced CTC. In addition, the height (H) of the colonic lesions was measured in CT. CT values were also measured in the aorta (A), superior mesenteric vein (V) and colonic wall. The contrast phase was defined by xA + (1 - x)V using x as a weighting factor for describing the different contrast phases ranging from the pure arterial phase (x=1) over the intermediate phases (x=0.9-0.1) to the pure venous phase (x=0). The CT values of the lesions were correlated with their height (H), the different phases (xA + (1 - x)V) and the ratio [xA + (1 - x)V]/H. The CT cut-off was linearly adjusted to the imaged contrast phase and height of the lesion by the line y = m[xA + (1 - x)V]/H + y{sub 0}. The slope m was determined by linear regression in the correlation (lesion {proportional_to}[xA + (1 - x)V]//H) and the Y-intercept y{sub 0} by the minimal shift of the line needed to maximize the accuracy of separating the colonic wall from the lesions. The CT value of the lesions correlated best with the intermediate phase: 0.4A+ 0.6V(r=0.8 for polyps {>=}10 mm, r=0.6 for carcinomas, r=0.4 for polyps <10 mm). The accuracy in the differentiation between lesions and normal colonic wall increased with the height implemented as divisor, reached 91% and was obtained by the dynamic cut-off described by the formula: cut-off(A,V,H) = 1.1[0.4A + 0.6V]/H + 69.8. The CT value of colonic polyps or carcinomas can be increased extrinsically by scanning in the phase in which 0.4A + 0.6V reaches its maximum. Differentiating lesions from normal colon based on CT values is possible in contrast-enhanced CTC and

  9. Microglandular adenosis associated with triple-negative breast cancer is a neoplastic lesion of triple-negative phenotype harbouring TP53 somatic mutations.

    Science.gov (United States)

    Guerini-Rocco, Elena; Piscuoglio, Salvatore; Ng, Charlotte K Y; Geyer, Felipe C; De Filippo, Maria R; Eberle, Carey A; Akram, Muzaffar; Fusco, Nicola; Ichihara, Shu; Sakr, Rita A; Yatabe, Yasushi; Vincent-Salomon, Anne; Rakha, Emad A; Ellis, Ian O; Wen, Y Hannah; Weigelt, Britta; Schnitt, Stuart J; Reis-Filho, Jorge S

    2016-04-01

    Microglandular adenosis (MGA) is a rare proliferative lesion of the breast composed of small glands lacking myoepithelial cells and lined by S100-positive, oestrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative epithelial cells. There is evidence to suggest that MGA may constitute a non-obligate precursor of triple-negative breast cancer (TNBC). We sought to define the genomic landscape of pure MGA and of MGA, atypical MGA (AMGA) and associated TNBCs, and to determine whether synchronous MGA, AMGA, and TNBCs would be clonally related. Two pure MGAs and eight cases of MGA and/or AMGA associated with in situ or invasive TNBC were collected, microdissected, and subjected to massively parallel sequencing targeting all coding regions of 236 genes recurrently mutated in breast cancer or related to DNA repair. Pure MGAs lacked clonal non-synonymous somatic mutations and displayed limited copy number alterations (CNAs); conversely, all MGAs (n = 7) and AMGAs (n = 3) associated with TNBC harboured at least one somatic non-synonymous mutation (range 3-14 and 1-10, respectively). In all cases where TNBCs were analyzed, identical TP53 mutations and similar patterns of gene CNAs were found in the MGA and/or AMGA and in the associated TNBC. In the MGA/AMGA associated with TNBC lacking TP53 mutations, somatic mutations affecting PI3K pathway-related genes (eg PTEN, PIK3CA, and INPP4B) and tyrosine kinase receptor signalling-related genes (eg ERBB3 and FGFR2) were identified. At diagnosis, MGAs associated with TNBC were found to display subclonal populations, and clonal shifts in the progression from MGA to AMGA and/or to TNBC were observed. Our results demonstrate the heterogeneity of MGAs, and that MGAs associated with TNBC, but not necessarily pure MGAs, are genetically advanced, clonal, and neoplastic lesions harbouring recurrent mutations in TP53 and/or other cancer genes, supporting the notion that a subset of MGAs and AMGAs may constitute

  10. Role of endoscopy in early oesophageal cancer.

    Science.gov (United States)

    Mannath, Jayan; Ragunath, Krish

    2016-12-01

    Incidence of oesophageal adenocarcinoma has increased exponentially in the West over the past few decades. Following detection of advanced cancers, 5-year survival rates remain bleak, making identification of early neoplasia, which has a better outcome, important. Detection of subtle oesophageal lesions during endoscopy can be challenging, and advanced imaging techniques might improve their detection. High-definition endoscopy has become a standard in most endoscopy centres, and this technology probably provides better delineation of mucosal features than standard-definition endoscopy. Various image enhancement techniques are now available with the development of new electronics and software systems. Image enhancement with chromoendoscopy using dyes has been a cost-effective option for many years, yet these techniques have been replaced in some contexts by electronic chromoendoscopy, which can be used with the press of a button. However, Lugol's chromoendoscopy remains the gold standard to identify squamous dysplasia. Identification and characterization of subtle neoplastic lesions could help to target biopsies and perform endoscopic resection for better local staging and definitive therapy. In vivo histology with techniques such as confocal endomicroscopy could make endotherapy feasible within a shorter timescale than when relying on histology on tissue samples. Once early neoplasia is identified, treatments include endoscopic resection, endoscopic submucosal dissection or various ablative techniques. Endotherapy has the advantage of being a less invasive technique than oesophagectomy, and is associated with lower mortality and morbidity. Endoscopic ablation therapies have evolved over the past few years, with radiofrequency ablation showing the best results in terms of success rates and complications in Barrett dysplasia.

  11. Early surgical treatment in unilateral coronoid hyperplasia and facial asymmetry.

    Science.gov (United States)

    Galiè, Manlio; Consorti, Giuseppe; Tieghi, Riccardo; Denes, Stefano Andrea; Fainardi, Enrico; Schmid, Judith Louisa; Neuschl, Matthias; Clauser, Luigi

    2010-01-01

    Unilateral coronoid hyperplasia is a rare condition in the pediatric age. It may be an unrecognized cause of restricted mouth opening in children.The limited jaw movement is due to the enlargement of the coronoid process of the mandible that impinges on the zygomatic arch during mouth opening. This pathologic condition is still unknown and often misdiagnosed.Although in the past the term osteochondroma has been used to describe most of the unilateral and a few of the bilateral cases, there is no histologic evidence that the process has a neoplastic origin.Microscopic examination of the removed coronoid process has revealed hyperplastic compact bone covered with a thin layer of normal cartilage.There are multiple causes of mandibular hypomobility, each of them associated with different anatomic structures and etiologies, and a large number of cases, mostly bilateral, are idiopathic in nature.Several theories of pathogenesis have been proposed: temporomandibular joint dysfunctions, mandibular hypomobility, temporalis hyperactivity, hormonal stimulus, persistent cartilage growth center, genetic inheritance, and family factors.Unilateral coronoid hyperplasia is usually due to a trauma or a pathologic condition and is associated with facial asymmetry, being more frequently seen in women with histologic chondromatous or neoplastic changes. A thorough clinical history should include information about the onset and progression of pain and other subjective symptoms.In this study, we present a case of unilateral hyperplasia of the coronoid process in a 3 year-old female who, to the best of our knowledge, is the youngest patient so far reported with such anomaly.Our findings support the recommendation that early surgical treatment and aggressive postoperative physical therapy should be taken into account to allow for recovery of morphology and growth function in children.

  12. MR imaging and ultrasonography findings of early myositis ossificans: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyung Ryeol [Jeju National University Hospital, Department of Radiology, Jeju-si, Jeju Special Self-Governing Province (Korea, Republic of); Park, So Young; Jin, Wook [Kyung Hee University Hospital at Gangdong, Department of Radiology, Seoul (Korea, Republic of); Won, Kyu Yeoun [Kyung Hee University Hospital at Gangdong, Department of Pathology, Seoul (Korea, Republic of)

    2016-10-15

    Myositis ossificans (MO) is a benign soft tissue lesion with non-neoplastic heterotopic bone formation. MO in the intermediate and mature stages can be easily diagnosed if characteristic imaging findings such as a peripheral zonal pattern of ossification with variable thickness is observed. However, it is difficult to correctly diagnose early MO because it can mimic malignancy clinically, radiologically, and histopathologically. We report a case of early pseudosarcomatous phase of non-traumatic MO with atypical imaging findings. A 59-year-old woman presented with pain followed by a mass in the left thigh within a week. MR imaging and ultrasonography showed an intramuscular lesion with preserved muscle fascicles in the vastus lateralis muscle. Intralesional ossification or calcification was not seen on ultrasonography. A diagnosis of myositis ossificans was made by ultrasonographically guided biopsy. (orig.)

  13. 食管、胃和结肠浅表性瘤变的巴黎分型%The Paris endoscopic classification of superficial neoplastic lesions: esophagus, stomach, and colon

    Institute of Scientific and Technical Information of China (English)

    Participants in the Paris Workshop

    2011-01-01

    An international group of endoscopists,surgeons,and pathologists gathered in Paris for an intensive workshop designed to explore the utility and clinical relevance of the Japanese endoscopic classification of superficial neoplastic lesions of the GI tract.This report summarizes the conclusions of the workshop and proposes a general framework for the endoscopic classification of superficial lesions of the esophagus,stomach,and colon.The clinical relevance of this classification is demonstrated in tables that show the relative proportion of each subtype in the esophagus,stomach,and colon,assessing the risk of submucosal invasion and the risk of lymph node metastases.

  14. Detection of Cervical Cancer and High Grade Neoplastic Lesions by a Combination of Liquid‐Based Sampling Preparation and DNA Measurements Using Automated Image Cytometry

    Directory of Open Access Journals (Sweden)

    Xiao Rong Sun

    2005-01-01

    DNA amount greater than 5c were to be referred to colposcopy and biopsy, then 50 lesions that had to be removed would have been discovered (10 CIN2, 15 CIN3/CIS and 25 cancers for the sensitivity of 54.3±6.2% at specificity of 96.9±0.6%. Conclusions: The study suggests that screening for high grade cervical neoplastic lesions and cervical cancer by DNA assisted cytology could be implemented with minimal use of skilled cytotechnologists, at least in those countries where it would be difficult to introduce population based screening for cervical cancer due to the lack of availability of such skilled cytotechnologists.

  15. EMT and CSC-like properties mediated by the IKKβ/IκBα/RelA signal pathway via the transcriptional regulator, Snail, are involved in the arsenite-induced neoplastic transformation of human keratinocytes.

    Science.gov (United States)

    Jiang, Rongrong; Li, Yuan; Xu, Yuan; Zhou, Yun; Pang, Ying; Shen, Lu; Zhao, Yue; Zhang, Jianping; Zhou, Jianwei; Wang, Xinru; Liu, Qizhan

    2013-06-01

    Exposure of humans to inorganic arsenic can cause skin cancer. The epithelial-mesenchymal transition (EMT) and acquisition of cancer stem cell (CSC)-like properties are essential steps in the initiation of human skin cancers; however, the mechanisms of action remain obscure. We have found that, during the neoplastic transformation induced by a low concentration (1.0 μM) of arsenite in human keratinocyte HaCaT cells, the cells undergo an EMT and then acquire a malignant CSC-like phenotype. With longer times for transformation of HaCaT cells, there were increased activations of IκB kinase β (IKKβ), inhibitor nuclear factor-kappa B alpha (IκBα), and nuclear factor κB (NF-κB) RelA and increases in the level of Snail. Further, during the transformation of HaCaT cells, the activation of NF-κB RelA up-regulated Snail levels. Inhibition of NF-κB RelA blocked the arsenite-induced EMT, acquisition of a CSC-like phenotype, and neoplastic transformation. These observations show that EMT, along with acquisition of a CSC-like phenotype mediated by IKKβ/IκBα/RelA signal pathway via Snail, contributes to a low concentration of arsenite-induced tumorigenesis.

  16. New Dimensional Staging of Bisphosphonate-Related Osteonecrosis of the Jaw Allowing a Guided Surgical Treatment Protocol: Long-Term Follow-Up of 266 Lesions in Neoplastic and Osteoporotic Patients from the University of Bari

    Directory of Open Access Journals (Sweden)

    Simonetta Franco

    2014-01-01

    Full Text Available Bisphosphonate-related osteonecrosis of the jaw (BRONJ is the most serious side effect in patients receiving bisphosphonates (BPs for neoplastic disease and osteoporosis. The aim of this study is to propose a new dimensional stage classification, guiding the surgical treatment of BRONJ patients, and to evaluate the success rate of this new management. From 2004 to 2013, 203 neoplastic and osteoporotic patients with 266 BRONJ lesions were referred to the Odontostomatology Unit of the University of Bari. All patients underwent surgery after suspension of BPs therapy and antibiotic treatment. The surgical procedure was complemented by piezosurgery and followed by the application of hyaluronate and amino acids. The new dimensional staging suggests the choice of the surgical approach, and allows the prediction of postoperative complications and soft and hard tissues healing time, guiding the surgical treatment protocol. This protocol could be a successful management strategy for BRONJ, considering the low recurrences rate and the good stabilisation of the surgical sites observed after a long-term follow-up.

  17. Application of stem cell markers in search for neoplastic germ cells in dysgenetic gonads, extragonadal tumours, and in semen of infertile men

    DEFF Research Database (Denmark)

    Hoei-Hansen, Christina E

    2008-01-01

    Germ cell tumours (GCTs) are a complex entity. Current areas of attention include early detection and avoidance of unnecessary over-treatment. Novel findings regarding diagnosis of GCTs located in various anatomical sites are described, particularly testicular GCTs and their common progenitor...... is suspected (i.e. in males investigated for infertility). To develop approaches for early detection CIS gene expression studies have been performed showing many similarities with embryonic stem cells with confirmation of established markers (i.e. PLAP, OCT-3/4, KIT) and identification of novel markers (i...... in semen, microarray-based tumour classification, additional serological GCT markers, and novel stem cell markers for immunohistochemical diagnosis of gonadal and extragonadal GCTs. Many CIS candidate genes are yet uninvestigated, and information from these could increase knowledge about CIS tumour...

  18. Stimulation of neoplastic mouse lung cell proliferation by alveolar macrophage-derived, insulin-like growth factor-1 can be blocked by inhibiting MEK and PI3K activation

    Directory of Open Access Journals (Sweden)

    Malkinson Alvin M

    2011-06-01

    Full Text Available Abstract Background Worldwide, lung cancer kills more people than breast, colon and prostate cancer combined. Alterations in macrophage number and function during lung tumorigenesis suggest that these immune effector cells stimulate lung cancer growth. Evidence from cancer models in other tissues suggests that cancer cells actively recruit growth factor-producing macrophages through a reciprocal signaling pathway. While the levels of lung macrophages increase during tumor progression in mouse models of lung cancer, and high pulmonary macrophage content correlates with a poor prognosis in human non-small cell lung cancer, the specific role of alveolar macrophages in lung tumorigenesis is not clear. Methods After culturing either an immortalized lung macrophage cell line or primary murine alveolar macrophages from naïve and lung-tumor bearing mice with primary tumor isolates and immortalized cell lines, the effects on epithelial proliferation and cellular kinase activation were determined. Insulin-like growth factor-1 (IGF-1 was quantified by ELISA, and macrophage conditioned media IGF-1 levels manipulated by IL-4 treatment, immuno-depletion and siRNA transfection. Results Primary macrophages from both naïve and lung-tumor bearing mice stimulated epithelial cell proliferation. The lungs of tumor-bearing mice contained 3.5-times more IGF-1 than naïve littermates, and media conditioned by freshly isolated tumor-educated macrophages contained more IGF-1 than media conditioned by naïve macrophages; IL-4 stimulated IGF-1 production by both macrophage subsets. The ability of macrophage conditioned media to stimulate neoplastic proliferation correlated with media IGF-1 levels, and recombinant IGF-1 alone was sufficient to induce epithelial proliferation in all cell lines evaluated. Macrophage-conditioned media and IGF-1 stimulated lung tumor cell growth in an additive manner, while EGF had no effect. Macrophage-derived factors increased p-Erk1/2, p

  19. Genetic analysis of the early natural history of epithelial ovarian carcinoma.

    Directory of Open Access Journals (Sweden)

    Bhavana Pothuri

    Full Text Available BACKGROUND: The high mortality rate associated with epithelial ovarian carcinoma (EOC reflects diagnosis commonly at an advanced stage, but improved early detection is hindered by uncertainty as to the histologic origin and early natural history of this malignancy. METHODOLOGY/PRINCIPAL FINDINGS: Here we report combined molecular genetic and morphologic analyses of normal human ovarian tissues and early stage cancers, from both BRCA mutation carriers and the general population, indicating that EOCs frequently arise from dysplastic precursor lesions within epithelial inclusion cysts. In pathologically normal ovaries, molecular evidence of oncogenic stress was observed specifically within epithelial inclusion cysts. To further explore potential very early events in ovarian tumorigenesis, ovarian tissues from women not known to be at high risk for ovarian cancer were subjected to laser catapult microdissection and gene expression profiling. These studies revealed a quasi-neoplastic expression signature in benign ovarian cystic inclusion epithelium compared to surface epithelium, specifically with respect to genes affecting signal transduction, cell cycle control, and mitotic spindle formation. Consistent with this gene expression profile, a significantly higher cell proliferation index (increased cell proliferation and decreased apoptosis was observed in histopathologically normal ovarian cystic compared to surface epithelium. Furthermore, aneuploidy was frequently identified in normal ovarian cystic epithelium but not in surface epithelium. CONCLUSIONS/SIGNIFICANCE: Together, these data indicate that EOC frequently arises in ovarian cystic inclusions, is preceded by an identifiable dysplastic precursor lesion, and that increased cell proliferation, decreased apoptosis, and aneuploidy are likely to represent very early aberrations in ovarian tumorigenesis.

  20. IL-2, IL-4, IFN-γ or TNF-α enhances BAFF-stimulated cell viability and survival by activating Erk1/2 and S6K1 pathways in neoplastic B-lymphoid cells.

    Science.gov (United States)

    Gui, Lin; Zeng, Qingyu; Xu, Zhigang; Zhang, Hai; Qin, Shanshan; Liu, Chunxiao; Xu, Chong; Qian, Zhou; Zhang, Shuangquan; Huang, Shile; Chen, Long

    2016-08-01

    B-cell activating factor of the TNF family (BAFF) has been documented to act as a critical factor in the development of aggressive B lymphocytes and autoimmune diseases. However, the effect of various cytokines on BAFF-elicited neoplastic B-lymphoid cells is not known. In this study, we exhibited that administration of human soluble BAFF (hsBAFF), IL-2, IL-4, IFN-γ, or TNF-α alone increased cell viability and survival in Raji cells concentration-dependently, yet a more robust viability/survival was seen in the cells co-treatment of IL-2, IL-4, IFN-γ, or TNF-α with hsBAFF, respectively. Further research revealed that both Erk1/2 and S6K1 signaling pathways were essential for IL-2, IL-4, IFN-γ, or TNF-α enhancement of the viability/survival in the hsBAFF-stimulated cells, as inhibition of Erk1/2 with U0126 or down-regulation of Erk1/2, or blockage of S6K1 with rapamycin or silencing S6K1, or silencing S6K1/Erk1/2, respectively, reduced the cell viability/survival in the cells treated with/without hsBAFF±IL-2, IL-4, IFN-γ, or TNF-α. These findings indicate that IL-2, IL-4, IFN-γ or TNF-α enhances BAFF-stimulated cell viability/survival by activating Erk1/2 and S6K1 signaling in neoplastic B-lymphoid cells. Our data suggest that modulation of IL-2, IL-4, IFN-γ and/or TNF-α levels, or inhibitors of Erk1/2 or S6K1 may be a new approach to prevent BAFF-induced aggressive B-cell malignancies.

  1. Sustained Early Disruption of Mitochondrial Function Contributes to Arsenic-Induced Prostate Tumorigenesis.

    Science.gov (United States)

    Singh, B; Kulawiec, M; Owens, K M; Singh, A; Singh, K K

    2016-10-01

    Arsenic is a well-known human carcinogen that affects millions of people worldwide, but the underlying mechanisms of carcinogenesis are unclear. Several epidemiological studies have suggested increased prostate cancer incidence and mortality due to exposure to arsenic. Due to lack of an animal model of arsenic-induced carcinogenesis, we used a prostate epithelial cell culture model to identify a role for mitochondria in arsenic-induced prostate cancer. Mitochondrial morphology and membrane potential was impacted within a few hours of arsenic exposure of non-neoplastic prostate epithelial cells. Chronic arsenic treatment induced mutations in mitochondrial genes and altered mitochondrial functions. Human non-neoplastic prostate epithelial cells continuously cultured for seven months in the presence of 5 µM arsenite showed tumorigenic properties in vitro and induced tumors in SCID mice, which indicated transformation of these cells. Protein and mRNA expression of subunits of mtOXPHOS complex I were decreased in arsenic-transformed cells. Alterations in complex I, a main site for reactive oxygen species (ROS) production as well as increased expression of ROS-producing NOX4 in arsenic-transformed cells suggested a role of oxidative stress in tumorigenic transformation of prostate epithelial cells. Whole genome cGH array analyses of arsenic-transformed prostate cells identified extensive genomic instability. Our study revealed mitochondrial dysfunction induced oxidative stress and decreased expression of p53 in arsenic-transformed cells as an underlying mechanism of the mitochondrial and nuclear genomic instability. These studies suggest that early changes in mitochondrial functions are sustained during prolong arsenic exposure. Overall, our study provides evidence that arsenic disruption of mitochondrial function is an early and key step in tumorigenic transformation of prostate epithelial cells.

  2. Autism: Why Act Early?

    Science.gov (United States)

    ... What's this? Submit Button Past Emails CDC Features Autism: Why Act Early? Language: English Español (Spanish) Recommend ... helped the world make sense." Florida teenager with Autism Spectrum Disorder "Because my parents acted early, I ...

  3. Cancer treatment -- early menopause

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000912.htm Cancer treatment - early menopause To use the sharing features on this page, please enable JavaScript. Certain types of cancer treatments can cause women to have early menopause. This ...

  4. Overview of Early Intervention

    Science.gov (United States)

    ... infant or toddler for early intervention (e.g., Down syndrome, Fragile X syndrome). Determining eligibility | The results of the evaluation will be used to determine your child’s eligibility for early intervention services. You and a ...

  5. Early Retirement Programs.

    Science.gov (United States)

    Everett, Peter W.

    1984-01-01

    Early retirement programs offer individuals an alternative to the work ethic while allowing them to maintain job security. Examples are given of several early, partial, and phased retirement programs currently being used in universities and public school systems. (DF)

  6. Specific posttranslational modification regulates early events in mammary carcinoma formation.

    Science.gov (United States)

    Guo, Hua-Bei; Johnson, Heather; Randolph, Matthew; Nagy, Tamas; Blalock, Ryan; Pierce, Michael

    2010-12-07

    The expression of an enzyme, GnT-V, that catalyzes a specific posttranslational modification of a family of glycoproteins, namely a branched N-glycan, is transcriptionally up-regulated during breast carcinoma oncogenesis. To determine the molecular basis of how early events in breast carcinoma formation are regulated by GnT-V, we studied both the early stages of mammary tumor formation by using 3D cell culture and a her-2 transgenic mouse mammary tumor model. Overexpression of GnT-V in MCF-10A mammary epithelial cells in 3D culture disrupted acinar morphogenesis with impaired hollow lumen formation, an early characteristic of mammary neoplastic transformation. The disrupted acinar morphogenesis of mammary tumor cells in 3D culture caused by her-2 expression was reversed in tumors that lacked GnT-V expression. Moreover, her-2-induced mammary tumor onset was significantly delayed in the GnT-V null tumors, evidence that the lack of the posttranslational modification catalyzed by GnT-V attenuated tumor formation. Inhibited activation of both PKB and ERK signaling pathways was observed in GnT-V null tumor cells. The proportion of tumor-initiating cells (TICs) in the mammary tumors from GnT-V null mice was significantly reduced compared with controls, and GnT-V null TICs displayed a reduced ability to form secondary tumors in NOD/SCID mice. These results demonstrate that GnT-V expression and its branched glycan products effectively modulate her-2-mediated signaling pathways that, in turn, regulate the relative proportion of tumor initiating cells and the latency of her-2-driven tumor onset.

  7. Mitochondrial DNA as a potential tool for early cancer detection

    Directory of Open Access Journals (Sweden)

    Parr Ryan L

    2006-01-01

    Full Text Available Abstract The recent surge in mitochondrial research has been driven by the identification of mitochondria-associated diseases and the role of mitochondria in apoptosis. Both of these aspects have identified mitochondrial analysis as a vital component of medical research. Moreover, mitochondria have been implicated in the process of carcinogenesis because of their vital role in energy production, nuclear-cytoplasmic signal integration and control of metabolic pathways. Interestingly, at some point during neoplastic transformation, there is an increase in reactive oxygen species, which damage the mitochondrial genome. This accelerates the somatic mutation rate of mitochondrial DNA. It has been proposed that these mutations may serve as an early indication of potential cancer development and may represent a means for tracking tumour progression. The purpose of this review is to explore the potential utility that these mutations may afford for the identification and monitoring of neoplasia and malignant transformation where appropriate body fluids or non-invasive tissue access is available for mitochondrial DNA recovery. Specifically, prostate, breast, colorectal, skin and lung cancers are discussed.

  8. Activation status of Wnt/ß-catenin signaling in normal and neoplastic breast tissues: relationship to HER2/neu expression in human and mouse.

    Directory of Open Access Journals (Sweden)

    Sara Khalil

    Full Text Available Wnt/ß-catenin signaling is strongly implicated in neoplasia, but the role of this pathway in human breast cancer has been controversial. Here, we examined Wnt/ß-catenin pathway activation as a function of breast cancer progression, and tested for a relationship with HER2/neu expression, using a human tissue microarray comprising benign breast tissues, ductal carcinoma in situ (DCIS, and invasive carcinomas. Cores were scored for membranous ß-catenin, a key functional component of adherens junctions, and for nucleocytoplasmic ß-catenin, a hallmark of Wnt/ß-catenin pathway activation. Only 82% of benign samples exhibited membrane-associated ß-catenin, indicating a finite frequency of false-negative staining. The frequency of membrane positivity was similar in DCIS samples, but was significantly reduced in carcinomas (45%, P<0.001, consistent with loss of adherens junctions during acquisition of invasiveness. Negative membrane status in cancers correlated with higher grade (P = 0.04 and estrogen receptor-negative status (P = 0.03, both indices of poor prognosis. Unexpectedly, a substantial frequency of nucleocytoplasmic ß-catenin was observed in benign breast tissues (36%, similar to that in carcinomas (35%. Positive-staining basal nuclei observed in benign breast may identify putative stem cells. An increased frequency of nucleocytoplasmic ß-catenin was observed in DCIS tumors (56%, suggesting that pathway activation may be an early event in human breast neoplasia. A correlation was observed between HER2/neu expression and nucleocytoplasmic ß-catenin in node-positive carcinomas (P = 0.02. Furthermore, cytoplasmic ß-catenin was detected in HER2/neu-induced mouse mammary tumors. The Axin2(NLSlacZ mouse strain, a previously validated reporter of mammary Wnt/ß-catenin signaling, was utilized to define in vivo transcriptional consequences of HER2/neu-induced ß-catenin accumulation. Discrete hyperplastic foci observed in mammary

  9. UTILITY OF A DUAL IMMUNOSTAIN LIKE P53 AND CK20 TO AID IN THE DIAGNOSIS AND CATEGORIZATION OF NEOPLASTIC BLADDER BIOPSIES

    Directory of Open Access Journals (Sweden)

    Dipkana

    2015-03-01

    Full Text Available INTRODUCTION : Urothelial neoplasms contribute significantly to the overall human cancer burden with approximately 260,000 new cases per year worldwide. Although over 50% cases, the lesions are diagnosed by biopsy at an early stage but the prognosis is sometimes difficult to asses s because of heterogeneity, multifocality and tumor recurrence. AIMS AND OBJECTIVE : To evaluate the scope of immunohistochemical expression of mutated p53 & CK20 in human urothelial neoplasms with regard to grade, stage and outcome of the patients. MATERIALS AND METHOD S : In this study fifty three (53 consecutive patients were taken from May’ 2012 to April’ 2013 . Histopathological examinations were performed and the grading was done according to the WHO/ISUP (2004 consensus classification of urothel ial neoplasms. Immunohistochemical staining for p53 & CK20 were performed. RESULTS: 11 cases were found to be of high grade papillary urothelial carcinoma,9 cases of invasive urothelial carcinoma, 29 cases of low grade papillary urothelial carcinoma and 4 patients with papillary urothelial neoplasms of low malignant potential (PUNLMP. Unfortunately not a single benign lesion was received in the study period. Mean percent positivity of p53 in case of high grade carcinoma is 75.45% with a p value of 0.001 an d mean percent positivity of CK20 in case of high grade carcinoma is 84.55% with a p value of 0.001; both are highly significant.

  10. Optimizing Early Retirement Decisions.

    Science.gov (United States)

    2007-11-02

    the military. The U.S. Army’s early retirement program is a temporary one designed to allow some soldiers to leave the service prior to 20 years of...whether it makes financial sense for an officer to select early retirement . A spreadsheet formulation is developed and used to indicate if and when...an officer should select early retirement . The program investigates the decision that various civilian salary levels and various assumed discount rates.

  11. Expressão de genes relacionados à função adrenocortical no estado de caquexia neoplásica = Expression of genes related to the adrenocortical function in the neoplastic cachexia process

    Directory of Open Access Journals (Sweden)

    Nicole de Angelis Scripes

    2009-04-01

    Full Text Available A glândula adrenal tem papel fundamental na resposta neuroendócrina,especialmente em situações em que há comprometimento da homeostasia. No processo de caquexia neoplásica, há prejuízo da homeostasia por alterações nutricionais e metabólicas do câncer em estágio avançado, envolvendo a resposta do eixo hipotálamo-hipófise-adrenal. Neste trabalho, foi utilizado um modelo animal de caquexia induzida pelo tumor de Walker-256 em ratos Wistar. Os animais (n=4 foram sacrificados dez dias após a inoculação de células tumorais e a glândula adrenal foi removida. O RNA foi extraído para o estudo da expressão de genes relacionados ao controle da esteroidogênese por RT-PCR semiquantitativa. A análise dos dados demonstrou expressão significativamente reduzida dos genes MC2R (receptor tipo 2 para melacortina, 3ßHSD I (3β-hidroxiesteroidedesidrogenase tipo I e TSPO (proteína translocadora em animais com caquexia neoplásica(valores de P=0,037; 0,0097 e 0,052, respectivamente, revelando falência do córtex da adrenal.The adrenal gland plays a crucial role in the neuroendocrine response, especially in situations where homeostasis is disturbed. In the neoplastic cachexia process, there is homeostasis impairment by nutritional and metabolic alterations of advanced-stage cancer, involving hypothalamus-pituitary-adrenal axis response. In thisassignment, an experimental model of cachexia induced by Walker-256 tumor was performed in Wistar rats. Animals (n=4 were sacrificed 10 days after inoculation of tumor cells, and the adrenal glands were excised. The RNA was isolated for the study of gene expression related to the steroidogenesis control by semi-quantitative RT-PCR. Data analysis showed a significant reduced expression of MC2R (melancortin type 2 receptor, 3ßHSD I (3-beta-hydroxysteroid dehydrogenase type I and TSPO (translocator protein genes in animals with neoplastic cachexia (P=0.037, 0.0097 and 0.052, respectively, revealing

  12. A eudesmane-type sesquiterpene isolated from Pluchea odorata (L.) Cass. combats three hallmarks of cancer cells: Unrestricted proliferation, escape from apoptosis and early metastatic outgrowth in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Blaschke, Michael [Department of Pharmacognosy, University of Vienna, Althanstrasse 14, A-1090 Vienna (Austria); Department of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20 (Austria); McKinnon, Ruxandra [Department of Pharmacognosy, University of Vienna, Althanstrasse 14, A-1090 Vienna (Austria); Nguyen, Chi Huu [Department of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20 (Austria); Department of Clinical Pharmacy and Diagnostics, University of Vienna, Althanstrasse 14, A-1090 Vienna (Austria); Holzner, Silvio [Department of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20 (Austria); Zehl, Martin [Department of Pharmacognosy, University of Vienna, Althanstrasse 14, A-1090 Vienna (Austria); Department of Pharmaceutical Chemistry, University of Vienna, Althanstrasse 14, A-1090 Vienna (Austria); Atanasov, Atanas Georgiev [Department of Pharmacognosy, University of Vienna, Althanstrasse 14, A-1090 Vienna (Austria); Schelch, Karin [Department of Medicine I, Institute of Cancer Research, Comprehensive Cancer Centre Vienna, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria); Krieger, Sigurd [Department of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20 (Austria); Diaz, Rene; Frisch, Richard [Institute for Ethnobiology, Playa Diana, San José/Petén (Guatemala); Feistel, Björn [Finzelberg GmbH & Co. KG, Koblenzer Strasse 48-54, D-56626 Andernach (Germany); Jäger, Walter [Department of Clinical Pharmacy and Diagnostics, University of Vienna, Althanstrasse 14, A-1090 Vienna (Austria); Ecker, Gerhard F. [Department of Pharmaceutical Chemistry, Division of Drug Design and Medicinal Chemistry, University of Vienna, Althanstraße 14, A-1090 Vienna (Austria); and others

    2015-07-15

    Highlights: • PO-1 perturbs cell cycle regulators and progression. • PO-1 inhibits HL-60 cell expansion. • PO-1 and PO-2 attenuate tumour cell intravasation through the endothelial barrier. - Abstract: Pluchea odorata is ethno pharmaceutically used to treat inflammation-associated disorders. The dichloromethane extract (DME) was tested in the carrageenan-induced rat paw oedema assay investigating its effect on inflammation that was inhibited by 37%. Also an in vitro anti-neoplastic potential was reported. However, rather limited information about the bio-activity of purified compounds and their cellular mechanisms are available. Therefore, two of the most abundant eudesmanes in P. odorata were isolated and their anti-neoplastic and anti-intravasative activities were studied. HL-60 cells were treated with P. odorata compounds and metabolic activity, cell number reduction, cell cycle progression and apoptosis induction were correlated with relevant protein expression. Tumour cell intravasation through lymph endothelial monolayers was measured and potential causal mechanisms were analyzed by Western blotting. Compound PO-1 decreased the metabolic activity of HL-60 cells (IC{sub 50} = 8.9 μM after 72 h) and 10 μM PO-1 induced apoptosis, while PO-2 showed just weak anti-neoplastic activities at concentrations beyond 100 μM. PO-1 arrested the cell cycle in G1 and this correlated with induction of JunB expression. Independent of this mechanism 25 μM PO-1 decreased MCF-7 spheroid intravasation through the lymph endothelial barrier. Hence, PO-1 inhibits an early step of metastasis, impairs unrestricted proliferation and induces apoptosis at low micromolar concentrations. These results warrant further testing in vivo to challenge the potential of PO-1 as novel lead compound.

  13. Early College High Schools

    Science.gov (United States)

    Dessoff, Alan

    2011-01-01

    For at-risk students who stand little chance of going to college, or even finishing high school, a growing number of districts have found a solution: Give them an early start in college while they still are in high school. The early college high school (ECHS) movement that began with funding from the Bill and Melinda Gates Foundation 10 years ago…

  14. Early Retirement Payoff

    Science.gov (United States)

    Fitzpatrick, Maria D.; Lovenheim, Michael F.

    2014-01-01

    As public budgets have grown tighter over the past decade, states and school districts have sought ways to control the growth of spending. One increasingly common strategy employed to rein in costs is to offer experienced teachers with high salaries financial incentives to retire early. Although early retirement incentive (ERI) programs have been…

  15. Early Epigenetic Downregulation of microRNA-192 Expression Promotes Pancreatic Cancer Progression.

    Science.gov (United States)

    Botla, Sandeep K; Savant, Soniya; Jandaghi, Pouria; Bauer, Andrea S; Mücke, Oliver; Moskalev, Evgeny A; Neoptolemos, John P; Costello, Eithne; Greenhalf, William; Scarpa, Aldo; Gaida, Matthias M; Büchler, Markus W; Strobel, Oliver; Hackert, Thilo; Giese, Nathalia A; Augustin, Hellmut G; Hoheisel, Jörg D

    2016-07-15

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by very early metastasis, suggesting the hypothesis that metastasis-associated changes may occur prior to actual tumor formation. In this study, we identified miR-192 as an epigenetically regulated suppressor gene with predictive value in this disease. miR-192 was downregulated by promoter methylation in both PDAC and chronic pancreatitis, the latter of which is a major risk factor for the development of PDAC. Functional studies in vitro and in vivo in mouse models of PDAC showed that overexpression of miR-192 was sufficient to reduce cell proliferation and invasion. Mechanistic analyses correlated changes in miR-192 promoter methylation and expression with epithelial-mesenchymal transition. Cell proliferation and invasion were linked to altered expression of the miR-192 target gene SERPINE1 that is encoding the protein plasminogen activator inhibitor-1 (PAI-1), an established regulator of these properties in PDAC cells. Notably, our data suggested that invasive capacity was altered even before neoplastic transformation occurred, as triggered by miR-192 downregulation. Overall, our results highlighted a role for miR-192 in explaining the early metastatic behavior of PDAC and suggested its relevance as a target to develop for early diagnostics and therapy. Cancer Res; 76(14); 4149-59. ©2016 AACR.

  16. Early Option Exercise

    DEFF Research Database (Denmark)

    Heje Pedersen, Lasse; Jensen, Mads Vestergaard

    A classic result by Merton (1973) is that, except just before expiration or dividend payments, one should never exercise a call option and never convert a convertible bond. We show theoretically that this result is overturned when investors face frictions. Early option exercise can be optimal when...... it reduces short-sale costs, transaction costs, or funding costs. We provide consistent empirical evidence, documenting billions of dollars of early exercise for options and convertible bonds using unique data on actual exercise decisions and frictions. Our model can explain as much as 98% of early exercises...

  17. Early Option Exercise

    DEFF Research Database (Denmark)

    Jensen, Mads Vestergaard; Heje Pedersen, Lasse

    2016-01-01

    A classic result by Merton (1973) is that, except just before expiration or dividend payments, one should never exercise a call option and never convert a convertible bond. We show theoretically that this result is overturned when investors face frictions. Early option exercise can be optimal when...... it reduces short-sale costs, transaction costs, or funding costs. We provide consistent empirical evidence, documenting billions of dollars of early exercise for options and convertible bonds using unique data on actual exercise decisions and frictions. Our model can explain as much as 98% of early exercises...

  18. Drawing up an individual risk index for development of metachronous neoplastic lesions in resected colorectal cancer Elaboración de un índice individual del riesgo para el desarrollo de lesiones neoplásicas metacrónicas en el cáncer colorrectal resecado

    OpenAIRE

    Ana Borda; José María Martínez-Peñuela; Fernando Borda; Miguel Muñoz-Navas; Francisco Javier Jiménez; Cristina Carretero

    2012-01-01

    Aim: to identify possible risk factors for the development of metachronous lesions in colorectal cancer (CRC) which would allow to establish a post-surgical individual prognostic index. Patients and methods: three hundred eighty-two surgically treated CRC were reviewed. We compared the incidence of metachronous lesions in 40 variables concerning patient clinical data and initial neoplastic findings. An individual risk index for metachronicity was drawn up including those variables which prese...

  19. Early Head Start Evaluation

    Data.gov (United States)

    U.S. Department of Health & Human Services — Longitudinal information from an evaluation where children were randomly assigned to Early Head Start or community services as usual;direct assessments and...

  20. Earth's early biosphere

    Science.gov (United States)

    Des Marais, D. J.

    1998-01-01

    Understanding our own early biosphere is essential to our search for life elsewhere, because life arose on Earth very early and rocky planets shared similar early histories. The biosphere arose before 3.8 Ga ago, was exclusively unicellular and was dominated by hyperthermophiles that utilized chemical sources of energy and employed a range of metabolic pathways for CO2 assimilation. Photosynthesis also arose very early. Oxygenic photosynthesis arose later but still prior to 2.7 Ga. The transition toward the modern global environment was paced by a decline in volcanic and hydrothermal activity. These developments allowed atmospheric O2 levels to increase. The O2 increase created new niches for aerobic life, most notably the more advanced Eukarya that eventually spawned the megascopic fauna and flora of our modern biosphere.

  1. (Reconceptualizing Early Childhood Education)?

    African Journals Online (AJOL)

    denise

    Second, I must stress the immensely precious and ..... 'useless' subjects such as emotions, sensitivity, .... a range of different sociological fields including early childhood, gender, .... The origins of intelligence in children (M. Cook, Trans.).

  2. Biogeochemistry: Early phosphorus redigested

    Science.gov (United States)

    Poulton, Simon W.

    2017-02-01

    Atmospheric oxygen was maintained at low levels throughout huge swathes of Earth's early history. Estimates of phosphorus availability through time suggest that scavenging from anoxic, iron-rich oceans stabilized this low-oxygen world.

  3. Embracing early literacy indicators

    DEFF Research Database (Denmark)

    Broström, Stig; Hansen, Ole Henrik; Jensen, Anders Skriver

    2010-01-01

    Abstract til paper om early literacy indikatorer. Det paper abstractet er knyttet til var en del af et inviteret, selvorganiseret symposium som afrapporterede EASE-projektet (www.ease-eu.com) på OMEP's 26. verdenskongres....

  4. Early Prediction of Preeclampsia

    Directory of Open Access Journals (Sweden)

    Leona C. Poon

    2014-01-01

    Full Text Available Effective screening for the development of early onset preeclampsia (PE can be provided in the first-trimester of pregnancy. Screening by a combination of maternal risk factors, uterine artery Doppler, mean arterial pressure, maternal serum pregnancy-associated plasma protein-A, and placental growth factor can identify about 95% of cases of early onset PE for a false-positive rate of 10%.

  5. Early Mover Advantages

    OpenAIRE

    Bijwaard, Govert; Janssen, Maarten; Maasland, Emiel

    2005-01-01

    This paper analyzes empirically whether and if so to what extent later entrants in the European mobile telephony industry have a disadvantage vis-à-vis incumbents and early mover entrants. To analyze this question a dynamic model of market share development and a series of static models are considered. There is clear evidence of early mover advantage, mainly caused by the influence of the penetration rate: it pays to enter when still few people have acquired a mobile telephone. Another import...

  6. Early childhood aggression

    OpenAIRE

    Alink, Lenneke Rosalie Agnes

    2006-01-01

    In this thesis the development, stability, and correlates of early childhood aggression were investigated. The normative development was examined in a general population sample using questionnaires completed by the parents of 12-, 24-, and 36-month-old children and again one year later. Results showed an early childhood aggression curve, with increasing rates of aggression in the second year of life and decreasing rates in the fourth year. One-year stabilities were moderate for 12-month-olds ...

  7. How early is early dark energy?

    CERN Document Server

    Pettorino, Valeria; Wetterich, Christof

    2013-01-01

    We investigate constraints on early dark energy (EDE) from the Cosmic Microwave Background (CMB) anisotropy, taking into account data from WMAP9 combined with latest small scale measurements from the South Pole Telescope (SPT). For a constant EDE fraction we propose a new parametrization with one less parameter but still enough to provide similar results to the ones previously studied in literature. The main emphasis of our analysis, however, compares a new set of different EDE parametrizations that reveal how CMB constraints depend on the redshift epoch at which Dark Energy was non negligible. We find that bounds on EDE get substantially weaker if dark energy starts to be non-negligible later, with early dark energy fraction Omega_e free to go up to about 5% at 2 sigma if the onset of EDE happens at z < 100. Tight bounds around 1-2% are obtained whenever dark energy is present at last scattering, even if its effects switch off afterwards. We show that the CMB mainly constrains the presence of Dark Energy ...

  8. Revisiting the structure of the anti-neoplastic glucans of Mycobacterium bovis Bacille Calmette-Guerin. Structural analysis of the extracellular and boiling water extract-derived glucans of the vaccine substrains.

    Science.gov (United States)

    Dinadayala, Premkumar; Lemassu, Anne; Granovski, Pierre; Cérantola, Stéphane; Winter, Nathalie; Daffé, Mamadou

    2004-03-26

    The attenuated strain of Mycobacterium bovis Bacille Calmette-Guérin (BCG), used worldwide to prevent tuberculosis and leprosy, is also clinically used as an immunotherapeutic agent against superficial bladder cancer. An anti-tumor polysaccharide has been isolated from the boiling water extract of the Tice substrain of BCG and tentatively characterized as consisting primarily of repeating units of 6-linked-glucosyl residues. Mycobacterium tuberculosis and other mycobacterial species produce a glycogen-like alpha-glucan composed of repeating units of 4-linked glucosyl residues substituted at some 6 positions by short oligoglucosyl units that also exhibits an anti-tumor activity. Therefore, the impression prevails that mycobacteria synthesize different types of anti-neoplastic glucans or, alternatively, the BCG substrains are singular in producing a unique type of glucan that may confer to them their immunotherapeutic property. The present study addresses this question through the comparative analysis of alpha-glucans purified from the extracellular materials and boiling water extracts of three vaccine substrains. The polysaccharides were purified, and their structural features were established by mono- and two-dimensional NMR spectroscopy and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of the enzymatic and chemical degradation products of the purified compounds. The glucans isolated by the two methods from the three substrains of BCG were shown to exhibit identical structural features shared with the glycogen-like alpha-glucan of M. tuberculosis and other mycobacteria. Incidentally, we observed an occasional release of dextrans from Sephadex columns that may explain the reported occurrence of 6-substituted alpha-glucans in mycobacteria.

  9. Cerebral neoplastic enhancing lesions: Multicenter, randomized, crossover intraindividual comparison between gadobutrol (1.0 M) and gadoterate meglumine (0.5 M) at 0.1 mmol Gd/kg body weight in a clinical setting

    Energy Technology Data Exchange (ETDEWEB)

    Anzalone, Nicoletta, E-mail: anzalone.nicoletta@hsr.it [Department of Neuroradiology, Scientific Institute H.S. Raffaele, Via Olgettina 60, 20132 Milan (Italy); Scarabino, Tommaso, E-mail: tscarabino@hotmail.com [“L. Bonomo” Hospital Center, Viale Istria 1, 70031 Andria (Italy); Venturi, Carlo, E-mail: c.venturi@ao-siena.toscana.it [U.O.C. Neuroimaging and Neurointerventional, “Santa Maria alle Scotte” Polyclinic, Viale Bracci 16, 53100 Siena (Italy); Cristaudo, Concetto, E-mail: concetto.cristaudo@tiscali.it [Cannizzaro Hospital, Via Messina, 829, 98125 Catania (Italy); Tartaro, Armando, E-mail: a.tartaro@radiol.unich.it [Institute for Advanced Biomedical Techniques, Clinical Sciences and Bioimaging Dept., G.D’Annunzio University, Via dei Vestini, 66100 Chieti (Italy); Scotti, Giuseppe, E-mail: scotti.giuseppe@hsr.it [University Scientific Institute, San Raffaele Hospital, Via Olgettina 60, 20090 Milano (Italy); Zimatore, Domenico, E-mail: dszimatore@hotmail.it [Maggiore Borgo Trento City Hospital, Piazzale Stefani 1, 37126 Verona (Italy); Floris, Roberto, E-mail: roberto.floris@uniroma2.it [Dept. of Diagnostic and Molecular Imaging, UOC of Neuroradiology, Tor Vergata Polyclinics, Viale Oxford 81, 00133 Roma (Italy); Carriero, Alessandro, E-mail: profcarriero@virgilio.it [“Maggiore della Carità” University Hospital, Corso Mazzini, 18, 28100 Novara (Italy); Longo, Marcello, E-mail: longomar@tin.it [“G. Martino” University Polyclinic, Via Consolare Valeria, 1, 98125 Messina (Italy); Cirillo, Mario, E-mail: emmecirillo@libero.it [Second University Hospital c/o CTO, Viale Colli Aminei, 21, 80131 Napoli (Italy); and others

    2013-01-15

    Objective: Two macrocyclic extracellular contrast agents, one-molar neutral gadobutrol and ionic gadoterate meglumine, were compared to determine the overall preference for one or the other in a clinical setting. Materials and methods: Multicenter, randomized, single-blind, intra-individually controlled, comparison study with a corresponding blinded read. Efficacy analysis was based on 136 patients who underwent identical MRI examinations: group A first received 1.0 M gadobutrol followed by 0.5 M gadoterate meglumine 48 h to 7 days later; group B had a reversed administration order. Three independent blinded readers assessed off-site their overall diagnostic preference (primary efficacy parameter) based on a matched pairs approach. Results: Superiority of gadobutrol over gadoterate meglumine was demonstrated for the qualitative assessment of overall preference across all readers by a statistically significant difference between both contrast agents for this primary endpoint. Preferences in lesion enhancement (secondary endpoint) were also found significantly in favor of gadobutrol. For preference in lesion delineation from surrounding tissue/edema and for internal structure only a trend towards a higher proportion for gadobutrol was found (except for internal structure reported by one reader, which showed a result of statistical significance). Lesion contrast and relative lesion enhancement (quantitative parameters) were statistically significantly higher for gadobutrol compared to gadoterate meglumine. Conclusion: Contrast-enhanced MRI of neoplastic brain lesions at a dose of 0.1 mmol Gd/kg body weight, assessed in a standardized off-site blinded reading, results in a significantly higher qualitative and quantitative preference for gadobutrol compared to gadoterate meglumine.

  10. Rapamycin inhibits BAFF-stimulated cell proliferation and survival by suppressing mTOR-mediated PP2A-Erk1/2 signaling pathway in normal and neoplastic B-lymphoid cells.

    Science.gov (United States)

    Zeng, Qingyu; Zhang, Hai; Qin, Jiamin; Xu, Zhigang; Gui, Lin; Liu, Beibei; Liu, Chunxiao; Xu, Chong; Liu, Wen; Zhang, Shuangquan; Huang, Shile; Chen, Long

    2015-12-01

    B-cell activating factor (BAFF) is involved in not only physiology of normal B cells, but also pathophysiology of aggressive B cells related to malignant and autoimmune diseases. Rapamycin, a lipophilic macrolide antibiotic, has recently shown to be effective in the treatment of human lupus erythematosus. However, how rapamycin inhibits BAFF-stimulated B-cell proliferation and survival has not been fully elucidated. Here, we show that rapamycin inhibited human soluble BAFF (hsBAFF)-induced cell proliferation and survival in normal and B-lymphoid (Raji and Daudi) cells by activation of PP2A and inactivation of Erk1/2. Pretreatment with PD98059, down-regulation of Erk1/2, expression of dominant negative MKK1, or overexpression of wild-type PP2A potentiated rapamycin's suppression of hsBAFF-activated Erk1/2 and B-cell proliferation/viability, whereas expression of constitutively active MKK1, inhibition of PP2A by okadaic acid, or expression of dominant negative PP2A attenuated the inhibitory effects of rapamycin. Furthermore, expression of a rapamycin-resistant and kinase-active mTOR (mTOR-T), but not a rapamycin-resistant and kinase-dead mTOR-T (mTOR-TE), conferred resistance to rapamycin's effects on PP2A, Erk1/2 and B-cell proliferation/viability, implying mTOR-dependent mechanism involved. The findings indicate that rapamycin inhibits BAFF-stimulated cell proliferation/survival by targeting mTOR-mediated PP2A-Erk1/2 signaling pathway in normal and neoplastic B-lymphoid cells. Our data highlight that rapamycin may be exploited for preventing excessive BAFF-induced aggressive B-cell malignancies and autoimmune diseases.

  11. Progress in anti-neoplastic effects and mechanisms of dihydroartemisinin%二氢青蒿素抗肿瘤作用及其机制研究进展

    Institute of Scientific and Technical Information of China (English)

    陆金健; 黄鸣清; 陈修平; 王一涛

    2012-01-01

    Dihydroartemisinin, an important artemisinin derivative, presents excellent anti-neoplastic potential. This article reviews the latest progress in the anti-cancer activity of dihydroartemisinin and the possible mechanisms including anti-proliferation, cell cycle arrest, apoptosis induction, anti-angiogenesis and anti-metastasis. Iron ( Ⅱ) or heme may be the direct target for dihydroartemisinin. The broad anti-cancer spectrum, the low toxicity to normal cells and the potential of anti-multi-drug resistant cells make it a likely new anti-cancer candidate compound.%二氢青篙素是青蒿素的重要衍生物,具有显著的抗疟作用.对多种肿瘤动物模型具有一定的肿瘤抑制作用,提示其具有抗肿瘤作用.二氢青蒿素的抗肿瘤作用机制可能与抑制肿瘤细胞增殖包括诱导肿瘤细胞周期阻滞和促进肿瘤细胞凋亡、抑制肿瘤新生血管生成以及抗肿瘤细胞侵袭和转移等有关.细胞内亚铁或亚铁血红素可能是二氢青蒿素抗肿瘤作用的直接靶点.由于二氢青蒿素具有广谱抗肿瘤作用、对正常细胞毒性小及对多药耐药细胞有效等优点,因此有可能被开发为新的抗肿瘤药物.

  12. Increased messenger RNA levels of the antagonist thyroid hormone receptor erbA-alpha 2 and decreased levels of erbA-alpha 1 and erbA-beta 1 receptor messenger RNAs in neoplastic rodent cells.

    Science.gov (United States)

    Too, C K; Guernsey, D L

    1992-04-15

    Nothern blot analysis of total RNA from the mouse C3H/10T1/2 cell line indicated that the erbA alpha gene transcribed three mRNA species of similar sizes (2.6, 5.5, 6.6 kilobases) as found in rodents. The 2.6-kilobase mRNA (erbA-alpha 2) was approximately 7- to 8-fold more abundant than either the 5.5- (erbA-alpha 1) or 6.6-kilobase species. The expression of the erbA-alpha 2 transcript increased 3- to 30-fold when "normal" mouse or rat cells were growth arrested by concluence. Triiodothyronine, at a concentration of 1 nM, had no effect on the levels of the erbA-alpha mRNA species in confluent cells nor on the levels of erbA-alpha 2 in proliferative normal or transformed C3H/10T1/2 cells. In log-phase growing cells there was a 2.5- to 5-fold increase in the relative expression of erbA-alpha 2 mRNA in transformed mouse C3H/10T1/2 cells, transformed cloned rat embryo fibroblasts (CREF), transformed rat embryo fibroblasts (REF), and a transformed temperature-sensitive rat mutant cell line (ts7E) when compared with their non-transformed counterparts. In contrast to the elevation of erbA-alpha 2 in transformed cells, erbA-alpha 1 and erbA-beta 1 mRNAs decreased in transformed mouse and rat cell lines. In conclusion, it is suggested that the increased levels of the erbA-alpha 2 transcript and the decreased levels of erbA-alpha 1 and erbA-beta 1 in neoplastic cells may account for the loss of thyroid hormone regulation of inducible pathways and decreased nuclear triiodothyronine binding as previously reported.

  13. 肿瘤细胞丰富的霍奇金淋巴瘤10例临床病理分析%A clinicopathological study of 10 cases of neoplastic cell rich Hodgkin's lymphoma

    Institute of Scientific and Technical Information of China (English)

    方婉婷; 杜金荣; 谢建兰; 于冉; 郑晓丹; 朱红; 周小鸽

    2010-01-01

    Objective To clarify clinical and morphological features and immunophenotype and Epstain-Barr virus infection of neoplastic cell rich Hodgkin's lymphoma (NCRHL)and to further improve our knowledge and pathological diagnosis for NCRHL. Methods 10 cases of NCRHL were analyzed for clinical features, morphology, immunophenotype, Epstein-Barr virus infection using routine eosin and haematoxylin stain, immunohistochemistry, Epstain-Barr virus encoded small RNA (EBER) in situ hybridization and combining clinical data. Results (1)NCRHL were more common in young people. The median age of the patients was 25.5 years old. The ratio of male to female was 1:2.3. Superficial lymph nodes were most frequently involved. Masses of mediastinum were seen commonly. Clinical manifestation of the patients included B symptom (6 cases), pruitus (5 cases) and anemia (1 case). (2)Architecture of lymph nodes were effected. Necrosis was seen in some cases. There were more tumor cells in NCRHL than that in the classical Hodgkin's lymphoma. The tumor cells were distributed in piece or patch or diffuse. The morphology of neoplastic cells was wore variable including Hodgkin-like cells, lacunar cell-like, mummy cell-like and anaplastic large cell-like, singular nucleated cells, and multinucleated giant cell-like cells. Numerous neutrophils and eosinophils were present in a few cases. Focal sheet, necrosis granulomatosis-like and diffuse growth pattern were found in NCRHL. (3)All of the cases were positive for CD30 and PAX-5.2/10 (20%) cases were CD15 positive. LCA, CD20 and CD3 were negative. (4)EBER was not detected in all 6 tested cases. (5)Follow up data was obtained in 8/10 cases, in which one patient was dead, one case relapsed in half a year,and the other 6 cases reached complete regression. Conclusion NRCHL is characterized mainly by neoplastic cell rich morphologically and focal sheet, necrosis granulomatosis-like and diffuse growth pattern.EBER was not detected in this tumor. Some cases

  14. 肿瘤性高钙血症患者血浆离子钙及总钙检测的诊断意义%Study on the Diagnostic Significance of Detection of Plasma Ionized Calcium and Total Calcium in Patients with Neoplastic Hypercalcemia

    Institute of Scientific and Technical Information of China (English)

    王凤岚; 冯万周

    2015-01-01

    calcium levels of the observation group were significantly lower than those of the control group , the differences were statistically significant ( P <0.05).The cTCa and nICa positive rates of the observation group were significantly higher than those of the control group,the differences were statistically significant(P <0.05).Patients with lung cancer accounted the most among the 17 patients with high calcium hematoma,followed by colon cancer,ovarian cancer,pan-creatic cancer,breast cancer,cervical cancer and lymphoma.Conclusion Through detecting the levels of corrected ionized calcium and total calcium , patients with neoplastic hypercalcemia can be early diagnosed and treated,thus the clinical symptoms and quality of life of the dying patients can be improved.

  15. Early bile duct cancer

    Institute of Scientific and Technical Information of China (English)

    Jae Myung Cha; Myung-Hwan Kim; Se Jin Jang

    2007-01-01

    Bile duct cancers are frequently diagnosed as advanced diseases. Over half of patients with advanced bile duct cancer present with unresectable malignancies and their prognosis has been very poor even after curative resections. Although there has been a need to diagnose bile duct cancer at its early stage, it has been a difficult goal to achieve due to our lack of knowledge regarding this disease entity. Early bile duct cancer may be defined as a carcinoma whose invasion is confined within the fibromuscular layer of the extrahepatic bile duct or intrahepatic large bile duct without distant metastasis irrespective of lymph node involvement. Approximately 3%-10% of resected bile duct cancers have been reported to be early cancers in the literature. The clinicopathological features of patients with early bile duct cancer differ from those of patients with advanced bile duct cancer, with more frequent asymptomatic presentation, characteristic histopathological findings,and excellent prognosis. This manuscript is organized to emphasize the need for convening an international consensus to develop the concept of early bile duct cancer.

  16. Early diagnosis of early stage lung cancer

    Directory of Open Access Journals (Sweden)

    Andrej Debeljak

    2005-11-01

    Full Text Available Background: For the detection of premalignant changes of bronchial mucosa and early stages of lung cancer frequent chest X-ray, spiral low dose computed tomography, fluorescence bronchoscopy, sputum cytology (also with automated systems with genetic and molecular changes in the sputum cells and bronchial mucosa were used. These screening methods of the high-risk groups for lung cancer achieved: earlier diagnosis of lung cancer in lower stage, higher operability, longer 5-year survival, but without mortality reduction.Conclusions: In the clinical practice we can examine higher risk groups for lung cancer in randomised control trials with multimodality approach: frequent chest low-dose fast spiral computed tomography, sputum cytology with genetic and molecular examinations and fluorescence bronchoscopy. Smoking cessation remains the best means to achieve mortality reduction from lung cancer.

  17. Telomerase in (pre)neoplastic cervical disease

    NARCIS (Netherlands)

    Wisman, GBA; De Jong, S; Meersma, GJ; Helder, MN; Hollema, H; de Vries, EGE; Keith, WN; van der Zee, AGJ

    2000-01-01

    This study was performed to determine upregulation of the human telomerase RNA component (hTR) and mRNA of the catalytic subunit of telomerase (hTERT) in (pre)malignant cervical lesions, to analyze possible intralesional heterogeneity of hTR expression, and to relate hTR and hTERT mRNA levels to tel

  18. Dysregulated FGF signalling in neoplastic disorders.

    Science.gov (United States)

    Tanner, Yasmine; Grose, Richard P

    2016-05-01

    The fibroblast growth factor (FGF) signalling pathway contributes to the regulation of a multitude of cellular functions, impacting on proliferation, survival, differentiation and migration. This biological importance is reflected by its prominent role in carcinogenesis; often being hijacked by cancer cells to offer growth or survival advantage. FGF signalling can contribute a driving force in the malignancy of different cancer types; through alterations in ligands, receptors or regulatory molecules. The dramatic advances in genomics technologies have highlighted how mutation, amplification, translocation or loss of elements in the FGF signalling network can contribute to cancer. Added to this are the stromal influences of FGF signalling. Dissection of the mechanisms that underlie the pro-tumourigenic effects resulting from perturbations to the FGF signalling network will be of utmost importance to the development of therapeutic approaches to treat FGF receptor (FGFR)-driven cancers. In this review, we will focus on the mechanisms of FGF deregulation, the prevalence of aberrations in different cancer types, and how we are progressing in the development of targeted therapies.

  19. Viral Oncolytic Therapeutics for Neoplastic Meningitis

    Science.gov (United States)

    2012-07-01

    endocytosis in the leptomeningeal space would be of great value for the development of drugs intended for the leptome- ningeal route. Protein injected...not been previously described. The obtained results are relevant to the development of drugs intended for delivery to CNS through leptomeningeal...real time. Quantitative investigation of leptomeningeal (intrathecal) pharmacokinetics by PET is highly instrumental in the development of drugs with

  20. Viral Oncolytic Therapeutics for Neoplastic Meningitis

    Science.gov (United States)

    2014-09-01

    the rat model. The therapeutic effect of HSV-1 oncolysis on meningeal metastases was presented ( oral ) at the annual meeting of the World Molecular...Abstracts, and Presentations Presentations & Abstracts: 1. Oral Presentation at WMIC, Seoul. “Novel oncolytic HSV-1 therapeutics for breast cancer...tomography of herpes simplex virus 1 oncolysis. Cancer Research. 2007; 67(7): 3295. 3. Kuruppu D, Tanabe KK. Viral oncolysis by herpes simplex virus and

  1. Minimally invasive approach to neoplastic breast disease

    NARCIS (Netherlands)

    Waaijer, L.

    2015-01-01

    Surgical excision is considered the primary treatment for breast cancer. Potentially less deforming approaches such as in situ ablative treatments aim to preserve the greatest amount of normal breast tissue. Previous studies on radiofrequency ablation (RFA) for the local control of small breast canc

  2. Host impairments in patients with neoplastic diseases

    NARCIS (Netherlands)

    Donnelly, J.P.; Blijlevens, N.M.A.; Velden, W.J.F.M. van der

    2014-01-01

    Healthy individuals possess an immune system comprising physical barriers, innate and acquired immunity as well as the indigenous microflora that populate the body surfaces. The immune system maintains constant vigilance over the body at the cellular level as well as at the interface between the hos

  3. Viral Oncolytic Therapeutics for Neoplastic Meningitis

    Science.gov (United States)

    2014-09-01

    CT scanner ( Neurologica , MA, USA). In the latter system, the imagers were aligned and equipped with a custom imaging bed extending through both...random coincidences, and tissue attenuation were applied. CT image reconstruc- tion was carried out using Neurologica software. All subse- quent image...dementia, incidental white matter lesions ,137 and other conditions; the mechanism of dilation is believed to be associated with inflammatory changes

  4. Telomerase in (pre)neoplastic cervical disease

    NARCIS (Netherlands)

    Wisman, GBA; De Jong, S; Meersma, GJ; Helder, MN; Hollema, H; de Vries, EGE; Keith, WN; van der Zee, AGJ

    2000-01-01

    This study was performed to determine upregulation of the human telomerase RNA component (hTR) and mRNA of the catalytic subunit of telomerase (hTERT) in (pre)malignant cervical lesions, to analyze possible intralesional heterogeneity of hTR expression, and to relate hTR and hTERT mRNA levels to tel

  5. Key point in dermoscopic differentiation between early nail apparatus melanoma and benign longitudinal melanonychia.

    Science.gov (United States)

    Koga, Hiroshi; Saida, Toshiaki; Uhara, Hisashi

    2011-01-01

    Longitudinal melanonychia presents in various conditions including neoplastic and reactive disorders. It is much more frequently seen in non-Caucasians than Caucasians. While most cases of nail apparatus melanoma start as longitudinal melanonychia, melanocytic nevi of the nail apparatus also typically accompany longitudinal melanonychia. Identifying the suspicious longitudinal melanonychia is therefore an important task for dermatologists. Dermoscopy provides useful information for making this decision. The most suspicious dermoscopic feature of early nail apparatus melanoma is irregular lines on a brown background. Evaluation of the irregularity may be rather subjective, but through experience, dermatologists can improve their diagnostic skills of longitudinal melanonychia, including benign conditions showing regular lines. Other important dermoscopic features of early nail apparatus melanoma are micro-Hutchinson's sign, a wide pigmented band, and triangular pigmentation on the nail plate. Although there is as yet no solid evidence concerning the frequency of dermoscopic follow up, we recommend checking the suspicious longitudinal melanonychia every 6 months. Moreover, patients with longitudinal melanonychia should be asked to return to the clinic quickly if the lesion shows obvious changes. Diagnosis of amelanotic or hypomelanotic melanoma affecting the nail apparatus is also challenging, but melanoma should be highly suspected if remnants of melanin granules are detected dermoscopically.

  6. Early Reionization in Cosmology

    CERN Document Server

    Durrer, R

    1993-01-01

    The cosmic microwave background (CMB) anisotropies have turned out to represent one of the most stringent 'bottle necks' for scenarios of large scale structure formation. As a possibility to relax this constraint, it has been proposed that early reionization can damp CMB fluctuations on small scales due to photon diffusion in the ionized plasma. As an example, I investigate the recently proposed scenario with cold dark matter (CDM) and texture seeds. There, an analysis of CMB anisotropies shows that early reionization is a crucial ingredient for this scenario. Without damping, the small scale anisotropies would dominate and exceed observed limits. In this paper I present analytical and numerical results for the amount of damping due to early reionization for CMB perturbations induced by a collapsing texture. Furthermore, the spectral distortion of the CMB due to Compton scattering of the hotter plasma electrons is calculated. Next I discuss the physical processes which lead to a system of coupled ordinary dif...

  7. Early detection of psychosis

    DEFF Research Database (Denmark)

    Larsen, T. K.; Melle, I.; Auestad, B.

    2011-01-01

    Background During the last decades we have seen a new focus on early treatment of psychosis. Several reviews have shown that duration of untreated psychosis (DUP) is correlated to better outcome. However, it is still unknown whether early treatment will lead to a better long-term outcome....... This study reports the effects of reducing DUP on 5-year course and outcome.Method During 1997â€"2000 a total of 281 consecutive patients aged >17 years with first episode non-affective psychosis were recruited, of which 192 participated in the 5-year follow-up. A comprehensive early detection (ED) programme...... with public information campaigns and low-threshold psychosis detection teams was established in one healthcare area (ED-area), but not in a comparable area (no-ED area). Both areas ran equivalent treatment programmes during the first 2 years and need-adapted treatment thereafter.Results At the start...

  8. Early Islamic Syria

    DEFF Research Database (Denmark)

    Walmsley, Alan

    After more than a century of neglect, a profound revolution is occurring in the way archaeology addresses and interprets developments in the social history of early Islamic Syria-Palestine. This concise book offers an innovative assessment of social and economic developments in Syria...... for considerable cultural and economic continuity rather than devastation and unrelenting decline. Much new, and increasingly non-elite, architectural evidence and an ever-growing corpus of material culture indicate that Syria-Palestine entered a new age of social richness in the early Islamic period, even...

  9. Early life vaccination

    DEFF Research Database (Denmark)

    Nazerai, Loulieta; Bassi, Maria Rosaria; Uddbäck, Ida Elin Maria

    2016-01-01

    the first period of life and provide a pertinent alternative in infant vaccinology. To address this, infant mice were vaccinated with three different adenoviral vectors and the CD8+ T-cell response after early life vaccination was explored. We assessed the frequency, polyfunctionality and in vivo...... cytotoxicity of the elicited memory CD8+ T cells, as well as the potential of these cells to respond to secondary infections and confer protection. We further tested the impact of maternal immunity against our replication-deficient adenoviral vector during early life vaccination. Overall, our results indicate...

  10. The Earth's early evolution.

    Science.gov (United States)

    Bowring, S A; Housh, T

    1995-09-15

    The Archean crust contains direct geochemical information of the Earth's early planetary differentiation. A major outstanding question in the Earth sciences is whether the volume of continental crust today represents nearly all that formed over Earth's history or whether its rates of creation and destruction have been approximately balanced since the Archean. Analysis of neodymium isotopic data from the oldest remnants of Archean crust suggests that crustal recycling is important and that preserved continental crust comprises fragments of crust that escaped recycling. Furthermore, the data suggest that the isotopic evolution of Earth's mantle reflects progressive eradication of primordial heterogeneities related to early differentiation.

  11. Early Cosmology Constrained

    CERN Document Server

    Verde, Licia; Pigozzo, Cassio; Heavens, Alan F; Jimenez, Raul

    2016-01-01

    We investigate our knowledge of early universe cosmology by exploring how much additional energy density can be placed in different components beyond those in the $\\Lambda$CDM model. To do this we use a method to separate early- and late-universe information enclosed in observational data, thus markedly reducing the model-dependency of the conclusions. We find that the 95\\% credibility regions for extra energy components of the early universe at recombination are: non-accelerating additional fluid density parameter $\\Omega_{\\rm MR} < 0.006$ and extra radiation parameterised as extra effective neutrino species $2.3 < N_{\\rm eff} < 3.2$ when imposing flatness. Our constraints thus show that even when analyzing the data in this largely model-independent way, the possibility of hiding extra energy components beyond $\\Lambda$CDM in the early universe is seriously constrained by current observations. We also find that the standard ruler, the sound horizon at radiation drag, can be well determined in a way ...

  12. Early Learning in CRESPAR.

    Science.gov (United States)

    Wasik, Barbara A.; Karweit, Nancy; Bond, Mary Alice; Woodruff, Lannette Burns; Jaeger, Gary; Adee, Sarah

    2000-01-01

    Summarizes research conducted by the Early Learning Program during the first 5 years of operation of the Center for Research on the Education of Children Placed At Risk (CRESPAR). Describes two integrated areas of research: practices that promote the development of language and literacy skills and systemic issues of school policy and teacher…

  13. Introduction to "Early psychosis

    DEFF Research Database (Denmark)

    McGorry, Patrick; Nordentoft, Merete; Simonsen, Erik

    2005-01-01

    warrants careful analysis. The Third International Early Psychosis Conference proved to be a watershed and was the largest and most vibrant meeting to that point. This preface aims to set the scene for a selection of contributions, derived from the array of new evidence reported in Copenhagen, and recently...

  14. Early childhood aggression

    NARCIS (Netherlands)

    Alink, Lenneke Rosalie Agnes

    2006-01-01

    In this thesis the development, stability, and correlates of early childhood aggression were investigated. The normative development was examined in a general population sample using questionnaires completed by the parents of 12-, 24-, and 36-month-old children and again one year later. Results show

  15. Early Mover Advantages

    NARCIS (Netherlands)

    G.E. Bijwaard (Govert); M.C.W. Janssen (Maarten); E. Maasland (Emiel)

    2004-01-01

    textabstractIn this paper we analyze empirically whether and if so to what extent later entrants in the European mobile telephony industry have a disadvantage vis-à-vis incumbents and early mover entrants. To analyze this question we consider a series of static models and a dynamic model of market s

  16. Teaching polymorphism early

    DEFF Research Database (Denmark)

    2005-01-01

    Is it possible to teach dynamic polymorphism early? What techniques could facilitate teaching it in Java. This panel will bring together people who have considered this question and attempted to implement it in various ways, some more completely than others. It will also give participants an oppo...

  17. Early Adolescent Ego Development.

    Science.gov (United States)

    James, Michael A.

    1980-01-01

    Presented are the theoretical characteristics of social identity in early adolescence (ages 10 to 15). It is suggested that no longer is identity thought to begin with adolescence, but may have its beginnings in the preteen years. The article draws heavily on Eriksonian concepts. (Editor/KC)

  18. Early Childhood Trauma

    Science.gov (United States)

    National Child Traumatic Stress Network, 2010

    2010-01-01

    Early childhood trauma generally refers to the traumatic experiences that occur to children aged 0-6. Because infants' and young children's reactions may be different from older children's, and because they may not be able to verbalize their reactions to threatening or dangerous events, many people assume that young age protects children from the…

  19. Early malignant syphilis*

    Science.gov (United States)

    Ortigosa, Yara Martins; Bendazzoli, Paulo Salomão; Barbosa, Angela Marques; Ortigosa, Luciena Cegatto Martins

    2016-01-01

    Early malignant syphilis is a rare and severe variant of secondary syphilis. It is clinically characterized by lesions, which can suppurate and be accompanied by systemic symptoms such as high fever, asthenia, myalgia, and torpor state. We report a diabetic patient with characteristic features of the disease showing favorable evolution of the lesions after appropriate treatment. PMID:28300925

  20. Early Developments, 2002.

    Science.gov (United States)

    Winton, Pam, Ed.; Buysse, Virginia, Ed.

    2002-01-01

    This document consists of the three 2002 issues of a journal reporting new research in early child development conducted by the Frank Porter Graham Child Development Center (FPG) at the University of North Carolina at Chapel Hill. Articles in the Winter 2002 issue highlight some current work at FPG on factors that enhance or inhibit social and…

  1. Creativity: The Early Years

    Science.gov (United States)

    Shade, Rick; Shade, Patti Garrett

    2016-01-01

    There is a myth that some people are creative and others are not. However, all children are born creative. They love to explore, ask questions, and are incredibly imaginative. Parents are key in nurturing their child's creativity in the early years. This article offers resources and strategies parents can use at different ages and stages (newborn,…

  2. Music in Early Childhood.

    Science.gov (United States)

    Feierabend, John

    1990-01-01

    Argues that music activities in early childhood education foster a variety of developmental skills. Analyzes Howard Gardner's theory of multiple intelligences, contending that music intelligence is a separate intelligence. Provides ways to identify and promote musical intelligence. Suggests methods for encouraging musical development. Using songs…

  3. Teaching polymorphism early

    DEFF Research Database (Denmark)

    2005-01-01

    Is it possible to teach dynamic polymorphism early? What techniques could facilitate teaching it in Java. This panel will bring together people who have considered this question and attempted to implement it in various ways, some more completely than others. It will also give participants...

  4. 7, 12 dimethylbenz(a)anthracene(DMBA)-induced "early" Squamous Cell carcinoma in the Golden Syrian hamster: evaluation of an animal model and comparison with "early" forms of human Squamous Cell car

    Science.gov (United States)

    Andrejevic-Blant, Snezana; Savary, Jean-Francois; Fontolliet, Charlotte; Monnier, Philippe

    1995-03-01

    To improve our knowledge on PDT of human early squamous cell carcinomas of the upper aero-digestive tract and to evaluate new photosensitizers, we have set up the Syrian hamster as an animal model. A 0.5% oily solution of DMBA was applied topically to the left buccal pouch mucosa 3 times weekly. The contralateral buccal pouch served as control. Groups of 5 animals were sacrificed at 6, 8, 10 and 12 weeks from the first applications. Tissue samples of the buccal mucosa were analyzed by histopathologic and immunohistochemical techniques and compared with preneoplastic and neoplastic changes which are seen in the human carcinogenesis of the upper aero-digestive tract. After 6 to 9 weeks from the beginning of the application, we observed different degrees of epithelial dysplasia and after 10 weeks microinvasive carcinomas. The sequence of dysplastic changes to early carcinoma was reproducible in different groups of animals, and they were closely comparable with the human forms of `early' squamous cell cancer. Hyper- and dyskeratosis were present at all stages of tumor development. We are particularly interested in (mu) -invasive tumor forms appearing 10 weeks after the first application because they are potentially amenable to photodynamic therapy.

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

    Science.gov (United States)

    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

    2015-01-01

    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

  6. Early Childhood Caries

    Directory of Open Access Journals (Sweden)

    Yumiko Kawashita

    2011-01-01

    Full Text Available Dental caries is one of the most common childhood diseases, and people continue to be susceptible to it throughout their lives. Although dental caries can be arrested and potentially even reversed in its early stages, it is often not self-limiting and progresses without proper care until the tooth is destroyed. Early childhood caries (ECC is often complicated by inappropriate feeding practices and heavy infection with mutans streptococci. Such children should be targeted with a professional preventive program that includes oral hygiene instructions for mothers or caregivers, along with fluoride and diet counseling. However, these strategies alone are not sufficient to prevent dental caries in high-risk children; prevention of ECC also requires addressing the socioeconomic factors that face many families in which ECC is endemic. The aim of this paper is to systematically review information about ECC and to describe why many children are suffering from dental caries.

  7. The Early Sarmatian Knight

    Directory of Open Access Journals (Sweden)

    Yablonsky Leonid T.

    2013-06-01

    Full Text Available During the study of the Early Sarmatian burials in the burial mounds near Filippovka village (Ilek district, Orenburg oblast, a large quantity of weapons and accessories were found, which make it possible to reconstruct the military costume. All the armament items from the burial can be divided into two major groups: offensive and defensive. The former includes bows and arrows, slingshots, spears, stilettos and war hammers (“bec de corbin” type; the latter is represented by a helmet and two varieties of scaly armor, made of iron and bone or horn. The accessories of the military costume found include sword-belt buckles with zoomorphic images, as well as a torque and a bracelet, which apparently served as insignia. The reconstructed image of an elite Early Sarmatian warrior is somewhat similar to the appearance of a Western European knight, but the Sarmatian knight was about 2000 years older.

  8. Early life vaccination

    DEFF Research Database (Denmark)

    Nazerai, Loulieta; Bassi, Maria Rosaria; Uddbäck, Ida Elin Maria;

    2016-01-01

    Intracellular pathogens represent a serious threat during early life. Importantly, even though the immune system of newborns may be characterized as developmentally immature, with a propensity to develop Th2 immunity, significant CD8+ T-cell responses may still be elicited in the context of optimal...... priming. Replication deficient adenoviral vectors have been demonstrated to induce potent CD8+ T-cell response in mice, primates and humans. The aim of the present study was therefore to assess whether replication-deficient adenovectors could overcome the risk of overwhelming antigen stimulation during...... the first period of life and provide a pertinent alternative in infant vaccinology. To address this, infant mice were vaccinated with three different adenoviral vectors and the CD8+ T-cell response after early life vaccination was explored. We assessed the frequency, polyfunctionality and in vivo...

  9. Samuel Goudsmit - Early Influences

    Science.gov (United States)

    Goudsmit, Esther

    2010-03-01

    Samuel Goudsmit, born in 1902 in The Hague, Netherlands, earned his Ph.D. at the University of Leiden in 1926 with Paul Ehrenfest. The present talk will describe some aspects of his background and early formative years in order to provide context for the broad range of his professional life. Sam belonged to a large tribe of paternal and maternal uncles, aunts and first cousins; including his parents, grandparents and sister Ro, they numbered forty. Sam was the first of the tribe to be educated beyond high school. Early interests as a child and later as a university student in the Netherlands prefigured his significant and diverse contributions in several realms including not only physics but also teaching, Egyptology and scientific Intelligence. Bibliographic sources will include: The American Institute of Physics' Oral History Transcripts and photographs from the Emilio Segre visual archives, memoirs and conversations of those who knew Sam and also letters to his daughter, Esther.

  10. Study of morphological alterations of the adrenal glands in the neoplastic cachexia Estudo das alterações morfológicas da glândula adrenal na caquexia neoplásica

    Directory of Open Access Journals (Sweden)

    Tânia Longo Mazzuco

    2009-01-01

    Full Text Available Advanced cancer occurs with nutritional and metabolic alterations that characterize neoplastic cachexia. When homeostasis is compromised, the adrenal glands have a fundamental role in the neuroendocrine response. Our purpose in this research was to study morphological alterations of the adrenal glands in the development of cancer associated to cachexia. Cachexia experimental model induced by Walker 256 tumor in Wistar rats, was used. Animals were sacrificed 12 days after tumor cells inoculation and adrenal glands removal for histopathologic analysis by means of hematoxylin and eosin stain. Nutritional parameters, cachexia index and adrenal glands weight, were evaluated. Animals with tumor presented cachexia index of 16,6 ± 4%. Adrenal glands average weight was significantly higher in the tumor group (40 mg ± 10 than in the control group (25 mg ± 3. Adrenal cortex of animals with cachexia showed hypertrophy of the zona fasciculata and reticular layer, with voluminous spongiocytes; vascular congestion and stasis were observed in the medullar region. Results were similar in the pair and ad libitum-fed groups. Animals with cancer cachexia showed compromised morphology of the adrenal glands which showed alterations related to stress response, suggesting increased cathecolamine secretion and activation of the hypothalamus-pituitary-adrenal axis.   Advanced cancer occurs with nutritional and metabolic alterations that characterize neoplastic cachexia. When homeostasis is compromised, the adrenal glands have a fundamental role in the neuroendocrine response. Our purpose in this research was to study morphological alterations of the adrenal glands in the development of cancer associated to cachexia. Cachexia experimental model induced by Walker 256 tumor in Wistar rats, was used. Animals were sacrificed 12 days after tumor cells inoculation and adrenal glands removal for histopathologic analysis by means of hematoxylin and eosin stain. Nutritional

  11. Early Permian bipedal reptile.

    Science.gov (United States)

    Berman, D S; Reisz, R R; Scott, D; Henrici, A C; Sumida, S S; Martens, T

    2000-11-03

    A 290-million-year-old reptilian skeleton from the Lower Permian (Asselian) of Germany provides evidence of abilities for cursorial bipedal locomotion, employing a parasagittal digitigrade posture. The skeleton is of a small bolosaurid, Eudibamus cursoris, gen. et sp. nov. and confirms the widespread distribution of Bolosauridae across Laurasia during this early stage of amniote evolution. E. cursoris is the oldest known representative of Parareptilia, a major clade of reptiles.

  12. Hands of early primates.

    Science.gov (United States)

    Boyer, Doug M; Yapuncich, Gabriel S; Chester, Stephen G B; Bloch, Jonathan I; Godinot, Marc

    2013-12-01

    Questions surrounding the origin and early evolution of primates continue to be the subject of debate. Though anatomy of the skull and inferred dietary shifts are often the focus, detailed studies of postcrania and inferred locomotor capabilities can also provide crucial data that advance understanding of transitions in early primate evolution. In particular, the hand skeleton includes characteristics thought to reflect foraging, locomotion, and posture. Here we review what is known about the early evolution of primate hands from a comparative perspective that incorporates data from the fossil record. Additionally, we provide new comparative data and documentation of skeletal morphology for Paleogene plesiadapiforms, notharctines, cercamoniines, adapines, and omomyiforms. Finally, we discuss implications of these data for understanding locomotor transitions during the origin and early evolutionary history of primates. Known plesiadapiform species cannot be differentiated from extant primates based on either intrinsic hand proportions or hand-to-body size proportions. Nonetheless, the presence of claws and a different metacarpophalangeal [corrected] joint form in plesiadapiforms indicate different grasping mechanics. Notharctines and cercamoniines have intrinsic hand proportions with extremely elongated proximal phalanges and digit rays relative to metacarpals, resembling tarsiers and galagos. But their hand-to-body size proportions are typical of many extant primates (unlike those of tarsiers, and possibly Teilhardina, which have extremely large hands). Non-adapine adapiforms and omomyids exhibit additional carpal features suggesting more limited dorsiflexion, greater ulnar deviation, and a more habitually divergent pollex than observed plesiadapiforms. Together, features differentiating adapiforms and omomyiforms from plesiadapiforms indicate increased reliance on vertical prehensile-clinging and grasp-leaping, possibly in combination with predatory behaviors in

  13. Early bioenergetic evolution

    Science.gov (United States)

    Sousa, Filipa L.; Thiergart, Thorsten; Landan, Giddy; Nelson-Sathi, Shijulal; Pereira, Inês A. C.; Allen, John F.; Lane, Nick; Martin, William F.

    2013-01-01

    Life is the harnessing of chemical energy in such a way that the energy-harnessing device makes a copy of itself. This paper outlines an energetically feasible path from a particular inorganic setting for the origin of life to the first free-living cells. The sources of energy available to early organic synthesis, early evolving systems and early cells stand in the foreground, as do the possible mechanisms of their conversion into harnessable chemical energy for synthetic reactions. With regard to the possible temporal sequence of events, we focus on: (i) alkaline hydrothermal vents as the far-from-equilibrium setting, (ii) the Wood–Ljungdahl (acetyl-CoA) pathway as the route that could have underpinned carbon assimilation for these processes, (iii) biochemical divergence, within the naturally formed inorganic compartments at a hydrothermal mound, of geochemically confined replicating entities with a complexity below that of free-living prokaryotes, and (iv) acetogenesis and methanogenesis as the ancestral forms of carbon and energy metabolism in the first free-living ancestors of the eubacteria and archaebacteria, respectively. In terms of the main evolutionary transitions in early bioenergetic evolution, we focus on: (i) thioester-dependent substrate-level phosphorylations, (ii) harnessing of naturally existing proton gradients at the vent–ocean interface via the ATP synthase, (iii) harnessing of Na+ gradients generated by H+/Na+ antiporters, (iv) flavin-based bifurcation-dependent gradient generation, and finally (v) quinone-based (and Q-cycle-dependent) proton gradient generation. Of those five transitions, the first four are posited to have taken place at the vent. Ultimately, all of these bioenergetic processes depend, even today, upon CO2 reduction with low-potential ferredoxin (Fd), generated either chemosynthetically or photosynthetically, suggesting a reaction of the type ‘reduced iron → reduced carbon’ at the beginning of bioenergetic evolution

  14. Early modern sport

    OpenAIRE

    Huggins, Mike

    2017-01-01

    The "early modern" has always suffered problems of periodization. Its beginnings overlap with the Late Middle Ages when sport and athletic exercise were moving away from military training. It encompasses the Renaissance, Reformation, and Counter-Reformation and the scientific shifts of the Age of Enlightenment, movements that were diverse chronologically, geographically, culturally and intellectually. Some historians link its beginnings to block-printing, the beginning of the Tudor period, or...

  15. Early Detection Of Cancer

    Directory of Open Access Journals (Sweden)

    V B Bhatnagar

    1987-04-01

    Full Text Available Farly detection of cancer is based upon three fundamental assumptions, firstly that the trea'ment of benign and precancerous lesions reduces the incidence of cancer, secondly, that the treatment of in situ cancers is conducive to total cure and thirdly that early diagnosis and management of invasive cancer ensures be.ter survival. When patient seeks medical advice for vague symptoms, which could however be due to a possible malignant tumour at a particular site, the alert clinician should investigate the patient immediately to exclude cancer. At this stage cancer is usually not significantly advanced.Currently the U. I. C. C. (International Union for Cancer Control} is studying the epidemiology of cancers in various countries The importance of this is two folds : Firstly by focussing attention on a section of population vulnerable to a particular cancer an early detection is facilitated Secondly by changing the causative factors responsible to a particular cancer, the incidence of that cancer can be reduced e. g. reduction in lung cancer following campaigns against ciguette smoking and reductioi in breast cancer after campaigns for advocating breast feeding of infants, lowering fat consumption and encouraging self palpation of breast regularly.Indeed early diagnosis of cancer implies diagnosis of cancer in almost a symptomatic stage It involves motiva’ion of the population towards acquisitio : of knowledge, attitude and practice.. Epidemiologies and clinicians should be able to recognise high risk cases exposed to particular neoplasia and knowledge of alarming symptoms should be pro- pogated for wide publicity through common available media and means. Probable cases should have regular clhrcal examination periodically and relevant investigations including radiological, imaging techniques and Bio-Chemical examination should be undertaken as and when desired Suspicious lesions should be investigated by specific tests including smear cytology

  16. Cytologic and DNA-Cytometric Early Diagnosis of Oral Cancer

    Directory of Open Access Journals (Sweden)

    Torsten W. Remmerbach

    2001-01-01

    DNA‐image cytometry is a very sensitive, highly specific and objective adjuvant tool for the early identification of neoplastic epithelial cells in oral smears.

  17. History of early atomic clocks

    Energy Technology Data Exchange (ETDEWEB)

    Ramsey, N.F. [Harvard Univ., Cambridge, MA (United States). Lyman Lab. of Physics

    2005-06-01

    This review of the history of early atomic clocks includes early atomic beam magnetic resonance, methods of separated and successive oscillatory fields, microwave absorption, optical pumping and atomic masers. (author)

  18. Early Life Exposures and Cancer

    Science.gov (United States)

    Early-life events and exposures have important consequences for cancer development later in life, however, epidemiological studies of early-life factors and cancer development later in life have had significant methodological challenges.

  19. Early prevention of obesity

    Directory of Open Access Journals (Sweden)

    Claudio Maffeis

    2014-06-01

    Full Text Available Childhood obesity is the metabolic disorder with the highest prevalence in both children and adults. Urgency to treat and prevent childhood obesity is based on the clear evidence that obesity tends to track from childhood to adulthood, is associated to morbidity also in childhood and to long-term mortality. Early life, i.e., intrauterine life and the first two years, is a sensitive window for prevention. Anatomical and functional maturation of the hypothalamic structures devoted to regulating energy intake and expenditure and body size mainly occurs in the first 1,000 days of life. Therefore, factors affecting the foetal exposition to maternal metabolic environment and early postnatal nutrition are crucial in modulating the definition of the metabolic programming processes in the brain. Maternal diseases, mainly malnutrition for defect or excess, obesity and diabetes, placental disorders and dysfunctions, maternal use of alcohol and drugs, smoking, affect long term metabolic programming of the foetus with lifelong consequences. Similarly, early nutrition contributes to complete the long-term metabolic regulating framework initiated in the uterus. Breastfeeding, adequate weaning, attention to portion size and diet composition are potential tools for reducing the obesity risk later in childhood. Longitudinal randomized controlled studies are needed for exploring the efficacy of obesity prevention strategies initiated after conception.Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy · October 22nd-25th, 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

  20. Early Onset Werner Syndrome

    Directory of Open Access Journals (Sweden)

    Berna İmge Aydoğan

    2015-09-01

    Full Text Available Werner syndrome (WS is a rare autosomal recessive adult-onset progeroid disorder characterized by the early onset of aged-appearance and age-related metabolic disorders. Symptoms of premature aging usually first develop in the second-third decades of life. We report a 27-year-old female who was admitted to our clinic at the age of eighteen with hyperglycemia. She was diagnosed with diabetes and type 4 dyslipidemia at the age of seven. In her family history, her parents were first cousins and she had three healthy brothers. On her first physical examination; she had bird-like face appearance, global hair loss, beaked nose, short stature and she was overweight. She had global hair loss with gray and thin hair. Hoarseness of voice and hyperkeratosis of skin were observed. She had bilateral cataracts and moderate sensorineural hearing loss. On psychiatric examination, borderline mental retardation was detected. She had severe insulin resistance and hypertriglyceridemia despite levothyroxine, gemfibrozil, omega-3 and intensive insulin treatment. Routine lipid apheresis was performed to lower the triglyceride levels reaching 5256 mg/dL. She also had focal segmental glomerulosclerosis, hepatosteatosis, osteoporosis and epilepsy. Disease was accompanied by several congenital deformities, such as Rathke’s cleft cyst, angiomyolipoma and femoral neck hypoplasia. WS is a rare genetic disorder characterized by multiple endocrine manifestations as well as soft tissue changes. We present a case of early disturbances that were diagnosed before typical clinical signs and symptoms. We propose that WS should be kept in mind when type 2 diabetes and hyperlipidemia are diagnosed early in childhood. Turk Jem 2015; 19: 99-104

  1. Early Childhood Special Music Education

    Science.gov (United States)

    Darrow, Alice-Ann

    2011-01-01

    The process of early intervention is a critical component of Early Childhood Special Music Education. Early intervention is the process of providing services, education, and support to young children who have disabilities or to children who are at-risk of developing needs that may affect their physical, cognitive, or emotional development. The…

  2. Expenditures for Early Intervention Services

    Science.gov (United States)

    Hebbeler, Kathleen; Levin, Jesse; Perez, Maria; Lam, Irene; Chambers, Jay G.

    2009-01-01

    What does it cost to provide early intervention services? Data collected as part of the National Early Intervention Longitudinal Study were used to determine expenditures for infants, toddlers, and their families receiving services through Part C programs. The study found that the national average total expenditure for early intervention services…

  3. Early solar physics

    CERN Document Server

    Meadows, A J

    1970-01-01

    Early Solar Physics reviews developments in solar physics, particularly the advent of solar spectroscopy and the discovery of relationships between the various layers of the solar atmosphere and between the different forms of solar activity. Topics covered include solar observations during 1843; chemical analysis of the solar atmosphere; the spectrum of a solar prominence; and the solar eclipse of December 12, 1871. Spectroscopic observations of the sun are also presented. This book is comprised of 30 chapters and begins with an overview of ideas about the sun in the mid-nineteenth century, fo

  4. Quantitative attenuation analysis for identification of early Barrett's neoplasia in volumetric laser endomicroscopy.

    Science.gov (United States)

    Swager, Anne-Fre; Faber, Dirk J; de Bruin, Daniel M; Weusten, Bas L; Meijer, Sybren L; Bergman, Jacques J; Curvers, Wouter L; van Leeuwen, Ton G

    2017-08-01

    Early neoplasia in Barrett’s esophagus (BE) is difficult to detect. Volumetric laser endomicroscopy (VLE) incorporates optical coherence tomography, providing a circumferential scan of the esophageal wall layers. The attenuation coefficient (μVLE) quantifies decay of detected backscattered light versus depth, and could potentially improve BE neoplasia detection. The aim is to investigate feasibility of μVLE for identification of early BE neoplasia. In vivo and ex vivo VLE scans with histological correlation from BE patients ± neoplasia were used. Quantification by μVLE was performed manually on areas of interest (AoIs) to differentiate neoplasia from nondysplastic (ND)BE. From ex vivo VLE scans from 16 patients (13 with neoplasia), 68 AoIs were analyzed. Median μVLE values (mm−1) were 3.7 [2.1 to 4.4 interquartile range (IQR)] for NDBE and 4.0 (2.5 to 4.9 IQR) for neoplasia, not statistically different (p=0.82). Fourteen in vivo scans were used: nine from neoplastic and five from NDBE patients. Median μVLE values were 1.8 (1.5 to 2.6 IQR) for NDBE and 2.1 (1.9 to 2.6 IQR) for neoplasia, with no statistically significant difference (p=0.37). In conclusion, there was no significant difference in μVLE values in VLE scans from early neoplasia versus NDBE. Future studies with a larger sample size should explore other quantitative methods for detection of neoplasia during BE surveillance.

  5. Processos proliferativos gengivais não neoplásicos em paciente sob tratamento ortodôntico Non-neoplastic proliferative gingival processes in patients undergoing orthodontic treatment

    Directory of Open Access Journals (Sweden)

    Irineu Gregnanin Pedron

    2010-12-01

    Full Text Available INTRODUÇÃO: a aparatologia ortodôntica dificulta a higiene bucal e pode contribuir para a formação de lesões gengivais, como os processos proliferativos gengivais não neoplásicos. Essas lesões, dependendo de alguns fatores - como o tempo de evolução, constituintes histopatológicos e condições bucais -, podem ser reversíveis, em alguns casos, por meio da orientação sobre higiene bucal e da terapia periodontal básica. Entretanto, na maioria das vezes há necessidade de tratamento cirúrgico. OBJETIVO: o propósito deste trabalho é relatar o caso de uma paciente portadora de aparatologia ortodôntica fixa que apresentou duas lesões gengivais distintas, diagnosticadas como granuloma piogênico e hiperplasia gengival inflamatória. Foram discutidas as características clínicas e histopatológicas, incidência e frequência, modalidades terapêuticas e prevenção de ambas as lesões, demonstrando a importância do encaminhamento do material colhido ao exame histopatológico, dada a possibilidade de diversas hipóteses diagnósticas. Em ambas as lesões foi realizada a exérese cirúrgica. RESULTADOS: a lesão na arcada superior, diagnosticada como granuloma piogênico, apresentou recorrência, sendo necessária terapia periodontal básicae repetiçãodoprocedimento cirúrgico. Alesão na arcada inferior foi diagnosticada como hiperplasia gengival, sendo removida cirurgicamente e acompanhada clinicamente, com prescrição de orientação da higiene bucal ao pacienteINTRODUCTION: Orthodontic appliances render oral hygiene difficult and may contribute to the development of gingival lesions such as non-neoplastic proliferative gingival processes. These lesions, depending on such factors as development time, histopathological components and oral conditions may be reversible in some cases - through oral hygiene advice and basic periodontal therapy. In most cases, however, surgical treatment is required. OBJECTIVES: The purpose of this

  6. {sup 18}F-FDG PET for exploration of para-neoplastic syndromes with anti-h.u. antibodies and small cell lung cancer: clinical case and literature review

    Energy Technology Data Exchange (ETDEWEB)

    Ricard, F.; Giammarile, F.; Houzard, C. [Centre Hospitalier Lyon, Dept. of Nuclear Medicine, 69 - Pierre Benite (France); Giammarile, F.; Houzard, C. [Lyon-1 Univ., EA 3738, 69 (France); Didelot, A.; Mauguiere, F. [Hopital Neurologique, U 301, 69 - Bron (France)

    2008-02-15

    Introduction. - Small cell lung cancer (S.C.L.C.) is a neuroendocrine tumour representing 20% of bronchopulmonary cancers. Its metastatic potential is high, so 2/3 of diagnoses are made at disseminated stage. Anti H.u. antibodies are part of the anti neuronal antibodies, often associated to S.C.L.C.. However, 16% of cancers have positive anti H.u. with no para neoplastic syndrome (P.N.S.). (Graus, Brain, 2001). P.N.S. associated with anti H.u. are encephalomyelitis, sensitive neuropathy, chronic pseudo intestinal obstruction, cerebellar degeneration and limbic encephalitis. Case report. - A 75-year-old patient was hospitalized for exploration of an atypical tri-facial neuralgia. Anti H.u. antibodies were found and P.N.S. of a S.C.L.C. was therefore suspected. The biopsy of a thoracic parietal adenopathy confirmed the diagnostic of S.C.L.C. metastasis. Conventional imaging and {sup 18}F-FDG (Fluorodeoxyglucose) PET/CT (Positron Emission Tomography/Computed Tomography)) did not localize the primary tumour, despite advanced dissemination stage, only showing lymphatic secondary locations at the left axillary and under the diaphragm areas. Literature review. - Younes-Mhenni (Brain, 2004, 20 patients); and Linke (Neurology, 2004, 13 patients) studied patients presenting with anti H.u. antibodies (13 and eight respectively) and other anti neuronal antibodies (Y.o., Ri, C.V.2, Tr) associated with different cancers. PET sensitivity was respectively 83.3 and 90% with a specificity of 25 and 67%. In both series, specificity of anti H.u. antibodies for S.C.L.C. was estimated at 53% and 62.5%. Size is a limiting factor for S.C.L.C. detection and Watanabe (Nihon Kokyuki Gakkai Zasshi, 2001) showed that sensitivity for detection of less than 1 cm tumour was 0% in five patients. Moreover, P.N.S. can precess S.C.L.C. detection for many years and PET/CT has to be repeated. (Gaillard, Revue neurologique, 2005).In two other studies (Schumacher, EJNM, 2001, 30 patients; and Niho, Lung

  7. Sonority and early words

    DEFF Research Database (Denmark)

    Kjærbæk, Laila; Boeg Thomsen, Ditte; Lambertsen, Claus

    2015-01-01

    Syllables play an important role in children’s early language acquisition, and children appear to rely on clear syllabic structures as a key to word acquisition (Vihman 1996; Oller 2000). However, not all languages present children with equally clear cues to syllabic structure, and since the spec......Syllables play an important role in children’s early language acquisition, and children appear to rely on clear syllabic structures as a key to word acquisition (Vihman 1996; Oller 2000). However, not all languages present children with equally clear cues to syllabic structure, and since...... acquisition therefore presents us with the opportunity to examine how children respond to the task of word learning when the input language offers less clear cues to syllabic structure than usually seen. To investigate the sound structure in Danish children’s lexical development, we need a model of syllable......-29 months. For the two children, the phonetic structure of the first ten words to occur is compared with that of the last ten words to occur before 30 months of age, and with that of ten words in between. Measures related to the sonority envelope, viz. sonority types and in particular sonority rises...

  8. Tattoo-Associated Skin Reaction: The Importance of an Early Diagnosis and Proper Treatment

    Directory of Open Access Journals (Sweden)

    Andrea Bassi

    2014-01-01

    Full Text Available Tattoo is going to be a very common practice especially among young people and we are witnessing a gradual increase of numerous potential complications to tattoo placement which are often seen by physicians, but generally unknown to the public. The most common skin reactions to tattoo include a transient acute inflammatory reaction due to trauma of the skin with needles and medical complications such as superficial and deep local infections, systemic infections, allergic contact dermatitis, photodermatitis, granulomatous and lichenoid reactions, and skin diseases localized on tattooed area (eczema, psoriasis, lichen, and morphea. Next to these inflammatory skin reactions we have to consider also the possibility of the development of cutaneous conditions such as pseudolymphomatous reactions and pseudoepitheliomatous hyperplasia. The aim of this study is to underline the importance of an early diagnosis by performing a histological examination especially when we are in front of suspected papulonodular lesions arising from a tattoo, followed by a proper treatment, since cutaneous neoplastic evolution is known to be a rare but possible complication.

  9. [Endoscopic Submucosal dissection and mucosectomy for the treatment of the epithelial neoplasia and early gastric cancer].

    Science.gov (United States)

    Barreda B, Fernando; Sanchez L, Juvenal

    2008-01-01

    In Japan, endoscopic mucosal resection and endoscopic submucosal dissection of early gastric cancer are accepted as a treatment options for cases of early gastric cancer where the probability of lymph node metastasis is nil or low. To establish the effectiveness of mucosectomy for the treatment of early gastric cancer and evaluate the extended indications for dysplasia lesions, also, we want to determine if the mucosectomy is relevant for lesions negative for neoplasia at the National Institute for Neoplastic Diseases (INEN), Lima, Peru. We call for estimating the utility and factibility of the endoscopic submucosa dissection with the needle knife. The study is an observational, prospective, analytical and cross longitudinal. The study was performed in 96 patients with Type 0 Neoplastic lesions at INEN from 1996 to 2008. The revised Vienna classification of gastrointestinal epithelial neoplasia was utilized. The indication for endoscopic mucosal resection as a radical treatment of early gastric cancer is according to the treatment guidelines for gastric cancer in Japan. The lesions were resected with a simple endoscopic snare, with the Olympus cap for some depressed lesions and the needle knife during the submucosal dissection. Lifting of the lesion with submucosal injection was done with saline solution with epinephrine or saline with distillate water. The statistical analysis included the SPPS-12 programme. 96 patients were treated by mucosectomy and endoscopic submucosal dissection from 1996 to 2008. The sample represents patients with a mean age over 50 years old and predominance of female. 55 patients belongs to category 1 of revised Vienna Classification, 9 patients are in the category 3, 31 patients are suitable in category 4 (20 with high grade adenoma/dysplasia and 11 with intramucosal carcinoma) and just 1 patient for the category 5. We resected 305 Type 0 lesions, 85 mucosal neoplasia, low grade (43) and high grade (31 adenoma/dysplasia in 20 patients

  10. Supermodels for early LHC

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, Christian W. [Theoretical Physics Group, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Berkeley Center for Theoretical Physics, University of California, Berkeley, CA 94720 (United States); Ligeti, Zoltan, E-mail: zligeti@lbl.go [Theoretical Physics Group, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Berkeley Center for Theoretical Physics, University of California, Berkeley, CA 94720 (United States); Schmaltz, Martin [Theoretical Physics Group, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Berkeley Center for Theoretical Physics, University of California, Berkeley, CA 94720 (United States); Physics Department, Boston University, Boston, MA 02215 (United States); Thaler, Jesse [Theoretical Physics Group, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Berkeley Center for Theoretical Physics, University of California, Berkeley, CA 94720 (United States); Walker, Devin G.E. [Theoretical Physics Group, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Berkeley Center for Theoretical Physics, University of California, Berkeley, CA 94720 (United States); Center for the Fundamental Laws of Nature, Jefferson Physical Laboratory, Harvard University, Cambridge, MA 02138 (United States)

    2010-06-21

    We investigate which new physics signatures could be discovered in the first year of the LHC, beyond the expected sensitivity of the Tevatron data by the end of 2010. We construct 'supermodels', for which the LHC sensitivity even with only 10 pb{sup -1} useful luminosity is greater than that of the Tevatron with 10 fb{sup -1}. The simplest supermodels involve s-channel resonances in the quark-antiquark and especially in the quark-quark channels. We concentrate on easily visible final states with small standard model backgrounds, and find that there are simple searches, besides those for Z{sup '} states, which could discover new physics in early LHC data. Many of these are well-suited to test searches for 'more conventional' models, often discussed for multi-fb{sup -1} data sets.

  11. Early times in tunneling

    CERN Document Server

    García-Calderón, G; Garcia-Calderon, Gaston; Villavicencio, Jorge

    2000-01-01

    Exact analytical solutions of the time-dependent Schr\\"odinger equation with the initial condition of an incident cutoff wave are used to investigate the traversal time for tunneling. The probability density starts from a vanishing value along the tunneling and transmitted regions of the potential. At the barrier width it exhibits, at early times, a distribution of traversal times that typically has a peak $\\tau_p$ and a width $\\Delta \\tau$. Numerical results for other tunneling times, as the phase-delay time, fall within $\\Delta \\tau$. The B\\"uttiker traversal time is the closest to $\\tau_p$. Our results resemble calculations based on Feynman paths if its noisy behaviour is ignored.

  12. [Early cardiotoxicity of Hydroxychloroquine].

    Science.gov (United States)

    Zerbib, Y; Guillaumont, M P; Touati, G; Duhaut, P; Schmidt, J

    2016-03-01

    Hydroxychloroquine (HCQ) is most frequently used in the treatment of systemic inflammatory diseases. Cardiac complications of anti-malarial drugs are uncommon, and most of the time are the result of a long-term exposition. In this case, cardiotoxicity is the consequence of the lysosomal dysfunction and the result of intracytoplasmic granular material inclusions. We report a 77-year-old woman who presented a very early and reversible cardiotoxicity, probably related to the quinidine like effect of the HCQ, 10 days after initiation of therapy for Whipple endocarditis. We discuss the different mechanisms of cardiotoxicity of anti-malarial drugs and their clinical manifestations. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  13. Artritis Temprana Early Arthritis

    Directory of Open Access Journals (Sweden)

    2011-02-01

    Full Text Available Hasta la década de los años ochenta se consideraba a la artritis reumatoide (AR como una enfermedad poco frecuente, de gravedad leve a moderada, que tenía una evolución lentamente, progresiva hacia el daño articular y la incapacidad. El aborde terapéutico convencional hasta ese momento, era el tratamiento clásico de la pirámide.Until the early the eighties was considered rheumatoid arthritis to (RA as a rare disease of mild to moderate severity, which had a slowly evolution towards joint damage and disability. The conventional therapeutic option until then, was the classic treatment of the pyramid.

  14. Sonority and early words

    DEFF Research Database (Denmark)

    Kjærbæk, Laila; Boeg Thomsen, Ditte; Lambertsen, Claus

    2015-01-01

    acquisition therefore presents us with the opportunity to examine how children respond to the task of word learning when the input language offers less clear cues to syllabic structure than usually seen. To investigate the sound structure in Danish children’s lexical development, we need a model of syllable...... structure; and as the theoretical basis for our analyses related to sonority we present Basbøll’s Sonority Syllable Model for phonotactics, which is based upon a non-circular version of a sonority hierarchy. We investigate spontaneous child language output in a longitudinal corpus with two children aged 9......Syllables play an important role in children’s early language acquisition, and children appear to rely on clear syllabic structures as a key to word acquisition (Vihman 1996; Oller 2000). However, not all languages present children with equally clear cues to syllabic structure, and since...

  15. Early-Onset Dementia

    DEFF Research Database (Denmark)

    Konijnenberg, Elles; Fereshtehnejad, Seyed-Mohammad; Kate, Mara Ten;

    2017-01-01

    BACKGROUND: Early-onset dementia (EOD) is a rare condition, with an often atypical clinical presentation, and it may therefore be challenging to diagnose. Specialized memory clinics vary in the type of patients seen, diagnostic procedures applied, and the pharmacological treatment given. The aim...... of this study was to investigate quality-of-care indicators in subjects with EOD from 3 tertiary memory clinics in 3 European countries. METHODS: We included 1325 newly diagnosed EOD patients, ages 65 years or younger, between January 1, 2007 and December 31, 2013, from the Danish Dementia Registry...... (Rigshospitalet, Copenhagen), the Swedish Dementia Registry ("SveDem", Karolinska University Hospital, Stockholm), and the Amsterdam Dementia Cohort (VU University Medical Center). RESULTS: The frequency of EOD among all dementia patients was significantly lower in Copenhagen (410, 20%) and Stockholm (284, 21...

  16. How numbers, nature and immune status of Foxp3+ regulatory T cells shape the early immunological events in tumor development.

    Directory of Open Access Journals (Sweden)

    Guillaume eDarrasse-Jeze

    2013-09-01

    Full Text Available The influence of CD4+CD25+Foxp3+ regulatory T cells (Tregs on cancer progression has been demonstrated in a large number of preclinical models and confirmed in several types of malignancies. Neoplastic processes trigger an increase of Treg numbers in draining lymph nodes, spleen, blood, and tumors, leading to the suppression of anti-tumor responses. Treg depletion before or early in tumor development may lead to complete tumor eradication and extends survival of mice and humans. However this strategy is ineffective in established tumors, highlighting the critical role of the early Treg-tumor encounters. In this review, after discussing old and new concepts of immunological tumor tolerance, we focus on the nature (thymus-derived vs. peripherally-derived and status (naïve or activated / memory of the regulatory T cells at tumor emergence. The recent discoveries in this field suggest that the activation status of Tregs and effector T cells (Teffs at the first encounter with the tumor are essential to shape the fate and speed of the immune response across a variety of tumor models. The relative timing of activation/recruitment of antitumor cells versus tolerogenic cells at tumor emergence appears to be crucial in the identification of tumor cells as friend or foe, which has broad implications for the design of cancer immunotherapies.

  17. CYR61 and TAZ Upregulation and Focal Epithelial to Mesenchymal Transition May Be Early Predictors of Barrett's Esophagus Malignant Progression.

    Science.gov (United States)

    Cardoso, Joana; Mesquita, Marta; Dias Pereira, António; Bettencourt-Dias, Mónica; Chaves, Paula; Pereira-Leal, José B

    2016-01-01

    Barrett's esophagus is the major risk factor for esophageal adenocarcinoma. It has a low but non-neglectable risk, high surveillance costs and no reliable risk stratification markers. We sought to identify early biomarkers, predictive of Barrett's malignant progression, using a meta-analysis approach on gene expression data. This in silico strategy was followed by experimental validation in a cohort of patients with extended follow up from the Instituto Português de Oncologia de Lisboa de Francisco Gentil EPE (Portugal). Bioinformatics and systems biology approaches singled out two candidate predictive markers for Barrett's progression, CYR61 and TAZ. Although previously implicated in other malignancies and in epithelial-to-mesenchymal transition phenotypes, our experimental validation shows for the first time that CYR61 and TAZ have the potential to be predictive biomarkers for cancer progression. Experimental validation by reverse transcriptase quantitative PCR and immunohistochemistry confirmed the up-regulation of both genes in Barrett's samples associated with high-grade dysplasia/adenocarcinoma. In our cohort CYR61 and TAZ up-regulation ranged from one to ten years prior to progression to adenocarcinoma in Barrett's esophagus index samples. Finally, we found that CYR61 and TAZ over-expression is correlated with early focal signs of epithelial to mesenchymal transition. Our results highlight both CYR61 and TAZ genes as potential predictive biomarkers for stratification of the risk for development of adenocarcinoma and suggest a potential mechanistic route for Barrett's esophagus neoplastic progression.

  18. Early invasive vulvar squamous cell carcinoma arising in a woman with vulvar pemphigus vulgaris and systemic lupus erythematosus.

    Science.gov (United States)

    Bifulco, Giuseppe; Mandato, Vincenzo D; Piccoli, Roberto; Giampaolino, Pierluigi; Mignogna, Chiara; Mignogna, Michele D; Costagliola, Luigi; Nappi, Carmine

    2010-06-23

    Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and mucous membranes. Genital involvement occurs when most other common sites are concurrently affected or are in remission. Systemic lupus erythematosus (SLE) is an autoimmune disease that may affect many parts of the body and the skin with occasional bullous lesions. Pemphigus vulgaris and SLE may be associated, albeit rarely. Here, we report the first case of a woman affected with SLE presenting with early invasive squamous cell carcinoma (SCC) arising from Pemphigus Vulgaris of the vulva. A 27-year-old Caucasian woman was admitted to our Gynaecology Unit for bleeding vegetant lesions of the vulva. Her history was characterized by systemic lupus erythematosus and PV. Biopsy showed concomitant PV and vulvar intraepithelial neoplasia (VIN) grade 3. One month later a new biopsy revealed progression from VIN 3 to early SCC. Despite chemotherapy, no remission of disease was observed. She died six months after diagnosis Our case underlines PV as another chronic inflammatory disease of the lower genital tract predisposing to VIN-SCC. It suggests the need for careful follow-up of patients with chronic inflammatory disease, especially when concomitant autoimmune disorders are present. Moreover, a biopsy should be always performed if there are PV lesions because of the possibility of neoplastic disease.

  19. Quantitative patterns of Hsps in tubular adenoma compared with normal and tumor tissues reveal the value of Hsp10 and Hsp60 in early diagnosis of large bowel cancer.

    Science.gov (United States)

    Rappa, Francesca; Pitruzzella, Alessandro; Marino Gammazza, Antonella; Barone, Rosario; Mocciaro, Emanuele; Tomasello, Giovanni; Carini, Francesco; Farina, Felicia; Zummo, Giovanni; Conway de Macario, Everly; Macario, Alberto Jl; Cappello, Francesco

    2016-09-01

    Large bowel carcinogenesis involves accumulation of genetic alterations leading to transformation of normal mucosa into dysplasia and, lastly, adenocarcinoma. It is pertinent to elucidate the molecular changes occurring in the pre-neoplastic lesions to facilitate early diagnosis and treatment. Heat shock proteins (Hsps), many of which are molecular chaperones, are implicated in carcinogenesis, and their variations with tumor progression encourage their study as biomarkers. There are many reports on Hsps and cancer but none to our knowledge on their systematic quantification in pre-neoplastic lesions of the large bowel. We performed immunohistochemical determinations of Hsp10, Hsp60, Hsp70, and Hsp90 in biopsies of large bowel tubular adenomas with moderate grade of dysplasia and compared to normal mucosa and adenocarcinoma with a moderate grade of differentiation (G2). A significant elevation of Hsp10 and Hsp60 only, i.e., in the absence of elevation of Hsp70 or Hsp90, in both epithelium and lamina propria was found in tubular adenoma by comparison with normal mucosa. In contrast, adenocarcinoma was characterized by the highest levels of Hsp10 and Hsp60 in epithelium and lamina propria, accompanied by the highest levels of Hsp70 only in epithelium and of Hsp90 only in lamina propria, by comparison with normal and tubular adenoma counterparts. Hsp10 and Hsp60 are promising biomarkers for early diagnosis of tubular adenoma and for its differentiation from more advanced malignant lesions. Hsp10 and Hsp60 may be implicated in carcinogenesis from its very early steps and, thus, are potentially convenient targets for therapy.

  20. Peer Bullying During Early Childhood

    OpenAIRE

    Uysal, Hatice; DİNÇER, Çağlayan

    2012-01-01

    Peer bullying during early childhood is discussed along with the literature reviewed in this article with the purpose of drawing attention to peer bullying during early childhood and its significance, and contributing to studies which are few in number in Turkey. Peer bullying during early childhood was considered with its definition and types, people who play key roles in peer bullying, factors (gender, age, parents, and friendship) that relate to peer bullying, and what should be done befor...

  1. Icebergs on early Mars

    Science.gov (United States)

    Uceda, E.; Fairen, A.; Woodworth-Lynas, C.; Palmero Rodriguez, A.

    2015-12-01

    The smooth topography of the Martian northern lowlands has been classically equated to an ancient ocean basin. The High-Resolution Imaging Science Experiment (HiRISE) onboard the Mars Reconnaissance Orbiter (MRO) is providing unprecedented images of the Martian surface at scales of 25 to 32 cm per pixel. The analysis of this high-resolution imaging reveals the presence of three differentiated geomorphologies throughout the northern lowlands of Mars and the Hellas basin, which are informative of the presence of icebergs floating in ancient oceans and/or seas. These morphologies are: (i) scattered scour marks, including curvilinear furrows several km long and some meters deep; (ii) boulders ranging in size from 0.5 m to ~2 m in diameter, distributed forming clusters with sizes from several hundred meters to 1-2 km; and (iii) flat-topped and conical circular fractured mounds. The association of plough marks, clusters of boulders and mounds on the northern plains of Mars can be related to the dual processes of ice keel scouring and ice rafting of both glacial and non-glacial detritus by a floating ice canopy and icebergs. These processes are well documented on Earth and result in distinct morphologies on the ocean floor, which are analogous to features observed in the Martian basins. Importantly, the features are located in elevated areas of the northern plains and Hellas, near the dichotomy boundary and on local topographic highs. Such distribution is expected, as these relatively shoal areas are where the iceberg-related features should occur on Mars: these areas had shallow water depths, less than the iceberg's keel depth, and therefore keels reached through the full depth of the water column to impinge on the sediments below. The presence of icebergs floating in cold oceans early in Mars' history imply the occurrence of continental glaciers forming in the highlands and streaming northward towards the lowlands, and towards the Hellas and Argyre Basins. Glacier

  2. The importance of early detection of lip cancer risk groups

    Science.gov (United States)

    Fratila, M.; Rosu, S.

    2014-03-01

    Oral maxillo-facial region cancer carries major importance in the tumour pathology of the organism being characterized by a high frequency as well as by the variety of the clinical anatomical and topographic forms through which it is presented. Over 60% of labial carcinoma begins as an asymptomatic ulceration, therefore patients do not pay due attention, considering it a "rebellious thrush" and they make a specialized medical appointment in an advanced stage of the tumor. In this study we pursued the frequency of the lip cancer pathology compared to the total CMF; the distribution the lip cancer by sex and age in patients who submitted to the specialized service; the originating environment of the patient with lip cancer; the anatomical location of the lip cancer; the frequency of relapses after treatment; the presence of adenopathy in the first consultation. The study was performed at the Clinic of Cranio-Maxillofacial Surgery, University of Medicine and Pharmacy "Victor Babes" Timişoara and pursued statistical aspects of the lip cancer incidence over a period of five years (2007-2012). Pre- and postoperative patients were monitored constantly, registering in individual sheets the evolution of the disease, monitoring the relapses after treatment and the presence of adenopathy in the first consultation. As shown in the statistics made in the last five years (2007-2012), from a total of 8135 cases with CMF pathology hospitalized in the Timisoara surgery clinic, 163 cases, or 2%, were cancer of the lip. Analyzing the gender distribution shows that males represent 81% of cases while the remaining 19% were found in women. From the study of age distribution, we found that the number of cases increases with age: 153 cases over 60 years old and 58 cases between 20 - 60 years. Personal statistics from the 212 cases of cancer of the lip reveal that 143 (67%) patients were from the rural areas and 69 (33%) from urban areas. Neoplastic pathology is constantly increasing both

  3. Early Attachment Relationships and the Early Childhood Curriculum

    Science.gov (United States)

    Cortazar, Alejandra; Herreros, Francisca

    2010-01-01

    This article explores the relationship between attachment theory and the early childhood curriculum. During the first years of life children develop early attachment relationships with their primary caregivers. These attachment relationships, either secure or insecure, will shape children's socio-emotional development. In the USA, the predominant…

  4. Critical Questions about Early Intervention and Early Childhood Special Education

    Science.gov (United States)

    Winer, Abby; Hebbeler, Kathy; Nelson, Robin; Gundler, Darla; Cate, Debbie; Hudson, Laura; Taylor, Cornelia; Peters, Mary Louise

    2015-01-01

    What is a high-quality statewide data system? One characteristic is that it provides the information needed to address important questions about early intervention and early childhood special education. But what are those questions? What questions should data users, such as program directors, advocates, and policymakers, be asking? The Center for…

  5. Early reionization by miniquasars

    CERN Document Server

    Madau, P; Oh, S P; Rees, Martin J; Volonteri, M; Madau, Piero; Rees, Martin J.; Volonteri, Marta; Haardt, Francesco

    2004-01-01

    Motivated by the recent detection by WMAP of a large optical depth to Thomson scattering -- implying a very early reionization epoch -- we assess a scenario where the universe was reionized by `miniquasars' powered by intermediate-mass black holes (IMBHs), the remnants of the first generation of massive stars. Pregalactic IMBHs form within minihalos above the cosmological Jeans mass collapsing at z=24, get incorporated through mergers into larger and larger systems, sink to the center owing to dynamical friction, and accrete cold material. The merger history of dark halos and associated IMBHs is followed by Monte Carlo realizations of the merger hierarchy in a LCDM cosmology. While seed IMBHs that are as rare as the 3.5-sigma peaks of the primordial density field evolve largely in isolation, a significant number of black hole binary systems will form if IMBHs populate the more numerous 3-sigma peaks instead. In the case of rapid binary coalescence a fraction of IMBHs will be displaced from galaxy centers and ...

  6. Early Repolarization Syndrome

    Directory of Open Access Journals (Sweden)

    Frederic Sacher

    2015-04-01

    Full Text Available The electrocardiographic pattern of early repolarization (ER is common, with a particularly high prevalence reported amongst athletes and adolescents. It has long been associated with benign outcome [1-3]. Recently, an association between inferolateral ER pattern and sudden cardiac death (SCD has been established by different groups [4-7]. Population-based studies have also reported an increased mortality rate among patients with inferolateral ER pattern compared to controls [7-9]. To bring back together these differences, it is important to focus on the definition of ER pattern used in these different studies as well as the population included. The definition of ER pattern associated with sudden cardiac death was the presence of J point elevation more than or equal to 0.1mV in at least 2 contiguous inferior and/or lateral leads of a standard 12-lead ECG and not ST elevation as it was often the case in the studies with benign outcome. Any study dealing with ER should clearly indicate the definition used. Otherwise it cannot be interpreted. Talking about definition, ER syndrome is an ER pattern (as defined above associated with symptoms (syncope or aborted SCD and/or familial history of SCD as mentioned in the last HRS/EHRA/APHRS Expert Consensus Statement on the Diagnosis and Management of Patients with Inherited Primary Arrhythmia Syndromes [10]. It is important to recognise that having only an ER pattern is not a disease.

  7. EARLY ENTRANCE COPRODUCTION PLANT

    Energy Technology Data Exchange (ETDEWEB)

    John S. Abughazaleh; Mushtaq Ahmed; Ashok Anand; John H. Anderson; Charles Benham; Fred D. Brent; Thomas E. Chance; William K. Davis; Raymond F. Drnevich; Larry Hall; Ming He; Stephen A. Lang; David Mintner; Wendy Moore; Jimmy O. Ong; George Potoczniak; Adela G. Sanchez; Charles H. Schrader; Lalit S. Shah; Kalapi D. Sheth; Phil J. Shires; Rae Song

    2001-05-17

    The overall objective of this project is the three-phase development of an Early Entrance Coproduction Plant (EECP) that produces at least one product from at least two of the following three categories: Electric power (or heat); Fuels; and Chemicals. The objective is to have these products produced by technologies capable of using synthesis gas derived from coal and/or some other carbonaceous feedstock, such as petroleum coke. The objective of Phase I was to determine the feasibility and define the concept for the EECP located at a specific site and to develop a Research, Development, and Testing (RD and T) Plan for implementation in Phase II. This objective has now been accomplished. A specific site, Motiva Refinery in Port Arthur, Texas, has been selected as the location best suited for the EECP. The accomplishments of Phase I are discussed in detail in this Phase I Concept Report. A RD and T Plan and a preliminary project financing plan have been developed and are submitted separately from this report.

  8. EARLY ENTRANCE COPRODUCTION PLANT

    Energy Technology Data Exchange (ETDEWEB)

    Mushtaq Ahmed; John H. Anderson; Charles Benham; Earl R. Berry; Fred Brent; Belma Demirel; Ming He; Troy Raybold; Manuel E. Quintana; Lalit S. Shah; Kenneth A. Yackly

    2003-06-09

    The overall objective of this project is the three phase development of an Early Entrance Coproduction Plant (EECP) which produces at least one product from at least two of the following three categories: (1) electric power (or heat), (2) fuels, and (3) chemicals. The objective is to have these products produced by technologies capable of using synthesis gas derived from coal and/or other carbonaceous feedstocks. The objectives of Phase I were to determine the feasibility and define the concept for the EECP located at a specific site; develop a Research, Development, and Testing (RD&T) Plan for implementation in Phase II; and prepare a Preliminary Project Financing Plan. The objective of Phase II is to implement the work as outlined in the Phase I RD&T Plan to enhance the development and commercial acceptance of coproduction technology that produces high-value products, particularly those that are critical to our domestic fuel and power requirements. The project will resolve critical knowledge and technology gaps on the integration of gasification and downstream processing to coproduce some combination of power, fuels, and chemicals from coal and/or other carbonaceous feedstocks. The objective of Phase III is to develop an engineering design package and a financing and testing plan for an EECP located at a specific site. The project's intended result is to provide the necessary technical, economic, and environmental information needed by industry to move the EECP forward to detailed design, construction, and operation.

  9. Freud's early clinical work.

    Science.gov (United States)

    Vogel, L Z

    1994-01-01

    Freud became a medical practitioner because it was impossible for him to pursue the desired career of a microscopic researcher. His education and training had not prepared him for the task of being a practicing physician. In his private practice he began treating some very intelligent, chaotic, demanding, volatile and disturbed patients. Anna von Lieben was one of these patients whom Freud treated very intensively for a long period of time. Elise Gomperz was another talented and severely pained early patient of Freud. Over a number of years, Freud was her psychiatrist and provided her with attentive care using a variety of treatment methods that were available to him at that time. Emmy von N.'s condition was also fluctuating and very demanding. The dramatic sense and chronic clinical course of these patients is compatible with the contemporary diagnostic category of Borderline Personality Disorder. Freud provided these patients with long-term supportive care while he attempted to cure them. At the same time, Freud committed himself to the theory of radical cure and downplayed the supportive, draining and difficult clinical work that he was doing.

  10. EARLY ENTRANCE COPRODUCTION PLANT

    Energy Technology Data Exchange (ETDEWEB)

    John S. Abughazaleh; Mushtaq Ahmed; Ashok Anand; John H. Anderson; Charles Benham; Fred D. Brent; Thomas E. Chance; William K. Davis; Raymond F. Drnevich; Larry Hall; Ming He; Stephen A. Lang; Jimmy O. Ong; Sarah J. Patel; George Potoczniak; Adela G. Sanchez; Charles H. Schrader; Lalit S. Shah; Phil J. Shires; Rae Song

    2000-10-26

    The overall objective of this project is the three phase development of an Early Entrance Coproduction Plant (EECP) which produces at least one product from at least two of the following three categories: (1) electric power (or heat), (2) fuels, and (3) chemicals. The objective is to have these products produced by technologies capable of using synthesis gas derived from coal and/or other carbonaceous feedstock. The objective of Phase I is to determine the feasibility and define the concept for the EECP located at a specific site and to develop a Research, Development, and Testing Plan (RD and T) for implementation in Phase II. The objective of Phase II is to implement the RD and T as outlined in the Phase I RD and T Plan to enhance the development and commercial acceptance of coproduction technology that produces high-value products, particularly those that are critical to our domestic fuel and power requirements. The project will resolve critical knowledge and technology gaps on the integration of gasification and downstream processing to coproduce some combination of power, fuels, and chemicals from coal and other feedstocks. The objective of Phase III is to develop an engineering design package and a financing plan for an EECP located at a specific site. The project's intended result is to provide the necessary technical, economic, and environmental information that will be needed to move the EECP forward to detailed design, construction, and operation by industry.

  11. Is credit for early action credible early action?

    Energy Technology Data Exchange (ETDEWEB)

    Rolfe, C. [West Coast Environmental Law Research Foundation, Vancouver, BC (Canada); Michaelowa, A.; Dutschke, M. [Hamburg Institute for Economic Research, Hamburg, (Germany)

    1999-12-01

    Credit for early action as a tool for greenhouse gas emissions reduction is compared with various market instruments as a means of narrowing the gap between projected emssions and those of the Kyoto Protocol. Market instruments work by creating a market price for emissions and use the market to encourage reductions at the lowest price, which is done by placing limits on greenhouse gas emissions and allowing the market to decide where reductions occur, or by imposing a carbon tax or emissions charge. While they can be applied within a sector, they are usually used to encourage reductions throughout the economy or across large sectors. Credit for early action also creates an incentive for emissions reductions throughout the economy or at least across many sectors. Credit for early action tools do not work by either imposing a carbon tax or emissions charge or placing limits on emissions, rather they promise that entities that take action against greenhouse gases prior to the imposition of a carbon tax or emissions limits will receive a credit against future taxes or limits. An overview is provided of the Kyoto Protocol and the rationale for taking early action, and a review is included of the theory and specific proposals for market instruments and credit for early action. A comparative analysis is provided of these approaches by examining their relative efficiency, environmental effectiveness, and impacts on the redistribution of wealth. Credit for early action is viewed as problematic on a number of counts and is seen as an interim strategy for imposition while political support for market instruments develop. The environmental effectiveness of credit for early action is very difficult to predict, and credit for early action programs do not yield the lowest cost emissions reductions. Credit for early action programs will not achieve compliance with the Kyoto Protocol at the lowest cost, and credits for early action will increase the compliance costs for those who

  12. Plasma matrix metalloproteinase 9 as an early surrogate biomarker of advanced colorectal neoplasia.

    Science.gov (United States)

    Gimeno-García, Antonio Z; Triñanes, Javier; Quintero, Enrique; Salido, Eduardo; Nicolás-Pérez, David; Adrián-de-Ganzo, Zaida; Alarcón-Fernández, Onofre; Abrante, Beatriz; Romero, Rafael; Carrillo, Marta; Ramos, Laura; Alonso, Inmaculada; Ortega, Juan; Jiménez, Alejandro

    2016-01-01

    Matrix metalloproteinases (MMPs) are overexpressed at different stages of colorectal carcinogenesis and could serve as early surrogate biomarkers of colorectal neoplasia. To assess the utility of plasma MMP2 and MMP9 levels in the detection of advanced colorectal neoplasia and their correlation with tissue levels. We analysed blood and tissue samples from patients with non-advanced adenomas (n=25), advanced adenomas (n=25), colorectal cancer (n=25) and healthy controls (n=75). Plasma and tissue gelatinase levels were determined by Luminex XMAP technology and gelatin zymography. Receiver operating characteristic (ROC) curve analysis was used to calculate the optimum cut-off for the detection of advanced colorectal neoplasia. Plasma MMP2 levels were similar between groups whatever the type of lesion. Plasma MMP9 levels were significantly higher in patients with neoplastic lesions than in healthy controls (median 292.3ng/ml vs. 139.08ng/ml, P<0.001). MMP9 levels were also higher in colorectal cancer than in non-advanced adenomas (median 314.6ng/ml vs. 274.3ng/ml, P=0.03). There was a significant correlation between plasma and tissue levels of MMP9 (r=0.5, P<0.001). The plasma MMP9 cut-off range with the highest diagnostic accuracy was between 173ng/ml and 204ng/ml (AUC=0.80 [95% CI: 0.72-0.86], P<0.001; sensitivity, 80-86% and specificity, 57-67%). Plasma MMP9 could be a surrogate biomarker for the early detection of advanced colorectal neoplasia, although its diagnostic performance could be increased by combination with other biomarkers. Copyright © 2015 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

  13. Early onset sebaceous carcinoma

    Directory of Open Access Journals (Sweden)

    Kaltreider Sara A

    2011-09-01

    Full Text Available Abstract Background Ocular sebaceous carcinoma can masquerade as benign lesions resulting in delay of diagnosis. Early recognition is even more difficult in young patients where the disease rarely occurs. Here, we provide a clinicopathological correlation of ocular sebaceous carcinoma in a young individual lacking history of hereditary cancer or immunosuppression. Findings A detailed histopathological study including p53 DNA sequencing was performed on an aggressive sebaceous carcinoma presenting in a healthy 32 year-old Caucasian woman. She had no history of retinoblastoma, evidence for a hereditary cancer syndrome, or radiation therapy. However, she potentially was at risk for excessive UV light exposure. A detailed review of the literature is also provided. A moderately well differentiated sebaceous carcinoma was established histopathologically arising from the meibomian gland of the upper eyelid. In most areas, the cytoplasm contained small but distinct Oil-red-O positive vacuoles. Direct sequencing of p53 identified a G:C→A:T mutation at a dipyrimidine site. The mutation results in substitution of arginine for the highly conserved glycine at residue 199 located at the p53 dimer-dimer interface. Energy minimization structural modeling predicts that G199R will neutralize negative charges contributed by nearby inter- and intramonomeric glutamate residues. Discussion This study points to the importance of recognizing that sebaceous carcinoma can occur in young patients with no evidence for hereditary cancer risk or radiation therapy. The G199R substitution is anticipated to alter the stability of the p53 tetrameric complex. The role of UV light in the etiology of sebaceous carcinoma deserves further study. Our findings, taken together with those of others, suggest that different environmental factors could lead to the development of sebaceous carcinoma in different patients.

  14. Expertise of Early Childhood Educators

    Science.gov (United States)

    Happo, Iiris; Määttä, Kaarina

    2011-01-01

    Every preschool age child in Finland has the right to day care and the expertise of educators is multidimensional. The aim of this article is to clarify the expertise of those early childhood educators, who have the competence of kindergarten teachers (n = 80). The data consisted of the early educators' stories of their growth towards expertise.…

  15. Early intervention services in psychosis

    DEFF Research Database (Denmark)

    Csillag, Claudio; Nordentoft, Merete; Mizuno, Masafumi

    2016-01-01

    AIM: Early intervention (EI) in psychosis is a comprehensive and evidence-based approach aimed at detection and treatment of psychotic symptoms in their early stages. This paper presents core features and noteworthy aspects of the evidence basis and limitations of EI, the importance of programme...

  16. Early Identification of Reading Difficulties

    DEFF Research Database (Denmark)

    Poulsen, Mads; Nielsen, Anne-Mette Veber; Juul, Holger

    2017-01-01

    Early screening for reading difficulties before the onset of instruction is desirable because it allows intervention that is targeted at prevention rather than remediation of reading difficulties. However, early screening may be too inaccurate to effectively allocate resources to those who need...

  17. Teachers in Early Childhood Policy

    Science.gov (United States)

    Kilderry, Anna

    2014-01-01

    This paper examines teacher accountability and authority in early childhood policy. It reports on data from a study that investigated the influences affecting early childhood teacher decision-making at the preschool level in Victoria, Australia. Using a question raised by Ball "Where are the teachers in all this [policy]?" provided a…

  18. Missouri: Early Head Start Initiative

    Science.gov (United States)

    Center for Law and Social Policy, Inc. (CLASP), 2012

    2012-01-01

    Missouri's Early Head Start/Child Care Partnership Project expands access to Early Head Start (EHS) services for children birth to age 3 by developing partnerships between federal Head Start, EHS contractors, and child care providers. Head Start and EHS contractors that participate in the initiative provide services through community child care…

  19. Early Childhood Inclusion in Spain

    Science.gov (United States)

    Giné, Climent; Balcells-Balcells, Anna; Cañadas, Margarita; Paniagua, Gema

    2016-01-01

    This article describes early childhood inclusion in educational settings in Spain. First, we address the legislative framework of preschool education in Spain and offer a brief analysis of some relevant issues, including the current situation of early childhood education and inclusion at this stage. Second, current policies and practices relating…

  20. Voluntary Incentive Early Retirement Programs.

    Science.gov (United States)

    Research Dialogues, 1988

    1988-01-01

    Arrangements in educational institutions for voluntary early retirement programs are discussed. Retirement at any age can be a profound and stressful lifetime change; and it can also represent a welcome transition into newly satisfying and rewarding opportunities. The focus is on: mandatory retirement (exceptions and the new meaning of "early");…

  1. Data Systems in Early Intervention.

    Science.gov (United States)

    Hebbeler, Kathleen

    This study compiled descriptive information about what states are doing or planning to do with early intervention data systems, a component of early intervention systems as specified in Part H of the Individuals with Disabilities Education Act. The study examined the uses of data systems in eight states: Colorado, Maine, Maryland, Massachusetts,…

  2. Optical redox ratio differentiates early tissue transformations in DMBA-induced hamster oral carcinogenesis based on autofluorescence spectroscopy coupled with multivariate analysis

    Science.gov (United States)

    Sethupathi, R.; Gurushankar, K.; Krishnakumar, N.

    2016-11-01

    Fluorescence intensity measurements have the potential to facilitate the diagnoses of many pathological conditions. The changes in fluorescence intensity may be influenced by factors such as tissue architectures, endogenous fluorophores, cellular metabolism and light penetration depth in tissue. Two of the most diagnostically important endogenous fluorophores are reduced nicotinamide dinucleotide (NADH) and flavin adenine dinucleotide (FAD), which can be used to monitor dramatic metabolic changes in cells and tissues. The goal of this study is to investigate changes in the endogenous fluorophore emission and to quantify metabolic changes in the redox state of various tissue transformation conditions with respect to control tissues in dimethyl benz[a] anthracene (DMBA)-induced hamster oral carcinogenesis for measuring emission spectrum at 320 nm excitation. In the present study, collagen, NADH and FAD emission of well-differentiated squamous cell carcinoma (WDSCC) showed decreased intensity at ~385 nm, ~450 nm and ~520 nm compared to hyperplasia, dysplasia and control tissues. Furthermore, a significant decrease in the optical redox ratio is observed in WDSCC tissues, which indicates an increased metabolic activity compared to the control tissues. Moreover, the principal component linear discriminant analysis (PC-LDA) algorithm together with the leave-one-out cross-validation (LOOCV) method yield an overall diagnostic sensitivity of 77.7% and a specificity of 88.8% in the classification of control, hyperplasia, dysplasia and WDSCC tissues, respectively. The results from this study demonstrated that fluorescence-based tissue analysis combined with PC-LDA has tremendous potential for the effective discrimination of control from neoplastic tissues; furthermore it also detects early neoplastic changes prior to definite morphologic alteration.

  3. Early sound distribution in auditorium

    Institute of Scientific and Technical Information of China (English)

    JIANG Guorong; WANG Jiqing

    2000-01-01

    The importance of early sound, i.e., the direct sound and the first reflections, has long been recognized in auditorium design, but the distributions of early sound in auditorium received less investigation in the past. As we know, the early sound level in the audience area varies not only with the source/receiver distance and room constant, but also related with the room geometry, the absorption arrangement and the location of the source and receiver. The early reflections are of discrete components, so it can not be predicted by the diffused field theory. This paper presents the results of measurement in four halls showing the attenuation rates of early sound level with the source/receiver distance are often much larger than the theoretical predictions. Therefore, they may give overestimated results in acoustical design.

  4. Early diagnosis and early intervention in cerebral palsy

    Directory of Open Access Journals (Sweden)

    Mijna eHadders-Algra

    2014-09-01

    Full Text Available This paper reviews the opportunities and challenges for early diagnosis and early intervention in cerebral palsy (CP. CP describes a group of disorders of the development of movement and posture, causing activity limitation, that are attributed to disturbances that occurred in the fetal or infant brain. Therefore the paper starts with a summary of relevant information from developmental neuroscience. Most lesions underlying CP occur in the second half of gestation, when developmental activity in the brain reaches its summit. Variations in timing of the damage not only result in different lesions, but also in different neuroplastic reactions and different associated neuropathologies. This turns CP into a heterogeneous entity. This may mean that the best early diagnostics and the best intervention methods may differ for various subgroups of children with CP. Next, the paper addresses possibilities for early diagnosis. It discusses the predictive value of neuromotor and neurological exams, neuro-imaging techniques and neurophysiological assessments. Prediction is best when complementary techniques are used in longitudinal series. Possibilities for early prediction of CP differ for infants admitted to neonatal intensive care and other infants. In the former group best prediction is achieved with the combination of neuro-imaging and the assessment of general movements, in the latter group best prediction is based on carefully documented milestones and neurological assessment. The last part reviews early intervention in infants developing CP. Most knowledge on early intervention is based on studies in high risk infants without CP. In these infants early intervention programs promote cognitive development until preschool age; motor development profits less. The few studies on early intervention in infants developing CP suggest that programs that stimulate all aspects of infant development by means of family coaching are most promising. More research is

  5. EARLY ENTRANCE COPRODUCTION PLANT

    Energy Technology Data Exchange (ETDEWEB)

    John Anderson; Charles Schrader

    2004-01-26

    In 1999, the U. S. Department of Energy (DOE) awarded a Cooperative Agreement to Texaco Energy Systems Inc. to provide a preliminary engineering design of an Early Entrance Coproduction Plant (EECP). Since the award, continuous and diligent work has been undertaken to achieve the design of an economical facility that makes strides toward attaining the goal of DOE's Vision 21 Program. The objective of the EECP is to convert coal and/or petroleum coke to power while coproducing transportation fuels, chemicals, and useful utilities such as steam. This objective is being pursued in a three-phase effort through the partnership of the DOE with prime contractor Texaco Energy Systems, LLC. (TES), the successor to Texaco Energy Systems, Inc. The key subcontractors to TES include General Electric (GE), Praxair, and Kellogg Brown and Root. ChevronTexaco provided gasification technology and Rentech Inc.'s Fischer-Tropsch (F-T) technology that has been developed for non-natural gas sources. GE provided gas turbine technology for the combustion of low energy content gas. Praxair provided air separation technology and KBR provided engineering to integrate the facility. A conceptual design was completed in Phase I and the report was accepted by the DOE in May 2001. The Phase I work identified risks and critical research, development, and testing that would improve the probability of technical success of the EECP. The objective of Phase II was to mitigate the risks by executing research, development, and testing. Results from the Phase II work are the subject of this report. As the work of Phase II concluded, it became evident that sufficient, but not necessarily complete, technical information and data would be available to begin Phase III - Preliminary Engineering Design. Work in Phase II requires additional technical development work to correctly apply technology at a specific site. The project's intended result is to provide the necessary technical, economic, and

  6. EARLY ENTRANCE COPRODUCTION PLANT

    Energy Technology Data Exchange (ETDEWEB)

    David Storm; Govanon Nongbri; Steve Decanio; Ming He; Lalit Shah; Charles Schrader; Earl Berry; Peter Ricci; Belma Demirel; Charles Benham; Mark Bohn

    2004-01-12

    The overall objective of this project is the three phase development of an Early Entrance Coproduction Plant (EECP) which uses petroleum coke to produce at least one product from at least two of the following three categories: (1) electric power (or heat), (2) fuels, and (3) chemicals using ChevronTexaco's proprietary gasification technology. The objective of Phase I is to determine the feasibility and define the concept for the EECP located at a specific site; develop a Research, Development, and Testing (RD&T) Plan to mitigate technical risks and barriers; and prepare a Preliminary Project Financing Plan. The objective of Phase II is to implement the work as outlined in the Phase I RD&T Plan to enhance the development and commercial acceptance of coproduction technology. The objective of Phase III is to develop an engineering design package and a financing and testing plan for an EECP located at a specific site. The project's intended result is to provide the necessary technical, economic, and environmental information needed by industry to move the EECP forward to detailed design, construction, and operation. The partners in this project are Texaco Energy Systems LLC or TES (a subsidiary of ChevronTexaco), General Electric (GE), Praxair, and Kellogg Brown & Root (KBR) in addition to the U.S. Department of Energy (DOE). TES is providing gasification technology and Fischer-Tropsch (F-T) technology developed by Rentech, Inc., GE is providing combustion turbine technology, Praxair is providing air separation technology, and KBR is providing engineering. During Phase I, a design basis for the Fischer-Tropsch Synthesis section was developed based on limited experience with the specified feed gas and operating conditions. The objective of this Task in Phase II RD&T work was to confirm the performance of the F-T reactor at the set design conditions. Although much of the research, development, and testing work were done by TES outside of this project, several

  7. What Works Clearinghouse Quick Review: "Early College, Early Success: Early College High School Initiative Impact Study"

    Science.gov (United States)

    What Works Clearinghouse, 2013

    2013-01-01

    The study examined in this quick review concerns whether attending Early College High Schools increased postsecondary outcomes. This study is a randomized experiment examining the impact of Early Colleges on a number of outcomes. The study had relatively low attrition rates (approximately 7% in the intervention group and 13% in the comparison…

  8. Peer Bullying During Early Childhood

    Directory of Open Access Journals (Sweden)

    Hatice UYSAL

    2012-10-01

    Full Text Available Peer bullying during early childhood is discussed along with the literature reviewed in this article with the purpose of drawing attention to peer bullying during early childhood and its significance, and contributing to studies which are few in number in Turkey. Peer bullying during early childhood was considered with its definition and types, people who play key roles in peer bullying, factors (gender, age, parents, and friendship that relate to peer bullying, and what should be done before and after peer bullying.

  9. Early traumatic events in psychopaths.

    Science.gov (United States)

    Borja, Karina; Ostrosky, Feggy

    2013-07-01

    The relationship between diverse early traumatic events and psychopathy was studied in 194 male inmates. Criminal history transcripts were revised, and clinical interviews were conducted to determine the level of psychopathy using the Psychopathy Checklist-Revised (PCL-R) Form, and the Early Trauma Inventory was applied to assess the incidence of abuse before 18 years of age. Psychopathic inmates presented a higher victimization level and were more exposed to certain types of intended abuse than sociopathic inmates, while the sum of events and emotional abuse were associated with the PCL-R score. Our studies support the influence of early adverse events in the development of psychopathic offenders.

  10. Early vision and visual attention

    Directory of Open Access Journals (Sweden)

    Gvozdenović Vasilije P.

    2003-01-01

    Full Text Available The question whether visual perception is spontaneous, sudden or is running through several phases, mediated by higher cognitive processes, was raised ever since the early work of Gestalt psychologists. In the early 1980s, Treisman proposed the feature integration theory of attention (FIT, based on the findings of neuroscience. Soon after publishing her theory a new scientific approach appeared investigating several visual perception phenomena. The most widely researched were the key constructs of FIT, like types of visual search and the role of the attention. The following review describes the main studies of early vision and visual attention.

  11. Morphogenesis of early stage melanoma

    Science.gov (United States)

    Chatelain, Clément; Amar, Martine Ben

    2015-08-01

    Melanoma early detection is possible by simple skin examination and can insure a high survival probability when successful. However it requires efficient methods for identifying malignant lesions from common moles. This paper provides an overview first of the biological and physical mechanisms controlling melanoma early evolution, and then of the clinical tools available today for detecting melanoma in vivo at an early stage. It highlights the lack of diagnosis methods rationally linking macroscopic observables to the microscopic properties of the tissue, which define the malignancy of the tumor. The possible inputs of multiscale models for improving these methods are shortly discussed.

  12. Early eruption of permanent canines.

    Science.gov (United States)

    Madhu, S

    2012-01-01

    Systemic and local factors can modify the eruption time of teeth. Generalized eruption time changes could be due to some systemic diseases like hyperthyroidism, hypophosphatasia, precocious puberty, Proteus syndrome, etc. Localized early eruption of permanent teeth could be due to early extraction of deciduous teeth. Presented here is an extremely rare case of early eruption of permanent canines in a 7-year old female child. Though the number of such cases is very limited, the clinician should poses adequate knowledge and keeps an open eye to identify such cases.

  13. Early eruption of permanent canines

    Directory of Open Access Journals (Sweden)

    S Madhu

    2012-01-01

    Full Text Available Systemic and local factors can modify the eruption time of teeth. Generalized eruption time changes could be due to some systemic diseases like hyperthyroidism, hypophosphatasia, precocious puberty, Proteus syndrome, etc. Localized early eruption of permanent teeth could be due to early extraction of deciduous teeth. Presented here is an extremely rare case of early eruption of permanent canines in a 7-year old female child. Though the number of such cases is very limited, the clinician should poses adequate knowledge and keeps an open eye to identify such cases.

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

    Science.gov (United States)

    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

  15. EARLY ENTRANCE COPRODUCTION PLANT

    Energy Technology Data Exchange (ETDEWEB)

    Charles Benham; Mark Bohn; John Anderson; Earl Berry; Fred Brent; Ming He; Randy Roberts; Lalit Shah; Marjan Roos

    2003-09-15

    The 1999 U. S. Department of Energy (DOE) award to Texaco Energy Systems Inc. (presently Texaco Energy Systems LLC, a subsidiary of ChevronTexaco) was made to provide a Preliminary Engineering Design of an Early Entrance Coproduction Plant (EECP). Since the award presentation, work has been undertaken to achieve an economical concept design that makes strides toward the DOE Vision 21 goal. The objective of the EECP is to convert coal and/or petroleum coke to electric power plus transportation fuels, chemicals and useful utilities such as steam. The use of petroleum coke was added as a fuel to reduce the cost of feedstock and also to increase the probability of commercial implementation of the EECP concept. This objective has been pursued in a three phase effort through the partnership of the DOE with prime contractor Texaco Energy Systems LLC and subcontractors General Electric (GE), Praxair, and Kellogg Brown and Root (KBR). ChevronTexaco is providing gasification technology and Rentech's Fischer-Tropsch technology that has been developed for non-natural gas feed sources. GE is providing gas turbine technology for the combustion of low energy content gas. Praxair is providing air separation technology, and KBR is providing engineering to integrate the facility. The objective of Phase I was to determine the feasibility and define the concept for the EECP located at a specific site; develop a Research, Development, and Testing (RD&T) Plan to mitigate technical risks and barriers; and prepare a Preliminary Project Financing Plan. The objective of Phase II is to implement the work as outlined in the Phase I RD&T Plan to enhance the development and commercial acceptance of coproduction technology. The objective of Phase III is to develop an engineering design package and a financing and testing plan for an EECP located at a specific site. Phase I Preliminary Concept Report was completed in 2000. The Phase I Preliminary Concept Report was prepared based on making

  16. EARLY ENTRANCE COPRODUCTION PLANT

    Energy Technology Data Exchange (ETDEWEB)

    John Anderson; Mark Anselmo; Earl Berry; Mark Bohn; Roko Bujas; Ming He; Ken Kwik; Charles H. Schrader; Lalit Shah; Dennis Slater; Donald Todd; Don Wall

    2003-08-21

    The overall objective of this project is the three phase development of an Early Entrance Coproduction Plant (EECP) which uses petroleum coke to produce at least one product from at least two of the following three categories: (1) electric power (or heat), (2) fuels, and (3) chemicals using ChevronTexaco's proprietary gasification technology. The objective of Phase I is to determine the feasibility and define the concept for the EECP located at a specific site; develop a Research, Development, and Testing (RD&T) Plan to mitigate technical risks and barriers; and prepare a Preliminary Project Financing Plan. The objective of Phase II is to implement the work as outlined in the Phase I RD&T Plan to enhance the development and commercial acceptance of coproduction technology. The objective of Phase III is to develop an engineering design package and a financing and testing plan for an EECP located at a specific site. The project's intended result is to provide the necessary technical, economic, and environmental information needed by industry to move the EECP forward to detailed design, construction, and operation. The partners in this project are Texaco Energy Systems LLC (TES), a subsidiary of ChevronTexaco, General Electric (GE), Praxair, and Kellogg Brown & Root (KBR) in addition to the U.S. Department of Energy (DOE). TES is providing gasification technology and Fischer-Tropsch (F-T) technology developed by Rentech, Inc. GE is providing combustion turbine technology, Praxair is providing air separation technology, and KBR is providing engineering. Each of the EECP subsystems were assessed for technical risks and barriers. A plan was identified to mitigate the identified risks (Phase II RD&T Plan, October 2000). The RD&T Plan identified catalyst/wax separation as a potential technical and economic risk. To mitigate risks to the proposed EECP, Phase II RD&T included tests of an alternative (to Rentech's Dynamic Settler) primary catalyst

  17. EARLY ENTRANCE COPRODUCTION PLANT

    Energy Technology Data Exchange (ETDEWEB)

    Fred D. Brent; Lalit Shah; Earl Berry; Charles H. Schrader; John Anderson; Ming He; James F. Stevens; Centha A. Davis; Michael Henley; Jerome Mayer; Harry Tsang; Jimell Erwin; Jennifer Adams; Michael Tillman; Chris Taylor; Marjan J. Roos; Robert F. Earhart

    2004-01-27

    The overall objective of this project is the three phase development of an Early Entrance Coproduction Plant (EECP) which uses petroleum coke to produce at least one product from at least two of the following three categories: (1) electric power (or heat), (2) fuels, and (3) chemicals using ChevronTexaco's proprietary gasification technology. The objective of Phase I is to determine the feasibility and define the concept for the EECP located at a specific site; develop a Research, Development, and Testing (RD&T) Plan to mitigate technical risks and barriers; and prepare a Preliminary Project Financing Plan. The objective of Phase II is to implement the work as outlined in the Phase I RD&T Plan to enhance the development and commercial acceptance of coproduction technology. The objective of Phase III is to develop an engineering design package and a financing and testing plan for an EECP located at a specific site. The project's intended result is to provide the necessary technical, economic, and environmental information needed by industry to move the EECP forward to detailed design, construction, and operation. The partners in this project are Texaco Energy Systems LLC or TES (a subsidiary of ChevronTexaco), General Electric (GE), Praxair, and Kellogg Brown & Root (KBR) in addition to the U.S. Department of Energy (DOE). TES is providing gasification technology and Fischer-Tropsch (F-T) technology developed by Rentech, GE is providing combustion turbine technology, Praxair is providing air separation technology, and KBR is providing engineering. Each of the EECP subsystems was assessed for technical risks and barriers. A plan was developed to mitigate the identified risks (Phase II RD&T Plan, October 2000). The potential technical and economic risks to the EECP from Task 2.5 can be mitigated by demonstrating that the end-use products derived from the upgrading of the F-T synthesis total liquid product can meet or exceed current specifications for the

  18. Early Retiree Reinsurance Program Reports

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Early Retiree Reinsurance Program (ERRP) was established by section 1102 of the Patient Protection and Affordable Care Act (the Affordable Care Act) enacted on...

  19. Early Retiree Reinsurance Program Reports

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Early Retiree Reinsurance Program (ERRP) was established by section 1102 of the Patient Protection and Affordable Care Act (the Affordable Care Act) enacted on...

  20. NGIPS Early Design Space Assessment

    Science.gov (United States)

    2014-07-17

    cycles). The results of this case are shown in Fig. 4. It can be seen that the fault causes a momentary outage of some loads and that the system...perform shipboard power system performance metric refinements, early- stage assessment computational tool investigation, and the application of these...early-stage design space exploration methods and tools were pursued in support of the Navy’s Next Generation Integrated Power Systems (NGIPS

  1. Axions in the early Universe

    Energy Technology Data Exchange (ETDEWEB)

    Graf, Peter; Steffen, Frank Daniel [Max-Planck-Institut fuer Physik, Muenchen (Germany)

    2010-07-01

    The smallness of the CP violating term in the QCD Lagrangian is the well known strong CP problem. If it is solved via the Peccei-Quinn (PQ) mechanism, the pseudo-Nambu-Goldstone boson associated with the spontaneous breaking of the new chiral U(1){sub PQ} symmetry is the axion. We study the behavior of axions in the early Universe and calculate the temperature at which the axion decouples from the early QCD plasma.

  2. NASA Early Career Fellowship Program

    Science.gov (United States)

    Smith, H. D.

    2012-12-01

    The Early Career Fellowship program was established in 2005 to facilitate the integration of outstanding early career planetary science researchers into established research funding programs by providing tools and experience useful to maintain a successful research program. Executing a successful research program requires a few key elements such as: successful proposal writing; adequate (paid) research time; management of a laboratory; collaboration and networking; frequent and high-quality publications; and adequate start-up equipment funds. These elements may be particularly critical for early career researchers searching for a tenure- track or equivalent position. The Early Career Fellowship program recognizes the importance of these skills and provides extra funding and resources to begin a successful research program. For consideration into The Early Career Fellowship program, the candidate needs to be the P. I. or Science P.I. of a funded research proposal from one of the participating R&A program areas, be within 7 years of earning a PhD, hold a non-tenure track position, and indicate the early career candidacy when submitting the research proposal. If the research proposal is funded and the discipline scientist nominates the candidate as an early career fellow, the candidate is then considered a Fellow and eligible to propose for Step 2. Upon obtaining a tenure-track equivalent position the Fellow submits a Step 2 proposal for up to one hundred thousand dollars in start-up funds. Start-up funds may be used for salary; undergraduate and/or graduate research assistants; supplies and instrument upgrades; travel to conferences, meetings, and advisory groups; time and travel for learning new skills; publication page charges; books and journal subscriptions; computer time and/or specialized software; and other justified research-specific needs. The early career fellowship program provides resources that a more established scientist would have acquired allowing

  3. EARLY ENTRANCE COPRODUCTION PLANT

    Energy Technology Data Exchange (ETDEWEB)

    Fred D. Brent; Lalit Shah; Earl Berry; Charles H. Schrader; John Anderson; J. Erwin; Matthew G. Banks; Terry L. Ullman

    2004-01-12

    The overall objective of this project is the three phase development of an Early Entrance Coproduction Plant (EECP) which uses petroleum coke to produce at least one product from at least two of the following three categories: (1) electric power (or heat), (2) fuels, and (3) chemicals using ChevronTexaco's proprietary gasification technology. The objective of Phase I is to determine the feasibility and define the concept for the EECP located at a specific site; develop a Research, Development, and Testing (RD&T) Plan to mitigate technical risks and barriers; and prepare a Preliminary Project Financing Plan. The objective of Phase II is to implement the work as outlined in the Phase I RD&T Plan to enhance the development and commercial acceptance of coproduction technology. The objective of Phase III is to develop an engineering design package and a financing and testing plan for an EECP located at a specific site. The project's intended result is to provide the necessary technical, economic, and environmental information needed by industry to move the EECP forward to detailed design, construction, and operation. The partners in this project are Texaco Energy Systems LLC or TES (a subsidiary of ChevronTexaco), General Electric (GE), Praxair, and Kellogg Brown & Root (KBR) in addition to the U.S. Department of Energy (DOE). TES is providing gasification technology and Fischer-Tropsch (F-T) technology developed by Rentech, GE is providing combustion turbine technology, Praxair is providing air separation technology, and KBR is providing engineering. Each of the EECP subsystems was assessed for technical risks and barriers. A plan was developed to mitigate the identified risks (Phase II RD&T Plan, October 2000). Phase II RD&T Task 2.6 identified as potential technical risks to the EECP the fuel/engine performance and emissions of the F-T diesel fuel products. Hydrotreating the neat F-T diesel product reduces potentially reactive olefins, oxygenates, and acids

  4. EARLY ENTRANCE COPRODUCTION PLANT

    Energy Technology Data Exchange (ETDEWEB)

    Fred D. Brent; Lalit Shah; Earl Berry; Charles H. Schrader; John Anderson; J. Erwin; Matthew G. Banks; Terry L. Ullman

    2004-01-12

    The overall objective of this project is the three phase development of an Early Entrance Coproduction Plant (EECP) which uses petroleum coke to produce at least one product from at least two of the following three categories: (1) electric power (or heat), (2) fuels, and (3) chemicals using ChevronTexaco's proprietary gasification technology. The objective of Phase I is to determine the feasibility and define the concept for the EECP located at a specific site; develop a Research, Development, and Testing (RD&T) Plan to mitigate technical risks and barriers; and prepare a Preliminary Project Financing Plan. The objective of Phase II is to implement the work as outlined in the Phase I RD&T Plan to enhance the development and commercial acceptance of coproduction technology. The objective of Phase III is to develop an engineering design package and a financing and testing plan for an EECP located at a specific site. The project's intended result is to provide the necessary technical, economic, and environmental information needed by industry to move the EECP forward to detailed design, construction, and operation. The partners in this project are Texaco Energy Systems LLC or TES (a subsidiary of ChevronTexaco), General Electric (GE), Praxair, and Kellogg Brown & Root (KBR) in addition to the U.S. Department of Energy (DOE). TES is providing gasification technology and Fischer-Tropsch (F-T) technology developed by Rentech, GE is providing combustion turbine technology, Praxair is providing air separation technology, and KBR is providing engineering. Each of the EECP subsystems was assessed for technical risks and barriers. A plan was developed to mitigate the identified risks (Phase II RD&T Plan, October 2000). Phase II RD&T Task 2.6 identified as potential technical risks to the EECP the fuel/engine performance and emissions of the F-T diesel fuel products. Hydrotreating the neat F-T diesel product reduces potentially reactive olefins, oxygenates, and acids

  5. [Autism: An early neurodevelopmental disorder].

    Science.gov (United States)

    Bonnet-Brilhault, F

    2017-02-27

    With approximately 67 million individuals affected worldwide, autism spectrum disorder (ASD) is the fastest growing neurodevelopmental disorder (United Nations, 2011), with a prevalence estimated to be 1/100. In France ASD affects approximately 600,000 individuals (from childhood to adulthood, half of whom are also mentally retarded), who thus have a major handicap in communication and in adapting to daily life, which leads autism to be recognized as a national public health priority. ASD is a neurodevelopmental disorder that affects several domains (i.e., socio-emotional, language, sensori-motor, executive functioning). These disorders are expressed early in life with an age of onset around 18 months. Despite evidence suggesting a strong genetic link with ASD, the genetic determinant remains unclear. The clinical picture is characterized by impairments in social interaction and communication and the presence of restrictive and repetitive behaviors (DSM-5, ICD-10). However, in addition to these two main dimensions there is significant comorbidity between ASD and other neurodevelopmental disorders such as attention deficit hyperactivity disorder or with genetic and medical conditions. One of the diagnostic features of ASD is its early emergence: symptoms must begin in early childhood for a diagnosis to be given. Due to brain plasticity, early interventions are essential to facilitate clinical improvement. Therefore, general practitioners and pediatricians are on the front line to detect early signs of ASD and to guide both medical explorations and early rehabilitation.

  6. Dietary Seaweed and Early Breast Cancer: A Randomized Trial

    Science.gov (United States)

    2006-05-01

    Sasaoka T, Kimura I. Effect of green tea on blood glucose levels and serum proteomic patterns in diabetic (db/db) mice and on glucose metabolism in...Institute 1998;90:1637-1647. Massion AO, Teas J, Hebert JR, Wertheimer MD, Kabat-Zinn J. Meditation, melatonin , and breast/prostate cancer...Massion AO, Teas J, Hebert JR. Meditation, melatonin , & cancer. Melatonin in Psychiatric & Neoplastic Disorders. Shafii M & Shafii S, Eds

  7. Improved polymerase chain reaction-based method to detect early-stage epitheliotropic T-cell lymphoma (mycosis fungoides) in formalin-fixed, paraffin-embedded skin biopsy specimens of the dog.

    Science.gov (United States)

    Chaubert, Pascal; Baur Chaubert, Audrey S; Sattler, Ursula; Forster, Ursula; Bornand, Valérie; Suter, Maja; Welle, Monika

    2010-01-01

    In the dog, early-stage epitheliotropic T-cell lymphoma (ETCL) can clinically and histologically mimic a large range of inflammatory dermatoses and often progresses rapidly to a more aggressive tumor stage. Early diagnosis of ETCL is essential to proceed with a specific oncologic therapy that is favorable for the prognosis. In the present study, an improved method for the detection of T-cell receptor gamma (TCRgamma) rearrangement was developed by designing a new set of consensus primers to amplify the different forms of rearranged canine TCRgamma gene sequences by polymerase chain reaction. The amplicons were analyzed by conventional polyacrylamide gel electrophoresis, which requires minimal specific equipment and may be performed in almost every pathology laboratory at low costs. The method proved to be highly specific and sensitive to detect early ETCL in formalin-fixed, paraffin-embedded biopsy specimens, providing an efficient tool for veterinary pathologists to distinguish early neoplastic from reactive cutaneous T-cell infiltrates (tumor-specific marker) or to discriminate T-cell lymphoma from B-cell lymphomas or nonlymphoid neoplasms (T-cell lineage marker). By direct sequencing analysis of amplified TCRgamma gene sequences, ETCL was found to rearrange exclusively the joining (J) 4 region, which suggests specific biology for primary cutaneous T-cell lymphomas. Also, a novel (seventh) functional J region in the TCRgamma gene, localized approximately 2.3 kb upstream of J5, was identified.

  8. Early Learner Engagement in the Clinical Workplace

    NARCIS (Netherlands)

    Chen, H.C.

    2015-01-01

    Introduction Recent calls for medical education reform advocate for the integration of knowledge with clinical experience through early clinical immersion. Yet, early learners rarely are invited to participate in workplace activities and early clinical experiences remain largely observational.

  9. Early Learner Engagement in the Clinical Workplace

    NARCIS (Netherlands)

    Chen, H.C.

    2015-01-01

    Introduction Recent calls for medical education reform advocate for the integration of knowledge with clinical experience through early clinical immersion. Yet, early learners rarely are invited to participate in workplace activities and early clinical experiences remain largely observational. We

  10. Can Ovarian Cancer Be Found Early?

    Science.gov (United States)

    ... Ovarian Cancer Early Detection, Diagnosis, and Staging Can Ovarian Cancer Be Found Early? About 20% of ovarian cancers ... cancer in its earliest stage. Ways to find ovarian cancer early Regular women's health exams During a pelvic ...

  11. Endoscopic submucosal dissection of early gastric neoplasia with a water jet-assisted knife: a Western, single-center experience.

    Science.gov (United States)

    Schumacher, Brigitte; Charton, Jean-Pierre; Nordmann, Thomas; Vieth, Michael; Enderle, Markus; Neuhaus, Horst

    2012-06-01

    Endoscopic submucosal dissection (ESD) of early gastric neoplasia has not yet been established in Western countries because of a lack of data and the difficult, time-consuming, and hazardous nature of the method. Some of the technical limitations may be overcome by use of a water jet-assisted knife, which allows a combination of a high-pressure water jet and electrosurgical interventions. To evaluate the efficacy and safety of water jet-assisted ESD (WESD) with a water jet-assisted knife in selected patients with early gastric neoplasia. Single-center, prospective study. This study involved 29 consecutive patients (13 female; median age 61 years; age range 35-93 years) with early gastric neoplasia that met the expanded criteria of the Japanese Gastric Cancer Association. Histology of biopsies had shown gastric adenocarcinoma in 21 cases, adenoma in 8 case, and suspicion of a GI stromal tumor in 1 case. The median maximal diameter of the lesions was 20 mm (range 10-40 mm). All procedures were done with patients under sedation with propofol. The water jet-assisted knife was used for setting coagulation markers around the neoplastic lesions, then for circumferential incision and dissection in combination with repeated submucosal injection of saline solution with a water jet system. Bleeding was treated with diathermia by use of the water jet-assisted knife or hemostatic forceps in case of failure or larger vessels. Clips were used for closure of perforations. Complete resection of neoplasia, procedure time, complication and recurrence rates. According to endoscopic criteria, complete resection of the targeted area could be achieved in all cases, with an en bloc resection rate of 90%. The median procedure duration was 74 minutes (range 15-402 minutes). Exchange of the device was needed in only 10 cases because of severe bleeding from larger vessels, which could be managed by use of hemostatic forceps. The 30-day morbidity rate was 4 of 30 (13.8%) because of

  12. Sophisticated digestive systems in early arthropods

    National Research Council Canada - National Science Library

    Vannier, Jean; Liu, Jianni; Lerosey-Aubril, Rudy; Vinther, Jakob; Daley, Allison C

    2014-01-01

    .... Here we describe exceptionally well-preserved complex digestive organs in early arthropods from the early Cambrian of China and Greenland with functional similarities to certain modern crustaceans...

  13. Avaliação do dano oxidativo ao DNA de células normais e neoplásicas da mucosa cólica de doentes com câncer colorretal Evaluation of DNA oxidative damage in normal and neoplastic cells of colonic mucosa in patients with colorectal cancer

    Directory of Open Access Journals (Sweden)

    Marcelo Lima Ribeiro

    2007-12-01

    levels of oxidative damage to the DNA in cells isolated from the colon mucosa in colorectal patients, and to compare normal and neoplastic tissues and make correlations with anatomopathological variables. METHOD: Thirty colorectal adenocarcinoma patients (eighteen women of mean age 60.6 ± 15.5 years who consecutively underwent operations performed by the same surgical team between 2005 and 2006 were studied. The oxidative damage to the DNA was evaluated by means of the alkaline version of the comet assay (single-cell gel electrophoresis, from fragments of normal and neoplastic colon tissue that were obtained immediately after removal of the surgical specimen. The extent of breakages of the DNA helices was assessed using an image intensification method, on 200 randomly chosen cells (100 from each tissue sample, by means of the Komet 5.5 program. The Tail Moment (T.M measured in each cell quantitatively represented the extent of the oxidative damage to the DNA. The statistical analysis on the variables considered was performed by means of the Student t, chi-squared and Kruskal-Wallis tests, with a significance level of 5% (p<0.05. RESULTS: It was found that, for all the patients studied, the cells obtained from the neoplastic tissue presented oxidative damage to the DNA that was greater than in the cells from normal tissue. The cells isolated from the neoplastic mucosal tissue of the colon presented extension of DNA strand breakage significantly greater (T.M. = 2.532 ± 0.945 than did the cells isolated from normal tissue (T.M. = 1.056 ± 0.460 (p=0.00001; C.I. 95%: -1.7705 to -1.1808. It was found that the patients at earlier stages of the Dukes and TNM classifications presented higher levels of oxidative damage than did those at more advanced stages (p=0.04 and p=0.001, respectively. CONCLUSIONS: The cells obtained from normal tissue of colorectal cancer patients presented signs of oxidative damage to the cell DNA, although at significant lower levels than in the

  14. High levels of aromatic amino acids in gastric juice during the early stages of gastric cancer progression.

    Directory of Open Access Journals (Sweden)

    Kai Deng

    Full Text Available BACKGROUND: Early-stage gastric cancer is mostly asymptomatic and can easily be missed easily by conventional gastroscopy. Currently, there are no useful biomarkers for the early detection of gastric cancer, and their identification of biomarkers is urgently needed. METHODS: Gastric juice was obtained from 185 subjects that were divided into three groups: non-neoplastic gastric disease (NGD, advanced gastric cancer and early gastric cancer (EGC. The levels of aromatic amino acids in the gastric juice were quantitated using high-performance liquid chromatography. RESULTS: The median values (25th to 75th percentile of tyrosine, phenylalanine and tryptophan in the gastric juice were 3.8 (1.7-7.5 µg/ml, 5.3 (2.3-9.9 µg/ml and 1.0 (0.4-2.8 µg/ml in NGD; 19.4 (5.8-72.4 µg/ml, 24.6 (11.5-73.7 µg/ml and 8.3 (2.1-28.0 µg/ml in EGC. Higher levels of tyrosine, phenylalanine and tryptophan in the gastric juice were observed in individuals of EGC groups compared those of the NGD group (NGD vs. EGC, P<0.0001. For the detection of EGC, the areas under the receiver operating characteristic curves (AUCs of each biomarker were as follows: tyrosine, 0.790 [95% confidence interval (CI, 0.703-0.877]; phenylalanine, 0.831 (95% CI, 0.750-0.911; and tryptophan, 0.819 (95% CI, 0.739-0.900. The sensitivity and specificity of phenylalanine were 75.5% and 81.4%, respectively, for detection of EGC. A multiple logistic regression analysis showed that high levels of aromatic amino acids in the gastric juice were associated with gastric cancer (adjusted β coefficients ranged from 1.801 to 4.414, P<0.001. CONCLUSION: Increased levels of tyrosine, phenylalanine and tryptophan in the gastric juice samples were detected in the early phase of gastric carcinogenesis. Thus, tyrosine, phenylalanine and tryptophan in gastric juice could be used as biomarkers for the early detection of gastric cancer. A gastric juice analysis is an efficient, economical and convenient method for

  15. Is photodynamic therapy a selective treatment? Analysis of local complications after endoscopic photodynamic therapy of early stage tumors of gastrointestinal, tracheobronchial, and urinary tracts

    Science.gov (United States)

    Spinelli, Pasquale; Dal Fante, Marco; Mancini, Andrea

    1995-03-01

    Selectivity is the most emphasized advantage of photodynamic therapy (PDT). However, at drug and light doses used for clinical applications, response from normal tissue surrounding the tumor reduces the real selectivity of the drug-light system and increases the surface of the area responding to the treatment. It is now evident that light irradiation of a sensitized patient produces damage at a various degree not only in the tumor but also in non-neoplastic tissues included in the field of irradiation. We report our experience in endoscopic PDT of early stage tumors in tracheobronchial, gastrointestinal and urinary tracts, describing early and late local complications caused by the damage of normal tissues adjacent to the tumors and included in the field of light irradiation. Among 44 patients treated, local complications, attributable to a poor selectivity of the modality, occurred in 6 patients (14%). In particular, the rate of local complications was 9% in patients treated for esophageal tumors, 14% in patients with gastric tumors, 9% in patients with tracheobronchial tumors, and 67% in bladder cancer patients. Clinical pictures as well as endoscopic findings at various intervals from treatment showed that mucositis is a common event following endoscopic PDT. It causes exudation and significant tissue inflammatory response, whose consequences are different in the various organs treated. Photoradiation must be, as much as possible, limited to the malignant area.

  16. Elevated nuclear S100P expression is associated with poor survival in early breast cancer patients.

    Science.gov (United States)

    Maciejczyk, Adam; Łacko, Aleksandra; Ekiert, Marcin; Jagoda, Ewa; Wysocka, Teresa; Matkowski, Rafał; Hałoń, Agnieszka; Györffy, Balázs; Lage, Hermann; Surowiak, Paweł

    2013-04-01

    S100P - low molecular weight acidic protein has been shown to be involved in processes of proliferation, survival, angiogenesis, multidrug resistance and metastasis in various human malignancies. In breast cancer, S100P expression is associated with immortalization of neoplastic cells and aggressive tumour behaviour, indicating that this protein may have adverse prognostic value. We analyzed nuclear and cytoplasmic expression of S100P in 85 stage II breast cancer patients with a median follow up of 17 years. Immunohistochemical reactions were performed on paraffin sections of primary tumours, using monoclonal antibodies against S100P. We also studied prognostic value of S100P mRNA expression using the KM plotter which assessed the effect of 22,277 genes on survival in 2422 breast cancer patients. Moreover, the relationship was examined between expression of S100P in cells of four breast cancer cell lines and their sensitivity to the 11 most frequently applied cytotoxic drugs. Univariate and multivariate analyses showed that higher expression of nuclear S100P (S100Pn) was typical for cases of a shorter overall survival and disease-free time. KM plotter analysis showed that elevated S100P expression was specific for cases of a relapse-free survival and distant metastases-free survival. No relationship could be documented between expression of S100P and sensitivity of breast cancer cells to cytostatic drugs. We demonstrated that a high S100Pn expression level was associated with poor survival in early stage breast cancer patients. Since preliminary data indicated that expression of S100P was up-regulated by activation of glucocorticoid receptor and several agents manifested potential to activate or inhibit S100P promoter activity, this protein might become a therapy target and warrants further studies with respect to its prognostic, predictive and potentially therapeutic value.

  17. Loss of disabled-2 expression is an early event in esophageal squamous tumorigenesis

    Institute of Scientific and Technical Information of China (English)

    Kumar Anupam; Chatopadhyay Tusharkant; Siddhartha Datta Gupta; Ralhan Ranju

    2006-01-01

    AIM: Disabled-2 (D4B2) is a candidate tumor-suppressor gene identified in ovarian cancer that negatively influences mitogenic signal transduction of growth factors and blocks ras activity. In a recent study, we observed down-regulation of DAB2 transcripts in ESCCs using cDNA microarrays. In the present study, we aimed to determine the clinical significance of loss of DAB2protein in esophageal tumorigenesis, hypothesizing that DAB2 promoter hypermethylation-mediated gene silencing may account for loss of the protein.METHODS: DAB2 expression was analyzed by immunohistochemistry in 50 primary esophageal squamous cell carcinomas (ESCCs), 30 distinct hyperplasia, 15 dysplasia and 10 non-malignant esophageal tissues. To determine whether promoter hypermethylation contributes to loss of DAB2 expression in ESCCs, methylation status of DAB2 promoter was analyzed in DAB2 immuno-negative tumors using methylation-specific PCR.RESULTS: Loss of DAB2 protein was observed in 5/30 (17%) hyperplasia, 10/15 (67%) dysplasia and 34/50 (68%) ESCCs. Significant loss of DAB2 protein was observed from esophageal normal mucosa to hyperplasia, dysplasia and invasive cancer (Ptrend < 0.001).Promoter hypermethylation of DAB2 was observed in 2of 10 (20%) DAB2 immuno-negative ESCCs.CONCLUSION: Loss of DAB2 protein expression occurs in early pre-neoplastic stages of development of esophageal cancer and is sustained down the tumorigenic pathway. Infrequent DAB2 promoter methylation in ESCCs suggests that epigenetic gene silencing is only one of the mechanisms causing loss of DAB2 expression in ESCCs.

  18. Matrix metalloproteinases 15 and 19 are stromal regulators of colorectal cancer development from the early stages.

    Science.gov (United States)

    Sena, Paola; Mariani, Francesco; Marzona, Laura; Benincasa, Marta; Ponz de Leon, Maurizio; Palumbo, Carla; Roncucci, Luca

    2012-07-01

    Matrix metalloproteinases (MMPs) have been well characterized for their ability to degrade extracellular matrix proteins and, thus, they have been studied to elucidate their involvement in both tumor development and progression. In the present study, attention was focused on MMP-15 and MMP-19, two less known members of the MMP family. The expression profile of MMP-15 and -19 was assayed in samples of normal colorectal mucosa, microadenomas and cancer using confocal analysis, western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Both qRT-PCR and western blotting showed that MMP-15 and MMP-19 appeared to be upregulated during colorectal tumorigenesis, with different expression patterns: MMP-15 expression level increases from normal mucosa to microadenomas, with a reduced level in cancer with respect to microadenomas; the semiquantitative immunofluorescence analysis showed a stromal localization of this protein in the early phases of neoplastic transformation. Increasing amount of MMP-19 mRNA and protein levels were observed in the progression of colonic lesions; MMP-19 staining increased in the normal mucosa-microadenoma-carcinoma sequence. Such different expression patterns, are probably due to the different roles played in colorectal tumorigenesis by these two molecules. Conflicting data on the role of these proteins in tumor progression have been reported, thus, an improved understanding of the biological roles of MMPs, in particular the lesser known members such as MMP-15 and 19, in colorectal cancer may lead to a re-evaluation of the use of MMP inhibitors and suggests the need of integrated translational studies on MMP expression patterns.

  19. Disruptive cell cycle regulation involving epigenetic downregulation of Cdkn2a (p16(Ink4a)) in early-stage liver tumor-promotion facilitating liver cell regeneration in rats.

    Science.gov (United States)

    Tsuchiya, Takuma; Wang, Liyun; Yafune, Atsunori; Kimura, Masayuki; Ohishi, Takumi; Suzuki, Kazuhiko; Mitsumori, Kunitoshi; Shibutani, Makoto

    2012-09-28

    Cell cycle aberration was immunohistochemically examined in relation to preneoplastic liver cell foci expressing glutathione S-transferase placental form (GST-P) at early stages of tumor-promotion in rats with thioacetamide (TAA), a hepatocarcinogen facilitating liver cell regeneration. Immunoexpression of p16(Ink4a) following exposure to other hepatocarcinogens/promoters and its DNA methylation status were also analyzed during early and late tumor-promotion stages. GST-P(+) liver cell foci increased cell proliferation and decreased apoptosis when compared with surrounding liver cells. In concordance with GST-P(+) foci, checkpoint proteins at G(1)/S (p21(Cip1), p27(Kip1) and p16(Ink4a)) and G(2)/M (phospho-checkpoint kinase 1, Cdc25c and phospho-Wee1) were either up- or downregulated. Cellular distribution within GST-P(+) foci was either increased or decreased with proteins related to G(2)-M phase or DNA damage (topoisomerase IIα, phospho-histone H2AX, phospho-histone H3 and Cdc2). In particular, p16(Ink4a) typically downregulated in GST-P(+) foci and regenerative nodules at early tumor-promotion stage with hepatocarcinogens facilitating liver cell regeneration and in neoplastic lesions at late tumor-promotion stage with hepatocarcinogens/promoters irrespective of regenerating potential. Hypermethylation at exon 2 of Cdkn2a was detected at both early- and late-stages. Thus, diverse disruptive expression of G(1)/S and G(2)/M proteins, which allows for clonal selection of GST-P(+) foci, results in the acquisition of multiple aberrant phenotypes to disrupt checkpoint function. Moreover, increased DNA-damage responses within GST-P(+) foci may be the signature of genetic alterations. Intraexonic hypermethylation may be responsible for p16(Ink4a)-downregulation, which facilitates cell cycle progression in early preneoplastic lesions produced by repeated cell regeneration and late-stage neoplastic lesions irrespective of the carcinogenic mechanism. Copyright © 2012

  20. Macro finance early warning system

    Institute of Scientific and Technical Information of China (English)

    Guihuan ZHENG; Xun ZHANG; Wei SHANG; Shanying XU

    2009-01-01

    In this paper, a financial early warning informa-tion system is developed based on the multi-dimensional cli-mate approach that is featured with a multi-dimensional in-dex construction and the relevant multi-dimensional analy-sis. Requirement analysis and design issues of building an information system supporting this multi-dimensional cli-mate approach are discussed in detail. And a case using this system to study the macro financial issues is presented to illustrate how the proposed multi-dimensional approach works in the information system we design. This research is an interdisciplinary work of economic theories, macro finan-cial empirical studies, and software engineering. With ad-vanced macro financial early warning theories implemented in a web application, the Macro Financial Early Warning System (FEWS) developed in this research has been proved to be effective in a trial running in the Forecasting research institute of the Chinese Academy of Sciences.

  1. Early Literacy and Early Numeracy: The Value of Including Early Literacy Skills in the Prediction of Numeracy Development

    Science.gov (United States)

    Purpura, David J.; Hume, Laura E.; Sims, Darcey M.; Lonigan, Cristopher J.

    2011-01-01

    The purpose of this study was to examine whether early literacy skills uniquely predict early numeracy skills development. During the first year of the study, 69 3- to 5-year-old preschoolers were assessed on the Preschool Early Numeracy Skills (PENS) test and the Test of Preschool Early Literacy Skills (TOPEL). Participants were assessed again a…

  2. Do Early Outs Work Out? Teacher Early Retirement Incentive Plans.

    Science.gov (United States)

    Brown, Herb R.; Repa, J. Theodore

    1993-01-01

    School districts offer teacher early retirement incentive plans (TERIPs) as an opportunity to hire less expensive teachers, reduce fringe benefits costs, and eliminate teaching positions. Discusses reasons for teachers to accept TERIP, and describes a computer model that allows school officials to calculate and compare costs incurred if an…

  3. Early exit: Estimating and explaining early exit from drug treatment

    Directory of Open Access Journals (Sweden)

    Sanders Melony

    2008-04-01

    Full Text Available Abstract Background Early exit (drop-out from drug treatment can mean that drug users do not derive the full benefits that treatment potentially offers. Additionally, it may mean that scarce treatment resources are used inefficiently. Understanding the factors that lead to early exit from treatment should enable services to operate more effectively and better reduce drug related harm. To date, few studies have focused on drop-out during the initial, engagement phase of treatment. This paper describes a mixed method study of early exit from English drug treatment services. Methods Quantitative data (n = 2,624 was derived from three English drug action team areas; two metropolitan and one provincial. Hierarchical linear modelling (HLM was used to investigate predictors of early-exit while controlling for differences between agencies. Qualitative interviews were conducted with 53 ex-clients and 16 members of staff from 10 agencies in these areas to explore their perspectives on early exit, its determinants and, how services could be improved. Results Almost a quarter of the quantitative sample (24.5% dropped out between assessment and 30 days in treatment. Predictors of early exit were: being younger; being homeless; and not being a current injector. Age and injection status were both consistently associated with exit between assessment and treatment entry. Those who were not in substitution treatment were significantly more likely to leave treatment at this stage. There were substantial variations between agencies, which point to the importance of system factors. Qualitative analysis identified several potential ways to improve services. Perceived problems included: opening hours; the service setting; under-utilisation of motivational enhancement techniques; lack of clarity about expectations; lengthy, repetitive assessment procedures; constrained treatment choices; low initial dosing of opioid substitution treatment; and the routine requirement

  4. Gesturing in the early universities.

    Science.gov (United States)

    O'Boyle, C

    2000-01-01

    Research into the oral and literary traditions of scholastic education usually emphasizes the significance of the world in late medieval pedagogy. This paper suggests that coded hand signals provided early university scholars with an important non-verbal means of communication too. Using illustrations of classroom scenes from early university manuscripts, this paper analyzes the artistic conventions for representating gestures that these images embody. By building up a typology of these gesticulations, it demonstrates that the producers of these images and their audience shared a perception of scholastic education that embraced a sophisticated understanding of the activities associated with university education.

  5. Shocks in the Early Universe.

    Science.gov (United States)

    Pen, Ue-Li; Turok, Neil

    2016-09-23

    We point out a surprising consequence of the usually assumed initial conditions for cosmological perturbations. Namely, a spectrum of Gaussian, linear, adiabatic, scalar, growing mode perturbations not only creates acoustic oscillations of the kind observed on very large scales today, it also leads to the production of shocks in the radiation fluid of the very early Universe. Shocks cause departures from local thermal equilibrium as well as create vorticity and gravitational waves. For a scale-invariant spectrum and standard model physics, shocks form for temperatures 1  GeVUniverse as early as 10^{-30}  sec after the big bang.

  6. Early Complications of Heart Transplantation

    Science.gov (United States)

    Schnee, Mark

    1987-01-01

    In cyclosporine-treated cardiac allograft recipients, rejection and infection are two principal early complications. The following report describes our approach to the diagnosis and management of rejection. Infectious complications are discussed elsewhere in this journal. Lymphoproliferative disorders have not been reported in our series of transplant recipients. Other early complications particularly related to cyclosporine immuno-suppressive therapy include systemic hypertension, renal insufficiency, hepatic toxicity, and pancreatitis. Each of these is illustrated by a representative group or patient profile. (Texas Heart Institute Journal 1987; 14:257-261) Images PMID:15227308

  7. Early Modern English:Morphology

    OpenAIRE

    2012-01-01

    By the end of the Middle English period there is already considerable loss of inflectional morphology, and in Early Modern English we see the last reflexes of a shift from synthetic Old English to analytic Modern English (Lass 1999: 139). In fact, the inflectional system of Early Modern English is not very different from what we have today (Go¨rlach 1991: 79). The changes in inflection which do take place between 1500 and 1700 show marked sociolinguistic differentiation and are the subject of...

  8. Early life origins of obesity.

    Science.gov (United States)

    Newnham, John P; Pennell, Craig E; Lye, Stephen J; Rampono, Jonathan; Challis, John R G

    2009-06-01

    There is increasing evidence that obesity has its origins in early life. Predisposition is based on interactions between the genome and environmental influences acting through epigenetic modifications. Individuals most at risk are those whose ancestral line has made a rapid transition from a traditional to a Westernized style of life. The process involves not only metabolism, but also behavior. As a result, those people who are most at risk of obesity may be those least likely to respond to educational programs based on lifestyle modification. Understanding the mechanisms and pathways that underpin the early origins of obesity is vital if we are to make progress in addressing this major problem of modern life.

  9. Early Planetary Differentiation: Comparative Planetology

    Science.gov (United States)

    Jones, John H.

    2006-01-01

    We currently have extensive data for four different terrestrial bodies of the inner solar system: Earth, the Moon, Mars, and the Eucrite Parent Body [EPB]. All formed early cores; but all(?) have mantles with elevated concentrations of highly sidero-phile elements, suggestive of the addition of a late "veneer". Two appear to have undergone extensive differentiation consistent with a global magma ocean. One appears to be inconsistent with a simple model of "low-pressure" chondritic differentiation. Thus, there seems to be no single, simple paradigm for understand-ing early differentiation.

  10. Avaliação dos fatores preditivos de invasão neoplásica do complexo areolomamilar em pacientes com câncer de mama Evaluation of the predictive factors involved in the neoplastic invasion of the nipple-areolar complex in patients with breast cancer

    Directory of Open Access Journals (Sweden)

    Ana Thereza da Cunha Uchôa Camacho

    2010-06-01

    Full Text Available INTRODUÇÃO: A escolha pela mastectomia com preservação do complexo areolomamilar (CAM, de melhor resultado estético, depende da ausência de envolvimento neoplásico do CAM. OBJETIVO: Identificar os fatores preditivos de invasão neoplásica do CAM. MÉTODO: Foi realizado estudo analítico, retrospectivo, clínico-patológico de 48 peças de mastectomia de pacientes portadoras de carcinoma da mama, atendidas no Hospital de Câncer da Paraíba - Fundação Napoleão Laureano, durante o período de abril de 2007 a janeiro de 2008, com idade média de 52,69 ± 10,72 anos. O CAM foi seccionado separadamente mediante cortes perpendiculares e paralelos a partir da papila, estendendo-se a 2 cm de profundidade do tecido retroareolar (com o intuito de incluir seios lactíferos e ductos coletores e segmentares, seguidos de cortes transversais até a base. RESULTADOS: Identificou-se frequência de envolvimento do CAM por carcinoma invasivo em 14,58% dos casos. Pacientes jovens (média 42,3 ± 4,7 anos, distância do tumor a mamilo/aréola INTRODUCTION: The choice for having mastectomy with preservation of the nipple-areolar complex (NAC, with better esthetic results, depends on the abscence of neoplastic invasion of the NAC. OBJECTIVE: To identify the predictive factors related to neoplastic NAC invasion. METHODS: We carried out a retrospective, analytical and clinical-pathologic study comprising 48 mastectomy specimens of breast carcinoma from patients treated at Cancer Institute of Paraíba - Napoleão Laureano Foundation (Hospital de Câncer da Paraíba - Fundação Napoleão Laureano from April 2007 to January 2008. The mean age was 52.69 ± 10.72. The NAC complex was sectioned separately and perpendicular and parallel cuts were performed from the papilla extending 2 cm deep into the retroareolar tissue (including collecting ducts, lactiferous sinuses and segmental ducts, followed by transverse cuts toward the deep margin. RESULTS: The frequency

  11. Identification of epigenetically downregulated Tmem70 and Ube2e2 in rat liver after 28-day treatment with hepatocarcinogenic thioacetamide showing gene product downregulation in hepatocellular preneoplastic and neoplastic lesions produced by tumor promotion.

    Science.gov (United States)

    Mizukami, Sayaka; Yafune, Atsunori; Watanabe, Yousuke; Nakajima, Kota; Jin, Meilan; Yoshida, Toshinori; Shibutani, Makoto

    2017-01-15

    The present study identified genes showing promoter region hypermethylation by CpG island microarrays in the liver of rats treated with hepatocarcinogen thioacetamide (TAA) for 28days. Among 47 hypermethylated genes, Hist1h2aa, Tmem70, Ube2e2, and Slk were confirmed to show hypermethylation by methylation-specific quantitative polymerase chain reaction (PCR) and pyrosequencing analyses as well as downregulation of transcript levels by real-time reverse transcription-PCR analysis in the livers of rats treated with TAA. All gene products of the 4 selected genes showed decreased immunoreactivity forming negative liver cell foci in a subpopulation of glutathione S-transferase placental form (GST-P)(+) foci in TAA-promoted rat livers in a two-stage hepatocarcinogenesis model. Among them, TMEM70 and UBE2E2 showed increased incidences of negative foci in GST-P(+) foci by promotion of all examined TAA, β-naphthoflavone, piperonyl butoxide, fenbendazole and phenobarbital, while HIST1H2AA and SLK did not respond to all promotive treatments. In the late stage of tumor promotion by TAA, the incidence of GST-P(+) proliferative lesions with downregulation of TMEM70 or UBE2E2 was higher in adenomas and carcinomas than liver cell foci. TMEM70 plays a role in mitochondrial oxidative phosphorylation, and UBE2E2 participates in the stabilization of cell cycle regulatory proteins. Therefore, our results indicate that aberrant epigenetic gene downregulation suggestive of a metabolic shift of cellular respiration from oxidative phosphorylation to glycolysis and aberrant cell cycle regulation facilitating cell proliferation from as early as 28days after hepatocarcinogen treatment contribute to tumor development.

  12. Factors that affect cancer patient compliance to oral anti-neoplastic therapy Factores que influyen en la adhesión de pacientes con cáncer a la terapia antineoplásica oral Fatores que influenciam a adesão de pacientes com câncer à terapia antineoplásica oral

    Directory of Open Access Journals (Sweden)

    Patrícia Andréa Crippa Marques

    2008-01-01

    Full Text Available OBJECTIVES: To identify factors that can affect compliance to treatment with neoplastic oral drugs in a group of cancer patients. METHODS: Interviews were performed on 61 patients diagnosed with cancer and under anti-neoplastic oral therapy in a private hospital. The interviews were carried out using instruments to assess compliance. RESULTS: Most patients (95% reported the oral treatment was not difficult. The Morisky and Green Test were positive in 28% of the patients. Factors that may affect following the treatment were significantly (pOBJETIVOS: Identificar los factores asociados a la adhesión al tratamiento con drogas de acción antineoplásica por vía oral en pacientes con cáncer. MÉTODOS: Fueron entrevistados 61 pacientes con cáncer sometidos a terapia antineoplásica por vía oral en un hospital particular, con la aplicación de instrumentos para evaluar la adhesión. RESULTADOS: La mayoría de los pacientes (95% refirió que el tratamiento oral no es difícil. El test Morisky y Green fue positivo en el 28% de los pacientes. Los factores que pueden influir en la realización del tratamiento se asociaron de forma significativa (pOBJETIVOS: Identificar fatores associados à adesão ao tratamento com drogas de ação antineoplásica por via oral em pacientes com câncer. MÉTODOS: Foram entrevistados 61 pacientes com câncer sob terapia antineoplásica via oral em hospital particular, com a aplicação de instrumentos para avaliar a adesão. RESULTADOS: A maioria dos pacientes (95% referiu que o tratamento oral não é difícil. O Teste Morisky e Green foi positivo em 28% dos pacientes. Os fatores que podem influenciar a realização do tratamento se associaram de forma significativa (p<0,05 com a variável tempo, os pacientes que apresentaram mais dificuldade, tinham mais tempo de tratamento. CONCLUSÕES: Os pacientes apresentaram atitudes positivas frente ao tratamento com medicamentos antineoplásicos orais, porém foram

  13. Expressão de genes relacionados à função adrenocortical no estado de caquexia neoplásica - DOI: 10.4025/actascihealthsci.v31i2.6759 Expression of genes related to the adrenocortical function in the neoplastic cachexia process- DOI: 10.4025/actascihealthsci.v31i2.6759

    Directory of Open Access Journals (Sweden)

    Maria Angélica Ehara Watanabe

    2009-09-01

    Full Text Available A glândula adrenal tem papel fundamental na resposta neuroendócrina, especialmente em situações em que há comprometimento da homeostasia. No processo de caquexia neoplásica, há prejuízo da homeostasia por alterações nutricionais e metabólicas do câncer em estágio avançado, envolvendo a resposta do eixo hipotálamo-hipófise-adrenal. Neste trabalho, foi utilizado um modelo animal de caquexia induzida pelo tumor de Walker-256 em ratos Wistar. Os animais (n=4 foram sacrificados dez dias após a inoculação de células tumorais e a glândula adrenal foi removida. O RNA foi extraído para o estudo da expressão de genes relacionados ao controle da esteroidogênese por RT-PCR semiquantitativa. A análise dos dados demonstrou expressão significativamente reduzida dos genes MC2R (receptor tipo 2 para melacortina, 3ßHSD I (3ß-hidroxiesteroide-desidrogenase tipo I e TSPO (proteína translocadora em animais com caquexia neoplásica (valores de P=0,037; 0,0097 e 0,052, respectivamente, revelando falência do córtex da adrenal.The adrenal gland plays a crucial role in the neuroendocrine response, especially in situations where homeostasis is disturbed. In the neoplastic cachexia process, there is homeostasis impairment by nutritional and metabolic alterations of advanced-stage cancer, involving hypothalamus-pituitary-adrenal axis response. In this assignment, an experimental model of cachexia induced by Walker-256 tumor was performed in Wistar rats. Animals (n=4 were sacrificed 10 days after inoculation of tumor cells, and the adrenal glands were excised. The RNA was isolated for the study of gene expression related to the steroidogenesis control by semi-quantitative RT-PCR. Data analysis showed a significant reduced expression of MC2R (melancortin type 2 receptor, 3ßHSD I (3-beta-hydroxysteroid dehydrogenase type I and TSPO (translocator protein genes in animals with neoplastic cachexia (P=0.037, 0.0097 and 0.052, respectively, revealing

  14. Effects of intraperitoneal injection of phenol, glycerin and acetic acid on neoplastic ascitis in guinea pigs Efeitos da injeção intraperitoneal de fenol, glicerina e ácido acético na ascite neoplásica em cobaias

    Directory of Open Access Journals (Sweden)

    Rogerio Saad-Hossne

    2008-12-01

    Full Text Available PURPOSE: To investigate the histolytic action of a solution composed by phenol, glycerin and acetic acid on neoplastic ascitis in guinea pigs. METHODS: Thirty-two guinea pigs were used. The animals were randomly distributed in experimental and control groups, and the effects of the peritoneal injection of the testing solution were studied. Saline solution was used for the control groups. Biochemical and anatomopathological (heart, lungs, kidneys, spleen and peritoneal serous membrane were evaluated at 24 hours and 4 weeks of development. RESULTS: It was observed that solution E, when infused into the peritoneal cavity, caused no clinical, histological or laboratory alterations in these animals when compared to those in the control group. CONCLUSION: Given our results, it would be interesting to study the effects of the proposed solution on cases with experimental neoplastic ascites with a later view to treating it in humans.OBJETIVO: Investigar a ação hìstolítica de uma solução composta de fenol, glicerina e ácido acético na ascite neoplásica em cobaias. MÉTODOS: Foram utilizadas 32 cobaias, distribuídas por sorteio, em grupos experimentais e controles e estudados os efeitos da injeção peritonial da solução teste. Nos grupos controles empregou-se solução fisiológica. Foram estudadas alterações bioquímicas, anatomopatológicas (coração, pulmões, rins, baço e serosa peritonial, com 24 horas e 4 semanas de evolução. RESULTADOS: Verificou-se que a solução E quando instilada na cavidade peritonial não provocou nenhuma alteração clinica, histologica ou laboratorial nestes animais, quando comparados com o grupo controle. CONCLUSÃO: Frente aos resultados obtidos, consideramos interessante estudar os efeitos da solução proposta em casos de ascite neoplásica experimental em animais, com posterior estudo em seres humanos.

  15. Excess Early Mortality in Schizophrenia

    DEFF Research Database (Denmark)

    Laursen, Thomas Munk; Nordentoft, Merete; Mortensen, Preben Bo

    2014-01-01

    Schizophrenia is often referred to as one of the most severe mental disorders, primarily because of the very high mortality rates of those with the disorder. This article reviews the literature on excess early mortality in persons with schizophrenia and suggests reasons for the high mortality as ...

  16. Electromigration early resistance increase measurements

    OpenAIRE

    Niehof, J; Flinn, P. A.; Maloney, T.J.

    1993-01-01

    An early resistance change measurement set-up, using an AC bridge technique, has been developed, and measurements have been performed. Large sample-to-sample variations occur. The characteristic time for the resistance change curve is shorter for resistance increase (under current stress) than for resistance decay (during recovery).

  17. The Climate of Early Mars

    Science.gov (United States)

    Wordsworth, Robin D.

    2016-06-01

    The nature of the early martian climate is one of the major unanswered questions of planetary science. Key challenges remain, but a new wave of orbital and in situ observations and improvements in climate modeling have led to significant advances over the past decade. Multiple lines of geologic evidence now point to an episodically warm surface during the late Noachian and early Hesperian periods 3-4 Ga. The low solar flux received by Mars in its first billion years and inefficiency of plausible greenhouse gases such as CO2 mean that the steady-state early martian climate was likely cold. A denser CO2 atmosphere would have caused adiabatic cooling of the surface and hence migration of water ice to the higher-altitude equatorial and southern regions of the planet. Transient warming caused melting of snow and ice deposits and a temporarily active hydrological cycle, leading to erosion of the valley networks and other fluvial features. Precise details of the warming mechanisms remain unclear, but impacts, volcanism, and orbital forcing all likely played an important role. The lack of evidence for glaciation across much of Mars's ancient terrain suggests the late Noachian surface water inventory was not sufficient to sustain a northern ocean. Though mainly inhospitable on the surface, early Mars may nonetheless have presented significant opportunities for the development of microbial life.

  18. Early Childhood Educator's Nutrition Handbook.

    Science.gov (United States)

    Olson, Christine; And Others

    This nutrition handbook is designed to provide enough information on nutrition and food habits to enable early childhood educators to add a nutrition dimension to children's learning activities. Topics covered are the role of nutrition in growth during the preschool years; nutrients and their functions; selecting a healthy diet; common nutritional…

  19. The Early Years: Mixing Materials

    Science.gov (United States)

    Ashbrook, Peggy

    2017-01-01

    Engaging children's interest, inspiring active exploration of materials, and fostering cooperation between children and adults is the best way to promote the construction of knowledge. Some popular early childhood activities can be expanded to provide experiences and time for children to build on their prior knowledge. This column discusses…

  20. Early Signs of Entrepreneurial Giftedness

    Science.gov (United States)

    Shavinina, Larisa V.

    2008-01-01

    Although successful entrepreneurship is important for the economic prosperity of any society, one should acknowledge that entrepreneurial giftedness is terra incognita from a research viewpoint. This article analyzes early manifestations of entrepreneurial giftedness in the cases of Richard Branson, Michael Dell, and Bill Gates and thus opens a…